Toxicology and Applied Pharmacology 1984-06-30

Experimental delayed hypersensitivity following inhalation of dicyclohexylmethane-4,4'-diisocyanate: a concentration-response relationship.

J Stadler, M H Karol

Index: Toxicol. Appl. Pharmacol. 74(2) , 244-9, (1984)

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Abstract

Exposure of workers to low-molecular-weight chemicals has been associated with delayed-onset hypersensitivity reactions in both the skin and the respiratory tract. The use of two animal models to examine factors affecting the production of delayed hypersensitivity to dicyclohexylmethane-4,4'-diisocyanate (HMDI) is described. Guinea pigs were exposed to HMDI by a "head-only" method and mice in a "nose-only" procedure. All animals were subsequently tested for dermal sensitivity by topical challenge with the isocyanate. In both species, a concentration-response relationship and "no-effect" concentration was observed between chamber concentration of HMDI and (a) severity of the dermal response and (b) number of animals responding. Guinea pigs developed skin sensitivity following inhalation of 3 micrograms/liter or greater HMDI for 2 hr/day on 3 consecutive days. Inhalation of 1.25 micrograms/liter did not result in sensitization. Contact sensitivity was detected in BALB/cBy mice following inhalation of 17 micrograms/liter or greater HMDI. No reactions occurred as a result of exposure to 7 micrograms/liter or less HMDI. Dermal contact of the head, as would occur during inhalation exposures, also resulted in contact sensitization. Identification of the concentration-response relationship for contact sensitization following inhalation exposure implies that safe exposure levels can be proposed to prevent cases of dermal sensitization to HMDI.