Treatment of rhesus monkeys (Macaca mulatta) with intravaginal rings loaded with levonorgestrel.

The effects of levonorgestrel-releasing intravaginal rings were investigated in 15 rhesus monkeys for 52 weeks. The intravaginal rings were designed to provide a sustained release of either three or ten times the human dose level of the hormone. Untreated placebo rings were used as a control. The devices were well retained. After insertion of the vaginal rings, a dose-related decrease in vaginal bleeding was observed. The vaginal microbial flora were assessed qualitatively and semi-quantitatively and although all groups including controls showed some changes in microbial populations, by the end of the study nearly all animals returned to a normal balanced microflora. Terminal studies showed that, at the high dose level, ovulation was suppressed and widespread atrophy of the uterine mucosal and glandular epithelium had occurred. A dose-related increase in mucus within the lumen of the endocervical canal was observed. Focal or diffuse atrophy of the vaginal mucosal epithelium was seen in the majority of levonorgestrel-treated animals.

Treatment of rhesus monkeys (Macaca mulatta) with intravaginal rings impregnated with either progesterone or norethisterone.

The effects of both progesterone- and norethisterone-loaded intravaginal rings were investigated in twenty-five rhesus monkeys for 52 weeks. The intravaginal rings were designed to provide a sustained release of either the human dosage level of the hormone or ten times this level. Untreated placebo rings were used for control purposes. The devices were well retained. With the exception of increased plasma fibrinogen levels in animals treated with norethisterone, no marked differences in either local or systemic toxicity between the progesterone and norethisterone intravaginal rings were apparent. Following insertion of the hormone-treated intravaginal rings, a dose-related decrease in vaginal bleeding was recorded. The vaginal microbial flora were assessed qualitatively and semiquantitatively and all groups including the placebo controls showed a changes in mcirobial populations. Terminal studies indicated that at high dose levels, ovulation was suppressed and widespread atrophy of the uterine mucosal and glandular endometrial epithelium had occurred. An increase in cervical mucus was observed within the lumen of the endocervical canal in a proportion of hormone-treated animals. In the vagina, a dose-related focal or diffuse atrophy of the mucosal epithelium was found.

Examination of the potential mutagenicity of hair dye constituents using the micronucleus test.

12 compounds which are constituents of hair dyes or chemically related aromatic amines, aminophenols, their nitroderivatives and aromatic hydroxyderivatives were examined for evidence of mutagenic potential by means of the micronucleus test. None of the compounds tested caused an increase in the incidence of micronucleated erythrocytes after oral dosing.