8292450 Associations of biomarkers of pesticide exposure with telomere length and mtDNA copy number in 5-year old children from agricultural families in Costa Rica, results from the ISA birth cohort

<h3>Objective</h3> Children from agricultural families are often para-occupationally exposed to pesticides. We associated urinary biomarkers of pesticide exposure with relative telomere length (rTL) and mtDNA copy number (mtDNA-cn) in 270 5-year-old children from agricultural families who participated in the Infants’ Environmental (ISA) birth cohort. <h3>Methods</h3> We repeatedly measured biomarkers of pesticide exposure in maternal urine during pregnancy and in children’s urine at 5-years. rTL and mtDNA-cn were determined in children’s saliva, relative to a single-copy hemoglobin beta gene, using real-time PCR. We associated log10 transformed mean urinary biomarker concentrations with log10 transformed rTL and mtDNA-cn, using separate multivariate linear regression and generalized additive models, and adjusted for possible confounders. <h3>Results</h3> Exposure to fungicides and 2,4-D was associated with changes in rTL and mtDNA-cn. Higher prenatal hydroxy-thiabendazole was associated with shorter rTL, while current 2,4-D was associated with longer rTL:%-change-in-β (95%CI) = -0.19 (-0.36, -0.02) and = 0.38 (0.01, 0.75) per tenfold increase in exposure, respectively. In addition, prenatal hydroxy-pyrimethanil was slightly associated with mtDNA-cn: β =0.33 (-0.05, 0.70) and 2,4-D was non-linearly associated with mtDNA-cn (estimated degrees of freedom of smoothed beta = 2.78, p=0.04), while current urinary ethylene thiourea (biomarker of mancozeb) and hydroxy-tebuconazole were associated with decreased and increased mtDNA-cn:%-change-in-β (95%CI) = -0.84 (1.71, 0.05) and 0.71 (0.01, 1.40), respectively. Biomarkers of pyrethroid and chlorpyrifos exposure were not associated with rTL or mtDNA-cn. <h3>Conclusions</h3> Prenatal and childhood exposure to fungicides and 2,4-D may alter rTL and mtDNA-cn, which is of concern as shorter TL may reflect an increased risk of age-related diseases. Longer TL might reflect changes in cellular aging, including increased cellular mutation risks. Finally, increased mtDNA-cn indicates compensation for oxidative stress, while decreased levels reflect oxidative stress.