The current use of studies on promoters and cocarcinogens in quantitative risk assessment

Several of the priority pollutants discussed in EPA's Ambient Water Quality Criteria documents have been reported to have promotion or cocarcinogenic activity. For example, phenol appears to have tumor-promoting activity in mice when repeatedly applied after initiation with either 7,12-dimethyl-1,2-benzanthracene (DMBA) or benzo(a)pyrene (BaP). Similarly, it has been reported that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent promoter of liver tumors as well as a cocarcinogen. However, in developing guidelines to derive ambient water quality criteria, it became apparent that satisfactory approaches had not been developed for using promotion/cocarcinogen data in human health risk estimation, nor were available promotion and/or cocarcinogen data on individual chemicals strong enough to permit a defensible quantitative risk estimation, if such approaches had existed. For this reason, the criteria derived for pollutants with reported promotion/cocarcinogenic activities were based on approaches for carcinogenic (e.g., TCDD), toxic (e.g., fluoranthene) or organoleptic effects (e.g., 2,4-dichlorophenol). Nonetheless, with advances in studies on both the biological mechanisms and dose/response patterns of promoters and cocarcinogens, it may be possible to develop a scientifically valid quantitative approach to use this type of data for derivation of ambient water quality criteria or other risk assessments. Some progress toward this goal and the problems associated with this effort are discussed.