Human Health Risk Assessment for Priority Substances

4.0 Approaches for the Assessment of "Toxic" under paragraph 11(c) of CEPA - Simple Mixtures

The approach to assessment of whether or not a simple mixture of chemical substances is "toxic" under CEPA is dependent upon the nature of the available data. Occasionally, the chemical composition of a mixture, levels of exposure of the general population to the mixture, and toxic effects of the mixture itself or its components, may be well characterized. Generally though, not all components of the mixture are known, and information on the levels of exposure and toxicological data either of the mixture itself or the components are limited and/or inadequate. Examples of some relevant approaches to the assessment of "toxic" under paragraph 11(c) of CEPA are provided below, though owing to the variation in the types and compositions and relevant toxicological data available, assessment on a case-by-case basis is especially critical.

4.1 Mixture-Based Approach

For those cases in which information is available on exposure of the general population to and the toxicological effects produced by the exposure of animals or humans to the simple mixture itself, the approach to assess whether or not it is "toxic" under paragraph 11(c) of CEPA is similar to that outlined above for single "threshold" or "non-threshold toxicants".

4.2 Component-Based Approach

An assessment of whether or not simple mixtures of chemical substances are "toxic" under paragraph 11(c) of CEPA can sometimes be based on the effects of some or all of the components present in the mixture. For those cases in which the components in the simple mixture have similar effects due to similar modes of action, and there is little indication for interaction between components, effects are generally considered to be additive.

One component-based approach for "threshold toxicants" involves expressing the total daily intake of the mixture as toxic equivalents [summing of the concentrations of individual compounds multiplied by the potency of that substance relative to that of the reference (generally most potent) substance]. This composite measure of intake is compared to a Tolerable Daily Intake for the reference substance, derived as presented above for "threshold toxicants".

In another approach for simple mixtures for which the components are classified in Groups III to VI in Appendix B, and for which the mechanisms of toxicity for the critical effect are similar, a "Hazard Index" (HI) can be derived as follows:

HI = E₁/TDI₁ + E₂/TDI₂ + E_i/TDI_i

where:

E_i = estimated total daily intake of the ith toxicant;
TDI_i Tolerable Daily Intake for the ith component of the mixture.

The HI is derived from the dose addition presented above but substitutes 1/TDI for the relative potency factor.

If the numerical value of the hazard index exceeds or could exceed one, the simple mixture is considered to be "toxic" under paragraph 11(c) of CEPA; if the numerical value of the index is one or less, the simple mixture is not considered to be "toxic" under the Act.

In cases where the simple mixture contains a high proportion of substances classified in Groups I or II of Appendices B and C ("Carcinogenic to Humans" or "Probably Carcinogenic to Humans"; "Human Germ Cell Mutagen" or "Probable Human Germ Cell Mutagen"), the mixture as a whole may be considered to be "toxic" under paragraph 11(c) of CEPA.

Such a determination is based on consideration of factors such as the extent of characterization of the chemical composition and toxicological effects of the simple mixture and the proportion of the total mixture which is composed of components classified in Groups I or II. For simple mixtures considered to be "toxic" owing to the classification of a major proportion of components in Groups I or II in Appendix B and/or C, where possible, the estimated daily intake of the components by the general population in Canada or concentrations in relevant environmental media are compared to quantitative estimates of carcinogenic or mutagenic potency (Exposure/Potency Index or EPI) to characterize risk and provide guidance in establishing priorities for further action following assessment of "toxic" under the Act.