Experiments are reported on some aspects of oestrogen toxicity in the Beagle dog and the non-human primate. Ethinyl estradiol produced in the dog, toxic changes in the reproductive system, blood and skin. Some females showed slight focal papilliform proliferation of the genital serosa. Ethinyl estradiol induced in rhesus monkeys biochemical changes indicating hepatic dysfunction. No histological changes were detected in the liver by light microscopy, but by electron microscopy minor ultratructural abnormalities were identified within hepatocytes. Bile flow increased when ethinyl estradiol was given to rhesus monkeys with an intact enterohepatic circulation. Ethinyl estradiol did not cause proliferative serosal lesions in female rhesus monkeys but hyperplasia of the fimbrial epithelium of the Fallopian tube was found. Ethinyl estradiol had no apparent effect on lactation in rhesus monkeys, although there was evidence of oestrogen secretion through the milk. The effects of ethinyl estradiol in neonatal rhesus monkeys were similar to those in adults. When given to pregnant rehesus monkeys during the period of organogenesis, ethinyl estradiol appeared to cause early embryonic death and abortion but no teratogenic effects were found in foetuses derived by caesarian section. The combined hepatotoxicity of ethinyl estradiol and chenodeoxycholic acid in baboons was essentially similar to that of chenodeoxycholic acid alone. High dose levels of diethylstilboestrol given to pregnant rhesus monkeys were apparently embryotoxic. Two infants were reared for 84 weeks; the female's reproductive tract was normal, but the male's prostate and seminal vesicles were small. Interpretation of oestrogen tumorigenicity to dogs depends on establishing baseline background data. The spontaneous incidence of mammary tumours and dyplasias in forty nulliparous 8-year old female Beagle dogs is described.
|Date of Award||1978|