氯乙烯遗传毒性及其基准剂量在职业接触限值中的应用

Genotoxicity of vinyl chloride and application of its benchmark dose(BMD)in occu pational exposure limit

目的探讨氯乙烯累积暴露造成的遗传毒性效应及其可能的影响因素,建立氯乙烯接触与遗传损伤效应间的剂量-反应关系,并估算氯乙烯致遗传毒性的基准剂量值。方法选择上海某氯碱化工厂氯乙烯作业工人为氯乙烯接触组(229人),对照组138人,使用调查问卷收集个人健康信息,采用胞质分裂阻滞微核评价外周血淋巴细胞DNA损伤;计算基准剂量(BMD),推算基准剂量的95%低限水平(BMDL)。结果对照组微核计数值为(1.23±0.11)‰,接触组微核计数值为(3.73±0.16)‰,两组比较,差异有统计学意义(P<0.01);氯乙烯累积接触量与微核率之间存在剂量-反应关系,得到BMD10的范围在7.20～9.64 mg/(m3.年),基准剂量下限值介于1.71～3.614mg/(m3.年)之间[2.86 mg/(m3.年)]。将工作年限按40年计,氯乙烯的时间加权平均阈限值应为0.072 mg/(m3.年)。结论氯乙烯作为确定的致癌物质,氯乙烯累积接触量与氯乙烯作业工人微核率之间存在相互关联;基于遗传毒性的职业接触限值的研究,有助于推动以保护职业有害物质接触人群为目标的职业安全制度的修订。

Objective To investigate the dose-effect relationship and impact factor between cumulative exposure dose （CED） of vinyl chloride monomer （VCM） and chromosomal damage, thereby to estimate its benchmark dose （BMD）. Methods Cytokinesis-block micronucleus （CBMN） assay was used in 229 VCM-exposed workers and 138 controls for the detection of chromosome damage in peripheral blood lymphocytes. The cumulative exposure dose （CED） of VCM was calculated based on the job type and duration of each worker and VCM concentration in workplaces. Dose-response relationship between CED of VCM and CBMN frequency was evaluated for the calculation of BMD. Results The results showed that the CBMN frequency in exposure group was （ 3.73 ± 0. 16 ） %o, significantly higher than that of control group [ （ 1.23 ± 0. 11 ） %0, P 〈 0.01 ] , the 95% lower confidence bound of BMD of CED was 2. 86 mg/m^3 per year for both genders; if assume the work life was 40 years, the estimated exposure limit should be 0. 072 mg,/m^3 per year. Conclusion VCM exposure may induce chromosomal damage even at the occupational exposure levels below the occupational health standard of China. Therefore, better doseresponse assessment and BMD estimation are demanded in order to improve the quantification of occupational exposure limits of VCM and to protect against cancer risk.