Noncarcinogenic risk

Noncarcinogenic risk is represented by the hazard index (HI), which is the ratio of the chronic daily intake to the RfD ... 

Carlson-Lynch H, Price PS, Swartout JC, Dourson ML, and Keenan RE (1999) Application of quantitative information on the uncertainty in the R to noncarcinogenic risk assessments. HERA 5(3) 527-547. 

Noncancer effects are not expressed in terms of a probabilistic approach. Instead, the potential for noncarcinogenic effects is evaluated by comparing an exposure level over a specified period (typically, a lifetime) with a reference dose (RfD) derived for a similar exposure period (9). Reference doses may also be found in toxicological databases, such as IRIS. Noncancer risk is presented as a ratio of exposure to toxicity and is called a hazard quotient (HQ) (9). Using these assumptions, noncarcinogenic risk is calculated by the following equation (9) ... 

To assess tlie overall potential for noncarcinogenic effects posed by more dian one chemical, a liazard index (HI) approach has been developed based on EPA s Guidelines for Healdi Risk Assessment of Chemical Mixtures. This approach assumes that simultaneous subtlu eshold exposures to several chemicals could result in an adverse healtli effect. It also assumes tliat tlie magnitude of the adverse effect will be proportional to tlie sum of the ratios of the subtlireshold exposures to acceptable exposures. The non cancer hazard index is equal to tlie sum of the hazard quotients, as described below, where E and tlie RfD represent the same exposure period (e.g., subclironic, clironic, or shorter-term). 

Estimates of exposure levels posing minimal risk to humans (Minimal Risk Levels or MRLs) have been made for methyl parathion. An MRL is defined as an estimate of daily human exposure to a substance that is likely to be without an appreciable risk of adverse effects (noncarcinogenic) over a specified duration of exposure. MRLs are derived when reliable and sufficient data exist to identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration within a given route of exposure. MRLs are based on noncancerous health effects only and do not consider carcinogenic effects. MRLs can be derived for acute, intermediate, and chronic duration exposures for inhalation and oral routes. Appropriate methodology does not exist to develop MRLs for dermal exposure. 

In the case of noncarcinogenic substances, there exists a threshold this is an exposure with a dose below which there would not be adverse effect on the population that is exposed. This is the reference dose (RfD), and it is defined as the daily exposure of a human population without appreciable effects during a lifetime. The RfD value is calculated by dividing the no observed effect level (NOEL) by uncertainty factors. When NOEL is unknown, the lowest observed effect level (LOEL) is used. NOEL and LOEL are usually obtained in animal studies. The main uncertainty factor, usually tenfold, used to calculate the RfD are the following the variations in interspecies (from animal test to human), presence of sensitive individuals (child and old people), extrapolation from subchronic to chronic, and the use of LOEL instead of NOEL. Noncancer risk is assessed through the comparison of the dose exposed calculated in the exposure assessment and the RfD. The quotient between both, called in some studies as hazard quotient, is commonly calculated (Eq. 2). According to this equation, population with quotient >1 will be at risk to develop some specific effect related to the contaminant of concern. 

Because the theoretical excess lifetime cancer risk for dimethylhydrazines was estimated from nonverified potency estimates and because AEGLs are applicable to rare events or single, once-in-a-lifetime exposures in a limited geographic area with a small population, the AEGL values based on noncarcinogenic endpoints were considered to be more appropriate. 

Additional information on hepatic lesions in species other than the rat and mouse would be useful in evaluating the risk to humans for both noncarcinogenic and carcinogenic effects from hexachloroethane exposure. 

For discrete responses, the BMR is typically chosen at 10% above the control response, the BMD 10 as an excess risk of 10% is considered to be at or near the limit of sensitivity in most carcinogenicity studies and in some noncarcinogenicity studies as well. If a study has greater than usual sensitivity, then a lower BMR can be used, although the BMDio and BMDLio should always be presented for comparison purposes. 

SSLs are risk-based concentrations derived from standardized equations combining exposure information assumptions with US-EPA toxicity data. For the ingestion, dermal, and inhalation pathways, toxicity criteria are used to define an acceptable level of contamination in soil, based on a one-in-a-million (10 individual excess cancer risk for carcinogens and a Hazard Quotient (HQ) of 1 for noncarcinogens. The hazard quotient is defined as the ratio of an exposure estimate over the Reference Dose or Concentration (Section 5.1), i.e., HQ = Exposure/(RfD or RfC). 

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