Risk characterization is the final phase of the health risk assessment process. It integrates the three phases: Hazard Identification, Dose-Response Assessment, and Exposure Assessment. This phase determines the probability of an adverse effect to a human population by a toxic substance and outlines permissible exposure levels from which standards of exposure are set.
An adverse effect is defined by the US Environmental Protection Agency as "..any biochemical, physiological, anatomical, pathological, and/or behavioral change that results in functional impairment that may affect the performance of the whole organism or reduce the ability of the organism to respond to an additional challenge."
Standards of exposure are set based on adverse health effects, costs and benefits, socio-economic considerations, and technological limits of detection. Permissible exposures are calculations which observe measurable adverse health effects only and are used to calculate permissible environmental concentrations.
Characterizing Risk for Non-carcinogens
The first step is to consider the permissible exposure (RfD) as was defined in the dose-response phase of the risk assessment, compared to the maximum daily dose (MDD) occurring within the target population, and which is calculated in the exposure assessment phase. If the MDD from the target population is smaller than the RfD, which includes a safety factor, the exposure is considered relatively 'safe'. If it is higher than the RfD and is approaching within 100 fold of the NOEL from the toxicity studies, then the exposure is considered 'unsafe'. There is no clear demarcation between 'safe' and 'unsafe' exposure levels. As of yet, there are far too many uncertainties associated with our knowledge of the effects of substances and individual human sensitivities. So, safe and unsafe are subjective terms, although safe exposures are based on conservative estimates. That is to say, they are more 'safe' than 'unsafe'.
Permissible concentrations for chemicals in the environment are calculated based on body weight, intake, frequency and duration of exposure, and the RfD. Permissible concentration is equal to:
RfD x Body weight
Intake x Duration x Frequency
These values are used to set regulatory standards for safe drinking water maximum contaminant levels, permissible exposure limits in the workplace, and pesticide residue limits in food and feed products. Note that for those with small body weights, such as children the permissible concentration levels within the environment will have to be lower.
The Risk of exposure for non-oncogenic effects is expressed as a Margin of Exposure (MOE). MOE is equivalent to:
A MOE over 10, after extrapolation to humans, is considered low risk. This means that the No Effects Level is a lot higher than the actual exposure occurring among the most exposed individuals within the target population.
Characterizing Risk for Carcinogens
Considering that carcinogens pose a risk at any dose and the probability of developing cancer would increase with dose, we can state that the probability can range from being negligibly low at low dose ranges or unacceptably high at high dose ranges. So, what risk is negligible? This has been a controversial question. There are a variety of arguments posed by both sides:
1) The public is exposed to many naturally occurring carcinogens all of the time
2) People expose themselves to large amounts of carcinogens willingly, such as tobacco use
On the other hand:
1) People should have the right to not be exposed to high risk agents against their will
2) Since oncogenicity is a step by step, cumulative process and we are exposed to many cancer causing agents, the risk should be set at negligible or zero levels.
Currently the risk value of one in a million is considered an insignificant risk and is used as a maximum value for defining permissible environmental concentrations. Risk values for carcinogens are calculated by multiplying the lifetime average daily dose (LADD) from the exposed population times the potency or slope factor as defined in the dose-response assessment phase of the risk assessment.
Let us assume an LADD of 0.002 mg/Kg body weight/day. We can use the potency of Aldrin at 17 (mg/Kg body weight/day)-1 from table 2 on the dose-response page:
= LADD x Slope factor
= 0.002 x 17
= one in 29
This is a very high value, statistically, one in 29 people exposed will get cancer from the lifetime average daily dose of 0.002 mg/Kg/day. Since we can't change the potency of Aldrin we must determine what daily dose over a lifetime would give us a maximum of one in a million risk:
= one in 1,000,000 / Slope factor
= 0.000001 / 17
= 0.00000006 LADD
The LADD must be reduced to attain a maximum risk of one in a million. Environmental concentrations would have to be dramatically reduced to meet the 'insignificant risk' of one in a million.
In order to fully characterize risk for a cancer causing agent the assessor must integrate the calculated risk value and the strength of evidence for carcinogenicity, which was introduced in the dose-response phase of the risk assessment. If the strength of evidence is very weak then there is not certainty with regards to carcinogenic action in humans. The strength of evidence is a qualitative measure of certainty that a chemical causes cancer in humans. If an agent is found to cause cancer in male mice only and in no other species it may be an indicator for a specific biochemical pathway found in male mice that does not exist in humans or other tested species. This is an example of weak evidence.
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This page was prepared by Theresa L. Pedersen, UCD EXTOXNET FAQ Team. September, 1997. I would like to thank Nu-may Ruby Reed, PhD for allowing me to draw freely from her lectures on Health Risk Assessment, which are the backbone of this page. Her lectures were conducted at the University of California, Davis in the fall quarter of 1996. Thanks again Ruby!