Use of Toxicological Data in Evaluating Chemical Safety

More than 70,000 chemicals are currently registered in the chemical substances inventory under the Toxic Substances Control Act (TSCA) in the United States (U.S.), and every year new chemicals are introduced to the market. Each chemical can produce toxic effects that may be reversible or irreversible. Exposure to chemicals in the workplace can result in a wide range of adverse health outcomes, for example pulmonary disease skin irritation and sensitization, neurotoxicity, lung and liver function impairment, cancer, and hereditary diseases. Toxicological data provide the basis for evaluating the potential health risks of chemicals to humans. Information from human and animal studies is used to characterize the nature of the toxic effects of chemicals and to predict their risk to human health under given exposures. The ultimate goal of using data from such studies is to determine “safe” levels of human exposure to toxic substances. Because it is not possible to assure absolute safety to everyone for any chemical, “safe” does not imply risk-free but a level of risk that is acceptable in our society. The purpose of this chapter is to provide an overview of the process of chemical safety evaluation in the context of the regulatory risk assessment paradigm from the perspective of occupational toxicology. Toxicological data from studies of the chemical in humans and animals, including physicochemical, toxicokinetic, and mechanistic data, are used in this evaluation. First, the adverse effects are identified and categorized by toxic end point. Next, the dose–response relationship for each end point is characterized, and the overall evidence is evaluated to determine the hazard class of the substance. If the toxicological database for a chemical is adequate, potential health risks to humans are then estimated, and exposure limits are derived by using risk assessment methodologies. Depending on the dose—response relationship (threshold or nonthreshold) of the adverse effect that is observed at the lowest dose (critical effect), three general risk assessment approaches can be applied: safety/uncertainty factor, low-dose extrapolation risk model, and a unified benchmark dose approach. Note that various risk assessment procedures have been developed over the years and continue to evolve as science advances. A new terminology has also emerged in large part from environmental risk assessment work that focuses on community exposures to chemicals. Toxicological principles are an integral part of chemical risk assessment, so basic toxicological concepts and references are included. Keywords: Toxicological data; Toxicity studies; Classification; Characterization; Dose-response relationships; Exposure limit derivation; Global harmonization; Hazard classification system; Uncertainty; Adequacy; Database; Structure—activity relationships