Toxicology short-term tests

In the case of a substance like Tris, or the food additive AF-2, the combination of an extremely widespread human exposure to the chemical and a positive result in a number of short-term tests should have been sufficient evidence to stop its use, considering that alternatives were available. Yet Tris and AF-2 were not removed from the market until the results from animal cancer tests indicated that they were carcinogens. It is becoming apparent that a positive result in many of these short-term test systems is meaningful, and that the systems may not only be a complement to animal cancer testing but may also provide much additional toxicological information as well. We... 

Danford, N. (1991) The genetie toxicology of or//zo-toluidine. Mutat. Res., 258, 207-236 Daniel, M.R. Dehnel, J.M. (1981) Cell transformation test with baby hamster kidney cells. In de Senes, F.J. Ashby, J., eds, Progress in Mutation Research, Volume 1, Evaluation of Short-Term Tests for Carcinogens. Report of the International Collaborative Program, Amsterdam, Elsevier Seienee, pp. 626-637... 

The feeding study is expected to detect acute, life-threatening toxicity and to indicate the target organs and appropriate doses for longer-duratlon toxicology testing when results of the short-term tests indicate the need. 

The Department of Health, Education and Welfare Committee to Coordinate Toxicology and Related Programs recently (Apr 77) advocated a battery of short-term tests (Figure 10) which would demonstrate point mutations, DNA damage, and chromosome... 

PDA (2000). Toxicological Principles for the Safety Assessment of Pood Ingredients Redbook 2000, July 2000. IV.C.l. Short-Term Tests for Genetic Toxicity, http //vm.cfsan.fda.gov/ redbook/red-ivcl. html. 

Brambilla, G., and Martelli, A. (2004). Failure of the standard battery of short-term tests in detecting some rodent and human genotoxic carcinogens. Toxicology 196, 1-19. 

G. M. Williams, A comparison of in vivo and in vitro metabolic activations systems, in Critical Reviews in Toxicology-Strategies for Short-term Testing for Mutagens/Carcinogens (B. Butterworth, ed.), pp. 96-97, C. R. C. Press, West Palm Beach, Fla. (1979). 

During the past five years, however, a new concept in toxicological evaluations has emerged.This new concept involves the implementation of shortterm in vitro and submammalian assays as indicators of chronic toxicity for mammals. Several factors have been instrumental in the increased emphasis on short-term tests, but the major one has been the increased costs associated with chronic toxicity studies in mammals. Costs for typical carcinogenicity studies in mice and rats in 1973 ranged from 65,000 to 75,000 per chemical. The... 

S. A. Thordn, Microcalorimetry and image analysing developed for short-term tests in toxicology using alveolar macrophages as target cells. Thesi.s, Lund, Sweden, 1991. 

Based on tests with laboratory animals, aniline may cause cancer. The National Cancer Institute (NCI) and the Chemical Industry Institute of Toxicology (CUT) conducted lifetime rodent feeding studies, and both studies found tumors of the spleen at high dosage (100 —300 mg/kg pet day of aniline chloride). CUT found no tumors at the 10—30 mg/kg per day feeding rates. The latter value is equivalent to a human 8-h inhalation level of 17—50 ppm aniline vapor. In a short term (10-d) inhalation toxicity test by Du Pont, a no-effect level of 17 ppm aniline vapor was found for rats. At high levels (47—87 ppm), there were blood-related effects which were largely reversible within a 13-d recovery period (70). 

The period of the test depends on whether long- or short-term effects are of interest. Acute toxicity is the effect of a single exposure or a series of exposures close together in a short period of time. Chronic toxicity is the effect of multiple exposures occurring over a long period of time. Chronic toxicity studies are difficult to perform because of the time involved most toxicological studies are based on acute exposures. The toxicological study can be complicated by latency, an exposure that results in a delayed response. 

The front end of this tier approach is a screen, the functional observation battery (FOB) Gad (1982) or Irwin (1968) screen. This is the tool of choice for initial (and for most of the compounds covered by this volume, the only screen tests for) identification of potentially neurotoxic chemicals. The use of such screens, other behavioural test methods, or what are generally called clinical observations does, however, warrant one major caution or consideration. That is that short-term (within 24 hr of dosing or exposure) observations are insufficient on their own to differentiate between pharmacologic (reversible in the short term) and toxicological (irreversible) effects. 

NTP. 1995. Printed long term technical reports and short term toxicity study reports. National Toxicology Program. Management status report. Division ofToxicology research and Testing. National Institute of Environmental Health Sciences. July 7, 1995. 

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