Yeast and worms may be small, but they have the potential to transform the way we evaluate chemicals in the United States.
A big challenge in preventing harmful chemical exposures is how long it takes to identify whether a chemical is toxic to human health. Fortunately, yeast and worms – high throughput (HTP) in vivo assays – allow us to predict human reproductive toxicity at a faster pace than ever before. They have also led to us uncovering an important class of chemicals that we should paying closer attention to – quaternary ammonium compounds, or QACs (pronounced “quocks”) – which are used in heavy duty cleaning products.
What we found
We used two HTP screening assays in yeast and worms to evaluate a host of chemicals for reproductive toxicity in our recent study published today in Reproductive Toxicology. We compared potencies of different chemicals between the two assays and found that several disinfectants called QACs were identified as highly potent reproductive toxicants in both assays (Figure 1), indicating these chemicals should be prioritized for evaluation in human health risk assessments and regulation.
We also evaluated how well the assays correlated with each other (Figure 2) and with the in vivo mammalian data in the public database of animal studies called ToxRefDB (Figure 3), and found moderate to good correlation across the three data sets, support for using these HTP assays in predicting mammalian reproductive toxicity (which is a good indicator they will be useful for predicting human reproductive toxicity). The assays were even more predictive of animal data from ToxRefDB than they were of each other, indicating they are more effective (i.e., more predictive of human toxicity) when used together than they are individually. In other words, they become even more powerful in terms of their ability to predict human reproductive toxicity when used in combination. Adding even more assays to the mix (i.e., using a machine learning algorithm) is likely to further improve their collective predictive value.
Why it’s important
Currently, most of the tens of thousands of chemicals in U.S. commerce lack adequate toxicity data, so more efficient and effective methods for uncovering reproductive harm are vital. Furthermore, infertility is a growing problem in the U.S. and around the world, and the ability to get pregnant and have a baby has a lot to do with germ cell development and function, which is what the assays test. This is an important factor that could be contributing to population declines observed in many countries. Pregnancy loss and birth defects can also often be traced back to problems with germ cell function. However, until now we haven’t been able to adequately study the role of environmental chemicals on germ cell development, since traditional experimental models (i.e., using animals) are more time consuming and expensive.
Thus, development and use of rapid screens can transform the way we evaluate reproductive toxicants. Additionally, advancing the use of the HTP assays, which can also be considered new approach methodologies (NAMs), will support the Environmental Protection Agency’s effort to integrate NAMs into current human health decision-making and chemical safety assessments. And that should lead to better regulatory decisions to protect health.
Julia R. Varshavsky, Juleen Lam, Courtney Cooper, Patrick Allard, Jennifer Fung, Ashwini Oke, Ravinder Kumar, Joshua F. Robinson, Tracey J. Woodruff, Analyzing high-throughput assay data to advance the rapid screening of environmental chemicals for human reproductive toxicity, Reproductive Toxicology, 2024, 108725, ISSN 0890-6238, https://doi.org/10.1016/j.reprotox.2024.108725.
About the author
Julia Varshavsky, PhD, MPH, is Assistant Professor, Department of Public Health and Health Sciences, Department of Environmental Engineering, at Northeastern University and a reproductive and developmental environmental epidemiologist interested in mechanisms of effect and key exposure windows to better understand how exposures lead to adverse outcomes.
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