An evaluation of 6 short-term tests for detecting organic chemical carcinogens

Abstract

Summary.-A number of tests have been described which are thought to be capable of identifying carcinogens without using the actual induction of cancer as an endpoint. This study compares the performance of 6 such tests on a selection of 120 organic chemicals. The tests studies were: (1) mutation of Salmonella typhimurium; (2) cell transformation; (3) degranulation of endoplasmic reticulum; (4) sebaceous gland suppression; (5) tetrazolium reduction and (6) subcutaneous implant. A further 4 tests were examined briefly, but were not included in the complete evaluation.The chemicals were classified into carcinogens (58) and non-carcinogens (62) on the basis of published experimental data, and into 1 of 4 broad chemical classes.There was considerable variation between tests in their ability to predict carcinogenicity, with the cell-transformation test and the bacterial-mutation test being the most accurate (94% and 93% accurate respectively). These 2 tests were considered to be of general use in screening, since they were clearly more accurate than the others. Statistical consideration of various combinations of these tests showed that the use of cell transformation and bacterial mutation together, provide an advantage over the use of either test alone. The inclusion of the other 4 tests in a screening battery predictably resulted in a great increase in overall inaccuracy and loss of discrimination, even though the detection of carcinogens is improved. All the tests were shown to generate both false positive and false negative results, a situation which may be controlled by the use, where possible, of appropriate chemical-class controls, to identify the test which is optimal for the class of chemical under test. Structural

Genetic risks caused by occupational chemicals. Use of experimental methods and occupational risk group monitoring in the detection of environmental chemicals causing mutations, cancer and malformations.

“…The demonstration of about a 90 0J0 correlation between known carcinogens and mutagenicity in the Ames system (96,118,119,140) implies that a positive test result indicates with high probability that the chemical is a potential carcinogen.…”

“…Survival and transformation frequency have been calculated. The test is not as rapid as the Ames test, but it seems to be a very promising system for a preliminary transformation screen (119).…”

Nitrobenzol [MAK Value Documentation in German language, 1998]

“…Abwesenheit von S9 Mix mit Konzentrationen bis zu 2500 ng/Platte verliefen die Untersuchungen negativ Benkendorf 1978;Chiu et al 1978;Fu et al 1985;Garner and Nutman 1977;Nohmi et al 1984;Purchase et al 1978;Suzuki et al 1983;Vance and Levin 1984). Unter Zugabe von Norharman und Anwesenheit von S9 Mix wirkte Nitrobenzol im Salmonella-typhimuriumStamm TA98 mutagen (Suzuki et al 1983;vgl.…”

Prediction of genotoxic potential of cosmetic ingredients by an in silico battery system consisting of a combination of an expert rule-based system and a statistics-based system

“…In the development of materials, such as drugs, pesticides, food additives and cosmetic ingredients, many candidate compounds are investigated by means of genotoxicity tests as a part of their safety evaluation (Zeiger, 2001). The Ames test is the most widely used assay to assess the mutagenic potential of chemicals (Ames et al, 1973;McCann et al, 1975;Sugimura et al, 1976;Purchase et al, 1978). The chromosomal aberration (CA) and the in vitro micronucleus (vitMN) tests are used to detect clastogenic potential (Ishidate et al, 1998;Matsushima et al, 1999;Sobol et al, 2012).…”