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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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A number of substances found in foods and in living organisms
can act as ligands to allyl hydrocarbon receptors (AhRs)44,
and the mechanisms of their action have recently become a hot
topic45. The effects of these
substances are believed to appear at low doses, though details
are poorly understood46.
Literature survey on the abundance and mechanism of action of
natural AhR ligands indicated that ligand-active substances are
found in extracts from green tea, oolong tea, coffee, apple
juice and tomato juice. A survey on general carcinogenesis
(including low-dose effects) identified a report that no
threshold concentration of diethylstilbestrol (DES) was
established for the tumor in the male and female genital organs
or other anomalies. Reports on similar findings on other
endocrine disruptors should be watched attentively.
Two-stage carcinogenesis by benzene hexachloride (α-BHC) at
0.01-500 ppm was studied with diethylnitrosamine (DEN) as the
initiator47. The 35-week
experiment yielded a tumor frequency curve convex downward with
a minimum at 0.1 ppm. In accordance with existing knowledge on
carcinogenesis, no report has been found that supports low-dose
carcinogenicity higher than the extrapolated value from data at
higher doses. The mechanism of action may depend on the dose, as
suggested by the fact that tamoxifen (TXP) acts as an E2 agonist
at high doses. Studies of later carcinogenesis in individuals
exposed in the perinatal period have not established low-dose
effects. As for cancer in the male genital organs, mammary gland
and female genital organs, Ashby claims that the experiment by
von Saal et al. which indicated the existence low-dose effects
was not reproducible. Possible factors contributing to this
discrepancy include farming conditions, genetic background, and
body weight of experimental animals as well as the phytoestrogen
content of the feeds.
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44 See notes 13 and
15.
45 See notes 13 and 15.
46 Ligands may be classified into
the dioxin type, benzo[a]pyrene type and indirubin type. The
first two show characteristic toxicity patterns, while the
metabolite ligands chiefly derived from foods are believed to
have low toxicity.
47 DEN was administered to 6-week
old male F344 rats once a week for three weeks. The doses were
0.01, 0.05, 0.1, 1.0, 50 and 500 ppm, with -BHC as the
promoter, mixed in the feed. |
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