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Toxicology/Dose-Response Assessment

overview Risk Characterization Exposure Assessment Hazard Identification Uncertainty Analysis The dose-response assessment provides quantitative estimates of the toxicity of each contaminant of concern. This information is derived from the scientific literature by regulatory toxicologists and is typically obtained from published databases. For non-cancer causing agents, a reference dose (RfD) describes the daily dose of contaminant to which an individual can be exposed without expecting adverse health effects. For cancer-causing agents, a cancer slope factor (CSF) describes the potency of the carcinogen.

Note that the route of exposure dictates which "dose" to use.

 

              • For ingestion, use "administered dose."
              • For dermal exposure, use "absorbed dose."
              • For inhalation, use "administered dose."  

For non-carcinogenic compounds a dose-response curve illustrates the relationship between the level of a dose and a particular biological response within the experimental population.

NOAEL : No observable adverse effect level

LOAEL: Lowest observable adverse effect level

 
Threshold Concentration
The threshold concentration is the concentration above which some effect (or response) will be produced and below which it will not.

Non-carcinogens:

Threshold level is the level of exposure below which it is unlikely that there would be deleterious health effects during a lifetime.

A reference dose (RfD) estimates the daily dose of a non-carcinogenic contaminant to which humans can be exposed to without expecting adverse health effects.

The RfD is calculated by starting with the NOAEL and then taking into account various uncertainty factors.  If no NOAEL is available, then a LOAEL or other benchmark dose can be used, but additional uncertainty factors must be applied. Reference doses are inclusive of sensitive subpopulations, such as children, the elderly, or people who are immune-compromised.  Behavioral differences, physiological differences, inter and intra individual variability all contribute to the way that different groups and individuals respond to chemicals.  Uncertainty factors are applied in the calculation of a reference dose to cover all of these possibilities when considering a safe dose. 

Carcinogens:

There is no threshold, because there is no level of exposure that does not pose a finite probability of generating a carcinogenic response. In other words, there is risk associated with all levels of exposure.

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