Neuromuscular effects of repeated exposure to the pesticide methyl bromide

Methyl bromide (MB) is a fumigant pesticide that remains in use for quarantine and pre-shipment applications. Although acute intoxication is associated with motor dysfunction, the effects of repeated occupational inhalation exposure on neuromuscular structures remain poorly characterized. This study evaluated functional and anatomical consequences of repeated MB inhalation exposure in adult male Sprague-Dawley rats. Animals were exposed to either clean air or 300 ppm MB by nose-only inhalation for 2 hours a day, 5 days a week, over 4 weeks. Neurobehavioral assessments included functional observation battery testing, gait analysis, rotarod performance, and open-field locomotor activity. Lumbar spinal cord and hindlimb skeletal muscles were analyzed using quantitative confocal microscopy to assess motoneuron soma morphology, astrocyte reactivity, and neuromuscular junction (NMJ) structure. Repeated MB exposure did not produce overt clinical toxicity, body weight loss, or measurable impairments in gait, motor coordination, or spontaneous locomotor activity. No differences in lumbar motoneuron number or spinal astrocyte reactivity were detected between groups. However, MB exposure selectively reduced soma cross-sectional areas of the largest lumbar motoneurons. In parallel, NMJs within the predominantly fast-twitch extensor digitorum longus muscle exhibited increased denervation and decreased postsynaptic nicotinic acetylcholine receptor occupancy relative to controls. These alterations were not observed in the predominantly slow-twitch soleus muscle. These findings demonstrate that repeated subacute MB exposure can induce subtle peripheral neuromuscular pathology in the absence of overt behavioral dysfunction. Furthermore, these findings suggest that distal motor terminals and associated synaptic structures may represent selective and early targets of MB neurotoxicity. Collectively, the results support the concept that repeated occupational-like MB exposure may produce subclinical peripheral motor system injury prior to the onset of detectable functional impairment.