Disposition of inhaled 1-chloro-2-propanol in [formula omitted] rats

Abstract

Propylene chlorohydrins, of which 1-chloro-2-propanol (1-CP) is a constituent, are used as intermediates in the manufacture of propylene oxide and have been identified as potential air pollutants. The objective of these studies was to determine whether changes in the inhaled exposure concentration would affect the disposition of 1-CP in rats. In addition, experiments were conducted to identify the carbon atom of 1-CP that is metabolized to CO 2. Rats were exposed nose-only to [ 14C]1-CP for 6 hr to 8.3 ± 1.0 ppm (26.1 ± 3.2 μg/liter air) or 77 ± 4 ppm (245 ± 13 μg/liter air) (mean ± SE). There were two major routes of elimination of 14C, urinary and exhalation of CO 2, which together accounted for about 80% of the total 14C in excreta and carcass. Half-times for elimination of 14C in urine and as 14CO 2 were between 3 and 7 hr with no effect of exposure concentration on the elimination half-times for either route. After the end of exposure, kidneys, livers, trachea, and nasal turbinates contained high concentrations of [ 14C]1-CP equivalents at both exposure concentrations (30–50 nmol 14C/g tissue for the 8 ppm exposure level and 200–350 nmol 14C/g tissue for the 80 ppm exposure level). Elimination of 14C from tissues was biphasic with about 50% of the material in a tissue being rapidly eliminated with a half-time of 1 to 3 hr and the remaining material slowly eliminated with a half-time of 40 to 80 hr. There was no effect of exposure concentration on elimination half-times in tissues. Major metabolites detected in urine and tissues (liver, kidney, and lung) were N-acetyl- S-(hydroxypropyl)cysteine and/or S-(2-hydroxypropyl)-cysteine. Little unmetabolized 1-CP (<1%) was detected in analyzed tissues or urine. We propose a metabolic scheme in which the major pathway for metabolism of 1-CP is to CO 2 (which is exhaled) and to cysteine conjugates and mercapturic acids that are excreted in the urine. Both carbon-2 and carbon-3 are metabolized in part to CO 2.