Comparative assessment of the acute skin irritation potential of detergent formulations using a novel human 4-h patch test method.

Predictive skin irritation test methods, which do not require use of animals, are needed for the pre-market assessment of detergent formulations. The utility of a novel and ethical human acute skin irritation patch test method, originally developed for chemical skin irritation assessment, was evaluated. In this IRB-approved method, subjects were patched under occlusion for increasing periods of time up to 4h in duration.

Role of inflammation in chemical-induced hepatotoxicity.

The liver, which is the major organ responsible for the metabolism of drugs and toxic chemicals, is also the primary target organ for many toxic chemicals. Increasing evidence has indicated that inflammatory processes are intimately involved in chemical-induced hepatotoxic processes, and like other inflammatory diseases, such as autoimmunity, are responsible for producing mediators that can effect liver damage or repair. This review will summarize our current understanding of how inflammatory processes influence hepatic pathology and repair following exposure to established hepatotoxic chemicals including carbon tetrachloride, an industrial chemical, and acetaminophen, a widely used analgesic.

The role of tumor necrosis factor alpha in chemical-induced hepatotoxicity.

Only recently have toxicologists come to understand the role of inflammation, and TNFalpha specifically, in classical toxicological processes. This relationship appears fairly complex, as inflammation and proliferation may well be only one facet of a time- and dose-dependent continuum of toxicological and repair processes. Not surprisingly, considerable efforts are being undertaken using our newly found understanding of molecular control to develop specific and safe chemical, biological, and molecular regulators of TNFalpha for potential therapeutic use.

Comparative pulmonary absorption, distribution, and toxicity of copper gallium diselenide, copper indium diselenide, and cadmium telluride in Sprague-Dawley rats.

Copper gallium diselenide (CGS), copper indium diselenide (CIS), and cadmium telluride (CdTe) are novel compounds used in the photovoltaic and semiconductor industries. This study was conducted to characterize the relative toxicities of these compounds and to evaluate the pulmonary absorption and distribution after intratracheal instillation. Female Sprague-Dawley rats were administered a single equimolar dose (70 mM) of CGS (21 mg/kg), CIS (24 mg/kg), CdTe (17 mg/kg), or saline by intratracheal instillation.

Acetaminophen-induced hepatotoxicity is associated with early changes in AP-1 DNA binding activity.

The AP-1 transcription factor family, which is involved in early response genes, consists of two groups of proteins, Fos-related antigens (fra) and Jun proteins. AP-1 is usually expressed at low basal cellular levels, but can be up-regulated by a variety of exogenous stimuli which results in synthesis of Fos and Jun proteins and increased AP-1 DNA binding activity. Changes in early immediate gene responses are associated with liver necrosis, inflammation and repair, although investigations into their role in drug-induced hepatotoxicity have not been actively examined.