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EC number: 201-245-8
CAS number: 80-05-7
Bisphenol A; BPA
Dietary carcinogenicity studies in rats and mice concluded that Bisphenol A was not carcinogenic in either species. No inhalation or dermal carcinogenicity studies were available, although in repeat exposure inhalation toxicity studies, Bisphenol A did not exhibit properties that raised concern for potential carcinogenicity. Overall, Bisphenol A has no carcinogenic potential.
The 2003 EU RAR concluded:
"There are no human data
contributing to the assessment of whether or not Bisphenol A is
carcinogenic, but a dietary carcinogenicity study in rats and mice
concluded that Bisphenol A was not carcinogenic in either species
because the tumour findings were not considered toxicologically
significant. No inhalation or dermal carcinogenicity studies were
available, although in repeat exposure inhalation toxicity studies,
Bisphenol A did not exhibit properties that raised concern for potential
carcinogenicity. Taking into account all the animal data available, it
was concluded that the animal evidence suggests that Bisphenol A does
not have carcinogenic potential."
The 2008 updated EU RAR
"The new information on the
potential carcinogenic and/or promoting effects of Bisphenol A in
prenatal and neonatal rat models supports the original conclusion that
Bisphenol A does not possess any significant carcinogenic potential.
This is based on one new study in which the full carcinogenic potential
of Bisphenol A on the mammary gland was examined in a prenatal model.
This study claimed that Bisphenol A induced preneoplastic and neoplastic
lesions of the mammary gland, but its validity was hampered by serious
methodological limitations and its findings are inconsistent with the
absence of preneoplastic lesions of the mammary gland in the offspring
from several standard multi-generation studies in rats and mice. Other
new studies suggest that prenatal or neonatal exposure to Bisphenol A
does not exert promoting activity on the carcinogenesis induced by
established carcinogens/initiators in specific organs."
Recent data taken into account
for the dossier update:
A recent study by US NCTR (Delclos
et al 2014) investigated mammary gland proliferation in rats. This study
was evaluated by SCOEL and EFSA. Ethinyl oestradiol was used as a
positive control of the estrogenic effects of Bisphenol A. The
dose-matched vehicle control was carboxymethylcellulose. The doses were:
(i) Bisphenol A 2.5, 8, 25, 80, 260, 840, 2700, 100 000, 300 000 μg/kg
bw per day, (ii) Vehicle, (iii) EE2 0.5, 5 μg/kg bw per day. The study
included a naïve control group and doses were administered by oral
gavage. The protocol and methods, including statistical analysis were of
the high quality and robust with treatment, body weight and litter
randomisation and appropriate inclusion and exclusion criteria
established prior to the start of the study. The target unit for
analysis was 20 litters and 18-23 were achieved. F0 females were dosed
from GD 6 up to labour onset and pups from PND 1 until tissue
harvesting, up to PND 90. Additional groups were exposed from GD 6 to
PND 21 for histopathological examination of the mammary glands.
Overall conclusion concerning
mammary gland: "Taking the incidences, the statistical testing
results, and all pathologists and study authors opinions together, the
authors of the NTP report (Gu and Mitkus, 2013), concluded that the
evidence for duct hyperplasia in the mammary gland of females on either
PND 21 or PND 90 was weak. They considered it an equivocal finding that
may be the reflection of normal variability and/or a reflection of
limits in tissue processing. Bisphenol A did not cause duct hyperplasia
in the mammary glands of male rats, while conversely the reference
estrogen EE2 induced hyperplasia in the male but not the female mammary
Recommendation 2014 concluded on carcinogenicity:
"Thus, there is currently no
convincing evidence of carcinogenicity of Bisphenol A when administered
either during the adulthood or perinatally. However, as concluded by
EFSA (2014), there are some data (including the data by Delclos et al
2014) that raise some concern for Bisphenol A effects on mammary gland
cell proliferation after pre- and perinatal exposure. Whether this is
linked to increased cancer incidence in later life or not remains to be
Opinion 2015 concluded:
morphological changes potentially related to carcinogenesis
"Earlier evidence for
Bisphenol A effects on cell proliferation and differentiation in the
mammary gland and other tissues (e.g. prostate or testis) has been
supported by recent studies. The proliferative changes in the mammary
gland reported in these new studies, including a non-human primate
study, are insufficient to conclude that there is a link to cancer
development in later life. However, there might be a possible role of
Bisphenol A in increasing the susceptibility to mammary gland
carcinogenesis later in life.
responses and possibly enhanced sensitivity to mammary gland carcinogens
seen in animal studies might be of relevance for human health and are
therefore included in the risk assessment.
Using a WoE approach,
the CEF Panel assigned a likelihood level of “likely” to Bisphenol A
induced proliferative changes in the mammary gland. Therefore, this
endpoint was brought forward for hazard characterisation and for
The CEF Panel
considered that the evidence for proliferative changes induced by
Bisphenol A in other organs (e.g. prostate or testis) is currently too
limited to reach any conclusion."
few epidemiological studies published to date have investigated a
possible association between exposure to Bisphenol A and incidence of
certain cancers, specifically breast cancer and meningioma. These
studies do not allow any conclusion to be drawn regarding the
carcinogenicity of Bisphenol A in humans.
A was not carcinogenic in two standard oral carcinogenicity studies in
rats and mice. In a more recent study, female but not male mice, exposed
to approximately 10 mg/kg bw per day Bisphenol A from in
utero up to postnatal day (PND)
21, developed significantly more hepatocellular tumours (adenomas and
carcinomas together) with or without preneoplastic lesions after a
stop-exposure period of 10 months. Additional rodent studies on
perinatal exposure to Bisphenol A investigated the potential
carcinogenic effect in mammary gland. Due to weaknesses in these studies
the results do not provide convincing evidence that Bisphenol A is
carcinogenic to the liver during adult life or in mammary gland
following perinatal exposure.
a WoE approach, the CEF Panel assigned a likelihood level of “unlikely
to - as likely as not -” to carcinogenic effects of Bisphenol A. Since
the likelihood level for this endpoint is less than "as likely as not”
(see Appendix A), this endpoint was not taken into account in the
evaluation of uncertainty for hazard characterisation and risk
Bisphenol A is included in Annex
VI of Regulation (EC) No 1272/2008. No classification regarding
carcinogenicity is required.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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