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CMM and HCN Background Information

The past practice of analyzing the consequences of each chemical component separately is often not conservative. Some chemicals in a mixture may target the same organ and have an additive impact. This approach does not consider this and may severely underestimate potential human health impacts.

A contrasting approach that involves adding all exposures from each chemical, regardless of the target-organ effects of the chemicals, tends to overestimate impacts and therefore be over-conservative. The heath impacts from chemicals that target different organs are often not simply additive to all target organs.

SCAPA's objective is to develop and maintain a default CMM for analyzing exposures to chemical mixtures that is based on target-organ effects. This approach tends to be more realistic and defensible than the two practices just mentioned.

The Basis of the CMM

The default CMM for analysis of exposures to chemical mixtures is based on the principles of the 1986 Environmental Protection Agency's "Guidelines for the Health Risk Assessment of Chemical Mixtures" (published on September 24, 1986 in the Federal Register 51(185):34014-34025). The CMM was approved for use by SCAPA in April 1996.

How the CMM Works: The Hazard Index Approach

When using the CMM, a hazard index (HI) is calculated for each component of a chemical mixture at the chosen receptor point. The “HIi” is the concentration of chemical “i” (Conci ) divided by the concentration limit for chemical “i” (Limiti ), or in equation form:

HIi = Conci/Limiti

An HIi < 1 means that the limit for that single chemical “i” has not been exceeded. However, if the hazard indices for all chemicals in a mixture are summed, and the cumulative hazard index is greater than one, then an unacceptable condition may exist and mitigating strategies may need to be considered. Unless the health effects of the components are known to be independent, the toxic consequences of all components should as an initial step in an assessment be considered to be additive. This represents the most conservative upper-bound approach for assessing exposures to mixtures.

If this upper-bound approach produces unacceptable results, the next step is to classify the chemicals in the mixture according to their toxic consequences. The toxicologic classification of specific chemicals can be done using the health code numbers (HCNs) established for each chemical.

How the CMM Works: Using HCNs in the CMM

HCNs are used in the CMM to identify the target-organ effects of each chemical in the mixture. Any chemicals that target the same or similar organs or operate by the same acute (short-term) or chronic (long-term) mode of toxicity should be considered additive to that target organ or by that same mode of toxicity. For simplicity in this discussion, target-organ effects and modes of toxicity are considered simply as target-organ effects.

HCNs are similar to medical diagnostic codes in that they are code numbers that identify a particular target organ or health effect. (See the full listing of HCNs.)

HCNs enable classification of chemicals by target-organ toxicity. Summation of hazard indices (HIs) for all chemicals in a mixture having the same toxic consequences (i.e., the same or similar HCNs) enables determination of the acceptability or unacceptability of exposure to any specific mixture of chemicals using this more discerning and realistic approach.

HCNs offer a convenient way of performing this exposure addition by numerically “binning” identical or similar target-organ effects. All of the individual exposure HI’s that are binned into the same or similar HCN bin are added together to yield an “HI sum” for that target-organ bin.

Any of the individual HI sums that exceed a value of 1.0 indicate that the exposure limit has been exceeded and that some kind of mitigating action should be taken to reduce the exposure to that target organ below the applicable limit. Some organizations have established an “action level,” typically 50% of the limit, which triggers initiation of mitigating strategies in an effort to assure that the limit itself is never exceeded.


HCNs are a binning technique for adding similar target-organ effect exposures from chemicals in a mixture. Their use offers a more discerning and realistic alternative to the ultra-conservative bounding technique of summing all HIs regardless of their target organ effect or the often non-conservative method of treating each chemical separately.

More Information

For more information on the SCAPA Chemical Mixtures Methodology and the role of HCNs in it, please read the following papers: