On September 28, 2005, the draft Report on the toxicology and carcinogenesis studies of diisopropylcarbodiimide in genetically modified mouse models received public review by the National Toxicology Program’s Board of Scientific Counselors’ Technical Reports Review Subcommittee. The review meeting was held at the National Institute of Environmental Health Sciences, Research Triangle Park, NC.

Dr. R.S. Chhabra, NIEHS, introduced the toxicology and carcinogenicity studies of diisopropylcarbodiimide in genetically modified mice by explaining the NTP’s exploration of the use of transgenic mice as a possible alternative test model by comparing results with the standard 2-year bioassay. He described the design and results of studies of diisopropylcarbodiimide in two transgenic mouse strains. No carcinogenic responses were noted in the genetically modified mouse studies or the 2-year rat and mouse studies. The proposed conclusions were no evidence of carcinogenic activity of diisopropylcarbodiimide in female p53 haploinsufficient mice administered 4.38, 8.75, 17.5, 35, or 70 mg/kg in ethanol. There were no treatment-related neoplasms or nonneoplastic lesions in female Tg.AC hemizygous mice administered 4.38, 8.75, 17.5, 35, or 70 mg/kg in ethanol for 20 weeks.

Dr. Vore, the first principal reviewer, thought the study was well conducted and written and had no scientific or editorial criticisms.

Dr. Sikka, the second principal reviewer, noted that the p53 protein was protective, rather than enhancing malignancy, as stated in the background information. He inquired why the study durations were shorter than in some other GMM studies reported.

Dr. Crump, the third principal reviewer, also agreed with the proposed conclusions. He inquired why one of the transgenic mouse studies was called a carcinogenicity study and the other a toxicology study.

Dr. Chhabra replied that the ideal study duration was being developed at the time the studies started; often papillomas were seen as early as 9 weeks for positive controls. Dr. J.R. Bucher, NIEHS, added that subsequent information has indicated that 9 months was closer to the optimum duration for maximizing study sensitivity.

Dr. Chhabra explained that a previous Technical Reports Review Subcommittee had felt the Tg.AC model, as a promotion reporter, was not a sufficient indicator of carcinogenicity while the p53 model might be; therefore, studies with the former were called toxicology studies and the latter carcinogenicity studies.

Dr. Vore moved and Dr. Elwell seconded that the conclusions be accepted as written. The motion was accepted unanimously with five votes.