A rapidly reversible effect of a single dose of phenoxybenzamine on the fertility of male rats.

Male Sprague-Dawley rats received a single subcutaneous injection of phenoxybenzamine and each was allowed to mate with an untreated receptive female at 5, 29 or 53 h post-injection. At 5 h the number of males ejaculating was reduced and fertility virtually abolished; at 29 h all males ejaculated, but fertility was still low; at 53 h the performance of the males was normal.

Dazoxiben, a prototype inhibitor of thromboxane synthesis, has little toxicity in laboratory animals.

Dazoxiben, an orally active specific inhibitor of thromboxane synthetase, was administered by mouth daily to dogs and rats for 6 months. Dogs showed no evidence of toxicity up to 300 mg day-1 kg-1, the highest dose level used. Rats showed no evidence of toxicity after 100 mg day-1 kg-1, but at 300 mg day-1 kg-1 there were slight increases in plasma calcium and urea concentrations and a moderate incidence of focal nephrosis; males showed a slightly increased platelet count. Studies in rats and rabbits at dose levels up to 400 mg day-1 kg-1, by mouth, revealed no adverse effects on male or female fertility, embryogenesis, parturition or postnatal development. As dazoxiben is well absorbed after oral administration, the generally negative outcome to these toxicity studies suggests that selective inhibitors of thromboxane synthesis may be largely free of adverse effects which might impede their therapeutic or prophylactic use in clinical medicine.

Reproductive studies with the anti-inflammatory agent, piroxicam: modification of classical protocols.

Reproductive toxicology studies were conducted in rabbits and rats given piroxicam, a non-steroidal anti-inflammatory agent (NSAI), orally at 2, 5 and 10 mg/kg/day. In teratology studies there was neither drug-related embryotoxicity nor teratogenicity. As piroxicam, like other NSAI, affects parturition in rats and leads to a progressive toxicity in lactating females, standard protocols were modified: dams of the female fertility study were treated from 2 weeks prior to mating until day 6 of gestation and females of the post-natal toxicity study were treated from parturition until day 12 of lactation. No other adverse effects on reproduction, fertility and postnatal development were observed.

Use of the New Zealand white rabbit in teratology: incidence of spontaneous and drug-induced malformations.

Cumulative data are presented on the occurrence of external, skeletal and visceral abnormalities in foetuses from teratology studies conducted in New Zealand White rabbits over a 10-yr period. The data, based on examinations of over 5500 control foetuses and 19,000 foetuses from treated dams, are derived from studies involving 58 compounds, five of which were judged to be teratogenic.