Relevance of Reported Chromosomal Effects to Humans Has Not Been Established
April 1, 2003
A new paper in Current Biology reports that exposure
to Bisphenol A (BPA) causes a chromosomal abnormality
in the oocytes of female mice and might be read to suggest
that the abnormality could lead to reproductive or developmental
effects. However, reproductive and developmental effects
were not examined in the new study and the experimental
system used has not been validated or standardized for
the evaluation of reproductive effects. Indeed, the
authors of the study note that the relevance of the
reported results to human health has not been established.
The potential for BPA to cause reproductive or developmental
effects has been comprehensively examined in two multi-generation
studies. In these studies BPA did not cause reproductive
or developmental effects at any environmentally relevant
dose. The weight of scientific evidence provided by
these studies, as well as others that have looked specifically
at reproductive or developmental effects, clearly supports
the safety of BPA and provides strong reassurance that
there is no basis for human health concerns from exposure
to environmentally relevant doses of BPA.
Relevance of Reported Chromosomal
Effects to Humans Not Established
A new paper published today in Current Biology1
reports that BPA causes a chromosomal abnormality known
as meiotic aneuploidy in the oocytes of female mice.
As noted in the paper, aneuploidy commonly occurs in
humans and is considered to be the leading cause of
miscarriage, congenital defects and mental retardation.
Maternal age is known to have a potent effect on aneuploidy.
Various potential environmental risk factors have also
been suggested, including exposure to environmental
chemicals. However, significant effects from environmental
factors have been small and difficult to verify or disputed,
making positive associations hard to establish.
Although the paper might be read to suggest that BPA
or other environmental chemicals could have an effect
on reproduction or development, no direct evidence to
support this suggestion is reported in the paper since
the experimental results did not examine reproduction
or development. Indeed, as noted by the authors, additional
research is needed to determine if their experimental
system might provide a sensitive, reliable, and reproducible
assay system for the evaluation of reproductive toxins.
At this point, the experimental system has not been
validated or standardized for use in assessing potential
risk to human health. Consequently, as further noted
by the authors, the relevance of the reported results
to humans has not been established.
Doses of BPA Do Not Cause Reproductive or Developmental
Since the Hunt et al. study did not examine reproduction
or development in their laboratory animals, additional
research is needed to determine if the reported chromosomal
abnormalities actually lead to functional effects. Although
not referenced in the paper, extensive research has
already been conducted to answer precisely this question.
Most notably, this includes a three-generation reproduction
and development study on BPA conducted at the Research
Triangle Institute under the direction of Dr. Rochelle
Tyl 2 , which is one of
the most comprehensive studies of its kind ever conducted.
In this study, Sprague-Dawley rats were fed a diet containing
BPA at levels lower than those tested by Hunt et al.
and ranging to levels more than a thousand times higher.
A wide range of endpoints was examined to determine
if BPA had any effect on the reproductive performance
of the animals or on the development of the offspring.
Analysis of the data for all of the endpoints for the
parental and three offspring generations revealed no
evidence for reproductive or developmental effects at
any environmentally relevant dose. This exceptionally
powerful study, which complied with Good Laboratory
Practice standards and was conducted in accordance with
internationally accepted guidelines, provides a definitive
conclusion that BPA does not cause reproductive or offspring
effects at low doses. Additional information on this
study is available at http://www.bisphenol-a.org/development/whatsNew/20020702DefinitivePeer.html.
The results of a similar two-generation study commissioned
by the Japanese National Institute of Health Sciences
fully support the conclusions of the three-generation
study.3 In this study, which
also covered doses ranging from below to above the doses
tested by Hunt et al., no effects on reproduction or
development were found at any dose. In addition, this
study also examined the offspring in two behavioral
tests, including a learning test, and found no effects
from exposure to BPA at any dose.
In addition, the results of a continuous breeding study
in mice, conducted by the U.S. National Toxicology Program4,
showed no effects on reproduction at a dose approximately
1000 times higher than the highest dose tested by Hunt
The weight of scientific evidence provided by these
studies clearly supports the safety of BPA and provides
strong reassurance that there is no basis for human
health concerns from exposure to environmentally relevant
doses of BPA. Additional information on the weight of
evidence is available at http://www.bisphenol-a.org/pdf/LowDoseUnprovenOctober2002.pdf
Consistent with this conclusion, the use of polycarbonate
plastic and epoxy resins for food contact applications
has been and continues to be recognized as safe by the
U.S. Food and Drug Administration, the European Commission
Scientific Committee on Food, the United Kingdom Food
Standards Agency, the Japanese Ministry for Health,
Labor and Welfare, and other regulatory authorities
1. "Bisphenol A Exposure Causes
Meiotic Aneuploidy in the Female Mouse", P. A.
Hunt, K. E. Koehler, M. Susiarjo, C. A. Hodges, A. Ilagen,
R. C. Voigt, S. Thomas, B. F. Thomas, and T. J. Hassold,
Current Biology (2003), 13:546-553.
2 "Three-Generation Reproductive
Toxicity Study of Dietary Bisphenol A in CD Sprague-Dawley
Rats", R. W. Tyl, C. B. Myers, M. C. Marr, B. F.
Thomas, A. R. Keimowitz, D. R. Brine, M. M. Veselica,
P. A. Fail, T. Y. Chang, J. C. Seely, R. L. Joiner,
J. H. Butala, S. S. Dimond, S. Z. Cagen, R. N. Shiotsuka,
G. D. Stropp, and J. M. Waechter, Toxicol. Sci. (2002)
68 (1): 121-146.
3 "Rat two-generation reproductive
toxicity study of bisphenol A", M. Ema, S. Fujii,
M. Furukawa, M. Kiguchi, T. Ikka, and A. Harazono, Reproductive
Toxicology (2001), 15:505-523.
4 "Bisphenol A: Reproduction and
Fertility Assessment in CD-1 Mice When Administered
in the Feed", NTP Report No. RACB 84080. Information
this study is available on the Internet at http://ntp-server.niehs.nih.gov/htdocs/RT-studies/RACB84080.html.