Toxicological Sciences, Vol 52, 269-277, Copyright © 1999 by Society of Toxicology
MS Marty, JW Crissman and EW Carney
The Endocrine Disrupter Screening and Testing Advisory Committee has
recommended the female pubertal onset assay as a Tier I test to detect
potential endocrine-disrupting chemicals (EDs). We evaluated this assay's
ability to detect EDs acting through various mechanisms. In two similar
experiments, weanling female rats were dosed for 20 days by gavage with
vehicle (0.5% methocel) or the following test compounds (mg/kg/day):
17beta-estradiol (E2; 0.1, 2, or 4), ketoconazole (KETO; 24, 50, or 100),
finasteride (FIN; 20), testolactone (TL; 220), fadrozole (FAD; 0.6, 1.2, or
6.0) or 6-propylthiouracil (PTU; 240). In vehicle-treated females, mean age
at pubertal onset, as evidenced by vaginal opening (VO), varied
interexperimentally from 32.3+/-1.6 days to 33.5+/-1.8 days. At 0.1 mg/kg
E2, age at VO was reduced slightly to 31.0+/-1.6 days, but not
significantly (alpha=0.05). Higher E2 doses (2.0 and 4.0) reduced age at VO
to 28 days. KETO delayed VO, but this delay was significant only at 100
mg/kg (39.7+/-2.4 days). FIN and TL had no effect on age at pubertal onset;
however, FAD significantly delayed VO. PTU delayed VO to 34.2+/-1.1 days
and altered thyroid weight, histology, and hormone levels. With each
compound, significant changes in age at VO were accompanied by decreased
uterine or ovarian weights. Thus, although this assay did not detect TL or
lower doses of E2 (0.1 mg/kg) or KETO (< or = 50 mg/kg), it was capable
of detecting EDs operating through a variety of mechanisms.
ARTICLES
Evaluation of the EDSTAC female pubertal assay in CD rats using 17beta- estradiol, steroid biosynthesis inhibitors, and a thyroid inhibitor
Health and Environmental Research Laboratory, The Dow Chemical Company, Midland, Michigan 48674, USA. mmarty@dow.com
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