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At least 19 recordsLinked to original sources
PubMed2006

Alternative approaches can greatly reduce the number of fish used for acute toxicity testing.

Acute toxicity tests with algae, daphnids, and fish are required for the classification and environmental risk assessment of chemicals. The degree of risk is determined by the lowest of these acute toxicity values. Many ecotoxicological programs are seeking to reduce the numbers of fish used in acute toxicity testing. The acute threshold test is a recently proposed strategy that uses, on average, only 10 (instead of 54) fish per chemical. We examined the consequences of reducing the number of fish used in toxicity testing on the ultimate outcome of risk assessments. We evaluated toxicity data sets for 507 compounds, including agrochemicals, industrial chemicals, and pharmaceuticals from our internal database. Theoretical applications of the acute threshold test gave similar results to those obtained with the standard fish median lethal concentration (LC50) test but required only 12% as many fish (3195 instead of 27,324 fish used for all compounds in the database). In 188 (90%) of the 208 cases for which a complete data set was available, the median effect concentration for algae or daphnids was lower than the LC50 for fish. These results show that replacement of the standard fish LC50 test by the acute threshold test would greatly reduce the number of fish needed for acute ecotoxicity testing without any loss of reliability.

Animals↗
PubMed2001

Use of newborn Girardia tigrina (Girard, 1850) in acute toxicity tests.

Acute toxicity tests, exposing Girardia tigrina to potassium dichromate (K(2)Cr(2)O(7)), showed good reproducibility. The 95% confidence intervals among tests were 0.0262+/-0.0141 g for 48-h LC(50) (N=6) and 0.0129+/-0.0078 g for 96-h LC(50) (N=5). The 96-h LC(50) for G. tigrina was below that of oligochaetes and above that of cladocera.

Animals↗
PubMed1984

[Acute toxicity test of garlic extract].

The acute toxicity toxicity test of garlic extract was studied in Wistar rats and ddY mice. The LD50 values of garlic extract by P.O., I.P. and S.C. administration were estimated over 30 ml/kg respectively in male and female of both rodents. In 30 ml/kg of I.P. group, five of ten in male rats and one of ten in female rats were died within a day after administration, however no specific signs due to garlic extract were observed in survivals for 7 days.

Animals↗
PubMed1983

Complete programme for acute toxicity testing - not only LD50 determination.

The objective of any experimenter should be to obtain the maximum amount of useful information in the most economical manner possible. In this context, 'useful' means study both of the principal or anticipated actions of the compound under examination, and also detection of additional responses to it. For efficient evaluation, including greater statistical rigour, a continuous or graded response and quantitative measurement is preferable, although much can be done by simply analysis of the presence or absence of responses, even if these are complex or dependent upon subjective criteria. Consistency of experimental conditions, and of diagnostic criteria are essential, whether in single, exploratory or comparative tests. Acute toxicity tests, like other experiments, should be designed pragmatically, therefore, confirming to the properties of the substance under examination, but also with general or holistic coverage, albeit less specific, to detect unanticipated actions. Greater or lesser weight may be given to these two classes of method, depending on whether the test is done as part of a general screen of a previously unknown substance, or as a specific control measure done to assay one particular property. Extrapolation of the results to man or other species is only possible with the caution proper to any experiment done under restricted and highly artificial conditions, but the value of acute toxicity data has often been shown by experience gained in man.

Animals↗
PubMed1989

Acute toxicity tests on 113 environmental chemicals.

Acute toxicity tests on 113 environmental chemicals were conducted by the order of the Japanese government agencies. the LD50s or LC50s for 23 household chemicals, 11 medical drugs, 10 drug additives, 20 food additives, 13 industrial chemicals, 14 environmental pollutants, 12 agricultural chemicals and 5 organic solvents are presented together with the major toxic signs and symptoms and macroscopic changes in tissues. These toxicity data will be useful as an information source for regulatory purposes and also for prediction of the potential for acute toxicity of a wide variety of new chemicals.

Animals↗
PubMedDate not supplied

Effect of olive mill wastewaters on the oxygen consumption by activated sludge microorganisms: an acute toxicity test method.

The test for inhibition of oxygen consumption by activated sludge (ISO 8192-1986 (E)) was evaluated as a tool for assessing, the acute toxicity of olive mill wastewaters (OMW). According to the ISO test, information generated by this method may be helpful in estimating the effect of a test material on bacterial communities in the aquatic environment, especially in aerobic biological treatment systems. However, the lack of standardized bioassay methodology for effluents imposed that the test conditions were modified and adapted. The experiments were conducted in the presence or absence of an easily biodegradable carbon source (glucose) with different contact times (20 min and 24 h). The results obtained showed a remarkable stimulatory effect of this effluent to the activated sludge microorganisms. In fact, the oxygen uptake rate values increase with increasing effluent concentrations and contact times up to 0.98 microl O(2) h(-1) mg(-1) dry weight for a 100% OMW sample, 24 h contact time, with blanks exhibiting an oxygen uptake rate of ca. 1/10 of this value (0.07-0.10). It seems that the application of the ISO test as an acute toxicity test for effluents should be reconsidered, with convenient adaptation for its utilization as a method of estimating the effect on bacterial communities present in aerobic biological treatment systems.

Bacteria, Aerobic↗
PubMed2004

Spirotox-Spirostomum ambiguum acute toxicity test-10 years of experience.

Spirotox is a short-term acute toxicity test with a large ciliated protozoan Spirostomum ambiguum. The test was created in the Department of Environmental Health Sciences, Medical University of Warsaw, Poland, during the early 1990s. It was presented for the first time during the 6th International Symposium on Toxicity Assessment, in Berlin in 1993. S. ambiguum was very resistant to a wide range of environmental conditions, especially to pH and dissolved oxygen. Over the last 10 years the sensitivity of S. ambiguum to many classes of toxicants was evaluated. Spirotox was found to be very sensitive to heavy metals, fungicides, and pharmaceuticals used to cure diseases of the human nervous system. On the other hand, it was generally less sensitive than standard bioassays to simple organics. Spirotox was also used for analysis of cyanobacterial blooms. Though it was moderately sensitive to hepatotoxins, the test seems to be a good tool for evaluation of the entire toxicity of blooms. The last but not the least of the applications of the Spirotox test was evaluation of the toxicity of extracts from medical devices. Protozoa, which are the simplest eukaryotes, seem to be good screening bioassays for monitoring the technology of medical device production.

Animals↗
PubMed1985

An up-and-down procedure for acute toxicity testing.

An up-and down method for acute toxicity (LD50) testing has been developed and statistically evaluated. Compared with the "classical" procedure, this method permits a major reduction in the number of animals used. In the up-and-down procedure, animals are dosed one at a time. If an animal survives, the dose for the next animal is increased; if it dies, the dose is decreased. A survey of 48 acute toxicity tests in rats showed that the great majority of the animals that ultimately died did so within 1 or 2 days. Because of this, it suffices to observe each animal for 1 or 2 days before dosing the next animal. It is recommended, however, that surviving animals be monitored for delayed death for a total of 7 days. The procedure for estimating the LD50 takes into account all deaths, and may be performed using widely available computer program packages. Testing in females alone is recommended, based on the observation that they were generally more sensitive in the survey of 48 studies; selective follow-up in males may sometimes be indicated. The procedure has been tested, by simulation, on 10 of the survey studies. It produced excellent agreement with the original studies. The 95% confidence interval for the LD50 averaged +/- 32% by the up-and-down method, compared with +/- 15% for conventional studies using 40 to 50 animals. The up-and-down procedure will require only 6 to 10 animals, provided that the initial estimate of the LD50 is within a factor of 2 of the true LD50. The method cannot be recommended for testing materials where deaths beyond 2 days postdosing are the rule.

Administration, Oral↗
PubMed2004

Opportunities for reduction in acute toxicity testing via improved design.

The conventional method for assessing acute oral toxicity (OECD Test Guideline 401) was designed to identify the median lethal dose (LD50), using the death of animals as an endpoint. Introduced as an alternative method (OECD Test Guideline 420), the Fixed Dose Procedure (FDP) relies on the observation of clear signs of toxicity, uses fewer animals and causes less suffering. More recently, the Acute Toxic Class method and the Up-and-Down Procedure have also been adopted as OECD test guidelines. Both of these methods also use fewer animals than the conventional method, although they still use death as an endpoint. Each of the three new methods incorporates a sequential dosing procedure, which results in increased efficiency. In 1999, with a view to replacing OECD Test Guideline 401, the OECD requested that the three new test guidelines be updated. This was to bring them in line with the regulatory needs of all OECD Member Countries, provide further reductions in the number of animals used, and introduce refinements to reduce the pain and distress experienced by the animals. This paper describes a statistical modelling approach for the evaluation of acute oral toxicity tests, by using the revised FDP for illustration. Opportunities for further design improvements are discussed.

Animal Use Alternatives↗
PubMed1998

13th Meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC): validation and acute toxicity testing.

Scientific principles demand that before newly developed alternative methods for safety testing are fully embraced by the industrial or regulatory community, they reliably and reproducibly predict the designated toxic end point. The process used to determine reliability and reproducibility is termed validation, and it generally culminates with a highly controlled, blinded study using multiple chemicals and laboratories. It is imperative that the validation study is designed to confirm the previously established reproducibility and predictive power of the assay. Much has been learned recently about the practical aspects of validation through investigation of alternative methods for acute toxicity testing, i.e., those methods that assess acute systemic toxicity, skin irritation, and eye irritation. Although considerable progress has been made--many alternative tests are now commonly used in various industrial settings--there have been few tests that have successfully passed a complete validation. Some of the barriers to successful validation have been a) lack of high-quality, reproducible animal data; b) insufficient knowledge of the fundamental biologic processes involved in acute toxicity; and c) the development of truly robust in vitro assays that can accurately respond to materials with a wide range of chemical and physical characteristics. It is recommended that to progress in the areas of eye and skin irritation we need to expand our knowledge of toxic markers in humans and the biochemical basis of irritation; progress in the area of acute systemic toxicity will require the development of in vitro models to determine gastrointestinal uptake, blood-brain barrier passage, and biotransformation.

Animal Testing Alternatives↗
PubMed1983

Acute toxicity testing in cultures of mouse neuroblastoma cells.

Cultured mouse neuroblastoma cells (C1300) may be used as models for nerve cells since they have a number of properties in common with their normal counterparts in vivo. In order to test the possibility of using C1300 cells as alternative to experimental animals when testing for acute toxicity, cells (clone 41A3) were exposed to a number of common chemicals (CH3HgCl, CdCl2,HgCl2 ppDDT, n-butanol, benzene, dioxan, n-propanol, aceton and t-butanol). The toxic effect was quantified by measuring the degree of cell detachment in the cultures. The concentrations of chemicals that caused 25% of the total cell number to detach (TD25) were used for comparison with LD50 values. In spite of the very simplified situation in culture, where the toxicity of a substance is little or not at all influenced by factors like penetration, storage, metabolism and excretion a good correlation (corr. coeff. 0,98) was obtained between TD25 values and LD50 values. Good correlations between in vitro and in vivo tests have also been reported by others. One possible explanation to these findings could be simplified in vivo toxicokinetics of these substances when tested in high doses for general effects like animal death. If so, simple in vitro tests may be used for predicting acute toxicity of certain groups of substances.

Animals↗
PubMed1990

Acute toxicity testing in the nonlethal dose range: a new approach.

A new modification of acute toxicity testing of chemicals in rats is presented. Instead of using death as the principal criterion of toxicity, it is based on a careful, standardized clinical assessment of toxic signs measured in the nonlethal dose range. Test compounds are administered to groups of rats at four dose levels, selected on the basis of pilot experiments. General indices of toxicity, i.e., body weight gain, food and water consumption, and body temperature, are recorded at regular intervals; activity in the home cage is monitored continuously with a newly developed passive infrared device; neurobehavioral dysfunctions are assessed repeatedly with a checklist; and routine hematology is done on the 4th day after administration of the test compounds. All measured signs of toxicity are scored in relation to the control groups so that the absolute magnitude of the score increases as a function of the deviation from the normal conditions of the animals. In order to take into consideration the course of intoxication and the rate of recovery, toxicity scores are added over the duration of the whole experiment. For each variable measured, the resulting total scores are converted into a relative point system, scaling from 0 to 10 points. These points are added to a single "total ToxScore" value for each dose group. A regression line is calculated for these total ToxScore points, and the dose giving 15 total ToxScore points is determined. Based on the results obtained with nine reference substances, a classification system is proposed that is comparable to that based on LD50 values. It is concluded that the proposed test procedure provides much more information on the signs of acute toxicity, the course of the intoxication, the slope of the dose-effect curve, and the rate of recovery than does the standard LD50 test. In addition, the degree of distress and suffering of the animals is reduced.

Acetanilides↗
PubMed1998

The impact of stress and discomfort on experimental outcome.

Stress refers to a physiological and emotional state of man and higher animals in which the autonomic regulation is overstrained and temporarily disturbed under the impact of conflicting stimuli. Stress activates, invigorates, acts life-sustaining, and initiates and drives adaptive changes towards improved fitness. While the positive action is commonly underestimated, much attention is given to the discomfort and the strain of efforts required during coping. The label of stress as being bad and the core of suffering has been applied with particular empathy to laboratory animals, for they are kept in captivity and are exposed to experimental procedures. The husbandry conditions to which the animals are adapted are commonly standardized. This applies to procedures for subacute and chronic toxicity testing. Acute toxicity tests are the classical example of stress research in which the demands on the organism exceed the limits of its regulative capacity. Stressors are: the test compound, the procedure proper and preceding treatment of the animal. The experimental stress contributes to model the real situation. The weighting between the stressors may modify the outcome of the test.

Animal Welfare↗