Toxicological Sciences 55, 116-123 (2000)
Copyright © 2000 by the Society of Toxicology
Neurotoxicology |
1-Bromopropane, an Alternative to Ozone Layer Depleting Solvents, Is Dose-Dependently Neurotoxic to Rats in Long-Term Inhalation Exposure
* Department of Occupational and Environmental Health, Graduate School of Medicine, and
Institute for Laboratory Animal Experiments, School of Medicine, Nagoya University, Nagoya, Japan;
National Institute of Industrial Health, Kanagawa, Japan;
§ Safety Assessment Laboratory, Sanwa Kagaku Kenkyusho Co. Ltd., Mie, Japan; and
¶ Department of Medical Technology, School of Health Sciences, Nagoya University, Nagoya, Japan
1-Bromopropane has been newly introduced as an alternative to ozone layer-depleting solvents. We aimed to clarify the dose-dependent effects of 1-bromopropane on the nervous system. Forty-four Wistar male rats were randomly divided into 4 groups of 11 each. The groups were exposed to 200, 400, or 800 ppm of 1-bromopropane or only fresh air 8 h per day for 12 weeks. Grip strength of forelimbs and hind limbs, maximum motor nerve conduction velocity (MCV), and distal latency (DL) of the tail nerve were measured in 9 rats of each group every 4 weeks. The other 2 rats of each group were perfused at the end of the experiment for morphological examinations. The rats of the 800-ppm group showed poor kicking and were not able to stand still on the slope. After a 12-week exposure, forelimb grip strength decreased significantly at 800 ppm and hind limb grip strength decreased significantly at both 400 and 800 ppm or after a 12-week exposure. MCV and DL of the tail nerve deteriorated significantly at 800 ppm. Ovoid or bubble-like debris of myelin sheaths was prominent in the unraveled muscular branch of the posterior tibial nerve in the 800-ppm group. Swelling of preterminal axons in the gracile nucleus increased in a dose-dependent manner. Plasma creatine phosphokinase (CPK) decreased dose-dependently with significant changes at 400 and 800 ppm. 1-Bromopropane induced weakness in the muscle strength of rat limbs and deterioration of MCV and DL in a dose-dependent manner, with morphological changes in peripheral nerve and preterminal axon in the gracile nucleus. 1-Bromopropane may be seriously neurotoxic to humans and should thus be used carefully in the workplace.
Key Words: 1-bromopropane; neurotoxicity; alternative to chlorofluorocarbons; neuropathy; motor nerve conduction velocity; distal latency; tibial nerve; Wallerian-like degeneration; preterminal; gracile nucleus; creatine phosphokinase.
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