Abstract
An alternative to the oral LD50 test, the acute toxic class (ATC) method (oral), was validated with 20 substances in an international collaborative study with nine laboratories in five countries. The ATC method is a stepwise procedure with the use of three animals per step. It has been designed with three fixed doses (25, 200 and 2000 mg/kg). In general, this testing is sufficient for allocation to the toxicity classes of the majority of the international classification systems currently in use. The selection of testing at additional fixed doses (5, 50 and 500 mg/kg) may be considered if further refinement is necessary or for specific allocation to those international classification systems with a cut-off value of 5 mg/kg. On average, two to four steps are necessary to complete a test. With the ATC method substances can be ranked in a similar or even better manner than with an LD50 test but it uses up to 90% fewer animals, the average being 70% fewer. This also results in substantially fewer moribund/dead animals. The ATC method is based on biometric evaluations that, together with the experimental results, demonstrate that this method is a sensitive and reliable alternative to the LD50 test.
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Bruce RD (1985) An up-and-down procedure for acute toxicity testing. Fundam Appl Toxicol 6: 151–157
Commission of the European Communities (1992a) Annex to Commission Directive 92/69/EEC of 31 July 1992 adapting to technical progress for the seventeenth time Council Directive 67/548/EEC on the approximation of laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances: Annex V, B 1 Acute toxicity (oral) Off J Eur Comm L 383: 110–112
Commission of the European Communities (1992b) Annex to Commission Directive 92/69/EEC of 31 July 1992 adapting to technical progress for the seventeenth time Council Directive 67/548/EEC on the approximation of laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances: Annex V, B.1 bis Acute toxicity (oral) — fixed dose method. Off J Eur Comm L 383: 113–116
Deichmann WB, LeBlanc TJ (1943) Determination of the approximate lethal dose with about six animals. J Ind Hyg Toxicol 25: 415–417
Diener W, Siccha L, Mischke U, Kayser D, Schlede E (1994) The biometric evaluation of the acute-toxic-class-method (oral). Arch Toxicol 68: 599–610
Diener W, Mischke U, Schlede E, Kayser D (1995) The biometrical evaluation of the OECD modified version of the acute-toxic-class method (oral). Arch Toxicol 69: 729–734
Kennedy GL, Ferenz RL, Burges BA (1986) Estimation of acute oral toxicity in rats by determination of the approximate lethal dose rather than the LD50. J Appl Toxicol 6: 145–148
Lorke D (1983) A new approach to practical acute toxicity testing. Arch Toxicol 54: 275–287
OECD (1981a) Guidelines for testing of chemicals No. 401: acute oral toxicity. OECD, Paris
OECD (1981b) Decision of the council concerning mutual acceptance of data in the assessment of chemicals. Annex 2, OECD Principles of Good Laboratory Practice. OECD, Paris
OECD (1987) Guidelines for testing of chemicals no. 401: acute oral toxicity. OECD, Paris
OECD (1992) Guidelines for testing of chemicals no. 420: acute oral toxicity — fixed dose method. OECD, Paris
Roll R, Höfer-Bosse Th, Kayser D (1986) New perspectives in acute toxicity testing of chemicals. Toxicol Lett Suppl 31: 86
Roll R, Riebschläger M, Mischke U, Kayser D (1989) Neue Wege zur Bestimmung der akuten Toxizität von Chemikalien. Bundesgesundheitsblatt 32: 336–341
Schlede E, Mischke U, Roll R, Kayser D (1992) A national validation study of the acute-toxic-class method — an alternative to the LD50 test. Arch Toxicol 66: 455–470
Van den Heuvel MJ, Clark DG, Fielder RJ, Koundakjian PP, Oliver GJA, Pelling D, Tomlinson NJ, Walker AP (1990) The international validation of a fixed-dose procedure as an alternative to the classical LD50 test. Food Chem Toxicol 28: 469–482
Yamanaka S, Hashimoto M, Tobe M, Kobayashi K, Sekizawa J, Nishimura M (1990) A simple method for screening assessment of acute toxicity of chemicals. Arch Toxicol 64: 262–268
Zbinden G, Flury-Roversi M (1981) Significance of the LD50-test for the toxicological evaluation of chemical substances. Arch Toxicol 47: 77–99
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Schlede, E., Mischke, U., Diener, W. et al. The international validation study of the acute toxic class method (oral). Arch Toxicol 69, 659–670 (1995). https://doi.org/10.1007/s002040050229
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DOI: https://doi.org/10.1007/s002040050229