|
 |
|
|
|
|
|
|
Hazard Identification
In this initial step, the potential for a xenobiotic to induce any type of toxic hazard is evaluated. Information is gathered and analyzed in a weight-of-evidence approach. The types of data usually consist of:
|
|
|
|  | human
epidemiology data
|
|
| | animal bioassay data
|
|
| | supporting data
|
|
Based on these results, one or more toxic hazards may be identified (such as cancer, birth defects, chronic toxicity, neurotoxicity). The primary hazard of concern is one in which there is a serious health consequence (such as cancer) that can occur at lower dosages than other serious toxic effects. The primary hazard of concern will be chosen for the dose-response assessment.
Human
epidemiology data are the most desirable and are given highest priority since they avoid the concern for species differences in the toxic response. Unfortunately, reliable
epidemiology studies are rarely available. Even when epidemiology studies have been conducted, they usually have incomplete and unreliable exposure histories. For this reason, it is rare that risk assessors can construct a reliable dose-response relationship for toxic effects based on epidemiology studies. More often, the human studies can only provide qualitative evidence that a causal relationship exists.
In practice, animal bioassay data are generally the primary data used in risk assessments. Animal studies are well-controlled experiments with known exposures and employ detailed, careful clinical, and pathological examinations. The use of laboratory animals to determine potential toxic effects in humans is a necessary and accepted procedure. It is a recognized fact that effects in laboratory animals are usually similar to those observed in humans at comparable dose levels. Exceptions are primarily attributable to differences in the pharmacokinetics and metabolism of the xenobiotics.
Supporting data derived from cell and biochemical studies may help the risk assessor make meaningful predictions as to likely human response. For example, often a chemical is tested with both human and animal cells to study its ability to produce cytotoxicity, mutations, and DNA damage. The cell studies can help identify the mechanism by which a substance has produced an effect in the animal bioassay. In addition, species differences may be revealed and taken into account.
A chemical's toxicity may be predicted based on its similarity in structure to that of chemical for which the toxicity is known. This is known as a structure-activity relationship (SAR). The SAR has only limited value in risk assessment due to exceptions to the predicted toxicity.
 
|
|
|
|
