US EPA

The Environmental Criteria and Assessment Office of the U.S. EPA is engaged in the development of risk assessment guidelines and methodologies as part of the regulatory program of the Agency. here is an increasing need for methods that address more complex exposure situations, including multichemical, multiroute, and partial-lifetime exposures. mprovements in the current methods are also needed. his paper discusses the following issues: to convert animal dose to equivalent human dose, an approach based on body surface area is being considered as an improvement to current methods that use body weight; to assess effects of less-than-lifetime exposures, separate approaches for carcinogens and noncarcinogens are proposed; existing low-dose extrapolation models have been modified to enable prediction of cancer incidence at a variety of exposure durations; for noncarcinogens, a graphical method for displaying dose-duration-effect relationships, which permits interpolation to any exposure duration, has been developed; for multi-route or multi-chemical exposures a scheme whereby doses are each adjusted for potency and then summed is proposed for noncarcinogens, except where the mixture constituents are known to act by dissimilar mechanisms, and a form of risk additivity is proposed for carcinogens; a rating scheme is proposed whereby high-risk subgroups can be used to weight the final assessment; and a numerical ranking scheme has been developed for the severity of toxic effects and to the doses that cause the effects.

Stara, J., R. Bruins, M. Dourson, L. Erdreich, R. Hertzberg, P. Durkin, AND W. Pepelko. RISK ASSESSMENT IS A DEVELOPING SCIENCE: APPROACHES TO IMPROVE EVALUATION OF SINGLE CHEMICALS AND CHEMICAL MIXTURES. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/D-89/033 (NTIS PB89223952).

In: Methods for Assessing the Effects of Mixtures of Chemicals; V.B. Vouk, G.C. Butler, A.C. Upton, D.V. Parke, S.C. Asher, Ed. 987 SCOPE