Chapter 8 - Practical Thresholds in the Derivation of Occupational Exposure Limits (OELs) for Carcinogens

Abstract

Until the mid-1990s the general dogma held valid that no health-based occupational exposure limits (OELs) and biological limit values (BLVs) can be derived for carcinogenic compounds. At the same time, there was growing scientific recognition that carcinogenic risk extrapolation to/from high/low doses, a key step in setting standards for carcinogenic substances, must consider the respective mode(s) of action. The dogma of no thresholds for occupational carcinogens was first challenged by the Deutsche Forschungsgemeinschaft when proposing to differentiate not only between genotoxic and nongenotoxic carcinogens, but also to derive health-based OELs for “genotoxic chemicals for which low carcinogenic potency can be expected on the basis of dose–response relationships and toxicokinetics, and for which the risk at low doses can be assessed.” It was the first time to consider for a group of (genotoxic) occupational carcinogens what was later called a “practical threshold.” This discourse was further implemented by the EUROTOX Speciality Section Carcinogenesis and was decisive for the acceptance of the concept of “practical thresholds” in the derivation of OELs and BLVs for carcinogenic substances by the Scientific Committee on Occupational Exposure Limits (SCOEL) of the European Union. The SCOEL system basically distinguishes between “perfect” and “practical” thresholds. “Perfect” thresholds are assigned to nongenotoxic carcinogens and “practical thresholds” to genotoxic carcinogens for which their mode of action suggests a thresholded nonlinear dose-response. In this chapter, modes of action of some examples of carcinogenic compounds are discussed, which were recently assigned by SCOEL as having a practical threshold. These compounds include the local nasal rodent carcinogens propylene oxide and naphthalene, as well as the metals nickel and cadmium. In the future, the concept of a practical threshold for carcinogens appears especially relevant for a number of metal compounds that trigger the formation of reactive oxygen.