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 us eful assay for antiandrogens. This suggestion was supported by referen ce to unpublished data on the antiandrogen vinclozolin which indicated reductions in the weight of accessory sex organs. The necessity for d osing during the full similar to 30 days of the protocol was not justi fied. An evaluation of this protocol has commenced by the dosing of vi nclozolin, 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. Signi ficant changes were observed in the absolute and relative weight of al l of the sex accessory organs for rats dosed for 7 or 14 days with cyp roterone acetate. The effects produced by vinclozolin and anastrozole when dosed for 7 or 14 days varied according to the duration of exposu re 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 vi nclozolin or anastrozole in arachis oil had resolved 10 days after the last of the seven doses. Data are presented using either hydroxy prop yl methyoxycellulose (HPMC) or arachis oil as vehicle, the former bein g-recommended for general use. These preliminary results are encouragi ng, and the evaluation of the second 2 weeks of the suggested 30-day p rotocol is proceeding. Concurrent control data indicate that the relat ive weight of the liver, testes, and epididymides increases over the f irst 14 days post weaning, while those of the kidney, the seminal vesi cles, and prostate decrease. These changes in relative tissue weight w ere much less than the increase in relative weight of the uterus obser ved in female animals at puberty. That indicates that successful use o f a final version of this assay will depend on access to inhouse contr ol tissue weight data and the use of appropriate animal group sizes. T hese preliminary data are presented to reduce duplication of effort in this rapidly expanding area of toxicology. (C) 1997 Academic Press.