Acute Oral Toxicity test. OECD 423:2001; EPA (Environmental Protection Agency) OPPTS 870.1100: 2002 (Office of Prevention, Pesticides and Toxic Substances, USA); Directive 92/69/EEC July 31, 1992, paragraph B.1.
Test with the Certificate of Good Laboratory Practices (GLPs).
To assess the characteristics of a toxic substance, the determination of acute oral toxicity is usually the initial step. This test provides information about the health hazards that could occur after short oral exposure. The information from an acute study can serve as a basis for classifying the substance and its corresponding labeling. The assessment of acute toxicity should include the relationship, if any, between the exposure of the animals to the tested substance and the occurrence and severity of all alterations, including behavioral and clinical abnormalities, the reversibility of the observed abnormalities, macroscopic lesions, changes in weight, effect on mortality, and any other toxic effect. The OECD and OPPTS standards establish the possibility of corroborating macroscopic observations by a microscopic pathological study.
In our laboratory this test is performed using mice or rats, as admitted by both the standard OECD-423: 2001 and EPA-OPPTS O870.1100: 2002. Both standards (OECD and EPA-OPPTS) are very similar in terms of the recommendation to obtain all the previous toxicological information of the products subjected to tests or their related ones; in the number of animals included in the tests, with small differences; regarding the sex of the animals; to ages and weights of the animals; to the acclimatization preconditions; maintenance of animal during the tests; food and drink; the preparation and administration of the test substances; administration of each dose; and results observations. Fundamentally, both standards differ in the amounts of substances to be administered to animals in the UPD (Up-and-Down) dosing scheme when a "Limit Test" or a main test is performed. The EPA-OPPTS standard uses as a dose in the limit test 5,000 mg/kg, while the OECD standard recommends 2,000 mg/kg as usual. When a complete main test is performed to calculate the lethal dose 50 (LD50), the EPA-OPPTS standard recommends the scheme with a progression factor of 3.2 (1.75, 5.5, 17.5, 55, 175, 550, 1,750 and 5000 mg/kg), although recommended when no toxicological information of the product is known, begin with the amount of 175 mg/kg. The OECD standard 423, recommends the amounts of 5, 50, 300 and 2,000 mg/kg. In both standards, in order to try to reduce experimental animals as much as possible, when a toxic effect is not expected, it is recommended to start with the "Limit test", using in the case of the EPA-OPPTS standard 5,000 mg/kg and in the case of the OECD-423 standard, 2,000 mg/kg. The OECD standard is very clear when establishing the UPD schemes to move from one dose to the next, both upwards and downwards according to the starting point, as well as to establish categories 1, 2, 3, 4 or 5 of toxicity of the product tested.