research article human elimination of organochlorine

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Research Article Human Elimination of Organochlorine Pesticides: Blood, Urine, and Sweat Study Stephen J. Genuis, 1,2 Kevin Lane, 3 and Detlef Birkholz 1 1 University of Alberta, Edmonton, AB, Canada T6G 2R7 2 University of Calgary, Calgary, AB, Canada T2N 4N1 3 Department of Chemistry, e King’s University, Edmonton, AB, Canada T6B 2H3 Correspondence should be addressed to Stephen J. Genuis; [email protected] Received 28 June 2016; Revised 2 September 2016; Accepted 7 September 2016 Academic Editor: Alex Boye Copyright © 2016 Stephen J. Genuis et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Many individuals have been exposed to organochlorinated pesticides (OCPs) through food, water, air, dermal expo- sure, and/or vertical transmission. Due to enterohepatic reabsorption and affinity to adipose tissue, OCPs are not efficiently elimi- nated from the human body and may accrue in tissues. Many epidemiological studies demonstrate significant exposure-disease rela- tionships suggesting OCPs can alter metabolic function and potentially lead to illness. ere is limited study of interventions to facil- itate OCP elimination from the human body. is study explored the efficacy of induced perspiration as a means to eliminate OCPs. Methods. Blood, urine, and sweat (BUS) were collected from 20 individuals. Analysis of 23 OCPs was performed using dual-column gas chromatography with electron-capture detectors. Results. Various OCPs and metabolites, including DDT, DDE, methoxychlor, endrin, and endosulfan sulfate, were excreted into perspiration. Generally, sweat samples showed more frequent OCP detection than serum or urine analysis. Many OCPs were not readily detected in blood testing while still being excreted and identified in sweat. No direct correlation was found among OCP concentrations in the blood, urine, or sweat compartments. Conclusions. Sweat analysis may be useful in detecting some accrued OCPs not found in regular serum testing. Induced perspiration may be a viable clinical tool for eliminating some OCPs. 1. Introduction Organochlorinated compounds have been used globally for many years as solvents, fumigants, and insecticides. In the 1930s, Swiss chemist and Nobel Prize recipient Paul Muller first discovered that the most well-known organochlorine agent dichlorodiphenyltrichloroethane (DDT) had signifi- cant insecticide properties [1]. Since then, this pest control agent has been utilized around the world to prevent the transmission of many vector-born diseases including malaria and typhus [2]. Alongside DDT, several other organochlo- rinated pesticides (OCPs) were subsequently developed and were also utilized to control various pests. With unfolding toxicological research, however, evidence of potential human health risks associated with exposure to these agents began to appear. Like many OCPs, it was eventually confirmed that DDT elicited toxic effects that harmed nontarget species, bioaccumulated in the animal food chain, and had a very slow rate of environmental degradation. As a result, the use of DDT was eventually banned in the United States in 1972 [3]. Due to the ability of OCPs to accumulate in body tissues, their long half-life of elimination from the body, and emerging evidence of potential toxicity to human health, many countries throughout the world went on to ban many of the agents within the OCP family [4]. e sequelae of the OCP experiment, however, continue to linger as human contamination with these chemical compounds is still evi- dent throughout the globe. Various factors are contributing to this reality, including the following: (i) the ongoing use of OCPs in some countries, (ii) the persistence of these agents within the environment and within the human body, (iii) the widespread use of international travel resulting in potential OCP exposure when visiting or relocating to jurisdictions Hindawi Publishing Corporation BioMed Research International Volume 2016, Article ID 1624643, 10 pages http://dx.doi.org/10.1155/2016/1624643

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Page 1: Research Article Human Elimination of Organochlorine

Research ArticleHuman Elimination of Organochlorine PesticidesBlood Urine and Sweat Study

Stephen J Genuis12 Kevin Lane3 and Detlef Birkholz1

1University of Alberta Edmonton AB Canada T6G 2R72University of Calgary Calgary AB Canada T2N 4N13Department of Chemistry The Kingrsquos University Edmonton AB Canada T6B 2H3

Correspondence should be addressed to Stephen J Genuis sgenuisshawca

Received 28 June 2016 Revised 2 September 2016 Accepted 7 September 2016

Academic Editor Alex Boye

Copyright copy 2016 Stephen J Genuis et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

Background Many individuals have been exposed to organochlorinated pesticides (OCPs) through food water air dermal expo-sure andor vertical transmission Due to enterohepatic reabsorption and affinity to adipose tissue OCPs are not efficiently elimi-nated from the humanbody andmay accrue in tissuesMany epidemiological studies demonstrate significant exposure-disease rela-tionships suggestingOCPs can altermetabolic function and potentially lead to illnessThere is limited study of interventions to facil-itate OCP elimination from the human bodyThis study explored the efficacy of induced perspiration as ameans to eliminate OCPsMethods Blood urine and sweat (BUS) were collected from 20 individuals Analysis of 23 OCPs was performed using dual-columngas chromatography with electron-capture detectors Results Various OCPs and metabolites including DDT DDE methoxychlorendrin and endosulfan sulfate were excreted into perspiration Generally sweat samples showed more frequent OCP detectionthan serum or urine analysis Many OCPs were not readily detected in blood testing while still being excreted and identified insweat No direct correlation was found among OCP concentrations in the blood urine or sweat compartments Conclusions Sweatanalysis may be useful in detecting some accrued OCPs not found in regular serum testing Induced perspiration may be a viableclinical tool for eliminating some OCPs

1 Introduction

Organochlorinated compounds have been used globally formany years as solvents fumigants and insecticides In the1930s Swiss chemist and Nobel Prize recipient Paul Mullerfirst discovered that the most well-known organochlorineagent dichlorodiphenyltrichloroethane (DDT) had signifi-cant insecticide properties [1] Since then this pest controlagent has been utilized around the world to prevent thetransmission of many vector-born diseases includingmalariaand typhus [2] Alongside DDT several other organochlo-rinated pesticides (OCPs) were subsequently developed andwere also utilized to control various pests With unfoldingtoxicological research however evidence of potential humanhealth risks associated with exposure to these agents beganto appear Like many OCPs it was eventually confirmed thatDDT elicited toxic effects that harmed nontarget species

bioaccumulated in the animal food chain and had a veryslow rate of environmental degradation As a result the useof DDT was eventually banned in the United States in 1972[3]

Due to the ability of OCPs to accumulate in bodytissues their long half-life of elimination from the body andemerging evidence of potential toxicity to human healthmany countries throughout the world went on to ban manyof the agents within the OCP family [4] The sequelae ofthe OCP experiment however continue to linger as humancontamination with these chemical compounds is still evi-dent throughout the globe Various factors are contributingto this reality including the following (i) the ongoing use ofOCPs in some countries (ii) the persistence of these agentswithin the environment and within the human body (iii) thewidespread use of international travel resulting in potentialOCP exposure when visiting or relocating to jurisdictions

Hindawi Publishing CorporationBioMed Research InternationalVolume 2016 Article ID 1624643 10 pageshttpdxdoiorg10115520161624643

2 BioMed Research International

Table 1 Organochlorine pesticide groupings based on chemicalstructure

Group Constituents

(i) DDT and analogues

DDTDDEDDDMethoxychlor

(ii) Hexachlorobenzene Hexachlorobenzene

(iii) Hexachlorocyclohexane 120572-HCH 120573-HCH 120575-HCH and120574-HCH

(iv) Cyclodiene

Endosulfan I and endosulfan IIHeptachlorAldrinDieldrinEndrin

(v) Chlordecone Kelevan andMirex

Chlordecone Kelevan andMirex

(vi) Toxaphene Toxaphene

where OCPs are still used (iv) the global exchange ofpotentially contaminated foodstuffs originating from juris-dictions where OCPs are still used and (v) the potential forvertical transmission of OCPs from contaminated mothersto offspring during pregnancy and lactation [5] As a resultOCPs continue to be found in individuals and populationgroups including infant children Individuals contaminatedwith OCP compounds remain at risk for adverse healthconsequences and some will potentially pass on these agentsto subsequent generations through vertical transmission

From a clinical perspective the question remains abouthow to assess and manage people who have health issuesrelated to xenobiotic contamination [6ndash8] As many persis-tent toxicants including OCPs can sequester and accrue intissues rather than remaining in the blood compartment [9]biomonitoring for such chemical agents through unprovokedblood and urine analysis does not necessarily reflect theactual body burden of these chemicals [10] Furthermore aspersistent organochlorine compounds have been associatedwith myriad health risks it might be possible to diminish therisk of adverse health sequelae and transgenerational spreadof OCPs if means were identified to facilitate elimination ofthese agents from the human body altogether

Existing medical literature suggests that elimination oforganochlorine compounds and other persistent chemicalagents from the human body can have significant clinicalbenefit in ameliorating health problems [10ndash12] Accordinglythe value of establishing interventions to facilitate eliminationof toxic chemical agents is thus apparent In this researchstudy we provide an overview of literature linking someOCPs with potential human health effects we endeavor todemonstrate that routine blood testing for OCPs may beinadequate for biomonitoring body burdens and we provideevidence that transdermal depuration through perspirationfacilitates elimination of various OCP compounds

2 Background

OCPs are lipophilic contact insecticides they have lowvapour pressures and slow rates of environmental degrada-tion These properties make them highly penetrable longlasting and extremely effective pesticide agents [13] Theseproperties also contribute to bioaccumulation within thehuman organism by the ready absorption into the body andsubsequent deposition into adipose tissue Like medicationsthe toxicity of OCPs is related to pharmacokinetics bioavail-ability and the molecular topology which is in turn relatedto their molecular size volatility and lipophilicity Thesefactors determine the absorption distribution metabolismexcretion and toxicity (ADMET) of each chemical agentAdditionally toxicity also depends on the age nutritionalstatus and innate detoxification capacity of the host aswell as the frequency intensity and nature of the toxicexposures [14] Based on their chemical structures OCPscan be grouped into 6 categories (Table 1) Similar chemicalstructures within each group account for the similar chemicalproperties and comparable ADMET outcomes

Uptake of OCPs into the human body may occur byingestion by inhalation by vertical transmission or bytransdermal mechanisms In addition exposure to OCPsin combination with other pollutants like inorganic toxicelements may facilitate an additive or synergistic effect [15]An interesting study of 702 adults over the age of 70 yearsfor example reported significantly higher mortality levels insmokers in the 2nd or 3rd tertile of OCP blood levels but notamong smokers in the lowest tertile of exposure [16]

In clinical practice patients presenting with the sequelaeof toxicant exposures are often challenging andmisdiagnosedas ldquothey will seldom present with a history of toxic exposuretheir symptoms are multisystem and multifactorial and thefindings of the physical exammay provide little confirmationof the intakerdquo [17] Additionally there is limited researchon the full long-term impact of OCPs and other accruedtoxicants within the human body As a result of the unfoldinghealth problems associated with bioaccumulation of adverseagents [18 19] and the likelihood of vertical transmission[20] and potential transgenerational impact [21] howeverthere is emerging attention to the development of effectiveinterventions to facilitate elimination of toxic compounds[6 22]

To date it has been realized that organochlorine insecti-cides exert pathobiological impact including carcinogenicityneurotoxicity hormone disruption and other toxic effects[5 23ndash28] Some studies have linked OCP exposure tosignificantly higher rates of cancers of the breast livertesticles and lung as well as sarcoma and non-Hodgkinrsquoslymphoma [26 29] OCP exposure has also been linked tohigher rates of endometriosis in women [28] and increasedrisk for diabetes and obesity [30ndash32] as well as higher risk forneurological disorders like Parkinsonrsquos disease [33 34] Stud-ies with children and adolescents have linked OCP exposureto neurological and psychiatric sequelae including abnormalreflexes reduced cognitive development depression andbehavioral problems [35] The potential to prevent andortreat such conditions by identifying individuals with a body

BioMed Research International 3

burden of these chemical agents and then treating them tofacilitate elimination of their accrued load of toxicants isworthy of exploration and further research

21 Biochemical and Pathophysiological Mechanisms of HarmAlthough designed as acute neurotoxins OCPs have beenfound to dysregulate human metabolic processes throughseveral different pathways These pathophysiological mech-anisms include mitochondrial damage [24 36] oxidativestress [37] cell death [38] endocrine disruption [39] andepigenetic modification [40 41] As discussed there is alsoevidence that concomitant contamination with OCPs alongwith other toxic chemical agents may exhibit synergisticeffects [15]

Additionally OCPs also exhibit synaptic dysregulation byaltering the cation channels (eg sodium) at the synapse innerve cells [42] Although this effect establishes their efficacyagainst insect pests the similarity between organismal synap-tic cation channels between species results in nonspecificityand inadvertent harm to nontarget organisms [43] Anotherpotential pathway of harm is the recently established mech-anism entitled ldquotoxicant induced loss of tolerancerdquo (TILT)[44] This pathophysiologic mechanism resulting in humanmultimorbidity is characterized by a toxicant burden (egpersistent OCPs) resulting in impaired tolerance and hyper-sensitivity [45]When triggered by an antigenic incident fromthe environment (eg pollen chemical agent or food) animmune response ensues potentially producing antibodiesand proinflammatory cytokines A multisystem responseresulting in a condition entitled ldquoSensitivity Related Illnessrdquo(SRI) is often the result [44] Unfolding research continuesto expound on various pathophysiological mechanisms ofdamage to the human organism

22 Human Exposure There is mounting evidence that indi-viduals and population groups are currently being exposed toa multitude of different types of chemical toxicants some ofwhich may accrue within the body The Centers for DiseaseControl for example recently released a study confirmingaccrual of multiple pollutants in most American adults andchildren [46] In a similar nation-wide epidemiological studyin Canada Health Canada also reported on an assortment ofstockpiled chemical toxicants within the general population[47]

An issue of particular concern is fetal and early lifeexposure to xenobiotics at critical times of development asa result of maternal exposure and bioaccumulation [48]Although OCPs were not specifically measured a recentcord-blood study revealed an accumulation of various tox-icants in neonates at birth [49] Studies on OCPs withinlactating women have confirmed OCP levels in some womenthat exceed Health Canadarsquos tolerable daily intake (TDI)guidelines [50]The potential clinical sequelae of such accrualwithin reproductive-aged women can be seen for examplein a large observational study examining specific OCP expo-sures (dicofol and endosulfan) [51] This research suggestsa correlation of increased risk of autistic spectrum disorderbased on the distance between maternal residence and thelocation of pesticide application [51] Such emerging work

on gestational and lactational exposures led to the recentldquoSpecial Communicationrdquo by the International Federationof Obstetrics and Gynecology [20] (an organization whichoversees much of the maternity care throughout the world)in an effort to bring global attention to the reality ofwidespread vertical transmission of toxicants and the myriadpediatric health problems resulting frommaternal xenobioticpollution

Although restrictive policies have been implemented forOCP usage in many jurisdictions these agents continue tobe found within individuals and population groups Thisis as discussed due to continued usage in some areas ofthe world vertical transmission to offspring and persistencewithin the human organism Why do they persist FollowingexposureOCP compounds are dechlorinated and conjugatedin the liver where biliary excretion is the main mechanismfor elimination However organochlorine compounds arereabsorbed to some degree in the enterohepatic circulationand this recycling phenomenon accounts for the persistencewithin the human body [52]

As a result of such persistence and the lipophilic natureof OCPs these chemical agents tend to store and bioaccu-mulate in adipose tissues Although the complete range oftoxicity relating to OCP exposure and bioaccumulation isnot fully understood and remains somewhat controversialmany adverse sequelae have been linked to exposure to suchagents as previously mentioned Accordingly interventionsare required to assist in facilitating elimination of OCPsin order to prevent or overcome adverse clinical sequelaeresulting from the potential physiological disruption causedby the enduring presence of these toxicants

Thus far there has been limited work on interventionsto facilitate elimination of OCPs [7 52ndash55] Schnare etal examined the use of induced perspiration as a meansto expedite elimination of PCBs PBBs and OCPs [56]Their work confirmed that enhancedmobilization and excre-tion via induced perspiration reduced the body burden ofhexachlorobenzene (HCB) and 10 polychlorinated biphenylcongeners [57] Removal of organochlorine compounds hasalso been facilitated by specific interventions which interruptthe enterohepatic circulation [7 52 58]Themain purpose ofthis study is to determine whether induced perspiration canbe used clinically to facilitate decorporation of the range ofboth parent OCPs as well as their metabolites

3 Materials and Methods

31 Participant Recruitment Nine males and 11 females withmean ages of 445 plusmn 144 years and 456 plusmn 103 yearsrespectively were recruited to participate in this study afterappropriate ethical approval was received from the HealthResearch Ethics Board of the University of Alberta 10 partic-ipants were patients with various clinical conditions and 10were otherwise healthy adults Participants with health issueswere recruited from the first authorrsquos clinical practice byinvitation and both healthy and sick individuals were selectedas samples of convenience by availability desire to participateand ease of contact Each participant in the study providedinformed consent and volunteered to give one 200mL

4 BioMed Research International

Table 2 Participant demographics and general clinical characteristics

Participant Gender Age Clinical diagnosis Technique used for sweat collection1 M 61 Diabetes obesity hypertension Exercise2 F 40 Rheumatoid arthritis Steam sauna3 M 38 Addiction disorder Steam sauna4 F 25 Bipolar disorder Steam sauna5 F 47 Lymphoma Steam sauna6 F 43 Fibromyalgia Steam sauna7 F 48 Depression Steam sauna8 F 40 Chronic fatigue Infrared sauna9 F 68 Diabetes fatigue obesity Steam sauna10 M 49 Chronic pain cognitive decline Exercise11 M 53 Healthy Exercise12 M 23 Healthy Infrared sauna13 M 21 Healthy Infrared sauna14 F 47 Healthy Infrared sauna15 M 53 Healthy Infrared sauna16 F 43 Healthy Infrared sauna17 F 51 Healthy Infrared sauna18 M 46 Healthy Infrared sauna19 M 57 Healthy Infrared sauna20 F 50 Healthy Infrared sauna

random sample of blood one sample of first morning urineand one 100mL sample of sweat Demographic and clinicalcharacteristics of all research participants are provided inTable 2

32 Samples Collection All blood samples were collected atoneDynaLIFE laboratory site in EdmontonAlberta Canadawith vacutainer blood collection equipment (BD VacutainerFranklin Lakes NJ 07417 USA) using 21-gauge stainlesssteel needles which were screwed into the ldquoBD VacutainerOne-Use Holderrdquo (REF 364815) The 10mL glass vacutainerwas directly inserted into the holder and into the backend of the needle This process and the use of glass bloodcollection tubes were used to prevent contamination Bloodwas collected directly into plain 10 mL glass vacutainer tubesallowed to clot and after 30 minutes were centrifuged for 10minutes at 2000 revolutions per minute (RPM) After serumwas separated off sampleswere picked up byALS laboratories(about 3 kilometres from the blood collection site) for storagepending analysisWhen received at ALS serum samples weretransferred to 4mLglass vials and stored in a freezer atminus20∘Cpending transfer to the analytical laboratory

For urine collection participants were instructed tocollect a first morning midstream urine sample directly intoa provided 500mL glass jar container with Teflon-lined lidon the same day that blood samples were collected Urinesamples were delivered by the participants directly to ALSlaboratories Edmonton Samples were transferred to 4 mLglass vials and stored in a freezer at minus20∘C pending transfer

For sweat collection participants were instructed tocollect perspiration from any site on their body directly intothe provided 500mL glass jar container with Teflon-lined

lid by placing the jar against their prewashed skin (withtoxicant-free soap water and nonplastic brush)when activelysweating or by using a stainless steel spatula against their skinto transfer perspiration directly into the glass jar Stainlesssteel made up primarily of iron chromium and nickel waschosen as it is the same material as the needles used instandard blood collections and is reported not to off-gasor leach at room or body temperature All but one of theparticipants (1920) provided 100mL of sweat Each of theglass bottles used for sampling in this study was provided byALS laboratories and had undergone extensive cleaning andrinsing The containers were deemed appropriate for sweatcollection with negligible risk of contamination laboratory-grade phosphate-free detergent wash acid rinse multiple hotand cold deionized water rinses oven dried capped andpacked in quality-controlled conditions

Sweat was collected within 1 week before or after collect-ing the blood and urine samples No specifications were givenas to how long sweating had commenced before collection10 participants collected sweat inside a dry infrared sauna7 collected sweat inside a steam sauna and 3 collectedsweat during and immediately after exercise no specificinstruction was given regarding the type or location ofexercise Participants were educated about the research andwere asked to meticulously avoid exposure to any potentialsources of toxicants around the time of collection Sweat wasdelivered by the participants directly to ALS laboratoriesSamples were transferred to 4mL glass vials and stored ina freezer at minus20∘C pending analysis No preservatives wereused in the jars provided for sweat and urine collection norin the serum storage vials

BioMed Research International 5

Table 3 Organochlorine pesticides analyzed

Group Parent Metabolite

DDT and analogues DDTMethoxychlor

DDE DDDNA

Hexachlorobenzene Hexachlorobenzene NA

Hexachlorocyclohexane 120572-BHC 120573-BHC 120575-BHC and120574-BHC NA

Cyclodiene

Endosulfan I endosulfan II Endosulfan sulfateAldrin Dieldrin

Endrin Endrin ketoneEndrin aldehyde

Heptachlor Heptachlor epoxidecis-chlordane trans-chlordane trans-nonachlor

Chlordeconelowast Kelevanlowast and Mirex Mirex NAToxaphenelowastlowastDid not test for this specific compound in this study

33 Laboratory Method Description Of the 6 categories ofOCPs 5 were analyzed (Table 3 toxaphene was not includedin this study) Organochlorine pesticide concentrations ofparent and metabolite compounds were analyzed usingdual-column gas chromatography with electron-capturedetectors (GC-ECD) A pair of surrogate standards tetra-chlorometaxylene (TCMX) and decachlorobiphenyl (DCB)were used to monitor the performance of the method

The methodology for determining the selected organo-chlorine pesticides was as follows Serum samples wereweighed into glass tubes (8 g) and 8mL of methanol wasadded to the serum samples Sweat and urine samples wereweighed into glass tubes (5 g) and 5mL of methanol wasadded to each of the samples Serial extraction of the bioactivecompounds was performed on serum sweat and urinesamples 3 times by adding 12mL of an ethyl ether hexanesolution (1 1 vv) and removing the supernatant via centrifu-gation The extract was then put through a sodium sulfatecolumn to dry The resulting extracts were combined andconcentrated to 1mL and put through a 12 g 2 deactivatedflorisil column Florisil was used to eliminate coelutingchlorophenols External standard calibration was used forquantification Method blanks were used to ensure qualitycontrol water and calf serum samples Instrument detectionlimits were determined to be 010 120583gkg Pentachloroni-trobenzene (PCNB) was added to the extracts as an internalstandard and the samples were analyzed by dual-column gaschromatography with electron-capture detectors (DB-5 andDB-1701)

4 Results and Discussion

The results of the study can be found in Tables 4 and 5The parent OCP compounds showed differential detection(Tables 4(a)ndash4(c)) and compounds detected in at least oneparticipantrsquos serum sample include aldrin DDT endosulfan Iand endosulfan II heptachlor mirex hexachlorobenzene 120572-HCH 120573-HCH and 120574-HCH Endrin 120575-HCH and methoxy-chlor were not detected in any of the participantrsquos serum

samples The parent compounds detected in at least oneparticipantrsquos urine sample include aldrin DDT endosulfan Iand endosulfan II endrinmirex 120574-HCH andmethoxychlorHeptachlor 120572-HCH 120573-HCH 120575-HCH and hexachloroben-zene were not detected in any participantrsquos urine sample Allof the parent compounds except the isomers of hexachloro-cyclohexane were detected in at least one participantrsquos sweatsample

The metabolite compounds also showed differentialdetection The metabolite compounds detected in at leastone participantrsquos serum sample include DDE endrin ketoneendrin aldehyde and heptachlor epoxide The metabolitesDDD endosulfan sulfate and dieldrin were not detected inany serum samples The metabolite compounds detected inat least one participantrsquos sweat sample include DDE DDDendosulfan sulfate dieldrin and endrin ketone Neitherendrin aldehyde nor heptachlor epoxide was detected in anysweat samples The metabolite compounds detected in atleast one participantrsquos urine sample include DDD endosulfansulfate dieldrin endrin aldehyde and heptachlor epoxideThe metabolites DDE and endrin ketone were not detectedin any urine samples

Of the parent compounds DDT methoxychlor andendrin as well as the metabolites DDE DDD and endo-sulfan sulfate appear to be readily excreted into sweat asthey are found in over half of the participants examined(Table 5) Additionally with the exception of DDE theseOCPs were not readily detected in blood testing while stillbeing excreted and identified in sweat This may indicatethat these OCP compounds are stored and sequestered intissues not evident in blood testing but are mobilized andexcreted during perspiration In contrast endosulfan I wasalmost exclusively detected in urine samples of over half ofthe participants (Table 5) Collectively the findings suggestthat these participants have been commonly exposed toDDTmethoxychlor endrin and endosulfan I and are also carryinga body burden of themetabolites DDEDDD and endosulfansulfate

6 BioMed Research International

Table 4 (a) Distribution of parent compounds in serum (SE) sweat (SW) and urine (U) (120583gkg) (b) Distribution of parent compounds inserum (SE) sweat (SW) and urine (U) (120583gkg) (c) Distribution of parent compounds in serum (SE) sweat (SW) and urine (U) (120583gkg)

(a)

SEAldrin

SWAldrin

UAldrin

SEDDT

SWDDT

UDDT

SEEndosulfan

I

SWEndosulfan

I

UEndosulfan

I119899lowast 2 5 2 2 14 3 1 1 13

Meanlowastlowast mdash 015 mdash mdash 049 mdash mdash mdash 014Medianlowastlowast mdash 014 mdash mdash 042 mdash mdash mdash 014Std Devlowastlowast mdash 0028 mdash mdash 023 mdash mdash mdash 0018Range 017ndash066 010ndash017 010ndash015 022ndash023 027ndash11 019ndash039 011 012 012ndash018lowast

119899 represents the number of participants with a detectable amount of the OCP from the 20 total participants examinedlowastlowastFor matrices having fewer than 5 individuals with detectable OCP levels the mean median and standard deviation measurements were not provided

(b)

SEEndrin

SWEndrin

UEndrin

SEHeptachlor

SWHeptachlor

UHeptachlor

SEMirex

SWMirex

UMirex

119899lowast 0 13 1 8 1 0 2 3 2

Meanlowastlowast mdash 018 mdash 037 mdash mdash mdash mdash mdashMedianlowastlowast mdash 015 mdash 033 mdash mdash mdash mdash mdashStd Devlowastlowast mdash 0083 mdash 017 mdash mdash mdash mdash mdashRange mdash 011ndash018 012 015ndash067 011 mdash 012ndash018 010ndash017 011ndash016lowast

119899 represents the number of participants with a detectable amount of the OCP from the 20 total participants examinedlowastlowastFor matrices having fewer than 5 individuals with detectable OCP levels the mean median and standard deviation measurements were not provided

(c)

SEMethoxychlor

SWMethoxychlor

UMethoxychlor

SEHexachlorobenzene

SWHexachlorobenzene

UHexachlorobenzene

119899lowast 0 16 3 6 1 0

Meanlowastlowast mdash 026 mdash 029 mdash mdashMedianlowastlowast mdash 022 mdash 030 mdash mdashStd Devlowastlowast mdash 013 mdash 011 mdash mdashRange mdash 013ndash070 014ndash019 018ndash049 011 mdashlowast

119899 represents the number of participants with a detectable amount of the OCP from the 20 total participants examinedlowastlowastFor matrices having fewer than 5 individuals with detectable OCP levels the mean median and standard deviation measurements were not provided

Most of the compounds examined were detected inless than half of the participants regardless of the matrix(Table 5) This likely reflects a reduced exposure level tothese compounds However hexachlorobenzene heptachlorand endrin ketone were detected in at least 30 of par-ticipants and were all predominantly detected in serumsamples (Table 5) Although some compounds were detectedin participant urine these levels typically occurred aroundthe limit of detection and at much lower levels than eitherserum or sweat analysis With the exception of endosulfan Ithis suggests that urine analysis is not reliable as an analytictool to measure the body burden of these compounds

The partitioning of these compounds in the body seemsto be related to their lipophilicity With the exception ofendosulfan I and its metabolite endosulfan sulfate all of thecompounds detected in over half of the participants havelog119870ow values above 5 (Table 6) This indicates that they arehighly lipophilic and fat soluble and are expected to sequesterin fat tissue In comparison to the compounds found

predominantly in sweat hexachlorobenzene and heptachlorhave reportedly similar degrees of lipophilicity but werepredominantly found in blood (Tables 4(a)ndash4(c)) Thereforethese findings may suggest that lipophilicity is not the onlyfactor affecting the partitioning of these compounds

There are limitations to the study and to interpretationof the results There has been discussion in lay circles thatdiffering means of thermal depuration by varying types ofsauna (such as infrared sauna versus steam sauna) exerciseor other perspiration induction activities may result indifferences in excretion rates through skinThis study did nothave an adequate data set to control for potential differencesin the excretion of the range of OCPs between usages of far-infrared sauna regular sauna or exercise Several other issuesmay impact the reliability and reproducibility of perspirationanalysis that were not considered including body site ofsampling timing of collection while perspiring differencesin skin characteristics between individuals temperature andhumidity of the surroundings and factors such as diet

BioMed Research International 7

Table 5 Percentage of individuals with detection of organochlorinepesticides within serum sweat and urine (119899 = 20)

Serum Sweat Urine441015840-DDT 10 70 15441015840-DDE 95 70 0441015840-DDD 0 65 35Methoxychlor 0 80 15Endosulfan I 5 5 65Endosulfan sulfate 0 85 10Endrin 0 50 5Aldrin 10 25 10Dieldrin 0 15 10trans-nonachlor 0 5 0BHC (hexachlorobenzene) 30 5 0120572-BHC 10 0 0120573-BHC 15 0 0120575-BHC 0 0 0120574-BHC 1 0 1Endosulfan II 10 10 5Endrin ketone 35 5 0Endrin aldehyde 5 0 5Heptachlor epoxide 5 0 15Heptachlor 40 5 0cis-chlordane 5 5 0trans-chlordane 10 15 10Mirex 5 15 15

pharmaceutical intake and supplement use Accordinglyattempts to accurately quantify the relative amount of toxi-cants released into perspiration are limited

Areas for future research in relation to induced perspi-ration might include an examination of (i) differences inrates of excretion into perspiration of assorted xenobioticsfrom diverse sites in the body (ii) whether there is diurnalvariation in the toxicant content of perspiration (iii) whetherhydration status affects the xenobiotic concentration of per-spiration (iv) dermal reabsorption potential of toxicants afterperspiration and (v) the release of xenobiotics in those infasting states compared to those without caloric restriction

5 Conclusion

As DDT DDE DDD methoxychlor endosulfan sulfate andendrin appear to be readily excreted into sweat inducedperspiration appears to be a potential clinical tool to diminishthe body burden of these agents With the exception ofDDE however these agents are not readily detected in bloodtesting This suggests that common blood analysis may nottruly represent the body burden of these compounds Asthe routine use of unprovoked blood testing may thus beinadequate for biomonitoring body burdens of OCPs theremay be clinical advantages to the induction of perspirationthrough methods like sauna andor exercise in order tocollect samples for biomonitoring and diagnosis of manyretained OCP compounds

Table 6 Octanolwater partition coefficient of key OCPs [65ndash70]

Compound log119870owAldrin 650Endrin 52Endosulfan I 383Endosulfate 366pp1015840-DDT 691pp1015840-DDE 651pp1015840-DDD 602Methoxychlor 508Heptachlor 610Hexachlorobenzene 573

In conclusion the previous four papers in this ldquobloodurine and sweat (BUS)rdquo series have demonstrated thatinduced perspiration is effective at facilitating the removal ofmany toxic elements as well as various organic compoundsbut not all [59ndash62] This OCP study provides evidence thattransdermal depuration through perspiration facilitates elim-ination of some parent and metabolite OCP compounds butnot all While the absolute amount of each OCP compoundreleased into sweat may be small according to this data anaverage adult may sweat more than one liter per hour duringexerciseUnder thermal stressmaximal rates of sweatingmaybe as high as two to four litershour [63] and sweating ratesfor ldquoacclimatizedrdquo people who regularly use saunas may be ashigh as two litershour [64] Accordingly regular sessions ofinduced perspiration should be considered cumulatively as apotential clinical modality to diminish body burdens ofmanyxenobiotics including OCP compounds

Additional Points

Key Findings

(a) DDT andor its metabolite(s) were found in nearlyevery participant regardless of age suggesting thatexposure is very common

(b) Nearly all organochlorine pesticide (OCP) parentcompounds and several metabolites were detected inperspiration suggesting that sweating may be effica-cious in diminishing the body burden of many ofthese toxicants

(c) There were some parent OCPs such as endosulfan Iand hexachlorobenzene and some metabolites suchas endrin ketone and heptachlor that were not readilyexcreted into perspiration

(d) Lipophilicity appeared to be a major factor influenc-ing the efficacy of transdermal OCP elimination butnot the exclusive determinant

(e) Only endosulfan I appeared to be predominantlydetected in urine suggesting that urine analysis haslimited value in detection of retained OCPs

8 BioMed Research International

Competing Interests

There is no conflict of interests regarding the publication ofthis paper

Acknowledgments

Thanks are due to Dr Peter Mahaffy and the Departmentof Chemistry at The Kingrsquos University for their thoughtfulassistance in this work

References

[1] Nobelprizeorg the official web site of the Nobel PrizePaul MullermdashBiographical httpwwwnobelprizeorgnobelprizesmedicinelaureates1948muller-biohtml

[2] K I Barnes D N Durrheim F Little et al ldquoEffect ofartemether-lumefantrine policy and improved vector controlon malaria burden in KwaZulu-Natal South Africardquo PLoSMedicine vol 2 no 11 article e330 2005

[3] United States Environmental Protection Agency ldquoDDT A briefhistory and statusrdquo 2016 httpswwwepagovingredients-used-pesticide-productsddt-brief-history-and-status

[4] United Nations Environment Programme Stockholm Conven-tion Protecting health and the environment from persistentorganic pollutants httpchmpopsintdefaultaspx

[5] S MWaliszewski A A Aguirre R M Infanzon and J SiliceoldquoCarry-over of persistent organochlorine pesticides throughplacenta to fetusrdquo Salud Publica de Mexico vol 42 no 5 pp384ndash390 2000

[6] S J Genuis ldquoElimination of persistent toxicants from thehuman bodyrdquo Human amp Experimental Toxicology vol 30 no1 pp 3ndash18 2010

[7] R E Herron and J B Fagan ldquoLipophil-mediated reduction oftoxicants in humans an evaluation of an ayurvedic detoxifica-tion procedurerdquo Alternative Therapies in Health and Medicinevol 8 no 5 pp 40ndash51 2002

[8] S J Genuis M E Sears G Schwalfenberg J Hope andR Bernhoft ldquoClinical detoxification elimination of persistenttoxicants from the human bodyrdquo The Scientific World Journalvol 2013 Article ID 238347 3 pages 2013

[9] S L Archibeque-Engle J D Tessari D T Winn T J KeefeT M Nett and T Zheng ldquoComparison of organochlorinepesticide and polychlorinated biphenyl residues in humanbreast adipose tissue and serumrdquo Journal of Toxicology andEnvironmental Health vol 52 no 4 pp 285ndash293 1997

[10] S J Genuis andK L Kelln ldquoToxicant exposure and bioaccumu-lation a common and potentially reversible cause of cognitivedysfunction and dementiardquo Behavioural Neurology vol 2015Article ID 620143 10 pages 2015

[11] T G Redgrave P Wallace R J Jandacek and P Tso ldquoTreat-ment with a dietary fat substitute decreased Arochlor 1254contamination in an obese diabetic malerdquo Journal of NutritionalBiochemistry vol 16 no 6 pp 383ndash384 2005

[12] G H Ross and M C Sternquist ldquoMethamphetamine exposureand chronic illness in police officers significant improvementwith sauna-based detoxification therapyrdquo Toxicology and Indus-trial Health vol 28 no 8 pp 758ndash768 2012

[13] P Williams R James and S Roberts Principles of ToxicologyJohn Wiley amp Sons New York NY USA 2000

[14] A K Pramanik and R C Hansen ldquoTranscutaneous gammabenzene hexachloride absorption and toxicity in infants andchildrenrdquo Archives of Dermatology vol 115 no 10 pp 1224ndash1225 1979

[15] V N Uversky J Li K Bower and A L Fink ldquoSynergisticeffects of pesticides andmetals on the fibrillation of120572-synucleinimplications for Parkinsonrsquos diseaserdquo NeuroToxicology vol 23no 4-5 pp 527ndash536 2002

[16] Y-M Lee S-G Bae S-H Lee D R Jacobs Jr and D-H LeeldquoAssociations between cigarette smoking and total mortalitydiffer depending on serum concentrations of persistent organicpollutants among the elderlyrdquo Journal of KoreanMedical Sciencevol 28 no 8 pp 1122ndash1128 2013

[17] P Bennett ldquoWorking Up the Toxic Patientrdquo httpwwwpeter-bennettcomresourcesdetoxificationworkingupthedetoxpa-tientpdf

[18] S J Genuis ldquoThe chemical erosion of human health adverseenvironmental exposure and in-utero pollutionmdashdeterminantsof congenital disorders and chronic diseaserdquo Journal of PerinatalMedicine vol 34 no 3 pp 185ndash195 2006

[19] E R Kabir M S Rahman and I Rahman ldquoA review onendocrine disruptors and their possible impacts on humanhealthrdquo Environmental Toxicology and Pharmacology vol 40no 1 pp 241ndash258 2015

[20] G C Di Renzo J A Conry J Blake et al ldquoInternational Fed-eration of Gynecology and Obstetrics opinion on reproductivehealth impacts of exposure to toxic environmental chemicalsrdquoInternational Journal of Gynecology amp Obstetrics vol 131 no 3pp 219ndash225 2015

[21] M K Skinner M Manikkam and C Guerrero-BosagnaldquoEpigenetic transgenerational actions of endocrine disruptorsrdquoReproductive Toxicology vol 31 no 3 pp 337ndash343 2011

[22] M E Sears and S J Genuis ldquoEnvironmental determinants ofchronic disease and medical approaches recognition avoid-ance supportive therapy and detoxificationrdquo Journal of Envi-ronmental and Public Health vol 2012 Article ID 356798 15pages 2012

[23] T M Crisp E D Clegg R L Cooper et al ldquoEnvironmentalendocrine disruption an effects assessment and analysisrdquo Envi-ronmental Health Perspectives vol 106 supplement 1 pp 11ndash561998

[24] M E A Benarbia D Macherel S Faure C Jacques R Andri-antsitohaina and Y Malthiery ldquoPlasmatic concentration oforganochlorine lindane acts as metabolic disruptors in HepG2liver cell line by inducing mitochondrial disorderrdquo Toxicologyand Applied Pharmacology vol 272 no 2 pp 325ndash334 2013

[25] C Charlier A Albert P Herman et al ldquoBreast cancer andserum organochlorine residuesrdquo Occupational and Environ-mental Medicine vol 60 no 5 pp 348ndash351 2003

[26] J Dich S H Zahm A Hanberg and H-O Adami ldquoPesticidesand cancerrdquo Cancer Causes and Control vol 8 no 3 pp 420ndash443 1997

[27] S Yasunaga KNishi S Nishimoto andT Sugahara ldquoMethoxy-chlor enhances degranulation ofmurinemast cells by regulatingFc120576RI-mediated signal transductionrdquo Journal of Immunotoxicol-ogy vol 12 no 3 pp 283ndash289 2015

[28] K Upson A J De Roos M L Thompson et al ldquoOrganochlo-rine pesticides and risk of endometriosis findings from apopulation-based case-control studyrdquo Environmental HealthPerspectives vol 121 no 11-12 pp 1319ndash1324 2013

[29] K A McGlynn S M Quraishi B I Graubard J-P Weber MV Rubertone and R L Erickson ldquoPersistent organochlorine

BioMed Research International 9

pesticides and risk of testicular germ cell tumorsrdquo Journal of theNational Cancer Institute vol 100 no 9 pp 663ndash671 2008

[30] D H Lee M W Steffes A Sjodin R S Jones L L Needhamand D R Jacobs Jr ldquoLow dose organochlorine pesticides andpolychlorinated biphenyls predict obesity dyslipidemia andinsulin resistance among people free of diabetesrdquo PLoS ONEvol 6 no 1 Article ID e15977 2011

[31] M Turyk H Anderson L Knobeloch P Imm and V PerskyldquoOrganochlorine exposure and incidence of diabetes in a cohortof great lakes sport fish consumersrdquo Environmental HealthPerspectives vol 117 no 7 pp 1076ndash1082 2009

[32] H K Son S A Kim J H Kang et al ldquoStrong associationsbetween low-dose organochlorine pesticides and type 2 dia-betes in Koreardquo Environment International vol 36 no 5 pp410ndash414 2010

[33] L Fleming J B Mann J Bean T Briggle and J R Sanchez-Ramos ldquoParkinsonrsquos disease and brain levels of organochlorinepesticidesrdquoAnnals of Neurology vol 36 no 1 pp 100ndash103 1994

[34] H J Heusinkveld and R H S Westerink ldquoOrganochlorineinsecticides lindane and dieldrin and their binary mixturedisturb calcium homeostasis in dopaminergic PC12 cellsrdquoEnvironmental Science and Technology vol 46 no 3 pp 1842ndash1848 2012

[35] J Jurewicz and W Hanke ldquoPrenatal and childhood exposureto pesticides and neurobehavioral development review ofepidemiological studiesrdquo International Journal of OccupationalMedicine and Environmental Health vol 21 no 2 pp 121ndash1322008

[36] E A Belyaeva T V Sokolova L V Emelyanova and I OZakharova ldquoMitochondrial electron transport chain in heavymetal-induced neurotoxicity effects of cadmium mercury andcopperrdquo The Scientific World Journal vol 2012 Article ID136063 14 pages 2012

[37] R Pathak S G Suke T Ahmed et al ldquoOrganochlorinepesticide residue levels and oxidative stress in preterm deliverycasesrdquoHumanampExperimental Toxicology vol 29 no 5 pp 351ndash358 2010

[38] M Zhao Y Zhang C Wang Z Fu W Liu and J GanldquoInduction of macrophage apoptosis by an organochlorineinsecticide acetofenaterdquo Chemical Research in Toxicology vol22 no 3 pp 504ndash510 2009

[39] W Mnif A I Hassine A Bouaziz A Bartegi O Thomas andB Roig ldquoEffect of endocrine disruptor pesticides a reviewrdquoInternational Journal of Environmental Research and PublicHealth vol 8 no 6 pp 2265ndash2303 2011

[40] L Hou X Zhang D Wang and A Baccarelli ldquoEnvironmentalchemical exposures and human epigeneticsrdquo International Jour-nal of Epidemiology vol 41 no 1 pp 79ndash105 2012

[41] G M Williams ldquoGenotoxic and epigenetic carcinogens theiridentification and significancerdquo Annals of the New YorkAcademy of Sciences vol 407 no 1 pp 328ndash333 1983

[42] B Hille ldquoPharmacological modifications of the sodium chan-nels of frog nerverdquo The Journal of General Physiology vol 51no 2 pp 199ndash219 1968

[43] S Gilbert A Small Dose of Toxicology CRC Press Boca RatonFla USA 2004

[44] S J Genuis ldquoSensitivity-related illness the escalating pandemicof allergy food intolerance and chemical sensitivityrdquoTheScienceof the Total Environment vol 408 no 24 pp 6047ndash6061 2010

[45] S J Genuis ldquoPandemic of idiopathic multimorbidityrdquo Cana-dian Family Physician vol 60 no 6 pp 511ndash514 2014

[46] Centers for Disease Control and Prevention Department ofHealth and Human Services Fourth National Report on HumanExposure to Environmental Chemicals CDC Atlanta Ga USA2013 httpwwwcdcgovexposurereportpdfFourthReportUpdatedTables Mar2013pdf

[47] Health Canada ldquoHuman biomonitoring of environmentalchemicalsrdquo 2015 httpwwwhealthcanadagccabiomoni-toring

[48] S J Genuis and R A Genuis ldquoPreconception care a newstandard of care within maternal health servicesrdquo BioMedResearch International vol 2016 Article ID 6150976 30 pages2016

[49] Environmental Working Group BPA and Other Cord BloodPollutants 2016 httpwwwewgorgresearchminority-cord-blood-reportbpa-and-other-cord-blood-pollutants

[50] A Sudaryanto T Kunisue N Kajiwara et al ldquoSpecific accumu-lation of organochlorines in human breastmilk from Indonesialevels distribution accumulation kinetics and infant healthriskrdquo Environmental Pollution vol 139 no 1 pp 107ndash117 2006

[51] E M Roberts P B English J K Grether G C Windham LSomberg and C Wolff ldquoMaternal residence near agriculturalpesticide applications and autism spectrum disorders amongchildren in the California Central Valleyrdquo Environmental HealthPerspectives vol 115 no 10 pp 1482ndash1489 2007

[52] R J Jandacek and S J Genuis ldquoAn assessment of the intestinallumen as a site for intervention in reducing body burdens oforganochlorine compoundsrdquo The Scientific World Journal vol2013 Article ID 205621 10 pages 2013

[53] W J Cohn J J Boylan R V Blanke M W Fariss J R Howelland P S Guzelian ldquoTreatment of chlordecone (Kepone) toxicitywith cholestyramine Results of a controlled clinical trialrdquo TheNew England Journal of Medicine vol 298 no 5 pp 243ndash2481978

[54] Y Mochida H Fukata Y Matsuno and C Mori ldquoReduction ofdioxins and polychlorinated biphenyls (PCBs) in human bodyrdquoFukuoka Igaku Zasshi vol 98 no 4 pp 106ndash113 2007

[55] K Rozman L Ballhorn and T Rozman ldquoMineral oil in the dietenhances fecal excretion of DDT in the rhesus monkeyrdquo Drugand Chemical Toxicology vol 6 no 3 pp 311ndash316 1983

[56] D W Schnare M Ben and M G Shields ldquoBody burdenreduction of PCBs PBBs and chlorinated pesticides in humansubjectsrdquo Ambio vol 13 pp 378ndash380 1984

[57] D W Schnare and P C Robinson ldquoReduction of human bodyburdens of hexachlorobenzene and polychlorinated biphenylsrdquoin Hexachlorobenzene Proceedings of an International Sym-posium C R Morris and J R P Cabral Eds pp 597ndash603International Agency for Research on Cancer Lyon France1986

[58] R J Jandacek and P Tso ldquoEnterohepatic circulation oforganochlorine compounds a site for nutritional interventionrdquoThe Journal of Nutritional Biochemistry vol 18 no 3 pp 163ndash167 2007

[59] S J Genuis D Birkholz I Rodushkin and S Beesoon ldquoBloodurine and sweat (BUS) study monitoring and eliminationof bioaccumulated toxic elementsrdquo Archives of EnvironmentalContamination and Toxicology vol 61 no 2 pp 344ndash357 2011

[60] S J Genuis S Beesoon R A Lobo and D Birkholz ldquoHumanelimination of phthalate compounds blood urine and sweat(BUS) studyrdquoThe Scientific World Journal vol 2012 Article ID615068 10 pages 2012

[61] S J Genuis S Beesoon and D Birkholz ldquoBiomonitoring andelimination of perfluorinated compounds and polychlorinated

10 BioMed Research International

biphenyls through perspiration blood urine and sweat studyrdquoISRN Toxicology vol 2013 Article ID 483832 7 pages 2013

[62] S J Genuis S Beesoon D Birkholz and R A Lobo ldquoHumanexcretion of bisphenol a blood urine and sweat (BUS) StudyrdquoJournal of Environmental and Public Health vol 2012 Article ID185731 10 pages 2012

[63] U W R Greger Comprehensive Human Physiology FromCellularMechanisms to Integration Springer Science ampBusinessMedia 2013

[64] A Eisalo and O J Luurila ldquoThe Finnish sauna and cardiovas-cular diseasesrdquo Annals of Clinical Research vol 20 no 4 pp267ndash270 1988

[65] J De Bruijn F Busser W Seinen and J Hermens ldquoDetermi-nation of octanolwater partition coefficients for hydrophobicorganic chemicals with the lsquoslow-stirringrsquo methodrdquo Environ-mental Toxicology andChemistry vol 8 no 6 pp 499ndash512 1989

[66] W de Wolf W Seinen and J L M Hermens ldquoBiotransforma-tion and toxicokinetics of trichloroanilines in fish in relation totheir hydrophobicityrdquoArchives of Environmental Contaminationand Toxicology vol 25 no 1 pp 110ndash117 1993

[67] C L A Hansch and D Hoekman Exploring QSAR AmericanChemical Society Washington DC USA 1995

[68] P H Howard and W M Meylan Handbook of Physical Prop-erties of Organic Chemicals Lewis Publishers Boca Raton FlaUSA 1997

[69] R H G Lewis Hawleyrsquos Condensed Chemical Dictionary JohnWiley amp Sons Hoboken NJ USA 15th edition 2007

[70] C D Simpson R J Wilcock T J Smith A L Wilkinsand A G Langdon ldquoDetermination of octanol-water partitioncoefficients for the major components of technical chlordanerdquoBulletin of Environmental Contamination and Toxicology vol55 no 1 pp 149ndash153 1995

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

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AntibioticsInternational Journal of

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StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

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Advances in Pharmacological Sciences

Tropical MedicineJournal of

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Medicinal ChemistryInternational Journal of

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BioMed Research International

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Autoimmune Diseases

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Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Page 2: Research Article Human Elimination of Organochlorine

2 BioMed Research International

Table 1 Organochlorine pesticide groupings based on chemicalstructure

Group Constituents

(i) DDT and analogues

DDTDDEDDDMethoxychlor

(ii) Hexachlorobenzene Hexachlorobenzene

(iii) Hexachlorocyclohexane 120572-HCH 120573-HCH 120575-HCH and120574-HCH

(iv) Cyclodiene

Endosulfan I and endosulfan IIHeptachlorAldrinDieldrinEndrin

(v) Chlordecone Kelevan andMirex

Chlordecone Kelevan andMirex

(vi) Toxaphene Toxaphene

where OCPs are still used (iv) the global exchange ofpotentially contaminated foodstuffs originating from juris-dictions where OCPs are still used and (v) the potential forvertical transmission of OCPs from contaminated mothersto offspring during pregnancy and lactation [5] As a resultOCPs continue to be found in individuals and populationgroups including infant children Individuals contaminatedwith OCP compounds remain at risk for adverse healthconsequences and some will potentially pass on these agentsto subsequent generations through vertical transmission

From a clinical perspective the question remains abouthow to assess and manage people who have health issuesrelated to xenobiotic contamination [6ndash8] As many persis-tent toxicants including OCPs can sequester and accrue intissues rather than remaining in the blood compartment [9]biomonitoring for such chemical agents through unprovokedblood and urine analysis does not necessarily reflect theactual body burden of these chemicals [10] Furthermore aspersistent organochlorine compounds have been associatedwith myriad health risks it might be possible to diminish therisk of adverse health sequelae and transgenerational spreadof OCPs if means were identified to facilitate elimination ofthese agents from the human body altogether

Existing medical literature suggests that elimination oforganochlorine compounds and other persistent chemicalagents from the human body can have significant clinicalbenefit in ameliorating health problems [10ndash12] Accordinglythe value of establishing interventions to facilitate eliminationof toxic chemical agents is thus apparent In this researchstudy we provide an overview of literature linking someOCPs with potential human health effects we endeavor todemonstrate that routine blood testing for OCPs may beinadequate for biomonitoring body burdens and we provideevidence that transdermal depuration through perspirationfacilitates elimination of various OCP compounds

2 Background

OCPs are lipophilic contact insecticides they have lowvapour pressures and slow rates of environmental degrada-tion These properties make them highly penetrable longlasting and extremely effective pesticide agents [13] Theseproperties also contribute to bioaccumulation within thehuman organism by the ready absorption into the body andsubsequent deposition into adipose tissue Like medicationsthe toxicity of OCPs is related to pharmacokinetics bioavail-ability and the molecular topology which is in turn relatedto their molecular size volatility and lipophilicity Thesefactors determine the absorption distribution metabolismexcretion and toxicity (ADMET) of each chemical agentAdditionally toxicity also depends on the age nutritionalstatus and innate detoxification capacity of the host aswell as the frequency intensity and nature of the toxicexposures [14] Based on their chemical structures OCPscan be grouped into 6 categories (Table 1) Similar chemicalstructures within each group account for the similar chemicalproperties and comparable ADMET outcomes

Uptake of OCPs into the human body may occur byingestion by inhalation by vertical transmission or bytransdermal mechanisms In addition exposure to OCPsin combination with other pollutants like inorganic toxicelements may facilitate an additive or synergistic effect [15]An interesting study of 702 adults over the age of 70 yearsfor example reported significantly higher mortality levels insmokers in the 2nd or 3rd tertile of OCP blood levels but notamong smokers in the lowest tertile of exposure [16]

In clinical practice patients presenting with the sequelaeof toxicant exposures are often challenging andmisdiagnosedas ldquothey will seldom present with a history of toxic exposuretheir symptoms are multisystem and multifactorial and thefindings of the physical exammay provide little confirmationof the intakerdquo [17] Additionally there is limited researchon the full long-term impact of OCPs and other accruedtoxicants within the human body As a result of the unfoldinghealth problems associated with bioaccumulation of adverseagents [18 19] and the likelihood of vertical transmission[20] and potential transgenerational impact [21] howeverthere is emerging attention to the development of effectiveinterventions to facilitate elimination of toxic compounds[6 22]

To date it has been realized that organochlorine insecti-cides exert pathobiological impact including carcinogenicityneurotoxicity hormone disruption and other toxic effects[5 23ndash28] Some studies have linked OCP exposure tosignificantly higher rates of cancers of the breast livertesticles and lung as well as sarcoma and non-Hodgkinrsquoslymphoma [26 29] OCP exposure has also been linked tohigher rates of endometriosis in women [28] and increasedrisk for diabetes and obesity [30ndash32] as well as higher risk forneurological disorders like Parkinsonrsquos disease [33 34] Stud-ies with children and adolescents have linked OCP exposureto neurological and psychiatric sequelae including abnormalreflexes reduced cognitive development depression andbehavioral problems [35] The potential to prevent andortreat such conditions by identifying individuals with a body

BioMed Research International 3

burden of these chemical agents and then treating them tofacilitate elimination of their accrued load of toxicants isworthy of exploration and further research

21 Biochemical and Pathophysiological Mechanisms of HarmAlthough designed as acute neurotoxins OCPs have beenfound to dysregulate human metabolic processes throughseveral different pathways These pathophysiological mech-anisms include mitochondrial damage [24 36] oxidativestress [37] cell death [38] endocrine disruption [39] andepigenetic modification [40 41] As discussed there is alsoevidence that concomitant contamination with OCPs alongwith other toxic chemical agents may exhibit synergisticeffects [15]

Additionally OCPs also exhibit synaptic dysregulation byaltering the cation channels (eg sodium) at the synapse innerve cells [42] Although this effect establishes their efficacyagainst insect pests the similarity between organismal synap-tic cation channels between species results in nonspecificityand inadvertent harm to nontarget organisms [43] Anotherpotential pathway of harm is the recently established mech-anism entitled ldquotoxicant induced loss of tolerancerdquo (TILT)[44] This pathophysiologic mechanism resulting in humanmultimorbidity is characterized by a toxicant burden (egpersistent OCPs) resulting in impaired tolerance and hyper-sensitivity [45]When triggered by an antigenic incident fromthe environment (eg pollen chemical agent or food) animmune response ensues potentially producing antibodiesand proinflammatory cytokines A multisystem responseresulting in a condition entitled ldquoSensitivity Related Illnessrdquo(SRI) is often the result [44] Unfolding research continuesto expound on various pathophysiological mechanisms ofdamage to the human organism

22 Human Exposure There is mounting evidence that indi-viduals and population groups are currently being exposed toa multitude of different types of chemical toxicants some ofwhich may accrue within the body The Centers for DiseaseControl for example recently released a study confirmingaccrual of multiple pollutants in most American adults andchildren [46] In a similar nation-wide epidemiological studyin Canada Health Canada also reported on an assortment ofstockpiled chemical toxicants within the general population[47]

An issue of particular concern is fetal and early lifeexposure to xenobiotics at critical times of development asa result of maternal exposure and bioaccumulation [48]Although OCPs were not specifically measured a recentcord-blood study revealed an accumulation of various tox-icants in neonates at birth [49] Studies on OCPs withinlactating women have confirmed OCP levels in some womenthat exceed Health Canadarsquos tolerable daily intake (TDI)guidelines [50]The potential clinical sequelae of such accrualwithin reproductive-aged women can be seen for examplein a large observational study examining specific OCP expo-sures (dicofol and endosulfan) [51] This research suggestsa correlation of increased risk of autistic spectrum disorderbased on the distance between maternal residence and thelocation of pesticide application [51] Such emerging work

on gestational and lactational exposures led to the recentldquoSpecial Communicationrdquo by the International Federationof Obstetrics and Gynecology [20] (an organization whichoversees much of the maternity care throughout the world)in an effort to bring global attention to the reality ofwidespread vertical transmission of toxicants and the myriadpediatric health problems resulting frommaternal xenobioticpollution

Although restrictive policies have been implemented forOCP usage in many jurisdictions these agents continue tobe found within individuals and population groups Thisis as discussed due to continued usage in some areas ofthe world vertical transmission to offspring and persistencewithin the human organism Why do they persist FollowingexposureOCP compounds are dechlorinated and conjugatedin the liver where biliary excretion is the main mechanismfor elimination However organochlorine compounds arereabsorbed to some degree in the enterohepatic circulationand this recycling phenomenon accounts for the persistencewithin the human body [52]

As a result of such persistence and the lipophilic natureof OCPs these chemical agents tend to store and bioaccu-mulate in adipose tissues Although the complete range oftoxicity relating to OCP exposure and bioaccumulation isnot fully understood and remains somewhat controversialmany adverse sequelae have been linked to exposure to suchagents as previously mentioned Accordingly interventionsare required to assist in facilitating elimination of OCPsin order to prevent or overcome adverse clinical sequelaeresulting from the potential physiological disruption causedby the enduring presence of these toxicants

Thus far there has been limited work on interventionsto facilitate elimination of OCPs [7 52ndash55] Schnare etal examined the use of induced perspiration as a meansto expedite elimination of PCBs PBBs and OCPs [56]Their work confirmed that enhancedmobilization and excre-tion via induced perspiration reduced the body burden ofhexachlorobenzene (HCB) and 10 polychlorinated biphenylcongeners [57] Removal of organochlorine compounds hasalso been facilitated by specific interventions which interruptthe enterohepatic circulation [7 52 58]Themain purpose ofthis study is to determine whether induced perspiration canbe used clinically to facilitate decorporation of the range ofboth parent OCPs as well as their metabolites

3 Materials and Methods

31 Participant Recruitment Nine males and 11 females withmean ages of 445 plusmn 144 years and 456 plusmn 103 yearsrespectively were recruited to participate in this study afterappropriate ethical approval was received from the HealthResearch Ethics Board of the University of Alberta 10 partic-ipants were patients with various clinical conditions and 10were otherwise healthy adults Participants with health issueswere recruited from the first authorrsquos clinical practice byinvitation and both healthy and sick individuals were selectedas samples of convenience by availability desire to participateand ease of contact Each participant in the study providedinformed consent and volunteered to give one 200mL

4 BioMed Research International

Table 2 Participant demographics and general clinical characteristics

Participant Gender Age Clinical diagnosis Technique used for sweat collection1 M 61 Diabetes obesity hypertension Exercise2 F 40 Rheumatoid arthritis Steam sauna3 M 38 Addiction disorder Steam sauna4 F 25 Bipolar disorder Steam sauna5 F 47 Lymphoma Steam sauna6 F 43 Fibromyalgia Steam sauna7 F 48 Depression Steam sauna8 F 40 Chronic fatigue Infrared sauna9 F 68 Diabetes fatigue obesity Steam sauna10 M 49 Chronic pain cognitive decline Exercise11 M 53 Healthy Exercise12 M 23 Healthy Infrared sauna13 M 21 Healthy Infrared sauna14 F 47 Healthy Infrared sauna15 M 53 Healthy Infrared sauna16 F 43 Healthy Infrared sauna17 F 51 Healthy Infrared sauna18 M 46 Healthy Infrared sauna19 M 57 Healthy Infrared sauna20 F 50 Healthy Infrared sauna

random sample of blood one sample of first morning urineand one 100mL sample of sweat Demographic and clinicalcharacteristics of all research participants are provided inTable 2

32 Samples Collection All blood samples were collected atoneDynaLIFE laboratory site in EdmontonAlberta Canadawith vacutainer blood collection equipment (BD VacutainerFranklin Lakes NJ 07417 USA) using 21-gauge stainlesssteel needles which were screwed into the ldquoBD VacutainerOne-Use Holderrdquo (REF 364815) The 10mL glass vacutainerwas directly inserted into the holder and into the backend of the needle This process and the use of glass bloodcollection tubes were used to prevent contamination Bloodwas collected directly into plain 10 mL glass vacutainer tubesallowed to clot and after 30 minutes were centrifuged for 10minutes at 2000 revolutions per minute (RPM) After serumwas separated off sampleswere picked up byALS laboratories(about 3 kilometres from the blood collection site) for storagepending analysisWhen received at ALS serum samples weretransferred to 4mLglass vials and stored in a freezer atminus20∘Cpending transfer to the analytical laboratory

For urine collection participants were instructed tocollect a first morning midstream urine sample directly intoa provided 500mL glass jar container with Teflon-lined lidon the same day that blood samples were collected Urinesamples were delivered by the participants directly to ALSlaboratories Edmonton Samples were transferred to 4 mLglass vials and stored in a freezer at minus20∘C pending transfer

For sweat collection participants were instructed tocollect perspiration from any site on their body directly intothe provided 500mL glass jar container with Teflon-lined

lid by placing the jar against their prewashed skin (withtoxicant-free soap water and nonplastic brush)when activelysweating or by using a stainless steel spatula against their skinto transfer perspiration directly into the glass jar Stainlesssteel made up primarily of iron chromium and nickel waschosen as it is the same material as the needles used instandard blood collections and is reported not to off-gasor leach at room or body temperature All but one of theparticipants (1920) provided 100mL of sweat Each of theglass bottles used for sampling in this study was provided byALS laboratories and had undergone extensive cleaning andrinsing The containers were deemed appropriate for sweatcollection with negligible risk of contamination laboratory-grade phosphate-free detergent wash acid rinse multiple hotand cold deionized water rinses oven dried capped andpacked in quality-controlled conditions

Sweat was collected within 1 week before or after collect-ing the blood and urine samples No specifications were givenas to how long sweating had commenced before collection10 participants collected sweat inside a dry infrared sauna7 collected sweat inside a steam sauna and 3 collectedsweat during and immediately after exercise no specificinstruction was given regarding the type or location ofexercise Participants were educated about the research andwere asked to meticulously avoid exposure to any potentialsources of toxicants around the time of collection Sweat wasdelivered by the participants directly to ALS laboratoriesSamples were transferred to 4mL glass vials and stored ina freezer at minus20∘C pending analysis No preservatives wereused in the jars provided for sweat and urine collection norin the serum storage vials

BioMed Research International 5

Table 3 Organochlorine pesticides analyzed

Group Parent Metabolite

DDT and analogues DDTMethoxychlor

DDE DDDNA

Hexachlorobenzene Hexachlorobenzene NA

Hexachlorocyclohexane 120572-BHC 120573-BHC 120575-BHC and120574-BHC NA

Cyclodiene

Endosulfan I endosulfan II Endosulfan sulfateAldrin Dieldrin

Endrin Endrin ketoneEndrin aldehyde

Heptachlor Heptachlor epoxidecis-chlordane trans-chlordane trans-nonachlor

Chlordeconelowast Kelevanlowast and Mirex Mirex NAToxaphenelowastlowastDid not test for this specific compound in this study

33 Laboratory Method Description Of the 6 categories ofOCPs 5 were analyzed (Table 3 toxaphene was not includedin this study) Organochlorine pesticide concentrations ofparent and metabolite compounds were analyzed usingdual-column gas chromatography with electron-capturedetectors (GC-ECD) A pair of surrogate standards tetra-chlorometaxylene (TCMX) and decachlorobiphenyl (DCB)were used to monitor the performance of the method

The methodology for determining the selected organo-chlorine pesticides was as follows Serum samples wereweighed into glass tubes (8 g) and 8mL of methanol wasadded to the serum samples Sweat and urine samples wereweighed into glass tubes (5 g) and 5mL of methanol wasadded to each of the samples Serial extraction of the bioactivecompounds was performed on serum sweat and urinesamples 3 times by adding 12mL of an ethyl ether hexanesolution (1 1 vv) and removing the supernatant via centrifu-gation The extract was then put through a sodium sulfatecolumn to dry The resulting extracts were combined andconcentrated to 1mL and put through a 12 g 2 deactivatedflorisil column Florisil was used to eliminate coelutingchlorophenols External standard calibration was used forquantification Method blanks were used to ensure qualitycontrol water and calf serum samples Instrument detectionlimits were determined to be 010 120583gkg Pentachloroni-trobenzene (PCNB) was added to the extracts as an internalstandard and the samples were analyzed by dual-column gaschromatography with electron-capture detectors (DB-5 andDB-1701)

4 Results and Discussion

The results of the study can be found in Tables 4 and 5The parent OCP compounds showed differential detection(Tables 4(a)ndash4(c)) and compounds detected in at least oneparticipantrsquos serum sample include aldrin DDT endosulfan Iand endosulfan II heptachlor mirex hexachlorobenzene 120572-HCH 120573-HCH and 120574-HCH Endrin 120575-HCH and methoxy-chlor were not detected in any of the participantrsquos serum

samples The parent compounds detected in at least oneparticipantrsquos urine sample include aldrin DDT endosulfan Iand endosulfan II endrinmirex 120574-HCH andmethoxychlorHeptachlor 120572-HCH 120573-HCH 120575-HCH and hexachloroben-zene were not detected in any participantrsquos urine sample Allof the parent compounds except the isomers of hexachloro-cyclohexane were detected in at least one participantrsquos sweatsample

The metabolite compounds also showed differentialdetection The metabolite compounds detected in at leastone participantrsquos serum sample include DDE endrin ketoneendrin aldehyde and heptachlor epoxide The metabolitesDDD endosulfan sulfate and dieldrin were not detected inany serum samples The metabolite compounds detected inat least one participantrsquos sweat sample include DDE DDDendosulfan sulfate dieldrin and endrin ketone Neitherendrin aldehyde nor heptachlor epoxide was detected in anysweat samples The metabolite compounds detected in atleast one participantrsquos urine sample include DDD endosulfansulfate dieldrin endrin aldehyde and heptachlor epoxideThe metabolites DDE and endrin ketone were not detectedin any urine samples

Of the parent compounds DDT methoxychlor andendrin as well as the metabolites DDE DDD and endo-sulfan sulfate appear to be readily excreted into sweat asthey are found in over half of the participants examined(Table 5) Additionally with the exception of DDE theseOCPs were not readily detected in blood testing while stillbeing excreted and identified in sweat This may indicatethat these OCP compounds are stored and sequestered intissues not evident in blood testing but are mobilized andexcreted during perspiration In contrast endosulfan I wasalmost exclusively detected in urine samples of over half ofthe participants (Table 5) Collectively the findings suggestthat these participants have been commonly exposed toDDTmethoxychlor endrin and endosulfan I and are also carryinga body burden of themetabolites DDEDDD and endosulfansulfate

6 BioMed Research International

Table 4 (a) Distribution of parent compounds in serum (SE) sweat (SW) and urine (U) (120583gkg) (b) Distribution of parent compounds inserum (SE) sweat (SW) and urine (U) (120583gkg) (c) Distribution of parent compounds in serum (SE) sweat (SW) and urine (U) (120583gkg)

(a)

SEAldrin

SWAldrin

UAldrin

SEDDT

SWDDT

UDDT

SEEndosulfan

I

SWEndosulfan

I

UEndosulfan

I119899lowast 2 5 2 2 14 3 1 1 13

Meanlowastlowast mdash 015 mdash mdash 049 mdash mdash mdash 014Medianlowastlowast mdash 014 mdash mdash 042 mdash mdash mdash 014Std Devlowastlowast mdash 0028 mdash mdash 023 mdash mdash mdash 0018Range 017ndash066 010ndash017 010ndash015 022ndash023 027ndash11 019ndash039 011 012 012ndash018lowast

119899 represents the number of participants with a detectable amount of the OCP from the 20 total participants examinedlowastlowastFor matrices having fewer than 5 individuals with detectable OCP levels the mean median and standard deviation measurements were not provided

(b)

SEEndrin

SWEndrin

UEndrin

SEHeptachlor

SWHeptachlor

UHeptachlor

SEMirex

SWMirex

UMirex

119899lowast 0 13 1 8 1 0 2 3 2

Meanlowastlowast mdash 018 mdash 037 mdash mdash mdash mdash mdashMedianlowastlowast mdash 015 mdash 033 mdash mdash mdash mdash mdashStd Devlowastlowast mdash 0083 mdash 017 mdash mdash mdash mdash mdashRange mdash 011ndash018 012 015ndash067 011 mdash 012ndash018 010ndash017 011ndash016lowast

119899 represents the number of participants with a detectable amount of the OCP from the 20 total participants examinedlowastlowastFor matrices having fewer than 5 individuals with detectable OCP levels the mean median and standard deviation measurements were not provided

(c)

SEMethoxychlor

SWMethoxychlor

UMethoxychlor

SEHexachlorobenzene

SWHexachlorobenzene

UHexachlorobenzene

119899lowast 0 16 3 6 1 0

Meanlowastlowast mdash 026 mdash 029 mdash mdashMedianlowastlowast mdash 022 mdash 030 mdash mdashStd Devlowastlowast mdash 013 mdash 011 mdash mdashRange mdash 013ndash070 014ndash019 018ndash049 011 mdashlowast

119899 represents the number of participants with a detectable amount of the OCP from the 20 total participants examinedlowastlowastFor matrices having fewer than 5 individuals with detectable OCP levels the mean median and standard deviation measurements were not provided

Most of the compounds examined were detected inless than half of the participants regardless of the matrix(Table 5) This likely reflects a reduced exposure level tothese compounds However hexachlorobenzene heptachlorand endrin ketone were detected in at least 30 of par-ticipants and were all predominantly detected in serumsamples (Table 5) Although some compounds were detectedin participant urine these levels typically occurred aroundthe limit of detection and at much lower levels than eitherserum or sweat analysis With the exception of endosulfan Ithis suggests that urine analysis is not reliable as an analytictool to measure the body burden of these compounds

The partitioning of these compounds in the body seemsto be related to their lipophilicity With the exception ofendosulfan I and its metabolite endosulfan sulfate all of thecompounds detected in over half of the participants havelog119870ow values above 5 (Table 6) This indicates that they arehighly lipophilic and fat soluble and are expected to sequesterin fat tissue In comparison to the compounds found

predominantly in sweat hexachlorobenzene and heptachlorhave reportedly similar degrees of lipophilicity but werepredominantly found in blood (Tables 4(a)ndash4(c)) Thereforethese findings may suggest that lipophilicity is not the onlyfactor affecting the partitioning of these compounds

There are limitations to the study and to interpretationof the results There has been discussion in lay circles thatdiffering means of thermal depuration by varying types ofsauna (such as infrared sauna versus steam sauna) exerciseor other perspiration induction activities may result indifferences in excretion rates through skinThis study did nothave an adequate data set to control for potential differencesin the excretion of the range of OCPs between usages of far-infrared sauna regular sauna or exercise Several other issuesmay impact the reliability and reproducibility of perspirationanalysis that were not considered including body site ofsampling timing of collection while perspiring differencesin skin characteristics between individuals temperature andhumidity of the surroundings and factors such as diet

BioMed Research International 7

Table 5 Percentage of individuals with detection of organochlorinepesticides within serum sweat and urine (119899 = 20)

Serum Sweat Urine441015840-DDT 10 70 15441015840-DDE 95 70 0441015840-DDD 0 65 35Methoxychlor 0 80 15Endosulfan I 5 5 65Endosulfan sulfate 0 85 10Endrin 0 50 5Aldrin 10 25 10Dieldrin 0 15 10trans-nonachlor 0 5 0BHC (hexachlorobenzene) 30 5 0120572-BHC 10 0 0120573-BHC 15 0 0120575-BHC 0 0 0120574-BHC 1 0 1Endosulfan II 10 10 5Endrin ketone 35 5 0Endrin aldehyde 5 0 5Heptachlor epoxide 5 0 15Heptachlor 40 5 0cis-chlordane 5 5 0trans-chlordane 10 15 10Mirex 5 15 15

pharmaceutical intake and supplement use Accordinglyattempts to accurately quantify the relative amount of toxi-cants released into perspiration are limited

Areas for future research in relation to induced perspi-ration might include an examination of (i) differences inrates of excretion into perspiration of assorted xenobioticsfrom diverse sites in the body (ii) whether there is diurnalvariation in the toxicant content of perspiration (iii) whetherhydration status affects the xenobiotic concentration of per-spiration (iv) dermal reabsorption potential of toxicants afterperspiration and (v) the release of xenobiotics in those infasting states compared to those without caloric restriction

5 Conclusion

As DDT DDE DDD methoxychlor endosulfan sulfate andendrin appear to be readily excreted into sweat inducedperspiration appears to be a potential clinical tool to diminishthe body burden of these agents With the exception ofDDE however these agents are not readily detected in bloodtesting This suggests that common blood analysis may nottruly represent the body burden of these compounds Asthe routine use of unprovoked blood testing may thus beinadequate for biomonitoring body burdens of OCPs theremay be clinical advantages to the induction of perspirationthrough methods like sauna andor exercise in order tocollect samples for biomonitoring and diagnosis of manyretained OCP compounds

Table 6 Octanolwater partition coefficient of key OCPs [65ndash70]

Compound log119870owAldrin 650Endrin 52Endosulfan I 383Endosulfate 366pp1015840-DDT 691pp1015840-DDE 651pp1015840-DDD 602Methoxychlor 508Heptachlor 610Hexachlorobenzene 573

In conclusion the previous four papers in this ldquobloodurine and sweat (BUS)rdquo series have demonstrated thatinduced perspiration is effective at facilitating the removal ofmany toxic elements as well as various organic compoundsbut not all [59ndash62] This OCP study provides evidence thattransdermal depuration through perspiration facilitates elim-ination of some parent and metabolite OCP compounds butnot all While the absolute amount of each OCP compoundreleased into sweat may be small according to this data anaverage adult may sweat more than one liter per hour duringexerciseUnder thermal stressmaximal rates of sweatingmaybe as high as two to four litershour [63] and sweating ratesfor ldquoacclimatizedrdquo people who regularly use saunas may be ashigh as two litershour [64] Accordingly regular sessions ofinduced perspiration should be considered cumulatively as apotential clinical modality to diminish body burdens ofmanyxenobiotics including OCP compounds

Additional Points

Key Findings

(a) DDT andor its metabolite(s) were found in nearlyevery participant regardless of age suggesting thatexposure is very common

(b) Nearly all organochlorine pesticide (OCP) parentcompounds and several metabolites were detected inperspiration suggesting that sweating may be effica-cious in diminishing the body burden of many ofthese toxicants

(c) There were some parent OCPs such as endosulfan Iand hexachlorobenzene and some metabolites suchas endrin ketone and heptachlor that were not readilyexcreted into perspiration

(d) Lipophilicity appeared to be a major factor influenc-ing the efficacy of transdermal OCP elimination butnot the exclusive determinant

(e) Only endosulfan I appeared to be predominantlydetected in urine suggesting that urine analysis haslimited value in detection of retained OCPs

8 BioMed Research International

Competing Interests

There is no conflict of interests regarding the publication ofthis paper

Acknowledgments

Thanks are due to Dr Peter Mahaffy and the Departmentof Chemistry at The Kingrsquos University for their thoughtfulassistance in this work

References

[1] Nobelprizeorg the official web site of the Nobel PrizePaul MullermdashBiographical httpwwwnobelprizeorgnobelprizesmedicinelaureates1948muller-biohtml

[2] K I Barnes D N Durrheim F Little et al ldquoEffect ofartemether-lumefantrine policy and improved vector controlon malaria burden in KwaZulu-Natal South Africardquo PLoSMedicine vol 2 no 11 article e330 2005

[3] United States Environmental Protection Agency ldquoDDT A briefhistory and statusrdquo 2016 httpswwwepagovingredients-used-pesticide-productsddt-brief-history-and-status

[4] United Nations Environment Programme Stockholm Conven-tion Protecting health and the environment from persistentorganic pollutants httpchmpopsintdefaultaspx

[5] S MWaliszewski A A Aguirre R M Infanzon and J SiliceoldquoCarry-over of persistent organochlorine pesticides throughplacenta to fetusrdquo Salud Publica de Mexico vol 42 no 5 pp384ndash390 2000

[6] S J Genuis ldquoElimination of persistent toxicants from thehuman bodyrdquo Human amp Experimental Toxicology vol 30 no1 pp 3ndash18 2010

[7] R E Herron and J B Fagan ldquoLipophil-mediated reduction oftoxicants in humans an evaluation of an ayurvedic detoxifica-tion procedurerdquo Alternative Therapies in Health and Medicinevol 8 no 5 pp 40ndash51 2002

[8] S J Genuis M E Sears G Schwalfenberg J Hope andR Bernhoft ldquoClinical detoxification elimination of persistenttoxicants from the human bodyrdquo The Scientific World Journalvol 2013 Article ID 238347 3 pages 2013

[9] S L Archibeque-Engle J D Tessari D T Winn T J KeefeT M Nett and T Zheng ldquoComparison of organochlorinepesticide and polychlorinated biphenyl residues in humanbreast adipose tissue and serumrdquo Journal of Toxicology andEnvironmental Health vol 52 no 4 pp 285ndash293 1997

[10] S J Genuis andK L Kelln ldquoToxicant exposure and bioaccumu-lation a common and potentially reversible cause of cognitivedysfunction and dementiardquo Behavioural Neurology vol 2015Article ID 620143 10 pages 2015

[11] T G Redgrave P Wallace R J Jandacek and P Tso ldquoTreat-ment with a dietary fat substitute decreased Arochlor 1254contamination in an obese diabetic malerdquo Journal of NutritionalBiochemistry vol 16 no 6 pp 383ndash384 2005

[12] G H Ross and M C Sternquist ldquoMethamphetamine exposureand chronic illness in police officers significant improvementwith sauna-based detoxification therapyrdquo Toxicology and Indus-trial Health vol 28 no 8 pp 758ndash768 2012

[13] P Williams R James and S Roberts Principles of ToxicologyJohn Wiley amp Sons New York NY USA 2000

[14] A K Pramanik and R C Hansen ldquoTranscutaneous gammabenzene hexachloride absorption and toxicity in infants andchildrenrdquo Archives of Dermatology vol 115 no 10 pp 1224ndash1225 1979

[15] V N Uversky J Li K Bower and A L Fink ldquoSynergisticeffects of pesticides andmetals on the fibrillation of120572-synucleinimplications for Parkinsonrsquos diseaserdquo NeuroToxicology vol 23no 4-5 pp 527ndash536 2002

[16] Y-M Lee S-G Bae S-H Lee D R Jacobs Jr and D-H LeeldquoAssociations between cigarette smoking and total mortalitydiffer depending on serum concentrations of persistent organicpollutants among the elderlyrdquo Journal of KoreanMedical Sciencevol 28 no 8 pp 1122ndash1128 2013

[17] P Bennett ldquoWorking Up the Toxic Patientrdquo httpwwwpeter-bennettcomresourcesdetoxificationworkingupthedetoxpa-tientpdf

[18] S J Genuis ldquoThe chemical erosion of human health adverseenvironmental exposure and in-utero pollutionmdashdeterminantsof congenital disorders and chronic diseaserdquo Journal of PerinatalMedicine vol 34 no 3 pp 185ndash195 2006

[19] E R Kabir M S Rahman and I Rahman ldquoA review onendocrine disruptors and their possible impacts on humanhealthrdquo Environmental Toxicology and Pharmacology vol 40no 1 pp 241ndash258 2015

[20] G C Di Renzo J A Conry J Blake et al ldquoInternational Fed-eration of Gynecology and Obstetrics opinion on reproductivehealth impacts of exposure to toxic environmental chemicalsrdquoInternational Journal of Gynecology amp Obstetrics vol 131 no 3pp 219ndash225 2015

[21] M K Skinner M Manikkam and C Guerrero-BosagnaldquoEpigenetic transgenerational actions of endocrine disruptorsrdquoReproductive Toxicology vol 31 no 3 pp 337ndash343 2011

[22] M E Sears and S J Genuis ldquoEnvironmental determinants ofchronic disease and medical approaches recognition avoid-ance supportive therapy and detoxificationrdquo Journal of Envi-ronmental and Public Health vol 2012 Article ID 356798 15pages 2012

[23] T M Crisp E D Clegg R L Cooper et al ldquoEnvironmentalendocrine disruption an effects assessment and analysisrdquo Envi-ronmental Health Perspectives vol 106 supplement 1 pp 11ndash561998

[24] M E A Benarbia D Macherel S Faure C Jacques R Andri-antsitohaina and Y Malthiery ldquoPlasmatic concentration oforganochlorine lindane acts as metabolic disruptors in HepG2liver cell line by inducing mitochondrial disorderrdquo Toxicologyand Applied Pharmacology vol 272 no 2 pp 325ndash334 2013

[25] C Charlier A Albert P Herman et al ldquoBreast cancer andserum organochlorine residuesrdquo Occupational and Environ-mental Medicine vol 60 no 5 pp 348ndash351 2003

[26] J Dich S H Zahm A Hanberg and H-O Adami ldquoPesticidesand cancerrdquo Cancer Causes and Control vol 8 no 3 pp 420ndash443 1997

[27] S Yasunaga KNishi S Nishimoto andT Sugahara ldquoMethoxy-chlor enhances degranulation ofmurinemast cells by regulatingFc120576RI-mediated signal transductionrdquo Journal of Immunotoxicol-ogy vol 12 no 3 pp 283ndash289 2015

[28] K Upson A J De Roos M L Thompson et al ldquoOrganochlo-rine pesticides and risk of endometriosis findings from apopulation-based case-control studyrdquo Environmental HealthPerspectives vol 121 no 11-12 pp 1319ndash1324 2013

[29] K A McGlynn S M Quraishi B I Graubard J-P Weber MV Rubertone and R L Erickson ldquoPersistent organochlorine

BioMed Research International 9

pesticides and risk of testicular germ cell tumorsrdquo Journal of theNational Cancer Institute vol 100 no 9 pp 663ndash671 2008

[30] D H Lee M W Steffes A Sjodin R S Jones L L Needhamand D R Jacobs Jr ldquoLow dose organochlorine pesticides andpolychlorinated biphenyls predict obesity dyslipidemia andinsulin resistance among people free of diabetesrdquo PLoS ONEvol 6 no 1 Article ID e15977 2011

[31] M Turyk H Anderson L Knobeloch P Imm and V PerskyldquoOrganochlorine exposure and incidence of diabetes in a cohortof great lakes sport fish consumersrdquo Environmental HealthPerspectives vol 117 no 7 pp 1076ndash1082 2009

[32] H K Son S A Kim J H Kang et al ldquoStrong associationsbetween low-dose organochlorine pesticides and type 2 dia-betes in Koreardquo Environment International vol 36 no 5 pp410ndash414 2010

[33] L Fleming J B Mann J Bean T Briggle and J R Sanchez-Ramos ldquoParkinsonrsquos disease and brain levels of organochlorinepesticidesrdquoAnnals of Neurology vol 36 no 1 pp 100ndash103 1994

[34] H J Heusinkveld and R H S Westerink ldquoOrganochlorineinsecticides lindane and dieldrin and their binary mixturedisturb calcium homeostasis in dopaminergic PC12 cellsrdquoEnvironmental Science and Technology vol 46 no 3 pp 1842ndash1848 2012

[35] J Jurewicz and W Hanke ldquoPrenatal and childhood exposureto pesticides and neurobehavioral development review ofepidemiological studiesrdquo International Journal of OccupationalMedicine and Environmental Health vol 21 no 2 pp 121ndash1322008

[36] E A Belyaeva T V Sokolova L V Emelyanova and I OZakharova ldquoMitochondrial electron transport chain in heavymetal-induced neurotoxicity effects of cadmium mercury andcopperrdquo The Scientific World Journal vol 2012 Article ID136063 14 pages 2012

[37] R Pathak S G Suke T Ahmed et al ldquoOrganochlorinepesticide residue levels and oxidative stress in preterm deliverycasesrdquoHumanampExperimental Toxicology vol 29 no 5 pp 351ndash358 2010

[38] M Zhao Y Zhang C Wang Z Fu W Liu and J GanldquoInduction of macrophage apoptosis by an organochlorineinsecticide acetofenaterdquo Chemical Research in Toxicology vol22 no 3 pp 504ndash510 2009

[39] W Mnif A I Hassine A Bouaziz A Bartegi O Thomas andB Roig ldquoEffect of endocrine disruptor pesticides a reviewrdquoInternational Journal of Environmental Research and PublicHealth vol 8 no 6 pp 2265ndash2303 2011

[40] L Hou X Zhang D Wang and A Baccarelli ldquoEnvironmentalchemical exposures and human epigeneticsrdquo International Jour-nal of Epidemiology vol 41 no 1 pp 79ndash105 2012

[41] G M Williams ldquoGenotoxic and epigenetic carcinogens theiridentification and significancerdquo Annals of the New YorkAcademy of Sciences vol 407 no 1 pp 328ndash333 1983

[42] B Hille ldquoPharmacological modifications of the sodium chan-nels of frog nerverdquo The Journal of General Physiology vol 51no 2 pp 199ndash219 1968

[43] S Gilbert A Small Dose of Toxicology CRC Press Boca RatonFla USA 2004

[44] S J Genuis ldquoSensitivity-related illness the escalating pandemicof allergy food intolerance and chemical sensitivityrdquoTheScienceof the Total Environment vol 408 no 24 pp 6047ndash6061 2010

[45] S J Genuis ldquoPandemic of idiopathic multimorbidityrdquo Cana-dian Family Physician vol 60 no 6 pp 511ndash514 2014

[46] Centers for Disease Control and Prevention Department ofHealth and Human Services Fourth National Report on HumanExposure to Environmental Chemicals CDC Atlanta Ga USA2013 httpwwwcdcgovexposurereportpdfFourthReportUpdatedTables Mar2013pdf

[47] Health Canada ldquoHuman biomonitoring of environmentalchemicalsrdquo 2015 httpwwwhealthcanadagccabiomoni-toring

[48] S J Genuis and R A Genuis ldquoPreconception care a newstandard of care within maternal health servicesrdquo BioMedResearch International vol 2016 Article ID 6150976 30 pages2016

[49] Environmental Working Group BPA and Other Cord BloodPollutants 2016 httpwwwewgorgresearchminority-cord-blood-reportbpa-and-other-cord-blood-pollutants

[50] A Sudaryanto T Kunisue N Kajiwara et al ldquoSpecific accumu-lation of organochlorines in human breastmilk from Indonesialevels distribution accumulation kinetics and infant healthriskrdquo Environmental Pollution vol 139 no 1 pp 107ndash117 2006

[51] E M Roberts P B English J K Grether G C Windham LSomberg and C Wolff ldquoMaternal residence near agriculturalpesticide applications and autism spectrum disorders amongchildren in the California Central Valleyrdquo Environmental HealthPerspectives vol 115 no 10 pp 1482ndash1489 2007

[52] R J Jandacek and S J Genuis ldquoAn assessment of the intestinallumen as a site for intervention in reducing body burdens oforganochlorine compoundsrdquo The Scientific World Journal vol2013 Article ID 205621 10 pages 2013

[53] W J Cohn J J Boylan R V Blanke M W Fariss J R Howelland P S Guzelian ldquoTreatment of chlordecone (Kepone) toxicitywith cholestyramine Results of a controlled clinical trialrdquo TheNew England Journal of Medicine vol 298 no 5 pp 243ndash2481978

[54] Y Mochida H Fukata Y Matsuno and C Mori ldquoReduction ofdioxins and polychlorinated biphenyls (PCBs) in human bodyrdquoFukuoka Igaku Zasshi vol 98 no 4 pp 106ndash113 2007

[55] K Rozman L Ballhorn and T Rozman ldquoMineral oil in the dietenhances fecal excretion of DDT in the rhesus monkeyrdquo Drugand Chemical Toxicology vol 6 no 3 pp 311ndash316 1983

[56] D W Schnare M Ben and M G Shields ldquoBody burdenreduction of PCBs PBBs and chlorinated pesticides in humansubjectsrdquo Ambio vol 13 pp 378ndash380 1984

[57] D W Schnare and P C Robinson ldquoReduction of human bodyburdens of hexachlorobenzene and polychlorinated biphenylsrdquoin Hexachlorobenzene Proceedings of an International Sym-posium C R Morris and J R P Cabral Eds pp 597ndash603International Agency for Research on Cancer Lyon France1986

[58] R J Jandacek and P Tso ldquoEnterohepatic circulation oforganochlorine compounds a site for nutritional interventionrdquoThe Journal of Nutritional Biochemistry vol 18 no 3 pp 163ndash167 2007

[59] S J Genuis D Birkholz I Rodushkin and S Beesoon ldquoBloodurine and sweat (BUS) study monitoring and eliminationof bioaccumulated toxic elementsrdquo Archives of EnvironmentalContamination and Toxicology vol 61 no 2 pp 344ndash357 2011

[60] S J Genuis S Beesoon R A Lobo and D Birkholz ldquoHumanelimination of phthalate compounds blood urine and sweat(BUS) studyrdquoThe Scientific World Journal vol 2012 Article ID615068 10 pages 2012

[61] S J Genuis S Beesoon and D Birkholz ldquoBiomonitoring andelimination of perfluorinated compounds and polychlorinated

10 BioMed Research International

biphenyls through perspiration blood urine and sweat studyrdquoISRN Toxicology vol 2013 Article ID 483832 7 pages 2013

[62] S J Genuis S Beesoon D Birkholz and R A Lobo ldquoHumanexcretion of bisphenol a blood urine and sweat (BUS) StudyrdquoJournal of Environmental and Public Health vol 2012 Article ID185731 10 pages 2012

[63] U W R Greger Comprehensive Human Physiology FromCellularMechanisms to Integration Springer Science ampBusinessMedia 2013

[64] A Eisalo and O J Luurila ldquoThe Finnish sauna and cardiovas-cular diseasesrdquo Annals of Clinical Research vol 20 no 4 pp267ndash270 1988

[65] J De Bruijn F Busser W Seinen and J Hermens ldquoDetermi-nation of octanolwater partition coefficients for hydrophobicorganic chemicals with the lsquoslow-stirringrsquo methodrdquo Environ-mental Toxicology andChemistry vol 8 no 6 pp 499ndash512 1989

[66] W de Wolf W Seinen and J L M Hermens ldquoBiotransforma-tion and toxicokinetics of trichloroanilines in fish in relation totheir hydrophobicityrdquoArchives of Environmental Contaminationand Toxicology vol 25 no 1 pp 110ndash117 1993

[67] C L A Hansch and D Hoekman Exploring QSAR AmericanChemical Society Washington DC USA 1995

[68] P H Howard and W M Meylan Handbook of Physical Prop-erties of Organic Chemicals Lewis Publishers Boca Raton FlaUSA 1997

[69] R H G Lewis Hawleyrsquos Condensed Chemical Dictionary JohnWiley amp Sons Hoboken NJ USA 15th edition 2007

[70] C D Simpson R J Wilcock T J Smith A L Wilkinsand A G Langdon ldquoDetermination of octanol-water partitioncoefficients for the major components of technical chlordanerdquoBulletin of Environmental Contamination and Toxicology vol55 no 1 pp 149ndash153 1995

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MEDIATORSINFLAMMATION

of

Page 3: Research Article Human Elimination of Organochlorine

BioMed Research International 3

burden of these chemical agents and then treating them tofacilitate elimination of their accrued load of toxicants isworthy of exploration and further research

21 Biochemical and Pathophysiological Mechanisms of HarmAlthough designed as acute neurotoxins OCPs have beenfound to dysregulate human metabolic processes throughseveral different pathways These pathophysiological mech-anisms include mitochondrial damage [24 36] oxidativestress [37] cell death [38] endocrine disruption [39] andepigenetic modification [40 41] As discussed there is alsoevidence that concomitant contamination with OCPs alongwith other toxic chemical agents may exhibit synergisticeffects [15]

Additionally OCPs also exhibit synaptic dysregulation byaltering the cation channels (eg sodium) at the synapse innerve cells [42] Although this effect establishes their efficacyagainst insect pests the similarity between organismal synap-tic cation channels between species results in nonspecificityand inadvertent harm to nontarget organisms [43] Anotherpotential pathway of harm is the recently established mech-anism entitled ldquotoxicant induced loss of tolerancerdquo (TILT)[44] This pathophysiologic mechanism resulting in humanmultimorbidity is characterized by a toxicant burden (egpersistent OCPs) resulting in impaired tolerance and hyper-sensitivity [45]When triggered by an antigenic incident fromthe environment (eg pollen chemical agent or food) animmune response ensues potentially producing antibodiesand proinflammatory cytokines A multisystem responseresulting in a condition entitled ldquoSensitivity Related Illnessrdquo(SRI) is often the result [44] Unfolding research continuesto expound on various pathophysiological mechanisms ofdamage to the human organism

22 Human Exposure There is mounting evidence that indi-viduals and population groups are currently being exposed toa multitude of different types of chemical toxicants some ofwhich may accrue within the body The Centers for DiseaseControl for example recently released a study confirmingaccrual of multiple pollutants in most American adults andchildren [46] In a similar nation-wide epidemiological studyin Canada Health Canada also reported on an assortment ofstockpiled chemical toxicants within the general population[47]

An issue of particular concern is fetal and early lifeexposure to xenobiotics at critical times of development asa result of maternal exposure and bioaccumulation [48]Although OCPs were not specifically measured a recentcord-blood study revealed an accumulation of various tox-icants in neonates at birth [49] Studies on OCPs withinlactating women have confirmed OCP levels in some womenthat exceed Health Canadarsquos tolerable daily intake (TDI)guidelines [50]The potential clinical sequelae of such accrualwithin reproductive-aged women can be seen for examplein a large observational study examining specific OCP expo-sures (dicofol and endosulfan) [51] This research suggestsa correlation of increased risk of autistic spectrum disorderbased on the distance between maternal residence and thelocation of pesticide application [51] Such emerging work

on gestational and lactational exposures led to the recentldquoSpecial Communicationrdquo by the International Federationof Obstetrics and Gynecology [20] (an organization whichoversees much of the maternity care throughout the world)in an effort to bring global attention to the reality ofwidespread vertical transmission of toxicants and the myriadpediatric health problems resulting frommaternal xenobioticpollution

Although restrictive policies have been implemented forOCP usage in many jurisdictions these agents continue tobe found within individuals and population groups Thisis as discussed due to continued usage in some areas ofthe world vertical transmission to offspring and persistencewithin the human organism Why do they persist FollowingexposureOCP compounds are dechlorinated and conjugatedin the liver where biliary excretion is the main mechanismfor elimination However organochlorine compounds arereabsorbed to some degree in the enterohepatic circulationand this recycling phenomenon accounts for the persistencewithin the human body [52]

As a result of such persistence and the lipophilic natureof OCPs these chemical agents tend to store and bioaccu-mulate in adipose tissues Although the complete range oftoxicity relating to OCP exposure and bioaccumulation isnot fully understood and remains somewhat controversialmany adverse sequelae have been linked to exposure to suchagents as previously mentioned Accordingly interventionsare required to assist in facilitating elimination of OCPsin order to prevent or overcome adverse clinical sequelaeresulting from the potential physiological disruption causedby the enduring presence of these toxicants

Thus far there has been limited work on interventionsto facilitate elimination of OCPs [7 52ndash55] Schnare etal examined the use of induced perspiration as a meansto expedite elimination of PCBs PBBs and OCPs [56]Their work confirmed that enhancedmobilization and excre-tion via induced perspiration reduced the body burden ofhexachlorobenzene (HCB) and 10 polychlorinated biphenylcongeners [57] Removal of organochlorine compounds hasalso been facilitated by specific interventions which interruptthe enterohepatic circulation [7 52 58]Themain purpose ofthis study is to determine whether induced perspiration canbe used clinically to facilitate decorporation of the range ofboth parent OCPs as well as their metabolites

3 Materials and Methods

31 Participant Recruitment Nine males and 11 females withmean ages of 445 plusmn 144 years and 456 plusmn 103 yearsrespectively were recruited to participate in this study afterappropriate ethical approval was received from the HealthResearch Ethics Board of the University of Alberta 10 partic-ipants were patients with various clinical conditions and 10were otherwise healthy adults Participants with health issueswere recruited from the first authorrsquos clinical practice byinvitation and both healthy and sick individuals were selectedas samples of convenience by availability desire to participateand ease of contact Each participant in the study providedinformed consent and volunteered to give one 200mL

4 BioMed Research International

Table 2 Participant demographics and general clinical characteristics

Participant Gender Age Clinical diagnosis Technique used for sweat collection1 M 61 Diabetes obesity hypertension Exercise2 F 40 Rheumatoid arthritis Steam sauna3 M 38 Addiction disorder Steam sauna4 F 25 Bipolar disorder Steam sauna5 F 47 Lymphoma Steam sauna6 F 43 Fibromyalgia Steam sauna7 F 48 Depression Steam sauna8 F 40 Chronic fatigue Infrared sauna9 F 68 Diabetes fatigue obesity Steam sauna10 M 49 Chronic pain cognitive decline Exercise11 M 53 Healthy Exercise12 M 23 Healthy Infrared sauna13 M 21 Healthy Infrared sauna14 F 47 Healthy Infrared sauna15 M 53 Healthy Infrared sauna16 F 43 Healthy Infrared sauna17 F 51 Healthy Infrared sauna18 M 46 Healthy Infrared sauna19 M 57 Healthy Infrared sauna20 F 50 Healthy Infrared sauna

random sample of blood one sample of first morning urineand one 100mL sample of sweat Demographic and clinicalcharacteristics of all research participants are provided inTable 2

32 Samples Collection All blood samples were collected atoneDynaLIFE laboratory site in EdmontonAlberta Canadawith vacutainer blood collection equipment (BD VacutainerFranklin Lakes NJ 07417 USA) using 21-gauge stainlesssteel needles which were screwed into the ldquoBD VacutainerOne-Use Holderrdquo (REF 364815) The 10mL glass vacutainerwas directly inserted into the holder and into the backend of the needle This process and the use of glass bloodcollection tubes were used to prevent contamination Bloodwas collected directly into plain 10 mL glass vacutainer tubesallowed to clot and after 30 minutes were centrifuged for 10minutes at 2000 revolutions per minute (RPM) After serumwas separated off sampleswere picked up byALS laboratories(about 3 kilometres from the blood collection site) for storagepending analysisWhen received at ALS serum samples weretransferred to 4mLglass vials and stored in a freezer atminus20∘Cpending transfer to the analytical laboratory

For urine collection participants were instructed tocollect a first morning midstream urine sample directly intoa provided 500mL glass jar container with Teflon-lined lidon the same day that blood samples were collected Urinesamples were delivered by the participants directly to ALSlaboratories Edmonton Samples were transferred to 4 mLglass vials and stored in a freezer at minus20∘C pending transfer

For sweat collection participants were instructed tocollect perspiration from any site on their body directly intothe provided 500mL glass jar container with Teflon-lined

lid by placing the jar against their prewashed skin (withtoxicant-free soap water and nonplastic brush)when activelysweating or by using a stainless steel spatula against their skinto transfer perspiration directly into the glass jar Stainlesssteel made up primarily of iron chromium and nickel waschosen as it is the same material as the needles used instandard blood collections and is reported not to off-gasor leach at room or body temperature All but one of theparticipants (1920) provided 100mL of sweat Each of theglass bottles used for sampling in this study was provided byALS laboratories and had undergone extensive cleaning andrinsing The containers were deemed appropriate for sweatcollection with negligible risk of contamination laboratory-grade phosphate-free detergent wash acid rinse multiple hotand cold deionized water rinses oven dried capped andpacked in quality-controlled conditions

Sweat was collected within 1 week before or after collect-ing the blood and urine samples No specifications were givenas to how long sweating had commenced before collection10 participants collected sweat inside a dry infrared sauna7 collected sweat inside a steam sauna and 3 collectedsweat during and immediately after exercise no specificinstruction was given regarding the type or location ofexercise Participants were educated about the research andwere asked to meticulously avoid exposure to any potentialsources of toxicants around the time of collection Sweat wasdelivered by the participants directly to ALS laboratoriesSamples were transferred to 4mL glass vials and stored ina freezer at minus20∘C pending analysis No preservatives wereused in the jars provided for sweat and urine collection norin the serum storage vials

BioMed Research International 5

Table 3 Organochlorine pesticides analyzed

Group Parent Metabolite

DDT and analogues DDTMethoxychlor

DDE DDDNA

Hexachlorobenzene Hexachlorobenzene NA

Hexachlorocyclohexane 120572-BHC 120573-BHC 120575-BHC and120574-BHC NA

Cyclodiene

Endosulfan I endosulfan II Endosulfan sulfateAldrin Dieldrin

Endrin Endrin ketoneEndrin aldehyde

Heptachlor Heptachlor epoxidecis-chlordane trans-chlordane trans-nonachlor

Chlordeconelowast Kelevanlowast and Mirex Mirex NAToxaphenelowastlowastDid not test for this specific compound in this study

33 Laboratory Method Description Of the 6 categories ofOCPs 5 were analyzed (Table 3 toxaphene was not includedin this study) Organochlorine pesticide concentrations ofparent and metabolite compounds were analyzed usingdual-column gas chromatography with electron-capturedetectors (GC-ECD) A pair of surrogate standards tetra-chlorometaxylene (TCMX) and decachlorobiphenyl (DCB)were used to monitor the performance of the method

The methodology for determining the selected organo-chlorine pesticides was as follows Serum samples wereweighed into glass tubes (8 g) and 8mL of methanol wasadded to the serum samples Sweat and urine samples wereweighed into glass tubes (5 g) and 5mL of methanol wasadded to each of the samples Serial extraction of the bioactivecompounds was performed on serum sweat and urinesamples 3 times by adding 12mL of an ethyl ether hexanesolution (1 1 vv) and removing the supernatant via centrifu-gation The extract was then put through a sodium sulfatecolumn to dry The resulting extracts were combined andconcentrated to 1mL and put through a 12 g 2 deactivatedflorisil column Florisil was used to eliminate coelutingchlorophenols External standard calibration was used forquantification Method blanks were used to ensure qualitycontrol water and calf serum samples Instrument detectionlimits were determined to be 010 120583gkg Pentachloroni-trobenzene (PCNB) was added to the extracts as an internalstandard and the samples were analyzed by dual-column gaschromatography with electron-capture detectors (DB-5 andDB-1701)

4 Results and Discussion

The results of the study can be found in Tables 4 and 5The parent OCP compounds showed differential detection(Tables 4(a)ndash4(c)) and compounds detected in at least oneparticipantrsquos serum sample include aldrin DDT endosulfan Iand endosulfan II heptachlor mirex hexachlorobenzene 120572-HCH 120573-HCH and 120574-HCH Endrin 120575-HCH and methoxy-chlor were not detected in any of the participantrsquos serum

samples The parent compounds detected in at least oneparticipantrsquos urine sample include aldrin DDT endosulfan Iand endosulfan II endrinmirex 120574-HCH andmethoxychlorHeptachlor 120572-HCH 120573-HCH 120575-HCH and hexachloroben-zene were not detected in any participantrsquos urine sample Allof the parent compounds except the isomers of hexachloro-cyclohexane were detected in at least one participantrsquos sweatsample

The metabolite compounds also showed differentialdetection The metabolite compounds detected in at leastone participantrsquos serum sample include DDE endrin ketoneendrin aldehyde and heptachlor epoxide The metabolitesDDD endosulfan sulfate and dieldrin were not detected inany serum samples The metabolite compounds detected inat least one participantrsquos sweat sample include DDE DDDendosulfan sulfate dieldrin and endrin ketone Neitherendrin aldehyde nor heptachlor epoxide was detected in anysweat samples The metabolite compounds detected in atleast one participantrsquos urine sample include DDD endosulfansulfate dieldrin endrin aldehyde and heptachlor epoxideThe metabolites DDE and endrin ketone were not detectedin any urine samples

Of the parent compounds DDT methoxychlor andendrin as well as the metabolites DDE DDD and endo-sulfan sulfate appear to be readily excreted into sweat asthey are found in over half of the participants examined(Table 5) Additionally with the exception of DDE theseOCPs were not readily detected in blood testing while stillbeing excreted and identified in sweat This may indicatethat these OCP compounds are stored and sequestered intissues not evident in blood testing but are mobilized andexcreted during perspiration In contrast endosulfan I wasalmost exclusively detected in urine samples of over half ofthe participants (Table 5) Collectively the findings suggestthat these participants have been commonly exposed toDDTmethoxychlor endrin and endosulfan I and are also carryinga body burden of themetabolites DDEDDD and endosulfansulfate

6 BioMed Research International

Table 4 (a) Distribution of parent compounds in serum (SE) sweat (SW) and urine (U) (120583gkg) (b) Distribution of parent compounds inserum (SE) sweat (SW) and urine (U) (120583gkg) (c) Distribution of parent compounds in serum (SE) sweat (SW) and urine (U) (120583gkg)

(a)

SEAldrin

SWAldrin

UAldrin

SEDDT

SWDDT

UDDT

SEEndosulfan

I

SWEndosulfan

I

UEndosulfan

I119899lowast 2 5 2 2 14 3 1 1 13

Meanlowastlowast mdash 015 mdash mdash 049 mdash mdash mdash 014Medianlowastlowast mdash 014 mdash mdash 042 mdash mdash mdash 014Std Devlowastlowast mdash 0028 mdash mdash 023 mdash mdash mdash 0018Range 017ndash066 010ndash017 010ndash015 022ndash023 027ndash11 019ndash039 011 012 012ndash018lowast

119899 represents the number of participants with a detectable amount of the OCP from the 20 total participants examinedlowastlowastFor matrices having fewer than 5 individuals with detectable OCP levels the mean median and standard deviation measurements were not provided

(b)

SEEndrin

SWEndrin

UEndrin

SEHeptachlor

SWHeptachlor

UHeptachlor

SEMirex

SWMirex

UMirex

119899lowast 0 13 1 8 1 0 2 3 2

Meanlowastlowast mdash 018 mdash 037 mdash mdash mdash mdash mdashMedianlowastlowast mdash 015 mdash 033 mdash mdash mdash mdash mdashStd Devlowastlowast mdash 0083 mdash 017 mdash mdash mdash mdash mdashRange mdash 011ndash018 012 015ndash067 011 mdash 012ndash018 010ndash017 011ndash016lowast

119899 represents the number of participants with a detectable amount of the OCP from the 20 total participants examinedlowastlowastFor matrices having fewer than 5 individuals with detectable OCP levels the mean median and standard deviation measurements were not provided

(c)

SEMethoxychlor

SWMethoxychlor

UMethoxychlor

SEHexachlorobenzene

SWHexachlorobenzene

UHexachlorobenzene

119899lowast 0 16 3 6 1 0

Meanlowastlowast mdash 026 mdash 029 mdash mdashMedianlowastlowast mdash 022 mdash 030 mdash mdashStd Devlowastlowast mdash 013 mdash 011 mdash mdashRange mdash 013ndash070 014ndash019 018ndash049 011 mdashlowast

119899 represents the number of participants with a detectable amount of the OCP from the 20 total participants examinedlowastlowastFor matrices having fewer than 5 individuals with detectable OCP levels the mean median and standard deviation measurements were not provided

Most of the compounds examined were detected inless than half of the participants regardless of the matrix(Table 5) This likely reflects a reduced exposure level tothese compounds However hexachlorobenzene heptachlorand endrin ketone were detected in at least 30 of par-ticipants and were all predominantly detected in serumsamples (Table 5) Although some compounds were detectedin participant urine these levels typically occurred aroundthe limit of detection and at much lower levels than eitherserum or sweat analysis With the exception of endosulfan Ithis suggests that urine analysis is not reliable as an analytictool to measure the body burden of these compounds

The partitioning of these compounds in the body seemsto be related to their lipophilicity With the exception ofendosulfan I and its metabolite endosulfan sulfate all of thecompounds detected in over half of the participants havelog119870ow values above 5 (Table 6) This indicates that they arehighly lipophilic and fat soluble and are expected to sequesterin fat tissue In comparison to the compounds found

predominantly in sweat hexachlorobenzene and heptachlorhave reportedly similar degrees of lipophilicity but werepredominantly found in blood (Tables 4(a)ndash4(c)) Thereforethese findings may suggest that lipophilicity is not the onlyfactor affecting the partitioning of these compounds

There are limitations to the study and to interpretationof the results There has been discussion in lay circles thatdiffering means of thermal depuration by varying types ofsauna (such as infrared sauna versus steam sauna) exerciseor other perspiration induction activities may result indifferences in excretion rates through skinThis study did nothave an adequate data set to control for potential differencesin the excretion of the range of OCPs between usages of far-infrared sauna regular sauna or exercise Several other issuesmay impact the reliability and reproducibility of perspirationanalysis that were not considered including body site ofsampling timing of collection while perspiring differencesin skin characteristics between individuals temperature andhumidity of the surroundings and factors such as diet

BioMed Research International 7

Table 5 Percentage of individuals with detection of organochlorinepesticides within serum sweat and urine (119899 = 20)

Serum Sweat Urine441015840-DDT 10 70 15441015840-DDE 95 70 0441015840-DDD 0 65 35Methoxychlor 0 80 15Endosulfan I 5 5 65Endosulfan sulfate 0 85 10Endrin 0 50 5Aldrin 10 25 10Dieldrin 0 15 10trans-nonachlor 0 5 0BHC (hexachlorobenzene) 30 5 0120572-BHC 10 0 0120573-BHC 15 0 0120575-BHC 0 0 0120574-BHC 1 0 1Endosulfan II 10 10 5Endrin ketone 35 5 0Endrin aldehyde 5 0 5Heptachlor epoxide 5 0 15Heptachlor 40 5 0cis-chlordane 5 5 0trans-chlordane 10 15 10Mirex 5 15 15

pharmaceutical intake and supplement use Accordinglyattempts to accurately quantify the relative amount of toxi-cants released into perspiration are limited

Areas for future research in relation to induced perspi-ration might include an examination of (i) differences inrates of excretion into perspiration of assorted xenobioticsfrom diverse sites in the body (ii) whether there is diurnalvariation in the toxicant content of perspiration (iii) whetherhydration status affects the xenobiotic concentration of per-spiration (iv) dermal reabsorption potential of toxicants afterperspiration and (v) the release of xenobiotics in those infasting states compared to those without caloric restriction

5 Conclusion

As DDT DDE DDD methoxychlor endosulfan sulfate andendrin appear to be readily excreted into sweat inducedperspiration appears to be a potential clinical tool to diminishthe body burden of these agents With the exception ofDDE however these agents are not readily detected in bloodtesting This suggests that common blood analysis may nottruly represent the body burden of these compounds Asthe routine use of unprovoked blood testing may thus beinadequate for biomonitoring body burdens of OCPs theremay be clinical advantages to the induction of perspirationthrough methods like sauna andor exercise in order tocollect samples for biomonitoring and diagnosis of manyretained OCP compounds

Table 6 Octanolwater partition coefficient of key OCPs [65ndash70]

Compound log119870owAldrin 650Endrin 52Endosulfan I 383Endosulfate 366pp1015840-DDT 691pp1015840-DDE 651pp1015840-DDD 602Methoxychlor 508Heptachlor 610Hexachlorobenzene 573

In conclusion the previous four papers in this ldquobloodurine and sweat (BUS)rdquo series have demonstrated thatinduced perspiration is effective at facilitating the removal ofmany toxic elements as well as various organic compoundsbut not all [59ndash62] This OCP study provides evidence thattransdermal depuration through perspiration facilitates elim-ination of some parent and metabolite OCP compounds butnot all While the absolute amount of each OCP compoundreleased into sweat may be small according to this data anaverage adult may sweat more than one liter per hour duringexerciseUnder thermal stressmaximal rates of sweatingmaybe as high as two to four litershour [63] and sweating ratesfor ldquoacclimatizedrdquo people who regularly use saunas may be ashigh as two litershour [64] Accordingly regular sessions ofinduced perspiration should be considered cumulatively as apotential clinical modality to diminish body burdens ofmanyxenobiotics including OCP compounds

Additional Points

Key Findings

(a) DDT andor its metabolite(s) were found in nearlyevery participant regardless of age suggesting thatexposure is very common

(b) Nearly all organochlorine pesticide (OCP) parentcompounds and several metabolites were detected inperspiration suggesting that sweating may be effica-cious in diminishing the body burden of many ofthese toxicants

(c) There were some parent OCPs such as endosulfan Iand hexachlorobenzene and some metabolites suchas endrin ketone and heptachlor that were not readilyexcreted into perspiration

(d) Lipophilicity appeared to be a major factor influenc-ing the efficacy of transdermal OCP elimination butnot the exclusive determinant

(e) Only endosulfan I appeared to be predominantlydetected in urine suggesting that urine analysis haslimited value in detection of retained OCPs

8 BioMed Research International

Competing Interests

There is no conflict of interests regarding the publication ofthis paper

Acknowledgments

Thanks are due to Dr Peter Mahaffy and the Departmentof Chemistry at The Kingrsquos University for their thoughtfulassistance in this work

References

[1] Nobelprizeorg the official web site of the Nobel PrizePaul MullermdashBiographical httpwwwnobelprizeorgnobelprizesmedicinelaureates1948muller-biohtml

[2] K I Barnes D N Durrheim F Little et al ldquoEffect ofartemether-lumefantrine policy and improved vector controlon malaria burden in KwaZulu-Natal South Africardquo PLoSMedicine vol 2 no 11 article e330 2005

[3] United States Environmental Protection Agency ldquoDDT A briefhistory and statusrdquo 2016 httpswwwepagovingredients-used-pesticide-productsddt-brief-history-and-status

[4] United Nations Environment Programme Stockholm Conven-tion Protecting health and the environment from persistentorganic pollutants httpchmpopsintdefaultaspx

[5] S MWaliszewski A A Aguirre R M Infanzon and J SiliceoldquoCarry-over of persistent organochlorine pesticides throughplacenta to fetusrdquo Salud Publica de Mexico vol 42 no 5 pp384ndash390 2000

[6] S J Genuis ldquoElimination of persistent toxicants from thehuman bodyrdquo Human amp Experimental Toxicology vol 30 no1 pp 3ndash18 2010

[7] R E Herron and J B Fagan ldquoLipophil-mediated reduction oftoxicants in humans an evaluation of an ayurvedic detoxifica-tion procedurerdquo Alternative Therapies in Health and Medicinevol 8 no 5 pp 40ndash51 2002

[8] S J Genuis M E Sears G Schwalfenberg J Hope andR Bernhoft ldquoClinical detoxification elimination of persistenttoxicants from the human bodyrdquo The Scientific World Journalvol 2013 Article ID 238347 3 pages 2013

[9] S L Archibeque-Engle J D Tessari D T Winn T J KeefeT M Nett and T Zheng ldquoComparison of organochlorinepesticide and polychlorinated biphenyl residues in humanbreast adipose tissue and serumrdquo Journal of Toxicology andEnvironmental Health vol 52 no 4 pp 285ndash293 1997

[10] S J Genuis andK L Kelln ldquoToxicant exposure and bioaccumu-lation a common and potentially reversible cause of cognitivedysfunction and dementiardquo Behavioural Neurology vol 2015Article ID 620143 10 pages 2015

[11] T G Redgrave P Wallace R J Jandacek and P Tso ldquoTreat-ment with a dietary fat substitute decreased Arochlor 1254contamination in an obese diabetic malerdquo Journal of NutritionalBiochemistry vol 16 no 6 pp 383ndash384 2005

[12] G H Ross and M C Sternquist ldquoMethamphetamine exposureand chronic illness in police officers significant improvementwith sauna-based detoxification therapyrdquo Toxicology and Indus-trial Health vol 28 no 8 pp 758ndash768 2012

[13] P Williams R James and S Roberts Principles of ToxicologyJohn Wiley amp Sons New York NY USA 2000

[14] A K Pramanik and R C Hansen ldquoTranscutaneous gammabenzene hexachloride absorption and toxicity in infants andchildrenrdquo Archives of Dermatology vol 115 no 10 pp 1224ndash1225 1979

[15] V N Uversky J Li K Bower and A L Fink ldquoSynergisticeffects of pesticides andmetals on the fibrillation of120572-synucleinimplications for Parkinsonrsquos diseaserdquo NeuroToxicology vol 23no 4-5 pp 527ndash536 2002

[16] Y-M Lee S-G Bae S-H Lee D R Jacobs Jr and D-H LeeldquoAssociations between cigarette smoking and total mortalitydiffer depending on serum concentrations of persistent organicpollutants among the elderlyrdquo Journal of KoreanMedical Sciencevol 28 no 8 pp 1122ndash1128 2013

[17] P Bennett ldquoWorking Up the Toxic Patientrdquo httpwwwpeter-bennettcomresourcesdetoxificationworkingupthedetoxpa-tientpdf

[18] S J Genuis ldquoThe chemical erosion of human health adverseenvironmental exposure and in-utero pollutionmdashdeterminantsof congenital disorders and chronic diseaserdquo Journal of PerinatalMedicine vol 34 no 3 pp 185ndash195 2006

[19] E R Kabir M S Rahman and I Rahman ldquoA review onendocrine disruptors and their possible impacts on humanhealthrdquo Environmental Toxicology and Pharmacology vol 40no 1 pp 241ndash258 2015

[20] G C Di Renzo J A Conry J Blake et al ldquoInternational Fed-eration of Gynecology and Obstetrics opinion on reproductivehealth impacts of exposure to toxic environmental chemicalsrdquoInternational Journal of Gynecology amp Obstetrics vol 131 no 3pp 219ndash225 2015

[21] M K Skinner M Manikkam and C Guerrero-BosagnaldquoEpigenetic transgenerational actions of endocrine disruptorsrdquoReproductive Toxicology vol 31 no 3 pp 337ndash343 2011

[22] M E Sears and S J Genuis ldquoEnvironmental determinants ofchronic disease and medical approaches recognition avoid-ance supportive therapy and detoxificationrdquo Journal of Envi-ronmental and Public Health vol 2012 Article ID 356798 15pages 2012

[23] T M Crisp E D Clegg R L Cooper et al ldquoEnvironmentalendocrine disruption an effects assessment and analysisrdquo Envi-ronmental Health Perspectives vol 106 supplement 1 pp 11ndash561998

[24] M E A Benarbia D Macherel S Faure C Jacques R Andri-antsitohaina and Y Malthiery ldquoPlasmatic concentration oforganochlorine lindane acts as metabolic disruptors in HepG2liver cell line by inducing mitochondrial disorderrdquo Toxicologyand Applied Pharmacology vol 272 no 2 pp 325ndash334 2013

[25] C Charlier A Albert P Herman et al ldquoBreast cancer andserum organochlorine residuesrdquo Occupational and Environ-mental Medicine vol 60 no 5 pp 348ndash351 2003

[26] J Dich S H Zahm A Hanberg and H-O Adami ldquoPesticidesand cancerrdquo Cancer Causes and Control vol 8 no 3 pp 420ndash443 1997

[27] S Yasunaga KNishi S Nishimoto andT Sugahara ldquoMethoxy-chlor enhances degranulation ofmurinemast cells by regulatingFc120576RI-mediated signal transductionrdquo Journal of Immunotoxicol-ogy vol 12 no 3 pp 283ndash289 2015

[28] K Upson A J De Roos M L Thompson et al ldquoOrganochlo-rine pesticides and risk of endometriosis findings from apopulation-based case-control studyrdquo Environmental HealthPerspectives vol 121 no 11-12 pp 1319ndash1324 2013

[29] K A McGlynn S M Quraishi B I Graubard J-P Weber MV Rubertone and R L Erickson ldquoPersistent organochlorine

BioMed Research International 9

pesticides and risk of testicular germ cell tumorsrdquo Journal of theNational Cancer Institute vol 100 no 9 pp 663ndash671 2008

[30] D H Lee M W Steffes A Sjodin R S Jones L L Needhamand D R Jacobs Jr ldquoLow dose organochlorine pesticides andpolychlorinated biphenyls predict obesity dyslipidemia andinsulin resistance among people free of diabetesrdquo PLoS ONEvol 6 no 1 Article ID e15977 2011

[31] M Turyk H Anderson L Knobeloch P Imm and V PerskyldquoOrganochlorine exposure and incidence of diabetes in a cohortof great lakes sport fish consumersrdquo Environmental HealthPerspectives vol 117 no 7 pp 1076ndash1082 2009

[32] H K Son S A Kim J H Kang et al ldquoStrong associationsbetween low-dose organochlorine pesticides and type 2 dia-betes in Koreardquo Environment International vol 36 no 5 pp410ndash414 2010

[33] L Fleming J B Mann J Bean T Briggle and J R Sanchez-Ramos ldquoParkinsonrsquos disease and brain levels of organochlorinepesticidesrdquoAnnals of Neurology vol 36 no 1 pp 100ndash103 1994

[34] H J Heusinkveld and R H S Westerink ldquoOrganochlorineinsecticides lindane and dieldrin and their binary mixturedisturb calcium homeostasis in dopaminergic PC12 cellsrdquoEnvironmental Science and Technology vol 46 no 3 pp 1842ndash1848 2012

[35] J Jurewicz and W Hanke ldquoPrenatal and childhood exposureto pesticides and neurobehavioral development review ofepidemiological studiesrdquo International Journal of OccupationalMedicine and Environmental Health vol 21 no 2 pp 121ndash1322008

[36] E A Belyaeva T V Sokolova L V Emelyanova and I OZakharova ldquoMitochondrial electron transport chain in heavymetal-induced neurotoxicity effects of cadmium mercury andcopperrdquo The Scientific World Journal vol 2012 Article ID136063 14 pages 2012

[37] R Pathak S G Suke T Ahmed et al ldquoOrganochlorinepesticide residue levels and oxidative stress in preterm deliverycasesrdquoHumanampExperimental Toxicology vol 29 no 5 pp 351ndash358 2010

[38] M Zhao Y Zhang C Wang Z Fu W Liu and J GanldquoInduction of macrophage apoptosis by an organochlorineinsecticide acetofenaterdquo Chemical Research in Toxicology vol22 no 3 pp 504ndash510 2009

[39] W Mnif A I Hassine A Bouaziz A Bartegi O Thomas andB Roig ldquoEffect of endocrine disruptor pesticides a reviewrdquoInternational Journal of Environmental Research and PublicHealth vol 8 no 6 pp 2265ndash2303 2011

[40] L Hou X Zhang D Wang and A Baccarelli ldquoEnvironmentalchemical exposures and human epigeneticsrdquo International Jour-nal of Epidemiology vol 41 no 1 pp 79ndash105 2012

[41] G M Williams ldquoGenotoxic and epigenetic carcinogens theiridentification and significancerdquo Annals of the New YorkAcademy of Sciences vol 407 no 1 pp 328ndash333 1983

[42] B Hille ldquoPharmacological modifications of the sodium chan-nels of frog nerverdquo The Journal of General Physiology vol 51no 2 pp 199ndash219 1968

[43] S Gilbert A Small Dose of Toxicology CRC Press Boca RatonFla USA 2004

[44] S J Genuis ldquoSensitivity-related illness the escalating pandemicof allergy food intolerance and chemical sensitivityrdquoTheScienceof the Total Environment vol 408 no 24 pp 6047ndash6061 2010

[45] S J Genuis ldquoPandemic of idiopathic multimorbidityrdquo Cana-dian Family Physician vol 60 no 6 pp 511ndash514 2014

[46] Centers for Disease Control and Prevention Department ofHealth and Human Services Fourth National Report on HumanExposure to Environmental Chemicals CDC Atlanta Ga USA2013 httpwwwcdcgovexposurereportpdfFourthReportUpdatedTables Mar2013pdf

[47] Health Canada ldquoHuman biomonitoring of environmentalchemicalsrdquo 2015 httpwwwhealthcanadagccabiomoni-toring

[48] S J Genuis and R A Genuis ldquoPreconception care a newstandard of care within maternal health servicesrdquo BioMedResearch International vol 2016 Article ID 6150976 30 pages2016

[49] Environmental Working Group BPA and Other Cord BloodPollutants 2016 httpwwwewgorgresearchminority-cord-blood-reportbpa-and-other-cord-blood-pollutants

[50] A Sudaryanto T Kunisue N Kajiwara et al ldquoSpecific accumu-lation of organochlorines in human breastmilk from Indonesialevels distribution accumulation kinetics and infant healthriskrdquo Environmental Pollution vol 139 no 1 pp 107ndash117 2006

[51] E M Roberts P B English J K Grether G C Windham LSomberg and C Wolff ldquoMaternal residence near agriculturalpesticide applications and autism spectrum disorders amongchildren in the California Central Valleyrdquo Environmental HealthPerspectives vol 115 no 10 pp 1482ndash1489 2007

[52] R J Jandacek and S J Genuis ldquoAn assessment of the intestinallumen as a site for intervention in reducing body burdens oforganochlorine compoundsrdquo The Scientific World Journal vol2013 Article ID 205621 10 pages 2013

[53] W J Cohn J J Boylan R V Blanke M W Fariss J R Howelland P S Guzelian ldquoTreatment of chlordecone (Kepone) toxicitywith cholestyramine Results of a controlled clinical trialrdquo TheNew England Journal of Medicine vol 298 no 5 pp 243ndash2481978

[54] Y Mochida H Fukata Y Matsuno and C Mori ldquoReduction ofdioxins and polychlorinated biphenyls (PCBs) in human bodyrdquoFukuoka Igaku Zasshi vol 98 no 4 pp 106ndash113 2007

[55] K Rozman L Ballhorn and T Rozman ldquoMineral oil in the dietenhances fecal excretion of DDT in the rhesus monkeyrdquo Drugand Chemical Toxicology vol 6 no 3 pp 311ndash316 1983

[56] D W Schnare M Ben and M G Shields ldquoBody burdenreduction of PCBs PBBs and chlorinated pesticides in humansubjectsrdquo Ambio vol 13 pp 378ndash380 1984

[57] D W Schnare and P C Robinson ldquoReduction of human bodyburdens of hexachlorobenzene and polychlorinated biphenylsrdquoin Hexachlorobenzene Proceedings of an International Sym-posium C R Morris and J R P Cabral Eds pp 597ndash603International Agency for Research on Cancer Lyon France1986

[58] R J Jandacek and P Tso ldquoEnterohepatic circulation oforganochlorine compounds a site for nutritional interventionrdquoThe Journal of Nutritional Biochemistry vol 18 no 3 pp 163ndash167 2007

[59] S J Genuis D Birkholz I Rodushkin and S Beesoon ldquoBloodurine and sweat (BUS) study monitoring and eliminationof bioaccumulated toxic elementsrdquo Archives of EnvironmentalContamination and Toxicology vol 61 no 2 pp 344ndash357 2011

[60] S J Genuis S Beesoon R A Lobo and D Birkholz ldquoHumanelimination of phthalate compounds blood urine and sweat(BUS) studyrdquoThe Scientific World Journal vol 2012 Article ID615068 10 pages 2012

[61] S J Genuis S Beesoon and D Birkholz ldquoBiomonitoring andelimination of perfluorinated compounds and polychlorinated

10 BioMed Research International

biphenyls through perspiration blood urine and sweat studyrdquoISRN Toxicology vol 2013 Article ID 483832 7 pages 2013

[62] S J Genuis S Beesoon D Birkholz and R A Lobo ldquoHumanexcretion of bisphenol a blood urine and sweat (BUS) StudyrdquoJournal of Environmental and Public Health vol 2012 Article ID185731 10 pages 2012

[63] U W R Greger Comprehensive Human Physiology FromCellularMechanisms to Integration Springer Science ampBusinessMedia 2013

[64] A Eisalo and O J Luurila ldquoThe Finnish sauna and cardiovas-cular diseasesrdquo Annals of Clinical Research vol 20 no 4 pp267ndash270 1988

[65] J De Bruijn F Busser W Seinen and J Hermens ldquoDetermi-nation of octanolwater partition coefficients for hydrophobicorganic chemicals with the lsquoslow-stirringrsquo methodrdquo Environ-mental Toxicology andChemistry vol 8 no 6 pp 499ndash512 1989

[66] W de Wolf W Seinen and J L M Hermens ldquoBiotransforma-tion and toxicokinetics of trichloroanilines in fish in relation totheir hydrophobicityrdquoArchives of Environmental Contaminationand Toxicology vol 25 no 1 pp 110ndash117 1993

[67] C L A Hansch and D Hoekman Exploring QSAR AmericanChemical Society Washington DC USA 1995

[68] P H Howard and W M Meylan Handbook of Physical Prop-erties of Organic Chemicals Lewis Publishers Boca Raton FlaUSA 1997

[69] R H G Lewis Hawleyrsquos Condensed Chemical Dictionary JohnWiley amp Sons Hoboken NJ USA 15th edition 2007

[70] C D Simpson R J Wilcock T J Smith A L Wilkinsand A G Langdon ldquoDetermination of octanol-water partitioncoefficients for the major components of technical chlordanerdquoBulletin of Environmental Contamination and Toxicology vol55 no 1 pp 149ndash153 1995

Submit your manuscripts athttpwwwhindawicom

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MEDIATORSINFLAMMATION

of

Page 4: Research Article Human Elimination of Organochlorine

4 BioMed Research International

Table 2 Participant demographics and general clinical characteristics

Participant Gender Age Clinical diagnosis Technique used for sweat collection1 M 61 Diabetes obesity hypertension Exercise2 F 40 Rheumatoid arthritis Steam sauna3 M 38 Addiction disorder Steam sauna4 F 25 Bipolar disorder Steam sauna5 F 47 Lymphoma Steam sauna6 F 43 Fibromyalgia Steam sauna7 F 48 Depression Steam sauna8 F 40 Chronic fatigue Infrared sauna9 F 68 Diabetes fatigue obesity Steam sauna10 M 49 Chronic pain cognitive decline Exercise11 M 53 Healthy Exercise12 M 23 Healthy Infrared sauna13 M 21 Healthy Infrared sauna14 F 47 Healthy Infrared sauna15 M 53 Healthy Infrared sauna16 F 43 Healthy Infrared sauna17 F 51 Healthy Infrared sauna18 M 46 Healthy Infrared sauna19 M 57 Healthy Infrared sauna20 F 50 Healthy Infrared sauna

random sample of blood one sample of first morning urineand one 100mL sample of sweat Demographic and clinicalcharacteristics of all research participants are provided inTable 2

32 Samples Collection All blood samples were collected atoneDynaLIFE laboratory site in EdmontonAlberta Canadawith vacutainer blood collection equipment (BD VacutainerFranklin Lakes NJ 07417 USA) using 21-gauge stainlesssteel needles which were screwed into the ldquoBD VacutainerOne-Use Holderrdquo (REF 364815) The 10mL glass vacutainerwas directly inserted into the holder and into the backend of the needle This process and the use of glass bloodcollection tubes were used to prevent contamination Bloodwas collected directly into plain 10 mL glass vacutainer tubesallowed to clot and after 30 minutes were centrifuged for 10minutes at 2000 revolutions per minute (RPM) After serumwas separated off sampleswere picked up byALS laboratories(about 3 kilometres from the blood collection site) for storagepending analysisWhen received at ALS serum samples weretransferred to 4mLglass vials and stored in a freezer atminus20∘Cpending transfer to the analytical laboratory

For urine collection participants were instructed tocollect a first morning midstream urine sample directly intoa provided 500mL glass jar container with Teflon-lined lidon the same day that blood samples were collected Urinesamples were delivered by the participants directly to ALSlaboratories Edmonton Samples were transferred to 4 mLglass vials and stored in a freezer at minus20∘C pending transfer

For sweat collection participants were instructed tocollect perspiration from any site on their body directly intothe provided 500mL glass jar container with Teflon-lined

lid by placing the jar against their prewashed skin (withtoxicant-free soap water and nonplastic brush)when activelysweating or by using a stainless steel spatula against their skinto transfer perspiration directly into the glass jar Stainlesssteel made up primarily of iron chromium and nickel waschosen as it is the same material as the needles used instandard blood collections and is reported not to off-gasor leach at room or body temperature All but one of theparticipants (1920) provided 100mL of sweat Each of theglass bottles used for sampling in this study was provided byALS laboratories and had undergone extensive cleaning andrinsing The containers were deemed appropriate for sweatcollection with negligible risk of contamination laboratory-grade phosphate-free detergent wash acid rinse multiple hotand cold deionized water rinses oven dried capped andpacked in quality-controlled conditions

Sweat was collected within 1 week before or after collect-ing the blood and urine samples No specifications were givenas to how long sweating had commenced before collection10 participants collected sweat inside a dry infrared sauna7 collected sweat inside a steam sauna and 3 collectedsweat during and immediately after exercise no specificinstruction was given regarding the type or location ofexercise Participants were educated about the research andwere asked to meticulously avoid exposure to any potentialsources of toxicants around the time of collection Sweat wasdelivered by the participants directly to ALS laboratoriesSamples were transferred to 4mL glass vials and stored ina freezer at minus20∘C pending analysis No preservatives wereused in the jars provided for sweat and urine collection norin the serum storage vials

BioMed Research International 5

Table 3 Organochlorine pesticides analyzed

Group Parent Metabolite

DDT and analogues DDTMethoxychlor

DDE DDDNA

Hexachlorobenzene Hexachlorobenzene NA

Hexachlorocyclohexane 120572-BHC 120573-BHC 120575-BHC and120574-BHC NA

Cyclodiene

Endosulfan I endosulfan II Endosulfan sulfateAldrin Dieldrin

Endrin Endrin ketoneEndrin aldehyde

Heptachlor Heptachlor epoxidecis-chlordane trans-chlordane trans-nonachlor

Chlordeconelowast Kelevanlowast and Mirex Mirex NAToxaphenelowastlowastDid not test for this specific compound in this study

33 Laboratory Method Description Of the 6 categories ofOCPs 5 were analyzed (Table 3 toxaphene was not includedin this study) Organochlorine pesticide concentrations ofparent and metabolite compounds were analyzed usingdual-column gas chromatography with electron-capturedetectors (GC-ECD) A pair of surrogate standards tetra-chlorometaxylene (TCMX) and decachlorobiphenyl (DCB)were used to monitor the performance of the method

The methodology for determining the selected organo-chlorine pesticides was as follows Serum samples wereweighed into glass tubes (8 g) and 8mL of methanol wasadded to the serum samples Sweat and urine samples wereweighed into glass tubes (5 g) and 5mL of methanol wasadded to each of the samples Serial extraction of the bioactivecompounds was performed on serum sweat and urinesamples 3 times by adding 12mL of an ethyl ether hexanesolution (1 1 vv) and removing the supernatant via centrifu-gation The extract was then put through a sodium sulfatecolumn to dry The resulting extracts were combined andconcentrated to 1mL and put through a 12 g 2 deactivatedflorisil column Florisil was used to eliminate coelutingchlorophenols External standard calibration was used forquantification Method blanks were used to ensure qualitycontrol water and calf serum samples Instrument detectionlimits were determined to be 010 120583gkg Pentachloroni-trobenzene (PCNB) was added to the extracts as an internalstandard and the samples were analyzed by dual-column gaschromatography with electron-capture detectors (DB-5 andDB-1701)

4 Results and Discussion

The results of the study can be found in Tables 4 and 5The parent OCP compounds showed differential detection(Tables 4(a)ndash4(c)) and compounds detected in at least oneparticipantrsquos serum sample include aldrin DDT endosulfan Iand endosulfan II heptachlor mirex hexachlorobenzene 120572-HCH 120573-HCH and 120574-HCH Endrin 120575-HCH and methoxy-chlor were not detected in any of the participantrsquos serum

samples The parent compounds detected in at least oneparticipantrsquos urine sample include aldrin DDT endosulfan Iand endosulfan II endrinmirex 120574-HCH andmethoxychlorHeptachlor 120572-HCH 120573-HCH 120575-HCH and hexachloroben-zene were not detected in any participantrsquos urine sample Allof the parent compounds except the isomers of hexachloro-cyclohexane were detected in at least one participantrsquos sweatsample

The metabolite compounds also showed differentialdetection The metabolite compounds detected in at leastone participantrsquos serum sample include DDE endrin ketoneendrin aldehyde and heptachlor epoxide The metabolitesDDD endosulfan sulfate and dieldrin were not detected inany serum samples The metabolite compounds detected inat least one participantrsquos sweat sample include DDE DDDendosulfan sulfate dieldrin and endrin ketone Neitherendrin aldehyde nor heptachlor epoxide was detected in anysweat samples The metabolite compounds detected in atleast one participantrsquos urine sample include DDD endosulfansulfate dieldrin endrin aldehyde and heptachlor epoxideThe metabolites DDE and endrin ketone were not detectedin any urine samples

Of the parent compounds DDT methoxychlor andendrin as well as the metabolites DDE DDD and endo-sulfan sulfate appear to be readily excreted into sweat asthey are found in over half of the participants examined(Table 5) Additionally with the exception of DDE theseOCPs were not readily detected in blood testing while stillbeing excreted and identified in sweat This may indicatethat these OCP compounds are stored and sequestered intissues not evident in blood testing but are mobilized andexcreted during perspiration In contrast endosulfan I wasalmost exclusively detected in urine samples of over half ofthe participants (Table 5) Collectively the findings suggestthat these participants have been commonly exposed toDDTmethoxychlor endrin and endosulfan I and are also carryinga body burden of themetabolites DDEDDD and endosulfansulfate

6 BioMed Research International

Table 4 (a) Distribution of parent compounds in serum (SE) sweat (SW) and urine (U) (120583gkg) (b) Distribution of parent compounds inserum (SE) sweat (SW) and urine (U) (120583gkg) (c) Distribution of parent compounds in serum (SE) sweat (SW) and urine (U) (120583gkg)

(a)

SEAldrin

SWAldrin

UAldrin

SEDDT

SWDDT

UDDT

SEEndosulfan

I

SWEndosulfan

I

UEndosulfan

I119899lowast 2 5 2 2 14 3 1 1 13

Meanlowastlowast mdash 015 mdash mdash 049 mdash mdash mdash 014Medianlowastlowast mdash 014 mdash mdash 042 mdash mdash mdash 014Std Devlowastlowast mdash 0028 mdash mdash 023 mdash mdash mdash 0018Range 017ndash066 010ndash017 010ndash015 022ndash023 027ndash11 019ndash039 011 012 012ndash018lowast

119899 represents the number of participants with a detectable amount of the OCP from the 20 total participants examinedlowastlowastFor matrices having fewer than 5 individuals with detectable OCP levels the mean median and standard deviation measurements were not provided

(b)

SEEndrin

SWEndrin

UEndrin

SEHeptachlor

SWHeptachlor

UHeptachlor

SEMirex

SWMirex

UMirex

119899lowast 0 13 1 8 1 0 2 3 2

Meanlowastlowast mdash 018 mdash 037 mdash mdash mdash mdash mdashMedianlowastlowast mdash 015 mdash 033 mdash mdash mdash mdash mdashStd Devlowastlowast mdash 0083 mdash 017 mdash mdash mdash mdash mdashRange mdash 011ndash018 012 015ndash067 011 mdash 012ndash018 010ndash017 011ndash016lowast

119899 represents the number of participants with a detectable amount of the OCP from the 20 total participants examinedlowastlowastFor matrices having fewer than 5 individuals with detectable OCP levels the mean median and standard deviation measurements were not provided

(c)

SEMethoxychlor

SWMethoxychlor

UMethoxychlor

SEHexachlorobenzene

SWHexachlorobenzene

UHexachlorobenzene

119899lowast 0 16 3 6 1 0

Meanlowastlowast mdash 026 mdash 029 mdash mdashMedianlowastlowast mdash 022 mdash 030 mdash mdashStd Devlowastlowast mdash 013 mdash 011 mdash mdashRange mdash 013ndash070 014ndash019 018ndash049 011 mdashlowast

119899 represents the number of participants with a detectable amount of the OCP from the 20 total participants examinedlowastlowastFor matrices having fewer than 5 individuals with detectable OCP levels the mean median and standard deviation measurements were not provided

Most of the compounds examined were detected inless than half of the participants regardless of the matrix(Table 5) This likely reflects a reduced exposure level tothese compounds However hexachlorobenzene heptachlorand endrin ketone were detected in at least 30 of par-ticipants and were all predominantly detected in serumsamples (Table 5) Although some compounds were detectedin participant urine these levels typically occurred aroundthe limit of detection and at much lower levels than eitherserum or sweat analysis With the exception of endosulfan Ithis suggests that urine analysis is not reliable as an analytictool to measure the body burden of these compounds

The partitioning of these compounds in the body seemsto be related to their lipophilicity With the exception ofendosulfan I and its metabolite endosulfan sulfate all of thecompounds detected in over half of the participants havelog119870ow values above 5 (Table 6) This indicates that they arehighly lipophilic and fat soluble and are expected to sequesterin fat tissue In comparison to the compounds found

predominantly in sweat hexachlorobenzene and heptachlorhave reportedly similar degrees of lipophilicity but werepredominantly found in blood (Tables 4(a)ndash4(c)) Thereforethese findings may suggest that lipophilicity is not the onlyfactor affecting the partitioning of these compounds

There are limitations to the study and to interpretationof the results There has been discussion in lay circles thatdiffering means of thermal depuration by varying types ofsauna (such as infrared sauna versus steam sauna) exerciseor other perspiration induction activities may result indifferences in excretion rates through skinThis study did nothave an adequate data set to control for potential differencesin the excretion of the range of OCPs between usages of far-infrared sauna regular sauna or exercise Several other issuesmay impact the reliability and reproducibility of perspirationanalysis that were not considered including body site ofsampling timing of collection while perspiring differencesin skin characteristics between individuals temperature andhumidity of the surroundings and factors such as diet

BioMed Research International 7

Table 5 Percentage of individuals with detection of organochlorinepesticides within serum sweat and urine (119899 = 20)

Serum Sweat Urine441015840-DDT 10 70 15441015840-DDE 95 70 0441015840-DDD 0 65 35Methoxychlor 0 80 15Endosulfan I 5 5 65Endosulfan sulfate 0 85 10Endrin 0 50 5Aldrin 10 25 10Dieldrin 0 15 10trans-nonachlor 0 5 0BHC (hexachlorobenzene) 30 5 0120572-BHC 10 0 0120573-BHC 15 0 0120575-BHC 0 0 0120574-BHC 1 0 1Endosulfan II 10 10 5Endrin ketone 35 5 0Endrin aldehyde 5 0 5Heptachlor epoxide 5 0 15Heptachlor 40 5 0cis-chlordane 5 5 0trans-chlordane 10 15 10Mirex 5 15 15

pharmaceutical intake and supplement use Accordinglyattempts to accurately quantify the relative amount of toxi-cants released into perspiration are limited

Areas for future research in relation to induced perspi-ration might include an examination of (i) differences inrates of excretion into perspiration of assorted xenobioticsfrom diverse sites in the body (ii) whether there is diurnalvariation in the toxicant content of perspiration (iii) whetherhydration status affects the xenobiotic concentration of per-spiration (iv) dermal reabsorption potential of toxicants afterperspiration and (v) the release of xenobiotics in those infasting states compared to those without caloric restriction

5 Conclusion

As DDT DDE DDD methoxychlor endosulfan sulfate andendrin appear to be readily excreted into sweat inducedperspiration appears to be a potential clinical tool to diminishthe body burden of these agents With the exception ofDDE however these agents are not readily detected in bloodtesting This suggests that common blood analysis may nottruly represent the body burden of these compounds Asthe routine use of unprovoked blood testing may thus beinadequate for biomonitoring body burdens of OCPs theremay be clinical advantages to the induction of perspirationthrough methods like sauna andor exercise in order tocollect samples for biomonitoring and diagnosis of manyretained OCP compounds

Table 6 Octanolwater partition coefficient of key OCPs [65ndash70]

Compound log119870owAldrin 650Endrin 52Endosulfan I 383Endosulfate 366pp1015840-DDT 691pp1015840-DDE 651pp1015840-DDD 602Methoxychlor 508Heptachlor 610Hexachlorobenzene 573

In conclusion the previous four papers in this ldquobloodurine and sweat (BUS)rdquo series have demonstrated thatinduced perspiration is effective at facilitating the removal ofmany toxic elements as well as various organic compoundsbut not all [59ndash62] This OCP study provides evidence thattransdermal depuration through perspiration facilitates elim-ination of some parent and metabolite OCP compounds butnot all While the absolute amount of each OCP compoundreleased into sweat may be small according to this data anaverage adult may sweat more than one liter per hour duringexerciseUnder thermal stressmaximal rates of sweatingmaybe as high as two to four litershour [63] and sweating ratesfor ldquoacclimatizedrdquo people who regularly use saunas may be ashigh as two litershour [64] Accordingly regular sessions ofinduced perspiration should be considered cumulatively as apotential clinical modality to diminish body burdens ofmanyxenobiotics including OCP compounds

Additional Points

Key Findings

(a) DDT andor its metabolite(s) were found in nearlyevery participant regardless of age suggesting thatexposure is very common

(b) Nearly all organochlorine pesticide (OCP) parentcompounds and several metabolites were detected inperspiration suggesting that sweating may be effica-cious in diminishing the body burden of many ofthese toxicants

(c) There were some parent OCPs such as endosulfan Iand hexachlorobenzene and some metabolites suchas endrin ketone and heptachlor that were not readilyexcreted into perspiration

(d) Lipophilicity appeared to be a major factor influenc-ing the efficacy of transdermal OCP elimination butnot the exclusive determinant

(e) Only endosulfan I appeared to be predominantlydetected in urine suggesting that urine analysis haslimited value in detection of retained OCPs

8 BioMed Research International

Competing Interests

There is no conflict of interests regarding the publication ofthis paper

Acknowledgments

Thanks are due to Dr Peter Mahaffy and the Departmentof Chemistry at The Kingrsquos University for their thoughtfulassistance in this work

References

[1] Nobelprizeorg the official web site of the Nobel PrizePaul MullermdashBiographical httpwwwnobelprizeorgnobelprizesmedicinelaureates1948muller-biohtml

[2] K I Barnes D N Durrheim F Little et al ldquoEffect ofartemether-lumefantrine policy and improved vector controlon malaria burden in KwaZulu-Natal South Africardquo PLoSMedicine vol 2 no 11 article e330 2005

[3] United States Environmental Protection Agency ldquoDDT A briefhistory and statusrdquo 2016 httpswwwepagovingredients-used-pesticide-productsddt-brief-history-and-status

[4] United Nations Environment Programme Stockholm Conven-tion Protecting health and the environment from persistentorganic pollutants httpchmpopsintdefaultaspx

[5] S MWaliszewski A A Aguirre R M Infanzon and J SiliceoldquoCarry-over of persistent organochlorine pesticides throughplacenta to fetusrdquo Salud Publica de Mexico vol 42 no 5 pp384ndash390 2000

[6] S J Genuis ldquoElimination of persistent toxicants from thehuman bodyrdquo Human amp Experimental Toxicology vol 30 no1 pp 3ndash18 2010

[7] R E Herron and J B Fagan ldquoLipophil-mediated reduction oftoxicants in humans an evaluation of an ayurvedic detoxifica-tion procedurerdquo Alternative Therapies in Health and Medicinevol 8 no 5 pp 40ndash51 2002

[8] S J Genuis M E Sears G Schwalfenberg J Hope andR Bernhoft ldquoClinical detoxification elimination of persistenttoxicants from the human bodyrdquo The Scientific World Journalvol 2013 Article ID 238347 3 pages 2013

[9] S L Archibeque-Engle J D Tessari D T Winn T J KeefeT M Nett and T Zheng ldquoComparison of organochlorinepesticide and polychlorinated biphenyl residues in humanbreast adipose tissue and serumrdquo Journal of Toxicology andEnvironmental Health vol 52 no 4 pp 285ndash293 1997

[10] S J Genuis andK L Kelln ldquoToxicant exposure and bioaccumu-lation a common and potentially reversible cause of cognitivedysfunction and dementiardquo Behavioural Neurology vol 2015Article ID 620143 10 pages 2015

[11] T G Redgrave P Wallace R J Jandacek and P Tso ldquoTreat-ment with a dietary fat substitute decreased Arochlor 1254contamination in an obese diabetic malerdquo Journal of NutritionalBiochemistry vol 16 no 6 pp 383ndash384 2005

[12] G H Ross and M C Sternquist ldquoMethamphetamine exposureand chronic illness in police officers significant improvementwith sauna-based detoxification therapyrdquo Toxicology and Indus-trial Health vol 28 no 8 pp 758ndash768 2012

[13] P Williams R James and S Roberts Principles of ToxicologyJohn Wiley amp Sons New York NY USA 2000

[14] A K Pramanik and R C Hansen ldquoTranscutaneous gammabenzene hexachloride absorption and toxicity in infants andchildrenrdquo Archives of Dermatology vol 115 no 10 pp 1224ndash1225 1979

[15] V N Uversky J Li K Bower and A L Fink ldquoSynergisticeffects of pesticides andmetals on the fibrillation of120572-synucleinimplications for Parkinsonrsquos diseaserdquo NeuroToxicology vol 23no 4-5 pp 527ndash536 2002

[16] Y-M Lee S-G Bae S-H Lee D R Jacobs Jr and D-H LeeldquoAssociations between cigarette smoking and total mortalitydiffer depending on serum concentrations of persistent organicpollutants among the elderlyrdquo Journal of KoreanMedical Sciencevol 28 no 8 pp 1122ndash1128 2013

[17] P Bennett ldquoWorking Up the Toxic Patientrdquo httpwwwpeter-bennettcomresourcesdetoxificationworkingupthedetoxpa-tientpdf

[18] S J Genuis ldquoThe chemical erosion of human health adverseenvironmental exposure and in-utero pollutionmdashdeterminantsof congenital disorders and chronic diseaserdquo Journal of PerinatalMedicine vol 34 no 3 pp 185ndash195 2006

[19] E R Kabir M S Rahman and I Rahman ldquoA review onendocrine disruptors and their possible impacts on humanhealthrdquo Environmental Toxicology and Pharmacology vol 40no 1 pp 241ndash258 2015

[20] G C Di Renzo J A Conry J Blake et al ldquoInternational Fed-eration of Gynecology and Obstetrics opinion on reproductivehealth impacts of exposure to toxic environmental chemicalsrdquoInternational Journal of Gynecology amp Obstetrics vol 131 no 3pp 219ndash225 2015

[21] M K Skinner M Manikkam and C Guerrero-BosagnaldquoEpigenetic transgenerational actions of endocrine disruptorsrdquoReproductive Toxicology vol 31 no 3 pp 337ndash343 2011

[22] M E Sears and S J Genuis ldquoEnvironmental determinants ofchronic disease and medical approaches recognition avoid-ance supportive therapy and detoxificationrdquo Journal of Envi-ronmental and Public Health vol 2012 Article ID 356798 15pages 2012

[23] T M Crisp E D Clegg R L Cooper et al ldquoEnvironmentalendocrine disruption an effects assessment and analysisrdquo Envi-ronmental Health Perspectives vol 106 supplement 1 pp 11ndash561998

[24] M E A Benarbia D Macherel S Faure C Jacques R Andri-antsitohaina and Y Malthiery ldquoPlasmatic concentration oforganochlorine lindane acts as metabolic disruptors in HepG2liver cell line by inducing mitochondrial disorderrdquo Toxicologyand Applied Pharmacology vol 272 no 2 pp 325ndash334 2013

[25] C Charlier A Albert P Herman et al ldquoBreast cancer andserum organochlorine residuesrdquo Occupational and Environ-mental Medicine vol 60 no 5 pp 348ndash351 2003

[26] J Dich S H Zahm A Hanberg and H-O Adami ldquoPesticidesand cancerrdquo Cancer Causes and Control vol 8 no 3 pp 420ndash443 1997

[27] S Yasunaga KNishi S Nishimoto andT Sugahara ldquoMethoxy-chlor enhances degranulation ofmurinemast cells by regulatingFc120576RI-mediated signal transductionrdquo Journal of Immunotoxicol-ogy vol 12 no 3 pp 283ndash289 2015

[28] K Upson A J De Roos M L Thompson et al ldquoOrganochlo-rine pesticides and risk of endometriosis findings from apopulation-based case-control studyrdquo Environmental HealthPerspectives vol 121 no 11-12 pp 1319ndash1324 2013

[29] K A McGlynn S M Quraishi B I Graubard J-P Weber MV Rubertone and R L Erickson ldquoPersistent organochlorine

BioMed Research International 9

pesticides and risk of testicular germ cell tumorsrdquo Journal of theNational Cancer Institute vol 100 no 9 pp 663ndash671 2008

[30] D H Lee M W Steffes A Sjodin R S Jones L L Needhamand D R Jacobs Jr ldquoLow dose organochlorine pesticides andpolychlorinated biphenyls predict obesity dyslipidemia andinsulin resistance among people free of diabetesrdquo PLoS ONEvol 6 no 1 Article ID e15977 2011

[31] M Turyk H Anderson L Knobeloch P Imm and V PerskyldquoOrganochlorine exposure and incidence of diabetes in a cohortof great lakes sport fish consumersrdquo Environmental HealthPerspectives vol 117 no 7 pp 1076ndash1082 2009

[32] H K Son S A Kim J H Kang et al ldquoStrong associationsbetween low-dose organochlorine pesticides and type 2 dia-betes in Koreardquo Environment International vol 36 no 5 pp410ndash414 2010

[33] L Fleming J B Mann J Bean T Briggle and J R Sanchez-Ramos ldquoParkinsonrsquos disease and brain levels of organochlorinepesticidesrdquoAnnals of Neurology vol 36 no 1 pp 100ndash103 1994

[34] H J Heusinkveld and R H S Westerink ldquoOrganochlorineinsecticides lindane and dieldrin and their binary mixturedisturb calcium homeostasis in dopaminergic PC12 cellsrdquoEnvironmental Science and Technology vol 46 no 3 pp 1842ndash1848 2012

[35] J Jurewicz and W Hanke ldquoPrenatal and childhood exposureto pesticides and neurobehavioral development review ofepidemiological studiesrdquo International Journal of OccupationalMedicine and Environmental Health vol 21 no 2 pp 121ndash1322008

[36] E A Belyaeva T V Sokolova L V Emelyanova and I OZakharova ldquoMitochondrial electron transport chain in heavymetal-induced neurotoxicity effects of cadmium mercury andcopperrdquo The Scientific World Journal vol 2012 Article ID136063 14 pages 2012

[37] R Pathak S G Suke T Ahmed et al ldquoOrganochlorinepesticide residue levels and oxidative stress in preterm deliverycasesrdquoHumanampExperimental Toxicology vol 29 no 5 pp 351ndash358 2010

[38] M Zhao Y Zhang C Wang Z Fu W Liu and J GanldquoInduction of macrophage apoptosis by an organochlorineinsecticide acetofenaterdquo Chemical Research in Toxicology vol22 no 3 pp 504ndash510 2009

[39] W Mnif A I Hassine A Bouaziz A Bartegi O Thomas andB Roig ldquoEffect of endocrine disruptor pesticides a reviewrdquoInternational Journal of Environmental Research and PublicHealth vol 8 no 6 pp 2265ndash2303 2011

[40] L Hou X Zhang D Wang and A Baccarelli ldquoEnvironmentalchemical exposures and human epigeneticsrdquo International Jour-nal of Epidemiology vol 41 no 1 pp 79ndash105 2012

[41] G M Williams ldquoGenotoxic and epigenetic carcinogens theiridentification and significancerdquo Annals of the New YorkAcademy of Sciences vol 407 no 1 pp 328ndash333 1983

[42] B Hille ldquoPharmacological modifications of the sodium chan-nels of frog nerverdquo The Journal of General Physiology vol 51no 2 pp 199ndash219 1968

[43] S Gilbert A Small Dose of Toxicology CRC Press Boca RatonFla USA 2004

[44] S J Genuis ldquoSensitivity-related illness the escalating pandemicof allergy food intolerance and chemical sensitivityrdquoTheScienceof the Total Environment vol 408 no 24 pp 6047ndash6061 2010

[45] S J Genuis ldquoPandemic of idiopathic multimorbidityrdquo Cana-dian Family Physician vol 60 no 6 pp 511ndash514 2014

[46] Centers for Disease Control and Prevention Department ofHealth and Human Services Fourth National Report on HumanExposure to Environmental Chemicals CDC Atlanta Ga USA2013 httpwwwcdcgovexposurereportpdfFourthReportUpdatedTables Mar2013pdf

[47] Health Canada ldquoHuman biomonitoring of environmentalchemicalsrdquo 2015 httpwwwhealthcanadagccabiomoni-toring

[48] S J Genuis and R A Genuis ldquoPreconception care a newstandard of care within maternal health servicesrdquo BioMedResearch International vol 2016 Article ID 6150976 30 pages2016

[49] Environmental Working Group BPA and Other Cord BloodPollutants 2016 httpwwwewgorgresearchminority-cord-blood-reportbpa-and-other-cord-blood-pollutants

[50] A Sudaryanto T Kunisue N Kajiwara et al ldquoSpecific accumu-lation of organochlorines in human breastmilk from Indonesialevels distribution accumulation kinetics and infant healthriskrdquo Environmental Pollution vol 139 no 1 pp 107ndash117 2006

[51] E M Roberts P B English J K Grether G C Windham LSomberg and C Wolff ldquoMaternal residence near agriculturalpesticide applications and autism spectrum disorders amongchildren in the California Central Valleyrdquo Environmental HealthPerspectives vol 115 no 10 pp 1482ndash1489 2007

[52] R J Jandacek and S J Genuis ldquoAn assessment of the intestinallumen as a site for intervention in reducing body burdens oforganochlorine compoundsrdquo The Scientific World Journal vol2013 Article ID 205621 10 pages 2013

[53] W J Cohn J J Boylan R V Blanke M W Fariss J R Howelland P S Guzelian ldquoTreatment of chlordecone (Kepone) toxicitywith cholestyramine Results of a controlled clinical trialrdquo TheNew England Journal of Medicine vol 298 no 5 pp 243ndash2481978

[54] Y Mochida H Fukata Y Matsuno and C Mori ldquoReduction ofdioxins and polychlorinated biphenyls (PCBs) in human bodyrdquoFukuoka Igaku Zasshi vol 98 no 4 pp 106ndash113 2007

[55] K Rozman L Ballhorn and T Rozman ldquoMineral oil in the dietenhances fecal excretion of DDT in the rhesus monkeyrdquo Drugand Chemical Toxicology vol 6 no 3 pp 311ndash316 1983

[56] D W Schnare M Ben and M G Shields ldquoBody burdenreduction of PCBs PBBs and chlorinated pesticides in humansubjectsrdquo Ambio vol 13 pp 378ndash380 1984

[57] D W Schnare and P C Robinson ldquoReduction of human bodyburdens of hexachlorobenzene and polychlorinated biphenylsrdquoin Hexachlorobenzene Proceedings of an International Sym-posium C R Morris and J R P Cabral Eds pp 597ndash603International Agency for Research on Cancer Lyon France1986

[58] R J Jandacek and P Tso ldquoEnterohepatic circulation oforganochlorine compounds a site for nutritional interventionrdquoThe Journal of Nutritional Biochemistry vol 18 no 3 pp 163ndash167 2007

[59] S J Genuis D Birkholz I Rodushkin and S Beesoon ldquoBloodurine and sweat (BUS) study monitoring and eliminationof bioaccumulated toxic elementsrdquo Archives of EnvironmentalContamination and Toxicology vol 61 no 2 pp 344ndash357 2011

[60] S J Genuis S Beesoon R A Lobo and D Birkholz ldquoHumanelimination of phthalate compounds blood urine and sweat(BUS) studyrdquoThe Scientific World Journal vol 2012 Article ID615068 10 pages 2012

[61] S J Genuis S Beesoon and D Birkholz ldquoBiomonitoring andelimination of perfluorinated compounds and polychlorinated

10 BioMed Research International

biphenyls through perspiration blood urine and sweat studyrdquoISRN Toxicology vol 2013 Article ID 483832 7 pages 2013

[62] S J Genuis S Beesoon D Birkholz and R A Lobo ldquoHumanexcretion of bisphenol a blood urine and sweat (BUS) StudyrdquoJournal of Environmental and Public Health vol 2012 Article ID185731 10 pages 2012

[63] U W R Greger Comprehensive Human Physiology FromCellularMechanisms to Integration Springer Science ampBusinessMedia 2013

[64] A Eisalo and O J Luurila ldquoThe Finnish sauna and cardiovas-cular diseasesrdquo Annals of Clinical Research vol 20 no 4 pp267ndash270 1988

[65] J De Bruijn F Busser W Seinen and J Hermens ldquoDetermi-nation of octanolwater partition coefficients for hydrophobicorganic chemicals with the lsquoslow-stirringrsquo methodrdquo Environ-mental Toxicology andChemistry vol 8 no 6 pp 499ndash512 1989

[66] W de Wolf W Seinen and J L M Hermens ldquoBiotransforma-tion and toxicokinetics of trichloroanilines in fish in relation totheir hydrophobicityrdquoArchives of Environmental Contaminationand Toxicology vol 25 no 1 pp 110ndash117 1993

[67] C L A Hansch and D Hoekman Exploring QSAR AmericanChemical Society Washington DC USA 1995

[68] P H Howard and W M Meylan Handbook of Physical Prop-erties of Organic Chemicals Lewis Publishers Boca Raton FlaUSA 1997

[69] R H G Lewis Hawleyrsquos Condensed Chemical Dictionary JohnWiley amp Sons Hoboken NJ USA 15th edition 2007

[70] C D Simpson R J Wilcock T J Smith A L Wilkinsand A G Langdon ldquoDetermination of octanol-water partitioncoefficients for the major components of technical chlordanerdquoBulletin of Environmental Contamination and Toxicology vol55 no 1 pp 149ndash153 1995

Submit your manuscripts athttpwwwhindawicom

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ToxinsJournal of

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MEDIATORSINFLAMMATION

of

Page 5: Research Article Human Elimination of Organochlorine

BioMed Research International 5

Table 3 Organochlorine pesticides analyzed

Group Parent Metabolite

DDT and analogues DDTMethoxychlor

DDE DDDNA

Hexachlorobenzene Hexachlorobenzene NA

Hexachlorocyclohexane 120572-BHC 120573-BHC 120575-BHC and120574-BHC NA

Cyclodiene

Endosulfan I endosulfan II Endosulfan sulfateAldrin Dieldrin

Endrin Endrin ketoneEndrin aldehyde

Heptachlor Heptachlor epoxidecis-chlordane trans-chlordane trans-nonachlor

Chlordeconelowast Kelevanlowast and Mirex Mirex NAToxaphenelowastlowastDid not test for this specific compound in this study

33 Laboratory Method Description Of the 6 categories ofOCPs 5 were analyzed (Table 3 toxaphene was not includedin this study) Organochlorine pesticide concentrations ofparent and metabolite compounds were analyzed usingdual-column gas chromatography with electron-capturedetectors (GC-ECD) A pair of surrogate standards tetra-chlorometaxylene (TCMX) and decachlorobiphenyl (DCB)were used to monitor the performance of the method

The methodology for determining the selected organo-chlorine pesticides was as follows Serum samples wereweighed into glass tubes (8 g) and 8mL of methanol wasadded to the serum samples Sweat and urine samples wereweighed into glass tubes (5 g) and 5mL of methanol wasadded to each of the samples Serial extraction of the bioactivecompounds was performed on serum sweat and urinesamples 3 times by adding 12mL of an ethyl ether hexanesolution (1 1 vv) and removing the supernatant via centrifu-gation The extract was then put through a sodium sulfatecolumn to dry The resulting extracts were combined andconcentrated to 1mL and put through a 12 g 2 deactivatedflorisil column Florisil was used to eliminate coelutingchlorophenols External standard calibration was used forquantification Method blanks were used to ensure qualitycontrol water and calf serum samples Instrument detectionlimits were determined to be 010 120583gkg Pentachloroni-trobenzene (PCNB) was added to the extracts as an internalstandard and the samples were analyzed by dual-column gaschromatography with electron-capture detectors (DB-5 andDB-1701)

4 Results and Discussion

The results of the study can be found in Tables 4 and 5The parent OCP compounds showed differential detection(Tables 4(a)ndash4(c)) and compounds detected in at least oneparticipantrsquos serum sample include aldrin DDT endosulfan Iand endosulfan II heptachlor mirex hexachlorobenzene 120572-HCH 120573-HCH and 120574-HCH Endrin 120575-HCH and methoxy-chlor were not detected in any of the participantrsquos serum

samples The parent compounds detected in at least oneparticipantrsquos urine sample include aldrin DDT endosulfan Iand endosulfan II endrinmirex 120574-HCH andmethoxychlorHeptachlor 120572-HCH 120573-HCH 120575-HCH and hexachloroben-zene were not detected in any participantrsquos urine sample Allof the parent compounds except the isomers of hexachloro-cyclohexane were detected in at least one participantrsquos sweatsample

The metabolite compounds also showed differentialdetection The metabolite compounds detected in at leastone participantrsquos serum sample include DDE endrin ketoneendrin aldehyde and heptachlor epoxide The metabolitesDDD endosulfan sulfate and dieldrin were not detected inany serum samples The metabolite compounds detected inat least one participantrsquos sweat sample include DDE DDDendosulfan sulfate dieldrin and endrin ketone Neitherendrin aldehyde nor heptachlor epoxide was detected in anysweat samples The metabolite compounds detected in atleast one participantrsquos urine sample include DDD endosulfansulfate dieldrin endrin aldehyde and heptachlor epoxideThe metabolites DDE and endrin ketone were not detectedin any urine samples

Of the parent compounds DDT methoxychlor andendrin as well as the metabolites DDE DDD and endo-sulfan sulfate appear to be readily excreted into sweat asthey are found in over half of the participants examined(Table 5) Additionally with the exception of DDE theseOCPs were not readily detected in blood testing while stillbeing excreted and identified in sweat This may indicatethat these OCP compounds are stored and sequestered intissues not evident in blood testing but are mobilized andexcreted during perspiration In contrast endosulfan I wasalmost exclusively detected in urine samples of over half ofthe participants (Table 5) Collectively the findings suggestthat these participants have been commonly exposed toDDTmethoxychlor endrin and endosulfan I and are also carryinga body burden of themetabolites DDEDDD and endosulfansulfate

6 BioMed Research International

Table 4 (a) Distribution of parent compounds in serum (SE) sweat (SW) and urine (U) (120583gkg) (b) Distribution of parent compounds inserum (SE) sweat (SW) and urine (U) (120583gkg) (c) Distribution of parent compounds in serum (SE) sweat (SW) and urine (U) (120583gkg)

(a)

SEAldrin

SWAldrin

UAldrin

SEDDT

SWDDT

UDDT

SEEndosulfan

I

SWEndosulfan

I

UEndosulfan

I119899lowast 2 5 2 2 14 3 1 1 13

Meanlowastlowast mdash 015 mdash mdash 049 mdash mdash mdash 014Medianlowastlowast mdash 014 mdash mdash 042 mdash mdash mdash 014Std Devlowastlowast mdash 0028 mdash mdash 023 mdash mdash mdash 0018Range 017ndash066 010ndash017 010ndash015 022ndash023 027ndash11 019ndash039 011 012 012ndash018lowast

119899 represents the number of participants with a detectable amount of the OCP from the 20 total participants examinedlowastlowastFor matrices having fewer than 5 individuals with detectable OCP levels the mean median and standard deviation measurements were not provided

(b)

SEEndrin

SWEndrin

UEndrin

SEHeptachlor

SWHeptachlor

UHeptachlor

SEMirex

SWMirex

UMirex

119899lowast 0 13 1 8 1 0 2 3 2

Meanlowastlowast mdash 018 mdash 037 mdash mdash mdash mdash mdashMedianlowastlowast mdash 015 mdash 033 mdash mdash mdash mdash mdashStd Devlowastlowast mdash 0083 mdash 017 mdash mdash mdash mdash mdashRange mdash 011ndash018 012 015ndash067 011 mdash 012ndash018 010ndash017 011ndash016lowast

119899 represents the number of participants with a detectable amount of the OCP from the 20 total participants examinedlowastlowastFor matrices having fewer than 5 individuals with detectable OCP levels the mean median and standard deviation measurements were not provided

(c)

SEMethoxychlor

SWMethoxychlor

UMethoxychlor

SEHexachlorobenzene

SWHexachlorobenzene

UHexachlorobenzene

119899lowast 0 16 3 6 1 0

Meanlowastlowast mdash 026 mdash 029 mdash mdashMedianlowastlowast mdash 022 mdash 030 mdash mdashStd Devlowastlowast mdash 013 mdash 011 mdash mdashRange mdash 013ndash070 014ndash019 018ndash049 011 mdashlowast

119899 represents the number of participants with a detectable amount of the OCP from the 20 total participants examinedlowastlowastFor matrices having fewer than 5 individuals with detectable OCP levels the mean median and standard deviation measurements were not provided

Most of the compounds examined were detected inless than half of the participants regardless of the matrix(Table 5) This likely reflects a reduced exposure level tothese compounds However hexachlorobenzene heptachlorand endrin ketone were detected in at least 30 of par-ticipants and were all predominantly detected in serumsamples (Table 5) Although some compounds were detectedin participant urine these levels typically occurred aroundthe limit of detection and at much lower levels than eitherserum or sweat analysis With the exception of endosulfan Ithis suggests that urine analysis is not reliable as an analytictool to measure the body burden of these compounds

The partitioning of these compounds in the body seemsto be related to their lipophilicity With the exception ofendosulfan I and its metabolite endosulfan sulfate all of thecompounds detected in over half of the participants havelog119870ow values above 5 (Table 6) This indicates that they arehighly lipophilic and fat soluble and are expected to sequesterin fat tissue In comparison to the compounds found

predominantly in sweat hexachlorobenzene and heptachlorhave reportedly similar degrees of lipophilicity but werepredominantly found in blood (Tables 4(a)ndash4(c)) Thereforethese findings may suggest that lipophilicity is not the onlyfactor affecting the partitioning of these compounds

There are limitations to the study and to interpretationof the results There has been discussion in lay circles thatdiffering means of thermal depuration by varying types ofsauna (such as infrared sauna versus steam sauna) exerciseor other perspiration induction activities may result indifferences in excretion rates through skinThis study did nothave an adequate data set to control for potential differencesin the excretion of the range of OCPs between usages of far-infrared sauna regular sauna or exercise Several other issuesmay impact the reliability and reproducibility of perspirationanalysis that were not considered including body site ofsampling timing of collection while perspiring differencesin skin characteristics between individuals temperature andhumidity of the surroundings and factors such as diet

BioMed Research International 7

Table 5 Percentage of individuals with detection of organochlorinepesticides within serum sweat and urine (119899 = 20)

Serum Sweat Urine441015840-DDT 10 70 15441015840-DDE 95 70 0441015840-DDD 0 65 35Methoxychlor 0 80 15Endosulfan I 5 5 65Endosulfan sulfate 0 85 10Endrin 0 50 5Aldrin 10 25 10Dieldrin 0 15 10trans-nonachlor 0 5 0BHC (hexachlorobenzene) 30 5 0120572-BHC 10 0 0120573-BHC 15 0 0120575-BHC 0 0 0120574-BHC 1 0 1Endosulfan II 10 10 5Endrin ketone 35 5 0Endrin aldehyde 5 0 5Heptachlor epoxide 5 0 15Heptachlor 40 5 0cis-chlordane 5 5 0trans-chlordane 10 15 10Mirex 5 15 15

pharmaceutical intake and supplement use Accordinglyattempts to accurately quantify the relative amount of toxi-cants released into perspiration are limited

Areas for future research in relation to induced perspi-ration might include an examination of (i) differences inrates of excretion into perspiration of assorted xenobioticsfrom diverse sites in the body (ii) whether there is diurnalvariation in the toxicant content of perspiration (iii) whetherhydration status affects the xenobiotic concentration of per-spiration (iv) dermal reabsorption potential of toxicants afterperspiration and (v) the release of xenobiotics in those infasting states compared to those without caloric restriction

5 Conclusion

As DDT DDE DDD methoxychlor endosulfan sulfate andendrin appear to be readily excreted into sweat inducedperspiration appears to be a potential clinical tool to diminishthe body burden of these agents With the exception ofDDE however these agents are not readily detected in bloodtesting This suggests that common blood analysis may nottruly represent the body burden of these compounds Asthe routine use of unprovoked blood testing may thus beinadequate for biomonitoring body burdens of OCPs theremay be clinical advantages to the induction of perspirationthrough methods like sauna andor exercise in order tocollect samples for biomonitoring and diagnosis of manyretained OCP compounds

Table 6 Octanolwater partition coefficient of key OCPs [65ndash70]

Compound log119870owAldrin 650Endrin 52Endosulfan I 383Endosulfate 366pp1015840-DDT 691pp1015840-DDE 651pp1015840-DDD 602Methoxychlor 508Heptachlor 610Hexachlorobenzene 573

In conclusion the previous four papers in this ldquobloodurine and sweat (BUS)rdquo series have demonstrated thatinduced perspiration is effective at facilitating the removal ofmany toxic elements as well as various organic compoundsbut not all [59ndash62] This OCP study provides evidence thattransdermal depuration through perspiration facilitates elim-ination of some parent and metabolite OCP compounds butnot all While the absolute amount of each OCP compoundreleased into sweat may be small according to this data anaverage adult may sweat more than one liter per hour duringexerciseUnder thermal stressmaximal rates of sweatingmaybe as high as two to four litershour [63] and sweating ratesfor ldquoacclimatizedrdquo people who regularly use saunas may be ashigh as two litershour [64] Accordingly regular sessions ofinduced perspiration should be considered cumulatively as apotential clinical modality to diminish body burdens ofmanyxenobiotics including OCP compounds

Additional Points

Key Findings

(a) DDT andor its metabolite(s) were found in nearlyevery participant regardless of age suggesting thatexposure is very common

(b) Nearly all organochlorine pesticide (OCP) parentcompounds and several metabolites were detected inperspiration suggesting that sweating may be effica-cious in diminishing the body burden of many ofthese toxicants

(c) There were some parent OCPs such as endosulfan Iand hexachlorobenzene and some metabolites suchas endrin ketone and heptachlor that were not readilyexcreted into perspiration

(d) Lipophilicity appeared to be a major factor influenc-ing the efficacy of transdermal OCP elimination butnot the exclusive determinant

(e) Only endosulfan I appeared to be predominantlydetected in urine suggesting that urine analysis haslimited value in detection of retained OCPs

8 BioMed Research International

Competing Interests

There is no conflict of interests regarding the publication ofthis paper

Acknowledgments

Thanks are due to Dr Peter Mahaffy and the Departmentof Chemistry at The Kingrsquos University for their thoughtfulassistance in this work

References

[1] Nobelprizeorg the official web site of the Nobel PrizePaul MullermdashBiographical httpwwwnobelprizeorgnobelprizesmedicinelaureates1948muller-biohtml

[2] K I Barnes D N Durrheim F Little et al ldquoEffect ofartemether-lumefantrine policy and improved vector controlon malaria burden in KwaZulu-Natal South Africardquo PLoSMedicine vol 2 no 11 article e330 2005

[3] United States Environmental Protection Agency ldquoDDT A briefhistory and statusrdquo 2016 httpswwwepagovingredients-used-pesticide-productsddt-brief-history-and-status

[4] United Nations Environment Programme Stockholm Conven-tion Protecting health and the environment from persistentorganic pollutants httpchmpopsintdefaultaspx

[5] S MWaliszewski A A Aguirre R M Infanzon and J SiliceoldquoCarry-over of persistent organochlorine pesticides throughplacenta to fetusrdquo Salud Publica de Mexico vol 42 no 5 pp384ndash390 2000

[6] S J Genuis ldquoElimination of persistent toxicants from thehuman bodyrdquo Human amp Experimental Toxicology vol 30 no1 pp 3ndash18 2010

[7] R E Herron and J B Fagan ldquoLipophil-mediated reduction oftoxicants in humans an evaluation of an ayurvedic detoxifica-tion procedurerdquo Alternative Therapies in Health and Medicinevol 8 no 5 pp 40ndash51 2002

[8] S J Genuis M E Sears G Schwalfenberg J Hope andR Bernhoft ldquoClinical detoxification elimination of persistenttoxicants from the human bodyrdquo The Scientific World Journalvol 2013 Article ID 238347 3 pages 2013

[9] S L Archibeque-Engle J D Tessari D T Winn T J KeefeT M Nett and T Zheng ldquoComparison of organochlorinepesticide and polychlorinated biphenyl residues in humanbreast adipose tissue and serumrdquo Journal of Toxicology andEnvironmental Health vol 52 no 4 pp 285ndash293 1997

[10] S J Genuis andK L Kelln ldquoToxicant exposure and bioaccumu-lation a common and potentially reversible cause of cognitivedysfunction and dementiardquo Behavioural Neurology vol 2015Article ID 620143 10 pages 2015

[11] T G Redgrave P Wallace R J Jandacek and P Tso ldquoTreat-ment with a dietary fat substitute decreased Arochlor 1254contamination in an obese diabetic malerdquo Journal of NutritionalBiochemistry vol 16 no 6 pp 383ndash384 2005

[12] G H Ross and M C Sternquist ldquoMethamphetamine exposureand chronic illness in police officers significant improvementwith sauna-based detoxification therapyrdquo Toxicology and Indus-trial Health vol 28 no 8 pp 758ndash768 2012

[13] P Williams R James and S Roberts Principles of ToxicologyJohn Wiley amp Sons New York NY USA 2000

[14] A K Pramanik and R C Hansen ldquoTranscutaneous gammabenzene hexachloride absorption and toxicity in infants andchildrenrdquo Archives of Dermatology vol 115 no 10 pp 1224ndash1225 1979

[15] V N Uversky J Li K Bower and A L Fink ldquoSynergisticeffects of pesticides andmetals on the fibrillation of120572-synucleinimplications for Parkinsonrsquos diseaserdquo NeuroToxicology vol 23no 4-5 pp 527ndash536 2002

[16] Y-M Lee S-G Bae S-H Lee D R Jacobs Jr and D-H LeeldquoAssociations between cigarette smoking and total mortalitydiffer depending on serum concentrations of persistent organicpollutants among the elderlyrdquo Journal of KoreanMedical Sciencevol 28 no 8 pp 1122ndash1128 2013

[17] P Bennett ldquoWorking Up the Toxic Patientrdquo httpwwwpeter-bennettcomresourcesdetoxificationworkingupthedetoxpa-tientpdf

[18] S J Genuis ldquoThe chemical erosion of human health adverseenvironmental exposure and in-utero pollutionmdashdeterminantsof congenital disorders and chronic diseaserdquo Journal of PerinatalMedicine vol 34 no 3 pp 185ndash195 2006

[19] E R Kabir M S Rahman and I Rahman ldquoA review onendocrine disruptors and their possible impacts on humanhealthrdquo Environmental Toxicology and Pharmacology vol 40no 1 pp 241ndash258 2015

[20] G C Di Renzo J A Conry J Blake et al ldquoInternational Fed-eration of Gynecology and Obstetrics opinion on reproductivehealth impacts of exposure to toxic environmental chemicalsrdquoInternational Journal of Gynecology amp Obstetrics vol 131 no 3pp 219ndash225 2015

[21] M K Skinner M Manikkam and C Guerrero-BosagnaldquoEpigenetic transgenerational actions of endocrine disruptorsrdquoReproductive Toxicology vol 31 no 3 pp 337ndash343 2011

[22] M E Sears and S J Genuis ldquoEnvironmental determinants ofchronic disease and medical approaches recognition avoid-ance supportive therapy and detoxificationrdquo Journal of Envi-ronmental and Public Health vol 2012 Article ID 356798 15pages 2012

[23] T M Crisp E D Clegg R L Cooper et al ldquoEnvironmentalendocrine disruption an effects assessment and analysisrdquo Envi-ronmental Health Perspectives vol 106 supplement 1 pp 11ndash561998

[24] M E A Benarbia D Macherel S Faure C Jacques R Andri-antsitohaina and Y Malthiery ldquoPlasmatic concentration oforganochlorine lindane acts as metabolic disruptors in HepG2liver cell line by inducing mitochondrial disorderrdquo Toxicologyand Applied Pharmacology vol 272 no 2 pp 325ndash334 2013

[25] C Charlier A Albert P Herman et al ldquoBreast cancer andserum organochlorine residuesrdquo Occupational and Environ-mental Medicine vol 60 no 5 pp 348ndash351 2003

[26] J Dich S H Zahm A Hanberg and H-O Adami ldquoPesticidesand cancerrdquo Cancer Causes and Control vol 8 no 3 pp 420ndash443 1997

[27] S Yasunaga KNishi S Nishimoto andT Sugahara ldquoMethoxy-chlor enhances degranulation ofmurinemast cells by regulatingFc120576RI-mediated signal transductionrdquo Journal of Immunotoxicol-ogy vol 12 no 3 pp 283ndash289 2015

[28] K Upson A J De Roos M L Thompson et al ldquoOrganochlo-rine pesticides and risk of endometriosis findings from apopulation-based case-control studyrdquo Environmental HealthPerspectives vol 121 no 11-12 pp 1319ndash1324 2013

[29] K A McGlynn S M Quraishi B I Graubard J-P Weber MV Rubertone and R L Erickson ldquoPersistent organochlorine

BioMed Research International 9

pesticides and risk of testicular germ cell tumorsrdquo Journal of theNational Cancer Institute vol 100 no 9 pp 663ndash671 2008

[30] D H Lee M W Steffes A Sjodin R S Jones L L Needhamand D R Jacobs Jr ldquoLow dose organochlorine pesticides andpolychlorinated biphenyls predict obesity dyslipidemia andinsulin resistance among people free of diabetesrdquo PLoS ONEvol 6 no 1 Article ID e15977 2011

[31] M Turyk H Anderson L Knobeloch P Imm and V PerskyldquoOrganochlorine exposure and incidence of diabetes in a cohortof great lakes sport fish consumersrdquo Environmental HealthPerspectives vol 117 no 7 pp 1076ndash1082 2009

[32] H K Son S A Kim J H Kang et al ldquoStrong associationsbetween low-dose organochlorine pesticides and type 2 dia-betes in Koreardquo Environment International vol 36 no 5 pp410ndash414 2010

[33] L Fleming J B Mann J Bean T Briggle and J R Sanchez-Ramos ldquoParkinsonrsquos disease and brain levels of organochlorinepesticidesrdquoAnnals of Neurology vol 36 no 1 pp 100ndash103 1994

[34] H J Heusinkveld and R H S Westerink ldquoOrganochlorineinsecticides lindane and dieldrin and their binary mixturedisturb calcium homeostasis in dopaminergic PC12 cellsrdquoEnvironmental Science and Technology vol 46 no 3 pp 1842ndash1848 2012

[35] J Jurewicz and W Hanke ldquoPrenatal and childhood exposureto pesticides and neurobehavioral development review ofepidemiological studiesrdquo International Journal of OccupationalMedicine and Environmental Health vol 21 no 2 pp 121ndash1322008

[36] E A Belyaeva T V Sokolova L V Emelyanova and I OZakharova ldquoMitochondrial electron transport chain in heavymetal-induced neurotoxicity effects of cadmium mercury andcopperrdquo The Scientific World Journal vol 2012 Article ID136063 14 pages 2012

[37] R Pathak S G Suke T Ahmed et al ldquoOrganochlorinepesticide residue levels and oxidative stress in preterm deliverycasesrdquoHumanampExperimental Toxicology vol 29 no 5 pp 351ndash358 2010

[38] M Zhao Y Zhang C Wang Z Fu W Liu and J GanldquoInduction of macrophage apoptosis by an organochlorineinsecticide acetofenaterdquo Chemical Research in Toxicology vol22 no 3 pp 504ndash510 2009

[39] W Mnif A I Hassine A Bouaziz A Bartegi O Thomas andB Roig ldquoEffect of endocrine disruptor pesticides a reviewrdquoInternational Journal of Environmental Research and PublicHealth vol 8 no 6 pp 2265ndash2303 2011

[40] L Hou X Zhang D Wang and A Baccarelli ldquoEnvironmentalchemical exposures and human epigeneticsrdquo International Jour-nal of Epidemiology vol 41 no 1 pp 79ndash105 2012

[41] G M Williams ldquoGenotoxic and epigenetic carcinogens theiridentification and significancerdquo Annals of the New YorkAcademy of Sciences vol 407 no 1 pp 328ndash333 1983

[42] B Hille ldquoPharmacological modifications of the sodium chan-nels of frog nerverdquo The Journal of General Physiology vol 51no 2 pp 199ndash219 1968

[43] S Gilbert A Small Dose of Toxicology CRC Press Boca RatonFla USA 2004

[44] S J Genuis ldquoSensitivity-related illness the escalating pandemicof allergy food intolerance and chemical sensitivityrdquoTheScienceof the Total Environment vol 408 no 24 pp 6047ndash6061 2010

[45] S J Genuis ldquoPandemic of idiopathic multimorbidityrdquo Cana-dian Family Physician vol 60 no 6 pp 511ndash514 2014

[46] Centers for Disease Control and Prevention Department ofHealth and Human Services Fourth National Report on HumanExposure to Environmental Chemicals CDC Atlanta Ga USA2013 httpwwwcdcgovexposurereportpdfFourthReportUpdatedTables Mar2013pdf

[47] Health Canada ldquoHuman biomonitoring of environmentalchemicalsrdquo 2015 httpwwwhealthcanadagccabiomoni-toring

[48] S J Genuis and R A Genuis ldquoPreconception care a newstandard of care within maternal health servicesrdquo BioMedResearch International vol 2016 Article ID 6150976 30 pages2016

[49] Environmental Working Group BPA and Other Cord BloodPollutants 2016 httpwwwewgorgresearchminority-cord-blood-reportbpa-and-other-cord-blood-pollutants

[50] A Sudaryanto T Kunisue N Kajiwara et al ldquoSpecific accumu-lation of organochlorines in human breastmilk from Indonesialevels distribution accumulation kinetics and infant healthriskrdquo Environmental Pollution vol 139 no 1 pp 107ndash117 2006

[51] E M Roberts P B English J K Grether G C Windham LSomberg and C Wolff ldquoMaternal residence near agriculturalpesticide applications and autism spectrum disorders amongchildren in the California Central Valleyrdquo Environmental HealthPerspectives vol 115 no 10 pp 1482ndash1489 2007

[52] R J Jandacek and S J Genuis ldquoAn assessment of the intestinallumen as a site for intervention in reducing body burdens oforganochlorine compoundsrdquo The Scientific World Journal vol2013 Article ID 205621 10 pages 2013

[53] W J Cohn J J Boylan R V Blanke M W Fariss J R Howelland P S Guzelian ldquoTreatment of chlordecone (Kepone) toxicitywith cholestyramine Results of a controlled clinical trialrdquo TheNew England Journal of Medicine vol 298 no 5 pp 243ndash2481978

[54] Y Mochida H Fukata Y Matsuno and C Mori ldquoReduction ofdioxins and polychlorinated biphenyls (PCBs) in human bodyrdquoFukuoka Igaku Zasshi vol 98 no 4 pp 106ndash113 2007

[55] K Rozman L Ballhorn and T Rozman ldquoMineral oil in the dietenhances fecal excretion of DDT in the rhesus monkeyrdquo Drugand Chemical Toxicology vol 6 no 3 pp 311ndash316 1983

[56] D W Schnare M Ben and M G Shields ldquoBody burdenreduction of PCBs PBBs and chlorinated pesticides in humansubjectsrdquo Ambio vol 13 pp 378ndash380 1984

[57] D W Schnare and P C Robinson ldquoReduction of human bodyburdens of hexachlorobenzene and polychlorinated biphenylsrdquoin Hexachlorobenzene Proceedings of an International Sym-posium C R Morris and J R P Cabral Eds pp 597ndash603International Agency for Research on Cancer Lyon France1986

[58] R J Jandacek and P Tso ldquoEnterohepatic circulation oforganochlorine compounds a site for nutritional interventionrdquoThe Journal of Nutritional Biochemistry vol 18 no 3 pp 163ndash167 2007

[59] S J Genuis D Birkholz I Rodushkin and S Beesoon ldquoBloodurine and sweat (BUS) study monitoring and eliminationof bioaccumulated toxic elementsrdquo Archives of EnvironmentalContamination and Toxicology vol 61 no 2 pp 344ndash357 2011

[60] S J Genuis S Beesoon R A Lobo and D Birkholz ldquoHumanelimination of phthalate compounds blood urine and sweat(BUS) studyrdquoThe Scientific World Journal vol 2012 Article ID615068 10 pages 2012

[61] S J Genuis S Beesoon and D Birkholz ldquoBiomonitoring andelimination of perfluorinated compounds and polychlorinated

10 BioMed Research International

biphenyls through perspiration blood urine and sweat studyrdquoISRN Toxicology vol 2013 Article ID 483832 7 pages 2013

[62] S J Genuis S Beesoon D Birkholz and R A Lobo ldquoHumanexcretion of bisphenol a blood urine and sweat (BUS) StudyrdquoJournal of Environmental and Public Health vol 2012 Article ID185731 10 pages 2012

[63] U W R Greger Comprehensive Human Physiology FromCellularMechanisms to Integration Springer Science ampBusinessMedia 2013

[64] A Eisalo and O J Luurila ldquoThe Finnish sauna and cardiovas-cular diseasesrdquo Annals of Clinical Research vol 20 no 4 pp267ndash270 1988

[65] J De Bruijn F Busser W Seinen and J Hermens ldquoDetermi-nation of octanolwater partition coefficients for hydrophobicorganic chemicals with the lsquoslow-stirringrsquo methodrdquo Environ-mental Toxicology andChemistry vol 8 no 6 pp 499ndash512 1989

[66] W de Wolf W Seinen and J L M Hermens ldquoBiotransforma-tion and toxicokinetics of trichloroanilines in fish in relation totheir hydrophobicityrdquoArchives of Environmental Contaminationand Toxicology vol 25 no 1 pp 110ndash117 1993

[67] C L A Hansch and D Hoekman Exploring QSAR AmericanChemical Society Washington DC USA 1995

[68] P H Howard and W M Meylan Handbook of Physical Prop-erties of Organic Chemicals Lewis Publishers Boca Raton FlaUSA 1997

[69] R H G Lewis Hawleyrsquos Condensed Chemical Dictionary JohnWiley amp Sons Hoboken NJ USA 15th edition 2007

[70] C D Simpson R J Wilcock T J Smith A L Wilkinsand A G Langdon ldquoDetermination of octanol-water partitioncoefficients for the major components of technical chlordanerdquoBulletin of Environmental Contamination and Toxicology vol55 no 1 pp 149ndash153 1995

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AddictionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Page 6: Research Article Human Elimination of Organochlorine

6 BioMed Research International

Table 4 (a) Distribution of parent compounds in serum (SE) sweat (SW) and urine (U) (120583gkg) (b) Distribution of parent compounds inserum (SE) sweat (SW) and urine (U) (120583gkg) (c) Distribution of parent compounds in serum (SE) sweat (SW) and urine (U) (120583gkg)

(a)

SEAldrin

SWAldrin

UAldrin

SEDDT

SWDDT

UDDT

SEEndosulfan

I

SWEndosulfan

I

UEndosulfan

I119899lowast 2 5 2 2 14 3 1 1 13

Meanlowastlowast mdash 015 mdash mdash 049 mdash mdash mdash 014Medianlowastlowast mdash 014 mdash mdash 042 mdash mdash mdash 014Std Devlowastlowast mdash 0028 mdash mdash 023 mdash mdash mdash 0018Range 017ndash066 010ndash017 010ndash015 022ndash023 027ndash11 019ndash039 011 012 012ndash018lowast

119899 represents the number of participants with a detectable amount of the OCP from the 20 total participants examinedlowastlowastFor matrices having fewer than 5 individuals with detectable OCP levels the mean median and standard deviation measurements were not provided

(b)

SEEndrin

SWEndrin

UEndrin

SEHeptachlor

SWHeptachlor

UHeptachlor

SEMirex

SWMirex

UMirex

119899lowast 0 13 1 8 1 0 2 3 2

Meanlowastlowast mdash 018 mdash 037 mdash mdash mdash mdash mdashMedianlowastlowast mdash 015 mdash 033 mdash mdash mdash mdash mdashStd Devlowastlowast mdash 0083 mdash 017 mdash mdash mdash mdash mdashRange mdash 011ndash018 012 015ndash067 011 mdash 012ndash018 010ndash017 011ndash016lowast

119899 represents the number of participants with a detectable amount of the OCP from the 20 total participants examinedlowastlowastFor matrices having fewer than 5 individuals with detectable OCP levels the mean median and standard deviation measurements were not provided

(c)

SEMethoxychlor

SWMethoxychlor

UMethoxychlor

SEHexachlorobenzene

SWHexachlorobenzene

UHexachlorobenzene

119899lowast 0 16 3 6 1 0

Meanlowastlowast mdash 026 mdash 029 mdash mdashMedianlowastlowast mdash 022 mdash 030 mdash mdashStd Devlowastlowast mdash 013 mdash 011 mdash mdashRange mdash 013ndash070 014ndash019 018ndash049 011 mdashlowast

119899 represents the number of participants with a detectable amount of the OCP from the 20 total participants examinedlowastlowastFor matrices having fewer than 5 individuals with detectable OCP levels the mean median and standard deviation measurements were not provided

Most of the compounds examined were detected inless than half of the participants regardless of the matrix(Table 5) This likely reflects a reduced exposure level tothese compounds However hexachlorobenzene heptachlorand endrin ketone were detected in at least 30 of par-ticipants and were all predominantly detected in serumsamples (Table 5) Although some compounds were detectedin participant urine these levels typically occurred aroundthe limit of detection and at much lower levels than eitherserum or sweat analysis With the exception of endosulfan Ithis suggests that urine analysis is not reliable as an analytictool to measure the body burden of these compounds

The partitioning of these compounds in the body seemsto be related to their lipophilicity With the exception ofendosulfan I and its metabolite endosulfan sulfate all of thecompounds detected in over half of the participants havelog119870ow values above 5 (Table 6) This indicates that they arehighly lipophilic and fat soluble and are expected to sequesterin fat tissue In comparison to the compounds found

predominantly in sweat hexachlorobenzene and heptachlorhave reportedly similar degrees of lipophilicity but werepredominantly found in blood (Tables 4(a)ndash4(c)) Thereforethese findings may suggest that lipophilicity is not the onlyfactor affecting the partitioning of these compounds

There are limitations to the study and to interpretationof the results There has been discussion in lay circles thatdiffering means of thermal depuration by varying types ofsauna (such as infrared sauna versus steam sauna) exerciseor other perspiration induction activities may result indifferences in excretion rates through skinThis study did nothave an adequate data set to control for potential differencesin the excretion of the range of OCPs between usages of far-infrared sauna regular sauna or exercise Several other issuesmay impact the reliability and reproducibility of perspirationanalysis that were not considered including body site ofsampling timing of collection while perspiring differencesin skin characteristics between individuals temperature andhumidity of the surroundings and factors such as diet

BioMed Research International 7

Table 5 Percentage of individuals with detection of organochlorinepesticides within serum sweat and urine (119899 = 20)

Serum Sweat Urine441015840-DDT 10 70 15441015840-DDE 95 70 0441015840-DDD 0 65 35Methoxychlor 0 80 15Endosulfan I 5 5 65Endosulfan sulfate 0 85 10Endrin 0 50 5Aldrin 10 25 10Dieldrin 0 15 10trans-nonachlor 0 5 0BHC (hexachlorobenzene) 30 5 0120572-BHC 10 0 0120573-BHC 15 0 0120575-BHC 0 0 0120574-BHC 1 0 1Endosulfan II 10 10 5Endrin ketone 35 5 0Endrin aldehyde 5 0 5Heptachlor epoxide 5 0 15Heptachlor 40 5 0cis-chlordane 5 5 0trans-chlordane 10 15 10Mirex 5 15 15

pharmaceutical intake and supplement use Accordinglyattempts to accurately quantify the relative amount of toxi-cants released into perspiration are limited

Areas for future research in relation to induced perspi-ration might include an examination of (i) differences inrates of excretion into perspiration of assorted xenobioticsfrom diverse sites in the body (ii) whether there is diurnalvariation in the toxicant content of perspiration (iii) whetherhydration status affects the xenobiotic concentration of per-spiration (iv) dermal reabsorption potential of toxicants afterperspiration and (v) the release of xenobiotics in those infasting states compared to those without caloric restriction

5 Conclusion

As DDT DDE DDD methoxychlor endosulfan sulfate andendrin appear to be readily excreted into sweat inducedperspiration appears to be a potential clinical tool to diminishthe body burden of these agents With the exception ofDDE however these agents are not readily detected in bloodtesting This suggests that common blood analysis may nottruly represent the body burden of these compounds Asthe routine use of unprovoked blood testing may thus beinadequate for biomonitoring body burdens of OCPs theremay be clinical advantages to the induction of perspirationthrough methods like sauna andor exercise in order tocollect samples for biomonitoring and diagnosis of manyretained OCP compounds

Table 6 Octanolwater partition coefficient of key OCPs [65ndash70]

Compound log119870owAldrin 650Endrin 52Endosulfan I 383Endosulfate 366pp1015840-DDT 691pp1015840-DDE 651pp1015840-DDD 602Methoxychlor 508Heptachlor 610Hexachlorobenzene 573

In conclusion the previous four papers in this ldquobloodurine and sweat (BUS)rdquo series have demonstrated thatinduced perspiration is effective at facilitating the removal ofmany toxic elements as well as various organic compoundsbut not all [59ndash62] This OCP study provides evidence thattransdermal depuration through perspiration facilitates elim-ination of some parent and metabolite OCP compounds butnot all While the absolute amount of each OCP compoundreleased into sweat may be small according to this data anaverage adult may sweat more than one liter per hour duringexerciseUnder thermal stressmaximal rates of sweatingmaybe as high as two to four litershour [63] and sweating ratesfor ldquoacclimatizedrdquo people who regularly use saunas may be ashigh as two litershour [64] Accordingly regular sessions ofinduced perspiration should be considered cumulatively as apotential clinical modality to diminish body burdens ofmanyxenobiotics including OCP compounds

Additional Points

Key Findings

(a) DDT andor its metabolite(s) were found in nearlyevery participant regardless of age suggesting thatexposure is very common

(b) Nearly all organochlorine pesticide (OCP) parentcompounds and several metabolites were detected inperspiration suggesting that sweating may be effica-cious in diminishing the body burden of many ofthese toxicants

(c) There were some parent OCPs such as endosulfan Iand hexachlorobenzene and some metabolites suchas endrin ketone and heptachlor that were not readilyexcreted into perspiration

(d) Lipophilicity appeared to be a major factor influenc-ing the efficacy of transdermal OCP elimination butnot the exclusive determinant

(e) Only endosulfan I appeared to be predominantlydetected in urine suggesting that urine analysis haslimited value in detection of retained OCPs

8 BioMed Research International

Competing Interests

There is no conflict of interests regarding the publication ofthis paper

Acknowledgments

Thanks are due to Dr Peter Mahaffy and the Departmentof Chemistry at The Kingrsquos University for their thoughtfulassistance in this work

References

[1] Nobelprizeorg the official web site of the Nobel PrizePaul MullermdashBiographical httpwwwnobelprizeorgnobelprizesmedicinelaureates1948muller-biohtml

[2] K I Barnes D N Durrheim F Little et al ldquoEffect ofartemether-lumefantrine policy and improved vector controlon malaria burden in KwaZulu-Natal South Africardquo PLoSMedicine vol 2 no 11 article e330 2005

[3] United States Environmental Protection Agency ldquoDDT A briefhistory and statusrdquo 2016 httpswwwepagovingredients-used-pesticide-productsddt-brief-history-and-status

[4] United Nations Environment Programme Stockholm Conven-tion Protecting health and the environment from persistentorganic pollutants httpchmpopsintdefaultaspx

[5] S MWaliszewski A A Aguirre R M Infanzon and J SiliceoldquoCarry-over of persistent organochlorine pesticides throughplacenta to fetusrdquo Salud Publica de Mexico vol 42 no 5 pp384ndash390 2000

[6] S J Genuis ldquoElimination of persistent toxicants from thehuman bodyrdquo Human amp Experimental Toxicology vol 30 no1 pp 3ndash18 2010

[7] R E Herron and J B Fagan ldquoLipophil-mediated reduction oftoxicants in humans an evaluation of an ayurvedic detoxifica-tion procedurerdquo Alternative Therapies in Health and Medicinevol 8 no 5 pp 40ndash51 2002

[8] S J Genuis M E Sears G Schwalfenberg J Hope andR Bernhoft ldquoClinical detoxification elimination of persistenttoxicants from the human bodyrdquo The Scientific World Journalvol 2013 Article ID 238347 3 pages 2013

[9] S L Archibeque-Engle J D Tessari D T Winn T J KeefeT M Nett and T Zheng ldquoComparison of organochlorinepesticide and polychlorinated biphenyl residues in humanbreast adipose tissue and serumrdquo Journal of Toxicology andEnvironmental Health vol 52 no 4 pp 285ndash293 1997

[10] S J Genuis andK L Kelln ldquoToxicant exposure and bioaccumu-lation a common and potentially reversible cause of cognitivedysfunction and dementiardquo Behavioural Neurology vol 2015Article ID 620143 10 pages 2015

[11] T G Redgrave P Wallace R J Jandacek and P Tso ldquoTreat-ment with a dietary fat substitute decreased Arochlor 1254contamination in an obese diabetic malerdquo Journal of NutritionalBiochemistry vol 16 no 6 pp 383ndash384 2005

[12] G H Ross and M C Sternquist ldquoMethamphetamine exposureand chronic illness in police officers significant improvementwith sauna-based detoxification therapyrdquo Toxicology and Indus-trial Health vol 28 no 8 pp 758ndash768 2012

[13] P Williams R James and S Roberts Principles of ToxicologyJohn Wiley amp Sons New York NY USA 2000

[14] A K Pramanik and R C Hansen ldquoTranscutaneous gammabenzene hexachloride absorption and toxicity in infants andchildrenrdquo Archives of Dermatology vol 115 no 10 pp 1224ndash1225 1979

[15] V N Uversky J Li K Bower and A L Fink ldquoSynergisticeffects of pesticides andmetals on the fibrillation of120572-synucleinimplications for Parkinsonrsquos diseaserdquo NeuroToxicology vol 23no 4-5 pp 527ndash536 2002

[16] Y-M Lee S-G Bae S-H Lee D R Jacobs Jr and D-H LeeldquoAssociations between cigarette smoking and total mortalitydiffer depending on serum concentrations of persistent organicpollutants among the elderlyrdquo Journal of KoreanMedical Sciencevol 28 no 8 pp 1122ndash1128 2013

[17] P Bennett ldquoWorking Up the Toxic Patientrdquo httpwwwpeter-bennettcomresourcesdetoxificationworkingupthedetoxpa-tientpdf

[18] S J Genuis ldquoThe chemical erosion of human health adverseenvironmental exposure and in-utero pollutionmdashdeterminantsof congenital disorders and chronic diseaserdquo Journal of PerinatalMedicine vol 34 no 3 pp 185ndash195 2006

[19] E R Kabir M S Rahman and I Rahman ldquoA review onendocrine disruptors and their possible impacts on humanhealthrdquo Environmental Toxicology and Pharmacology vol 40no 1 pp 241ndash258 2015

[20] G C Di Renzo J A Conry J Blake et al ldquoInternational Fed-eration of Gynecology and Obstetrics opinion on reproductivehealth impacts of exposure to toxic environmental chemicalsrdquoInternational Journal of Gynecology amp Obstetrics vol 131 no 3pp 219ndash225 2015

[21] M K Skinner M Manikkam and C Guerrero-BosagnaldquoEpigenetic transgenerational actions of endocrine disruptorsrdquoReproductive Toxicology vol 31 no 3 pp 337ndash343 2011

[22] M E Sears and S J Genuis ldquoEnvironmental determinants ofchronic disease and medical approaches recognition avoid-ance supportive therapy and detoxificationrdquo Journal of Envi-ronmental and Public Health vol 2012 Article ID 356798 15pages 2012

[23] T M Crisp E D Clegg R L Cooper et al ldquoEnvironmentalendocrine disruption an effects assessment and analysisrdquo Envi-ronmental Health Perspectives vol 106 supplement 1 pp 11ndash561998

[24] M E A Benarbia D Macherel S Faure C Jacques R Andri-antsitohaina and Y Malthiery ldquoPlasmatic concentration oforganochlorine lindane acts as metabolic disruptors in HepG2liver cell line by inducing mitochondrial disorderrdquo Toxicologyand Applied Pharmacology vol 272 no 2 pp 325ndash334 2013

[25] C Charlier A Albert P Herman et al ldquoBreast cancer andserum organochlorine residuesrdquo Occupational and Environ-mental Medicine vol 60 no 5 pp 348ndash351 2003

[26] J Dich S H Zahm A Hanberg and H-O Adami ldquoPesticidesand cancerrdquo Cancer Causes and Control vol 8 no 3 pp 420ndash443 1997

[27] S Yasunaga KNishi S Nishimoto andT Sugahara ldquoMethoxy-chlor enhances degranulation ofmurinemast cells by regulatingFc120576RI-mediated signal transductionrdquo Journal of Immunotoxicol-ogy vol 12 no 3 pp 283ndash289 2015

[28] K Upson A J De Roos M L Thompson et al ldquoOrganochlo-rine pesticides and risk of endometriosis findings from apopulation-based case-control studyrdquo Environmental HealthPerspectives vol 121 no 11-12 pp 1319ndash1324 2013

[29] K A McGlynn S M Quraishi B I Graubard J-P Weber MV Rubertone and R L Erickson ldquoPersistent organochlorine

BioMed Research International 9

pesticides and risk of testicular germ cell tumorsrdquo Journal of theNational Cancer Institute vol 100 no 9 pp 663ndash671 2008

[30] D H Lee M W Steffes A Sjodin R S Jones L L Needhamand D R Jacobs Jr ldquoLow dose organochlorine pesticides andpolychlorinated biphenyls predict obesity dyslipidemia andinsulin resistance among people free of diabetesrdquo PLoS ONEvol 6 no 1 Article ID e15977 2011

[31] M Turyk H Anderson L Knobeloch P Imm and V PerskyldquoOrganochlorine exposure and incidence of diabetes in a cohortof great lakes sport fish consumersrdquo Environmental HealthPerspectives vol 117 no 7 pp 1076ndash1082 2009

[32] H K Son S A Kim J H Kang et al ldquoStrong associationsbetween low-dose organochlorine pesticides and type 2 dia-betes in Koreardquo Environment International vol 36 no 5 pp410ndash414 2010

[33] L Fleming J B Mann J Bean T Briggle and J R Sanchez-Ramos ldquoParkinsonrsquos disease and brain levels of organochlorinepesticidesrdquoAnnals of Neurology vol 36 no 1 pp 100ndash103 1994

[34] H J Heusinkveld and R H S Westerink ldquoOrganochlorineinsecticides lindane and dieldrin and their binary mixturedisturb calcium homeostasis in dopaminergic PC12 cellsrdquoEnvironmental Science and Technology vol 46 no 3 pp 1842ndash1848 2012

[35] J Jurewicz and W Hanke ldquoPrenatal and childhood exposureto pesticides and neurobehavioral development review ofepidemiological studiesrdquo International Journal of OccupationalMedicine and Environmental Health vol 21 no 2 pp 121ndash1322008

[36] E A Belyaeva T V Sokolova L V Emelyanova and I OZakharova ldquoMitochondrial electron transport chain in heavymetal-induced neurotoxicity effects of cadmium mercury andcopperrdquo The Scientific World Journal vol 2012 Article ID136063 14 pages 2012

[37] R Pathak S G Suke T Ahmed et al ldquoOrganochlorinepesticide residue levels and oxidative stress in preterm deliverycasesrdquoHumanampExperimental Toxicology vol 29 no 5 pp 351ndash358 2010

[38] M Zhao Y Zhang C Wang Z Fu W Liu and J GanldquoInduction of macrophage apoptosis by an organochlorineinsecticide acetofenaterdquo Chemical Research in Toxicology vol22 no 3 pp 504ndash510 2009

[39] W Mnif A I Hassine A Bouaziz A Bartegi O Thomas andB Roig ldquoEffect of endocrine disruptor pesticides a reviewrdquoInternational Journal of Environmental Research and PublicHealth vol 8 no 6 pp 2265ndash2303 2011

[40] L Hou X Zhang D Wang and A Baccarelli ldquoEnvironmentalchemical exposures and human epigeneticsrdquo International Jour-nal of Epidemiology vol 41 no 1 pp 79ndash105 2012

[41] G M Williams ldquoGenotoxic and epigenetic carcinogens theiridentification and significancerdquo Annals of the New YorkAcademy of Sciences vol 407 no 1 pp 328ndash333 1983

[42] B Hille ldquoPharmacological modifications of the sodium chan-nels of frog nerverdquo The Journal of General Physiology vol 51no 2 pp 199ndash219 1968

[43] S Gilbert A Small Dose of Toxicology CRC Press Boca RatonFla USA 2004

[44] S J Genuis ldquoSensitivity-related illness the escalating pandemicof allergy food intolerance and chemical sensitivityrdquoTheScienceof the Total Environment vol 408 no 24 pp 6047ndash6061 2010

[45] S J Genuis ldquoPandemic of idiopathic multimorbidityrdquo Cana-dian Family Physician vol 60 no 6 pp 511ndash514 2014

[46] Centers for Disease Control and Prevention Department ofHealth and Human Services Fourth National Report on HumanExposure to Environmental Chemicals CDC Atlanta Ga USA2013 httpwwwcdcgovexposurereportpdfFourthReportUpdatedTables Mar2013pdf

[47] Health Canada ldquoHuman biomonitoring of environmentalchemicalsrdquo 2015 httpwwwhealthcanadagccabiomoni-toring

[48] S J Genuis and R A Genuis ldquoPreconception care a newstandard of care within maternal health servicesrdquo BioMedResearch International vol 2016 Article ID 6150976 30 pages2016

[49] Environmental Working Group BPA and Other Cord BloodPollutants 2016 httpwwwewgorgresearchminority-cord-blood-reportbpa-and-other-cord-blood-pollutants

[50] A Sudaryanto T Kunisue N Kajiwara et al ldquoSpecific accumu-lation of organochlorines in human breastmilk from Indonesialevels distribution accumulation kinetics and infant healthriskrdquo Environmental Pollution vol 139 no 1 pp 107ndash117 2006

[51] E M Roberts P B English J K Grether G C Windham LSomberg and C Wolff ldquoMaternal residence near agriculturalpesticide applications and autism spectrum disorders amongchildren in the California Central Valleyrdquo Environmental HealthPerspectives vol 115 no 10 pp 1482ndash1489 2007

[52] R J Jandacek and S J Genuis ldquoAn assessment of the intestinallumen as a site for intervention in reducing body burdens oforganochlorine compoundsrdquo The Scientific World Journal vol2013 Article ID 205621 10 pages 2013

[53] W J Cohn J J Boylan R V Blanke M W Fariss J R Howelland P S Guzelian ldquoTreatment of chlordecone (Kepone) toxicitywith cholestyramine Results of a controlled clinical trialrdquo TheNew England Journal of Medicine vol 298 no 5 pp 243ndash2481978

[54] Y Mochida H Fukata Y Matsuno and C Mori ldquoReduction ofdioxins and polychlorinated biphenyls (PCBs) in human bodyrdquoFukuoka Igaku Zasshi vol 98 no 4 pp 106ndash113 2007

[55] K Rozman L Ballhorn and T Rozman ldquoMineral oil in the dietenhances fecal excretion of DDT in the rhesus monkeyrdquo Drugand Chemical Toxicology vol 6 no 3 pp 311ndash316 1983

[56] D W Schnare M Ben and M G Shields ldquoBody burdenreduction of PCBs PBBs and chlorinated pesticides in humansubjectsrdquo Ambio vol 13 pp 378ndash380 1984

[57] D W Schnare and P C Robinson ldquoReduction of human bodyburdens of hexachlorobenzene and polychlorinated biphenylsrdquoin Hexachlorobenzene Proceedings of an International Sym-posium C R Morris and J R P Cabral Eds pp 597ndash603International Agency for Research on Cancer Lyon France1986

[58] R J Jandacek and P Tso ldquoEnterohepatic circulation oforganochlorine compounds a site for nutritional interventionrdquoThe Journal of Nutritional Biochemistry vol 18 no 3 pp 163ndash167 2007

[59] S J Genuis D Birkholz I Rodushkin and S Beesoon ldquoBloodurine and sweat (BUS) study monitoring and eliminationof bioaccumulated toxic elementsrdquo Archives of EnvironmentalContamination and Toxicology vol 61 no 2 pp 344ndash357 2011

[60] S J Genuis S Beesoon R A Lobo and D Birkholz ldquoHumanelimination of phthalate compounds blood urine and sweat(BUS) studyrdquoThe Scientific World Journal vol 2012 Article ID615068 10 pages 2012

[61] S J Genuis S Beesoon and D Birkholz ldquoBiomonitoring andelimination of perfluorinated compounds and polychlorinated

10 BioMed Research International

biphenyls through perspiration blood urine and sweat studyrdquoISRN Toxicology vol 2013 Article ID 483832 7 pages 2013

[62] S J Genuis S Beesoon D Birkholz and R A Lobo ldquoHumanexcretion of bisphenol a blood urine and sweat (BUS) StudyrdquoJournal of Environmental and Public Health vol 2012 Article ID185731 10 pages 2012

[63] U W R Greger Comprehensive Human Physiology FromCellularMechanisms to Integration Springer Science ampBusinessMedia 2013

[64] A Eisalo and O J Luurila ldquoThe Finnish sauna and cardiovas-cular diseasesrdquo Annals of Clinical Research vol 20 no 4 pp267ndash270 1988

[65] J De Bruijn F Busser W Seinen and J Hermens ldquoDetermi-nation of octanolwater partition coefficients for hydrophobicorganic chemicals with the lsquoslow-stirringrsquo methodrdquo Environ-mental Toxicology andChemistry vol 8 no 6 pp 499ndash512 1989

[66] W de Wolf W Seinen and J L M Hermens ldquoBiotransforma-tion and toxicokinetics of trichloroanilines in fish in relation totheir hydrophobicityrdquoArchives of Environmental Contaminationand Toxicology vol 25 no 1 pp 110ndash117 1993

[67] C L A Hansch and D Hoekman Exploring QSAR AmericanChemical Society Washington DC USA 1995

[68] P H Howard and W M Meylan Handbook of Physical Prop-erties of Organic Chemicals Lewis Publishers Boca Raton FlaUSA 1997

[69] R H G Lewis Hawleyrsquos Condensed Chemical Dictionary JohnWiley amp Sons Hoboken NJ USA 15th edition 2007

[70] C D Simpson R J Wilcock T J Smith A L Wilkinsand A G Langdon ldquoDetermination of octanol-water partitioncoefficients for the major components of technical chlordanerdquoBulletin of Environmental Contamination and Toxicology vol55 no 1 pp 149ndash153 1995

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AddictionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Page 7: Research Article Human Elimination of Organochlorine

BioMed Research International 7

Table 5 Percentage of individuals with detection of organochlorinepesticides within serum sweat and urine (119899 = 20)

Serum Sweat Urine441015840-DDT 10 70 15441015840-DDE 95 70 0441015840-DDD 0 65 35Methoxychlor 0 80 15Endosulfan I 5 5 65Endosulfan sulfate 0 85 10Endrin 0 50 5Aldrin 10 25 10Dieldrin 0 15 10trans-nonachlor 0 5 0BHC (hexachlorobenzene) 30 5 0120572-BHC 10 0 0120573-BHC 15 0 0120575-BHC 0 0 0120574-BHC 1 0 1Endosulfan II 10 10 5Endrin ketone 35 5 0Endrin aldehyde 5 0 5Heptachlor epoxide 5 0 15Heptachlor 40 5 0cis-chlordane 5 5 0trans-chlordane 10 15 10Mirex 5 15 15

pharmaceutical intake and supplement use Accordinglyattempts to accurately quantify the relative amount of toxi-cants released into perspiration are limited

Areas for future research in relation to induced perspi-ration might include an examination of (i) differences inrates of excretion into perspiration of assorted xenobioticsfrom diverse sites in the body (ii) whether there is diurnalvariation in the toxicant content of perspiration (iii) whetherhydration status affects the xenobiotic concentration of per-spiration (iv) dermal reabsorption potential of toxicants afterperspiration and (v) the release of xenobiotics in those infasting states compared to those without caloric restriction

5 Conclusion

As DDT DDE DDD methoxychlor endosulfan sulfate andendrin appear to be readily excreted into sweat inducedperspiration appears to be a potential clinical tool to diminishthe body burden of these agents With the exception ofDDE however these agents are not readily detected in bloodtesting This suggests that common blood analysis may nottruly represent the body burden of these compounds Asthe routine use of unprovoked blood testing may thus beinadequate for biomonitoring body burdens of OCPs theremay be clinical advantages to the induction of perspirationthrough methods like sauna andor exercise in order tocollect samples for biomonitoring and diagnosis of manyretained OCP compounds

Table 6 Octanolwater partition coefficient of key OCPs [65ndash70]

Compound log119870owAldrin 650Endrin 52Endosulfan I 383Endosulfate 366pp1015840-DDT 691pp1015840-DDE 651pp1015840-DDD 602Methoxychlor 508Heptachlor 610Hexachlorobenzene 573

In conclusion the previous four papers in this ldquobloodurine and sweat (BUS)rdquo series have demonstrated thatinduced perspiration is effective at facilitating the removal ofmany toxic elements as well as various organic compoundsbut not all [59ndash62] This OCP study provides evidence thattransdermal depuration through perspiration facilitates elim-ination of some parent and metabolite OCP compounds butnot all While the absolute amount of each OCP compoundreleased into sweat may be small according to this data anaverage adult may sweat more than one liter per hour duringexerciseUnder thermal stressmaximal rates of sweatingmaybe as high as two to four litershour [63] and sweating ratesfor ldquoacclimatizedrdquo people who regularly use saunas may be ashigh as two litershour [64] Accordingly regular sessions ofinduced perspiration should be considered cumulatively as apotential clinical modality to diminish body burdens ofmanyxenobiotics including OCP compounds

Additional Points

Key Findings

(a) DDT andor its metabolite(s) were found in nearlyevery participant regardless of age suggesting thatexposure is very common

(b) Nearly all organochlorine pesticide (OCP) parentcompounds and several metabolites were detected inperspiration suggesting that sweating may be effica-cious in diminishing the body burden of many ofthese toxicants

(c) There were some parent OCPs such as endosulfan Iand hexachlorobenzene and some metabolites suchas endrin ketone and heptachlor that were not readilyexcreted into perspiration

(d) Lipophilicity appeared to be a major factor influenc-ing the efficacy of transdermal OCP elimination butnot the exclusive determinant

(e) Only endosulfan I appeared to be predominantlydetected in urine suggesting that urine analysis haslimited value in detection of retained OCPs

8 BioMed Research International

Competing Interests

There is no conflict of interests regarding the publication ofthis paper

Acknowledgments

Thanks are due to Dr Peter Mahaffy and the Departmentof Chemistry at The Kingrsquos University for their thoughtfulassistance in this work

References

[1] Nobelprizeorg the official web site of the Nobel PrizePaul MullermdashBiographical httpwwwnobelprizeorgnobelprizesmedicinelaureates1948muller-biohtml

[2] K I Barnes D N Durrheim F Little et al ldquoEffect ofartemether-lumefantrine policy and improved vector controlon malaria burden in KwaZulu-Natal South Africardquo PLoSMedicine vol 2 no 11 article e330 2005

[3] United States Environmental Protection Agency ldquoDDT A briefhistory and statusrdquo 2016 httpswwwepagovingredients-used-pesticide-productsddt-brief-history-and-status

[4] United Nations Environment Programme Stockholm Conven-tion Protecting health and the environment from persistentorganic pollutants httpchmpopsintdefaultaspx

[5] S MWaliszewski A A Aguirre R M Infanzon and J SiliceoldquoCarry-over of persistent organochlorine pesticides throughplacenta to fetusrdquo Salud Publica de Mexico vol 42 no 5 pp384ndash390 2000

[6] S J Genuis ldquoElimination of persistent toxicants from thehuman bodyrdquo Human amp Experimental Toxicology vol 30 no1 pp 3ndash18 2010

[7] R E Herron and J B Fagan ldquoLipophil-mediated reduction oftoxicants in humans an evaluation of an ayurvedic detoxifica-tion procedurerdquo Alternative Therapies in Health and Medicinevol 8 no 5 pp 40ndash51 2002

[8] S J Genuis M E Sears G Schwalfenberg J Hope andR Bernhoft ldquoClinical detoxification elimination of persistenttoxicants from the human bodyrdquo The Scientific World Journalvol 2013 Article ID 238347 3 pages 2013

[9] S L Archibeque-Engle J D Tessari D T Winn T J KeefeT M Nett and T Zheng ldquoComparison of organochlorinepesticide and polychlorinated biphenyl residues in humanbreast adipose tissue and serumrdquo Journal of Toxicology andEnvironmental Health vol 52 no 4 pp 285ndash293 1997

[10] S J Genuis andK L Kelln ldquoToxicant exposure and bioaccumu-lation a common and potentially reversible cause of cognitivedysfunction and dementiardquo Behavioural Neurology vol 2015Article ID 620143 10 pages 2015

[11] T G Redgrave P Wallace R J Jandacek and P Tso ldquoTreat-ment with a dietary fat substitute decreased Arochlor 1254contamination in an obese diabetic malerdquo Journal of NutritionalBiochemistry vol 16 no 6 pp 383ndash384 2005

[12] G H Ross and M C Sternquist ldquoMethamphetamine exposureand chronic illness in police officers significant improvementwith sauna-based detoxification therapyrdquo Toxicology and Indus-trial Health vol 28 no 8 pp 758ndash768 2012

[13] P Williams R James and S Roberts Principles of ToxicologyJohn Wiley amp Sons New York NY USA 2000

[14] A K Pramanik and R C Hansen ldquoTranscutaneous gammabenzene hexachloride absorption and toxicity in infants andchildrenrdquo Archives of Dermatology vol 115 no 10 pp 1224ndash1225 1979

[15] V N Uversky J Li K Bower and A L Fink ldquoSynergisticeffects of pesticides andmetals on the fibrillation of120572-synucleinimplications for Parkinsonrsquos diseaserdquo NeuroToxicology vol 23no 4-5 pp 527ndash536 2002

[16] Y-M Lee S-G Bae S-H Lee D R Jacobs Jr and D-H LeeldquoAssociations between cigarette smoking and total mortalitydiffer depending on serum concentrations of persistent organicpollutants among the elderlyrdquo Journal of KoreanMedical Sciencevol 28 no 8 pp 1122ndash1128 2013

[17] P Bennett ldquoWorking Up the Toxic Patientrdquo httpwwwpeter-bennettcomresourcesdetoxificationworkingupthedetoxpa-tientpdf

[18] S J Genuis ldquoThe chemical erosion of human health adverseenvironmental exposure and in-utero pollutionmdashdeterminantsof congenital disorders and chronic diseaserdquo Journal of PerinatalMedicine vol 34 no 3 pp 185ndash195 2006

[19] E R Kabir M S Rahman and I Rahman ldquoA review onendocrine disruptors and their possible impacts on humanhealthrdquo Environmental Toxicology and Pharmacology vol 40no 1 pp 241ndash258 2015

[20] G C Di Renzo J A Conry J Blake et al ldquoInternational Fed-eration of Gynecology and Obstetrics opinion on reproductivehealth impacts of exposure to toxic environmental chemicalsrdquoInternational Journal of Gynecology amp Obstetrics vol 131 no 3pp 219ndash225 2015

[21] M K Skinner M Manikkam and C Guerrero-BosagnaldquoEpigenetic transgenerational actions of endocrine disruptorsrdquoReproductive Toxicology vol 31 no 3 pp 337ndash343 2011

[22] M E Sears and S J Genuis ldquoEnvironmental determinants ofchronic disease and medical approaches recognition avoid-ance supportive therapy and detoxificationrdquo Journal of Envi-ronmental and Public Health vol 2012 Article ID 356798 15pages 2012

[23] T M Crisp E D Clegg R L Cooper et al ldquoEnvironmentalendocrine disruption an effects assessment and analysisrdquo Envi-ronmental Health Perspectives vol 106 supplement 1 pp 11ndash561998

[24] M E A Benarbia D Macherel S Faure C Jacques R Andri-antsitohaina and Y Malthiery ldquoPlasmatic concentration oforganochlorine lindane acts as metabolic disruptors in HepG2liver cell line by inducing mitochondrial disorderrdquo Toxicologyand Applied Pharmacology vol 272 no 2 pp 325ndash334 2013

[25] C Charlier A Albert P Herman et al ldquoBreast cancer andserum organochlorine residuesrdquo Occupational and Environ-mental Medicine vol 60 no 5 pp 348ndash351 2003

[26] J Dich S H Zahm A Hanberg and H-O Adami ldquoPesticidesand cancerrdquo Cancer Causes and Control vol 8 no 3 pp 420ndash443 1997

[27] S Yasunaga KNishi S Nishimoto andT Sugahara ldquoMethoxy-chlor enhances degranulation ofmurinemast cells by regulatingFc120576RI-mediated signal transductionrdquo Journal of Immunotoxicol-ogy vol 12 no 3 pp 283ndash289 2015

[28] K Upson A J De Roos M L Thompson et al ldquoOrganochlo-rine pesticides and risk of endometriosis findings from apopulation-based case-control studyrdquo Environmental HealthPerspectives vol 121 no 11-12 pp 1319ndash1324 2013

[29] K A McGlynn S M Quraishi B I Graubard J-P Weber MV Rubertone and R L Erickson ldquoPersistent organochlorine

BioMed Research International 9

pesticides and risk of testicular germ cell tumorsrdquo Journal of theNational Cancer Institute vol 100 no 9 pp 663ndash671 2008

[30] D H Lee M W Steffes A Sjodin R S Jones L L Needhamand D R Jacobs Jr ldquoLow dose organochlorine pesticides andpolychlorinated biphenyls predict obesity dyslipidemia andinsulin resistance among people free of diabetesrdquo PLoS ONEvol 6 no 1 Article ID e15977 2011

[31] M Turyk H Anderson L Knobeloch P Imm and V PerskyldquoOrganochlorine exposure and incidence of diabetes in a cohortof great lakes sport fish consumersrdquo Environmental HealthPerspectives vol 117 no 7 pp 1076ndash1082 2009

[32] H K Son S A Kim J H Kang et al ldquoStrong associationsbetween low-dose organochlorine pesticides and type 2 dia-betes in Koreardquo Environment International vol 36 no 5 pp410ndash414 2010

[33] L Fleming J B Mann J Bean T Briggle and J R Sanchez-Ramos ldquoParkinsonrsquos disease and brain levels of organochlorinepesticidesrdquoAnnals of Neurology vol 36 no 1 pp 100ndash103 1994

[34] H J Heusinkveld and R H S Westerink ldquoOrganochlorineinsecticides lindane and dieldrin and their binary mixturedisturb calcium homeostasis in dopaminergic PC12 cellsrdquoEnvironmental Science and Technology vol 46 no 3 pp 1842ndash1848 2012

[35] J Jurewicz and W Hanke ldquoPrenatal and childhood exposureto pesticides and neurobehavioral development review ofepidemiological studiesrdquo International Journal of OccupationalMedicine and Environmental Health vol 21 no 2 pp 121ndash1322008

[36] E A Belyaeva T V Sokolova L V Emelyanova and I OZakharova ldquoMitochondrial electron transport chain in heavymetal-induced neurotoxicity effects of cadmium mercury andcopperrdquo The Scientific World Journal vol 2012 Article ID136063 14 pages 2012

[37] R Pathak S G Suke T Ahmed et al ldquoOrganochlorinepesticide residue levels and oxidative stress in preterm deliverycasesrdquoHumanampExperimental Toxicology vol 29 no 5 pp 351ndash358 2010

[38] M Zhao Y Zhang C Wang Z Fu W Liu and J GanldquoInduction of macrophage apoptosis by an organochlorineinsecticide acetofenaterdquo Chemical Research in Toxicology vol22 no 3 pp 504ndash510 2009

[39] W Mnif A I Hassine A Bouaziz A Bartegi O Thomas andB Roig ldquoEffect of endocrine disruptor pesticides a reviewrdquoInternational Journal of Environmental Research and PublicHealth vol 8 no 6 pp 2265ndash2303 2011

[40] L Hou X Zhang D Wang and A Baccarelli ldquoEnvironmentalchemical exposures and human epigeneticsrdquo International Jour-nal of Epidemiology vol 41 no 1 pp 79ndash105 2012

[41] G M Williams ldquoGenotoxic and epigenetic carcinogens theiridentification and significancerdquo Annals of the New YorkAcademy of Sciences vol 407 no 1 pp 328ndash333 1983

[42] B Hille ldquoPharmacological modifications of the sodium chan-nels of frog nerverdquo The Journal of General Physiology vol 51no 2 pp 199ndash219 1968

[43] S Gilbert A Small Dose of Toxicology CRC Press Boca RatonFla USA 2004

[44] S J Genuis ldquoSensitivity-related illness the escalating pandemicof allergy food intolerance and chemical sensitivityrdquoTheScienceof the Total Environment vol 408 no 24 pp 6047ndash6061 2010

[45] S J Genuis ldquoPandemic of idiopathic multimorbidityrdquo Cana-dian Family Physician vol 60 no 6 pp 511ndash514 2014

[46] Centers for Disease Control and Prevention Department ofHealth and Human Services Fourth National Report on HumanExposure to Environmental Chemicals CDC Atlanta Ga USA2013 httpwwwcdcgovexposurereportpdfFourthReportUpdatedTables Mar2013pdf

[47] Health Canada ldquoHuman biomonitoring of environmentalchemicalsrdquo 2015 httpwwwhealthcanadagccabiomoni-toring

[48] S J Genuis and R A Genuis ldquoPreconception care a newstandard of care within maternal health servicesrdquo BioMedResearch International vol 2016 Article ID 6150976 30 pages2016

[49] Environmental Working Group BPA and Other Cord BloodPollutants 2016 httpwwwewgorgresearchminority-cord-blood-reportbpa-and-other-cord-blood-pollutants

[50] A Sudaryanto T Kunisue N Kajiwara et al ldquoSpecific accumu-lation of organochlorines in human breastmilk from Indonesialevels distribution accumulation kinetics and infant healthriskrdquo Environmental Pollution vol 139 no 1 pp 107ndash117 2006

[51] E M Roberts P B English J K Grether G C Windham LSomberg and C Wolff ldquoMaternal residence near agriculturalpesticide applications and autism spectrum disorders amongchildren in the California Central Valleyrdquo Environmental HealthPerspectives vol 115 no 10 pp 1482ndash1489 2007

[52] R J Jandacek and S J Genuis ldquoAn assessment of the intestinallumen as a site for intervention in reducing body burdens oforganochlorine compoundsrdquo The Scientific World Journal vol2013 Article ID 205621 10 pages 2013

[53] W J Cohn J J Boylan R V Blanke M W Fariss J R Howelland P S Guzelian ldquoTreatment of chlordecone (Kepone) toxicitywith cholestyramine Results of a controlled clinical trialrdquo TheNew England Journal of Medicine vol 298 no 5 pp 243ndash2481978

[54] Y Mochida H Fukata Y Matsuno and C Mori ldquoReduction ofdioxins and polychlorinated biphenyls (PCBs) in human bodyrdquoFukuoka Igaku Zasshi vol 98 no 4 pp 106ndash113 2007

[55] K Rozman L Ballhorn and T Rozman ldquoMineral oil in the dietenhances fecal excretion of DDT in the rhesus monkeyrdquo Drugand Chemical Toxicology vol 6 no 3 pp 311ndash316 1983

[56] D W Schnare M Ben and M G Shields ldquoBody burdenreduction of PCBs PBBs and chlorinated pesticides in humansubjectsrdquo Ambio vol 13 pp 378ndash380 1984

[57] D W Schnare and P C Robinson ldquoReduction of human bodyburdens of hexachlorobenzene and polychlorinated biphenylsrdquoin Hexachlorobenzene Proceedings of an International Sym-posium C R Morris and J R P Cabral Eds pp 597ndash603International Agency for Research on Cancer Lyon France1986

[58] R J Jandacek and P Tso ldquoEnterohepatic circulation oforganochlorine compounds a site for nutritional interventionrdquoThe Journal of Nutritional Biochemistry vol 18 no 3 pp 163ndash167 2007

[59] S J Genuis D Birkholz I Rodushkin and S Beesoon ldquoBloodurine and sweat (BUS) study monitoring and eliminationof bioaccumulated toxic elementsrdquo Archives of EnvironmentalContamination and Toxicology vol 61 no 2 pp 344ndash357 2011

[60] S J Genuis S Beesoon R A Lobo and D Birkholz ldquoHumanelimination of phthalate compounds blood urine and sweat(BUS) studyrdquoThe Scientific World Journal vol 2012 Article ID615068 10 pages 2012

[61] S J Genuis S Beesoon and D Birkholz ldquoBiomonitoring andelimination of perfluorinated compounds and polychlorinated

10 BioMed Research International

biphenyls through perspiration blood urine and sweat studyrdquoISRN Toxicology vol 2013 Article ID 483832 7 pages 2013

[62] S J Genuis S Beesoon D Birkholz and R A Lobo ldquoHumanexcretion of bisphenol a blood urine and sweat (BUS) StudyrdquoJournal of Environmental and Public Health vol 2012 Article ID185731 10 pages 2012

[63] U W R Greger Comprehensive Human Physiology FromCellularMechanisms to Integration Springer Science ampBusinessMedia 2013

[64] A Eisalo and O J Luurila ldquoThe Finnish sauna and cardiovas-cular diseasesrdquo Annals of Clinical Research vol 20 no 4 pp267ndash270 1988

[65] J De Bruijn F Busser W Seinen and J Hermens ldquoDetermi-nation of octanolwater partition coefficients for hydrophobicorganic chemicals with the lsquoslow-stirringrsquo methodrdquo Environ-mental Toxicology andChemistry vol 8 no 6 pp 499ndash512 1989

[66] W de Wolf W Seinen and J L M Hermens ldquoBiotransforma-tion and toxicokinetics of trichloroanilines in fish in relation totheir hydrophobicityrdquoArchives of Environmental Contaminationand Toxicology vol 25 no 1 pp 110ndash117 1993

[67] C L A Hansch and D Hoekman Exploring QSAR AmericanChemical Society Washington DC USA 1995

[68] P H Howard and W M Meylan Handbook of Physical Prop-erties of Organic Chemicals Lewis Publishers Boca Raton FlaUSA 1997

[69] R H G Lewis Hawleyrsquos Condensed Chemical Dictionary JohnWiley amp Sons Hoboken NJ USA 15th edition 2007

[70] C D Simpson R J Wilcock T J Smith A L Wilkinsand A G Langdon ldquoDetermination of octanol-water partitioncoefficients for the major components of technical chlordanerdquoBulletin of Environmental Contamination and Toxicology vol55 no 1 pp 149ndash153 1995

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AddictionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Page 8: Research Article Human Elimination of Organochlorine

8 BioMed Research International

Competing Interests

There is no conflict of interests regarding the publication ofthis paper

Acknowledgments

Thanks are due to Dr Peter Mahaffy and the Departmentof Chemistry at The Kingrsquos University for their thoughtfulassistance in this work

References

[1] Nobelprizeorg the official web site of the Nobel PrizePaul MullermdashBiographical httpwwwnobelprizeorgnobelprizesmedicinelaureates1948muller-biohtml

[2] K I Barnes D N Durrheim F Little et al ldquoEffect ofartemether-lumefantrine policy and improved vector controlon malaria burden in KwaZulu-Natal South Africardquo PLoSMedicine vol 2 no 11 article e330 2005

[3] United States Environmental Protection Agency ldquoDDT A briefhistory and statusrdquo 2016 httpswwwepagovingredients-used-pesticide-productsddt-brief-history-and-status

[4] United Nations Environment Programme Stockholm Conven-tion Protecting health and the environment from persistentorganic pollutants httpchmpopsintdefaultaspx

[5] S MWaliszewski A A Aguirre R M Infanzon and J SiliceoldquoCarry-over of persistent organochlorine pesticides throughplacenta to fetusrdquo Salud Publica de Mexico vol 42 no 5 pp384ndash390 2000

[6] S J Genuis ldquoElimination of persistent toxicants from thehuman bodyrdquo Human amp Experimental Toxicology vol 30 no1 pp 3ndash18 2010

[7] R E Herron and J B Fagan ldquoLipophil-mediated reduction oftoxicants in humans an evaluation of an ayurvedic detoxifica-tion procedurerdquo Alternative Therapies in Health and Medicinevol 8 no 5 pp 40ndash51 2002

[8] S J Genuis M E Sears G Schwalfenberg J Hope andR Bernhoft ldquoClinical detoxification elimination of persistenttoxicants from the human bodyrdquo The Scientific World Journalvol 2013 Article ID 238347 3 pages 2013

[9] S L Archibeque-Engle J D Tessari D T Winn T J KeefeT M Nett and T Zheng ldquoComparison of organochlorinepesticide and polychlorinated biphenyl residues in humanbreast adipose tissue and serumrdquo Journal of Toxicology andEnvironmental Health vol 52 no 4 pp 285ndash293 1997

[10] S J Genuis andK L Kelln ldquoToxicant exposure and bioaccumu-lation a common and potentially reversible cause of cognitivedysfunction and dementiardquo Behavioural Neurology vol 2015Article ID 620143 10 pages 2015

[11] T G Redgrave P Wallace R J Jandacek and P Tso ldquoTreat-ment with a dietary fat substitute decreased Arochlor 1254contamination in an obese diabetic malerdquo Journal of NutritionalBiochemistry vol 16 no 6 pp 383ndash384 2005

[12] G H Ross and M C Sternquist ldquoMethamphetamine exposureand chronic illness in police officers significant improvementwith sauna-based detoxification therapyrdquo Toxicology and Indus-trial Health vol 28 no 8 pp 758ndash768 2012

[13] P Williams R James and S Roberts Principles of ToxicologyJohn Wiley amp Sons New York NY USA 2000

[14] A K Pramanik and R C Hansen ldquoTranscutaneous gammabenzene hexachloride absorption and toxicity in infants andchildrenrdquo Archives of Dermatology vol 115 no 10 pp 1224ndash1225 1979

[15] V N Uversky J Li K Bower and A L Fink ldquoSynergisticeffects of pesticides andmetals on the fibrillation of120572-synucleinimplications for Parkinsonrsquos diseaserdquo NeuroToxicology vol 23no 4-5 pp 527ndash536 2002

[16] Y-M Lee S-G Bae S-H Lee D R Jacobs Jr and D-H LeeldquoAssociations between cigarette smoking and total mortalitydiffer depending on serum concentrations of persistent organicpollutants among the elderlyrdquo Journal of KoreanMedical Sciencevol 28 no 8 pp 1122ndash1128 2013

[17] P Bennett ldquoWorking Up the Toxic Patientrdquo httpwwwpeter-bennettcomresourcesdetoxificationworkingupthedetoxpa-tientpdf

[18] S J Genuis ldquoThe chemical erosion of human health adverseenvironmental exposure and in-utero pollutionmdashdeterminantsof congenital disorders and chronic diseaserdquo Journal of PerinatalMedicine vol 34 no 3 pp 185ndash195 2006

[19] E R Kabir M S Rahman and I Rahman ldquoA review onendocrine disruptors and their possible impacts on humanhealthrdquo Environmental Toxicology and Pharmacology vol 40no 1 pp 241ndash258 2015

[20] G C Di Renzo J A Conry J Blake et al ldquoInternational Fed-eration of Gynecology and Obstetrics opinion on reproductivehealth impacts of exposure to toxic environmental chemicalsrdquoInternational Journal of Gynecology amp Obstetrics vol 131 no 3pp 219ndash225 2015

[21] M K Skinner M Manikkam and C Guerrero-BosagnaldquoEpigenetic transgenerational actions of endocrine disruptorsrdquoReproductive Toxicology vol 31 no 3 pp 337ndash343 2011

[22] M E Sears and S J Genuis ldquoEnvironmental determinants ofchronic disease and medical approaches recognition avoid-ance supportive therapy and detoxificationrdquo Journal of Envi-ronmental and Public Health vol 2012 Article ID 356798 15pages 2012

[23] T M Crisp E D Clegg R L Cooper et al ldquoEnvironmentalendocrine disruption an effects assessment and analysisrdquo Envi-ronmental Health Perspectives vol 106 supplement 1 pp 11ndash561998

[24] M E A Benarbia D Macherel S Faure C Jacques R Andri-antsitohaina and Y Malthiery ldquoPlasmatic concentration oforganochlorine lindane acts as metabolic disruptors in HepG2liver cell line by inducing mitochondrial disorderrdquo Toxicologyand Applied Pharmacology vol 272 no 2 pp 325ndash334 2013

[25] C Charlier A Albert P Herman et al ldquoBreast cancer andserum organochlorine residuesrdquo Occupational and Environ-mental Medicine vol 60 no 5 pp 348ndash351 2003

[26] J Dich S H Zahm A Hanberg and H-O Adami ldquoPesticidesand cancerrdquo Cancer Causes and Control vol 8 no 3 pp 420ndash443 1997

[27] S Yasunaga KNishi S Nishimoto andT Sugahara ldquoMethoxy-chlor enhances degranulation ofmurinemast cells by regulatingFc120576RI-mediated signal transductionrdquo Journal of Immunotoxicol-ogy vol 12 no 3 pp 283ndash289 2015

[28] K Upson A J De Roos M L Thompson et al ldquoOrganochlo-rine pesticides and risk of endometriosis findings from apopulation-based case-control studyrdquo Environmental HealthPerspectives vol 121 no 11-12 pp 1319ndash1324 2013

[29] K A McGlynn S M Quraishi B I Graubard J-P Weber MV Rubertone and R L Erickson ldquoPersistent organochlorine

BioMed Research International 9

pesticides and risk of testicular germ cell tumorsrdquo Journal of theNational Cancer Institute vol 100 no 9 pp 663ndash671 2008

[30] D H Lee M W Steffes A Sjodin R S Jones L L Needhamand D R Jacobs Jr ldquoLow dose organochlorine pesticides andpolychlorinated biphenyls predict obesity dyslipidemia andinsulin resistance among people free of diabetesrdquo PLoS ONEvol 6 no 1 Article ID e15977 2011

[31] M Turyk H Anderson L Knobeloch P Imm and V PerskyldquoOrganochlorine exposure and incidence of diabetes in a cohortof great lakes sport fish consumersrdquo Environmental HealthPerspectives vol 117 no 7 pp 1076ndash1082 2009

[32] H K Son S A Kim J H Kang et al ldquoStrong associationsbetween low-dose organochlorine pesticides and type 2 dia-betes in Koreardquo Environment International vol 36 no 5 pp410ndash414 2010

[33] L Fleming J B Mann J Bean T Briggle and J R Sanchez-Ramos ldquoParkinsonrsquos disease and brain levels of organochlorinepesticidesrdquoAnnals of Neurology vol 36 no 1 pp 100ndash103 1994

[34] H J Heusinkveld and R H S Westerink ldquoOrganochlorineinsecticides lindane and dieldrin and their binary mixturedisturb calcium homeostasis in dopaminergic PC12 cellsrdquoEnvironmental Science and Technology vol 46 no 3 pp 1842ndash1848 2012

[35] J Jurewicz and W Hanke ldquoPrenatal and childhood exposureto pesticides and neurobehavioral development review ofepidemiological studiesrdquo International Journal of OccupationalMedicine and Environmental Health vol 21 no 2 pp 121ndash1322008

[36] E A Belyaeva T V Sokolova L V Emelyanova and I OZakharova ldquoMitochondrial electron transport chain in heavymetal-induced neurotoxicity effects of cadmium mercury andcopperrdquo The Scientific World Journal vol 2012 Article ID136063 14 pages 2012

[37] R Pathak S G Suke T Ahmed et al ldquoOrganochlorinepesticide residue levels and oxidative stress in preterm deliverycasesrdquoHumanampExperimental Toxicology vol 29 no 5 pp 351ndash358 2010

[38] M Zhao Y Zhang C Wang Z Fu W Liu and J GanldquoInduction of macrophage apoptosis by an organochlorineinsecticide acetofenaterdquo Chemical Research in Toxicology vol22 no 3 pp 504ndash510 2009

[39] W Mnif A I Hassine A Bouaziz A Bartegi O Thomas andB Roig ldquoEffect of endocrine disruptor pesticides a reviewrdquoInternational Journal of Environmental Research and PublicHealth vol 8 no 6 pp 2265ndash2303 2011

[40] L Hou X Zhang D Wang and A Baccarelli ldquoEnvironmentalchemical exposures and human epigeneticsrdquo International Jour-nal of Epidemiology vol 41 no 1 pp 79ndash105 2012

[41] G M Williams ldquoGenotoxic and epigenetic carcinogens theiridentification and significancerdquo Annals of the New YorkAcademy of Sciences vol 407 no 1 pp 328ndash333 1983

[42] B Hille ldquoPharmacological modifications of the sodium chan-nels of frog nerverdquo The Journal of General Physiology vol 51no 2 pp 199ndash219 1968

[43] S Gilbert A Small Dose of Toxicology CRC Press Boca RatonFla USA 2004

[44] S J Genuis ldquoSensitivity-related illness the escalating pandemicof allergy food intolerance and chemical sensitivityrdquoTheScienceof the Total Environment vol 408 no 24 pp 6047ndash6061 2010

[45] S J Genuis ldquoPandemic of idiopathic multimorbidityrdquo Cana-dian Family Physician vol 60 no 6 pp 511ndash514 2014

[46] Centers for Disease Control and Prevention Department ofHealth and Human Services Fourth National Report on HumanExposure to Environmental Chemicals CDC Atlanta Ga USA2013 httpwwwcdcgovexposurereportpdfFourthReportUpdatedTables Mar2013pdf

[47] Health Canada ldquoHuman biomonitoring of environmentalchemicalsrdquo 2015 httpwwwhealthcanadagccabiomoni-toring

[48] S J Genuis and R A Genuis ldquoPreconception care a newstandard of care within maternal health servicesrdquo BioMedResearch International vol 2016 Article ID 6150976 30 pages2016

[49] Environmental Working Group BPA and Other Cord BloodPollutants 2016 httpwwwewgorgresearchminority-cord-blood-reportbpa-and-other-cord-blood-pollutants

[50] A Sudaryanto T Kunisue N Kajiwara et al ldquoSpecific accumu-lation of organochlorines in human breastmilk from Indonesialevels distribution accumulation kinetics and infant healthriskrdquo Environmental Pollution vol 139 no 1 pp 107ndash117 2006

[51] E M Roberts P B English J K Grether G C Windham LSomberg and C Wolff ldquoMaternal residence near agriculturalpesticide applications and autism spectrum disorders amongchildren in the California Central Valleyrdquo Environmental HealthPerspectives vol 115 no 10 pp 1482ndash1489 2007

[52] R J Jandacek and S J Genuis ldquoAn assessment of the intestinallumen as a site for intervention in reducing body burdens oforganochlorine compoundsrdquo The Scientific World Journal vol2013 Article ID 205621 10 pages 2013

[53] W J Cohn J J Boylan R V Blanke M W Fariss J R Howelland P S Guzelian ldquoTreatment of chlordecone (Kepone) toxicitywith cholestyramine Results of a controlled clinical trialrdquo TheNew England Journal of Medicine vol 298 no 5 pp 243ndash2481978

[54] Y Mochida H Fukata Y Matsuno and C Mori ldquoReduction ofdioxins and polychlorinated biphenyls (PCBs) in human bodyrdquoFukuoka Igaku Zasshi vol 98 no 4 pp 106ndash113 2007

[55] K Rozman L Ballhorn and T Rozman ldquoMineral oil in the dietenhances fecal excretion of DDT in the rhesus monkeyrdquo Drugand Chemical Toxicology vol 6 no 3 pp 311ndash316 1983

[56] D W Schnare M Ben and M G Shields ldquoBody burdenreduction of PCBs PBBs and chlorinated pesticides in humansubjectsrdquo Ambio vol 13 pp 378ndash380 1984

[57] D W Schnare and P C Robinson ldquoReduction of human bodyburdens of hexachlorobenzene and polychlorinated biphenylsrdquoin Hexachlorobenzene Proceedings of an International Sym-posium C R Morris and J R P Cabral Eds pp 597ndash603International Agency for Research on Cancer Lyon France1986

[58] R J Jandacek and P Tso ldquoEnterohepatic circulation oforganochlorine compounds a site for nutritional interventionrdquoThe Journal of Nutritional Biochemistry vol 18 no 3 pp 163ndash167 2007

[59] S J Genuis D Birkholz I Rodushkin and S Beesoon ldquoBloodurine and sweat (BUS) study monitoring and eliminationof bioaccumulated toxic elementsrdquo Archives of EnvironmentalContamination and Toxicology vol 61 no 2 pp 344ndash357 2011

[60] S J Genuis S Beesoon R A Lobo and D Birkholz ldquoHumanelimination of phthalate compounds blood urine and sweat(BUS) studyrdquoThe Scientific World Journal vol 2012 Article ID615068 10 pages 2012

[61] S J Genuis S Beesoon and D Birkholz ldquoBiomonitoring andelimination of perfluorinated compounds and polychlorinated

10 BioMed Research International

biphenyls through perspiration blood urine and sweat studyrdquoISRN Toxicology vol 2013 Article ID 483832 7 pages 2013

[62] S J Genuis S Beesoon D Birkholz and R A Lobo ldquoHumanexcretion of bisphenol a blood urine and sweat (BUS) StudyrdquoJournal of Environmental and Public Health vol 2012 Article ID185731 10 pages 2012

[63] U W R Greger Comprehensive Human Physiology FromCellularMechanisms to Integration Springer Science ampBusinessMedia 2013

[64] A Eisalo and O J Luurila ldquoThe Finnish sauna and cardiovas-cular diseasesrdquo Annals of Clinical Research vol 20 no 4 pp267ndash270 1988

[65] J De Bruijn F Busser W Seinen and J Hermens ldquoDetermi-nation of octanolwater partition coefficients for hydrophobicorganic chemicals with the lsquoslow-stirringrsquo methodrdquo Environ-mental Toxicology andChemistry vol 8 no 6 pp 499ndash512 1989

[66] W de Wolf W Seinen and J L M Hermens ldquoBiotransforma-tion and toxicokinetics of trichloroanilines in fish in relation totheir hydrophobicityrdquoArchives of Environmental Contaminationand Toxicology vol 25 no 1 pp 110ndash117 1993

[67] C L A Hansch and D Hoekman Exploring QSAR AmericanChemical Society Washington DC USA 1995

[68] P H Howard and W M Meylan Handbook of Physical Prop-erties of Organic Chemicals Lewis Publishers Boca Raton FlaUSA 1997

[69] R H G Lewis Hawleyrsquos Condensed Chemical Dictionary JohnWiley amp Sons Hoboken NJ USA 15th edition 2007

[70] C D Simpson R J Wilcock T J Smith A L Wilkinsand A G Langdon ldquoDetermination of octanol-water partitioncoefficients for the major components of technical chlordanerdquoBulletin of Environmental Contamination and Toxicology vol55 no 1 pp 149ndash153 1995

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AddictionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Page 9: Research Article Human Elimination of Organochlorine

BioMed Research International 9

pesticides and risk of testicular germ cell tumorsrdquo Journal of theNational Cancer Institute vol 100 no 9 pp 663ndash671 2008

[30] D H Lee M W Steffes A Sjodin R S Jones L L Needhamand D R Jacobs Jr ldquoLow dose organochlorine pesticides andpolychlorinated biphenyls predict obesity dyslipidemia andinsulin resistance among people free of diabetesrdquo PLoS ONEvol 6 no 1 Article ID e15977 2011

[31] M Turyk H Anderson L Knobeloch P Imm and V PerskyldquoOrganochlorine exposure and incidence of diabetes in a cohortof great lakes sport fish consumersrdquo Environmental HealthPerspectives vol 117 no 7 pp 1076ndash1082 2009

[32] H K Son S A Kim J H Kang et al ldquoStrong associationsbetween low-dose organochlorine pesticides and type 2 dia-betes in Koreardquo Environment International vol 36 no 5 pp410ndash414 2010

[33] L Fleming J B Mann J Bean T Briggle and J R Sanchez-Ramos ldquoParkinsonrsquos disease and brain levels of organochlorinepesticidesrdquoAnnals of Neurology vol 36 no 1 pp 100ndash103 1994

[34] H J Heusinkveld and R H S Westerink ldquoOrganochlorineinsecticides lindane and dieldrin and their binary mixturedisturb calcium homeostasis in dopaminergic PC12 cellsrdquoEnvironmental Science and Technology vol 46 no 3 pp 1842ndash1848 2012

[35] J Jurewicz and W Hanke ldquoPrenatal and childhood exposureto pesticides and neurobehavioral development review ofepidemiological studiesrdquo International Journal of OccupationalMedicine and Environmental Health vol 21 no 2 pp 121ndash1322008

[36] E A Belyaeva T V Sokolova L V Emelyanova and I OZakharova ldquoMitochondrial electron transport chain in heavymetal-induced neurotoxicity effects of cadmium mercury andcopperrdquo The Scientific World Journal vol 2012 Article ID136063 14 pages 2012

[37] R Pathak S G Suke T Ahmed et al ldquoOrganochlorinepesticide residue levels and oxidative stress in preterm deliverycasesrdquoHumanampExperimental Toxicology vol 29 no 5 pp 351ndash358 2010

[38] M Zhao Y Zhang C Wang Z Fu W Liu and J GanldquoInduction of macrophage apoptosis by an organochlorineinsecticide acetofenaterdquo Chemical Research in Toxicology vol22 no 3 pp 504ndash510 2009

[39] W Mnif A I Hassine A Bouaziz A Bartegi O Thomas andB Roig ldquoEffect of endocrine disruptor pesticides a reviewrdquoInternational Journal of Environmental Research and PublicHealth vol 8 no 6 pp 2265ndash2303 2011

[40] L Hou X Zhang D Wang and A Baccarelli ldquoEnvironmentalchemical exposures and human epigeneticsrdquo International Jour-nal of Epidemiology vol 41 no 1 pp 79ndash105 2012

[41] G M Williams ldquoGenotoxic and epigenetic carcinogens theiridentification and significancerdquo Annals of the New YorkAcademy of Sciences vol 407 no 1 pp 328ndash333 1983

[42] B Hille ldquoPharmacological modifications of the sodium chan-nels of frog nerverdquo The Journal of General Physiology vol 51no 2 pp 199ndash219 1968

[43] S Gilbert A Small Dose of Toxicology CRC Press Boca RatonFla USA 2004

[44] S J Genuis ldquoSensitivity-related illness the escalating pandemicof allergy food intolerance and chemical sensitivityrdquoTheScienceof the Total Environment vol 408 no 24 pp 6047ndash6061 2010

[45] S J Genuis ldquoPandemic of idiopathic multimorbidityrdquo Cana-dian Family Physician vol 60 no 6 pp 511ndash514 2014

[46] Centers for Disease Control and Prevention Department ofHealth and Human Services Fourth National Report on HumanExposure to Environmental Chemicals CDC Atlanta Ga USA2013 httpwwwcdcgovexposurereportpdfFourthReportUpdatedTables Mar2013pdf

[47] Health Canada ldquoHuman biomonitoring of environmentalchemicalsrdquo 2015 httpwwwhealthcanadagccabiomoni-toring

[48] S J Genuis and R A Genuis ldquoPreconception care a newstandard of care within maternal health servicesrdquo BioMedResearch International vol 2016 Article ID 6150976 30 pages2016

[49] Environmental Working Group BPA and Other Cord BloodPollutants 2016 httpwwwewgorgresearchminority-cord-blood-reportbpa-and-other-cord-blood-pollutants

[50] A Sudaryanto T Kunisue N Kajiwara et al ldquoSpecific accumu-lation of organochlorines in human breastmilk from Indonesialevels distribution accumulation kinetics and infant healthriskrdquo Environmental Pollution vol 139 no 1 pp 107ndash117 2006

[51] E M Roberts P B English J K Grether G C Windham LSomberg and C Wolff ldquoMaternal residence near agriculturalpesticide applications and autism spectrum disorders amongchildren in the California Central Valleyrdquo Environmental HealthPerspectives vol 115 no 10 pp 1482ndash1489 2007

[52] R J Jandacek and S J Genuis ldquoAn assessment of the intestinallumen as a site for intervention in reducing body burdens oforganochlorine compoundsrdquo The Scientific World Journal vol2013 Article ID 205621 10 pages 2013

[53] W J Cohn J J Boylan R V Blanke M W Fariss J R Howelland P S Guzelian ldquoTreatment of chlordecone (Kepone) toxicitywith cholestyramine Results of a controlled clinical trialrdquo TheNew England Journal of Medicine vol 298 no 5 pp 243ndash2481978

[54] Y Mochida H Fukata Y Matsuno and C Mori ldquoReduction ofdioxins and polychlorinated biphenyls (PCBs) in human bodyrdquoFukuoka Igaku Zasshi vol 98 no 4 pp 106ndash113 2007

[55] K Rozman L Ballhorn and T Rozman ldquoMineral oil in the dietenhances fecal excretion of DDT in the rhesus monkeyrdquo Drugand Chemical Toxicology vol 6 no 3 pp 311ndash316 1983

[56] D W Schnare M Ben and M G Shields ldquoBody burdenreduction of PCBs PBBs and chlorinated pesticides in humansubjectsrdquo Ambio vol 13 pp 378ndash380 1984

[57] D W Schnare and P C Robinson ldquoReduction of human bodyburdens of hexachlorobenzene and polychlorinated biphenylsrdquoin Hexachlorobenzene Proceedings of an International Sym-posium C R Morris and J R P Cabral Eds pp 597ndash603International Agency for Research on Cancer Lyon France1986

[58] R J Jandacek and P Tso ldquoEnterohepatic circulation oforganochlorine compounds a site for nutritional interventionrdquoThe Journal of Nutritional Biochemistry vol 18 no 3 pp 163ndash167 2007

[59] S J Genuis D Birkholz I Rodushkin and S Beesoon ldquoBloodurine and sweat (BUS) study monitoring and eliminationof bioaccumulated toxic elementsrdquo Archives of EnvironmentalContamination and Toxicology vol 61 no 2 pp 344ndash357 2011

[60] S J Genuis S Beesoon R A Lobo and D Birkholz ldquoHumanelimination of phthalate compounds blood urine and sweat(BUS) studyrdquoThe Scientific World Journal vol 2012 Article ID615068 10 pages 2012

[61] S J Genuis S Beesoon and D Birkholz ldquoBiomonitoring andelimination of perfluorinated compounds and polychlorinated

10 BioMed Research International

biphenyls through perspiration blood urine and sweat studyrdquoISRN Toxicology vol 2013 Article ID 483832 7 pages 2013

[62] S J Genuis S Beesoon D Birkholz and R A Lobo ldquoHumanexcretion of bisphenol a blood urine and sweat (BUS) StudyrdquoJournal of Environmental and Public Health vol 2012 Article ID185731 10 pages 2012

[63] U W R Greger Comprehensive Human Physiology FromCellularMechanisms to Integration Springer Science ampBusinessMedia 2013

[64] A Eisalo and O J Luurila ldquoThe Finnish sauna and cardiovas-cular diseasesrdquo Annals of Clinical Research vol 20 no 4 pp267ndash270 1988

[65] J De Bruijn F Busser W Seinen and J Hermens ldquoDetermi-nation of octanolwater partition coefficients for hydrophobicorganic chemicals with the lsquoslow-stirringrsquo methodrdquo Environ-mental Toxicology andChemistry vol 8 no 6 pp 499ndash512 1989

[66] W de Wolf W Seinen and J L M Hermens ldquoBiotransforma-tion and toxicokinetics of trichloroanilines in fish in relation totheir hydrophobicityrdquoArchives of Environmental Contaminationand Toxicology vol 25 no 1 pp 110ndash117 1993

[67] C L A Hansch and D Hoekman Exploring QSAR AmericanChemical Society Washington DC USA 1995

[68] P H Howard and W M Meylan Handbook of Physical Prop-erties of Organic Chemicals Lewis Publishers Boca Raton FlaUSA 1997

[69] R H G Lewis Hawleyrsquos Condensed Chemical Dictionary JohnWiley amp Sons Hoboken NJ USA 15th edition 2007

[70] C D Simpson R J Wilcock T J Smith A L Wilkinsand A G Langdon ldquoDetermination of octanol-water partitioncoefficients for the major components of technical chlordanerdquoBulletin of Environmental Contamination and Toxicology vol55 no 1 pp 149ndash153 1995

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AddictionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Page 10: Research Article Human Elimination of Organochlorine

10 BioMed Research International

biphenyls through perspiration blood urine and sweat studyrdquoISRN Toxicology vol 2013 Article ID 483832 7 pages 2013

[62] S J Genuis S Beesoon D Birkholz and R A Lobo ldquoHumanexcretion of bisphenol a blood urine and sweat (BUS) StudyrdquoJournal of Environmental and Public Health vol 2012 Article ID185731 10 pages 2012

[63] U W R Greger Comprehensive Human Physiology FromCellularMechanisms to Integration Springer Science ampBusinessMedia 2013

[64] A Eisalo and O J Luurila ldquoThe Finnish sauna and cardiovas-cular diseasesrdquo Annals of Clinical Research vol 20 no 4 pp267ndash270 1988

[65] J De Bruijn F Busser W Seinen and J Hermens ldquoDetermi-nation of octanolwater partition coefficients for hydrophobicorganic chemicals with the lsquoslow-stirringrsquo methodrdquo Environ-mental Toxicology andChemistry vol 8 no 6 pp 499ndash512 1989

[66] W de Wolf W Seinen and J L M Hermens ldquoBiotransforma-tion and toxicokinetics of trichloroanilines in fish in relation totheir hydrophobicityrdquoArchives of Environmental Contaminationand Toxicology vol 25 no 1 pp 110ndash117 1993

[67] C L A Hansch and D Hoekman Exploring QSAR AmericanChemical Society Washington DC USA 1995

[68] P H Howard and W M Meylan Handbook of Physical Prop-erties of Organic Chemicals Lewis Publishers Boca Raton FlaUSA 1997

[69] R H G Lewis Hawleyrsquos Condensed Chemical Dictionary JohnWiley amp Sons Hoboken NJ USA 15th edition 2007

[70] C D Simpson R J Wilcock T J Smith A L Wilkinsand A G Langdon ldquoDetermination of octanol-water partitioncoefficients for the major components of technical chlordanerdquoBulletin of Environmental Contamination and Toxicology vol55 no 1 pp 149ndash153 1995

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AddictionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Page 11: Research Article Human Elimination of Organochlorine

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AddictionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of