Department of Environmental Health, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Int J Hyg Environ Health. 2023 Jun;251:114188. doi: 10.1016/j.ijheh.2023.114188. Epub 2023 May 23.
Neonicotinoid insecticides (NEOs) are emerging synthetic insecticides used in various pest management regimens worldwide. Toxicology studies have indicated the obesogenic potential of NEOs, but their associations with adiposity measures are largely unknown.
We aimed to assess urinary levels of NEOs/metabolites and their associations with children's adiposity measures, and to further investigate the potential role of oxidative stress.
This study included 380 children who participated in the 7th year's follow-up of the Laizhou Wan Birth Cohort in northern China. Urinary levels of seven NEOs and two metabolites and a biomarker of lipid peroxidation named 8-iso-prostaglandin-F2α (8-iso-PGF2α) were detected. A total of nine indicators of adiposity were measured. Body mass index (BMI) z-score ≥85th percentile was defined as overweight/obesity, and waist-to-height ratio (WHtR) ≥0.5 was considered as abdominal obesity. Multiple linear regression, binary logistic regression and mediation analysis were performed.
Six NEOs [imidacloprid (IMI, 99.7%), clothianidin (CLO, 98.9%), dinotefuran (DIN, 97.6%), thiamethoxam (THM, 95.5%), acetamiprid (ACE, 82.9%), thiacloprid (THD, 77.6%)] and two metabolites [N-desmethyl-acetamiprid (N-DMA, 100.0%), 6-chloronicotinic acid (6-CINA, 97.9%)] exhibited high detection rates. Multiple linear regressions showed positive associations of waist circumference with urinary levels of IMI and THM, of WHtR with IMI and THM levels, and of body fat percentage with 6-CINA levels. In contrast, exposure to N-DMA was negatively associated with body fat percentage and fat mass index. Binary logistic regressions further revealed that higher IMI levels were associated with overweight/obesity (OR = 1.556, 95% CI: 1.100, 2.201) and abdominal obesity (OR = 1.478, 95% CI: 1.078, 2.026) in children. 8-iso-PGF2α demonstrated 27.92%, 69.52% and 35.37% mediating effects in the positive associations of IMI, THD and THM with WHtR, respectively. Sex modified the associations of DIN with body fat mass (p = 0.032), body fat percentage (p = 0.009), fat mass index (p = 0.037) and the overweight/obesity rate (p = 0.046), with negative associations in girls and nonsignificant positive associations in boys.
School-age children in northern China were widely exposed to NEOs/metabolites. Urinary levels of NEOs/metabolites were associated with adiposity measures through the mediating role of 8-iso-PGF2α. These associations were mixed, and a sex-specific effect might exist.
新烟碱类杀虫剂（NEOs）是一种新兴的合成杀虫剂，在全球范围内用于各种害虫管理方案。毒理学研究表明 NEOs 具有致肥胖的潜力，但它们与肥胖指标的关系在很大程度上尚不清楚。
我们旨在评估新烟碱类杀虫剂/代谢物的尿液水平及其与儿童肥胖指标的相关性，并进一步研究氧化应激的潜在作用。
本研究纳入了 380 名参加中国北方莱州湾出生队列研究第 7 年随访的儿童。检测了七种新烟碱类杀虫剂和两种代谢物以及一种脂质过氧化生物标志物 8-异前列腺素 F2α（8-iso-PGF2α）的尿液水平。共测量了九个肥胖指标。BMI 得分≥第 85 百分位数定义为超重/肥胖，腰围与身高比（WHtR）≥0.5 定义为腹部肥胖。采用多元线性回归、二分类逻辑回归和中介分析进行分析。
六种新烟碱类杀虫剂[吡虫啉（IMI，99.7%）、噻虫嗪（CLO，98.9%）、噻虫胺（DIN，97.6%）、噻虫啉（THM，95.5%）、乙酰甲胺磷（ACE，82.9%）、噻虫嗪（THD，77.6%）]和两种代谢物[N-去甲基乙酰甲胺磷（N-DMA，100.0%）、6-氯烟碱酸（6-CINA，97.9%）]的检出率较高。多元线性回归显示，腰围与 IMI 和 THM 尿液水平呈正相关，WHtR 与 IMI 和 THM 水平呈正相关，体脂百分比与 6-CINA 水平呈正相关。相比之下，N-DMA 的暴露与体脂百分比和脂肪质量指数呈负相关。二分类逻辑回归进一步显示，较高的 IMI 水平与儿童超重/肥胖（OR=1.556，95%CI：1.100，2.201）和腹部肥胖（OR=1.478，95%CI：1.078，2.026）有关。8-iso-PGF2α 分别在 IMI、THD 和 THM 与 WHtR 的正相关关系中表现出 27.92%、69.52%和 35.37%的中介作用。性别修饰了 DIN 与体脂肪量（p=0.032）、体脂肪百分比（p=0.009）、脂肪质量指数（p=0.037）和超重/肥胖率（p=0.046）的相关性，在女孩中呈负相关，在男孩中呈无显著意义的正相关。
中国北方的学龄儿童广泛接触新烟碱类杀虫剂/代谢物。新烟碱类杀虫剂/代谢物的尿液水平通过 8-iso-PGF2α 的中介作用与肥胖指标相关。这些关联是混杂的，可能存在性别特异性效应。
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