Short-term toxicological tests

Presently available short-term toxicological tests... 

Ankley G.T., K.M. Jensen, M.D. Kahl, J.J. Korte, and E.A. Makynen (2001). Description and evaluation of a short-term reproduction test with Fathead minnow Pinnephales promelas). Environmental Toxicology and Chemistry 20 1276-1290. 

Jop, K.M., Askew, A.M., Terrio, K.F. and Simoes, A T. (1992) Application of the short-term chronic test with Ceriodaphnia dubia in identifying sources of toxicity in industrial wastewaters, Bulletin of Environmental Contamination and Toxicology 49 (5), 765-771. 

Naimo, T.J., Cope, W.G. and Bartsch, M.R. (2000) Sediment-contact and survival of fingernail clams implications for conducting short-term laboratory tests, Environmental Toxicology 15 (1), 23 - 27. 

Ankley, G.T., Jensen, K.M., Kahl, M.D., Korte, J.J. and Makynen E.A. (2001) Description and Evaluation of a Short-Term Reproduction Test with the Fathead Minnow (Pimephales promelas), Environmental Toxicology and Chemistry 20 (6), 1276-1290. 

NOEL (no observed ejfect level) This represents the highest concentration or dose that does not show any experimental evidence of an effect on test organisms. Technically, a NOEL could be applied also to a short-term acute test. Nevertheless, in toxicological praxis a NOEL should be derived from a relatively wide data set, including long-term chronic experiments. At the other end of the real toxicity threshold lies the LOEL (lowest oh served effect level). 

Birds and mammals Acute, short-term, reproduction test Mainly a.i. tests, data from mammalian toxicology are used... 

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. 

Bailey, H.D., Liu, D.H.W., and Javitz, H.A. Time/toxicity relationships in short-term static, dynamic and plug-flow bioassays, in Aquatic Toxicology and Hazard Assessment Eighth Symposium, ASTM Special Technical Publication 891, Bahner, R.C. and Hansen, D.J., Eds. (Philadelphia, PA American Society for Testing and Materials, 1985), pp. 193-212. 

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... 

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