New approach to risk assessment of central neurotoxicity induced by 1-bromopropane using animal models.
1-Bromopropane (1-BP) induces central as well as peripheral neurotoxicity in workers. We have reported the dysfunction of feedback inhibition (i.e. disinhibition) in the rat hippocampus following exposure to 1-BP at concentrations of 1500 and 700 ppm. For risk assessment, we studied disinhibition of the CA1 region and the dentate gyrus in hippocampal slices obtained from control and 1-BP-exposed (200 and 400 ppm) rats, and determined the bromide concentration in the brain. Granule cell disinhibition was observed after inhalation exposure to 400 ppm 1-BP for 8 or 12 weeks, suggesting that the dentate gyrus was more sensitive than the CA1 region to 1-BP exposure. The lowest observed adverse effect level and the no observed adverse effect level of 1-BP inhalation for disinhibition were 400 and 200 ppm, respectively. The concentration of bromides in the brain increased from 2.9+/-1.5 to 85.0+/-25.4 microg/g-wet brain at week 4 of 400 ppm inhalation, and no further increase was observed even when the exposure period was extended for up to 12 weeks. The relationship between total dose (ppm-h) and the exposure concentration of 1-BP was investigated at different exposure concentrations. Disinhibition and death by inhalation depended on the total dose, and their occurrence appeared earlier as the exposure concentration increased. The results demonstrated a novel model for risk assessment of central neurotoxicity induced by 1-BP inhalation.
Fueta
Yukiko
Y
Department of Medical Technology I, School of Health Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu 807-8555, Japan. yukiko@med.uoeh-u.ac.jp
Ishidao
Toru
T
Ueno
Susumu
S
Yoshida
Yasuhiro
Y
Kunugita
Naoki
N
Hori
Hajime
H
D000393:Air Pollutants / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018891:Dentate Gyrus / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000378:metabolism / Q000633:toxicity; D019570:Inhalation Exposure; D008297:Male; D023421:Models, Animal; D009433:Neural Inhibition / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D019055:No-Observed-Adverse-Effect Level; D017966:Pyramidal Cells / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018570:Risk Assessment; D012997:Solvents / Q000378:metabolism / Q000633:toxicity*; D013997:Time Factors; D018675:Toxicity Tests / Q000379:methods*
D000393:Air Pollutants; D015415:Biomarkers; D006842:Hydrocarbons, Brominated; D012997:Solvents; C005218:methyl bromide; C118559:1-bromopropane