To support a mixture risk assessment with a focus on developmental neurotoxicity we evaluated the strength of evidence for associations of cadmium exposures with declines in IQ by conducting a systematic review and confidence rating. We searched peer-reviewed studies published in English between 2012 and July 2021 and identified 15 eligible studies (11 prospective cohort studies, and 4 cross-sectional studies). Of the 10 studies that observed associations of cadmium exposure with child IQ declines, two achieved an overall “High (H)” confidence rating, five a “Medium to High (M/H)”, one a “Medium (M)” and two a “Low (L)” confidence rating. Five studies did not detect significant associations between cadmium exposure and reduced cognitive ability; of these, two received a “High (H)” confidence rating, two an overall rating of “Medium to High (M/H)” and one a “Medium (M)” rating. The null findings reported by the “High (H)” and Medium to High (M/H)” studies could partly be explained by low exposures to cadmium or confounding with high levels of lead. By using a one-compartment toxicokinetic model in a reverse dosimetry approach, we estimated that a daily intake of 0.2 μg/kg body weight/day corresponds to urinary cadmium levels no longer associated with cognitive declines observed in a “High (H)”-confidence study. This estimate is 1.8-fold lower than the current health-based guidance value (HBGV) for kidney toxicity of 0.36 μg/kg bodyweight/day established by the European Food Safety Authority (EFSA). Our value does not have the normative character associated with health-based guidance values and is intended only as a reasonable estimate for the purpose of mixture risk assessments. However, with cadmium exposures in Europe between 0.28 (middle bound) and up to 0.52 μg/kg bodyweight/day (95th percentile), our review suggests that pregnant women and children are poorly protected against neurodevelopmental effects. This warrants a revision of the current HBGV.

中文翻译：

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镉暴露和认知能力恶化：基于系统评价和置信度评级的混合物风险评估参考剂量估计

为了支持以发育神经毒性为重点的混合风险评估，我们通过进行系统评价和置信度评级，评估了镉暴露与智商下降之间关联的证据强度。我们检索了 2012 年至 2021 年 7 月期间以英语发表的同行评审研究，并确定了 15 项符合条件的研究（11 项前瞻性队列研究和 4 项横断面研究）。在观察到镉暴露与儿童智商下降相关的 10 项研究中，两项获得总体“高 (H)”置信度评级，五项获得“中到高 (M/H)”，一项获得“中 (M)”和两个“低（L）”置信度。五项研究未发现镉暴露与认知能力降低之间存在显着关联；其中，两个获得了“高（H）”的信心评级，两个“中到高（M / H）”的整体评级和一个“中（M）”评级。“高 (H)”和“中到高 (M/H)”研究报告的无效结果可以部分解释为镉暴露量低或与高水平铅混杂。通过在反向剂量学方法中使用单室毒代动力学模型，我们估计每天摄入 0.2 μg/kg 体重/天对应的尿镉水平不再与在“高 (H)”-信心研究。这一估计值比欧洲食品安全局 (EFSA) 制定的当前基于健康的肾脏毒性指导值 (HBGV) 0.36 μg/kg 体重/天低 1.8 倍。我们的值不具有与基于健康的指导值相关的规范性特征，仅作为混合物风险评估的合理估计。然而，欧洲的镉暴露量在 0.28（中间界限）和高达 0.52 μg/kg 体重/天（第 95 个百分位）之间，我们的审查表明孕妇和儿童对神经发育影响的保护很差。这需要对当前的 HBGV 进行修订。