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While the biological effects of endocrine disruptors are
generally evaluated by in vivo experiments on animals, it has
been pointed out that effects on animals of exposure to
chemicals via the raising and experimental environment (feed,
litter, water bottle, air, etc.) should be understood for
reliable estimation of the low-dose effects.
Accordingly an analytical method was developed for determining
phytoestrogens, in addition to the abovementioned three
substances, in animal feeds and other materials in the
environment. Its application to actual samples has started.
Small amounts of the analytes were found in feeds with
concentrations varying among lots. Low-background feed products
are commercially available.
Some litter products contained significantly high concentrations
of the analytes, although it is not clear to what extent they
affect experimental results.
Attention must be paid, therefore, to substances contained in
water, water bottle, feed, litter and air in raising and feeding
environment of experimental animals.
[Future tasks]
Information should be continuously gathered on efficient,
precise and sensitive analytical methods to enhance the
Guideline.
(3) Low-dose issue
[Results]
1) Endogenous hormones are maintained at very low
concentrations, though fluctuating, in the living body. They
inherently act at low concentrations; any excessive amount is
eliminated. The same mechanism applies to exogenous hormone-like
substances. Their disruptive actions are, however, largely
mitigated by adaptation to the endogenous hormone system in
mature organisms, as shown by research results in the past.
2) Morphogenetic stages in which physiological functions are
unstable, such as the embryonic, fetal, neonatal and adolescent
periods, are increasingly attracting attention as the focus of
investigation of action mechanisms.
3) The low-dose issue is a complex of closely related factors
such as existence of a threshold, additive/multiplicative nature
of actions, and dose-response relationship, which are addressed
simultaneously.
4) Elucidation of the mechanisms of action of hormone-like
substances and signal interaction between allylhydrocarbon
receptors and estrogen receptors have been revealing the variety
of mechanisms involved, which will influence studies of the
low-dose issue or synergistic effects.
5) Effects on the homeostatic regulatory systems, including the
reproductive, immune and nerve systems, are important topics in
endocrine disruptor studies. Data have been accumulated but not
yet sufficient for elucidation of the mechanisms of action.
6) Discovery of membrane receptors contributed to understanding
of non-genetic actions of hormone-like substances, and suggests
possible existence of unknown factors involved in the endocrine
disruptor problem.
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