Yin Hongyin, Zhang Chunling, Guo Ying, Shao Xiaoying, Zeng Tao, Zhao Xiulan, Xie Keqin
Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong Province, China ; Jinan Municipal Center for Disease Control & Prevention, Jinan, Shandong Province, China.
Nutrition Department, Shandong Jiaotong Hospital, Jinan, Shandong Province, China.
PLoS One. 2014 Jan 22;9(1):e86108. doi: 10.1371/journal.pone.0086108. eCollection 2014.
Pyrrole adducts might be used as a biomarker for monitoring occupational exposure to n-hexane, but the Biological Exposure Indices of pyrrole adducts in serum and urine are still unknown. The current study was designed to investigate the biological exposure limit of pyrrole adducts for hazard assessment of n-hexane.
Male Wistar rats were given daily dose of 500, 1000, 1500, 2000, 4000 mg/kg bw n-hexane by gavage for 24 weeks. The levels of pyrrole adducts in serum and urine were determined at 8, 24 hours postdose once a week. The Biological Exposure Indices was evaluated by neurological evaluation and the levels of pyrrole adducts. The difference in pyrrole adducts formation between humans and rats were estimated by using in vitro test.
Dose-dependent effects were observed between the doses of n-hexane and pyrrole adducts in serum and urine, and the levels of pyrrole adduct in serum and urine approached a plateau at week 4. There was a significantly negative correlation between the time to paralysis and the level of pyrrole adducts in serum and urine, while a positive correlation between gait score and levels of pyrrole adducts in serum and urine was observed. In vitro, pyrrole adducts formed in human serum was about two times more than those in rat serum at the same level of 2,5-HD.
It was concluded that the BEIs of pyrrole adducts in humans were 23.1 ± 5.91 nmol/ml in serum 8 h postdose, 11.7 ± 2.64 nmol/ml in serum 24 h postdose, 253.8 ± 36.3 nmol/ml in urine 8 h postdose and 54.6 ± 15.42 nmol/ml in urine 24 h postdose.
吡咯加合物可能用作监测职业性正己烷暴露的生物标志物，但血清和尿液中吡咯加合物的生物暴露指数仍不清楚。本研究旨在调查吡咯加合物的生物暴露限值，用于正己烷的危害评估。
将雄性Wistar大鼠每天经口灌胃给予500、1000、1500、2000、4000mg/kg体重的正己烷，持续24周。每周在给药后8、24小时测定血清和尿液中吡咯加合物的水平。通过神经学评估和吡咯加合物水平评估生物暴露指数。利用体外试验估计人与大鼠之间吡咯加合物形成的差异。
观察到正己烷剂量与血清和尿液中吡咯加合物之间存在剂量依赖性效应，血清和尿液中吡咯加合物水平在第4周接近平台期。麻痹时间与血清和尿液中吡咯加合物水平之间存在显著负相关，而步态评分与血清和尿液中吡咯加合物水平之间存在正相关。在体外，在相同2,5-己二酮水平下，人血清中形成的吡咯加合物比大鼠血清中的约多两倍。
得出结论，人血清中吡咯加合物的生物暴露指数在给药后8小时为23.1±5.91nmol/ml，给药后24小时为11.7±2.64nmol/ml，给药后8小时尿液中为253.8±36.3nmol/ml，给药后24小时尿液中为54.6±15.42nmol/ml。
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