3.4.1. INTEGRATED RISK INFORMATION SYSTEM (IRIS) – ENVIRONMENTAL PROTECTION AGENCY
The IRIS, prepared and maintained by EPA, is an electronic database containing information on human health effects that may result from exposure to various chemicals in the environment. IRIS contains descriptive and quantitative information and includes oral reference doses (RfDs) and inhalation reference concentrations (RfCs) for chronic noncarcinogenic health effects and oral slope factors and inhalation unit risks for carcinogenic effects. RfDs are usually provided in units of mg/kg-day, and RfCs in units of mg/m3. Oral/Cancer Slope Factors (CSF) are usually provided in units of (mg/kg-day)-1, and Inhalation Unit Risk values (IUR) are provided in (microgram per cubic meter [µg/m3])-1. RfDs, CSFs, and IURs are not directly comparable to environmental concentrations. However, they can be used in equations, along with exposure assumptions, to derive health-based exposure guidelines that can be compared directly to environmental concentrations.
EPA IRIS values represent the Agency’s consensus for chronic toxicity values. Many other federal and state agencies also make IRIS their preferred source of toxicity values. IRIS assessments are externally peer-reviewed before they are released as final assessments.
- Reference Doses and Reference Concentrations
RfDs and RfCs are generally defined as an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. It can be derived from a NOAEL, a LOAEL, or a benchmark dose, with default or data-derived uncertainty factors generally applied to reflect limitations of the data used.110
- Oral/Cancer Slope Factors
The CSF is defined as a plausible upper bound on the increased cancer risk from a lifetime exposure to an agent. This estimate is usually expressed as a dose in units of proportion (of a population) affected per mg/kg-day.
- Inhalation Unit Risk Values
The upper bound excess lifetime cancer risk estimated to result from repeated exposure to an agent at a concentration of 1 µg/m3 in air. The interpretation of IUR would be as follows: if unit risk = 2 x 10- 6 per µg/m3, 2 excess cancer cases (upper bound estimate) are expected to develop per 1,000,000 people if exposed daily for a lifetime to 1 microgram of the chemical in 1 cubic meter of air.
3.4.2. PROVISIONAL PEER-REVIEWED TOXICITY VALUES (PPRTVS) – ENVIRONMENTAL PROTECTION AGENCY
EPA's Office of Research and Development/National Center for Environmental Assessment/Superfund Health Risk Technical Support Center (STSC) develops PPRTVs on a chemical-specific basis when requested by EPA’s Superfund program.111 The PPRTVs are developed specifically for, and used by, the Superfund Program. Although subject to review and public comment on a site-specific basis as part of the site decision-making process, the PPRTVs are provisional values, and are not widely disseminated.
IRIS normally represents the official EPA scientific position regarding the toxicity of a chemical based on the data available at the time of the review. When no IRIS values are available, the second tier is EPA’s PPRTVs. Generally, PPRTVs are derived for one of two reasons. First, the STSC is conducting a batch-wise review of the toxicity values previously published in the Health Effects Assessment Summary Tables (HEAST). As such reviews are completed, those toxicity values are removed from HEAST, and any new toxicity value developed in such a review will be placed in the PPRTV database. Second, Regional Superfund Offices may request a PPRTV for contaminants lacking a relevant IRIS value. The STSC uses the same methodologies to derive PPRTVs in either case.
Where an appropriate toxicity value is not available, a PPRTV may be developed by EPA for a chemical of concern following a nationally significant or large-scale release. SMEs and decision-makers could then review the supporting documents and derivation of the PPRTV to determine its appropriateness in developing a site- or situation-specific decision.
3.4.3. ACUTE INTERMEDIATE AND CHRONIC MINIMUM RISK LEVELS (MRLS) – AGENCY FOR TOXIC SUBSTANCES AND DISEASE REGISTRY
The ATSDR has developed MRLs in response to mandates under the CERCLA, as amended by the Superfund Amendments and Reauthorization Act.112
An MRL is an estimate of the daily human exposure to a hazardous substance that is likely to be without appreciable risk of adverse noncarcinogenic health effects over a specified duration of exposure. These values are not regulatory numbers but are used by ATSDR health assessors and others to identify contaminants and potential health effects that may be of concern at hazardous waste sites.
MRLs are set below levels that, based on current information, might cause adverse health effects in the persons most sensitive to such substance-induced effects. Most MRLs contain some degree of uncertainty because of the lack of precise toxicological information on persons who might be most sensitive (e.g., infants, elderly, and the nutritionally or immunologically compromised) to effects of hazardous substances. In deriving MRLs, ATSDR uses a health-protective approach to address these uncertainties by applying uncertainty factors and modifying factors to the toxicity data. ATSDR states that exposure to a level above the MRL does not necessarily mean that adverse health effects will occur.
MRLs are derived for exposure durations of 1 to 14 days via the oral and inhalation routes of exposure. While ATSDR refers to this duration as acute, it corresponds to the EPA/IRIS short-term exposure scenario (see Section 2.2). In addition, ATSDR derives oral and inhalation MRLs for longer-term exposure durations: intermediate (>14 to 364 days) and chronic (365 days and longer).
MRLs receive extensive internal and external peer-review.
3.4.4. ACUTE AND CHRONIC REFERENCE EXPOSURE LEVELS (CA-RELS) – STATE OF CALIFORNIA ENVIRONMENTAL PROTECTION AGENCY
The California EPA (CalEPA) Office of Environmental Health Hazard Assessment has published reviews of the acute health effects for 51 chemical contaminants and recommends acute CA-RELs for each chemical based on the appropriate and sensitive adverse health effect.113 The CA-RELs are distinct from the NIOSH occupational RELs. The CA-RELs have a heavy emphasis on the utilization of available human data, with two-thirds of the acute CA-RELs based on observed human health outcomes. The final values incorporate uncertainty factors similar to those used in deriving RfCs for chronic exposures. CalEPA derives acute (1-hour) inhalation CA-RELs for hazardous airborne substances. The acute CA-REL represents an exposure that is not likely to cause adverse effects in a human population, including sensitive subgroups, exposed to that concentration for 1 hour on an intermittent basis.114
Cal-EPA also publishes chronic CA-RELs for 80 substances.115 Chronic CA-RELs are concentrations or doses at or below which adverse health effects are not likely to occur. A central assumption is that a population threshold exists below which adverse effects will not occur in a population; however, such a threshold is not observable and can only be estimated. Areas of uncertainty in estimating effects among a diverse human population exposed continuously over a lifetime are addressed using extrapolation and uncertainty factors. Protection against carcinogenicity and against adverse health effects of short-term exposures are not considered in these guidelines. For this reason, chemicals should be evaluated separately for their carcinogenic potential and additional acute health effects that may occur.
Cal EPA’s Toxicity Criteria Database provides peer-reviewed toxicity values that address both cancer and noncancer effects.116
3.4.5. GENERAL POPULATION LIMITS (GPLS) FOR CHEMICAL WARFARE AGENTS – CENTERS FOR DISEASE CONTROL AND PREVENTION
CDC recommends GPLs, which are long-term (lifetime) exposure limits for several chemical warfare agents in air, applicable to populations surrounding chemical weapons disposal sites. GPLs have been developed for GA, GB, VX, HD, and L.117, 118
3.4.6. OTHER PEER-REVIEWED VALUES OR CONCENTRATION LEVELS
In the absence of chemical-specific toxicity values from one of the above sources (EPA, ATSDR or Cal- EPA), one should consider other peer-reviewed published values. For example, the NRC/NAS has reviewed and published the RfDs for six chemical warfare agents (GA, GB, GD, VX, HD, and L) and a CSF for sulfur mustard.119 Additionally, a set of peer-reviewed studies developed site and situation-specific clearance goals for an airport CWA attack scenario.120, 121