TABLE 1.
Comparison of Quantitative Methods for Assessment of Cumulative Health Risks from Chemical Mixtures4
| Approach | Methodology |
| HIINT approach using evidence or mathematical theory on pairwise interactions; HIINT = ∑i f(HQ)pair (extensive data requirements) | Assumes sum of interactions between pairs of chemicals represent the whole mixture. Requires pairwise effect data for major constituents of the mixture. |
| Toxicity equivalency factor (TEF) approach; DoseTEQ = ∑(dosei for TEFi) (moderate data requirements) | Assumes the action of each chemical in the mixture is fully represented by an index chemical. Doses of all mixture constituents are treated as equivalent to the weighted sum of the activity of the mixture components. |
| Margin of exposure (MOE) approach using TEF; MOE = NOAEL ÷ DoseTEQ (moderate data requirements) | Assumes addititvity of effects for mixture constituents. Appears to avoid the extrapolations inherent in uncertainty factors, but introduces the added responsibility to make explicit and account for the scientific concerns that gave rise to uncertainty factors in the first place. Single number summary for exposure obscures distributional nature of exposures. |
| HI approach using NOAEL or BMD; HI = (HQ2)i = (Exposure Metrici ÷ NOAELi or BMDi) (minimal data requirements) | Assumes additivity of effects for mixture constituents. NOAELs and BMDs used for comparison instead of RfDs or RfCs, but single comparison value still makes it difficult to discern scientific judgments about uncertain factors and hides distributional nature of exposures. |
| HI approach using RfD or RfC; HI = (HQ2)i = ∑(Exposure Metrici ÷ RfDi or RfCi) (minimal data requirements) | Assumes additivity of effects for mixture constituents. Simplest approach with least resource requirements, but depends on scientific judgment to translate NOAELs or LOAELs into RfDs or RfCs. Not a true quantitative risk assessment, just a single comparison value that obscures scientific judgments about uncertainty factors and masks distributional nature of exposures. |
Note. BMD=benchmark dose; HI=hazard index; HIINT=interaction-based hazard index; HQ=hazard quotient; LOAEL=lowest observed adverse effect level; NOAEL=no observed adverse effect level; RfC=reference concentration; RfD=reference dose; TEQ=toxicity equivalency.