Retinopathy from inhaling 4,4′-methylenedianiline aerosols

Abstract

4,4′-Methylenedianiline (MDA) is an important chemical intermediate in the production of isocyanates and polyurethane elastomers and polymers. The health hazards from acute inhalation exposure to the aerosols were evaluated. Guinea pigs of albino and pigmented strains were exposed nose-only to the aerosols of MDA in polyethylene glycol 200 (PEG) solution. The exposure was 4 hr per day, 5 days per week for a total of 10 exposures in 2 weeks. The time-weighted average aerosol concentration was 0.44 ± 0.09 mg/liter and the optical number length mean diameter of the aerosol particle was 2.4μm with σ g of 2.1. During exposures, no overt respiratory distress was observed. Two weeks after the exposures, the guinea pigs were tested for possible dermal sensitization by being challenged with dermal applications of MDA-PEG solutions at concentrations of 0, 2, 20, and 200 mg/ml. Neither dermal irritation nor allergic response was detected under this experimental condition. Thereafter, the animals were tracheostomized for measurements of changes in lung insufflation pressure for detecting possible changes in the distensibility of the lungs from a challenge dose of an aerosol of MDA-PEG at a concentration of 200 mg/ml. No significant changes were observed under this testing condition. Finally, the animals were euthanized for histopathologic examinations of eye, lung, liver, and kidney. The most remarkable finding was the degeneration of the inner and outer segments of the photoreceptor cells and the pigmented epithelial cell layer of the retinas of both albino and pigmented strains of guinea pigs. Since the retinal lesions in both strains of guinea pigs were similar, the retinal changes were, therefore, not related to the affinity between melanin and MDA. Examination of other tissues revealed small pulmonary granulomas or mild granulomatous pneumonitis in most MDA-exposed animals but no remarkable residual lesions in the liver and kidney 2 to 3 weeks postexposure.