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EC number: 201-245-8
CAS number: 80-05-7
Bisphenol A; BPA
The 2003 EU RAR concluded:
"No human data regarding mutagenicity
are available. However, Bisphenol A appears to have demonstrated
aneugenic potential in vitro, positive results being observed without
metabolic activation in a micronucleus test in Chinese hamster V79 cells
and in a non-conventional aneuploidy assay in cultured Syrian hamster
embryo cells. Additionally, in cell-free and cellular systems there is
information that shows Bisphenol A disrupts microtubule formation.
Bisphenol A has been shown to produce adduct spots in a post-labelling
assay with isolated DNA and a peroxidase activation system, but it does
not appear to produce either gene mutations or structural chromosome
aberrations in bacteria, fungi or mammalian cells in vitro. However,
some deficiencies in the conduct of these studies have been noted and
the negative results cannot be taken as entirely conclusive. Bisphenol A
does not appear to be aneugenic in vivo, since a recently conducted,
standard mouse bone marrow micronucleus test has given a negative
result. Bisphenol A was negative in a briefly reported dominant lethal
study in rats but, given the limited details provided, this is not
regarded as an adequate negative result. The only other data in somatic
cells in vivo are from a 32P-postlabelling assay, which showed that
Bisphenol A is capable of producing DNA adduct spots in rat liver
following oral administration. These adduct spots were not characterised
Considering all of the available
genotoxicity data, and the absence of significant tumour findings in
animal carcinogenicity studies (see below), it does not appear that
Bisphenol A has significant mutagenic potential in vivo. Any aneugenic
potential of Bisphenol A seems to be limited to in vitro test systems
and is not of concern. The relevance of the finding that Bisphenol A can
produce rat hepatic DNA adduct spots in a postlabelling assay is not
entirely clear. However, given the absence of positive results for gene
mutation and clastogenicity in cultured mammalian cell tests, it seems
unlikely that these are of concern for human health."
The 2008 updated EU RAR concluded:
"New data from a study indicating
effects of Bisphenol A on meiosis in female mice cannot be taken as
conclusive evidence of an effect of Bisphenol A on germ cell meiosis
because of the several methodological weaknesses and flaws identified in
the study, the reporting inadequacies, and the known mutagenicity and
toxicity profile of Bisphenol A. In addition, these findings have not
been confirmed in more recent publications. Thus, the original
conclusion that Bisphenol A has no significant mutagenic potential in
vivo is still valid."
Additional recent information
concerning the observations reported discussed in the 2008 updated EU
RAR was discussed in the initial dossier submitted in 2010:
Two in vivo studies (Hunt et
al.(2003) and Susiarjo et al. (2007)) evaluated during the 2008 EU RAR
reported that short-term oral exposure to low doses of Bisphenol A (≥
0.020 mg/kg bw/day) in peripubertal or pregnant mice can interfere with
meiotic divisions in development of female germ cells (“egg” or
“oocyte”). An increase in hyperploid (aneuploid) metaphase II oocytes
was observed following treatment with 0.020 mg/kg bw/day. There was not
a significant increase in aneuploid embryos.
Two subsequent in vivo studies
(Pacchierotti et al.(2008), Eichenlaub-Ritter et al. (2008)) attempted
to replicate these findings. Consistent with the previous findings, they
detected no significant effects of Bisphenol A exposure on the frequency
of aneuploidy in “zygotes” (fertilised oocytes) produced from female
mice treated before puberty or as adults with a similar range of doses.
In addition, Eichenlaub-Ritter et al. (2008) found no effects of
Bisphenol A exposure on aneuploid oocytes and Pacchierotti et al. (2008)
found no increase in aneuploid or diploid sperm following exposure of
male mice to Bisphenol A. The authors concluded that the aneuploidy
predicted by the Hunt group could not be confirmed.
In addition, in a recent study published
by the Hunt group, Muhlhauser et al. (2009), the authors could not
replicate their initial findings on “congression failure” but report
effects on chromosome alignment and/or spindle formation. The authors
state “After publishing our findings [Hunt et al., 2003], we initiated
studies to assess the effect of long term Bisphenol A exposure on the
growing follicle. To our surprise, levels of Bisphenol A that were
sufficient to elicit an effect on meiotic chromosome dynamics during the
previous two years of study suddenly produced little or no effect. In an
analysis of possible changes in experimental protocol, the only change
identified was the lot of animal feed.” The authors report frequencies
of abnormal oocytes in the absence and presence of Bisphenol A in two
different diets (casein based and soy based). The reported frequencies
of abnormal oocytes of the Bisphenol A/casein group are lower than the
background value reported in the soy-based diet.
Overall, the initial observations
reported by the Hunt laboratory were not reproduced in the same
laboratory or in other independent laboratories. Therefore, the
conclusion from the 2003 EU RAR and the 2008 EU RAR Update is still
valid; Bisphenol A has no significant mutagenic potential in vivo.
SCOEL Recommendation 2014 concluded
“Considering all of the available
genotoxicity data and the absence of significant tumour findings in
animal carcinogenicity studies (see Section 3.8), it does not appear
that Bisphenol A has significant mutagenic or genotoxic potential in
EFSA Opinion 2015 concluded on
“The available data support that
Bisphenol A is not mutagenic (in bacteria or mammalian cells), or
clastogenic (micronuclei and chromosomal aberrations). The potential of
Bisphenol A to produce aneuploidy in vitro was not expressed in vivo.
The positive finding in the postlabelling assays in vitro and in vivo is
unlikely to be of concern, given the lack of mutagenicity and
clastogenicity of Bisphenol A in vitro and in vivo.
Using a WoE approach, the CEF Panel
assigned a likelihood level of “unlikely” to Bisphenol A genotoxicity.”
Bisphenol A is included in Annex
VI of Regulation (EC) No 1272/2008. No classification regarding genetic
toxicity 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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