C Guidelines for Determining When Dose Addition of Similar-Acting Substances in Class I: Potable Resource Groundwaters is Appropriate

Section 620 Section 620.APPENDIX C   Guidelines for Determining When Dose Addition of Similar-Acting Substances in Class I: Potable Resource Groundwaters is Appropriate a)         Substances must be considered similar-acting if: 1)         The substances have the same target in an organism (e.g., the same organ, organ system, receptor, or enzyme); or 2)         The substances have the same mode of toxic action.  These actions may include, for example, central nervous system depression, liver toxicity, and cholinesterase inhibition. b)         Substances that have fundamentally different mechanisms of toxicity (threshold toxicants vs. carcinogens) must not be considered similar-acting. However, carcinogens that also cause a threshold toxic effect must be considered in a mixture with other similar-acting substances having the same threshold toxic effect. In that case, an acceptable level of the carcinogen must be derived for its threshold effect, using the procedures specified in Appendix A. c)         Substances that are components of a complex mixture of related compounds produced as commercial products (e.g., PCBs or technical grade chlordane) are not mixtures, as defined in Appendix B.  These complex mixtures are equivalent to a single substance. In that case, the Human Threshold Toxicant Advisory Concentration (HTTAC) must be derived for threshold effects of the complex mixture, using the procedures specified in Appendix A, if valid toxicological or epidemiological data are available for the complex mixture.  If the complex mixture is a carcinogen, the Human Nonthreshold Toxicant Advisory Concentration (HNTAC) is the one-in-one-million cancer risk concentration, calculated from methods located at Appendix A.  The guidance level is either the HTTAC or HNTAC, whichever is less unless the lower concentration is less than the substance's lowest appropriate LLOQ specified in "Test Methods for Evaluating Solid Wastes, Physical/Chemical Methods", EPA Publication No. SW-846, incorporated by reference in Section 620.125, or the substance's lowest appropriate LCMRL specified in the drinking water methods incorporated by reference in Section 620.125.  If the lower concentration between the HTTAC and HNTAC of the substance is less than its lowest appropriate LLOQ or LCMRL, the guidance level is the lowest appropriate LLOQ or LCMRL.