Minimal Risk Levels (MRLs)
The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) [42 U.S.C. 9604 et seq.], as amended by the Superfund Amendments and Reauthorization Act (SARA) [Pub. L. 99 499], requires that the Agency for Toxic Substances and Disease Registry (ATSDR) develop jointly with the U.S. Environmental Protection Agency (EPA), in order of priority, a list of hazardous substances most commonly found at facilities on the CERCLA National Priorities List (NPL) (42 U.S.C. 9604(i)(2)); prepare toxicological profiles for each substance included on the priority list of hazardous substances, and to ascertain significant human exposure levels (SHELs) for hazardous substances in the environment, and the associated acute, subacute, and chronic health effects (42 U.S.C. 9604(i)(3)); and assure the initiation of a research program to fill identified data needs associated with the substances (42 U.S.C. 9604(i)(5)).
The ATSDR Minimal Risk Levels (MRLs) were developed as an initial response to the mandate. Following discussions with scientists within the Department of Health and Human Services (HHS) and the EPA, ATSDR chose to adopt a practice similar to that of the EPA's Reference Dose (RfD) and Reference Concentration (RfC) for deriving substance specific health guidance levels for non neoplastic endpoints. An MRL is an estimate of the daily human exposure to a hazardous substance that is likely to be without appreciable risk of adverse noncancer health effects over a specified duration of exposure. These substance specific estimates, which are intended to serve as screening levels, are used by ATSDR health assessors and other responders to identify contaminants and potential health effects that may be of concern at hazardous waste sites. It is important to note that MRLs are not intended to define clean up or action levels for ATSDR or other Agencies.
The toxicological profiles include an examination, summary, and interpretation of available toxicological information and epidemiologic evaluations of a hazardous substance. During the development of toxicological profiles, MRLs are derived when ATSDR determines that reliable and sufficient data exist to identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration for a given route of exposure to the substance. MRLs are based on noncancer health effects only and are not based on a consideration of cancer effects. Inhalation MRLs are exposure concentrations expressed in units of parts per million (ppm) for gases and volatiles, or milligrams per cubic meter (mg/m3) for particles. Oral MRLs are expressed as daily human doses in units of milligrams per kilogram per day (mg/kg/day). Radiation MRLs are expressed as external exposures in units of millisieverts.
ATSDR uses the no observed adverse effect level/uncertainty factor (NOAEL/UF) approach to derive MRLs for hazardous substances. They are set below levels that, based on current information, might cause adverse health effects in the people most sensitive to such substance induced effects. MRLs are derived for acute (1-14 days), intermediate (>14-364 days), and chronic (365 days and longer) exposure durations, and for the oral and inhalation routes of exposure. Currently MRLs for the dermal route of exposure are not derived because ATSDR has not yet identified a method suitable for this route of exposure. MRLs are generally based on the most sensitive substance-induced end point considered to be of relevance to humans. ATSDR does not use serious health effects (such as irreparable damage to the liver or kidneys, or birth defects) as a basis for establishing MRLs. Exposure to a level above the MRL does not mean that adverse health effects will occur.
MRLs are intended to serve as a screening tool to help public health professionals decide where to look more closely. They may also be viewed as a mechanism to identify those hazardous waste sites that are not expected to cause adverse health effects. Most MRLs contain some degree of uncertainty because of the lack of precise toxicological information on the people who might be most sensitive (e.g., infants, elderly, and nutritionally or immunologically compromised) to effects of hazardous substances. ATSDR uses a conservative (i.e., protective) approach to address these uncertainties consistent with the public health principle of prevention. Although human data are preferred, MRLs often must be based on animal studies because relevant human studies are lacking. In the absence of evidence to the contrary, ATSDR assumes that humans are more sensitive than animals to the effects of hazardous substances that certain persons may be particularly sensitive. Thus the resulting MRL may be as much as a hundredfold below levels shown to be nontoxic in laboratory animals. When adequate information is available, physiologically based pharmacokinetic (PBPK) modeling and benchmark dose (BMD) modeling have also been used as an adjunct to the NOAEL/UF approach in deriving MRLs.
Proposed MRLs undergo a rigorous review process. They are reviewed by the Health Effects/MRL Workgroup within the Division of Toxicology and Environmental Medicine; and expert panel of external peer reviewers; the agency wide MRL Workgroup, with participation from other federal agencies, including EPA; and are submitted for public comment through the toxicological profile public comment period. Each MRL is subject to change as new information becomes available concomitant with updating the toxicological profile of the substance. MRLs in the most recent toxicological profiles supersede previously published levels. To date, 143 inhalation MRLs, 241 oral MRLs and 8 external radiation MRLs have been derived. A listing of the current published MRLs by route and duration of exposure is provided as follows.
ATSDR Contact Person for MRLs:
Dr. Selene Chou
Division of Toxicology and Environmental Medicine
Agency for Toxic Substances and Disease Registry
1600 Clifton Road, Mailstop F62
Atlanta, Georgia 30333