Health effects classification and its role in the derivation of minimal risk levels: renal effects.

The Agency for Toxic Substances and Disease Registry (ATSDR) derives minimal risk levels (MRLs) for priority hazardous substances. MRLs are health guidance values intended to serve as screening levels for health assessors to select contaminants of concern and to assess potential health effects at hazardous waste sites and areas affected by unplanned releases. Current MRLs are published in ATSDR toxicological profiles and are listed at the ATSDR website at . To date, ATSDR has derived 125 inhalation MRLs, 207 oral MRLs, and eight external radiation MRLs; 19 MRLs are based on renal effects. This article reports on endpoints used to derive the MRLs. It also presents the ranking of effects into less serious and serious categories as described in ATSDR's Guidance for Developing Toxicological Profiles.

Health effects classification and its role in the derivation of minimal risk levels: hepatic effects.

The Agency for Toxic Substances and Disease Registry (ATSDR) derives health based guidance values called minimal risk levels (MRLs) to assist with assessment of risks posed by exposures to hazardous chemicals. Current MRLs are posted on ATSDR's web site (www.atsdr.cdc.gov). From the total 326 MRLs currently posted, 79 MRLs are based on hepatic endpoints. The paper reports on endpoints used for the derivation of these MRLs and the use of uncertainty factors. It also describes the ranking of effects into less serious and serious categories as described in ATSDR's Guidance for Developing Toxicological Profiles.

Case studies--arsenic.

Arsenic is found naturally in the environment. People may be exposed to arsenic by eating food, drinking water, breathing air, or by skin contact with soil or water that contains arsenic. In the U.S., the diet is a predominant source of exposure for the general population with smaller amounts coming from drinking water and air. Children may also be exposed to arsenic because of hand to mouth contact or eating dirt. In addition to the normal levels of arsenic in air, water, soil, and food, people could by exposed to higher levels in several ways such as in areas containing unusually high natural levels of arsenic in rocks which can lead to unusually high levels of arsenic in soil or water. People living in an area like this could take in elevated amounts of arsenic in drinking water. Workers in an occupation that involves arsenic production or use (for example, copper or lead smelting, wood treatment, pesticide application) could be exposed to elevated levels of arsenic at work. People who saw or sand arsenic-treated wood could inhale/ingest some of the sawdust which contains high levels of arsenic. Similarly, when pressure-treated wood is burned, high levels of arsenic could be released in the smoke. In agricultural areas where arsenic pesticides were used on crops the soil could contain high levels of arsenic. Some hazardous waste sites contain large quantities of arsenic. Arsenic ranks #1 on the ATSDR/EPA priority list of hazardous substances. Arsenic has been found in at least 1,014 current or former NPL sites. At the hazardous waster sites evaluated by ATSDR, exposure to arsenic in soil predominated over exposure to water, and no exposure to air had been recorded. However, there is no information on morbidity or mortality from exposure to arsenic in soil at hazardous waste sites. Exposure assessment, community and tribal involvement, and evaluation and surveillance of health effects are among the ATSDR future Superfund research program priority focus areas. Examples of exposures to arsenic in drinking water, diet and pesticide are given.

Evaluating toxicologic end points to derive minimal risk levels for hazardous substances.

The Agency for Toxic Substances and Disease Registry (ATSDR) uses chemical-specific minimal risk levels (MRLs) to assist in evaluating public health risks associated with exposure to hazardous substances. MRLs are estimates of daily human exposure to a chemical that are likely to be without an appreciable risk of adverse noncancer health effects over a specified duration of exposure. MRLs serve as screening levels for health assessors to identify contaminants and potential health effects that may be of concern for populations living near hazardous waste sites and chemical releases. MRLs are derived from toxicologic data complied from a comprehensive literature search and are presented in ATSDR's toxicological profile for that substance. They are based on the most sensitive substance-induced end point considered to be of relevance to humans. MRLs for each substance are derived for acute (1-14 days), intermediate (15-364 days), and chronic (365 days and longer) exposure durations, and for the oral and inhalation routes of exposure. In this paper, we present an overview of the approach used for evaluating the toxicologic end points in deriving the MRLs. Examples are given to illustrate the agency's efforts to achieve increased understanding, reduced uncertainty and improved public health guidance.