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  • Title: Evaluation of the cytotoxicity and genotoxicity of the spermicides nonoxynol-9 and octoxynol-9.
    Author: Buttar HS, Swierenga SH, Matula TI.
    Journal: Toxicol Lett; 1986 Apr; 31(1):65-73. PubMed ID: 3012825.
    Abstract:
    The cytotoxic and genotoxic potentials of the spermicidal agents, nonoxynol-9 (N-9) and octoxynol-9 (0-9), were evaluated in in vitro test systems using rat liver cells. N-9 was also tested for the induction of sperm abnormalities in mice. Dose-related cytocidal effects were seen after the addition of N-9 and O-9 to the culture medium for 24 h. The mean concentrations of N-9 and O-9 necessary to decrease the number of viable cells by 50% (LC50) were 24 and 43 micrograms/ml of media, respectively. The spermicides neither induced DNA repair in freshly isolated hepatocytes, nor caused any mutations at HGPRT locus in the T51B rat liver cell line. There was also a lack of malignant transformation response in the low-calcium assay. Further, the germinal cells of mice remained unaffected by N-9. In vitro test systems were employed to evaluate the cytotoxicity and genotoxicity of the vaginal spermicide nonoxynol-9 (N-9) and the related nonionic detergent Triton X-100 (0-9). N-9 is typically used in concentrations of 2-12.5%, or vaginal applications of 50-140 mg, or up to 1 g in the vaginal sponge. Data from rats suggest that N-9 is excreted by the liver and kidneys unmetabolized, but no data on fate of absorbed N-9 are available in women. The tests performed here were the rat liver cell cytotoxicity assay on T51B line cells, the rat liver DNA repair assay using autoradiography with freshly isolated cells, a mutation assay using T51B rat liver cells exposed to azaguanine, a transformation assay with these cells grown in low calcium medium, and a sperm abnormality assay using hybrid male mice. On a molar basis, N-9 was 1.8 times more cytotoxic than 0.9. The LC50s were 24 and 43 mcg/ml respectively. Other work has shown that a level of 100 mcg/ml of N-9 per ml human semen is needed to immobilize sperm within a few minutes. Both detergents exhibited thresholds below which they failed to kill cells. Neither agent had any effect on DNA synthesis, mutation or transformation. No effect was registered on sperm when the detergents were injected ip in male mice at doses up to 60 mg/kg/day for 5 days, although a few mice died from this treatment. Whether the agents reached the testes was not determined.
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