Toxicity test designs

As protozoa and nematodes live in pore water in the soil, most of the methods are adapted from toxicity tests designed for aquatic samples. Among the protozoa the tests with cihates Tetrahymena pyriformis, Tetrahymena thermophiia, Colpoda cucullus, Colpoda inflata, Colpoda steinii, Paramecium caudatum, and Paramecium aurelia have been developed [ 102,112-117]. It is the opinion of some authors that the sensitivity of infusorians is higher than that of microorganisms [115,116]. 

Iterative series of chemical manipulations (e.g., pH adjustment, filtration, aeration) followed by toxicity testing designed to determine the contaminant responsible for the observed toxicity in the original sample. Volume 1(10), Volume 2(5,10). 

An acute toxicity test designed to test chemicals for potential eye irritation usucdly conducted in rabbits. 

Aquatic Toxicity. The standard tests to measure the effect of substances on the aquatic environment are designed to deal with those that are reasonably soluble ia water. Unfortunately this is a disadvantage for the primary phthalates because they have a very low water solubiUty (ca 50 p.g/L) and this can lead to erroneous test results. The most common problem is seen ia toxicity tests on daphnia where the poorly water-soluble substance forms a thin film on the water surface within which the daphnia become entrapped and die. These deaths are clearly not due to the toxicity of the substance but due to unsuitable test design. 

EinaHy, the ecotoxicological studies, designed to assess the impact of the substance on the environment, embrace acute toxicity tests to fish and Daphnia, and a battery of tests for the biodegradabiUty of the substance and its biological oxygen demand characteristics. 

Biological sui veys should be used together with whole-effluent and ambient toxicity testing, and chemical-specific analyses to assess the attainment/nonattainment of designated aquatic hfe uses in state water-quahty standards. ... 

In general, traditionally designed acute toxicity tests can be divided into three types that can be called the minimal acute toxicity test, the complete acute toxicity test, and the supplemented acute toxicity test. Of these, the minimal protocol is by... 

This chapter briefly describes the current standard study designs and then focuses on current issues in developmental and reproductive toxicity testing. 

Some biotechnologically derived pharmaceuticals will cross-react with species that can be evaluated toxicologically, while others cross-react only with nonhuman primates such as the chimpanzee, a protected species. In this case, a well-designed safety, or Phase 0 study at doses higher than the proposed clinical dose may provide valuable safety information. However, a lack of cross-reactivity with any nonhuman species does not necessarily make preclinical safety evaluation impossible, not does it limit toxicity testing to species in which the protein lacks relevant pharmacological activity. Some alternative possibilities are summarized in Table 12.9. 

Modified Buehler. Buehler (1964) developed the first test system to use an occlusive patch to maximize dermal exposure and to increase the test sensitivity (Buehler, 1964). Although, this assay is still insensitive for some xenobiotics that may not sufficiently traverse the epidermis, it is particularly useful for compounds that are either highly irritating by intradermal injection or cannot be dissolved or suspended in a form that is conducive to injection. Other advantages are that the test produces few false positives, rarely overpredicts the potency of sensitizers, and is less likely to produce limiting system toxicity or ulceration at the induction sites. Figure 15.4 shows the test design in its current (OECD) form. 

Metabolism and pharmacokinetic studies have greater relevance when conducted in both sexes of young adult animals of the same species and strain used for other toxicity tests with the test substance. The number of animals used in metabolism and pharmacokinetic studies would be sufficient to reliably estimate population variability. This usually means a separate (but parallel) set of groups of animals in rodent studies. A single set of intravenous and oral dosing results from adult animals, when combined with some in vitro kinetic results, may provide an adequate data set for the design and interpretation of short-term, subchronic and chronic toxicity studies. 

Accordingly, the use of flow cytometry can improve the design of toxicity bioassays, as the detection limit of this apparatus includes cellular concentrations equal to those of microalgal populations found in natural conditions. Comparison of compositions utilised in some known toxicity tests for microalgaes are shown in Table 7.1.1. 

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