The weanling male rat as an assay for endocrine disruption: preliminary observations.
Kelce and Wilson (J. Mol. Med. 75, 198-207, 1997) have suggested that dosing chemicals to newly weaned male rats for 1 month may yield a useful assay for antiandrogens. This suggestion was supported by reference to unpublished data on the antiandrogen vinclozolin which indicated reductions in the weight of accessory sex organs. The necessity for dosing during the full approximately 30 days of the protocol was not justified. An evaluation of this protocol has commenced by the dosing of vinclozolin, cyproterone acetate, and anastrozole daily to newly weaned male rats for 3, 7, or 14 days. No changes were observed in accessory sex organs when vinclozolin or anastrozole was dosed for 3 days. Significant changes were observed in the absolute and relative weight of all of the sex accessory organs for rats dosed for 7 or 14 days with cyproterone acetate. The effects produced by vinclozolin and anastrozole when dosed for 7 or 14 days varied according to the duration of exposure with the main effects on the accessory sex organs being seen after 14 days of dosing. The effects produced after 7 days of dosing with vinclozolin or anastrozole in arachis oil had resolved 10 days after the last of the seven doses. Data are presented using either hydroxy propyl methyoxycellulose (HPMC) or arachis oil as vehicle, the former being recommended for general use. These preliminary results are encouraging, and the evaluation of the second 2 weeks of the suggested 30-day protocol is proceeding. Concurrent control data indicate that the relative weight of the liver, testes, and epididymides increases over the first 14 days post-weaning, while those of the kidney, the seminal vesicles, and prostate decrease. These changes in relative tissue weight were much less than the increase in relative weight of the uterus observed in female animals at puberty. That indicates that successful use of a final version of this assay will depend on access to inhouse control tissue weight data and the use of appropriate animal group sizes. These preliminary data are presented to reduce duplication of effort in this rapidly expanding area of toxicology.
Ashby
J
J
Zeneca Central Toxicological Laboratory, Macclesfield, Cheshire, United Kingdom.
Lefevre
P A
PA
D000077384:Anastrozole; D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D017373:Cyproterone Acetate / Q000633:toxicity; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004700:Endocrine System Diseases / Q000139:chemically induced*; D005260:Female; D007785:Lactose / Q000031:analogs & derivatives / Q000633:toxicity; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000633:toxicity; D009570:Nitriles / Q000633:toxicity; D009929:Organ Size / Q000187:drug effects; D010078:Oxazines; D010080:Oxazoles / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D014116:Toxicology / Q000379:methods*; D014230:Triazoles / Q000633:toxicity; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects; D014886:Weaning
D000726:Androgen Antagonists; D009570:Nitriles; D010078:Oxazines; D010080:Oxazoles; D014230:Triazoles; D000077384:Anastrozole; D017373:Cyproterone Acetate; D008747:Methylcellulose; C071191:MK 458; D007785:Lactose; C025643:vinclozolin