Bisphenot A in our food: sârnê toxicotogicatstudies but different risk assessment and riskmanagement decisions around the worldMarie-Louise Scippo, Department of Food Sciences, Faculty of veterinary medicine, University of Liège, Belgium

INTRODUCTION

BisphenoI A tBPA] [2,2-bis-(4-hydroxy-phenytl propane, CAS no 80-05-71 [figure'il is an industriat chemicaI compoundsynthesized from the condensation of twophenot groups and one acetone molecute[the A in bispheno[ A stands for acetone).Other synonyms for bisphenoI A areL,4' -dihydroxy-2,2-diphenytpropane loff i-ciat IUPAC nomenctaturel, 4,4'-{propan-

I Food Science A Law 2Ol'l Os.rndd II

2-ytidenel diphenot, p, p'-isopropytidene-bisphenoI or 4,4'-isopropytidenediphe-no[-It is used as a monomer in the manufac-turing of potymers such as polycarbonatelfigure 2] and the epoxy resins lfigure 3],as wett as antioxidant and inhibiter of endol potymerization in potyvrnyl ch[orideptastics {PVCI. The potycarbonate is usedin materia[s intended to come into contactwith food, [ike certain reusabte ptastic

Marie-Louise Scippo

bottles, feeding botttes, plates, gobtets,cups, etc., white the epoxy resins are usedin the internaI coating of cans. However,onty 3 % of at[ the potycarbonate producedas well as 10 0/o of the epoxy resins areused in materiats intended to come intocontact with foodstuffs (Ptastics Europe,20071. The other uses are sun gtasses,buitding materials, CD-R0M, medicat de-vices, etc.

5âmenvâttingBisphenot A [BPAI [2,2-bis-t4-hydroxyphenytlpropaan. CAS n" 80-05-7] is een industriëte chemische stof, gesyntheti-seerd uit de condensatie van twee fenotgroepen en één aceton motecu[e [de A in bisphenot A staat voor aceton). Anderesynoniemen voor bisphenot A zijn 1+,4'-dihydroxy-2,2-diphenytpropane {officieet IUPAC-nomenclatuur}, 4,4'-[propan-2-ytidenel difenot, p, p'-isopropytidenebispheno[, of4,4'-isopropytidenediphenot.Het wordt gebruikt ats een monomeer bij de productie van potymeren zoals polycarbonaat en de epoxyharsen, atsookats antioxidant en polymerisatie-inhibitor binnen potyvinytchtoride IPVC]. Het polycarbonaat wordt gebruikt in mate-riaten die bedoetd zijn om in contact te komen met voeding, zoats bepaalde herbruikbare ptastic flessen, zuigf[essen,borden, drinkbekers, kopjes, enz. terwijI de epoxyharsen gebruikt worden ats dektagen van voedse[- en drankblik.jes.Niettemin wordt stechts 3 o/o van alte geproduceerde potycarbonaat en 10 o/o van de epoxyharsen gebruikt in materiatendie bedoeld zijn om in contact te komen met levensmiddelen lPlastics Europe, 2007]. Andere toepassingen zijn zonne-britten, bouwmaterialen, cd's, medische hulpmiddeten, enz.

RésuméLe bisphénol A IBPAI [2,2-bis-[4-hydroxyphényUpropane, CAS n' 80-05-71 est un composé chimique industriel issude [a condensation de deux groupes de phénot et une motécule d'acétone lte A de bisphénot A réfère à ['acétone].D'autres synonymes pour [e bisphénol A sont 4,4'-dihydroxy-2,2-diphénytpropane {nomenclature officielte IUPAC],4.4'-tpropan-2-ytidène)diphénot, p, p'-isopropytidènebisphénot, ou 4,4'-isopropytidènediphéno[.Le bisphénot A est utitisé comme monomère pour [a fabrication de potymères tets que [e potycarbonate et tes résinesépoxy, comme antioxydant et comme inhibiteur de po[ymérisation dans [e potychtorure de vinyte [PVC]. Le potycarbo-nate est utitisé dans tes matériaux qui entrent en contact avec les denrées alimentaires, comme certaines bouteillesen ptastique réutitisabtes, des biberons, des assiettes, des gobetets, des tasses etc., tandis que les résines époxy sontutitisées comme revêtement intérieur des boîtes de conserves.Tout de même, ce n'est que 3 o/o de [a production totate du potycarbonate et 10 % des résines époxy qui sont utitisésdans des matériaux destinés à entrer en contact âvec tes denrées alimentaires IPtastics Europe, 2007]. D'autres appti-cations sont les lunettes de soteit, les matériaux de construction, tes CD, les moyens médicaux, etc.

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Figure l: chemica[ structure of bispheno[ A

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A kind of controversy exists since 2008about the good decision to take aboutbisphenot A in baby feeding botttes. Ca-nada and some states of the USA banish itsince 2008, while in the European Union,the decision has just been taken lEuro-pean Commision, 2011) and witl enterin force on 1 "i March 201 1, for the ban ofmanufacture of feeding bottles containingBPA, and on 1" June 2011, for the banof ptacing on the market feeding botttescontaining BPA.

This kind of decision is a part of the riskmanagement process, which has to beconducted by pubtic authorities.The previous step beforê risk manage-ment is risk assessment, which is a scien-tific evatuation. Risk assessment is basedon toxicotogica[ studies, as welt as expo-sure studies, in the aim to assess the risk,for the consumer, [inked to the ingestionof the substance of interest via food.

Here betow are presented the risk as-sessment studies performed for BPA invarious countries untit now.It witL be shown that different risk as-sessment conclusions and different riskmanâgement decisions resuttèd from theevaluation of the same toxicotogicat stu-dies published in the literature.

0pinion on BPA oî the Scientific committêeon Food ISCFI and the European food sa-fetyauthoriÿ IEFSAI

The toxic effects of BPA were eva[uated forthe first time in 1984 by the SCF lScienti-fic committee on food - SCF, 1986), whichestablished a tolerable daity intake lTDl)

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of 0.05 mg/kg of body weight, on the ba-sis of chronic oral exposure studies {?0days) carried out in rats and mice. A "no

adverse effect levet" (NOAEL) of 25 mg/kg body weightlday was found, related toa reduction in the body weight of the ani-mats, to which a factor of uncertainty of500 had been apptied because of incom-plete data.

The risks for heatth retâted to the BPAwere then re-evatuated in 2002 by the SCFwhich established this time â provisionâlTDI of 0.01 mg/kg body weight, on thebasis of studies carried out in rats [oralexposure during 90 days, study on 3 ge-nerations). The N0AEL, stitt retated to thebody weight, was of 5 mg/kg boy weight/day ICSAH, 2002].

ln 2006, the EFSA estabtished a TDI forBPA of 0.05 mg/kg body weight, on thebasis of an unchanged NOAEL, comparedto the preceding opinion, of 5 mg/kg bodyweight/day, but to which a factor of uncer-tainty of 100 instead of 500 was apptied,because the databases were more com-plete than in 2002 {EFSA, 2006).

ln 2008, the EFSA pubtished an opinion onthe toxicokinetics of BPA and confirmedthe TDI of 0.05 mg/kg body weight. Theopinion stated that the differences in toxi-cokinetics according to the age betweenanimals and humans did not justify ioincrease the factor of uncertainty, on thebasis that newborns woutd be abte to me-tabotize BPA [this deduction came fromstructure - activity relationship studies]IEFSA, 2008].

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Figure 3: chemical structure of an epoxy resin

It is wett known that chemicaI substancescan be reteased from ptastic materiatsand articles intended to come into contactwith food, and [imits of migration arementioned in the European Legistation fora[t permitted substances in such plasticmateriats. At the momeni, the [egistationstill in force is the Directive 200217218C

IEC, 2002], transposed in Betgium in theRoyat Decree of 3 Juty 2005 which witt bereptaced, on 1't May 201 1, by the Reguta-tion [EU) N'10/2011 tEU.2011]. For BPA,a specific [rmit of migration [SLM) is fixedsince 2004 to 0.6 mg/kg food product, andis not changed in the new regulation.

BPA is described as an endocrine disrup-tor because many studies showed that ithas estrogenic properties. lt is in parti-cular able to bind and activate the humanestrogen receptor but, with a capacity1,000 to 5,000 times less than the endo-genous 178-oestradiot, the naturaI tigandof this receptor IFASFC, 2009].BPA is ctassified as a substance repro-poison of category 3 la[arming substancefor the ferti[ity of the mankind - INSERM,20 1 0).

Because of that characteristic, the BPAhas a very bad reputation. BPA was veryoften cited in the media these last months,mainty about potycarbonate baby feedingbotttes, which can retease BPA when theircontent is heated lwhich correspond to anormal use of these botttes] however theamounts released are far [ower than theSLM {De Coensel et al., 2009J. The conse-quence of this retease is the exposure ofthe baby to an endocrine disrupting che-micat, which is not very reassuring for themothen

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Very recentty, on September 30th, 2010,

the EFSA published its most recent opi-nion based on an evatuation which had

been carried with 3 distinct objectives:1J to evatuate the studY Pubtished

by Stump and co-workers in 2009'

concerning the devetoPmentaIneurotoxicity of BPA in the rat;

2) to re-examine the reLent scientificliterature, in order to re-evatuatethe risk related to BPA and the de-termination of its TDI;

3) to give an opinion on the risk eva-tuation reatized bÿ the nationaIfood institute, TechnicaI Universityof Denmark IDTU, æ10] and to tryto substantiate tlç subsequentbanishment, in Derlmark. of BPAin the feeding bott[es.

With regard to item '1, fottowing an etabo-rate statistical expertise {EFSA. 2010}, theËFSA conctuded that the study of Stumpand co-workers [2009] does atLow to drawconclusions.

iWith regard to item 2, the foltowingconctusions were emitted: I

- the studies of the toxicokinetics o{ BPAshowed that BPA was etifninated morequickty in the primates than in the ro-dents. The premature children are ableto metabolize and excrete tsPA efficientiy.The same conclusion is atLo emitted forthe "s[ow metabolisers" [i:eopte amongwhom the isoenzymes of Fletabotisationare less activel. :

- the exposure of the fetus ln utero and theinfant nursed by his mother seems [imi-ted.- recent epidemiotogical §tudies havingshown a link between the €rxposure to theBPA lestimated on the basis of urinaryconcentration) and effects on the aduttheatth Ion the cardiovascutar systemand the reproductive apparatus) and onthe behaviour of young girts, cannot betaken into account in the risk evaluation,because of weaknesses in these studies.- the studies of the toxic effects of lowdoses of BPA [. NOAELI on developmentand reproduction, carried out in rats, can-not be regarded as vatid.- according to a study on the sexuaI beha-viour of femates rats, the BPA in viro doesnot seem to have an estrogenic effect(contrary to the rats treated with estro-gens used as positive controtsJ.- two recent studies indicate that the BPA,fotlowing an exposure during Iactation[Jenkins et a{.. 2009] or in ufero lBetan-court et at., 20101, woutd increase thesensitivity of mammary gtand to devetopcancer, after exposure to carcinogenicsubstances. The two studies present [imi-tations and cannot be taken into accountbut the EFSA indicates that the potentialeffects announced shou[d be further stu-died.- severaI studies showed effects of BPAon the immune system, but they cannotbe validated because of experimental [i-mitations.- several in vitro and ln vivo studies [butnot corresponding to the criteria setec-ted by the panel of experts of EFSA tobe taken into account in the risk eva[ua-

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tionl showed modifications Irncluding low

doses) on the [eve[ of receptors, on the

immune system, the ce[ protiferation, the

apoptose, and at a genomic and epigene-

tic tevet. These modifications are in reta-

tion to the potential endocrine disturbingeffect of BPA. These studies present [imi-tations and it is difficutt to deduce a ctear

mode of action at low doses as we[[ as an

effect on the human health.

With regard to the third point, the DTU in

Denmark had advanced three argumentsIDTU,2010]:- the uncertainty retated to the effect of

BPA on the capacity of learning Istudy of

Stump et al., 20091;

- the existence of a doubt about the mo-notonous propriety of the dose-responsecurve of the BPA [which does not take into

account the effects at low doses];- certain effects were not studied: trai-ning and memory, anxious behaviour and

gender-specif ic behaviour lsexuaI dimor-phisml.For the reasons mentioned above Iconcer-ning the first 2 pointsl, the EFSA did notregard the arguments advanced by theOTU as retevant.

This opinron of the EFSA {EFSA, 20 1 0} atsomentions a minority opinion of an expertfrom the CEF panel {panet on food contactmateriats, enzymes, f[avourings and pro-cessing aidsl who wished to mark its dis-sension with the conctusions of the maio-rity of the other experts published in theopinion on BPA IEFSA, 201 0] and to informof its concern with respect to the possibteeffect of BPA on the human heatth, takinginto account of some uncertainties in re-centty pubtished toxicologicaI studies.

ùpinion on BPA of the ANSES, the lormerEFSA (French Agency for Food, Environ-mental and Ùccupational Health & Safetyl

The ANSES pubtished on opinion, on 0c-tober 20th, 2009, in the aim to answerthree questions;

1 ] Does the study of the toxicity of BPA onthe nervous system development [Ame-rican Chemistry Counci[, 2009], carriedout according to guidetine n" 426 of theOrganization for Economic Co-operationand Devetopment (OECDI, show negativeeffects of BPA on the offspring consecu-tive to BPA exposure during gestation andbreast-feedi ng?The experts estimate that this study doesnot show any neurotoxic effect in the offs-pring of mothers treated with doses of BPA

corresponding to the N1AEL. But at higherdoses, the study does not altow to drawconclusions, taking into account the ab'sence of investigation on the origin of theconvu[sions observed in same rats.

2) Does this study at[ow to assess thelack of toxicity of the BPA at tow doses,on the neurologicaI and behaviouraI de-vetopment? Do the recent literature dataconfirm atarming effects in terms of pu-btic health, after exposure to very lowdoses of BPA? Do these data resutt in mo-

difying the toxicotogical reTerence dose

retained to estabtish the TDI?

ln the studies of the literature, the effects

observed with very low doses of BPA cor-

respond ta subtte functional modifications

{ne,urological, hormonal or metabolicl and

are to be interpreted as warning signal be-

cause their fatal consequences for the hu-

man heatth are not established. However,

these studles display important methodo-

togicaL blas and do not aLlow to establish a

dose-response retatianship nor to define a

toxicotogicaL dose of reference to establlsh

a newTDt. ln the current position of knowle-

dge, it is not possible to correlate the data

of exposure recorded in humans with the

effects observed in vivo in animals, because

of i nsuf f ici e nt t oxico k i netics data.

3) ln a more general way, is the metho-dotogy of risk evatuation based on the

concept of the TDI wetl adapted to endo-

crine disruptors, such as BPA?

The TDI corresponds to the maximum quan'

tity of a contaminant which can be consu'

med daity during the whole life without

harmfut effects for the human heatth. ln the

case of endocrine disruptors compounds,

being able to exert different effecB accor-ding to the stage of development {criticalwindows of exposure during which harmfuL

effects can appear, in particuLar the pre-

natal period), the TDI does not appear tobe the best approach for risk eva[uation. ln

addition, the guideline no 426 of 1ECD does

not appear entirely adapted to characterizesubtle eflects on the nervous system, suchas they could be observed with endocrinedisruptors and in particular with BPA.

ln its oprnion, the ANSES indicates thepresence of warning signa[s observed tn

in vitro and m vivo studies, with âmountstower than the NOAEL [5 mg/kg Pc/day),whose significance should be determined.

The ANSES recommends to use the prtn-ciple of the M0E [Margin 0f Exposure] toevatuate the risk retated to the exposureto BPA, but for that, it would be neces-sary to determine the significance of thewarning signats and to possibly re-exa-mine the toxicological dose of referenceIANSES,20lO}.

ùpinion on BPA of the German federal ins'tituta tor risk assessment: BîR (Bunde-

sin stitut f ü r Ri si kobewertu ng I

0n Juty 29th, 2010, BfR published an opi-nion concerning the studies of Stump andcollaborators [2009] and of Ryan et al.(20 1 0). The purpose of the study of Stumpet al. was to measure thê neurotoxicity ofthe BPA and its effects on the behaviour inrats, after exposure to various amounts,inctuding tow doses- The study of Ryân

and co-workers aimed to measure theoestrogenic effects in the offspring of fe-male rats whose mothers had been trea-ted with BPA during gestation and lacta-tion.According to BfR, none of the two studiesbrings substantiaI proof of a specific toxiceffect of BPA tBfR. 2010).

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The conclusion of the BfR is in agreementwith that of EFSA, who atso invalidatedthe study of Stump ef al., fotlowing a tho-rough statistical anatysis which showedweaknesses in the experimental design{EFSA. 2010}. With regard to thë study ofRyan et ai., the EFSA concluded that thestudy was vatid and that it did not showany effect of low doses of BPA on the de-velopment of an abnormat sexual beha-viour in female rats.

0pinion on BPA of Hêalth Canada

ln 2008, Heatth Canada published a riskevaluation about the neurobehaviorat toxi-city of BPA. Heatth Canada conctuded thatevidences of the neurotoxicity of the BPAwere timited. On the websitè of HeatthCanada it can be found that ["Heatth Ca-nada's Food Diràcroràte has concludêd thatthe current dietàr,y exposure to BPA throughfood packaging uses is not expected to posea heatth risk to the general population, in-cLuding newborrs and infants". However,by measure of precaution and to timit theexposure of the infants Iapptication of theprinciple of exposure -ALARA" - As LowAs Reasonabty Achievabte), the Canadiangovernment prohibited the use of potycar-bonate for the manufacturing of feedingbottles {coming into effect of this prohibi-tion on March 11th.2010].

Opinion on BPA of the ^ratioral

Japaneseinstitute of AdÿAnced lndustrial Scienceand Technology lAlSTl

ln 20û5, the AlSTprbtished a risk evalua-tion of the BPAbn human heatth, on thebasis of the toxicotogical profite of theBPA leffects on the body weight, the tiverand reprotoxicityl and on estimates of thehuman exposure.For the 3 types of effects observed, theNOAEL or BenchMark Dose Limit IBMDL]varied from 5 to 50 mg/kg PC/day, with aMOE from 85,0û0 to 1,800,000. ln an ex-treme scenario lworst case), the M0E was> 1,000. The AIST thus conctuded that thelevels of exposure to BPA did not posean unacceptable heatth risk for humanheatth.

opinion on BPA of the National ToxicologyProgram - Center lor thê Eveluation ofRisks to Human Reproduction NfP - CE-RHN IUSAI

The NTP indicates that the possib[e ef-fects of BPA on the brain, the behaviourand the prostate in the foetus, the youngchildren and the chitdren exposed to theBPA are worrying ["the NTP has someconcern" l.The effects on mammary gland and thedevelopment of an earty puberty. in thefetus, infants and the chitdren exposedto BPA, are stightty worrying {"minimalconcern ").

or the growth of the chitd are regarded as

negtigibte {"negtigibte concern").The effects of BPA on the reproductionare regarded as negtigibte ["negtigibteconcern") for the non occupâtlonatly ex-posédèdùtts and not very worrying {"mi-nimaI concern") for the professionatty ex-posed adutt INTP-CERHR, 2008j.

Opinion on BPA ol the Food and 0rgani'zation Agriculture [FAol and the WorldH ea lth 0 rga nization lW H 0 I

A joint FAOÀVHO expert meeting was or-ganized in Ottawa, Canada, from 1 to 5

November 201 0, in order 1o review toxico-togical and heatth aspects of bisphenot A.

Even if, at that time, we coutd read in themedia [Le Soir,1211112010) that fottowingthat meeting, the WH0 considered thatit was too early to ban bisphenol A frombaby feeding botttes, the summary re-port of the meetrng [WHO, 2018] ctearty"identified a number of gaps in knowledgeand provided a range of recommendationsfor the generation of further informationand the design of new studies to better un'derstand the risk to human heaLth posed by

BPA'.

Apinion on BPA of the Belgian SuperiorHealth Council

Recentty, to answer a question from theMinister of Public Heatth, the Betgian Su-perior Heatth CounciI recommended thedecrease, to a tevet as low as possibte ofthe exposure of young chitdren to BPÀ

ISHC, 20101, on the basis of uncertaintiesabout toxic effects of BPA, in particular tolow doses.

c0NcLustoNs

The questions here below seem to remainstrtt without answers.

What about the effects of Low doses af BPA?Ctassica[ty, the toxic effects retated toa chemical substance fottow to a Iineardose-response curve.It is not the same for substances actingon receptors lsuch as the endocrinedisruptors) because the receptors canbe actrvated with low doses and inhibitedwith stronger concentrations. ln thesecases, the dose-response curves appear"bett-shaped" instead of [inear. Such ef-fects with low doses were described forBPA, but in studies disptaying certainweaknesses which do not altow to va[i-date the resutts in order to re-examinedownwards the TDI IEFSA, 2010J.

Which aLternatives to BPA in plastic ma-teriaI are intended to come in contact withfood?A tot "BPA free" baby feeding bottles areatready found on the European market,even if the BPA banishment is not yet in

The potycarbonate botttes can be replaced

by sulfonic potyether or potypropytene

botttes. ln its recent opinion {BfR, 2010),

BfR pointed out that the potypropytene

can release more substances in the food

than potycarbonate, and that the toxicityof sulfonic potyether was less studiedthan that of BPA. The best a[ternative thusremains the gtass baby feeding bottte.

What about the other ways of exposure to

BPA than materials in contact with food?

Other ways of exposure [e.9. toys and

other objects in potycarbonate or PVCI

represent a considerabte source of ex-posure to the BPA. This remark is atso

stressed in the study of Geens etal. [2010),who have shown that the urinary concen-tration of BPA in human is not completetyexplained by the exposure through BPA

containing food consumption, suggestingthat other way of exposure are not negti-gible. A recent study showed for examplethe possible absorption of BPA from a

dermal exposure {Zatko et al., 2010). Thisderma[ exposure could occur through forexampte thermal paper coated with bis-phenot A used for store receipts [Bieder-man eta1.,2010).

It is clear that further research is needed

to ctarify the effects on heatth of bisphe-nol A, as wetl as to asses the safety ofatternatives of BPA in ptastic materia[sintended to come in contact with food.It is rmportant, in particular, to c[artfy theeffects of [ow doses of BPA and to deter-mine the best approach for risk assess-ment {TDl or margin of exposurel.Finatty, the other ways of exposure to

BPA than food consumption shou[d be in-vestigated, knowing that onty 3 % of thepotycarbonate is used in plastic materiatintended to come in contact with food{Ptastics Ëurope, 2007).

REFERENCES

AIST {nationat institute of Advanced ln-dustria[ Science and Technotogy, Japan){2005). Bispheno[ A Risk Assessment Do-cument. Japan: Avaitable from lsummaryin Engtishl: http://unit.aist.go"jplriss/crm/mainmenu/BPA_Summary_Eng tish.pdf

American Chemistry Councit {2009i. DNTstudy: A dietary devetopmental neuro-toxicity study of bisphenot A in rats, WIL-186056, September 2009, 4796 p.

ANSES lFrench Agency for Food, Envi-ronmental and occupationat Heatth &Safety) [2010). Avis du 29 janvier 2010 del'Agence française de sécurité sanitairedes atiments retatif à ['analyse critiquedes résuttats d'une étude de toxicité surte dévetoppement du système nerveuxainsi que d'autres données pubtiées ré-cemment sur les effets toxiques du bis-phénot A. Paris: Availabte from http://www.anses.fr/.

T2

The consequences of the exposure of the apptication.pregnant woman to BPA on fetal morta[i- The question is: are these atternatives to Betancourt, A.M., Mobtey, J.A.. Russo, J.ty,thereductionof theweighttothebirth, BPAsafe? and Lamartiniere, C.A. [2010a]. 'Proteo-

mic anatysis in mammary gtands of rat

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offspring exposed ln utero to bisphenoI A",J o u rna I of P roteom i cs', 73 : 1 2l+1 - 1 253.

Betancourt, A.M., Eltoum, LA., Desmond,R.4., Russo, J. and Lamartiniere, C.A.

[2010b). "/n utero Exposure to BisphenolA Shifts the Window of Susceptibitity forMammary Carcinogenesis in the Rat",Environmental Health Perspectives, [Epubahead of printl.

BfR - Bundesrnstitut für Risikobewertung{2010}. Bisphenot A: Studies by Stumpet al. (20101 and Ryan et a{. [2010] pro-vide no indications for adverse effectson neurological devetopment and beha-viour. BfR Opinion Nr. 035/2010. Arraitabtefrom: http://urww.bfr.bund.de/cml290/bisphenot_a_studys*by_stump_et_at_20 1 0_and_ryan-et_at_20 1 0. Pdf

"

Biedermann, S.. Tschudin.'lP, Grob, K.

[2010]. "Transfer of bisphenoI A fromthermaI printer paper to the skin", AnalBioanat Chem. 398;571 -576. ..

De Coenset, N., David, F., Sandra, P{2009). "Study on the migration of bisphe-nol A from baby botttes by stir bar sorptiveextraction-thermaI desorption-capittaryGC-MS", J. Sep. Sci. 32:382?-3836.

DïU [Danmarks Tekniske Universitet fo-devareinstituttets) [20'101. ."Eva[uation bythe DTU Food lnstitute of the industry'snew developmental neurotoxicity study{DNT, 0ECD fG 426ll of bisphenoI A andthe significance of the study for the Foodlnstitute's assessment ofithe potentiaIharmfuI effects of bisphenôt A on the de-vetopment of the nervous system and be-haviour. Avartable f rom: http ://www.food.dt u.dk/Ad min/Pub IiclD own toad. aspx?f ite=Fites%2f Fiter%2f Nyheder%2fVu rdering_BPA-stud ie. pdf.

EFSA lEuropean Food Safety Authority).0pinion of the Scientific Panel on FoodAdditives, Ftavourings, Processrng Aidsand Materials in Contact with Food on arequest from the Commission retated to2,2. BIS(4.HYDROXYPH ENYL} PRO PAN E

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