Considerations and procedures in the derivation of ATSDR minimal risk levels

Minimal risk levels (MRLs) are health-based guidance values derived for individual substances by conducting a thorough review of the literature, identifying appropriate target organs of response, and identifying a dose level where a no adverse effect or the lowest adverse effect level is seen. This level is then evaluated for uncertainty in the data base and for other extenuating factors and subsequently adjusted with uncertainty or modifying factors. The resulting calculation yields the MRL that is defined as 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. Typically, MRLs are derived for different durations of exposure (acute, intermediate, chronic) and for different routes of exposure (oral, inhalation). The MRLs serve as useful reference values in evaluating human health from exposure to substances found at hazardous waste sites. Because of numerous requests of various programs, recent work has focused on expanding the applicability of MRLs to other situations and routes of exposure (dermal, food supply, intramuscular) beyond the traditional oral and inhalation exposure routes at waste sites. Results of work, in conjunction with the Agency for Toxic Substances and Disease Registry's computational toxicology laboratory, shows that the use of computational methods, such as physiologically based pharmacokinetic modeling, may allow the MRL process to be adapted to unique durations and routes of exposure such as intramuscular injections.