Toxicity determination

Some Chemical Considerations Relevant to the Mouse Bioassay. Net toxicity, determined by mouse bioassay, has served as a traditional measure of toxin quantity and, despite the development of HPLC and other detection methods for the saxi-toxins, continues to be used. In this assay, as in most others, the molar specific potencies of the various saxitoxins differ, thus, net toxicity of a toxin sample with an undefined mixture of the saxitoxins can provide only a rough approximation of the net molar concentration. Still, to the extent that limits can be placed on variation in toxin composition, the mouse assay can in principle provide useful data on trends in net toxin concentration. However, the somewhat protean chemistry of the saxitoxins makes it difficult to define conditions under which the composition of a mixture of toxins will remain constant thus, attaining a reproducible level of mouse bioassay toxicity is difficult. It is therefore useful to review briefly some of the chemical factors that should be considered when employing the mouse bioassay for the saxitoxins or when interpreting results. Similar concepts will apply to other assays. 

One of the studies at the Fraunhofer Institute clearly indicated that the toxicity resulting from chronic inhalation of diesel engine exhaust was due to the particulate component of the exhaust and not the gases (21). Rats were exposed by inhalation over most of their life span to filtered or unfiltered diesel exhaust. Exposures were 19 h/day, 5 days/wk with soot concentrations of 4 mg/m3. All of the measures of toxicity determined, including decreases in body weight, alveolar clearance, and various measures of lung function, as well as the induction of lung tumors, were observed only In animals exposed to the unfiltered exhaust. 

In the pharmaceutical industry, acute toxicity testing has uses other than for product safety determinations. First, as in other industries, acute toxicity determinations are part of industrial hygiene or occupational health environmental impact assessments (Deichmann and Gerarde, 1969). These requirements demand testing not only for finished products but frequently of intermediates as well. These issues and requirements, however, are discussed in Chapter 2 and are not directly addressed here. 

E. Borenfreund and J. A. Puerner. Toxicity determined in vitro by morphological alterations and neutral red absorption. Toxicol. Lett. 24 119-124 (1985). 

There are two types of laboratory tests toxicity determinations on wildlife and aquatic organisms and the use of model ecosystems to measure bioaccumulation and transport of toxicants and their degradation products. 

Persoone, G. and Vangheluwe, M.L. (2000) Toxicity determination of the sediments of the river Seine in France by application of a battery of microbiotests, in G. Persoone, C. Janssen and W.M. De Coen (eds.), New Microbiotests for Routine Toxicity Screening and Biomonitoring, Kluwer Academic / Plenum Publishers, New York, pp. 427-439. 

In the case of whole-sediment toxicity determination, the necessary dilutions can be made with reference sediment material. A standardized method whereby polluted sediments can be diluted with unpolluted sediments for sediment-contact tests is currently being researched (Hoss and Krebs, 2003). Hence, the pT-method is capable of capturing the toxic effects of both soluble and adsorbed contaminants in a given sample, assuming that appropriate toxicity tests (i.e., solid-phase contact tests on whole sediment and tests on porewater or elutriates) are used. 

FIGURE 17.3 FED and FEC contribution for well-ventilated conditions from the principal fire gas toxicants determined in different polymers. 

FIGURE 17.4 FED and FEC contribution for under-ventilated conditions from the principal fire gas toxicants determined in different polymers. (Adapted from Robinson, J.E. et al., Proceedings of the 11th International Conference, Interflam, London, U.K., 2007.)... 

Toxicity test procedure in higher animals (e.g., rats, mice, rabbits, dogs, and monkeys) is different from that in lower animals because the number of available animals usually is limited. As mentioned earlier, it is not economical or practical to use a few hundred mammals for the evaluation of a single toxicity test. The limitation in number has necessitated several adjustments to assure the validity of toxicity determinations in higher animals. Typically, in the pesticide industry, three types of tests are required acute, subacute, and chronic. 

The QSAR paradigm has been shown to be particularly useful in environmental toxicology, especially in acute toxicity determinations of xe-nobiotics (223). There has recently been an emphasis on "transparent, mechanistically comprehensive QSAR for toxicity," a move that is welcomed by many researchers in the field (224, 225). Cronin and Schultz developed QSAR 1.101 to describe the polar, narcotic toxicity of a large set of substituted phenols. A number of phenols with ionizableor reactive groups (e.g., —COOH, SIO, — NH2, or — NHCOCHg) were omitted from the final analysis (226). 

Rosen, H., Blumenthal, A., Panasevlch, R., McCollum, J. 1963 Dlmetti l Sulfoxide DMSOJ as a Solvent In Acute Toxicity Determinations. Proc. Soc. Exp. Biol. Mad. 120 511-514. 

Metabolism of a chemical plays an essential role in the toxicity evaluation of a chemical. It will usually result in the conversion to a more water-soluble metabolite, enhancing the excretion ratio and shortening the half-life of the chemical in vitro. However, biotransformation may also result in a metabolite with a higher reactivity, thus increasing the toxic potential of exposure to the chemical. Because in many cases in vitro systems do not account for this bioactivation, this factor is considered an important drawback of in vitro toxicity determinations [18]. 

Ahne, W. Use of fish cell cultures for toxicity determination in order to reduce and replace the fish tests. Zentbl. Bakteriol. Mikrobiol. Hyg. [B] 180 480-504, 1985. 

Gilles D. 1976. Health hazard evaluation Toxicity determination report 75-147-318. Westinghouse Electric Corporation, East Pittsburgh, PA. Cincinnati, OH U.S. Department of Health and Human Services. Public Health Service, Centers for Disease Control, National Institute for Occupational Safety and Health. NTIS PB264802. 

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