Uterotropic action in rats of amsonic acid and three of its synthetic precursors

Abstract

Prompted by reports of sexual impotence among chemical factory workers exposed to amsonic acid (4,4'‐diaminostilbene‐2,2'‐disulfonic acid; CAS 81–11–8) and its synthetic precursors 4,4'‐dinitrostilbene‐2,2'‐disulfonic acid (DNSDSA; CAS 128–42–7), 2‐methyl‐5‐nitrobenzenesulfonic acid (MNBSA; CAS 121–03–09), and 4‐nitrotoluene (CAS 99–99–0), the uterine‐weight‐increasing actions of single intraperitoneal doses of these chemicals were determined at 24 h after treatment in weanling female rats and compared to the results of similar experiments with diethylstilbestrol (DES; CAS 56–53–01), a synthetic estrogen chemically related to amsonic acid and DNSDSA. Doses of 100 mg/kg or less of amsonic acid were either without effects or produced equivocal effects, while uterine weights were increased after doses of 300 and 1000 mg/kg; doses of 3000 mg/kg were clearly toxic. Neither DNSDSA nor MNBSA increased uterine weight after doses that were not overtly toxic. Doses of 10 mg/kg or less of 4‐nitrotoluene were without effect, but doses of 30 and 100 mg/kg increased uterine weights without producing overt toxicity; doses of 1000 mg/kg were clearly toxic. While both amsonic acid and 4‐nitrotoluene exhibited uterotropic effects, they were both much weaker than DES in this respect. Other experiments indicated that the time course of the effects of approximately equiactive doses of amsonic acid and DES were very similar, and that the responses to oral doses of amsonic acid were not appreciably different from the responses to the same doses given intra‐peritoneally. Finally, a sample of amsonic acid taken from the workplace of the complaining workers was also found to have uterotropic activity. These experiments suggest that amsonic acid and 4‐nitrotoluene have estrogenic activity, and thus provide a possible mechanistic explanation for the complaints of impotency in factory workers exposed to these substances.