Extrapolation-procedures for carcinogenic and noncarcinogenic compounds

Abstract

One fundamental goal of regulatory toxicology is to establish safe levels of human exposure to toxic compounds. This is usually performed within the framework of risk assessment (see chapter “Toxicological Risk Assessment”) and risk management: Using both data describing human exposure (exposure assessment) and results from the characterization of the toxicity (hazard characterization), the risk of the compound can then be characterized (risk characterization) in a framed approach through health-based guidance values (HBGVs), or related measures are used for that purpose. In the absence of information to establish dose–response relationships at exposure levels such low as they are generally experienced by humans, high-dose to low-dose extrapolation is generally used. Whereas epidemiological findings of the agent’s toxicity are directly applicable to humans, toxicological results detected in experimental animals need in addition the extrapolation from the specific animal species to human. To estimate the magnitude of expected effects at lower doses reflecting human exposure or corresponding to acceptable risks for humans set by regulatory practices, appropriate extrapolation is required. This chapter focuses on the low-dose extrapolation of animal data but presents at the same time general methodology also applicable to human data to establish HBGVs for humans.