Krishnan K, Paterson J, Williams D T
Faculté de Médecine, Université de Montréal, CP 6128, Succursale A, Montréal, Quebec, H3C 3J7, Canada.
Regul Toxicol Pharmacol. 1997 Oct;26(2):179-87. doi: 10.1006/rtph.1997.1151.
The objectives of this article are: (i) to review the current approaches of Health Canada to the risk assessment of drinking water contaminants, and (ii) to examine the applicability of mixture risk assessment methods to drinking water contaminants. Health Canada's current approaches to drinking water risk assessment, like those of many regulatory agencies, focus almost solely on the effects of individual chemicals. As such, no formal method is currently used for developing mixtures guidelines or for modifying guidelines of individual chemicals to account for the possibility of the occurrence of interactions (supraadditive or infraadditive). Recent interest in the risk assessment of mixtures, at least in part, stems from concerns over the potential health risks of mixtures of very commonly occurring compounds in Canadian drinking water supplies, namely the disinfection by-products. Before any mixtures methods can be considered for incorporation into Health Canada's current approaches to the risk assessment of drinking water contaminants, it is essential to consider the limitations and data requirements of the various mixture risk assessment methods (i.e., whole mixture approach, similar mixture approach, components-based approaches, interactions-based assessment). Among the existing mixture risk assessment methods, the components-based and interactions-based approaches could be applicable to drinking water contaminants. Specifically, among the components-based approaches, dose-addition, response-addition, and the toxic equivalency factor approaches are the most applicable ones for drinking water contaminants. Until an interactions-based, mechanistic risk assessment approach (e.g., physiological model-based approach) becomes available for routine use, the components-based approaches remain the default methods for consideration. Progress in the development and validation of an interactions-based risk assessment methodology should facilitate a more realistic assessment of risk due to drinking water contaminants without increasing the levels of uncertainty in risk estimates above those associated with existing single-chemical methods.
（i）回顾加拿大卫生部目前对饮用水污染物进行风险评估的方法，以及（ii）研究混合风险评估方法在饮用水污染物方面的适用性。加拿大卫生部目前对饮用水风险评估的方法，与许多监管机构的方法一样，几乎完全集中在单一化学品的影响上。因此，目前没有正式的方法用于制定混合物准则或修改单一化学品的准则，以考虑相互作用（超加性或次加性）发生的可能性。最近对混合物风险评估的关注，至少部分源于对加拿大饮用水供应中非常常见的化合物混合物（即消毒副产物）潜在健康风险的担忧。在考虑将任何混合物方法纳入加拿大卫生部目前对饮用水污染物的风险评估方法之前，必须考虑各种混合风险评估方法（即整体混合物方法、相似混合物方法、基于成分的方法、基于相互作用的评估）的局限性和数据要求。在现有的混合风险评估方法中，基于成分的方法和基于相互作用的方法可能适用于饮用水污染物。具体而言，在基于成分的方法中，剂量相加、反应相加和毒性当量因子方法是最适用于饮用水污染物的方法。在基于相互作用的、机械的风险评估方法（例如基于生理模型的方法）可用于常规使用之前，基于成分的方法仍然是默认的考虑方法。基于相互作用的风险评估方法在开发和验证方面的进展应有助于更实际地评估饮用水污染物带来的风险，而不会使风险估计中的不确定性水平高于现有单一化学品方法所涉及的不确定性水平。
