Pharmacokinetics, pharmacodynamics and aspects of neurotoxic effects of four inhaled aliphatic chlorohydrocarbon solvents as relevant in man

Abstract

Intermittent inhalation exposure of adult male rats to dichloromethane, trichloroethylene, 1,1,1-trichloroethane, perchloroethylene or to a combination of trichloroethylene and 1,1,1-trichloroethane for 5 days, for 6 h daily, induced significantly different accumulations of solvent molecules in the body. Adipose tissue served as a storage site for these solvents. The fat-stored molecules were not totally mobilized during the intermissions in exposure. Co-exposure of trichloroethylene and 1,1,1-trichloroethane induced higher accumulations than those induced by exposure to a single solvent in both the body and the brain. This increase in the accumulation of trichloroethylene might be due to competition with 1,1,1-trichloroethane for a binding site in the oxidative enzyme complex. Behavioural and neurochemical effects on trichloroethylene and dichloromethane exposure may be due to the formation of reactive metabolites. Experiments with 1,1,1-trichloroethane singly or in combination with trichloroethylene showed no observable behavioural effects. Perchloroethylene-induced effects were similarly small although, it caused the highest body concentration detected in these experiments. The metabolic activation of solvent molecules appears to also be a significant factor in neurotoxicity. Therefore biochemical interactions of agents occurring simultaneously in the environment, merit further consideration.