EPA Scientists Develop New Methods to Evaluate Chemicals
Published August 13, 2018
EPA scientists are developing and evaluating new methods to evaluate chemicals for potential health effects. These methods are fast, cost effective, and reduce our reliance on traditional methods which use laboratory animals.
There are thousands of chemicals currently in use and hundreds of new chemicals are introduced into the market each year. Under different federal statutes, EPA makes a broad range of decisions to protect public health and the environment from unintended consequences of using chemicals. Decisions about chemicals are also made by other Federal Agencies, State Environmental and Health Agencies, International Governmental Agencies, and Industry. These decisions are guided by specific federal laws, including laws related to pesticides, drinking water contaminants, commercial and industrial chemicals, chemicals found on contaminated sites, and endocrine disrupting chemicals.
EPA’s Endocrine Disruptor Screening Program (EDSP) is charged with examining the effects of chemicals on the endocrine system, a complicated network of glands, hormones, and receptors. Scientific research suggests that some chemicals can disrupt the endocrine system, which regulates biological processes in the body, including brain development, reproduction, metabolism, and blood sugar maintenance. Steroidogenesis, the production of steroid hormones from cholesterol, is particularly important to researchers studying endocrine disruption because steroid hormones act as chemical messengers to regulate processes in the body, including reproduction and development. Disruption of steroidogenesis can result in adverse health outcomes including sterility and hypertension.
EPA scientists are developing and evaluating new methods to test chemicals for potential health effects, including endocrine disruption. Some of these methods use automated chemical screening technologies, called high-throughput screening assays, to expose in vitro cells and proteins to chemicals. The cells and proteins are then screened for changes in biological activity that suggest potential negative health effects.
EPA scientists recently published an article in Toxicological Sciences about their analysis of a high-throughput screening assay which detects chemical effects on steroidogenesis. The new assay, called the high-throughput H295R assay (HT-H295R), can quickly and efficiently screen hundreds to thousands of chemicals and has the potential to become an alternative to or even replace the existing steroidogenesis assay, H295R. Both assays can be used to detect chemical effects on steroidogenesis, but the new assay has potential to increase the efficiency of screening efforts and fill data gaps for large numbers of chemicals using fewer resources. The scientists conducted a thorough analysis of the assay using 656 chemicals and computed 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 the 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.
This work demonstrates the value of the high-throughput screening methods to advance efforts to rapidly identify and prioritize large numbers of chemicals based on potential endocrine disrupting activity. The high-throughput assay analyzed in this publication is part of EPA’s ToxCast research effort, one of the new chemical evaluation methods being developed by EPA’s Chemical Safety for Sustainability Research Program, which has screened over 2,000 chemicals in over 700 high-throughput assays.