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.

Alteration of Brain Levels of Neurotransmitters and Amino Acids in Male F344 Rats Induced by Three-week Repeated Inhalation Exposure to 1-Bromopropane

“…The reproductive and hematopoietic toxicity of 2BP has led to a decrease in its use and its replacement with 1-bromopropane (1BP). However, the results of animal experiments indicate that 1BP is toxic to the peripheral nerves 6,7) . The grip strength of all four limbs of male Wistar rats decreased following exposure to 800 ppm of 1BP for 8 h per day for 8 wk.…”

Health hazard evaluation report: HETA #99-0260-2906, Marx Industries, Inc., Sawmills, North Carolina.

“…59 In another study of the effects of chronic inhalational exposure, Ichihara and colleagues divided male rats into four groups and exposed them to 1-BP at concentrations of 0, 200, 400, or 800 ppm for 8 hours a day for 12 weeks. 61 Those rats exposed to airborne concentrations of 0, 200 and 400 ppm developed no difficulties with their balance or their ability to walk. Those rats exposed to airborne concentrations of 800 ppm developed weakness in their hind limbs and consequently could not maintain their position on an inclined surface.…”

“…Ichihara reported that the effects on MCV and DL were not seen in either group of animals exposed to 1-BP at 200 ppm or 400 ppm, but became evident among animals exposed at 800 ppm. 61 Yu and colleagues found MCV values slowed considerably and DL values became significantly prolonged as compared to control animals after 4 weeks of exposure to 1-BP at levels of 1000 ppm. 49,62 This same research group noted that the onset of decrease in MCV and prolongation in DL occurred earlier in those rats exposed to 1-BP at 1000 ppm than in those exposed to 2-BP at 1000 ppm.…”

“…61 During the course of the 12 weeks, the rats were monitored for clinical signs of neurological effects. After 4 weeks, rats exposed to 1-BP at 200 ppm exhibited a decrease in hind limb grip strength that then resolved spontaneously.…”

Control of Hazardous Substances at Small Workplaces

“…4), and cautioned the producers and providers of 2-bromopropane to carefully supply it to workplaces 10) . However some foreign makers started producing and providing 1-bromopropane by claiming that 1-bromopropane was much less toxic than 2-bromopropane in terms of reproductive toxicity and mutagenicity according to their experiments.…”