GRANULOMATOUS DERMATITIS IN NEW-ZEALAND WHITE-RABBITS FOLLOWING 9-DAYREPEATED CUTANEOUS EXPOSURE TO METHYLDIMETHOXYSILANE

Male and female New Zealand White rabbits were exposed to 0.0, 0.05, 0 .1, or 0.2 ml/kg of undiluted methyldimethoxysilane (MDMS), correspond ing to 43, 85, or 171 mg/kg, applied under occlusive dressing to the c lipped dorsal trunk skin for nine doses over an 11 day period. Five an imals/group/gender (10/gender in the 85 mg/kg/day group) were euthaniz ed at the end of the exposure period. Five animals/group/gender from t he high-dose and control groups were retained for a 2 week recovery pe riod and then euthanized. The only abnormal findings involved the trea ted skin. Clinical observations included mild to moderate irritation o f the treated skin, affecting mainly high-dose group animals euthanize d immediately after the exposure period, with females being slightly m ore sensitive. Significant gross and microscopic lesions were seen in the treated skin of animals receiving 0.1 ml/kg/day and higher. Gross lesions consisted of erythema, ecchymoses, exfoliation, excoriation, f issures, ulceration, and necrosis. Microscopic lesions included hyperk eratosis, acanthosis, congestion, hemorrhage, epidermitis, dermatitis, and ulceration. Dermal fibrosis and prominent granulomatous inflammat ion, associated with pigmented granular foreign material, was found in the superficial dermis. After the 2 week recovery period, exfoliation was the only gross skin lesion found in high dose group animals. Micr oscopic skin lesions consisted of marked granulomatous dermatitis and a fibrotic reaction associated with the foreign material, as well as r esidual lesions of surface irrigation. Scanning electron microscopic e xamination of the skin of recovery group animals revealed scattered el ectron-dense deposits in the superficial dermis, which were proven, on elemental analysis, to contain silicon, possibly in the form of a pol ymer from absorbed MDMS or its breakdown products. There were no abnor mal clinical pathologic findings in animals euthanized immediately aft er exposure,but significant monocytopenia occurred in high-dose-group male rabbits from the recovery group, which may be due to sequestratio n of circulating monocytes in the skin at the site of granulomatous in flammation.