The primary goal of toxicology and safety testing is to identify agents that have the potential to cause adverse effects in humans. Unfortunately, many of these tests have not changed significantly in the past 30 years and most are inefficient, costly, and rely heavily on the use of animals. The rodent cancer bioassay is one of these safety tests and was originally established as a screen to identify potential carcinogens that would be further analyzed in human epidemiological studies. Today, the rodent cancer bioassay has evolved into the primary means to determine the carcinogenic potential of a chemical and generate quantitative information on dose-response behavior in chemical risk assessments. Due to the resource-intensive nature of these studies, each bioassay costs $2 to $4 million and takes over three years to complete. Over the past 30 years, only 1,468 chemicals have been tested in a rodent cancer bioassay. By comparison, approximately 9,000 chemicals are used by industry in quantities greater than 10,000 lbs and nearly 90,000 chemicals have been inventoried by the U.S. Environmental Protection Agency as part of the Toxic Substances Control Act. Given the disparity between the number of chemicals tested in a rodent cancer bioassay and the number of chemicals used by industry, a more efficient and economical system of identifying chemical carcinogens needs to be developed.
Keywords: toxicology, chemical carcinogenesis, lung
Overall design: Five-week old female B6C3F1 mice were exposed for 13 weeks in the following dose groups: 1) 1,5-Naphthalenediamine, CAS No. 2243-62-1, feed, 2000 ppm, positive lung carcinogen; 2) 2,3-Benzofuran, CAS No. 271-89-6, gavage, 240 mg/kg, positive lung carcinogen; 3) 2,2-Bis(bromomethyl)-1,3-propanediol, CAS No. 3296-90-0, feed, 1250 ppm, positive lung carcinogen; 4) N-Methylolacrylamide, CAS No. 924-42-5, gavage (water), 50 mg/kg, positive lung carcinogen; 5) 1,2-Dibromoethane, CAS No. 106-93-4, gavage (corn oil), 62 mg/kg, positive lung carcinogen; 6) Coumarin, CAS No. 91-64-5, gavage (corn oil), 200 mg/kg, positive lung carcinogen; 7) Benzene, CAS No. 71-43-2, gavage (corn oil), 100 mg/kg, positive lung carcinogen; 8) N-(1-naphthyl)ethylenediamine dihydrochloride, CAS No. 1465-25-4, feed, 2000 ppm, negative lung carcinogen; 9) Pentachloronitrobenzene, CAS No. 82-68-8, feed, 8187 ppm, negative lung carcinogen; 10) 4-Nitroanthranilic acid, CAS No. 619-17-0, feed, 10000 ppm, negative lung carcinogen; 11) 2-Chloromethylpyridine hydrochloride, CAS No. 6959-47-3, gavage (water), 250 mg/kg, negative lung carcinogen; 12) Diazinon, CAS No. 333-41-5, feed, 200 ppm, negative lung carcinogen; 13) Malathion, CAS No. 121-75-5, feed, 16000 ppm, negative lung carcinogen; 14) Corn oil control, gavage; 15) Water control, gavage; 16) Rodent diet control, feed. Feed animals were exposed 7 days/week and gavage animals were exposed 5 days/week (5 ml/kg). After 13 weeks, animals were euthanized and lungs were collected. The right lobe was used for microarray analysis. Microarray analysis was performed on the lungs of three to four mice per treatment group.
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