New approach to risk assessment of central neurotoxicity induced by 1-bromopropane using animal models
New approach to risk assessment of central neurotoxicity induced by 1-bromopropane using animal models
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DOI：
10.1016/j.neuro.2006.05.003
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发表时间：
2007-03-01
期刊：
影响因子：
3.4
通讯作者：
Hori, Hajime
中科院分区：
文献类型：
--
作者：
Fueta, Yukiko;Ishidao, Toru;Hori, Hajime
1-溴丙烷（I-BP）可引起工人的中枢和外周神经毒性。我们已经报道了大鼠海马中的反馈抑制（即去抑制）功能障碍，暴露于浓度为1500和700 ppm的I-BP后。为了进行风险评估，我们研究了从对照组和1-BP暴露（200和400 ppm）大鼠中获得的海马切片中CA 1区和齿状回的去抑制作用，并测定了大脑中的溴化物浓度。吸入暴露于400 ppm 1 -BP 8或12周后，观察到颗粒细胞去抑制，表明齿状回比CA 1区更敏感的I-BP暴露。I-BP吸入解除抑制的最低观察到的不良反应水平和未观察到的不良反应水平分别为400和200 ppm。在吸入400 ppm的第4周，脑中溴化物的浓度从2.9 +/- 1.5 μ g/g湿脑增加到85.0 +/- 25.4 μ g/g湿脑，即使暴露期延长至12周，也没有观察到进一步增加。在不同的暴露浓度下，研究了总剂量（ppm-h）与1 -BP暴露浓度的关系。吸入引起的抑制解除和死亡取决于总剂量，随着暴露浓度的增加，其发生时间提前。结果表明，1-BP吸入引起的中枢神经毒性的风险评估的新模型。(c)2006年爱思唯尔公司All rights reserved.
I-Bromopropane (I-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 I -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 I-BP exposure. The lowest observed adverse effect level and the no observed adverse effect level of I -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 mu g/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. (c) 2006 Elsevier Inc. All rights reserved.