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On 13 August 2018 the U.S. Environmental Protection Agency (EPA) published a "Science Matters" article titled "EPA Scientists Develop New Methods to Evaluate Chemicals." The communication relays the efforts of EPA’s Endocrine Disruptor Screening Program (EDSP) towards innovative steroidgenesis assays that could screen potential endocrine disruptors faster.
The new assay has been coined with the name high-throughput H295R or HT-H295R assay. A thorough review is available in the peer reviewed journal Toxicological Sciences.
Screening for potential endocrine disruptors: Then and Now
Then: EPA-OECD's H295R assay
A steroidgenesis assay using human adrenocarcinoma (H295R) cells has been widely used as the predictor of endocrine disruption activities. The assay was developed as a part of a collaborative effort between the EPA and the Organisation for Economic Co-operation and Development (OECD).
Now: Groundbreaking screening for endocrine disruptors
EPA's EDSP sought to improve the assay and developed an HT-H295R assay as part of its ToxCast research for the Chemical Safety for Sustainability Research Program. The program is tasked with measuring 11 hormones, including progestagens, corticosteroids, androgens, and estrogens. The EDSP evaluated the assay by using 656 chemicals and computing "a numeric value to indicate which chemicals may have the strongest effects on the interrelated system of 11 steroid hormones (including estrogen and androgen) that are normally produced in H295R cells. This number, called the maximum mean Mahalanobis distance (or maxmMd), is helpful for distilling information for the various hormones produced in the H295R cells down to a single value that can be used to prioritize which chemicals should receive additional evaluation or testing."
EPA found that the maxmMd values were high for strong modulators such as prochloraz and mifepristone, and lower for moderate modulators such as atrazine and molinate. Further, the HT-H295R assay proved to be faster and more efficient in comparison to the H295R assay with accuracies of 0.90/0.75 for increased/decreased testosterone, and 0.81/0.91 for estradiol production.
The new assay has the potential to help fill data gaps for large numbers of chemicals. It would facilitate the rapid identification and prioritization of a large number of chemicals that could be linked to endocrine disruption (ED) effects.
For more information, please access the peer reviewed publication in the Toxicological Sciences journal under the title "High-Throughput H295R Steroidogenesis Assay: Utility as an Alternative and a Statistical Approach to Characterize Effects on Steroidogenesis."