In response to emerging concerns that substances may alter the function of endocrine systems and result in adverse effects to human health, the U.S. Congress included a provision in the Food Quality Protection Act of 1996 adding section 408 to the Federal Food Drug and Cosmetic Act (FFDCA). This section of the FFDCA requires EPA to:
… develop a screening program, using appropriate validated test systems and other scientifically relevant information, to determine whether certain substances may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other such endocrine effect as the Administrator may designate [21 U.S.C. 346 (p)]
In fulfillment of these requirements EPA has been developing and validating in vitro and in vivo assays to determine the potential of chemicals to interact with the endocrine systems and related functions in humans and wildlife. The EPA is recommending a two-tiered approach in the evaluation process. The Tier 1 Screening battery of assays is based on EPA's Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) recommendations and aims to identify chemicals affecting the estrogen, androgen & thyroid hormone systems. Tier 2 testing is intended to confirm, characterize and quantify those effects for estrogen, androgen and thyroid active chemicals.
Included in EPS's EDSP Tier 1 Screening battery is the cell-based H295R Steroidogenesis Assay which uses the H295R human adrenocortical carcinoma cell line. The H295R Steroidogenesis Assay is currently in the last phase of validation of the Test Method Validation Program for the Organization for Economic Cooperation & Development (OECD), which will ultimately result in the development of an OECD Test Guideline for assessing the potential of chemicals to affect steroid hormone synthesis.
ENTRIX, Inc. and the Toxicology Centre at the University of Saskatchewan have developed and validated the H295R Steroidogenesis Assay with research grants from the EPA as part of US EPA's EDSP and OECD's method validation program. The project has been directed by Professor John P. Giesy of the University of Saskatchewan 's Toxicology Centre and Dr. Markus Hecker of ENTRIX. Drs. Giesy and Hecker have been instrumental in the development and validation of the test protocols and the quality criteria guidelines required by regulatory agencies. In addition, Professor Giesy and ENTRIX scientists have an excellent understanding of the endocrine disruptor issues through their years of research and have numerous publications in the area of chemical-induced effects on endocrine function.
EPA published in the Federal Register a list of 73 pesticide active ingredients and HPV/pesticide inert chemicals selected for initial Tier 1 screening. This initial list for testing was prioritized from a universe of 87,000 chemicals included on the TSCA Inventory, active pesticide ingredients, and ingredients in cosmetics and food additives.
In response to these upcoming screening requirements, Canada Ecotoxicity Testing & Screening, Inc. (CETES), was founded to provide clients GLP-compliant testing solutions in support of their testing requirements under EPA's EDSP and other mandatory national or international testing programs world wide.