1-Bromopropane, an Alternative to Ozone Layer Depleting Solvents, Is Dose-Dependently Neurotoxic to Rats in Long-Term Inhalation Exposure

• Published in: Toxicological sciences Vol. 55; no. 1; pp. 116 - 123
• Main Authors: Ichihara, Gaku, Kitoh, Junzoh, Yu, Xiaozhong, Asaeda, Nobuyuki, Iwai, Hisakazu, Kumazawa, Toshihiko, Shibata, Eiji, Yamada, Tetsuya, Wang, Hailan, Xie, Zhenlin, Takeuchi, Yasuhiro
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.05.2000
• Subjects: 1-Bromopropane; Administration, Inhalation; alternative to chlorofluorocarbons; Animals; Axons - drug effects; Axons - pathology; Body Weight - drug effects; Brain - drug effects; Central Nervous System - pathology; creatine phosphokinase; distal latency; Electrophysiology; Enzymes - blood; gracile nucleus; Hand Strength - physiology; Hydrocarbons, Brominated - administration & dosage; Hydrocarbons, Brominated - toxicity; Male; motor nerve conduction velocity; Muscle, Skeletal - innervation; Muscle, Skeletal - pathology; Nervous System Diseases - chemically induced; Nervous System Diseases - pathology; Neural Conduction - drug effects; neuropathy; neurotoxicity; Organ Size - drug effects; Peripheral Nerves - pathology; preterminal; Rats; Rats, Wistar; Solvents - administration & dosage; Solvents - toxicity; Tail - innervation; tibial nerve; Walking - physiology; Wallerian-like degeneration
• ISSN: 1096-6080; 1096-0929; 1096-0929
• DOI: 10.1093/toxsci/55.1.116

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.