Synergy and other ineffective mixture risk definitions.

Journal Article · Mon Apr 08 04:00:00 EDT 2002 · Sci. Total Environ.

DOI:https://doi.org/10.1016/S0048-9697(01)01113-5· OSTI ID:949415

Hertzberg, R; MacDonell, M

A substantial effort has been spent over the past few decades to label toxicologic interaction outcomes as synergistic, antagonistic, or additive. Although useful in influencing the emotions of the public and the press, these labels have contributed fairly little to our understanding of joint toxic action. Part of the difficulty is that their underlying toxicological concepts are only defined for two chemical mixtures, while most environmental and occupational exposures are to mixtures of many more chemicals. Furthermore, the mathematical characterizations of synergism and antagonism are inextricably linked to the prevailing definition of 'no interaction,' instead of some intrinsic toxicological property. For example, the US EPA has selected dose addition as the no-interaction definition for mixture risk assessment, so that synergism would represent toxic effects that exceed those predicted from dose addition. For now, labels such as synergism are useful to regulatory agencies, both for qualitative indications of public health risk as well as numerical decision tools for mixture risk characterization. Efforts to quantify interaction designations for use in risk assessment formulas, however, are highly simplified and carry large uncertainties. Several research directions, such as pharmacokinetic measurements and models, and toxicogenomics, should promote significant improvements by providing multi-component data that will allow biologically based mathematical models of joint toxicity to replace these pairwise interaction labels in mixture risk assessment procedures.

• Research Organization: Argonne National Laboratory (ANL)
• Sponsoring Organization: EPA
• DOE Contract Number: AC02-06CH11357
• OSTI ID: 949415
• Report Number(s): ANL/EA/JA-40733
• Journal Information: Sci. Total Environ., Journal Name: Sci. Total Environ. Journal Issue: 1-2 ; Apr. 8, 2002 Vol. 288; ISSN STENDL; ISSN 0048-9697
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
MATHEMATICAL MODELS
MIXTURES
OCCUPATIONAL EXPOSURE
PUBLIC HEALTH
RISK ASSESSMENT
SYNERGISM
TOXICITY
US EPA