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Advisory Committee on Health Effects of Endocrine Disruptors
The Supplement II to the Intermediary Report
1.3.2 |
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Effects on behavior are attracting much attention, but relevant
reports have appeared since a few years ago only, and are still
limited in number. Administration of 1.5 mg/kg BPA (cf. NOAEL 50
mg/kg39) to pregnant Wister
rats caused feminization of the offspring manifested by behavior
and smaller locus cruleus40.
Substances with antiandrogen-like activities also triggered
changes in behavior41. Rats
borne by a Wistar rat to which 0.1 ppm BPA was administered
during a week immediately before delivery showed no sex
difference (i.e. feminized) in behavior against stresses42.
Similar change was observed for olfactory response.
(4) Overview of information gathered
Literature review on low-dose effects of BPA is in progress43
to help risk evaluation. A database is now being built which is
to contain 168 reports published from 2000 to 2004 after
evaluation of reliability and other features.
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39 According to US-NTP
test (1982) on chronic toxicity and carcinogenicity by
continuous oral administration for 2 years. Separately, Furukawa
et al. (1994) have reported 500 mg/kg/day based on repeated
administration for 13 weeks.
40 Aou et al. found feminization in
behavior in open-field tests and smaller locus cerleus in adult
rats borne by a Wistar rat to which 1.5 mg/kg BPA (cf. NOAEL 50
mg/kg) was administered during pregnancy (Kubo K, Arai O, Ogata
R, Omura M, Hori T, Aou S. Exposure to bisphenol A during the
fetal and suckling periods disrupts sexual differentiation of
the locus coeruleus and of behavior in the rat. Neurosci Lett,
304, 73-76,2001. / Kubo K, Arai O, Omura M, Watanabe R, Ogata R,
Aou S. Low dose effects of bisphenol A on sexual differentiation
of the brain and behavior in rats. Neurosci Res. 45, 345-356,
2003).
41 Hotchkis AK, Ostby JS,
Vandenburgh JG, Gray LE Jr. Androgens and environmental
anti-androgens affect reproductive development and play behavior
in the Sprague-Dawley rat. Environ Health Perspect. 110(suppl
3): 435-439, 2002.
42 Kawai K, Nozaki T, Nishikata H,
Aou S, Takii M, Kubo C. Fetal exposure to bisphenol A induces
aggressive behavior in pubescent male ice. Environmental Health
Perspective 111, 175-178, 2003.
43 A group of 14 specialists reviews
168 reports published from 2000 to 2004 to confirm the presence
of data on low-dose effects and builds a database containing
them. Predetermined index entries include: author name, original
title, source, organism studied, target organs, effect level
(cell, tissue, individual), exposure route, period of exposure
(e.g. fetal), concentration exposed or dose, reliability of
records, and summary. Organisms studied comprise rat in 88
papers, mouse in 53, human in 27 and others in 27. Target organs
are nerve system in 16, immune system in 8, reproductive system
in 91, others in 42; effect levels are cell in 56, tissue in 52,
individual in 63, and others in 24; periods of exposure are
embryonic or fetal in 35, perinatal in 22, after delivery in 41,
adult in 54, others (incl. cell strain) in 45 (statistics
incomplete). |
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