Cancer development from in utero exposure has been documented for a variety of agents with the most commonly studied compounds exhibiting mutagenic and genotoxic carcinogen properties. Age-dependent adjustment factors (ADAFs) are applied by the US Environmental Protection Agency to many such carcinogens when assessing cancer risk from early postnatal (PN) exposures; however, this approach has not been widely considered for transplacental (TP) exposure. To explore this question and further evaluate prenatal susceptibility a database of early life animal studies developed by California Office of Environmental Health Hazard Assessment (OEHHA) enhanced with additional literature searching was evaluated. Nine genotoxic carcinogens and one mixture (cigarette smoke) have data available via TP only, PN only and adult-only protocols. Potency comparisons across these lifestages displayed similarly greater potency in male liver and brain compared to adult-only exposure. Both TP and PN exposures were not markedly different than adult-only for other targets such as female liver and blood-borne tumors. Similarity in TP and PN targets and potency for carcinogen action suggests that a 10-fold ADAF may be applied for TP exposure as is currently applied to PN exposure. A similar conclusion was reached by OEHHA. The implications of this heightened TP vulnerability are greatest for less-than-lifetime exposure and this approach might be used to assess the level of cancer risk from exposures during pregnancy. A case example employing a mutagenic flame retardant was used to exemplify application of a TP ADAF for evaluating risks during pregnancy.

中文翻译：

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不同生命阶段致癌效力的比较：对评估经胎盘癌症风险的影响。

子宫内暴露导致癌症的发展已被记录为多种药物的结果，其中最常研究的化合物表现出诱变和基因毒性致癌特性。美国环境保护署在评估产后早期 (PN) 暴露引起的癌症风险时，对许多此类致癌物应用了年龄依赖性调整因子 (ADAF)；然而，这种方法尚未被广泛考虑用于经胎盘（TP）暴露。为了探讨这个问题并进一步评估产前易感性，对加州环境健康危害评估办公室 (OEHHA) 开发的早期动物研究数据库进行了评估，并通过额外的文献检索进行了增强。九种遗传毒性致癌物和一种混合物（香烟烟雾）可通过仅 TP、仅 PN 和仅成人协议获得数据。这些生命阶段的效力比较显示，与仅成人暴露相比，男性肝脏和大脑的效力同样更高。对于其他目标（例如女性肝脏和血源性肿瘤），TP 和 PN 暴露与仅限成人没有显着差异。TP 和 PN 目标以及致癌作用效力的相似性表明，10 倍 ADAF 可以应用于 TP 暴露，就像目前应用于 PN 暴露一样。OEHHA 也得出了类似的结论。这种TP脆弱性的提高对于非终生接触的影响最大，这种方法可用于评估怀孕期间接触所导致的癌症风险水平。以使用诱变阻燃剂的案例来举例说明 TP ADAF 在评估怀孕期间风险的应用。