1986 Stokinger Lecture: Threshold Limit Values—Challenges and Opportunities

Abstract

There have been many challenges to the development of Threshold Limit Values (TLVs) over the years. Three current challenges for both the setting of TLVs as well as the use of TLVs are described. The setting of TLVs for carcinogens will need to take into account new research on DNA adducts as potential evidence for genotoxic mechanisms of carcinogens. In addition, the extrapolation of tumors in animals to potential carcinogenicity in humans should take into account secondary pathways at higher doses that may not be relevant at lower doses and may not be scientifically appropriate for extrapolation to humans. Gerontogens are defined as agents that affect aging processes. They may not exist in the pure sense of affecting only aging processes independent of disease processes. Nevertheless the prospect of an increased population of older workers presents a challenge to define whether or not chemicals cause premature aging or whether or not the health status of the older worker affects the detoxification mechanisms important to validation of specific TLVs. A continuing challenge to industrial hygienists is the need for tentative TLVs on minor, intermediate or new chemicals. It is suggested that a compilation of current practices to meet this challenge may help to develop some guiding principles. Finally it is considered that the use of TLVs provide opportunities to validate extrapolations from animals to humans, to provide scientific support for basic principles used in setting TLVs, and to revise TLVs on an annual basis when new information is provided.