Abstract: 347

ENVIRONMENTAL ANTIANDROGENS: THE MALFORMATION PATTERN VARIES WITH THE MECHANISM OF ANTIANDROGENIC ACTION.

LE Gray Jr^{1 *}, M Price¹ , C Lambright¹ , C Wolf¹ , A Hotchkiss² , L Parks¹ , J Ostby¹
USEPA, EB, NHEERL, Research Triangle Park, NC ¹
North Carolina State University, Dept Zoology, Raleigh, NC ²

Antiandrogenic chemicals alter sexual differentiation by a variety of mechanisms and, as a consequence, they induce different profiles of effects. Here, we describe the effects of 10 known or suspected antiandrogens including vinclozolin (V, 3-200 mg/kg/d), procymidone (P, 25-200), iprodione (I, 100), chlozolinate (C, 100), linuron (L, 100), p,p' DDE (100), ketoconazole (K, 12-100), dibutyl (DBP, 500) and diethylhexyl (DEHP, 750) phthalate, and the Leydig cell toxicant ethane dimethane sulfonate (EDS, 50). Dose response studies also were conducted with V, P, K, L and DBP. Anogenital distance (AGD), nipple/areola development and reproductive organ weights were measured in male offspring. Six of the 10 chemicals altered male sexual differentiation (V, P, DBP, DEHP, L, and DDE). V, P, p,p'-DDE and L are AR antagonists, while DBP and DEHP do not appear to be AR ligands. The AR-ligands, V, P, and DDE all produce a flutamide-like profile with varying degrees of potency. DBP and DEHP produce a different profile which includes a surprisingly high incidence of epididymal and testicular lesions. L induces a low incidence of hypospadias along with an unanticipated incidence of malformed epididymides, suggesting that L displays multiple mechanisms of endocrine toxicity. In general, reduced AGD, accompanied by an increase in areola development is associated with alterations in other androgen-dependent tissues. Examination of the dose-response data indicate that both 1) threshold and 2) nonthreshold dose responses are common. In summary, AGD and areola incidence are disrupted by in utero exposures regardless of the mechanism of antiandrogenicity, while the incidence of prostatic, vesicular, epididymal and testicular malformations varies considerably depending upon the mechanism of antiandrogenic action. This abstract does not reflect USEPA policy.

    This abstract is being presented on Monday, August 2 at 8:00 AM to 10:15 AM at CUB 2nd Floor Ballroom.