Toxicological approaches to complex mixtures.

Abstract

This paper reviews the role of toxicological studies in understanding the health effects of environmental exposures to mixtures. The approach taken is to review mixtures that have received the greatest emphasis from toxicology; major mixtures research programs; the toxicologist's view of mixtures and approaches to their study; and the complementary roles of toxicological, clinical, and epidemiological studies. Studies of tobacco smoke, engine exhaust, combustion products, and air pollutants comprise most of the past research on mixtures. Because of their great experimental control over subjects, exposures, and endpoints, toxicologists tend to consider a wider range of toxic interactions among mixture components and sequential exposures than is practical for human studies. The three fundamental experimental approaches used by toxicologists are integrative (studying the mixture as a whole), dissective (dissecting a mixture to determine causative constituents), and synthetic (studying interactions between agents in simple combinations). Toxicology provides information on potential hazards, mechanisms by which mixture constituents interact to cause effects, and exposure dose-effect relationships; but extrapolation from laboratory data to quantitative human health risks is problematic. Toxicological, clinical, and epidemiological approaches are complementary but are seldom coordinated. Fostering synergistic interactions among the disciplines in studying the risks from mixtures could be advantageous. -Environ Health Perspect 101 (Suppl 4): 155-165 (1993).

Current assessment of the carcinogenic hazard of diesel exhaust

“…59 Early attention was drawn to the organic fraction of soot and its most active constituents. Later study confirmed that diesel exhaust was carcinogenic by inhalation, Downloaded by [University of Montana] at 13:48 01 April 2015 and that the pulmonary carcinogenicity in chronically exposed rats was associated with the soot fraction.…”

Anticholinesterase Pesticides Interactions

“…Of course, measurement of concentrations of OP and CM parent compounds and their metabolites in biological tissues and fluids is of paramount importance in interaction studies (Jain, 2006). For information on toxicological evaluation of chemical mixtures, readers are referred to publications by Chaturvedi (1993) and Mauderly (1993). Recently, Padilla (2006) suggested that the study of the interaction of anti-ChE pesticides should make use of a doseadditive experimental design with varying ratios of the components to fully characterize the interaction profile.…”

Issues that Must be Addressed for Risk Assessment of Mixed Exposures: The U.S. EPA Experience with Air Quality

“…However, these associations are often made with some degree of skepticism, since they are merely associations, not definitive causal links. Toxicology studies of mixtures, which theoretically can provide more definitive information, are scattered throughout the literature Mauderly, 1993). Yet despite the control that such studies provide, there is still little understanding of the significance of mixed exposures in determining health effects, especially at low exposure levels or where there are episodic or sequential events.…”

“…There are several fundamental reviews of the knowledge base and classical thinking with regard to mixtures toxicology Feron & Groten, 2002;Hansen et al, 1998;Leaderer et al, 1993;Mauderly, 1993;Zeliger, 2003). Similarly, in 1988, the National Research Council (NRC) Committee on Methods for the In Vivo Toxicity Testing of Complex Mixtures published a comprehensive treatise in an attempt to put forth a standardized approach, which might improve the collective understanding of mixtures (National Research Council, 1988).…”