Short-term in vivo tests

The rat liver foci assay is a short-term in vivo test to predict carcinogenic potential of a chemical. In this assay, 1,2-dibromoethane has both initiating and promoting activity, which correlates well with its carcinogenic effects in animals. 

World Health Organization (WHO), Environmental Health Criteria 109, Carcinogens, Summary Report on the Evaluation of Short-Term in Vivo Tests, World Health Organization, Geneva, 1990. 

Carcinogens, summary report on the evaluation of short-term in vivo tests (No. 109,1990)... 

V. (1984) Evaluation of diallate and triallate herbicides for genotoxic effects in a battery of in vitro and short-term in vivo tests. Mutat. Res., 136, 173-183... 

International Collaborative Study to Evaluate Short-Term in Vivo Tests for Carcinogens... 

By mouse skin painting it is also possible to examine the biological activities of fractions of the total particulate material. This can be done in a complete test system, i.e. looking only at the material of interest applied repeatedly to the skin, or in a test system where the material of interest is looked at either as a tumor initiator or tumor promotor. Tumor initiation and tumor promotion assessment offer some promise as relatively short-term in vivo tests especially when a tumor susceptible mouse like SENCAR is utilized. 

Apart from antibodies detected by (a) the schizont-infected red cell agglutination test, (b) the agglutination of sporozoites, (c) complement fixation, (d) passive hemagglutination and by the direct and indirect immunofluorescent methods [for review, see reference (V4)], malarial antibodies have also been detected by malarial antigens prepared from heavily infected human placenta, infected human brain, and short-term in vivo cultures of cells from heavily parasitized subjects (Wll) (see Tables 7 and 8). 

Short-term in vivo and in vitro tests that can give an indication of initiation and promotion activity may also provide supportive evidence for a particular stochastic response. However, lack of positive results for genetic toxicity does not necessarily provide a basis for discounting positive results in long-term animal studies. 

Schuler RL, Hardin BD, Niemeier RW, et al. 1984. Results of testing 15 glycol ethers in a short-term in vivo reproductive toxicity assay. Environ Health Perspect 57 141-146. 

In summary, these studies have demonstrated the general utility of short-term tests to evaulate the mutagenic and carcinogenic potential of environmental chemicals. It is now clear that to provide a comprehensive evaluation, it will be necessary to supplement such short-term in vitro asssays as the Ames Salmonella test and an in vitro assay for chromosome aberrations in mammalian cells in culture with short-term in vivo assays. At present, the best candidates for these in vivo assays are (1) the mouse bone marrow micronucleus assay, and (2) the assay for unscheduled DNA synthesis in rat liver cells. 

Drags for which several other tests for photoreactivity, such as in vitro photogenotoxicity, adduct formation, human photoirritation, or short-term in vivo nonclinical tests, are positive... 

The objectives of this research are to develop short-term in vitro fatigue test methodologies that will predict long-term in vivo performance of elastomers used in cardiac assistance and related devices and to evaluate the fatigue life of candidate materials for potential use in these applications. 

WHO/IPCS. 1990. Summary report on the evaluation of short-term tests for carcinogens (coUahorative study on in vivo tests). Environmental Health Criteria 109. Geneva WHO. http //www.inchem.org/documents/ ehc/ehc/ehc 109. htm... 

Additional tests may either be short or medium-term in vivo rodent test systems, usually using the mouse. These models of carcinogenesis may use transgenic or neonatal rodents. The guideline also includes models... 

The stepwise procedure usually starts with the determination of the LD50, a short term repeated exposure test in rodents and the evaluation of genotoxicity by an in vitro bacterial test system (Ames-test) and for cytogenicity in mammalian cells. In case of indication for genotoxicity the results are verified in vivo usually by the mouse bone marrow micronucleus test. For further evaluation the compound additional tests including studies on toxicokinetics or the toxic mechanisms will follow. Such information provides information on the reactivity of the test compound, its... 

As a result of large international collaborative studies to evaluate various short-term In vitro and In vivo tests, it has become clear that both approaches are needed and that any battery of assays designed to evaluate environmental chemicals must include both In vitro and In vivo short-term tests. The use of the Ames assay in isolation has resulted in premature, and sometimes false, indictment of potentially useful chemicals. A data base developed with the use of this test alone Is inadequate for the evaluation of a chemical s mutagenic and carcinogenic potential in laboratory animals and humans. 

With pressures from the animal rights movement, an impetus has been generated for the development of in vitro and/or computer models to reduce the level of in vivo testing. In the seventies, the hope of the future was placed in what was then considered a potential replacement technique for the lifetime rodent bioassay for cancer assessment—the short-term mutagenicity tests, particularly the Ames Evaluation (16). Brusick (17) has shown that the correlation between a positive mouse bioassay and a positive rat bioassay for a selected group of materials is no better than the... 

The initial attempts were the synthesis of compounds represented earlier by structure A, where the ester function was built into proximity of the propanolamine. Even though shortened duration was achieved when a short-term infusion (40 min) was carried out, their duration tended to increase considerably after the administration of the infusion itself was prolonged (ca. 3 hours). A particularly novel spontaneous inactivation mechanism independent of enzyme activity was found to occur with compounds of structure A, where n was at least three (Eq. 10.1). This intramolecular cyclization reaction (which also occurs in vitro at neutral or basic pH), while not producing a carboxylate, does result in a predictably inactive tertiary amide product. In vivo testing of the gamma-lactam derivative did in fact show it to be inactive. 

Several issues are important in the selection of tests for hemocompatibility of medical devices or biomaterials. In vivo testing in animals may be convenient however, species differences in blood reactivity must be considered and these may limit the predictability of any given test in the human clinical situation. While species differences may complicate hemocompatibility evaluation, the utilization of animals in short- and long-term testing is considered to be appropriate for evaluating thrombosis and tissue interaction. European community law prohibits the use of nonhuman primates for blood compatibility and medical device testing, even though blood values and reactivity between humans and nonhuman primates are very similar. Hemocompatibility evaluation in animals is... 

The current testing philosophy appears to be moving in the direction of applying predictive short-term tests in the early planning stages of chemical development and using in vivo tests only where the situation warrants. Many... 

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