Polyvinyl alcohol is produced primarily for use in textile sizing, adhesives, polymerization aids, and paper coatings. It is also used in surgical drapes, towels, and gauze sponges; protective gloves; cosmetic formulations; topical ophthalmic preparations; plastic sponge implants for reconstructive surgery; and intravaginal contraceptive foam and film. In addition, polyvinyl alcohol is used with magnesium sulfate to dilate the cervix of women prior to induction of labor. It is estimated that hundreds of thousands of women in the United States use an intravaginal product containing polyvinyl alcohol each year. The Food and Drug Administration nominated low-viscosity polyvinyl alcohol for a 2-year study because of concern about the lack of information about the long-term toxic and carcinogenic effects by the intravaginal route. Female B6C3F1 mice received polyvinyl alcohol (approximately 99% pure) in deionized water by intravaginal administration for 30 days or 2 years.
30-Day Study in Mice:
Three groups of 50 female B6C3F1 mice were used in this intravaginal study. The vehicle control group received only 20 µL of a deionized water vehicle. The other two groups each received 20 µL of 25% polyvinyl alcohol in deionized water. Animals in one dose group were returned to their cages after dosing; animals in the other dose group were restrained in a vertical nose-down position in restraint bags for several minutes after dosing. Animals were dosed daily for 30 consecutive days. All mice survived to the end of the study. The final mean body weights and body weight gains of dosed mice were similar to those of the vehicle control group. Abnormalities noted in the vaginal area after dosing included vaginal plugs, secretions, and swelling. These vaginal changes were minimal to mild and occurred in vehicle controls as well as in dosed mice. Restraint of mice after dosing appeared to eliminate vaginal secretions but increased both the incidence of vaginal irritation and the severity of vaginal opening swelling. At necropsy, mildly enlarged uterine horns were observed in 10 vehicle control mice, three 25% mice, and seven 25% (restrained) mice. No chemical-related lesions were observed.
2-Year Study in Mice:
Three groups of 100 female B6C3F1 mice were used in this intravaginal study: an untreated control group, a vehicle control group receiving 20 µL deionized water vehicle only, and a dosed group receiving 20 µL 25% polyvinyl alcohol in deionized water. Animals were dosed 5 days per week, excluding holidays, for 104 to 105 weeks.
Survival, Body Weights, and Clinical Findings
Survival of dosed mice was similar to that of the two control groups. The final mean body weight of vehicle control mice was less than that of the untreated control group. The mean body weights of the dosed mice were less than those of the untreated controls from week 17 until the end of the study. The only clinical finding was vaginal irritation, observed in six mice in the vehicle control group and 11 mice in the dosed group.
No neoplasms or nonneoplastic lesions related to chemical treatment were observed. The incidences of reproductive tract nonneoplastic lesions in the dosed group did not differ significantly from those in the vehicle control group; similarly, the incidences of reproductive tract nonneoplastic lesions in the vehicle control group did not differ significantly from those in the untreated control group.
Under the conditions of this 2-year study, there was no evidence of carcinogenic activity of polyvinyl alcohol (molecular weight approximately 24,000) in female B6C3F1 mice administered 20 µL of a 25% solution intravaginally. There were no neoplasms or nonneoplastic lesions considered related to treatment with polyvinyl alcohol.