Comparison of human exposures to selected chemicals with thresholds from NTP carcinogenicity studies in rodents. 2003

William J Waddell
Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, Kentucky, USA. bwaddell@louisville.edu

The National Toxicology Program (NTP) Technical Reports online database was reviewed to find chemicals that were reported to show clear evidence of carcinogenicity in the NTP rodent studies and for which data on human exposure could be found. Six representative compounds were selected. Three volatile compounds: ethyl benzene, perchloroethylene, and methylene chloride; two drugs in current use: phenytoin and primidone; and one naturally occurring, widely used, flavor: allyl isothiocyanate, were selected. The carcinogenicity data from each of the NTP Technical Reports were plotted using the Rozman scale to determine the threshold for carcinogenicity from the rodent studies. The human exposures for each chemical were calculated and compared with that threshold. The thresholds for carcinogenicity of the three volatile compounds were several orders of magnitude above the levels present in ambient air in the USA. The Threshold Limit Value (TLV) of the American Conference of Governmental Industrial Hygienists (ACGIH) for these three compounds varied between several orders of magnitude below the carcinogenicity threshold to being at the threshold. The maximum recommended doses of both drugs were at the carcinogenicity threshold. The estimated mean daily human consumption of the natural flavor was less than 100 x below the carcinogenicity threshold. This method of comparison between human exposure and animal carcinogenicity studies is more objective and informative than those in current use.

UI MeSH Term Description Entries
D008297 Male Males
D008452 Maximum Allowable Concentration The maximum exposure to a biologically active physical or chemical agent that is allowed during an 8-hour period (a workday) in a population of workers, or during a 24-hour period in the general population, which does not appear to cause appreciable harm, whether immediate or delayed for any period, in the target population. (From Lewis Dictionary of Toxicology, 1st ed) Maximum Permissible Exposure Level,MPEL,Maximum Permissible Exposure Concentration,Allowable Concentration, Maximum,Allowable Concentrations, Maximum,Concentration, Maximum Allowable,Concentrations, Maximum Allowable,MPELs,Maximum Allowable Concentrations
D009313 National Health Programs Components of a national health care system which administer specific services, e.g., national health insurance. National Health Insurance, Non-U.S.,Health Services, National,National Health Insurance,National Health Insurance, Non U.S.,National Health Services,Services, National Health,Health Insurance, National,Health Program, National,Health Programs, National,Health Service, National,Insurance, National Health,National Health Program,National Health Service,Program, National Health,Programs, National Health,Service, National Health
D009316 National Institutes of Health (U.S.) An operating division of the US Department of Health and Human Services. It is concerned with the overall planning, promoting, and administering of programs pertaining to health and medical research. United States National Institutes of Health,National Institutes of Health
D009374 Neoplasms, Experimental Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms. Experimental Neoplasms,Experimental Neoplasm,Neoplasm, Experimental
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D002277 Carcinoma A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm and not a synonym for "cancer." Carcinoma, Anaplastic,Carcinoma, Spindle-Cell,Carcinoma, Undifferentiated,Carcinomatosis,Epithelial Neoplasms, Malignant,Epithelioma,Epithelial Tumors, Malignant,Malignant Epithelial Neoplasms,Neoplasms, Malignant Epithelial,Anaplastic Carcinoma,Anaplastic Carcinomas,Carcinoma, Spindle Cell,Carcinomas,Carcinomatoses,Epithelial Neoplasm, Malignant,Epithelial Tumor, Malignant,Epitheliomas,Malignant Epithelial Neoplasm,Malignant Epithelial Tumor,Malignant Epithelial Tumors,Neoplasm, Malignant Epithelial,Spindle-Cell Carcinoma,Spindle-Cell Carcinomas,Tumor, Malignant Epithelial,Undifferentiated Carcinoma,Undifferentiated Carcinomas
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004781 Environmental Exposure The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. Exposure, Environmental,Environmental Exposures,Exposures, Environmental
D005260 Female Females

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