School of Environment, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou, China.
School of Environment, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou, China; Department of Environmental Science, Institute of Biomedical Studies, Baylor University, Waco, TX, USA.
Environ Int. 2019 Apr;125:9-24. doi: 10.1016/j.envint.2019.01.040. Epub 2019 Jan 26.
Neonicotinoid insecticides have become one of the most widely used insecticides over the past two decades. Recent studies have shown considerable risk of neonicotinoids to beneficial insects, however, their health risks to mammals are still under debate. Limited empirical mammalian toxicity information for neonicotinoids inherently presents challenges to environmental health practitioners performing health hazard and risk assessment. Therefore, we first compiled and examined publicly available hazard data for neonicotinoids, and knowledge gaps on mammals were identified. Probabilistic hazard assessment using chemical toxicity distributions (CTDs) was subsequently conducted, and initial thresholds of toxicological concern were derived for rat, dog, mouse, and rabbit under comparative experimental scenarios. Using the rat model, for example, oral 5% threshold concentrations (TC5s) of 0.11 (0.02, 0.36) and 0.23 (0.001, 3.2) mg/kg bw/day were estimated using chronic developmental and reproductive no observed adverse effect levels (NOAELs), respectively, while acute TC5 of 0.71 (0.25, 1.6) mg/kg bw/day was identified using neurological NOAELs. Comparatively, dermal and inhalational TC5s were estimated as 1583 (1172, 1777) and 451 (294, 615) mg/kg bw/day (equivalent to 486 (322, 622) mg/m), respectively, using acute median lethal doses. Uncertainty factors (UFs) were also estimated using both CTD comparisons and individual UF probability distribution approaches to test whether rodent oral toxicity information or default 10-fold UF approach can provide sufficient protection for mammals. These initially identified UFs were generally smaller than default values (e.g., 10) employed by regulatory stakeholders, yet larger UFs were occasionally noted. Our findings appear particularly useful for environmental health practitioners when conducting screening-level risk assessment for neonicotinoids, and provide an example for health hazard assessment of pesticides with limited toxicity information.
新烟碱类杀虫剂在过去二十年中已成为使用最广泛的杀虫剂之一。最近的研究表明，新烟碱类杀虫剂对有益昆虫存在相当大的风险，然而，它们对哺乳动物的健康风险仍存在争议。由于新烟碱类杀虫剂的有限的哺乳动物毒性信息，这给进行健康危害和风险评估的环境健康从业者带来了挑战。因此，我们首先编译并检查了新烟碱类杀虫剂的公开可用危害数据，并确定了哺乳动物的知识空白。随后，使用化学毒性分布（CTD）进行了概率危害评估，并在比较实验场景下为大鼠、狗、小鼠和兔推导了初步的毒理学关注阈值。例如，使用大鼠模型，分别使用慢性发育和生殖无观察到不良效应水平（NOAEL）的口服 5%阈值浓度（TC5）0.11（0.02，0.36）和 0.23（0.001，3.2）mg/kg bw/day 估算，而使用神经学 NOAEL 估算急性 TC5 为 0.71（0.25，1.6）mg/kg bw/day。相比之下，使用急性中值致死剂量估算经皮和吸入 TC5 分别为 1583（1172，1777）和 451（294，615）mg/kg bw/day（相当于 486（322，622）mg/m）。还使用 CTD 比较和个体 UF 概率分布方法估算了不确定性因素（UF），以测试啮齿动物口服毒性信息或默认的 10 倍 UF 方法是否可以为哺乳动物提供足够的保护。这些最初确定的 UF 通常小于监管利益相关者使用的默认值（例如 10），但偶尔也会注意到较大的 UF。当进行新烟碱类杀虫剂的筛选水平风险评估时，我们的研究结果似乎对环境健康从业者特别有用，并为具有有限毒性信息的农药的健康危害评估提供了一个示例。
