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Health-Based Guidance Values for Substances on the Second Priority Substances List

2. Explanation of Terms

Different approaches were adopted for assessments of those chemicals for which the weight of evidence indicated that the critical effect (cancer) is mediated through direct interaction with genetic material, resulting in a probability of harm at all levels of exposure, and those for which there is assumed to be a threshold (i.e., a level of exposure below which there is considered to be no risk). For substances for which the critical effect is considered to have a threshold, TIs or TCs have been developed by dividing effect levels observed in studies in exposed populations or animal species by uncertainty factors.

For carcinogenic effects for which the weight of evidence indicates that the mode of action involves direct interaction with genetic material, potency is generally expressed as the concentration (TC₀₅) or dose (TD₀₅) that induces a 5% increase in the incidence of, or deaths due to, tumours considered to be associated with exposure, observed in epidemiological studies in human populations or bioassays in experimental animals.

Wherever data are sufficient, based on understanding of mode of action, relevant toxicokinetic or toxicodynamic information is incorporated in lieu of default values into TIs/TCs or quantitative estimates of potency to address interspecies differences or human variability.

For those substances for which values for both carcinogenic and non-carcinogenic effects are presented, it is recommended that the more conservative of the TD₀₅s/TC₀₅s divided by a suitable margin or TIs/TCs be adopted, in part, as the basis for development of reference points against which the quality of various media can be judged.

In general, depending upon the sources and physical/chemical properties of a substance, exposure via one of the routes addressed herein (i.e., inhalation and ingestion) for specific chemical substances will predominate. Where, for specific substances, there is potential for significant intake via both ingestion and inhalation, however, it is important that this be taken into account in the development of media-specific values (i.e., exposure via inhalation and ingestion should, in total, not exceed the TI/TC or TD₀₅/TC₀₅ divided by a suitable margin; see examples in IPCS, 1994). As a basis for consideration of relevant media, proportions of total exposure contributed via each medium based on estimates of human exposure to the PSL2 substances are presented in Section 3.3.

2.1 Tolerable Intake (TI)

TIs (Section 3.1), expressed on a body weight basis (e.g., mg/kg-bw per day), are the total intakes by ingestion to which it is believed that a person can be exposed daily over a lifetime without deleterious effect. Absolute values per day for various age groups can be developed by multiplying the TI by the average body weight of the age group under consideration. It should be noted, however, that exceedance of such calculated intakes by a particular age group for a small proportion of the life span does not necessarily imply that exposure constitutes an undue risk to health. In assessments for Priority Substances under CEPA 1999, mean body weights of various age groups were considered to be as follows (EHD, 1998):

2.2 Tolerable Concentration (TC)

TCs (Section 3.1) (often expressed in mg/m³) are concentrations (generally airborne) to which it is believed that a person can be exposed continuously over a lifetime without deleterious effect.

2.3 Tumorigenic Dose₀₅ (TD₀₅)

For Existing Substances under CEPA 1999, tumorigenic potencies for carcinogens acting through direct interaction with genetic material are estimated in the range of the experimental data in animal species or epidemiological studies and expressed generally as the TD₀₅ (Section 3.2). The TD₀₅ is the total intake (often expressed in mg/kg-bw per day) associated with a 5% increase in the incidence of, or mortality due to, tumours, scaled, where appropriate, to reflect adequate quantitative data on interspecies variations in toxicokinetics or toxicodynamics.

This measure of dose-response is considerably more accurate than estimates of risk predicted based on extrapolation over many orders of magnitude from experimental studies in animals to the much lower levels of contaminants to which the general population is likely to be exposed, generally in the absence of information on mode of action. In view of these considerable uncertainties, these risks are not specified in absolute terms of predicted incidence or numbers of excess deaths per unit of the population.

Since it is assumed, for carcinogens acting through direct interaction with genetic material, that there is some probability of harm to human health at any level of exposure, continuing efforts should be made to reduce exposure to such compounds to the greatest extent possible. However, incremental risks associated with exposure to low levels of such substances may be sufficiently small so as to be essentially negligible compared with other risks encountered in society. As examples, therefore, values based on division of the TD₀₅ by margins of 5000 and 50 000 are presented in Section 3.2. These values afford protection similar to that associated with the range of low-dose risk estimates generally considered by various agencies to be "essentially negligible" (i.e., 10-⁵ to 10-⁶).

It should not be inferred that Health Canada deems any of these values as "acceptable" from a societal viewpoint. As indicated above, the department encourages reduction, to the extent possible, of exposure of the general public to compounds that are carcinogenic with likely mode of action involving direct interaction with genetic material.

As is the case for TIs, absolute values per day for various age groups can be developed by multiplying the TI by the average body weight of the age group under consideration, although exceedance of these absolute values by a particular age group (constituting a small proportion of the life span) does not necessarily imply that exposure constitutes an undue risk to health.

2.4 Tumorigenic Concentration₀₅ (TC⁰⁵)

The TC₀₅ (Section 3.2) is the concentration, generally in air (expressed, for example, in mg/m³), associated with a 5% increase in the incidence of, or mortality due to, tumours. As for the TD₀₅ values described above, as examples, values based on division of the TC₀₅ by margins of 5000 and 50 000 are presented in Section 3.2. These afford protection similar to that associated with the range for low-dose risk estimates generally considered by various agencies to be "essentially negligible" (i.e., 10-⁵ to 10-⁶).

Again, Health Canada does not deem any of these values as "acceptable" from a societal viewpoint, but rather, as indicated above, encourages reduction, to the extent possible, of exposure of the general public to compounds that are carcinogenic with likely mode of action involving direct interaction with genetic material.