Bisphenol A in our food : same toxicological studies but different risk assessment and risk management decisions around the world.

Bisphenot A in

our

food: sârnê toxicotogicat

studies

but

different

risk

assessment and

risk

management decisions around the

world

Marie-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 compound synthesized from the condensation of two phenot groups and one acetone molecute [the A in bispheno[ A stands for acetone).

Other

synonyms

for

bisphenoI

A

are

L,4' -dihydroxy-2,2-diphenytpropane loff

i-ciat

IUPAC nomenctaturel,

4,4'-{propan-I Food Science A Law 2Ol'l Os.rndd I

I

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 polycarbonate lfigure 2] and the epoxy resins lfigure 3], as wett as antioxidant and inhibiter of end

ol

potymerization

in

potyvrnyl ch[oride ptastics {PVCI. The potycarbonate is used

in materia[s intended to come into contact

with food, [ike certain

reusabte ptastic

Marie-Louise Scippo

bottles, feeding botttes, plates, gobtets, cups, etc., white the epoxy resins are used in

the

internaI coating of cans. However,

onty 3 % of at[ the potycarbonate produced as

well as

10 0/o _of

_the

_{epoxy resins are}

used

in

materiats intended

to

come into contact

with

foodstuffs (Ptastics Europe, 20071. The

other

uses

are sun

gtasses, buitding materials, CD-R0M, medicat de-vices, etc.

5âmenvâtting

Bisphenot 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). Andere synoniemen 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, atsook ats 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 materiaten}

die bedoeld zijn om in contact te komen met levensmiddelen lPlastics Europe, 2007]. Andere toepassingen zijn zonne-britten, bouwmaterialen, cd's, medische hulpmiddeten, enz.

Résumé

Le bisphénol A IBPAI [2,2-bis-[4-hydroxyphényUpropane, CAS

n'

80-05-71 est un composé chimique industriel issu de [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 résines

époxy, 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 bouteilles en ptastique réutitisabtes, des biberons, des assiettes, des gobetets, des tasses etc., tandis que les résines époxy sont utitisées 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}

utitisés dans 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.

9

os,ou I

HCI

Figure

l:

chemica[ structure of bispheno[ A

ci-1..

_{| '//}

_\\

Ll / \''r t ",- )

|\,,'

CH,

ÜH

r', H[-r

,:-|l

a- F{

Fiqure 2: synthesis of potycarbonate from bisphenot A

o

()

UH

:

A kind of

controversy exists since 2008

about the

good decision

to

take

about bisphenot

A in

baby feeding botttes. Ca-nada and some states of the USA banish it since 2008, while in

the

European Union,

the

decision has

just

been taken

lEuro-pean

Commision, 2011)

and

witl

enter in force on 1 _{"i March} 201 1, for the ban of

manufacture of feeding bottles containing BPA, and

on 1"

June 2011,

for the

ban

of ptacing on

the

market feeding botttes containing BPA.

This kind of decision is a part of the risk management process,

which has

to

be

conducted by pubtic authorities.

The

previous

step

beforê

risk

manage-ment is risk assessment, which is a scien-tific evatuation. Risk assessment is based

on toxicotogica[ studies, as welt as expo-sure studies, in the aim to assess the risk, for the consumer, [inked to the ingestion

of the substance of interest via food.

Here

betow

are

presented

the risk

as-sessment studies performed

for

BPA in

various countries untit now.

It

witL

be

shown

that different risk

as-sessment conclusions and different risk manâgement decisions resuttèd from the evaluation of the same toxicotogicat stu-dies published in the literature.

0pinion on BPA oî the Scientific committêe on Food ISCFI and the European food

sa-fetyauthoriÿ

IEFSAI

The toxic effects of BPA were eva[uated for the

first

time in 1984 by the SCF lScienti-fic committee on food

-

SCF, 1986), which established a tolerable daity intake lTDl)

ch.

ülr

{l

fl

of 0.05 mg/kg of body weight, on the

ba-sis of

chronic

oral

exposure studies {?0

days) carried out in rats and mice. A "no adverse effect levet" (NOAEL)

of

25 mg/ kg body weightlday was found, related to a reduction in the body weight of the ani-mats, to which a factor of uncertainty of 500 had been apptied because of incom-plete data.

The

risks

for

heatth retâted

to the

BPA

were then re-evatuated in 2002 by the SCF

which established this time â provisionâl TDI

of

0.01

mg/kg

body

weight, on

the basis of studies carried

out in rats

[oral exposure during 90 days, study on 3 ge-nerations). The N0AEL, stitt retated to the body weight, was of 5 mg/kg boy weight/

day ICSAH, 2002].

ln

2006,

the

EFSA estabtished

a

TDI for BPA

of

0.05

mg/kg

body weight, on the basis of an unchanged NOAEL, compared to the preceding opinion, of 5 mg/kg body

weight/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 on

the

toxicokinetics

of

BPA and confirmed

the

TDI

of

0.05 mg/kg body weight. The

opinion stated that the differences in toxi-cokinetics according to

the

age between

animals and

humans

did not justify io

increase the factor of uncertainty, on the basis that newborns woutd be abte to me-tabotize BPA

[this

deduction came from

structure

-

activity relationship studies]

IEFSA, 2008].

i,rH

]

,:

Y

'''

lr l. L _,;

ü

"--

ô

r'

'-

_l'

iil

_,

i--

...:.)

Figure 3: chemical structure of an epoxy resin

It is wett known that chemicaI substances

can be

reteased

from ptastic

materiats and articles intended to come into contact

with food, and [imits

of

migration

are mentioned in the European Legistation for

a[t

permitted substances

in

such plastic materiats. At the momeni, the [egistation

still in

force

is the

Directive 200217218C

IEC, 2002], transposed

in

Betgium in the

Royat Decree of 3 Juty 2005 which witt be

reptaced, 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 fixed since 2004 to 0.6 mg/kg food product, and

is not changed in the new regulation.

BPA is described as an endocrine

disrup-tor

because many studies showed

that

it has estrogenic properties.

lt

is in

parti-cular able to bind and activate the human

estrogen receptor but, with

a

capacity

1,000

to

5,000

times

less than

the

endo-genous 178-oestradiot, the naturaI tigand

of this receptor IFASFC, 2009].

BPA

is

ctassified

as a

substance repro-poison of category 3 la[arming substance for the ferti[ity of the mankind

-

INSERM,

20 1 0).

Because

of

that

characteristic,

the

BPA

has a very bad reputation. BPA was very often cited in the media these last months, mainty about potycarbonate baby feeding botttes, which can retease BPA when their content is heated lwhich correspond to a

normal use of these botttes] however the amounts released are

far

[ower than the SLM {De Coensel et al., 2009J. The conse-quence of this retease is the exposure of

the baby to an endocrine disrupting che-micat, which is not very reassuring for the mothen 'tt- i.

il

JI

n

IO

I

ræo Scienæ a uw 2011{s.indd 10 7/06/11 O9:a6

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

devetoPmentaI neurotoxicity of BPA in the rat;

2)

to re-examine the reLent scientific

literature,

in

order

to

re-evatuate the risk related to BPA and the de-termination of its TDI;

3)

to give an opinion on the risk

eva-tuation reatized bÿ

the

nationaI food institute, TechnicaI University of Denmark IDTU, æ10] and to

try

to

substantiate

tlç

subsequent banishment,

in

Derlmark.

of

BPA

in the feeding bott[es.

With regard to item '1, _{fottowing an}

etabo-rate statistical expertise {EFSA. 2010}, the

ËFSA conctuded that

the

study of Stump and co-workers [2009] does atLow to draw

conclusions.

i

With

regard

to

item

2,

the

foltowing conctusions were emitted: I

-

the studies of the toxicokinetics o{ BPA

showed

that

BPA

was

etifninated more quickty

in the primates than in the

ro-dents. The premature

children are

able to metabolize and excrete tsPA efficientiy. The same conclusion

is

atLo emitted for

the "s[ow

metabolisers" [i:eopte among whom

the

isoenzymes

of

Fletabotisation are less

activel.

:

- the exposure of the fetus ln utero and the infant nursed by his mother seems [imi-ted.

-

recent

epidemiotogical §tudies having shown a link between the €rxposure to the BPA lestimated

on the

basis

of

urinary concentration)

and effects on the

adutt

heatth

Ion

the

cardiovascutar system and

the

reproductive apparatus) and on

the

behaviour

of

young

girts,

cannot be

taken into account in

the risk

evaluation, because of weaknesses in these studies.

-

the

studies

of the toxic

effects

of

low doses of BPA

[.

NOAELI on development and 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 does

not 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 the sensitivity

of

mammary gtand

to

devetop

cancer, after

exposure

to

carcinogenic substances. The two studies present [imi-tations and cannot be taken into account but

the

EFSA indicates

that

the potential effects announced shou[d be

further

stu-died.

-

severaI studies showed effects

of

BPA

on

the

immune system,

but

they cannot be validated because of experimental [i-mitations.

-

several

in

vitro and ln vivo studies [but

not

corresponding

to the criteria

setec-ted

by

the

panel

of

experts

of

EFSA to be taken into account in the

risk

eva[ua-I fooascience&Law2o1l-Os.indd 1t

I

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 disturbing effect 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 arguments IDTU,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-response curve 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 not regard

the

arguments advanced

by

the

OTU as retevant.

This opinron of the EFSA {EFSA, 20 1 0} atso

mentions a minority opinion of an expert from the CEF panel {panet on food contact materiats, 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 the opinion on BPA IEFSA, 201 0] and to inform of its concern with respect to the possibte effect of BPA on the human heatth, taking into account of some uncertainties in re-centty pubtished toxicologicaI studies.

ùpinion on BPA

of

the ANSES, the

lormer

EFSA (French Agency

for

Food, Environ-mental and Ùccupational Health & Safetyl The ANSES pubtished on opinion, on

0c-tober

20th, 2009,

in the aim to

answer three questions;

1 ] Does the study of the toxicity of BPA on

the

nervous system development

[Ame-rican

Chemistry Counci[, 2009], carried out according

to

guidetine

n"

426 of the Organization

for

Economic Co-operation and Devetopment (OECDI, show negative effects of BPA on the offspring consecu-tive to BPA exposure during gestation and

breast-feedi ng?

The experts estimate that this study does

not show any neurotoxic effect

in

the offs-pring of mothers treated with doses of BPA

corresponding to the N1AEL. But at higher doses, the study does

not

altow

to

draw conclusions,

taking

into account

the

ab'

sence of investigation on the origin

of

the

convu[sions observed in same rats.

2)

Does

this

study at[ow

to

assess the lack of toxicity of

the

BPA

at

tow doses, on

the

neurologicaI and behaviouraI de-vetopment? Do the recent

literature

data

confirm atarming effects in terms of

pu-btic health, after

exposure

to

very

low doses 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 {critical windows of exposure during which harmfuL

effects can appear,

in

particuLar

the

pre-natal period), the TDI does not appear to

be the best approach for risk eva[uation. ln addition, the guideline no 426 of 1ECD does not appear entirely adapted to characterize subtle eflects on the nervous system, such as they could be observed with endocrine disruptors and in particular with BPA.

ln its

oprnion,

the

ANSES indicates the presence of warning signa[s observed tn

in vitro and m vivo studies,

with

âmounts tower 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] to evatuate the

risk

retated to the exposure

to

BPA,

but for that, it

would be neces-sary to determine

the

significance of the

warning

signats and

to

possibly re-exa-mine

the

toxicological dose

of

reference IANSES,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 and

collaborators [2009]

and

of

Ryan

et

al. (20 1 0). The purpose of the study of Stump

et al. was to measure thê neurotoxicity of the BPA and its effects on the behaviour in rats,

after

exposure

to

various amounts, inctuding tow doses- The study

of

Ryân

and co-workers aimed

to

measure the oestrogenic 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 studies brings substantiaI proof of a specific toxic effect of BPA tBfR. 2010).

s

II

7/06/11 oera6

The conclusion of the BfR is in agreement

with that of

EFSA,

who

atso invalidated the study of Stump ef al., fotlowing a tho-rough

statistical

anatysis

which

showed weaknesses

in the

experimental design

{EFSA. 2010}. With regard to thë study of

Ryan et ai.,

the

EFSA concluded

that

the study was vatid and

that

it did

not show any 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

risk evaluation about the neurobehaviorat toxi-city of BPA. Heatth Canada conctuded that evidences of the neurotoxicity of the BPA

were timited.

On

the

websitè

of

Heatth Canada

it

can be found

that

["Heatth Ca-nada's Food Diràcroràte has concludêd that

the current dietàr,y exposure to BPA through

food packaging uses is not expected to pose

a

heatth risk to the general population,

in-cLuding newborrs

and

infants". However,

by measure of precaution and to timit the exposure of the infants Iapptication of the principle

of

exposure -ALARA"

-

As Low As Reasonabty Achievabte), the Canadian government prohibited the use of potycar-bonate

for the

manufacturing

of

feeding bottles {coming into effect of this prohibi-tion on March 11th.2010].

Opinion

on

BPA

of

the

^ratioral

Japanese

institute

of

AdÿAnced

lndustrial

Science and Technology lAlSTl

ln 20û5, the AlSTprbtished a risk evalua-tion of

the

BPAbn human heatth, on the basis

of the

toxicotogical

profite of

the

BPA leffects on

the

body weight, the tiver and reprotoxicityl and on estimates of the human exposure.

For

the 3

types

of

effects observed, the

NOAEL or BenchMark Dose Limit IBMDL] varied

from

5 to 50 mg/kg PC/day, with a MOE

from

85,0û0

to

1,800,000.

ln

an ex-treme scenario lworst case), the M0E was

> 1,000. The AIST thus conctuded that the levels

of

exposure

to

BPA

did not

pose

an

unacceptable heatth

risk for

human heatth.

opinion on BPA of the National Toxicology

Program

-

Center

lor

thê

Eveluation

of

Risks to Human Reproduction

NfP -

CE-RHN IUSAI

The NTP indicates

that the

possib[e ef-fects of BPA on

the

brain,

the

behaviour and the prostate in the foetus, the young

children and the chitdren exposed to the BPA

are worrying ["the

NTP

has

some concern" l.

The effects

on

mammary gland and the development

of an

earty puberty.

in

the

fetus, infants and the chitdren

exposed

to

BPA,

are

stightty

worrying

{"minimal

concern ").

or the growth of the chitd are regarded as

negtigibte {"negtigibte concern"). The effects

of

BPA

on the

reproduction

are

regarded

as negtigibte

["negtigibte concern")

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

World

H 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 the media [Le Soir,1211112010) that fottowing

that

meeting,

the WH0

considered that

it

was too early to ban bisphenol A from baby feeding botttes,

the summary

re-port

of

the

meetrng [WHO, 2018] ctearty "identified a number of gaps in knowledge and provided a range of recommendations

for

the generation

of further

information and the design of new studies to better un' derstand the risk to human heaLth posed by

BPA'.

Apinion

on

BPA

of

the

Belgian Superior Health Council

Recentty, to answer

a

question from the Minister of Public Heatth, the Betgian

Su-perior

Heatth CounciI recommended the decrease, to a tevet as low as possibte of

the

exposure

of

young chitdren

to

BPÀ ISHC, 20101, on the basis of uncertainties about toxic effects of BPA, in particular to low doses.

c0NcLustoNs

The questions here below seem to remain strtt without answers.

What about the effects of Low doses af BPA?

Ctassica[ty,

the toxic effects retated

to

a

chemical substance fottow

to a

Iinear dose-response curve.

It is

not

the

same

for

substances acting

on

receptors lsuch

as the

endocrine

disruptors)

because

the

receptors

can

be actrvated with low doses and inhibited

with

stronger

concentrations.

ln

these cases,

the

dose-response curves appear "bett-shaped" instead of [inear. Such ef-fects

with

low doses were described for BPA,

but

in

studies

disptaying certain weaknesses

which do not

altow

to

va[i-date

the

resutts

in order to

re-examine downwards the TDI IEFSA, 2010J.

Which aLternatives

to

BPA

in

plastic ma-teriaI are intended to come in contact with food?

A tot "BPA free" baby feeding bottles are atready 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 toxicity

of

sulfonic

potyether

was less

studied than that of BPA. The best a[ternative thus remains 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 completety explained by

the

exposure through BPA

containing food consumption, suggesting that other way of exposure are not negti-gible. A recent study showed for example

the

possible absorption

of

BPA

from

a

dermal exposure {Zatko et al., 2010). This derma[ exposure could occur through for exampte

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 of atternatives

of

BPA

in

ptastic materia[s intended to come in contact with food. It is rmportant, in particular, to c[artfy the effects 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 the potycarbonate is used in plastic materiat intended

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 lsummary

in

Engtishl:

http://unit.aist.go"jplriss/ crm/mainmenu/BPA_Summary_Eng tish. pdf

American Chemistry Councit {2009i. DNT

study:

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 de

l'Agence française

de sécurité

sanitaire

des

atiments

retatif

à

['analyse critique des résuttats d'une étude de toxicité sur

te

dévetoppement

du

système nerveux

ainsi

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

I

ræOScienceaUw2Oll-Os.indd 12 _{7/06t11 Os:a6}

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

Bisphenol A Shifts the Window of Susceptibitity for

Mammary

Carcinogenesis

in

the

Rat", Environmental Health Perspectives, [Epub ahead of printl.

BfR

-

Bundesrnstitut für Risikobewertung {2010}. Bisphenot

A:

Studies

by

Stump et

al.

(20101 and Ryan et a{. [2010]

pro-vide no

indications

for

adverse effects

on

neurological devetopment

and

beha-viour. BfR Opinion Nr. 035/2010. Arraitabte

from:

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

from

thermaI printer

paper

to the skin",

Anal

Bioanat 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 sorptive

extraction-thermaI

desorption-capittary GC-MS", J. Sep. Sci. 32:382?-3836.

DïU

[Danmarks Tekniske Universitet fo-devareinstituttets) [20'101. _."Eva[uation by

the

DTU Food

lnstitute of the

industry's

new

developmental neurotoxicity study {DNT, 0ECD

fG

426ll

of

bisphenoI A and the significance of the study for the Food

lnstitute's

assessment

ofithe

potentiaI harmfuI 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 it e=Fites%2f Fiter%2f Nyheder%2fVu

rderi

ng_BPA-stud ie. pdf.

EFSA lEuropean Food Safety Authority).

0pinion of the

Scientific Panel

on

Food

Additives, Ftavourings, Processrng Aids and Materials

in

Contact

with

Food on a

request

from the

Commission retated to 2,2. BIS(4.HYDROXYPH ENYL} PRO PAN E

[Bisphenot

A].

Ouestion

number

EFSA-0-2005-100,

The

EFSA

Journat

2006;

42811-75.

Availab[e

from:

http://www.

ef sa. europa.eu/f r/scdocs/scdoc I 428.htm. EFSA (European Food Safety Authority). Toxicokinetics of Bisphenol A

-

Scientific Opinion

of the

Panel

on

Food additives, Ftavourings, Processing

aids and

Mate-riats in Contact with Food [AFC]. The EFSA

Journal

2008; 759:1-10. Availabte from: http://www. efsa. eu ro pa. eu/frlscdocs/sc

-doc/759.htm.

EFSA (European Food Safety Authorityl. Scientific opinion on BisphenoI A: evatua-tion of a study investigating its neurodeve-topmentaI toxicity, review of recent scien-tific [iterature on its toxicity and advice on

the Danish risk assessment of Bisphenot A. The EFSA Journal 2010; 8:1829. Avai-[abte from: http://www.ef sa.europa.eu/frl scdocs/doc/1

829.pdf-EFSA lEuropean Food Safety Authority].

Scientific

report. StatisticaI

re-analysis

of

the Biet

maze dâta

ôf the

Stump et

al.

t20'l0l study:

"DevelopmentaI neu-rotoxicity study of dietary bisphenoI

A

in

Sprague-Dawtey rats". The EFSA Journal 2010;8:1836.

European Commission [2002).

Commis-sion Directive

200217218C

of

6

August 2002 retating to ptastic materials and

ar-ticles intended to come into contact with foodstuffs. 0fficial Journa[; L 220:1 8-58. European Commission. Updated Risk As-sessment Report of

4'-lsopropylidenedi-phenot IEis4'-lsopropylidenedi-phenot-Al {human

heatthJ.

FinaI

approved

version awaiting

pubti-cation, Aprit 2008. Avaitabte

from: http://

ecb. jrc. it/docu m ents/Exist in gc hem icaIs/ RISK_ASSESSM ENT/ADDEN DU

M/bis-phenota_add_325.pdf.

European Commission {2011}. Regu-tation [EU]

N"

10/2011

of

14 January

201 1 on ptastic materiats and artictes intended

to

come into

contact with food. 0J

L

12, 15.1.7011, p. 189

European Commission [2011).

Com-mission

Directive

201118/EU

of

28 .January 2011 amending Directive

20021721EC as regards the restriction of use of BisphenoI A in plastic infant feeding bottles. 0J L 26,29.1.2011, p. 11 -1 4.

FASFC {Federat agency

for the

safety of the food chain). Risques chimiques émer-gents

-

Etude de cas:

les

perturbateurs endocriniens (dossier Sci Com 2007/07bis:

auto-saisine). Bruxe[[es:

AFSCA; 2009.

Avaitabte

from:

http://www.afsca.be/co-mitescientif ique/avis/2009.asp.

Geens, T., Goeyens, L. and Covaci, A. Are non-food sources

important for the

hu-man exposure to bisphenot-A? 30th lnter-nationaI symposium on ha[ogenated per-sistent organic poltutants IPOPsJ. Dioxin;

20'10 Sep 12-17; San Antonio, USA.

Heatth Canada 1201'l) Food and nutrition

-

Bisphenot

A.

http://www.hc-sc.gc.cal

fn -a n/securit/packag -embatt/bpa/i ndex-eng.php.

INSERM

Ilnstilut

Nationat de ta Santé Et

de [a Recherche Médicate]. Bisphénol. A:

Effets

sur

[a reproduction. Rapport préti-minaire. Paris: INSERM; 2010.

Jenkins, S., Raghuraman, N., Eltoum, 1.,

Carpenter,

M.,

Russo,

J.

and

Lamarti-niere,

C.A.

Ora[

Exposure

to

Bisphenot

A

lncreases

Dimethylbenzanthracene-lnduced Mammary Cancer

in

Rats.

En-vironmentaI Heatth

Perspectives 2009;

1 17:910-5.

NTP-CERHR INationat Toxicologicat Pro-gram

-

Center for the Evatuation of Risks

to

Human Reproduction, 2008). NTP-CE-RHR Monograph on the Potentiâl Human Reproductive and Devetopmentat Effects

of

Bisphenol

A.

NIH Pubtication No.

0B-5994; 2008. Avaitabte

from:

http://cerhr.

niehs.nih. gov/evals/bisphenot/bisphenot.

pdf.

OECD {Organization

for

Economic

Co-operation and DevelopmentJ. 0ECD

Gui-detines

for

the

Testing

of

Chemicats

/

Section

4:

Health Effects, Test No. 426:

DevetopmentaI Neurotoxicity Study.

Avai-[ab[e

from;

http://www.oecdbookshop.

orgloecd/di sptây.asp?ci d=sou rceoecd & [a

ng=fr&sf 1 =Dl&st1 =5L4FG25J9WZR.

P[astics

Europe (2007i.

Applications

of

Bisphenot

A.

Availabte

from: http://

www. bisphenot-a -europe. o rglu p[oad

s/

B PAo/oa pp Ii cat i o n s. Pdf .

Royal Decree (2005].

Arrêté royal du

3 juiLl.et 2005

retatif

aux matériâux

et

aux objets en matière plastique destinés à

en-trer

en contact avec les denrées atimen-taires. Moniteur betge, 29.VI1.2005, ed. 2, pp. 33608-33638.

Ryan, 8.C., Hotchkiss, 4.K., Crofton, K.M.

and Gray, L.E. Jr. /n utero and lactationaI exposure

to

bisphenol

A, in

contrast to ethinyt estradiol, does not

âtter

sexually dimorphic behavior, puberty, fertiIity, and

anatomy of femate LE rats. Toxico[ogicat Sciences 2010; 1 14:133-48.

SCF {Scientific Committee

on

Foodl

t1986). EUR 10778 Report of the Scientific Committee for Food {17th series}. Luxem-bourg:

0ffice for 0fficiat

Pubtications of

thê

European Communities. Catatogue

No

CD-NA-10778-EN-C. Avaitable from: http

:l/ec.europa.eu/food/f

s/sc I sct I re

-ports_en.print. htmt.

SCF {Scientific Committee on Food) (2002).

0pinion of the

Scientific Committee on

Food

on

Bisphenol

A.

Brussets; CSAH, 2002. Avaitabte f rom: http:l/ec.europa.eu/

food/f s/sc/scf/out 1 28-en.pdf.

SHC [Superior Heatth Counci[]

t2010]

Avis

n'

8697 sur [e bisphéno[ A. Avaitabte

f

rom:

http://www.heatth.betgium.be/

eportat/Aboutu s/related institutions/Su pe-riorHeatthCouncil/pubtications/index.htm.

Stump, 0.G., Beck, M.J.,

Radovsky, A.,

Garman, R.H.,

Freshwater,

L.,

Sheets.

L.P et

al.

DevetopmentaI neurotoxicity study of dietary bisphenol A

in

Sprague-Dawley rats. Toxicotogical Sciences 2û10; 115:1 67 -82.

U.S. FDA (Food and Drug Administrationl [20'l0b]. Update

on

Bisphenol

A for

Use

in

Food Contact Apptications. Avaitabte

from:

http://www.fda.gov/NewsEvents/ PubticHeatthFocus/ucm 1 97739.htm.

WHO [20101

Joint

FAO/WH0 Expert

Mee-ting

to

Review ToxicotogicaI

and

Heatth Aspects of Bisphenot A. Summary report. Avaitabte f

rom:

http://www.who.int/food-safety/chem/ch emica Is/b isphen

ot_re-tease/en/index. htmt.

Zatko, D., Jacques, C., Duptan, H., Bruel,

S.,

Perdu, E. Viabte

skin

efficientty ab-sorbs and metabolizes bisphenot A. Che-mosphere 20,l 0, 20 1 1 , 82: 424-430.

s

t3

,aUU, O',OU I

I

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