Detection of the fungicide transformation product 4-hydroxychlorothalonil in serum of pregnant women from Sweden and Costa Rica

Abstract

Background 4-hydroxychlorothalonil (HCT, R182281), a transformation product of the fungicide chlorothalonil, was recently identified in human serum and breast milk. There are indications that HCT may be more toxic and environmentally persistent than chlorothalonil. Objective Our aim was to investigate serum concentrations of HCT in pregnant women in Sweden and Costa Rica. Methods We developed a quantitative analytical method for HCT using liquid chromatography tandem mass spectrometry. We measured HCT in 1808 serum samples from pregnant women from the general population in Sweden (1997–2015) and in 632 samples from 393 pregnant women from an agricultural population in Costa Rica (2010–2011). In Swedish samples, we assessed time trends and investigated seasonality. In the Costa Rican samples, we evaluated variability between and within women and explanatory variables of HCT concentrations. Results HCT was detected in all serum samples, and the limit of detection was 0.1 µg/L. The median HCT concentration in the Swedish samples was 4.1 µg/L (interquartile range [IQR] of 2.9 − 5.8 µg/L), and 3.9 times higher in the Costa Rican samples (median: 16.1 µg/L; IQR: 10.6 − 25.0 µg/L). We found clear seasonal variation with higher concentrations in the first half of each year among Swedish women. In the Costa Rican study, women working in agriculture and living near banana plantations had higher HCT concentrations, whilst higher parity and having a partner working in agriculture were associated with decreased HCT, and no clear seasonal pattern was observed. Impact statement For the first time, this study quantifies human exposure to the fungicide chlorothalonil and/or its transformation product 4-hydroxychlorothalonil (HCT, R182281) and finds higher serum concentrations in women from a tropical agricultural setting as compared with women from the general population in Sweden.

Longitudinal Exposomics in a Multiomic Wellness Cohort Reveals Distinctive and Dynamic Environmental Chemical Mixtures in Blood

“…Chlorothalonil-4-hydroxy was confirmed and semi-quantified in 100% of plasma samples (1.1-11.5 ng/mL, median 3.7 ng/mL; Table 1, Figure S9 ). This finding is consistent with a targeted study of pregnant Swedish women (1997–2015) where it was also detected in all samples (median 4.1 ng/mL),(44) yet it remains rarely monitored in humans. It is a known transformation product of the fungicide chlorothalonil, which has not been permitted for agricultural use in Sweden since the 1990s,(45) and has been banned in the EU since 2019 due to its carcinogenic properties and risk to fish and amphibians.…”

“…Another example was the fungicide transformation product, chlorothalonil-4-hydroxy (ICC 0.80, 100% DF; here confirmed at Level 1). The half-life of chlorothalonil-4-hydroxy in humans has not yet been determined, but the high ICC reported here and in a previous study of Costa Rican women (ICC 0.81)(44) emphasizes the importance of further studies for this environmentally persistent chemical. Other Type 2 substances nevertheless included analytes with reported fast elimination half-lives in the range of days or hours.…”