About Minimal Risk Levels

What to know

  • MRLs are an estimate of how much of a hazard substance a human can be exposed to on a daily basis without health risks (not including cancer).
  • MRLs are meant to serve as screening tool to help public health professionals decide where to look more closely.
  • MRLs are not intended to define clean up or action levels for ATSDR or other Agencies.
Four flasks filled with different colored chemicals in four flasks on books against a green background.

Background

The ATSDR Minimal Risk Levels (MRLs) were initially developed in response to the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). ATSDR held discussions with scientists within the Department of Health and Human Services (HHS) and the Environmental Protection Agency (EPA). ATSDR then chose to adopt a practice similar to that of the EPA’s Reference Dose (RfD) and Reference Concentration (RfC). These sources outline recommendations 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 non-cancer health effects over a specified duration of exposure. These substance specific estimates are intended to serve as screening levels. They are then used by ATSDR health assessors and other responders to identify contaminants and potential health effects that may be of concern at hazardous waste sites.

MRL intent‎

MRLs are intended to serve as a screening tool to help public health professionals decide where to look more closely. MRLs are not intended to define clean up or action levels for ATSDR or other Agencies.

Our approach

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 non-cancer health effects only and are not based on a consideration of cancer effects.

Purpose of MRLs

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.

Units

Inhalation MRLs are exposure concentrations expressed in units of parts per million (ppm) for gases and volatiles. For particles, they are expressed in units of milligrams per cubic meter (mg/m3). 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.

Exposure durations

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. MRL exposure durations derived for oral and inhalation exposure are:

  • Acute (1-14 days)
  • Intermediate (>14-364 days)
  • Chronic (365 days and longer)

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 as a basis for establishing MRLs. This includes irreparable damage to the liver or kidneys, or birth defects. Exposure to a level above the MRL does not mean that adverse health effects will occur.

Degree of uncertainty

Most MRLs contain some degree of uncertainty. This is due to the lack of precise toxicological information on the people who might be most sensitive to effects of hazardous substances. These groups include infants, elderly, and nutritionally or immunologically compromised.

Animal based MRL studies

ATSDR uses a conservative or protective approach to address these uncertainties consistent with the public health principle of prevention. Although human data is 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.

ATSDR also assumes that certain persons may be particularly sensitive. Because of this, 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. PBPK and BMD are used as an adjunct to the NOAEL/UF approach in deriving MRLs.

Reviewing MRLs

Proposed MRLs undergo a rigorous review process. They are reviewed by the Health Effects/MRL Workgroup within the Division of Toxicology and Human Health Sciences. This consists of:

  • An expert panel of external peer reviewers
  • The agency wide MRL Workgroup
  • Participation from other federal agencies, including EPA

The proposed MRLS are then 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.

Policy

The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA),1 as amended by the Superfund Amendments and Reauthorization Act (SARA)2, 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)3
  • Prepare toxicological profiles for each substance included on the priority list of hazardous substances.
  • Ascertain significant human exposure levels (SHELs) for hazardous substances in the environment, and the associated acute, subacute, and chronic health effects.4
  • Assure the initiation of a research program to fill identified data needs associated with the substances.5

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))
  • Assure the initiation of a research program to fill identified data needs associated with the substances (42 U.S.C. 9604(i)(5))
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Content Source:
Agency for Toxic Substances and Disease Registry
  1. 42 U.S.C 9604 et seq. (Response Authorities)
  2. Pub. L. 99 499 (Superfund Amendments and Reauthorization Act of 1986)
  3. 42 U.S.C. 9604(i)(2)
  4. 42 U.S.C. 9604(i)(3)
  5. 42 U.S.C. 9604(i)(5)