patient reviews on hydroxyzine 1,000, and 10,000 nM. (A) Percentage of dead cells based on SYTOX green labeling and (B) NeuN positive cells after treatment (for 7 d) with azoxystrobin or azoxystrobin-acid (vehicle-subtracted; the percentage of cell death in vehicle control group was 7.3%). (C, D) NeuN staining of mouse cortical neuron cultures treated with DMSO or 1,000 nM azoxystrobin. Values are means±SEM (n=4). Data can be found in “Results” section. *(p<0.05), **(p<0.01) indicate values significantly different from vehicle-treated controls. Analysis of variance followed by post hoc Dunnett’s test was performed to determine the statistical significance of the results. Note: SEM, standard error of the mean. Credit: <i>Environmental Health Perspectives</i> (2022). DOI: 10.1289/EHP9808″ width=”500″ height=”422″>
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. 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.
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