Acute oral toxicity.

The purposes of acute toxicity testing are to obtain information on the biologic activity of a chemical and gain insight into its mechanism of action. The information on acute systemic toxicity generated by the test is used in hazard identification and risk management in the context of production, handling, and use of chemicals. The LD50 value, defined as the statistically derived dose that, when administered in an acute toxicity test, is expected to cause death in 50% of the treated animals in a given period, is currently the basis for toxicologic classification of chemicals. For a classical LD50 study, laboratory mice and rats are the species typically selected. Often both sexes must be used for regulatory purposes. When oral administration is combined with parenteral, information on the bioavailability of the tested compound is obtained. The result of the extensive discussions on the significance of the LD50 value and the concomitant development of alternative procedures is that authorities today do not usually demand classical LD50 tests involving a large number of animals. The limit test, the fixed-dose procedure, the toxic class method, and the up-and-down methods all represent simplified alternatives using only a few animals. Efforts have also been made to develop in vitro systems; e.g., it has been suggested that acute systemic toxicity can be broken down into a number of biokinetic, cellular, and molecular elements, each of which can be identified and quantified in appropriate models. The various elements may then be used in different combinations to model large numbers of toxic events to predict hazard and classify compounds.

[1]  B Ekwall,et al.  Preliminary studies on the validity of in vitro measurement of drug toxicity using HeLa cells. III. Lethal action to man of 43 drugs related to the HeLa cell toxicity of the lethal drug concentrations. , 1980, Toxicology letters.

[2]  E Walum,et al.  MEIC Evaluation of Acute Systemic Toxicity: Part V. Rodent and Human Toxicity Data for the 50 Reference Chemicals. , 1998, Alternatives to laboratory animals : ATLA.

[3]  S. Garattini Toxic effects of chemicals: difficulties in extrapolating data from animals to man. , 1985, Critical reviews in toxicology.

[4]  R J Fielder,et al.  The international validation of a fixed-dose procedure as an alternative to the classical LD50 test. , 1990, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[5]  B. Isomaa,et al.  MEIC Evaluation of Acute Systemic Toxicity: Part VI. The Prediction of Human Toxicity by Rodent LD50 Values and Results From 61 In Vitro Methods. , 1998, Alternatives to laboratory animals : ATLA.

[6]  M. Gülden,et al.  An in vitro toxicity testing strategy for the classification and labelling of chemicals according to their potential acute lethal potency. , 1994, Toxicology in vitro : an international journal published in association with BIBRA.

[7]  S. Garattini NOTES ON XENOBIOTIC METABOLISM , 1983, Annals of the New York Academy of Sciences.

[8]  M. Balls,et al.  Comparison of the in vitro cytotoxicities and acute in vivo toxicities of 59 chemicals. , 1987, Molecular toxicology.

[9]  Alexander M. Mood,et al.  A Method for Obtaining and Analyzing Sensitivity Data , 1948 .

[10]  Michael Balls,et al.  Acute Toxicity Testing in Vitro and the Classification and Labelling of Chemicals , 1996 .

[11]  Pierluigi Nicotera,et al.  In Vitro Neurotoxicity Testing , 1994 .

[12]  R. D. Bruce An up-and-down procedure for acute toxicity testing. , 1985, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[13]  Sirpa Kärenlampi,et al.  MEIC evaluation of acute systemic toxicity .2. In vitro results from 68 toxicity assays used to test the first 30 reference chemicals and a comparative cytotoxicity analysis. , 1996 .

[14]  R. Heywood,et al.  The LD50 test: some considerations of precision. , 1982, Toxicology letters.

[15]  R D Bruce,et al.  Comparison of the up-and-down method and the fixed-dose procedure for acute oral toxicity testing. , 1991, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[16]  W. J. Dixon Staircase bioassay: The up-and-down method , 1991, Neuroscience & Biobehavioral Reviews.

[17]  R N Hill,et al.  Comparison of the up-and-down, conventional LD50, and fixed-dose acute toxicity procedures. , 1995, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[18]  E. Walum,et al.  Dynamic Qualities of Validation and the Evolution of New In Vitro Toxicological Tests , 1996 .

[19]  E. Walum,et al.  On the application of cultured neuroblastoma cells in chemical toxicity screening. , 1984, Journal of toxicology and environmental health.

[20]  P. Tamborini,et al.  Acute toxicity testing in the nonlethal dose range: a new approach. , 1990, Regulatory toxicology and pharmacology : RTP.

[21]  A. Whitehead,et al.  The fixed-dose procedure and the acute-toxic-class method: a mathematical comparison , 1995, Human & experimental toxicology.

[22]  E Paget The LD50 test. , 1983, Acta pharmacologica et toxicologica.

[23]  M. van den Heuvel A New Approach to the Classification of Substances and Preparations on the Basis of their Acute Toxicity , 1984 .

[24]  Johan Högberg,et al.  Validation of In Vitro Cytotoxicity Tests — Past and Present Strategies , 1991 .