Clinico-pathological changes induced in rats treated with amine-curing agent for epoxy resin, bis(4-amino-3-methylcyclohexyl)methane.

S Ohshima, T Shibata, N Sasaki, H Okuda, H Nishizawa, M Ohsawa, M Matsumoto, E Nakayama

Index: J. Toxicol. Sci. 11(2) , 79-93, (1986)

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Abstract

Amine-curing agent for epoxy resin, bis(4-amino-3-methyl-cyclohexyl)methane (commercial name; Laromin C) has been suspected to have induced in the workers some toxic signs such as collagen disease like scleroderma or polymyositis. Subacute toxicity of this agent was studied in rats following repeated oral administration. The agent was given orally at 5 dose levels (25 mg/kg to 100 mg/kg per one dose) for periods ranging from 10 days to 4 weeks. After the completion of administration, clinico-biochemical tests and histopathological examinations were carried out. In a few cases, skeletal muscles and choroid plexus of the brain were examined by electronmicroscopy. Clinico-biochemical tests revealed some elevation of muscle-derived components such as GOT and CPK as seen in the myopathic diseases. Histologically, various degrees of atrophy, degeneration and regeneration of muscle fibers and a numerical increase of interstitial cells were observed in the skeletal muscles. Electronmicroscopical examination of the gastrocnemius muscle revealed intrasarcoplasmic osmiophilic round-shaped inclusion bodies, sometimes with lamellar structure, which were suggestive of some lipidosis. The epithelial cells of choroid plexus in the brain ventricles represented various degrees of vacuolar changes lightmicroscopically, which were suggested to be dilated smooth endoplasmic reticulum electronmicroscopically. Although scleroderma-like changes were not observed in our experiments, the results suggest that this amine-curing agent for epoxy resin could be one of the causative agents which induced toxic lesions like some collagen diseases including muscle lesions in the workers. In addition, it is considered that the agent may have systemic toxic effects.