Whittaker Margaret H, Gebhart Ann Marie, Miller Thea Clipson, Hammer Frank
ToxServices LLC, Washington, DC 20036, USA.
Toxicol Ind Health. 2004 Sep;20(6-10):149-63. doi: 10.1191/0748233704th199oa.
2-Mercaptobenzothiazole (MBT) is used as a vulcanization accelerator in rubber products that come into contact with potable drinking water. When such products are evaluated for contact with potable water and submitted for ANSI/NSF Standard 61 certification, any chemical extracting from these products must be below an appropriate action level of exposure. As defined by Standard 61, a total allowable concentration (TAC) is the maximum concentration of a nonregulated contaminant allowed in a public drinking water supply, and the single product allowable concentration (SPAC) is 10% of the TAC. Currently, MBT has a TAC of 40 microg/L and a SPAC of 4 microg/L. A comprehensive health effects evaluation of MBT was performed to determine whether these action levels should be revised. Epidemiological investigations indicate that workers occupationally exposed to MBT have an increased risk of death from bladder cancer. Genotoxicity investigations in bacterial and mammalian test systems provide some evidence indicating that MBT has the potential to induce mutations and chromosomal aberrations. Toxicity studies in rats and mice chronically exposed to MBT identified increases in various tumours, such as adrenal gland tumours, pituitary gland tumours, liver tumours and renal pelvis tumours. The biological significance of most of these tumours is questionable due to a variety of factors, such as a lack of dose-response between tumour incidence and dose, and the effect of test article vehicle (corn oil) upon tumour rates. Potential human health effects of exposure to MBT can be predicted from an NTP 2-year cancer study in rats, as well as epidemiological investigations in occupationally exposed workers. A comprehensive review of the epidemiological and toxicological dataset for MBT indicates that the induction of renal pelvis transitional cell tumours is the most sensitive and relevant health effects endpoint upon which to base a revised TAC and SPAC. A multistage model was used to extrapolate to low-dose MBT exposures due to the genotoxicity and clastogenicity of MBT. A TAC of 600 microg/L was derived for MBT, and was based upon an LED10 of 157.681 mg/kg per day. A SPAC of 60 microg/L was derived by multiplying the revised TAC by 0.10, and rounding to one significant figure. These revised action levels are based upon the most sensitive health effects endpoint, as well as current cancer risk assessment methodology.
2-巯基苯并噻唑（MBT）在与饮用水接触的橡胶制品中用作硫化促进剂。当对这类产品进行与饮用水接触的评估并提交美国国家标准学会/美国国家卫生基金会（ANSI/NSF）标准61认证时，从这些产品中提取的任何化学物质的含量都必须低于适当的暴露行动水平。根据标准61的定义，总允许浓度（TAC）是公共饮用水供应中允许的非管制污染物的最大浓度，单一产品允许浓度（SPAC）是TAC的10%。目前，MBT的TAC为40微克/升，SPAC为4微克/升。对MBT进行了全面的健康影响评估，以确定是否应修订这些行动水平。流行病学调查表明，职业接触MBT的工人患膀胱癌死亡的风险增加。在细菌和哺乳动物测试系统中进行的遗传毒性研究提供了一些证据，表明MBT有诱导突变和染色体畸变的潜力。对长期接触MBT的大鼠和小鼠进行的毒性研究发现，各种肿瘤有所增加，如肾上腺肿瘤、垂体肿瘤、肝肿瘤和肾盂肿瘤。由于多种因素，如肿瘤发生率与剂量之间缺乏剂量反应关系以及受试物载体（玉米油）对肿瘤发生率的影响，这些肿瘤中大多数的生物学意义值得怀疑。接触MBT对人类健康的潜在影响可以从美国国家毒理学计划（NTP）对大鼠进行的为期两年的癌症研究以及对职业接触工人的流行病学调查中预测。对MBT的流行病学和毒理学数据集进行的全面审查表明，肾盂移行细胞肿瘤的诱导是修订TAC和SPAC最敏感和相关的健康影响终点。由于MBT具有遗传毒性和致断裂性，因此使用多阶段模型外推至低剂量MBT暴露情况。得出MBT的TAC为600微克/升，这是基于每天157.681毫克/千克的10%低效应剂量（LED10）。通过将修订后的TAC乘以0.10并四舍五入到一位有效数字，得出SPAC为60微克/升。这些修订后的行动水平基于最敏感的健康影响终点以及当前的癌症风险评估方法。
