Farris G M, Robinson S N, Gaido K W, Wong B A, Wong V A, Leonard L, Shah R
Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina, USA.
Environ Health Perspect. 1996 Dec;104 Suppl 6(Suppl 6):1275-6. doi: 10.1289/ehp.961041275.
Evaluation of benzene-induced hematotoxicity following exposure to low concentration is important for understanding mechanisms of toxicity and determining the dose response at benzene levels close to the current occupational exposure limit (1 ppm). Male B6C3F1 mice were exposed to 0, 1, 10, 100, or 200 ppm benzene by inhalation for 6 hr/day, 5 days/week, for 1, 2, 4, or 8 weeks. At each sampling time, we evaluated primitive and committed progenitor cells, differentiating and maturing lineage-specific cells, and stromal cells in the bone marrow; T and B lymphocytes of the spleen and thymus; micronucleated reticulocytes and erythrocytes; and standard blood parameters. At 100 and 200 ppm benzene, there were rapid and significant reductions in number of reticulocytes in the blood, B lymphocytes in the bone marrow and spleen, and an increased frequency of micronucleated reticulocytes in the bone marrow. At 10 ppm, the only parameter affected was a transient reduction in the number of splenic B lymphocytes. There were no significant effects induced by 1 ppm benzene in this study. The present study suggests numbers of B lymphocytes and maturing erythrocytes, and frequency of micronucleated reticulocytes are sensitive indicators of benzene-induced hematotoxicity and will be useful in further investigation of the hematotoxicity induced by 10 to 100 ppm benzene.
评估低浓度苯暴露后的血液毒性对于理解毒性机制以及确定接近当前职业暴露限值(1 ppm)的苯水平下的剂量反应至关重要。雄性B6C3F1小鼠通过吸入方式暴露于0、1、10、100或200 ppm的苯中,每天6小时,每周5天,持续1、2、4或8周。在每个采样时间,我们评估了骨髓中的原始和定向祖细胞、分化和成熟的谱系特异性细胞以及基质细胞;脾脏和胸腺中的T和B淋巴细胞;微核网织红细胞和红细胞;以及标准血液参数。在100和200 ppm苯暴露组中,血液中网织红细胞数量、骨髓和脾脏中的B淋巴细胞数量迅速且显著减少,骨髓中微核网织红细胞的频率增加。在10 ppm时,唯一受影响的参数是脾脏B淋巴细胞数量的短暂减少。在本研究中,1 ppm苯未引起显著影响。本研究表明,B淋巴细胞数量、成熟红细胞数量以及微核网织红细胞频率是苯诱导血液毒性的敏感指标,将有助于进一步研究10至100 ppm苯诱导的血液毒性。