Protocol for the Derivation of Environmental and Human ... - CCME

Part C, Section 2
Section 2
Investigation of Contaminant Toxicology
Health Canada has determined the reference dose {Tolerable Daily Intake (TDI) for threshold
substances and Risk Specific Doses (RSD) associated with risks of 10 -4 , 10 -5 , 10 -6 and 10 -7 for nonthreshold
substances} for all contaminants being addressed by the NCSRP. Some important aspects of
developing TDI and RSDs are described in Section 2.
Hazard assessment determines the health effect potentially attributable to a contaminant (e.g.,
carcinogenic, hepatotoxic, teratogenic) and estimates the reference dose believed to be associated with
a defined level of incidence of that effect in the population. For a threshold substance, exposure less
than the reference dose should pose a zero probability of incidence of an adverse effect in the
population. For a non-threshold substance (i.e., a carcinogen or a germ cell mutagen), the critical risk
specific dose may define a risk level of 1 in 1 million. Methods of chemical evaluation employed by the
Environmental Health Directorate of Health Canada, are described in Richardson and Myers (1993),
Armstrong and Newhook (1992), Meek (1989), Environmental Health Directorate (1989, 1990,
1991) and Health Canada (1994). The toxicological evaluation and exposure assessment can typically
fit within a generalized framework for human health risk assessment (see Figure 16).
Toxic effects from exposure to environmental contaminants may be classified in the following broad
categories:
• organ-specific,
• neurological/behaviourial,
• reproductive/developmental,
• immunological, carcinogenic, and mutagenic.
These effects can be manifested at the biochemical, cellular, histopathological, and morphological levels.
Effects vary, depending upon the dosage, route of exposure (e.g., ingestion, inhalation, or dermal
contact), frequency and/or duration of exposure, species (and strain in the case of some animals),
physiological state, sex, and age of the exposed population. Toxicological effects from exposure to
chemical substances may be brief or prolonged, reversible or irreversible, immediate or delayed. The
nature, number, severity, incidence and/or prevalence of specific toxicological effects in populations (of
either humans or animal species) exposed to various chemicals generally increase with increasing dose
or level of exposure; this is commonly referred to as the exposure- or dose-response relationship.
For most environmental contaminants, data on the toxicological effects resulting from exposure are
restricted to information obtained from studies involving experimental animals. Occasionally, information
derived from studies of human populations (principally epidemiological investigations) forms an integral
part of the database upon which the assessment is based. Clearly, data on direct effects in humans are
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