埃尔夫队列中的法国儿童产前接触毒死蜱的情况

IF 4.5 2区医学 Q1 INFECTIOUS DISEASES

International journal of hygiene and environmental health Pub Date : 2024-10-18 DOI:10.1016/j.ijheh.2024.114480

Elisa Thépaut , Cleo Tebby , Michèle Bisson , Céline Brochot , Aude Ratier , Cécile Zaros , Stéphane Personne , Karen Chardon , Florence Zeman

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引用次数: 0

摘要

背景有机磷农药毒死蜱在2020年被禁用之前曾在欧盟广泛使用，并与神经发育障碍有关。本研究的目的是利用在Elfe孕妇中测量的生物监测数据和基于生理学的药代动力学（PBPK）方法估算胎儿对毒死蜱的暴露量，并将暴露量与毒理学参考值进行比较。方法基于现有的毒死蜱成人模型开发了妊娠-PBPK 模型，并针对神经发育影响提出了新的毒理学参考值。假设孕妇持续接触毒死蜱，根据尿液中的二烷基磷酸酯（DAP）水平估算孕妇的接触量，并与现有毒理学参考值和新提出的毒理学参考值草案进行比较。然后，利用所开发的妊娠-生化过程模型预测胎儿体内靶组织中的浓度。此外，还对毒死蜱特异性代谢物（TCPy）的尿液浓度进行了预测，以便与其他生物监测数据进行比较。毒死蜱特异性代谢物 TCPy 的预测尿排泄量与在其他欧洲队列中观察到的排泄量范围相同（平均值：2.13 μg/L）。孕妇及其胎儿脑中毒死蜱的预测水平相似，是血液中毒死蜱预测水平的 10 倍。据估计，分别有 6% 和 20% 的孕妇暴露于超过一般人群参考值和毒理学参考值草案的水平。预测了妊娠末期胎儿目标组织（大脑和血液）中毒死蜱的体内浓度。根据一项保守的假设，一小部分人口被确定接触了超过毒理学参考值的毒死蜱。

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Prenatal exposure to chlorpyrifos of French children from the Elfe cohort

Background

The organophosphate pesticide chlorpyrifos was widely used in the European Union before its ban in 2020 and was associated with neurodevelopmental disorders. However, within the concept of Developmental Origins of Health and Disease, in utero exposure to chlorpyrifos can lead to neurodevelopmental effects in developing children.

Objective

The aim of this study was to estimate fetal exposure to chlorpyrifos using biomonitoring data measured in Elfe pregnant women and a physiologically based pharmacokinetic (PBPK) approach and compare exposure to toxicological reference values.

Methods

A pregnancy-PBPK model was developed based on an existing adult chlorpyrifos model and a new toxicological reference value was proposed for neurodevelopmental effects. The pregnant women exposure was estimated based on dialkylphosphate (DAP) levels in urine assuming constant exposure to chlorpyrifos and compared to both the existing toxicological reference value and the new proposed draft toxicological reference value. Fetal internal concentrations in target tissues were then predicted using the developed pregnancy-PBPK model. Urinary concentrations of the chlorpyrifos-specific metabolite (TCPy) were also predicted for comparison with other biomonitoring data.

Results

The median daily exposure to chlorpyrifos for the French pregnant women from the Elfe cohort was estimated at 6.3x10⁻⁴ μg/kg body weight/day. The predicted urinary excretion of TCPy, the chlorpyrifos-specific metabolite, is in the same range as observed in other European cohorts (mean: 2.13 μg/L). Predicted brain chlorpyrifos levels were similar in pregnant women and their fetus and were 10-fold higher than the predicted blood chlorpyrifos levels. It was estimated that 6% and 20% of the pregnant women population had been exposed to levels exceeding the general population and draft toxicological reference values, respectively.

Conclusions

Prenatal exposure to chlorpyrifos was estimated for the French population based on data from the Elfe cohort. Internal chlorpyrifos concentrations in target tissues (brain and blood) were predicted for fetuses at the end of the pregnancy. Under a conservative assumption, a small percentage of the population was identified as being exposed to levels exceeding the toxicological reference values.

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来源期刊

International journal of hygiene and environmental health 医学-传染病学

CiteScore

11.50

自引率

5.00%

发文量

151

审稿时长

22 days

期刊介绍： The International Journal of Hygiene and Environmental Health serves as a multidisciplinary forum for original reports on exposure assessment and the reactions to and consequences of human exposure to the biological, chemical, and physical environment. Research reports, short communications, reviews, scientific comments, technical notes, and editorials will be peer-reviewed before acceptance for publication. Priority will be given to articles on epidemiological aspects of environmental toxicology, health risk assessments, susceptible (sub) populations, sanitation and clean water, human biomonitoring, environmental medicine, and public health aspects of exposure-related outcomes.