Six interaction profiles for simple mixtures.

The Agency for Toxic Substances and Disease Registry (ATSDR) has a program for chemical mixtures that encompasses research on chemical mixtures toxicity, health risk assessment, and development of innovative computational methods. ATSDR prepared a guidance document that instructs users on how to conduct health risk assessment on chemical mixtures (Guidance Manual for the Assessment of Joint Toxic Action of Chemical Mixtures). ATSDR also developed six interaction profiles for chemical mixtures. Two profiles were developed for persistent environmental chemicals that are often found in contaminated fish and also can be detected in human breast milk. The mixture included chlorinated dibenzo-p-dioxins, hexachlorobenzene, dichlorodiphenyl dichloroethane, methyl mercury, and polychlorinated biphenyls. Two profiles each were developed for mixtures of metals and mixtures of volatile organic chemicals (VOCs) that are frequently found at hazardous waste sites. The two metal profiles dealt with (a) lead, manganese, zinc, and copper; and (b) arsenic, cadmium, chromium, and lead; the two VOCs mixtures dealt with (a) 1,1,1-trichloroethane, 1,1-dichloroethane, trichloroethylene, and tetrachloroethylene; and (b) benzene, ethylbenzene, toluene, and xylenes (BTEX). Weight-of-evidence methodology was used to assess the joint toxic action for most of the mixtures. Physiologically based pharmacokinetic modeling was used for BTEX. In most cases, a target-organ toxicity dose modification of the hazard index approach is recommended for conducting exposure-based assessments of noncancer health hazards.