Use of genomics in toxicology and epidemiology: findings and recommendations of a workshop.

The sequencing of the human genome has revolutionized biology and led to an astounding variety of technologies and bioinformatics tools, enabling researchers to study expression of genes, the function of proteins, metabolism, and genetic differences within populations and between individuals. These scientific advances are making an impact in the medical research community and hold great promise for prevention, diagnosis, and treatment of diseases. This developing field also holds great promise for improving the scientific basis for understanding the potential impacts of chemicals on health and the environment.

Recognition of adverse and nonadverse effects in toxicity studies.

One of the most important quantitative outputs from toxicity studies is identification of the highest exposure level (dose or concentration) that does not cause treatment related effects that could be considered relevant to human health risk assessment. A review of regulatory and other scientific literature and of current practices has revealed a lack of consistency in definition and application of frequently used terms such as No Observed Effect Level (NOEL), No Observed Adverse Effect Level (NOAEL), adverse effect, biologically significant effect, or toxicologically significant effect. Moreover, no coherent criteria were found that could be used to guide consistent interpretation of toxicity studies, including the recognition and differentiation between adverse and nonadverse effects.

The challenge posed by endocrine-disrupting chemicals.

Rapid regulatory developments in the area of environmental endocrine disruption present a series of potential problems that are identified and illustrated with examples taken from the recent literature. A list of priorities is provided, including the need for additional epidemiological and wildlife studies, the derivation of a coordinated testing strategy, agreement on the toxicities expected of endocrine disrupting agents, and acceptance that whole animal assays will be uniquely critical in this area of toxicology. The intrinsic difficulty of attempting to simultaneously study all aspects of endocrine disruption indicates the need to reduce the scope of the problem, which can be achieved by first studying toxicities mediated by sex hormone receptors.

A two-generation reproduction study in rats receiving drinking water containing vinyl acetate.

Vinyl acetate (VA) is a commonly used chemical in polymerization and copolymerization processes and as a chemical intermediate. As part of a collaborative effort between VA producers of the United States and British Petroleum, the present study was carried out to provide a base set of data for risk assessment. Groups of male and female Crl:CD(SD)BR rats were given 0, 200, 1000, or 5000 ppm VA via the drinking water over two generations.

Chronic toxicity and oncogenicity study with vinyl acetate in the rat: in utero exposure in drinking water.

The purpose of this study was to evaluate vinyl acetate for potential chronic toxicity and oncogenicity when given to rats in drinking water from the time of gestation. Target concentrations were 0, 200, 1000, and 5000 ppm (v/v). Drinking water solutions were prepared daily and analyzed at approximately 4-week intervals.