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Assessing Cancer Risks from Short-Term Exposures in Children

机译：从儿童的短期接触评估癌症风险

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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.
机译：对于大多数具有IRIS癌症潜力估计值的化学药品，其基础数据库在早期生命暴露方面是不足的。此数据缺口阻止了与此时间段相关的癌症效力因素的推导，因此评估可能无法完全解决儿童的风险。本文提供了与各种致癌物的成年动物数据相比，幼体动物生物测定数据的综述。该比较表明，与成年人的短期暴露相比，生命早期的短期暴露可能比成年人的短期暴露产生更大的肿瘤反应，但是与成年人的长期暴露相比，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范围：（1）不要在整个生命周期内不按比例分配儿童的暴露量，也不将其与其他年龄段的暴露量混合使用； （2）将成年动物或人类流行病学研究的癌症斜率因子应用于儿童的暴露剂量，以计算与生命早期有关的癌症风险； （3）将年龄较大的儿童/成人的患癌风险增加到年龄较大的儿童/成人的患癌风险中，以产生一生的总癌症风险。拟议的方法允许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EPA当前用于氯乙烯的方法非常相似。当前的分析发现，早期生命和成人癌症生物测定的数据库支持将这种方法从氯乙烯扩展到其他多种作用方式的致癌物。只要有可能，应通过特定于特定致癌物的早期数据来增强这种方法。

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