In an article published on March 12, 2018 in Chemical & Engineering News, Britt E. Erickson provided a detailed overview of the history and progress in the development of in vitro assays to detected endocrine disrupting chemicals (EDCs) within the Endocrine Disruptor Screening Program (EDSP) run by the U.S. Environmental Protection Agency (EPA).
Originally, EDSP was operating with a battery of five in vitro and six in vivo assays to screen for chemical effects on estrogen, androgen, and thyroid hormone systems. However, the testing has been very slow and costly. Therefore, EPA decided “to put EDSP on hold” and instead invest in developing “high-throughput methods to replace the 11 EDSP assays.”
The already available assays are (i) “an ER model that replaces two in vitro assays for ER . . . and an in vivo uterotrophic test;” (ii) an “AR model that accurately predicts androgenic and antiandrogenic activity;” (iii) “a high-throughput steroidogenesis model.” Additionally, “three new thyroid assays targeting enzymes and other proteins critical for thyroid hormone production and the uptake and recycling of iodide” are being tested currently, with the goal of integrating them “into a ‘thyrollicle’ model to better predict the effects of chemicals on thyroid cells, which are arranged in spheres called follicles.” According to Erickson, the EPA “expects to have all the methods ready to begin [EDSP] screening again by 2020.”
In Europe, the large EU-ToxRisk project (FPF reported) “is beginning to have evidence that its battery of alternative tests and models may be able to predict chemical toxicity for read-across purposes,” informed an article published by Chemical Watch on March 14, 2018. EU-ToxRisk focuses on developing alternative test methods for predicting developmental and reproductive toxicity, as well as repeated-dose systemic toxicity in the lungs, kidneys, liver and nervous system. The project is based on a set of case studies built along adverse outcome pathways (AOPs), reviewed in detail by Emma Davies in a global business briefing article published by Chemical Watch in March 2018.
Read more
Britt Erickson (March 12, 2018). “Endocrine disruptor assays go fast track.” Chemical & Engineering News
Chemical Watch (March 14, 2018). “EU-ToxRisk makes progress on predicting chemical toxicity.”
Emma Davies (2018). “Read-across steps forward.” Chemical Watch
References
Browne, P., et al. (2015). “Screening chemicals for estrogen receptor using a computational model.” Environmental Science & Technology 49:8804-8814.
Kleinstreuer, N., et al. (2016). “Development and validation of a computational model for androgen receptor activity.” Chemical Research in Toxicology 30:946-964.
Haggard, D., et al. (2017). “High-throughput H295R steroidogenesis assay: Utility as an alternative and a statistical approach to characterize effects on steroidogenesis.” Toxicological Sciences (published December 1, 2017).
Friedman, K., et al. (2016). “Tiered high-throughput screening approach to identify thyroperoxidase inhibitors within the ToxCast phase I and II chemical libraries.” Toxicological Sciences 151:160-180.
Hallinger, D., et al. (2017). “Development of a screening approach to detect thyroid disrupting chemicals that inhibit the human sodium iodide symporter (NIS).” Toxicology In Vitro 40:66-78.
Hornung, M., et al. (2017). “Screening the ToxCast phase 1 chemical library for inhibition of deiodinase type 1 activity.” Toxicological Sciences (published on December 7, 2017).
