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Compendium of Papers on MRLs and Health Effects

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The Agency for Toxic Substances and Disease Registry (ATSDR) is mandated by the congress to address potential public health impacts associated with environmental exposures to hazardous substances from waste sites and releases of hazardous substances into the environment. ATSDR develops in order of priority a list of hazardous substances most commonly found at facilities on the CERCLA National Priority List. The agency is directed to prepare toxicological profiles for priority hazardous substances, ascertain significant human exposure levels for these substances in the environment and the associated health effects, and identify research areas needed to fill data gaps.

In order to determine the relationship between exposures to hazardous substances and the occurrence of adverse health outcomes, ATSDR has developed a list of priority health conditions (PHCs) to provide a focus for investigations in studies with measurable and observable outcomes among different levels of exposure or a range of health effects (ATSDR 1993). The studies of PHCs will provide the greatest likelihood of finding human health effects among individuals exposed to hazardous substances.

In response to congressional mandate to ascertain significant human exposure levels to hazardous substances, ATSDR develops minimal risk levels (MRLs) for priority hazardous substances most frequently found at hazardous waste sites. The MRLs are derived based on the most sensitive non-cancer adverse health endpoints which are consistent with the ATSDR PHCs.

This compendium is intended to serve as a guide to the evaluation of the biological significance of non-cancer health effects, and other issues relevant to derivation of health guidance values such as MRLs.

Introduction

The Agency for Toxic Substances and Disease Registry (ATSDR) is mandated by Congress to address potential public health impacts associated with environmental exposures to hazardous substances from waste sites and releases of hazardous substances into the environment. ATSDR develops in order of priority, a list of hazardous substances most commonly found at facilities on the CERCLA National Priority List. The agency is also directed to prepare toxicological profiles for priority hazardous substances, ascertain significant human exposure levels for these substances in the environment and the associated health effects, and identify research areas needed to fill data gaps.

To further focus these efforts, ATSDR developed a list of priority health conditions (PHCs) to evaluate potential health risks to persons living near hazardous waste sites and to determine needed programs and applied human health activities involving hazardous substances identified at the sites (ATSDR 1993). The PHCs also assist ATSDR programs in the prevention or mitigation of adverse human health effects and diminished quality of life resulting from exposure to hazardous substances in the environment. The selection of PHCs was based on existing knowledge of toxicology and experience in assessing and evaluating hazardous substances and adverse health outcomes. The ATSDR PHCs are:

Birth defects and reproductive disorders
Cancer
Immune function disorders
Kidney dysfunction
Liver dysfunction
Lung & respiratory diseases
Neurotoxic disorders

In order to address the congressional mandate to ascertain levels of exposure that present a significant risk to human health, ATSDR develops minimal risk levels (MRLs) for priority hazardous substances most frequently found at hazardous waste sites. The MRLs are health guidance values derived based on the most sensitive non-cancer adverse health endpoints. These endpoints are consistent with the ATSDR PHCs. This compendium is comprised of scientific journal publications authored by ATSDR scientists on health implications of environmental exposures and issues concerning health guidance values. The topics cover the precision, uses, and limitations of public health guidance values, methodology for MRL derivation, and evaluation of toxicological end points to derive MRLs. Classification of specific health end points and their roles in the derivation of MRLs are also presented; the end points are neurological, respiratory, developmental, reproductive, hematological, hepatic, renal, and immunological. Other topics dealing with uncertainty factors and reducing uncertainty in the derivation health guidance values are also included. More recent issues on health guidance values for chemical mixtures, and application of computational toxicology methods are also presented.

References

ATSDR, 1993. Priority Health Conditions. An integrated strategy to evaluate the relationship between illness and exposures to hazardous substances. Edited by Lybarger, JA, Spengler, RF, and De Rosa, CT. U.S. Department of Health and Human Services, Agency for Toxic Substances and Disease Registry, Atlanta, Georgia

List of Papers

List of MRL Papers List of MRL Papers [PDF, 12KB]
Public Health Implications of Environmental Exposures Public Health Implications of Environmental Exposures [PDF, 1MB]
Evaluating toxicologic end points to derive minimal risk levels for hazardous substances Evaluating toxicologic end points to derive minimal risk levels for hazardous substances [PDF, 360KB]
Minimal risk levels (MRLs) for hazardous substances. Minimal risk levels (MRLs) for hazardous substances. [PDF, 950KB]
Utilizing uncertainty factors in minimal risk levels derivation Utilizing uncertainty factors in minimal risk levels derivation [PDF, 917KB]
Health effects classification and its role in the derivation of minimal risk levels: Neurological effects Health effects classification and its role in the derivation of minimal risk levels: Neurological effects [PDF, 772KB]
Health effects classification and its role in the derivation of minimal risk levels: Respiratory effects Health effects classification and its role in the derivation of minimal risk levels: Respiratory effects [PDF, 964KB]
Health effects classification and its role in the derivation of minimal risk levels: Developmental effects. Health effects classification and its role in the derivation of minimal risk levels: Developmental effects [PDF, 618KB]
The use of hematological effects in the development of minimal risk levels The use of hematological effects in the development of minimal risk levels [PDF, 569KB]
Health effects classification and its role in the derivation of minimal risk levels: Reproductive and endocrine effects Health effects classification and its role in the derivation of minimal risk levels: Reproductive and endocrine effects [PDF, 829KB]
Health effects classification and its role in the derivation of minimal risk levels: Hepatic effects Health effects classification and its role in the derivation of minimal risk levels: Hepatic effects [PDF, 913KB]
Health effects classification and its role in the derivation of minimal risk levels: Renal effects Health effects classification and its role in the derivation of minimal risk levels: Renal effects [PDF, 576KB]
Health effects classification and its role in the derivation of minimal risk levels: Immunological effects Health effects classification and its role in the derivation of minimal risk levels: Immunological effects [PDF, 157KB]
The precision, uses, and limitation of public health guidance values The precision, uses, and limitation of public health guidance values [PDF, 1MB]
Applications of computational toxicology methods at the Agency for Toxic Substances and Disease Registry Applications of computational toxicology methods at the Agency for Toxic Substances and Disease Registry [PDF, 603KB]
Reducing uncertainty in the derivation and application of health guidance values in public health practice. Dioxin as a case study. Reducing uncertainty in the derivation and application of health guidance values in public health practice. Dioxin as a case study. [PDF, 819KB]
Public health guidance values for chemical mixtures: Current practice and future directions Public health guidance values for chemical mixtures: Current practice and future directions [PDF, 781KB]

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This page was updated on 09/26/2007