Detection of Azoxystrobin Fungicide and Metabolite Azoxystrobin-Acid in Pregnant Women and Children, Estimation of Daily Intake, and Evaluation of Placental and Lactational Transfer in Mice

Abstract

Background: Azoxystrobin (AZ) is a broad-spectrum strobilurin fungicide that is used in agriculture and was recently added to mold- and mildew-resistant wallboards. AZ was found to have toxic effects in animals at embryonic stages and was listed as a frontline target for biomonitoring in children. Objectives: This study investigated exposure to AZ in pregnant women and young children, whether AZ could be transferred from an exposed mother to offspring, and whether AZ or one of its primary metabolites, AZ-acid, was neurotoxic in vitro . Methods: We quantified AZ-acid, a sensitive indicator of AZ exposure, in urine samples collected from 8 pregnant women (12 urine samples) and 67 children (40–84 months old; 96 urine samples) with high-resolution mass spectrometry. Gestational and lactational transfer was assessed in C57Bl/6 mice. Neurotoxicity of AZ and AZ-acid was investigated in vitro with mouse cortical neuron cultures. Results: AZ-acid was present above the limit of quantification ( ) in 100% of the urine samples from pregnant women and in 70% of the urine samples from children, with median concentration of 0.10 and , and maximal concentration of 2.70 and , respectively. Studies in mice revealed that AZ transferred from the mother to offspring during gestation by crossing the placenta and entered the developing brain. AZ was also transferred to offspring via lactation. High levels of cytotoxicity were observed in embryonic mouse cortical neurons at concentrations that modeled environmentally relevant exposures. Discussion: Our study suggested that pregnant women and children were exposed to AZ, and at least 10% of the children (2 out of 20 that were evaluated at two ages) showed evidence of chronic exposure. Future studies are warranted to evaluate whether chronic AZ exposure affects human health and development. https://doi.org/10.1289/EHP9808

Precision environmental health monitoring by longitudinal exposome and multi-omics profiling

“…For example, Paenibacillus was positively correlated with the temperature, consistent with the literature that members of Paenibacillus are heat resistant and grow well in warmer temperatures ( Kaur et al 2018 ). Azoxystrobin, ethylparaben, and captan are fungicides or antifungal agents ( Rodrigues et al 2013 ; European Food Safety Authority [EFSA] et al 2020 ; Hu et al 2022 ) that negatively correlated with different fungi ( Fig. 2 F).…”

Azoxystrobin Disrupts Colonic Barrier Function in Mice via Metabolic Disorders Mediated by Gut Microbiota

“…In addition, the environmental concentrations of AZO had been reported as high as 34 μg/L in river water in Shanghai, China . In particular, a recent study found that AZO’s metabolite AZO-acid was detected in the urine of pregnant women and children in the United States . Over the past decade, the adverse effects of AZO on environmental organisms have received increasing attention. − AZO exposure could significantly reduce egg production and fertilization rate, resulting in sex-dependent reproductive toxicity in adult zebrafish (Danio rerio) .…”

Establishment of a Human Cell-Based in Vitro Battery to Assess Developmental Neurotoxicity Hazard of Chemicals

“…However, a large part of signaling systems is covered already by the recent development of neural network formation assays (Frank et al, 2017;Nimtz et al, 2020). An interesting endpoint to comprehensively capture neuronal differentiation is transcriptome profiling (Pallocca et al, 2016;Shinde et al, 2017;Simon et al, 2019;Dreser et al, 2020;Meisig et al, 2020;Hu et al, 2022). This was exemplified here by the UKN1 assay.…”