OECD validation program of the H295R steroidogenesis assay: Phase 3. Final inter-laboratory validation study

Background, goals, and scope In response to increasing concerns regarding the potential of chemicals to interact with the endocrine system of humans and wildlife, various national and international programs have been initiated with the aim to develop new guidelines for the screening and testing of t...

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Published in:Environmental science and pollution research international 2011-03, Vol.18 (3), p.503-515
Main Authors: Hecker, Markus, Hollert, Henner, Cooper, Ralph, Vinggaard, Anne Marie, Akahori, Yumi, Murphy, Margaret, Nellemann, Christine, Higley, Eric, Newsted, John, Laskey, John, Buckalew, Angela, Grund, Stefanie, Maletz, Sibylle, Giesy, John, Timm, Gary
Format: Article
Language:English
Subjects:
17β-Estradiol
Aquatic Pollution
Assays
Atmospheric Protection/Air Quality Control/Air Pollution
Bioassays
Biological Assay - methods
Cell Line, Tumor
Cell Survival - drug effects
Cell viability
Chemicals
Cooperation
Earth and Environmental Science
Ecotoxicology
Endocrine disruption
Endocrine Disruptors - toxicity
Endocrine system
Environment
Environmental Chemistry
Environmental Health
Environmental protection
estradiol
Estradiol - metabolism
Estrogen Antagonists - toxicity
Estrogens
H295R
Hazardous Substances - toxicity
Homeostasis
Hormone production
Hormones
Humans
Inhibitors
Laboratories
OECD
Organizations
Research Article
Sex steroid
Steroid hormones
Steroidogenesis
Steroids
Steroids - toxicity
Studies
Testosterone
Testosterone - antagonists & inhibitors
Testosterone - metabolism
Toxicology
Transferability
Validation
Validation studies
Waste Water Technology
Water Management
Water Pollution Control
Wildlife
Wildlife conservation
Wnt protein
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Summary:Background, goals, and scope In response to increasing concerns regarding the potential of chemicals to interact with the endocrine system of humans and wildlife, various national and international programs have been initiated with the aim to develop new guidelines for the screening and testing of these chemicals in vertebrates. Here, we report on the validation of an in vitro assay, the H295R steroidogenesis assay, to detect chemicals with the potential to inhibit or induce the production of the sex steroid hormones testosterone (T) and 17β-estradiol (E2) in preparation for the development of an Organization for Economic Cooperation and Development (OECD) test guideline. Methods A previously optimized and pre-validated protocol was used to assess the potential of 28 chemicals of diverse structures and properties to validate the H295R steroidogenesis assay. These chemicals are comprised of known endocrine-active chemicals and “negative” chemicals that were not expected to have effects on the targeted endpoints, as well as a number of test chemicals with unknown modes of action at the level of the steroidogenic pathway. A total of seven laboratories from seven countries participated in this effort. In addition to effects on hormone production, confounding factors, such as cell viability and possible direct interference of test substances with antibody-based hormone detection assays, were assessed. Prior to and during the conduct of exposure experiments, each laboratory had to demonstrate that they were able to conduct the assay within the margin of predefined performance criteria. Results With a few exceptions, all laboratories met the key quality performance parameters, and only 2% and 7% of all experiments for T and E2, respectively, were excluded due to exceedance of these parameters. Of the 28 chemicals analyzed, 13 and 14 tested affected production of T and E2, respectively, while 11 and 8 did not result in significant effects on T and E2 production, respectively. Four and six chemicals produced ambiguous results for effects on T and E2 production, respectively. However, four of these cases each for T and E2 were associated with only one laboratory after a personnel change occurred. Significant interference of test chemicals with some of the antibody-based hormone detection systems occurred for four chemicals. Only one of these chemicals, however, significantly affected the ability of the detection system to categorize the chemical as affecting E2 or T
ISSN:0944-1344
1614-7499
DOI:10.1007/s11356-010-0396-x