title: 1-Bromopropane, an alternative to ozone layer depleting solvents, is dose-dependently neurotoxic to rats in long-term inhalation exposure.
abstract: 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.
authors.affiliation: Department of Occupational and Environmental Health, Graduate School of Medicine, Nagoya University, Nagoya, Japan. gak@med.nagoya-u.ac.jp
authors.forename: G
authors.initials: G
authors.lastname: Ichihara
authors.forename: J
authors.initials: J
authors.lastname: Kitoh
authors.forename: X
authors.initials: X
authors.lastname: Yu
authors.forename: N
authors.initials: N
authors.lastname: Asaeda
authors.forename: H
authors.initials: H
authors.lastname: Iwai
authors.forename: T
authors.initials: T
authors.lastname: Kumazawa
authors.forename: E
authors.initials: E
authors.lastname: Shibata
authors.forename: T
authors.initials: T
authors.lastname: Yamada
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: Z
authors.initials: Z
authors.lastname: Xie
authors.forename: Y
authors.initials: Y
authors.lastname: Takeuchi
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D002490:Central Nervous System / Q000473:pathology; D004594:Electrophysiology; D004798:Enzymes / Q000097:blood; D018737:Hand Strength / Q000502:physiology; D006842:Hydrocarbons, Brominated / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D018482:Muscle, Skeletal / Q000294:innervation / Q000473:pathology; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology; D009431:Neural Conduction / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010525:Peripheral Nerves / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012997:Solvents / Q000008:administration & dosage / Q000633:toxicity*; D013623:Tail / Q000294:innervation; D016138:Walking / Q000502:physiology
chemical_list: D004798:Enzymes; D006842:Hydrocarbons, Brominated; D012997:Solvents; C118559:1-bromopropane