Acute toxicity study

Acute Toxicity. ThioglycoHc acid, its esters and 3-mercaptopropionic acid are considered moderately toxic on the basis of acute toxicity studies. These are presented in Table 4. 

Acute Toxicity Studies. These studies should provide the following information the nature of any local or systemic adverse effects occurring as a consequence of a single exposure to the test material an indication of the exposure conditions producing the adverse effects, in particular, information on dose—response relationships, including minimum and no-effects exposure levels and data of use in the design of short-term repeated exposure studies. 

Acute toxicity studies are often dominated by consideration of lethaUty, including calculation of the median lethal dose. By routes other than inhalation, this is expressed as the LD q with 95% confidence limits. For inhalation experiments, it is convenient to calculate the atmospheric concentration of test material producing a 50% mortaUty over a specified period of time, usually 4 h ie, the 4-h LC q. It is desirable to know the nature, time to onset, dose—related severity, and reversibiUty of sublethal toxic effects. 

Monomethyltirf. Acute toxicity studies were identified for monomethyltin for algae, invertebrates, and fish. Chronic NOECs were available for algae and invertebrates. A chronic NOEC of 0.007 mg/1 for monomethyltin chloride in Scenedesmus subspica-tus was the lowest reported result. Since there were no long-term test results available for fish, it was necessary to apply an uncertainty factor of 50 to the critical study. 

Monobutyltirr. Four acute toxicity studies were identified for monobutyltin chloride. The critical study was an acute EC50, based on immobilization, for Daphnia magna at a concentration of 25 mg/1. All four tests were acute, and, in the absence of long-term tests, it was decided to apply an uncertainty factor of 1000. 

Dioctyltirv. Acute toxicity studies were identified for dioctyltin for invertebrates and fish. Chronic NOECs were available for algae and invertebrates. 

Kinkead ER, Horton JR, Gaworski CL. 1985. Acute toxicity studies on two air force hydraulic fluids (MLO 82-233 and MLO 82-585). Harry G. Armstrong Aerospace Medical Research Laboratory Technical Report AAMRL-TR-85-070. 

As previously mentioned, early in vivo acute toxicity studies indicated that the action of Type II pyrethroids on the nervous system was different from that of the Type I pyrethroids. Deltamethrin decreased the acetylcholine content of the cerebellum, whereas DDT, a well-established voltage-sensitive sodium channel agonist, and cismethrin, caused no significant reduction [2]. 

Further acute toxicity study (dermal and/or inhalation)... 

TABLE 5.6. Example of Clinical Observations Broken Down by Dosage Group and Sex in an Acute Toxicity Study of the Drug SC-3740711... 

TABLE 5.7. Minimal Acute Toxicity Study Summary of the Drug SC-34871... 

TABLE 5.8. Examples of Body Weight Changes in Rats from Minimal Acute Toxicity Studies... 

Strictly speaking, an acute toxicity study is conducted to examine the effect of a single dose of a single compound. In designing specific toxicity screens, however, deviation from this principle is permissible if it increases screen sensitivity. For example, the sensitivity of mice to many indirect hepatotoxins will be enhanced by prior treatment with phenobarbital. Hence, the sensitivity of a hepatotoxicity screen will be enhanced if the mice are pretreated for three days with phenobarbital. 

DePass, L., Myers, R., Weaver, E. and Weil, C. (1984). An assessment of the importance of number of dosage levels, number of animals per dosage level, sex, and method of LD50 and slope calculations in acute toxicity studies. In Acute Toxicity Testing Alternative Approaches, Vol 2 (Goldberg, A., ed.). Mary Ann Liebert, Inc. New York, pp. 139-153. 

Historically, the goal of acute toxicity studies was to define a lethal dose range following a single administration or the administration of a few closely spaced doses. More recently, these studies have been designed to evaluate a high dose that causes significant toxicity but not necessarily lethality. If deaths occur, rarely are such studies expected to provide sufficient information to determine the cause of death. 

A number of clinical chemistry parameters are commonly determined on the blood and urine collected from animals in chronic, subchronic, and occasionally, acute toxicity studies. In the past (and still, in some places), the accepted practice has been... 

Chu I, Villeneuve DC, Secours VE, et al. 1980c. 2,8-Dihydromirex A twenty-eight day sub-acute toxicity study in the rat. J Environ Sci Health 15(1 ) 87-107. 

Mihail F. 1978. S 276 (Disyston active ingredient) acute toxicity studies. Report no. 7602a. AG Bayer, Institute fur Toxicologie, West Germany. 

Identifying the LD50 is not the only purpose of the acute toxicity study. The LD50 provides a reasonably reliable indication of the relative acute toxicities of chemicals, and this is obviously important. But an even more important reason exists for conducting such tests, and that is to prepare the way for more extensive study of subchronic and chronic exposure. 

Grau, M.T., Romero, A., Villamayor, F., Sacristan, A., and Ortiz, J.A. Acute toxicity studies of ebrotidine, Arzneim. Forsch.,... 

Kennedy, G.D., Jr. Acute toxicity studies with oxamyl, Fundam. Appl. Toxicol., 6(3) 423-429, 1986. 

Acute toxicity refers to the adverse effects, which occur within a given, usually short time, following a single, usually high exposure to a substance. In older literature, acute toxicity is sometimes used synonymously with lethal effect or LD50, which was the only endpoint in older acute toxicity tests. Nowadays, acute toxicity studies are designed to reveal more subtle effects. 

In addition to these standard acute toxicity studies, the OECD, US-EPA, and EU have developed a specific test guideline for delayed neurotoxicity of organophosphorus substances in the domestic laying hen following acute exposure, see Table 4.6. 

Acute toxicity studies (Section 4.4.3) can give some indications of general toxicity based on the observations for clinical signs of toxicity, recording of body weight, and gross and microscopic examination of organs and tissues. 

Svirbely JL Toxicity tests of decaborane for laboratory animals. I. Acute toxicity studies. Arch Ind Health 11 132-137, 1955... 

Lawrence W, et al Toxicity of ethylene chlorohydrin. I. Acute toxicity studies. J Pharm Sci 60 568-571, 1971... 

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