The discovery of a common fungicide in pregnant women and children

summary: Researchers have detected biomarkers of the common fungicide azoxystrobin (AZ) in the urine of pregnant women and children aged 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 measured the biomarker concentration of the commonly used fungicide azoxystrobin (AZ) in the urine of pregnant women and children aged 40-84 months. They also documented the transfer of mothers from A to Z to the embryos of mice and mice at the age of weaning.

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

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

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

Zylka, a WR Kenan Distinguished Professor of Cell Biology and Physiology at 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 class of fungicides caused changes in gene expression. Denotes encephalitis, a process seen in individuals with autism and age-related cognitive conditions.

These chemicals stimulate the production of free radicals and disrupt microtubules — parts of nerve cells important for cell division, transporting chemicals between cells, and maintaining cell shape.

The agricultural industry began using A-Z and related strobilorin-class fungicides in the mid-1990s, and use increased dramatically to 1,000 tons applied to US vegetable, nut, potato, fruit and grape crops, as well as grains and herbs. grass.

AZ is found in large quantities in surface waters 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 wall panels, which are now commonly used in residential and commercial construction.

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

In zebrafish, AZ altered gene expression associated with cell death in larvae and induced oxidative stress in larvae and adults. After parental AZ exposure in zebrafish, a markedly higher rate of mortality and malformations was observed in the offspring.

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

However, there is not much information about whether humans – especially young children and expectant mothers – are exposed to harmful amounts of AZ, or whether the fungicide can be transferred from mother to fetus, and if so, what the health implications are.

Zylka’s lab conducted experiments, led by first author Wenxin Hu, PhD, and a UNC-Chapel Hill postdoctoral researcher, to measure the concentration of a biomarker for exposure to AZ (AZ-acid) in the urine of pregnant women and separately. A group of children aged 40 to 84 months.

This shows a pregnant woman
These chemicals stimulate the production of free radicals and disrupt microtubules — parts of nerve cells important for cell division, transporting chemicals between cells, and maintaining cell shape. The image is in the public domain

AZ-acid was present in 100% of urine samples from pregnant women and in 70% of urine samples from children, with mean concentrations of 0.10 and 0.07 ng/mL (ng/mL) and maximum concentrations of 2.70 and 6.32 ng/mL, respectively.

The experiments further revealed that AZ crossed the placenta and entered the developing brain of rat fetuses, and AZ was transmitted to the offspring during lactation.

“Azoxystrobin has been detected in house dust, and some samples show high concentrations,” Zylka said. “Our current research shows that azoxystrobin is metabolized by humans, which means that humans eat it. Some of the children had persistently high levels of the metabolite, indicating that they were chronically exposed to azoxystrobin.

“This fungicide is on the way to becoming as widespread in the home as other chemicals such as pyrethroids, plasticizers and flame retardants. We urge the scientific community to intensify efforts and determine whether 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
picture: The image is in the public domain

original search: open access.
Detection of Azoxystrobin Fungicide and Azoxystrobin-Acid Metabolite in Pregnant Women and Children, Estimation of Daily Intake, Evaluation of Placental Transmission and Lactation in MiceWritten by Wenxin Hu et al. Environmental Health Perspectives


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

background:

Azoxystrobin (AZ) is a broad-spectrum stropilorene fungicide used in agriculture and has recently been added to mold and mildew resistant wall panels. AZ has been found to have toxic effects on animals in the embryonic stages and has been listed as a major target for vital monitoring in children.

Goals:

This study examined exposure to AZ in pregnant women and young children, whether AZ could be transferred from the exposed mother to the offspring, and whether AZ or one of its primary metabolites, AZ-acid, was neurotoxic. in the laboratory.

Techniques:

We quantitatively quantified AZ acid, a sensitive indicator of A-Z exposure, in urine samples collected from 8 pregnant women (12 urine samples) and 67 children (40–84 months; 96 urine samples) using high-resolution mass spectrometry. Pregnancy transfer and lactation were evaluated in C57Bl/6 mice. The neurotoxicity of AZ and AZ-acid . was investigated in the laboratory with mouse cortical neuron cultures.

consequences:

AZ-acid was present above the quantification limit (0.01 ng/mL 0.01 ng/mL) in 100% of urine samples from pregnant women and in 70% of urine samples from children, with mean concentrations of 0.10 and 0.07 ng/mL 0.07 ng/mL. ml, and maximum concentrations of 2.70 and 6.32 ng/ml 6.32 ng/ml, respectively. Studies in mice revealed that AZ passed from mother to offspring during pregnancy by crossing the placenta and entering the developing brain. AZ was also passed on to the offspring by lactation. High levels of cytotoxicity have been observed in mouse fetal cortical neurons at concentrations representing environmentally relevant exposures.

Debate:

Our study suggested that pregnant women and children were exposed to AZ, and at least 10% of children (2 of 20 assessed at 2 years of age) showed evidence of chronic exposure. Future studies are warranted to assess whether chronic A to Z exposure affects human health and development. https://doi.org/10.1289/EHP9808