In utero exposure to atrazine analytes and early menarche in the Avon Longitudinal Study of Parents and Children Cohort

Abstract

Background Evidence from experimental studies suggests that atrazine and its analytes alter the timing of puberty in laboratory animals. Such associations have not been investigated in humans. Objective To determine the association between in utero exposure to atrazine analytes and earlier menarche attainment in a nested case-control study of the population-based Avon Longitudinal Study of Parents and Children. Methods Cases were girls who reported menarche before 11.5 years while controls were girls who reported menarche at or after 11.5 years. Seven atrazine analyte concentrations were measured in maternal gestational urine samples (sample gestation week median (IQR): 12 (8–17)) during the period 1991–1992, for 174 cases and 195 controls using high performance liquid chromatography-tandem mass spectrometry. We evaluated the study association using multivariate logistic regression, adjusting for potential confounders. We used multiple imputation to impute missing confounder data for 29% of the study participants. Results Diaminochlorotriazine (DACT) was the most frequently detected analyte (58% > limit of detection [LOD]) followed by desethyl atrazine (6%), desethyl atrazine mercapturate (3%), atrazine mercapturate (1%), hydroxyl atrazine (1%), atrazine (1%) and desisopropyl atrazine (0.5%). Because of low detection of other analytes, only DACT was included in the exposure–outcome analyses. The adjusted odds of early menarche for girls with DACT exposures≥median was 1.13 (95% Confidence Interval [95% CI]:0.82, 1.55) and exposure < median was 1.01 (95% CI: 0.73, 1.42) compared to girls with exposure < LOD (reference). In the subset that excluded girls with missing data, the adjusted odds of early menarche for girls with DACT exposures≥median was 1.86 (95% CI: 1.03, 3.38) and exposure < median was 1.26 (95% CI: 0.65, 2.24) compared to the reference. Conclusions This study is the first to examine the association between timing of menarche and atrazine analytes. We found a weak, non-significant association between in-utero exposure to atrazine metabolite DACT and early menarche, though the association was significant in the subset of girls with complete confounder information. Further exploration of the role of these exposures in female reproduction in other cohorts is needed.

In utero Exposure to Atrazine Disrupts Rat Fetal Testis Development

“…A previous study has shown that the median level of a major ATR metabolite diaminochlorotriazine in human urine samples was 0.32 ng/mL (0.16–0.45 ng/mL) ( Namulanda et al, 2017 ), which is far lower than doses used in the current study (25–100 mg/kg). However, most toxicological studies adopted 1–100 mg/kg ATR dose range ( Babic-Gojmerac et al, 1989 ; Friedmann, 2002 ; Stoker et al, 2002 ).…”

A Systematic Literature Review of Factors Affecting the Timing of Menarche: The Potential for Climate Change to Impact Women’s Health

“…Another study investigating the effects of breast cancer incidence and atomic bomb survivors in Japan and its relationship to timing of menarche found that the breast cancer incidence due to radiation was high regardless of the stage of the breast's differentiation, indicating that radiation exposure itself maybe a breast carcinogen [58]. Exposure to endocrine-disrupting chemicals [59] and hair products [59], and in utero exposure to atrazine [60] were all associated with early menarche ( Figure 3A). On the other hand, in utero exposure to organochlorine did not appear to alter the timing of menarche [61].…”

Reproductive Health Risks Associated with Occupational and Environmental Exposure to Pesticides

“…A nested case-control study found a weak, non-significant association of in utero exposure with the atrazine metabolite diaminochlorotriazine (DACT), measured in gestational maternal urine specimens (median = 12 weeks), and with early menarche [48]. The study was conducted within a larger prospective cohort, in which the offspring of 14,775 women were mailed an annual health questionnaire from 8 to 17 years of age.…”