Complex Mixtures Methods for In Vivo Toxicity Testing (1988) / Chapter Skim
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Appendix C: Case Studies on Strategies for Testing the Toxicity of Complex Mixtures
Appendix C: Case Studies on Strategies for Testing the Toxicity of Complex Mixtures
Pages 168-178
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From page 168... ...
The cases chosen represent a range of mixtures and a range of toxic end points. The end points were carcinogenesis and mutagenesis caused by cigarette smoke and fractions, systemic toxicity of fire atmospheres, and neuropathy associated with hydrocarbon and oxygenated solvents.
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From page 169... ...
The smoke particles are charged with 10~2 electrons per gram of smoke and have reducing activity when freshly inhaled. The gaseous phase of tobacco smoke does not induce malignant tumors of the respiratory tract in laboratory animals.
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have demonstrated that tobacco smoke has transplacental carcinogenic effects in hamsters. Compounds that require metabolic activation to an active carcinogenic form such as N-nitrosamine, benzoLa~pyrene, o-toluidine, ethylcarbamate, and vinyl chloride act as transplacental carcinogens.
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From page 171... ...
We can, however, identify groups of agents from a knowledge of their chemical similarity to agents generated in a standard control substance. We can learn something about the potency of tobacco smoke by comparing the composition of tobaccos grown in different soils, after different periods of aging, after the use of various fertilizer additives, and after treatment with different methods, such as nicotine and tar extraction.
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For example, all include the testing of complete samples and measurement of the acute inhalation toxicity in experimental animals. Complete chemical analysis of combustion products was not considered the proper approach, because toxic components might be missed, either through lack of
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From page 173... ...
The effect-driven chemical analysis was used to determine that a fire-retarded laboratory formulation of rigid polyurethane foam produced a highly toxic bicyclic phosphate ester when thermally decomposed (Petajan et al., 19751. Thus, the testing strategy used to determine the toxicity of the thermaldegradation products of materials has historically consisted of tests of comparative toxic potency combined with effect-driven chemical analysis.
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From page 174... ...
The experimental design was based on a matrix that indicated what concentrations and combinations of gases were lethal (Figure C-21. With that matrix, a testing strategy that uses single and combined primary gases can be applied to predict toxicity as follows.
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From page 175... ...
If the material produces combustion products that are significantly more toxic than was predicted, according to the pure-gas relationships, further studies are necessary to determine what other toxic products or interactions have occurred. As more data are collected on materials, more gases will be added to the model, and the predictions will become more accurate.
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From page 176... ...
The final experiment (Egan et al., 1980) , not cited in the major reviews referred to earlier, showed that both "nhexane-free hexane mixture" and the possibly interacting agent methyl ethyl ketone fail to produce the characteristic neuropathy.
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1982. Further Development of a Test Method for the Assessment of the Acute Inhalation Toxicity of Combustion Products.
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