Studies on the mechanism of haloacetonitriles toxicity: quantitative whole body autoradiographic distribution of [2- 14C]chloroacetonitrile in rats

Abstract

Chloroacetonitrile (CAN), a drinking water disinfectant by-product, possesses mutagenic and carcinogenic properties. The objective of this study was to investigate the biologic fate of CAN, using whole body autoradiographic (WBA) techniques. Male Sprague—Dawley rats were treated with a tracer dose of [2- 14C]CAN (i.v., 88 μCi/kg, spec. act. 4.07 mCi/mmol). At various time intervals (0.08, 1, 3, 6, 12, 24, and 48 h) after treatment, rats were processed for WBA. Over 12 h after administration, the radioactivity excreted in urine, feces, and exhaled as 14CO 2 accounted for 51%, 2.7%, and 12% of the dose, respectively. Only 0.8% of the administered dose was exhaled as unchanged CAN. At an early time interval (5 min) extensive accumulation of radioactivity was observed in liver, kidney, and gastrointestinal (G.I.) walls. In addition, high levels of 14C were detected in the thyroid gland, lung bronchioles, adrenal cortex, salivary gland, and testes. At 1 h following administration, the olfactory bulb, olfactory receptor area of the brain and lumbar cistern showed high accumulations of radioactive CAN or its equivalents. At 3, 6, and 12 h after treatment, the radioactivity diffused homogeneously in all tissues and reconcentrated in several organs at later time periods (24 and 48 h). Our studies indicate extensive metabolic biotransformation of CAN in rats. The retention of radioactivity in the tissues of the thyroid gland, G.I., testes, brain and eye suggest that those organs are potential target sites of CAN toxicity.