Summary: Researchers have detected biomarkers for the common fungicide azoxystrobin (AZ) in the urine of pregnant women and children between the ages of 40-84 months. In mouse models, AZ entered the brains of mice in-utero and killed some embryonic cortical neurons.

Source: UNC-Chapel Hill

For the first time, UNC-Chapel Hill researchers have measured the concentration of a biomarker of the commonly used fungicide azoxystrobin (AZ) in the urine of pregnant women and children ranging from 40–84 months of age. They also documented maternal transfer of AZ to mouse embryos and weaning-age mice.

The researchers’ experimental data, published in the journal Environmental Health Perspectives, also found that AZ entered the brain of mice in utero at concentrations that modeled environmentally relevant exposures. Using similar concentrations, the researchers then found that AZ killed some embryonic cortical neurons in cultures.

“The most concerning aspect of our research is that this fungicide is now widely being used in certain brands of mold-resistant wallboards,” said senior author Mark Zylka, Ph.D., director of the UNC Neuroscience Center.

“Our study shows that pregnant women and children are exposed to azoxystrobin at much higher levels than expected from food sources alone.”

Zylka, who is the W.R. Kenan Distinguished Professor of Cell Biology and Physiology at the UNC School of Medicine, began studying the effects of this fungicide on brain cells several years ago when he and colleagues found that members of this fungicide class caused gene expression changes that are indicative of brain inflammation, a process seen in individuals with autism and age-related cognitive conditions.

These chemicals stimulate free radical production and disrupt microtubules—parts of neurons important for cell division, the transport of chemicals between cells, and the maintenance of cell shape.

The agricultural industry began using AZ and related strobilurin-class fungicides in the mid-1990s, and usage has increased exponentially to 1,000 tons applied to vegetable, nut, potato, fruit and grapevine crops in the United States, as well as to cereals and turf grass.

AZ has been found in large amounts in surface water due to agricultural runoff. It is known to be harmful to aquatic life and invertebrates.

Later, AZ was added to specific brands of mold and mildew-resistant wallboards, now commonly used in residential and commercial construction.

In the past decade, several experimental studies found AZ has the potential to cause developmental toxicity and neurotoxicity. In cortical neuron cultures prepared from embryonic mice, AZ induced reactive oxygen species (free radicals) that can damage cells.

In zebrafish, AZ altered cell death-related gene expression in larvae and caused oxidative stress in larvae and in adults. Following parental AZ exposure in zebrafish, a significantly higher incidence of mortality and malformations was observed in offspring.

These studies suggested that AZ is toxic at embryonic stages, and as a result of these studies, scientists identified it as a major front-line target chemical for biomonitoring in the United States.

Yet, there isn’t much information about whether humans—especially young children and pregnant mothers—are exposed to detrimental amounts of AZ, or whether the fungicide can be transferred from mother to embryos, and if so, what are the health ramifications.

Zylka’s lab conducted experiments, led by first author Wenxin Hu, Ph.D., a UNC-Chapel Hill postdoctoral researcher, to measure the concentration of a biomarker of AZ exposure (AZ-acid) in the urine of pregnant women and in a separate group of children ranging from 40 to 84 months old.

These chemicals stimulate free radical production and disrupt microtubules—parts of neurons important for cell division, the transport of chemicals between cells, and the maintenance of cell shape. Image is in the public domain

AZ-acid was present 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 0.07 ng/mL (nanograms per milliliter) and max concentration of 2.70 and 6.32 ng/mL, respectively.

Experiments further revealed that AZ crossed the placenta and entered the developing brain of mouse embryos, and AZ transferred to offspring during lactation.

“Azoxystrobin has been detected in house dust, with some samples showing high concentrations,” Zylka said. “Our current research shows that azoxystrobin is being metabolized by humans, which means humans are ingesting it. Some of the children had persistently high levels of the metabolite, suggesting they are chronically exposed to azoxystrobin.

“This fungicide is on track to become as prevalent in the home as other chemicals like pyrethroids, plasticizers, and flame retardants. We urge the scientific community to ramp up efforts and determine if chronic exposure to azoxystrobin affects humans during fetal development and after birth.”

About this neurodevelopment and environmental neuroscience research news

Author: Press Office
Source: UNC-Chapel Hill
Contact: Press Office – UNC-Chapel Hill
Image: The image is in the public domain

Original Research: Open access.
“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” by Wenxin Hu et al. Environmental Health Perspectives


Abstract

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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

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 (0.01 ng/mL0.01 ng/mL) 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 0.07 ng/mL0.07 ng/mL, and maximal concentration of 2.70 and 6.32 ng/mL6.32 ng/mL, 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



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