Ginsberg Gary L
Connecticut Department of Public Health, Division of Environmental Epidemiology & Occupational Health, PO Box 340308, MS 11CHA, Hartford, CT 06134-0308, USA.
Risk Anal. 2003 Feb;23(1):19-34. doi: 10.1111/1539-6924.00287.
For the vast majority of chemicals that have cancer potency estimates on IRIS, the underlying database is deficient with respect to early-life exposures. This data gap has prevented derivation of cancer potency factors that are relevant to this time period, and so assessments may not fully address children's risks. This article provides a review of juvenile animal bioassay data in comparison to adult animal data for a broad array of carcinogens. This comparison indicates that short-term exposures in early life are likely to yield a greater tumor response than short-term exposures in adults, but similar tumor response when compared to long-term exposures in adults. This evidence is brought into a risk assessment context by proposing an approach that: (1) does not prorate children's exposures over the entire life span or mix them with exposures that occur at other ages; (2) applies the cancer slope factor from adult animal or human epidemiology studies to the children's exposure dose to calculate the cancer risk associated with the early-life period; and (3) adds the cancer risk for young children to that for older children/adults to yield a total lifetime cancer risk. The proposed approach allows for the unique exposure and pharmacokinetic factors associated with young children to be fully weighted in the cancer risk assessment. It is very similar to the approach currently used by U.S. EPA for vinyl chloride. The current analysis finds that the database of early life and adult cancer bioassays supports extension of this approach from vinyl chloride to other carcinogens of diverse mode of action. This approach should be enhanced by early-life data specific to the particular carcinogen under analysis whenever possible.
对于综合风险信息系统（IRIS）上有癌症效力估计值的绝大多数化学物质而言，其基础数据库在早期生命暴露方面存在缺陷。这一数据缺口阻碍了与该时期相关的癌症效力因子的推导，因此评估可能无法充分解决儿童面临的风险。本文对一系列致癌物的幼年动物生物测定数据与成年动物数据进行了综述比较。这种比较表明，生命早期的短期暴露可能比成年期的短期暴露产生更大的肿瘤反应，但与成年期的长期暴露相比，肿瘤反应相似。通过提出一种方法，将这一证据纳入风险评估背景中，该方法：（1）不按比例在整个生命周期内分摊儿童的暴露量，也不将其与其他年龄段发生的暴露量混合；（2）将成年动物或人类流行病学研究中的癌症斜率因子应用于儿童的暴露剂量，以计算与早期生命阶段相关的癌症风险；（3）将幼儿的癌症风险与大龄儿童/成年人的癌症风险相加，得出终身总癌症风险。所提出的方法能够在癌症风险评估中充分权衡与幼儿相关的独特暴露和药代动力学因素。它与美国环境保护局（U.S. EPA）目前用于氯乙烯的方法非常相似。当前的分析发现，早期生命和成年癌症生物测定数据库支持将这种方法从氯乙烯扩展到其他作用方式多样的致癌物。只要有可能，应通过针对所分析特定致癌物的早期生命数据来加强这种方法。
