Human Health Risk and Environmental Analysis

This site is maintained and operated through an Interagency Agreement between the EPA/Office of Superfund Remediation and Technology Innovation and DOE/ORNL/Environmental Sciences Division. For questions or comments please contact Linda Gaines in EPA/OSRTI.

User's Guide: Chemical Toxicity

The PPRTV electronic library summarizes provisional toxicity values for contaminants in the table, when no IRIS value on that contaminant is available.


The RfD or RfC is an estimate (with uncertainty spanning perhaps an order of magnitude) of the daily exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects. In the case of a subchronic RfD or RfC, the exposure occurs only during a limited portion (generally less than seven years) of the lifetime, while chronic exposures occur over a longer portion of a lifetime (generally more than seven years). The RfD and RfC values are listed with the headings "Subchronic" and "Chronic". The critical dose, or point of departure, is either a No-Observed-Adverse-Effect Level (NOAEL), a Lowest-Observed-Adverse-Effect Level (LOAEL), or a benchmark dose/concentration (BMD/C). (See Technical Information: Effect Level Definitions, for more information.) The RfD or RfC is derived by dividing the point of departure by the composite or total uncertainty factor (UF) times a modifying factor (MF):

RfC or RfD=(NOAEL) or (LOAEL)/(UF x MF)

An example of this information is shown in the summary for Aldrin. Notice that a Chronic RfD for Aldrin is available on IRIS, so it is not listed here.

PPRTVs are derived using the methodologies from EPA's Integrated Risk Information System (IRIS) program. Several methodologies are used by the IRIS Program to derive oral noncancer toxicity values (as an RfD) which can be accessed on EPA's IRIS website

The current methodology for the derivation of inhalation RfCs is detailed in "Methods for Derivation of Inhalation Reference Concentrations and Application of Inhalation Dosimetry" (U.S. EPA, 1994, EPA/600/8-90/066F). It should be noted that these methods are different from those used for oral RfDs because of (1) the dynamics of the respiratory system and its diversity across species and (2) differences in the physicochemical properties of contaminants (such as the size and shape of a particle or whether the contaminant is an aerosol or a gas). Parameters such as deposition, clearance mechanisms and the physicochemical properties of the inhaled agent are considered in the determination of the effective dose delivered to the target organ.

The RfD or RfC is used as a reference point for gauging the potential effects of other exposures. Usually, exposures that are less than the RfD or RfC are not likely to be associated with health risks. As the frequency and intensity of exposures exceeding the RfD or RfC increases, the probability increases that adverse health effects may be observed in a human population. Nonetheless, a clear distinction that would categorize all exposures below the RfD or RfC as "acceptable" (below the noncancer toxic effect threshhold1) and all exposures in excess of the RfD or RfC as "unacceptable" (causing adverse effects) cannot be made. In addition, RfD and RfC values, and particularly those with limitations in the quality or quantity of supporting data, are subject to change as additional information becomes available.

RfD and RfC values that have been derived for carcinogens are based on noncancer endpoints only and should not be assumed to be protective against carcinogenicity.


In assessing the carcinogenic potential of a contaminant, PPRTV assessments use the 1999 Guidelines for Carcinogen Risk Assessment (NCEA-F-0644) to establish the following descriptions for summarizing the weight of evidence as to whether a contaminant is or may be carcinogenic.

  • Carcinogenic to Humans
  • Likely to be Carcinogenic to Humans
  • Suggestive Evidence of Carcinogenicity, but Not Sufficient to Assess Human Carcinogenic Potential
  • Data Are Inadequate for An Assessment of Human Carcinogenic Potential
  • Not Likely to be Carcinogenic to Humans

Quantitative carcinogenic risk assessments are performed for chemicals which are carcinogenic or likely to be carcinogenic and on a case-by-case basis for contaminants which have suggestive evidence of carcinogenicity, but not for contaminants which have inadequate data or which are not likely carcinogenic. Cancer slope factors (formerly called cancer potency factors) are estimated through the use of mathematical extrapolation models, most commonly the linearized multistage model. The models estimate the largest possible linear slope (within the 95% confidence limit) at low extrapolated doses that is consistent with the data. The slope factor or risk is characterized as an upper-bound estimate (i.e., the true risk to humans is not likely to exceed the upper-bound estimate and in fact may be lower).

Quantitative carcinogenic estimates include the following:

[slope factor] = risk per unit dose = risk per mg/kg/day

[slope factor or unit risk] for inhalation exposure = risk per concentration unit in air = risk per µg/m3

An example of this information is shown in Nitroglycerin.

Also given in the example are the references for the chemical. The reference is identified by the chemical name.

Quantitative carcinogenic estimates are specific for the route of exposure. Footnotes are used to indicate when the values for inhalation or oral exposure are based on extrapolation from another route of exposure.

To estimate risk-specific concentrations in air from the [slope factor or unit risk] in air, the specified level of risk is divided by the [slope factor or unit risk] for air. Hence, the air concentration (in µg/m3) corresponding to an upper-bound increased lifetime cancer risk of 1x10-5 is calculated as follows:

µg/m3 in air = (1 x 10-5)/[slope factor or unit risk] in (µg/m3)-1


1   Unlike the linear response often assumed for cancer risk, EPA's Risk Assessment Guidance for Superfund (RAGS) assumes that there is a threshold for noncancer adverse effects, below which even sensitive subpopulations are unlikely to experience deleterious or adverse toxic effects (RAGS Volume I, Part A, sections 7.2 and 8.2.1). Recently, some EPA cancer assessments indicate that there may be thresholds for some carcinogens below which there may be no significant potential for cancer to occur.