Performance of short-term tests for detection of human carcinogens

The performance of short-term tests for detection of carcinogens has been validated by several investigators and international collaborative programmes. A large number of chemicals have been tested by the Salmonella/microsome assay and high values of sensitivity and specificity, often greater than 70%, were reported. For 71 human carcinogens classified in Groups 1, 2A and 2B by the International Agency for Research on Cancer (IARC), the Salmonella/microsome test showed a sensitivity of 62.1%: 36 were positive out of 58 chemicals tested. Similar or rather higher values were obtained with Escherichia coli mutation assay (72.0%, 18/25), mutation assays in fungi (78.9%, 30/38), mutation assays in insects (65.7%, 23/35), and assays measuring DNA damage in prokaryotes (80.5%, 33/41). In assays using mammalian cells, tests on chromosomal anomaly showed a relatively high sensitivity: 61.7% (29/47) in chromosomal structural aberration assays and 80.6% (25/31) in sister chromatid exchange (SCE) assays. Comparable values were also obtained in mutation assays of mammalian cells (73.0%, 27/37) and cell transformation assays (87.5%, 21/24). Results of monitoring of exposed populations did not necessarily show a high sensitivity to human carcinogens (44.4%, 12/27). Human carcinogen data were further analysed in order to find a combination of tests which may increase the predictive value. Among human carcinogens, 17 chemicals are not mutagenic in the Salmonella/microsome assay. Although 9 of 17 chemicals (asbestos, hormones, chlorinated compounds and 1,4-dioxane) were not positive in any short-term assays, some gave positive results in a variety of assays, e.g. arsenic and benzene were positive in assays of chromosomal anomaly in mammalian cells in vitro. Combinations of the Salmonella/microsome assay with certain tests using mammalian cells were found to increase the sensitivity significantly. Chromosomal anomaly assays of mammalian cells in vitro seem to be most relevant for detection of human carcinogens when used in combination with the Salmonella/microsome assay.