Toxicity testing types

Table 5.3 Summary of major toxicity test types, matrices and species commonly utilized in the USA.

Daylight fluorescent pigments (qv) are considered to be nontoxic. Since they are combinations of polymers and dyestuffs, the combined effect of the ingredients must be taken into account when considering the net toxic effect of these materials. Table 5 gives results of laboratory animal toxicity tests of standard modified melamine—formaldehyde-type pigments, the Day-Glo A Series, and the products recommended for plastic mol ding, Day-Glo Z-series. 

There are many guidelines that need to be followed and which are common to all types of toxicity testing, the most important of which are as follows ... 

Mice are utilized for testing antiseptics for appHcation to cuts, wounds, and incisions (339). The test bacteria, type 1 pneumococcus and hemolytic streptococcus, ate appHed to the taHs of anaesthetized mice. The tip of the taH is then dipped into the antiseptic for 2 min, after which one-half inch of the taH is removed and inserted into the peritoneal cavity and the incision is closed. If after 10 days the animals survive, the product is considered satisfactory for use as a skin antiseptic. The blood of dead animals is sampled and streaked on blood agar for confirmation of infection from the test bacteria as the cause of death. Since lack of toxicity is another requirement of a product to be appHed to wounds, this test has been combined with a toxicity test (340). 

There is a continuing interest in the development of biomarker assays for use in environmental risk assessment. As discussed elsewhere (Section 16.6), there are both scientific and ethical reasons for seeking to introduce in vitro assays into protocols for the regulatory testing of chemicals. Animal welfare organizations would like to see the replacement of toxicity tests by more animal-friendly alternatives for all types of risk assessment—whether for environmental risks or for human health. 

Cytochrome P450-type monooxygenase systems, which have a generally low substrate specificity, are widely distributed in the species of fish used for toxicity testing (Funari et al. 1987). 

Many of these properties would obviously limit applicability of non-continuous cell lines in the industrial-scale production of recombinant proteins. However, such cell types are routinely cultured for research purposes, toxicity testing, etc. 

Toxicology and environmental health studies often lack a firm foundation of baseline data, and the NASGLP is a perfect starting point for a baseline data survey. During the field component of the survey, the crews collected two composite samples. One represented the top 5 cm of the soil directly below the litter layer (which will include a lot of the airborne components if they are present), and a second came from the 0-30-cm interval, independent of which soil horizon this may represent. Within this interval (the active layer), most of the interactions between biota and the non-living soil components take place, and thus is the important interval for this type if study. Environment Canada s Biological Methods Division selected one of the northern New Brunswick sites to collect a bulk sample in an attempt to create reference sites across Canada for standardized toxicity test methods. 

Category A lists three types of studies for human health effects basic acute toxicity tests, a 28-day animal study (referred to in other discussions as a "sub-chronic" test), and a series of two (or more) screening tests for mutagenicity and carcinogenicity. 

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... 

Another possible use of in vitro developmental toxicity tests would be to select the least developmentally toxic backup from among a group of structurally related compounds with similar pharmacological activity [use (2) in the list above], for example, when a lead compound causes malformations in vivo and is also positive in a screen that is related to the type of malformation induced. However, even for this limited role for a developmental toxicity screen, it would probably also be desirable to have a measure of the comparative matemotoxicity of the various agents and/or information on the pharmacokinetics and distribution of the agents in vivo. 

From a regulatory standpoint, the FDA s concern regarding safety involves the toxicity, degradants, and impurities of excipients, as discussed in other chapters in this book. In addition, other chapters of this book address types of toxicity concerns, toxicity testing strategies, and exposure and risk assessment of excipients. 

Study Type. Metabolic and pharmacokinetic data from a rodent species and a nonrodent species (usually the dog) used for repeat dose safety assessments (14 days, 28 days, 90 days or six months) are recommended. If a dose dependency is observed in metabolic and pharmacokinetic or toxicity studies with one species, the same range of doses should be used in metabolic and pharmacokinetic studies with other species. If human metabolism and pharmacokinetic data also are available, this information should be used to help select test species for the full range of toxicity tests, and may help to justify using data from a particular species as a human surrogate in safety assessment and risk assessment. 

In general, existing information is related to single species and acute toxicity these types of tests form the basis for the derivation of safe concentrations for a given chemical in the environment, according to EC regulation [6]. The data for surfactants other than anionic... 

Most microalgal toxicity tests procedures recommend the use of initial cellular concentrations of 104 cells mL 1. This cellular concentration should be selected because it is the minimum cellular concentration that can be measured in haematocytometers (Neubauer chambers). Furthermore, natural cellular concentrations in non-polluted conditions (in marine environments) are often below the concentration mentioned. The importance of cellular density at the beginning of the test has been demonstrated for certain toxicants [43]. The lower the cellular concentration, the higher the sensitivity of the test, at least for certain types of xenobiotics, such as heavy metals. 

Let us skip by the question of the adequacy of the animal tests used to identify these agents. The general quality of the animal test is obviously of great importance in the overall evaluation and these questions cannot be ignored in the case of cancer bioassays any more than they can in any other type of toxicity test. But the more interesting questions arise when we move beyond the question of study quality. 

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