Using dose addition to estimate cumulative risks from exposures to multiple chemicals

The Food Quality Protection Act (FQPA) of 1996 requires the EPA to consider the cumulative risk from exposure to multiple chemicals that have a common mechanism of toxicity. Three methods, hazard index (HI), point-of-departur e index (PODI), and toxicity equivalence factor (TEF), have commonly been c onsidered to estimate the cumulative risk. These methods are based on estim ates of ED10 (point of departure) and reference doses from the dose-respons e functions of individual chemicals. They do not incorporate the actual dos e-response function of the mixture from multiple chemical exposures. Dose a ddition is considered to be an appropriate approach to cumulative risk asse ssment because it assumes that the chemicals of interest act in accordance with a common mode of action (a similar action). This paper proposes a form al statistical procedure to estimate the cumulative risk by fitting the dos e-response model of the mixture under dose addition. The relative potency b etween two chemicals is estimated directly from the joint dose response mod el of the mixture. An example data set of four drugs representing four chem icals is used to illustrate the proposed procedure and compare it to the HI , PODI, and TEF methods.