Comparison of human exposures to selected chemicals with thresholds from NTP carcinogenicity studies in rodents.
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.
Waddell
William J
WJ
Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, Kentucky, USA. bwaddell@louisville.edu
D000236:Adenoma / Q000139:chemically induced; D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D002277:Carcinoma / Q000139:chemically induced; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure; D005260:Female; D006078:Government Programs; D006801:Humans; D008297:Male; D008452:Maximum Allowable Concentration; D051379:Mice; D009313:National Health Programs; D009316:National Institutes of Health (U.S.); D009374:Neoplasms, Experimental / Q000139:chemically induced; D051381:Rats; D018570:Risk Assessment; D014481:United States
D002273:Carcinogens