Association between exposure to 15 herbicides and prehypertension: A cross-sectional study based on dose-response relationship and mixed exposure analysis

Background: Prehypertension precedes hypertension and cardiovascular diseases and imposes heavy global public health burden. Herbicides are widely used agricultural pesticides; Rural Chinese residents suffer high exposure through occupational and dietary pathways. Limited evidence exists among Asian rural populations regarding single and mixed herbicide exposure linked to prehypertension, including dose-response trends and mixture interaction effects.

Objective: This study aimed to comprehensively evaluate associations between 15 common herbicides and prehypertension, encompassing single-herbicide effects, dose-response relationships, combined mixture effects, and relative contributions of individual herbicides within the mixture
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Methods: A cross-sectional survey recruited 4,550 rural residents aged 1879 in Henan Province. GC-MS/MS detected serum concentrations of 15 herbicides. Multivariate logistic regression analyzed single pollutant correlations, Restricted Cubic Spline (RCS) models fitted dose-response curves. Quantile g-computation (Qg) and BKMR assessed overall mixture effects, while XGBoost combined with SHAP analysis quantified each herbicides independent risk contribution.

Results: After adjusting for 12 covariates, 10 of 15 herbicides were significantly and positively associated with prehypertension (ORs: 1.0611.156, all P<0.05), with prometryn showing the strongest association (OR=1.156, 95%CI: 1.0191.311). RCS models identified significant linear dose-response relationships for 4 herbicides (acetochlor, ametryn, atrazine, and benoxacor). Both Qg and BKMR confirmed a significant positive overall mixed exposure effect, with oxyfluorfen as the dominant contributor, followed by butachlor, trifluralin, oxadiazon, and cyanazine. SHAP analysis corroborated these findings, identifying oxyfluorfen (mean|SHAP|=0.076), trifluralin (0.075), and fluazifop-butyl (0.071) as the top three herbicide contributors, all with positive SHAP values consistent with Qg and BKMR results.

Conclusions: Both single and mixed herbicide exposures are significantly associated with elevated prehypertension risk in rural Chinese adults. Convergent evidence from multiple analytical approaches consistently identifies oxyfluorfen, trifluralin, and fluazifop-butyl as key contributing herbicides, providing a scientific foundation for environmental health risk assessment and targeted prevention of prehypertension in rural Asian populations.

Keywords: Herbicide Exposure, Prehypertension, Dose-Response Relationship, Mixed Exposure Analysis, Machine Learning.

Fangyuan Lin is a master’s student at Zhengzhou University, China. Her research focuses on environmental health and chronic metabolic diseases, primarily hypertension and high-normal blood pressure. She is currently participating in a prospective cohort study of rural populations in Henan within her research group and is familiar with using Gas Chromatography-Tandem Mass Spectrometry (GC-MS/MS).