Oxidative stress of glyphosate, AMPA and metabolites of pyrethroids and chlorpyrifos pesticides among primary school children in Cyprus

Abstract

Background: Exposure to various pesticides, such as pyrethroids and chlorpyrifos, has been previously associated with adverse effects on children's health. Scientific evidence on the human toxicity of glyphosate (GLY) and its primary metabolite, aminomethylphosphonic acid (AMPA) is limited, particularly for children. This study aimed to i) assess the exposure determinants of the studied pesticides measured in children in Cyprus, and ii) determine the association between the urinary pesticides and the biomarkers of DNA and lipid oxidative damage.

Methods: A children's health study was set up in Cyprus (ORGANIKO study) by aligning it with the methodology and tools used in the European Human Biomonitoring Initiative (HBM4EU). Urinary GLY and AMPA, pyrethroid metabolites and the chlorpyrifos metabolite TCPy were measured in 177 children aged 10-11 years old, using mass spectrometry. Oxidative stress was assessed with 8-iso-prostaglandin F2a (8-iso-PGF2α) as a marker of lipid damage and 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a DNA oxidative damage marker, both measured with immunoassays. Questionnaires about demographic characteristics, pesticide usage, and dietary habits were filled out by the parents. Μultivariable regression models examined associations between pesticides and biomarkers of effect using two creatinine adjustments (cr1: adding it as covariate and cr2: biomarkers of exposure and effect were creatinine-adjusted).

Results: Parental educational level was a significant predictor of urinary pyrethroids but not for GLY/AMPA. Median [interquartile range, IQR] values for GLY and AMPA were <LOQ [<LOQ, 0.19] μg/L and 0.18 [0.10, 0.29] μg/L, respectively, while a moderate correlation was shown between GLY and AMPA (r = 0.45). 8-OHdG was positively associated with AMPA (beta = 0.17; 95% CI: 0.02, 0.31, p = 0.03 cr2, and beta = 0.12; 95% CI: 0.0,0.24, p = 0.06, cr1), albeit not with GLY (p > 0.05). Similar significant associations with 8-OHdG were shown for a pyrethroid metabolite (3-PBA) and the chlorpyrifos metabolite (TCPy). No associations were observed between the aforementioned pesticides and 8-iso-PGF2α (p > 0.05).

Conclusions: This is the first children's health dataset demonstrating the association between AMPA and DNA oxidative damage, globally. More data is needed to replicate the observed trends in other children's populations around the globe.

Keywords: AMPA; Children; Glyphosate; Human biomonitoring; Oxidative stress; Pesticides.