Abrading the skin of guinea pigs was investigated as a method to enhance the sensitivity of a topical occlusive method for detecting potential contact sensitizers. Three studies were conducted using isoeugenol in petrolatum as the sensitizer.In each of the studies, the concentration of isoeugenol that produced strong irritation to nonabraded skin during induction produced the strongest sen-sitization reactions at the challenge applications. Of the groups induced with the highest nonirritating concentration of isoeugenol, the incidence and severity of reactions were highest overall in the abraded animals.The results of these studies suggest that abrading the skin may increase the sensitivity of the closed patch guinea pig test procedure by enhancing skin penetration of the sensitizing agent.

A new occlusive patch test system employing a plastic chamber, the Hill Top Chamber (HTC), was evaluated as a method of application in rabbit dermal irritancy testing. Two commercial bar soaps were tested at 20%, 10%, 5%, 2.5%, and 1.25% concentrations in distilled water using both the HTC and the standard gauze patch methods of application. Each solution was applied to both intact and abraded skin sites on the dorsal flank, clipped free of hair, of six New Zealand albino rabbits (2.0–4.0 kg). The solutions were applied by gauze patch on one side of the animal and by HTC on the other side. The trunk of each animal was then wrapped with an impervious cover, which was left in place for 24 hr. After 24 hr, the wrap, patches, and chambers were removed. The application sites were scored for erythema and edema upon patch removal and again at 72 hr according to the standard Draize scale and the primary irritation index for each solution by both methods was calculated. The scores for both erythema and edema at each time interval and the scores for both the HTC and gauze patch were compared statistically using analysis of variance and Duncan's multiple range test. There were statistically significant differences between the irritancy scores for the HTC and the gauze patch. However, since these differences were considered within normal variance, they were not regarded as being biologically significant. Although the HTC did not display any superiority in this regard, it possesses many features that make it preferable to the gauze patches. The HTC proved to be an appropriate device for applying liquid materials in the Draize rabbit dermal irritancy test and offers features that recommend it over the standard gauze patch. The validity of using the HTC as a means of applying other forms of test materials, however, remains to be determined.

Studies were conducted to compare the sensitivities of the vaginal mucous membranes of the albino rabbit and albino rat to irritation by the surfactant nonoxynol-9. The purpose of this comparison was to evaluate the rat as a model for screening vaginal products for their potential irritancy. Nonoxynol-9 at various concentrations in distilled water was administered intravaginally by lavage once a day for four consecutive days. On day 5, the animals were killed and the vaginal tissues were processed and examined histopathologically. Using a predetermined semiquantitative scoring system, it was found that the intensity of irritation was concentration dependent in both species. In the rabbit, the irritation was significantly greater than that in the rat, being mild with concentrations of 2.5 and 5% and moderate to severe at 12.5 and 25%. In the rat, irritation was negligible up to 12.5%, becoming mild at 25% and more moderate at 75%. Thus the vaginal mucosa of the rabbit is more sensitive than that of the rat and may be expected to give a more exaggerated representation of the irritation potential of a compound to the human vagina than would the rat mucosa.

Studies were conducted to determine the effect of the pH of a vaginal douche on its irritation potential for the vaginal mucosa of the albino rabbit and albino rat. The pH of a liquid douche formulation was varied by modification of the lactic acid/sodium bicarbonate ratio and the resulting preparations were administered intravaginally by lavage once a day for four consecutive days. On day 5, the animals were killed and the vaginal tissues were processed and examined histopathologically. Using a predetermined semiquantitative scoring system, it was found that the irritation potential of the formulation under study was pH dependent in the rabbit but not in the rat. As the pH was decreased, the degree of irritation became more severe in the rabbit; at pH 3· and below, irritation was sufficiently severe for the formulation to be considered unacceptable for human use. Only minimal irritation was seen in the rat at any of the pH levels tested. The sensitivity of the rabbit vaginal mucosa is greater than that of the rat and the response is pH dependent below pH 3.0. This exaggerated response must be taken into consideration when the rabbit is used for assessing the vaginal-irritation potential of douches. The rabbit, having a vaginal mucosa more sensitive than that of the rat, remains an appropriate model for measuring the potential irritancy of new douche products, because comparisons can be made with products of known irritancy.