Wh CWhat are C

Everything in yourEverything in yourradiation and soun

Chemicals are plapother living things

Ch i l ?Chemicals?

r life except lightr life except light, nd waves.

ants, food, cars, , , ,

Rachel CarsonRachel Carson Clean Water ActClean Air ActResource ConservatResource Conservat

Recovery Act1976

Toxic Substances CoToxic Substances Co

1962196219721970

tion &tion &

ontrol Act 1976ontrol Act 1976

Comprehensive EnvResponse CompenResponse, CompenLiability Act CERCL

(Superfund)

Worker Right to Kno

Superfund AmendmeReauthorization Aceaut o at o c

ironmental nsation andnsation and LA

1980

ow 1986

ents and ct (SARA) 1986ct (S ) 986

Ch i l I dChemical-Ind

Acute- mucous memdrowsiness-immedDelayed-hepatotoxiDelayed-hepatotoxiChronic toxicity-cirCarcinogenicity-he

d d Effduced Effects

mbrane irritation, iate/transienticity- 48/72 hoursicity- 48/72 hoursrrhosis of the liverpatocarcinoma

Chemical IndChemical-Ind

M t i itMutagenicity- germTeratogenicity- birtg yOrgan toxicity:

N t i it?Neurotoxicity?Hepatotoxicityp y

duced Effectsduced Effects(cont.)(cont.)

ll / ti llm cells/somatic cellsth defects

A S d b AAs Stated by A

The Hallmark of anis the ability whenis the ability, whenchange one’s min

Admiral William C• Retired Chairma

of Staff

Ad i l CAdmiral Crowe:

n educated person n facts warrant ton facts warrant to

nd.

Crowean of the Joint Chiefs

The number of stobeen decreasing fthe same time, thethe same time, therate has also beenwould be foolish towould be foolish tocorrelation as evidb i b bibring babies.

orks in Europe has pfor decades. At e European birthe European birth n decreasing. We o accept this higho accept this high dence that storks

Doses of Commmon Substances

Example oRespons

1 0 0

7 0

8 09 0

1 0 0

%

4 05 06 07 0

po

nse

%

2 0

3 04 0

Res

p

01 0

1 0 1 0 0

D o se (

of a Dose-se Curve

1 ,0 0 0 1 0 ,0 0 0 1 0 0 ,0 0 0

m g /kg /d ay)

What concentrationair, water, soil, foproducts are safeproducts are safe

Chemicals produced th dand these are dos

n of chemicals in od, consumer

e?e?e specific effects

l t dse related.

R = TR T

Risk = Toxicity xwhere

T = toxicity of a specif

E = amount of exposuE = amount of exposuto a specified chem

T x ET x E

x Exposure

fic chemical

re a population hasre a population has mical

P bl SProblem S

Acceptable risk levpPublic alarmist reacPl i i k iPlacing risk in pers

SStatement

velsction to any risk

tispective

T f Ri kTypes of Risk

Linear: Used to porpcarcinogenicity

Threshold: Used toforms of toxicityforms of toxicity

AAssessments

rtray the risk of y

o model all other

A l T i iActual Toxicity

Agents LD50

PCBsAlcoholTable saltIron

14,00010,000

4,0001 500Iron

DDTStrychnineNicotine

1,500100

21

TCDDBotulinus toxin

0.0010.00001

d R kiy and Ranking

Expected Human Dose

1 Quart1 Pint-1 Quart1 Pint1 Ounce-1 Pint1 Ounce-1 Pint1 Teaspoon-1 Ounce4 Drops1 Drop

1Less Than 1 DropLess Than 1 Drop

Teratogenicity

1 I idi N t Y1. Insidious Nature (Cause is MildRelative to the Effect)

Yes

2. Duration and TimeBetween Causeand Effect

Weeks

3. Irreversible

4. Greater Susceptibilityof Immature Tissues

Yes

Yesof Immature Tissues

5. Differences Altered Develop-ment at Tissue/Organ Level

Mutagenicity Carcinogenicity

Y YYes Yes

Generations Years

Yes Yes

No Yes/No

Altered Uncontrolled Nucleotide ProliferationSequence- at CellularMolecular LevelLevel: DNA

Hazard Ide

What adverseWhat adverse can the chemcan the chem

ntification-

health effectshealth effects ical produce?ical produce?

Hazard Evh t th dwhat are the dose res

for the adversee

(%)

onse

Res

pox

ic R

Tovaluation-

l ti hisponse relationships health effects?

LD50

Sources oInformInform

Material Safety Data Integrated Risk InformHazardous SubstancHazardous Substanc

of Toxicity mationmation

Sheets (MSDS)mation System (IRIS)

ces Database (HSDB)ces Database (HSDB)

Arsenic trioArsenic trio

Route of entryi h l ti? inhalation: yes

? skin: yesy? ingestion: yes

? symptoms may includepulmonary edema, cyap y , yrestlessness, lassitude

oxide MSDSoxide MSDS

CarcinogenicityNTP? NTP: yes

? IARC: yesy? OSHA: yes

e chest pain, dyspnea, nosis, giddiness, , g ,

e, headache, hypotension

A i iArsenic trio

Emergency/First A? inhalation: remov

artificial respiratp? skin: may cause

sensitizationsensitization? ingestion: lethal

id MSDSoxide MSDS

Aid Procedureve to fresh air, ion or oxygenygitching, burning,

dose is 120 mg

ChloroforChlorofor

Route of entry? inhalation: yes? inhalation: yes? skin: yes? ingestion: yes

? exposure may cause bdizziness, vomiting, seswelling, disorientation

rm MSDSrm MSDS

Carcinogenicity? NTP: no? NTP: no? IARC: yes? OSHA: no

burns, nausea, headache, evere inflammation, n

Chl fChlorofor

Emergency/First Aid? inhalation: remove

artificial respiratioartificial respiratio? skin: flush with wa? ingestion: induce

MSDSrm MSDS

d Proceduree to fresh air, on or oxygenon or oxygenater 15-20 min.vomiting

An Example of DoDOSE

N b f 32Number of 325 mg ASPIRIN tablets

ose and ResponseRESPONSE

• Reduce risk of heart• Reduce risk of heartattacks

• Relief of headaches• Relief of headaches,minor aches & painsRelief of arthritis and• Relief of arthritis andrheumatoid condition

• Treatment of acuterheumatic fever

• Adult lethal dose

Risk Ass

is the proce--is the procedetermine ifexcess risk,allowed by pallowed by p

sessment

ess used toess used to f there is , above that public policypublic policy

The four basicThe four basicof risk assess

Hazard IdHazard IdHazard EExposureRi k E tiRisk Esti

c componentsc components sment include:

dentificationdentificationEvaluatione Evaluation

timation

R = TR = TRisk = Toxicit

wherewhereT= toxicity of a specifE= amount of exposu

to a specific chemto a specific chem

T x ET x Ety x Exposure

fic chemicalure a population has icalical

TOXITOXIis a measure of tis a measure of tsubstance to pro

ff li ieffect on a living

CITYCITYthe potential of athe potential of a oduce a harmful g system.

Three Pathways thrCan Be Expose

Inha(bre(b e

OraO a

DerDer

concon

rough which People d to Chemicals:

alation eathing)eat g)

al (ingestion)a ( gest o )

rmalrmal (skin

ntact)ntact)

The DifferenExposure

nce Between and Dose

Exposure = t itopportunity

for contact

The DifferenExposure

nce Between and Dose

Dose = the amount of aamount of a chemical in the body

E EExposure E

AbsorppDistribuMetaboExcretioExcretio

E l iEvaluation

ptionputionolismonon

Absorption DistributionpAbsorptiontract lungstract, lungs, Distribution

Metabolismrest of body,Metabolism

x = absoy = metay meta

Excretion vli th hliver throughthrough urin

n Metabolism Excretionn into gastrointestinal

and through the skinand through the skinn from blood stream to

m X enzymes Y, including fat, brain, liver

m X enzymes Yrbed, distributed chemicalbolitebolite

via exhaled breath; from h bil /f f kidh bile/feces; from kidneys ne

The HALThe HALof a chemicaldefined as thetime it takes ttime it takes tget rid of ONEamount of the

LF LIFELF-LIFE in the body is ye amount of the body tothe body to E HALF of an e chemical.

Biologica

CHEMICALSH

unleCHEMICALSBenzene

C d i

unle1-10Cadmium

Caffeine103.

EthanolToluene

2-72

EthylbenzeneXylene

4-20Xylene

Tetrachlorethylene2033

l Half-LifeHALF-LIFE (in humans ess otherwise noted)ess otherwise noted)-3 hours0 300-30 years.5 hours-4 hours2 hours (whole blood)-7 hours (for metabolite)0-30 hours0 30 hours3-72 hours

CHEMICALS OCHEMICALS O

chemical species in the risk assesin the risk asses

OF CONCERN =OF CONCERN =

studied in detail ssment processssment process

Since different chdifferent types odifferent types oresults of the risare different for eare different for etype of health effy

TypeypChemicals that

Eff t Aft ChEffects After Ch

hemicals cause f health effects,f health effects, k assessment each differenteach different fect.

e 1:t Cause Health

i Eronic Exposures

Threshold = DosThreshold = Dosno effect is seen

NOAEL N ObNOAEL = No ObAdverse Effect L

se below whichse below which n

blservable Level

ChronicChronic Threshold

1 0 0

1 2 0

8 0

1 0 0

nse

%

dosesNOAEL

Th h4 0

6 0

Res

pon doses

causing no effect

Threshdose

0

2 0

no effect

00 1 0 5 0 1 0 0 5 0 0

Dose (m

ToxicityToxicityd/NOAEL

h ldhold

0 1 0 0 0 5 0 0 0 1 0 0 0 0 5 0 0 0 0 1 0 0 0 0 0mg/kg/day)

What is a SWho Determin

Safe Values are sli t b tpolicy to be prote

public healthp• IRIS (Integrated RSystem USEPA)System, USEPA)• HEAST (Health EfSummary Tables, U

Safe Dose?es that Value?

set by public ti f thective of the

Risk Information

ffects Assessment USEPA)

What is a sWhat is a sWho determin

Values are calledDoses (ingestionpathways) -- RfDpathways) RfDReference Concth i h l tithe inhalation pa

safe dose?safe dose?es that value?

d Reference n and dermal

DDcentrations (for

th ) RfCathway) -- RfC

RfDRfD = (U(U

Where: UF = UnWhere: UF = UnMF = Mo

Because the thresholdBecause the thresholddifficult to know for ceprovide a factor of safeprovide a factor of safeof the public health.

NOAELNOAELUF x MF)UF x MF)ncertainty Factorncertainty Factorodifying Factory g

d dose value isd dose value is ertain, the UF and MF ety that is protectiveety that is protective

S f FSafety FaMultiples of 10Accounts for:Accounts for:

uncertainty in usingdetermine doses fordetermine doses forvariation in suscept

dexposedprofessional judgmethe substance itself

SFactor = SF

animal studies to r humansr humansibility among people

ent and knowledge of

Does the SafetyDoes the Safety

YEYE

y Factor Work?y Factor Work?

ESES.

ChronicSafety Factor/R

1 0 0

1 2 0

R f8 0

1 0 0

nse

%

Reference Dose

4 0

6 0

Res

pon

NOASafety Factor

0

2 0

NOAFactor

00 1 0 5 0 1 0 0 5 0 0

Dose (m

ToxicityReference Dose

AELAEL

1 0 0 0 5 0 0 0 1 0 0 0 0 5 0 0 0 0 1 0 0 0 0 0m g/kg/day)

H d QHazard Q

a method to assdose may potenhealth effecthealth effectratio of exposurpsubstance to the(RfD) for that su(RfD) for that su

Q iQuotient

sess whether a tially have a

re (dose) of a ( )e reference dose bstancebstance

Generalized Hazard

Hazard Quotient = CCQ

RfD: reference doseCC: Conc. of contaminaCR: contact rateCR: contact rateED: exposure duration EF: exposure frequency

d Quotient Equation

C•CR•CF•EF•EDBW•AT

RfDRfD

antsCF: conversion factorCF: conversion factor

AT: averaging timey BW: body weight

Hazard Quotient =Hazard Quotient = Dose (mg/kg/day)Dose (mg/kg/day)RfD (mg/kg/day)

If the hazard quoqthan one (a persto more of the sto more of the sis acceptable unpolicy), there is that a health effethat a health effe

otient is greater gson is exposed ubstance thanubstance than

nder public a possibility ect may occur.ect may occur.

H dHazard

Calculated as sum oHazard Index = sum

Used when potentiaexposure to moreexposure to more

that may affect a sptorgan systems

d I dd Index

of hazard quotientsm of Hazard Quotients

(individual organ or system)

al exists for e than one substancee than one substance

pecific target organ or

Results of the RisChemicals Causi

After ChronicAfter ChronicThe Answ

A NumbA ProbaA “Yes”A Yes

The Answ“Maybe

sk Assessment for ng Health Effects c Exposures:c Exposures: wer is NOT:berability”/“No”/ Nower IS: e”/“No”

TYPTYP

CARCINOGENI

PE 2:PE 2:

IC CHEMICALS

EPA Weight-of-Evidenc

Group A. Human Carcinogsufficient evidence from epsufficient evidence from epsupport a cause-effect relasubstance and cancer.substance and cancer.

Group B. Probable HumanB l ifi d th bB1: classified on the b

evidence from animal studiepidemiological evidenceepidemiological evidence

B2sufficient evidence from ansufficient evidence from anepidemiological data that isexistent

e Classification System

gen--indicates that there is pidemiological studies topidemiological studies to tionship between

n Carcinogen--b i f ffi i tbasis of sufficient ies and limited

: classified on basis of nimal studies andnimal studies and s inadequate or non-

EPA Weight-of-Evidenc

G C P ibl HGroup C. Possible Humanthat there is limited evidenand no epidemiological daand no epidemiological da

Group D Not ClassifiableGroup D. Not Classifiableicity-data from human epidstudies are inadequate orstudies are inadequate or assessment as to the subshazard is possiblehazard is possible

e Classification System ( t )

C i i di t

(cont.)

n Carcinogen--indicates nce from animal studies ataata

e as to Human Carcinogene as to Human Carcinogen-demiological and animals completely lacking so nocompletely lacking, so no stance’s cancer -causing

EPA Weight-of-Evidenc

G E E id f NGroup E. Evidence of NonHumans- substances in thnegative in at least two adenegative in at least two adeanimal cancer tests in diffeadequate epidemiologicaladequate epidemiological Classification in group E isevidence; substance may pevidence; substance may pcertain conditions.

e Classification System( t )

i i it f

(cont.)

ncarcinogenicity for is category have tested equate (defined by EPA)equate (defined by EPA) erent species and in and animal studiesand animal studies. s based on available prove carcinogenic underprove carcinogenic under

To be protectppublic healthestablished pthere is no ththere is no thvalue for anyy

tive of the , EPA has

policy that hresholdhreshold carcinogeng

Dose ResponseDose Response 1 2 0

Lowest8 0

1 0 0

%)

Lowest Dose

6 0

8 0

nse

(% Given

2 0

4 0

Res

po

n

0

2 0

0 5 0 1 0 0 5 0

R

0 5 0 1 0 0 5 0

Do s e (m

for Carcinogensfor Carcinogens

0 1 ,0 0 0 5 ,0 0 0 1 0 ,0 0 0 5 0 ,0 0 00 1 ,0 0 0 5 ,0 0 0 1 0 ,0 0 0 5 0 ,0 0 0

m g /kg /d a y)

Dose Response1 2 0

Dose Response

8 0

1 0 0

%)

Extrapolated linthe smallest dos

6 0

8 0

nse

(% the smallest dos

known to cause effect to zero

2 0

4 0

Res

po

n effect to zero

0

2 0

0 5 0 1 0 0 5 0

R

0 5 0 1 0 0 5 0

Do s e (m

for Carcinogensfor Carcinogens

e from sese and

0 1 ,0 0 0 5 ,0 0 0 1 0 ,0 0 0 5 0 ,0 0 00 1 ,0 0 0 5 ,0 0 0 1 0 ,0 0 0 5 0 ,0 0 0

m g /kg /d a y)

Ri k CSF CCRisk = CSF•CC

CSF: cancer slope factoCC: Conc. of contaminaCC: Conc. of contaminaCR: contact rateED d tiED: exposure duration EF: exposure frequency

C CR CF EF EDC•CR•CF•EF•EDBW•ATBW AT

or antsants

CF: conversion factor AT i ti AT: averaging time

y BW: body weight

Food RelaFood-Rela

Risk

Eating one tablespoon of peanut butter per day

Drinking one pint of milk per day

Eating one-half pound of steak pe

ated Risksated Risks

AverageLifetime Risk

1.4x10 - 4

1.4x10 - 4

2.1x10 - 5er week

Everyday CaEveryday Ca

IncidentAll cancers

One transcontinental round trip by air

Natural background radiation at sea lg

Average diagnostic X-ray

Smoking

Sharing A room with a smoker

*Estimated based on exposure to cosmic*Estimated based on exposure to cosmic

Source: Crouch and Wilson, 1982

ancer Risksancer RisksAverage

0.25

gLifetime Risk

r per year* 7 x 10 -5

level 1.4 x 10 -4

1.4 x 10 -4

8.4 x 10 -2

7.0 x 10 -4

c raysc rays

Estimated Average ALifetime Risks of DeLifetime Risks of De

Residents from S

Incident

Motor vehicle accident

Falls

Drowning

FiresFires

Firearms

Electrocution

Floods

Lightning

Animal bite or sting

Source: Crouch and Wilson, 1

Annual and Average ath for United States

Average Average

ath for United States Specific Incidents

AnnualRisk

LifetimeRisk

2.4 x 10 -4 1.7 x 10 -2

6.2 x 10 -5 4.3 x 10 -3

3.6 x 10 -5 2.5 x 10 -3

2 8 x 10 -5 1 7 x 10 -32.8 x 10 5 1.7 x 10 3

1.0 x 10 -5 7.0 x 10 -4

5.3 x 10 -6 3.9 x 10 -4

6.0 x 10 -7 4.2 x 10 -5

5.0 x 10 -7 3.5 x 10 -5

2.4 x 10 -7 1.7 x 10 -5

1982

FFor carcrisk will berisk will be

Ri k Ri kRiskTotal = Risk Be

Risk Nickel + RisRisk Nickel Ris

icinogens, e additivee additive.

Ri knzene + RiskChromium

skTetrachlorethyleneskTetrachlorethylene

Results oResults oAssessment foAssessment fo

Compare CaNumber with

Answer is “Y

of the Riskof the Risk or Carcinogensor Carcinogens

alculated Risk h Public Policy

Yes”/ “No”

“It should be emphalinearized multistageto a plausible upperto a plausible upperthat is consistent wi

h i f imechanism of carcinan estimate, howevenecessarily give a reof the risk The trueof the risk. The trueunknown and may b

--US Environmental P

asized that the e procedure leads r limit to the riskr limit to the risk ith some

i S hnogenesis. Such er, does not ealistic prediction e value of the risk ise value of the risk is be as low as zero.”

Protection Agency, 1986

Cancer risk isCancer risk is

It is lost in tIt is lost in tnatural occu

s unverifiables unverifiable

he noise ofhe noise of urrence.

Indoor Air as a SoIndoor Air as a SoExposures an

Indoor air concentraIndoor air concentraare typically much gconcentrations and tare derived from sououtdoor air.

ource of Chemicalource of Chemical nd Discomfort

ations of chemicalsations of chemicals reater than outdoor these indoor levels urces unrelated to

Indoor Air as a SoExposure and

For example:We have shown that abouresult in sharply increasin5-11 hr may be increased

d t dcompared to exposures dactivity… These common sources result in personalsources result in personalobserved outdoor concenmanufacturing and petroleg p

ource of Chemical d Discomfort

ut 20 common activities can g personal exposures over by factors of 10-100

i i d f littluring periods of little activities and indoor

l exposures that far exceedl exposures that far exceed trations, even in chemical eum refining areas. g

(Wallace et al., 1989)

Rational Approach toof Possible Toxof Possible Toxto Environmen

Exposure Dos

Environmental Testing BiologicEnvironmental Testing

a) Air

b) Water

Biologic

a) Blood

b) Urineb) Water

c) Soil

b) Urine

c) Breat

d) Food d) Tissu

o Medical Evaluation xic Exposuresxic Exposures

ntal Chemicals

HealthEffectse

al Testing Medical Testingal Testing

d

e

Medical Testing

a) History

b) Physical Exame

th

b) Physical Exam.

c) Laboratory

ue d) Radiology

StrucStruccturesctures

B di MButadiene M

60

70

40

50

Activation

10

20

30Detoxification

0

10

Humans

Cancer ?

M b liMetabolism

Rats M ice

? ?

Comparison op of DNA Repairp

Chemicals that IndNephropathy and KidneNephropathy and Kidne

Chemical 2u-NephropChemical 2u-Nephrop

Unleaded Gasoline +

1,4-Dichlorobenzene +

d-Limonene +

Isophorone +

duce 2u-Globulin ey Tumors in Male Ratsey Tumors in Male Rats

pathy Kidney Tumor Responsepathy Kidney Tumor Response(Male Rats Only)

+

+

+

+

Chemicals that IndNephropathy and KidneNephropathy and Kidne

Chemical 2u NephropChemical 2u-Nephrop

DimethylMethylphosphonate +

Perchloroethylene +

Pentachloroethane +

Hexachloroethane +

duce 2u-Globulin ey Tumors in Male Ratsey Tumors in Male Rats

(Cont.)pathy Kidney Tumor Responsepathy Kidney Tumor Response

(Male Rats Only)

+

+

+

+

Absence of in Human

2u-Globulin n Kidneys

Rodents Are PooC iCarcinogens

or Predictors of F HFor Humans

The Standard carcinogenb l t liare an obsolescent relic o

decades. At that time, exsense But now tremendosense. But now tremendoanalytical and other procenew toxicology and far monew toxicology and far mothe dose levels at which p

Philip H Abelson SciencPhilip H. Abelson. SciencNumber 4975: 1357. Sep

tests that use rodentsf th i f tof the ignorance of past

xtreme caution madeous improvements ofous improvements ofedures make possible aore realistic evaluation ofore realistic evaluation ofpathological effects occur.ce Volume 29ce, Volume 29,ptember 21, 1990.

Toxicity DataToxicity DataA rational approach towardsA rational approach towards

chemical might pose requoriented research to four

For example, let us look at tp ,(MTD). Approximately twcarcinogens would not be

id d iconsidered as carcinogen

Federal Register Vol. 57, No. 13July 17, 1992, Pg. 31723

a Evaluationa Evaluations assessing the risk that as assessing the risk that a uires mechanism-of-action-principal points.

the maximum tolerated dose wo-thirds of the NTP e positive, i.e., not be

if h MTD dns, if the MTD was not used.

38

Rebuttals ofRebuttals of to Use in T

Poor predictor ofptoxicity

L d fLow degree of coHigh degree of faHigh degree of fa

Animal DataAnimal Data Toxic Torts

f target organ g g

doncordancealse positivesalse positives

Chemical EsseChemical Essethat Causes Can

USEPA safe dose caUSEPAby USEPA pr

NationalResearchCouncil

dose recommby National RCouncilCouncil Council

ential to Healthential to Health ncer in Rodents

alculated less than=rocedures

less than2 Units

=

mendedResearch

400 Units=

PAHs in Coal-Tar ShShampoo (mg/kg)(mg/kg)

Cancer PoteOverestimate

ency Factorse Actual Risk

RegulationRegulation

They Do NThey Do N

ns Protectns Protect

Not PredictNot Predict

Carcinogens andgReleased D

Carcinogens - 15,850,466 lbg , ,Known Human CarcinoProbable Human CarcinProbable Human CarcinProbable Human Carcin

Neurotoxicants - 10,329,084

d Neurotoxicants During 1991

bs.ogens (A) - 6,128,266 lbs.nogens (B1) - 802 583 lbsnogens (B1) - 802,583 lbs.nogens (B2) - 8,919,618 lbs.

4 lbs.

NeurotoxicanHouston/Galve

N-Butyl Alcohol - 3Carbon Disulfide -Carbon Disulfide -Styrene - 2,455,35X lenes 2 361 74Xylenes - 2,361,74Cumene - 1,215,43Freon 113 - 263,972,6-Dinitrotoluene Acrylamide - 714 lb

ts Released inston Area, 1991

3,067,693 lbs962 663 lbs962,663 lbs

53 lbs47 lbs47 lbs34 lbs70 lbs- 1,500 lbsbs

Rational Approach to Possible Toxic ExposuPossible Toxic Exposu

Chemicals and C

DoseExposure

CausaC it

a) Exposure and dose

Criter

b) Literature precedencc) Confounder analysisd) T litd) Temporalitye) Biological plausibilit

Medical Evaluation of ures to Environmentalures to Environmental

Causation Criteria

e HealthEffects

ation iria

ces

ty and consistency

SympSympThere are very few sympty y p

specific for a particularin the diagnosis of the

Symptoms are medically bj ti id…any subjective eviden

patient’s condition, i.e., sby the patient; a changeby the patient; a change indicative of some bodilyIllustrated Medical Dictio

ptomsptomstoms that are relatively yr disease and thus useful disease.

defined as:f di fnce of disease or of a

such evidence as perceived in a patient’s conditionin a patient s condition

y or mental state. (Dorland’s nary, 27th edition)y, )

SigSigSigns provide some ta

which assists in thewhich assists in the the true cause of thediseasedisease.

A sign is defined asA sign is defined as…any objective evide

evidence as is percepevidence as is percepphysician, as opposedsensations (symptoms( y pIllustrated Medical Dic

gnsgnsangible form of evidence final determination offinal determination of

e symptoms and the

ence of a disease, such tible to the examiningtible to the examining

d to the subjective s) of the patient. (Dorland’s ) p (ctionary, 27th edition)

Individual RisSt

1/1 0001/1,000 Esophag

1/1,000Hear

1/1,000 v1/1,000 vLung

1/1,000 Liver

1/1,000Kidne

1/1,000Diabete

1/1,000 CConc

Lifestyle risrisks from e

clinicalExemplary 45-Year-Old MaleFit t i di b ti kFit, normo-tensive, non-diabetic, non-smoker,

non-drinker, normal body weight.Risk of death from all causes in next

10 years - 3.8 % (3.8 x 10-2)

sk Evaluationrokevs 9/1 000vs. 9/1,000

geal Cancer 0 vs. 3/1,000rt Attackvs 69/1,000vs 69/1,000

g Cancervs 12/1,000Cirrhosis

0 vs 2/1,000ey Failure0 vs 2/1,000es Mellitusvs 22/1,000l iclusion:

ks far outweighenvironmental/l exposure 45-Year-Old Male

M bidl b h t i di b tiMorbidly obese, hypertension, diabetic,smoker, drinker, sedentary.

Risk of death from all causes in next10 years - 16.3 % (1.63 x 10-1)

Comparison oComparison o

1 4 0 0 0 0

1 6 0 0 0 0

1 8 0 0 0 0

1 0 0 0 0 0

1 2 0 0 0 0

1 4 0 0 0 0

C h a n c e s in

4 0 0 0 0

6 0 0 0 0

8 0 0 0 01 , 0 0 0 , 0 0 0

0

2 0 0 0 0

E P A EA c c e p t a b leP o p u la tio n

R is k

Y

of Risk of Deathof Risk of Death

x e m p la ry 4 5 - 4 5 - Y e a r -O ldp yY e a r -O ld M a le M a le

ContributContributQualitative characterizatQualitative characterizat

Need to account for direNeed to account for direof risk in an assessme

Voluntary actions (such buying a jet ski, RV or snowmobile) contribute)to involuntary risk in ot

tory Risktory Risktion of contributory risktion of contributory risk

ect and indirect sourcesect and indirect sources ent

as

e thers

ContributoAn RV is bought

The RV maker released toxics while making the RV

Whe

Lights

Seatbel

Total To ic EmissionsTotal Toxic Emissions =

Direct Emissions &

ory RiskThe RV maker’s suppliers released toxics in making components

The suppliers to the suppliers released toxics

Plastics

Glass

Filaments

eels

lts

& Indirect Emissions

Common CarcinCommon Carcin

WhiWhi

(Fu(

nogenic Hazardsnogenic Hazards

te Breadte Bread

urfural))

Common CarcinCommon Carcin

(

nogenic Hazardsnogenic Hazards

CARROTS

(Caffeic acid)

Common CarcinCommon Carcinnogenic Hazardsnogenic Hazards

MUSHROOMSMUSHROOMS

(Hydrazines)(Hydrazines)

Common CarcinCommon Carcinnogenic Hazardsnogenic Hazards

All chargrilled f d t ifood contains Polycyclic y yAromatic HydrocarbonsHydrocarbons (PAHs)

Common CarcinAssociated with DailyAssociated with Daily

Cosmic ray risks

•one transcontinental flight

•airline pilot, 50 hrs/month p

Other radiation risks

•natural background at seanatural background at sea

Smoking

l•cancer only

•all effects (including heart

Miscellaneous

•regular use of contraceptiv

nogenic Hazards y Lifestyle 1:100 000y Lifestyle, 1:100,000

t per year 21

at 35,000 feet 35

a level 105a level 105

8 4008,400

t disease 21,000

ve pills 140

Post Risk AFolloFollo

Where risk asseWhere risk asserisk manageme

Assessment w upw-up

essment stops,essment stops, ent begins

Risk ManRisk ManIf the answer is “YEand/orand/orIf the answer is “MA

i h lth ffcausing health effeexposures,p ,

Undertake appropriaUndertake appropria

nagementnagementES” for carcinogens,

AYBE” for chemicals t ft h icts after chronic

ate risk managementate risk management

Ri k MRisk Man

Will be undertakenexposures Will be undertakenWill be undertakenpermitting procesWill be undertakenhealthhealth

tnagement

n by controlling

n as part of then as part of the sn to protect public