High-Throughput Screening of Chemical Effects on Steroidogenesis Using H295R Human Adrenocortical Carcinoma Cells.

Disruption of steroidogenesis by environmental chemicals can result in altered hormone levels causing adverse reproductive and developmental effects. A high-throughput assay using H295R human adrenocortical carcinoma cells was used to evaluate the effect of 2060 chemical samples on steroidogenesis via high-performance liquid chromatography followed by tandem mass spectrometry quantification of 10 steroid hormones, including progestagens, glucocorticoids, androgens, and estrogens. The study employed a 3 stage screening strategy.

Polyester monomers lack ability to bind and activate both androgenic and estrogenic receptors as determined by in vitro and in silico methods.

The paper presents results from the screening of seven monomers used by Eastman Chemical to make various polymers. Ethylene glycol, diethylene glycol, polytetramethylene glycol, isophthalic acid, monosodium-5-sulfoisophthalic acid, 1,4-cyclohexanedicarboxylic acid, and dimethylcyclohexanedicarboxylate were screened for potential androgenicity or estrogenicity. The following studies were conducted: QSAR for binding to the AR and ER, in vitro Androgen Receptor Binding Assay, in vitro Estrogen Receptor Binding Assays (alpha and beta isoforms), in vitro Androgen Receptor Transactivation Assay in human cells, and in vitro Estrogen Receptor Transactivation Assay in human cells.

Integrated Testing Strategies (ITS) for safety assessment.

Integrated testing strategies (ITS), as opposed to single definitive tests or fixed batteries of tests, are expected to efficiently combine different information sources in a quantifiable fashion to satisfy an information need, in this case for regulatory safety assessments. With increasing awareness of the limitations of each individual tool and the development of highly targeted tests and predictions, the need for combining pieces of evidence increases. The discussions that took place during this workshop, which brought together a group of experts coming from different related areas, illustrate the current state of the art of ITS, as well as promising developments and identifiable challenges.

Building shared experience to advance practical application of pathway-based toxicology: liver toxicity mode-of-action.

A workshop sponsored by the Human Toxicology Project Consortium (HTPC), "Building Shared Experience to Advance Practical Application of Pathway-Based Toxicology: Liver Toxicity Mode-of-Action" brought together experts from a wide range of perspectives to inform the process of pathway development and to advance two prototype pathways initially developed by the European Commission Joint Research Center (JRC): liver-specific fibrosis and steatosis. The first half of the workshop focused on the theory and practice of pathway development; the second on liver disease and the two prototype pathways. Participants agreed pathway development is extremely useful for organizing information and found that focusing the theoretical discussion on a specific AOP is extremely helpful.

Lessons learned, challenges, and opportunities: the U.S. Endocrine Disruptor Screening Program.

In 1996, the U.S. Congress passed the Food Quality Protection Act and amended the Safe Drinking Water Act (SDWA) requiring the U.

Lack of androgenicity and estrogenicity of the three monomers used in Eastman's Tritan™ copolyesters.

Eastman Tritan™ copolyester, a novel plastic from Eastman is manufactured utilizing three monomers, di-methylterephthalate (DMT), 1,4-cyclohexanedimethanol (CHDM), and 2,2,4,4-tetramethyl-1,3-cyclobutanediol (TMCD) in various ratios. As with most any polymer, the monomers along with the high molecular weight oligomers, whose toxicity is most commonly represented by the monomers, make up the predominate amount of free chemicals available for leaching into the environment and/or foods. In light of the high level of public concern about the presence of endocrine (primarily estrogenic) activity ascribed to certain plastics and chemicals in the environment, Tritan's™ monomers were evaluated using QSAR for binding to the androgen receptor and estrogen receptors (alpha and beta) as well as a battery of in vitro and in vivo techniques to determine their potential androgenicity or estrogenicity.

In vitro effects of ethanol and mouthrinse on permeability in an oral buccal mucosal tissue construct.

The current study investigated the influence of ethanol and ethanol-containing mouthrinses on model chemical permeability in an in vitro oral buccal mucosal construct (EpiOral, ORL-200, MatTek). Innate ethanol transport and metabolism in the tissue construct was also studied. Caffeine flux in buccal tissue was measured after pre-treatment with < 26.