Propylene chlorohydrins: toxicology, metabolism and environmental fate

Abstract

Propylene chlorohydrins are commercially important industrial chemicals and their roles as intermediates for the production of ethylene oxide and propylene oxide underscore their value to the chemical industry. Despite their eminence as valuable chemicals and the large production volume, relatively little toxicologic information is available in the literature. From a different perspective, propylene chlorohydrins are of concern as residues in foods as a result of fumigation of foods with propylene oxide. In this presentation, consolidation of the existing information on the toxicology, metabolism, and environmental occurence of propylene chlorohydrins was attempted. Propylene chlorohydrins have a fairly high order of acute toxicity. Single dose LD50 values are in the range of 100 to 500 mg/kg. Although there appeared to be no primary skin irritation effects on the rabbits, propylene chlorohydrins do cause marked corneal injury on coming into direct contact with the eyes. From the limited information available on the subchronic toxicity studies in rats, repeated peroral dosing may induce mortality, depression of body weight gain, and organ weight changes at doses ranging from 75 to 200 mg/kg/d. The dietary route of exposure may not be adequate for toxicity studies because of the volatility of the chemicals. Repeated gavage dosing at 250 mg/kg/d is fatal to rats. Target organ toxicity with respect to clinical pathology analytes and/or morphological changes is not adequately defined at the present time. Because of the reported neurotoxicity and testicular toxicity of a close analog, 1-amino-3-chloro-2-propanol, the nervous system and testis should be considered as potential target organs. 1-Chloro-2-propanol was evaluated in the strain A mouse lung adenoma assay and there was no evidence of the induction of lung tumors. There are at present no chronic toxicity/carcinogenicity studies of propylene chlorohydrins although they are urgently needed. There is convincing evidence that at least 1-chloro-2-propanol is mutagenic in several different assay systems. Biotransformation of 1-chloro-2-propanol may proceed via: (1) dechlorination followed by glutathione conjugation leading toward the formation of N-acetyl-S-(2-hydroxypropyl)cysteine as a major metabolite; (2) oxidation to β-chlorolactaldehyde and β-chlorolactate. Most of the existing information came from the studies involving halopropanes.