Granulomatous Dermatitis in New Zealand White Rabbits Following 9-Day Repeated Cutaneous Exposure to Methyldimethoxysilane

Abstract

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), corresponding to 43, 85, or 171 mg/kg, applied under occlusive dressing to the clipped dorsal trunk skin for nine doses over an 11 day period. Five animals/group/gender (10/gender in the 85 mg/kg/day group) were euthanized at the end of the exposure period. Five animals/group/gender from the high-dose and control groups were retained for a 2 week recovery period and then euthanized. The only abnormal findings involved the treated skin. Clinical observations included mild to moderate irritation of the treated skin, affecting mainly high-dose group animals euthanized immediately after the exposure period, with females being slightly more 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, fissures, ulceration, and necrosis. Microscopic lesions included hyperkeratosis, acanthosis, congestion, hemorrhage, epidermitis, dermatitis, and ulceration. Dermal fibrosis and prominent granulomatous inflammation, 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. Microscopic skin lesions consisted of marked granulomatous dermatitis and a fibrotic reaction associated with the foreign material, as well as microscopic examination of the skin of recovery group animals revealed scattered electron-dense deposits in the superficial dermis, which were proven, on elemental analysis, to contain silicon, possibly in the form of a polymer from absorbed MDMS or its breakdown products. There were no abnormal clinical pathologic findings in animals euthanized immediately after exposure, but a significant monocytopenia occurred in high-dose-group male rabbits from the recovery group, which may be due to sequentration of circulating monocytes in the skin at the site of granulomatous inflammation.