© 1982 Oxford University Press
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Genital Tract Toxicity of Nonoxynol-9 in Female Rats: Temporal Development, Reversibility and Sequelae of the Induced Lesions
*Health and Welfare Canada, Health Protection Branch, Food and Drug Directorates, Pathology Tunney's Pasture, Ottawa, Ontario, K1A oL2, Canada Reproductive Toxicology Sections Tunney's Pasture, Ottawa, Ontario, K1A oL2, Canada
Genital Tract Toxicity of Nonoxynol-9 in Female Rats: Temporal Development, Reversibility, and Sequelae of the Induced Lesions. Tryphonas, L. and Buttar, H.S. (1982). Fundam. Appl. Toxicol. 2:211-219. The morphologic reactions of the genital tract of adult female rats were studied over a six week period following the intravaginal administration of the vaginal spermicide nonoxynol-9 (N-9). A 5% (W/V) solution of N-9 was administered as a single pulse (0.1 mL/100 g) under ether anesthesia. The vulval labia were apposed for up to 24 hours by metallic clips to prevent leakage of the solution and groups of rats were killed at 1.5, 3, 6, 12, and 24 hours and at 1, 2, 3, 4, and 6 weeks later. Unequivocal gross lesions first observed 6 hours post-treatment included distension of the vagina by a greenish, opaque, flocculent fluid and a moderate enlargement of the iliac lymph nodes. At 1 week, only a small amount of vaginal exudate was discernible in two out of ten rats and after 2 weeks free exudate was no longer present. Beginning 1 week and persisting 6 weeks after treatment, distension, stenosis, and occlusion were seen in 50–85% of the treated females, but the overall incidence of individual and combined lesions varied among groups. Histologically, degenerative epithelial changes and acute inflammation in response to N-9 treatment appeared in the vagina, cervix, and uterus 1.5 hours post-treatment, reached maximal severity at 24 hours, were abated by the end of the first week and were entirely absent after the second week. The vaginal inflammatory response extended to the muscular layer beginning 3 hours post-treatment. Distension of the genital tract was characterized by atrophy of the mucosa and the muscular layer, and stenosis and occlusion were associated with lamina propria tissue proliferation or fusion along the line of apposition. It is concluded: that N-9 is capable of inducing mucosal damage and eliciting acute necrotizing inflammation in the uterus, cervix and vagina; that stenosis and occlusion evidently resulting from delayed re-epithelialization of denuded laminae propriae give rise to distension of parts lying cephalad, and; that the rat is a promising animal model for studying the vaginal toxicity of N-9 and possibly other spermicidal agents.