TABLE 8-1A Information Levels for Assessment of Toxicity and Mode of Action of Chemicals in Model Systems

Information Level

Information Level 1

Information Level 2

Information Level 3

Information Level 4

Experimental description

High-throughput biochemical and cellular assays.

Identify potentially vulnerable pathways in development, e.g., the 17 signaling pathways, molecular stress pathways, and the main toxicokinetic pathways (DMEs).

Identify molecular interactions of toxicants and target molecules, and activity changes

Developmental assays with genetically optimized and sensitized nonmammalian animals.

Identify potentially vulnerable developmental pathways, target organs, and times of susceptibility in development.

In vivo mammalian developmental toxicity testing.

Use genetically optimized animals for relevant sensitive tests.

Identify potentially vulnerable pathways, target organs, and times of susceptibility.

Link dose-response relationships to both developmental and functional (e.g., behavioral) changes.

Detailed mechanistic studies to understand mode of action for selected developmental toxicants.

Toxicokinetic and dynamic processes of chemicals would be identified and quantitatively assessed.

Animal tests of toxicant sensitivities of polymorphisms.

Analysis of differences of test animals and humans, regarding DMEs and signaling components.

Application

Use to assess most chemicals (>100,000) used by humans or released into the environment.

Assess combinations of chemicals.

Collect dose-response data.

Use to assess many chemicals, doses, and combinations.

Use to assess relative toxicity of related compounds.

Use for hazard assessment of chemicals of likely high exposure or concern to humans.

Can generate useful dose-response data relevant for mammalian evaluation.

Gain information on toxicant sensitivity of polymorphisms.

Use for a few chemicals where significant human exposure is likely or where knowledge about toxicant mechanism or about animal vs. human differences would be useful for human risk assessments.

Assays per year

105-106

103-104

102

10 studies



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