Toxicity chemical mixtures

Human toxicology of chemical mixtures toxic consequences beyond the impact of one-component product and environmental exposures / Harold I. Zeliger. p. cm. 

For a more thorough discussion of the topic of the application of PBPK modeling to the analysis of chemical mixture toxicity and interactions, the reader is encouraged to consult a chapter on PBPK modeling of chemical mixtures [2],... 

Children very often do arts and crafts projects. In doing so they use adhesives, paints, marker pens, cleaners, and other chemical mixtures. Toxic chemicals released from such products include [9] ... 

Table 7.4 Toxic hazards from incompatible chemical mixtures...

Where high operating temperatures are required, high-temperature thermal fluid systems may be used instead of pressurized water or steam systems. These systems operate at atmospheric pressure using non-toxic media such as petroleum oil for temperatures up to 300°C or synthetic chemical mixtures where temperatures in excess of this are required (up to 400°C). Some advantages and disadvantages of thermal fluid or heat transfer oil systems are listed below. 

Safe, S. (1998) Hazard and Risk Assessment of Chemical Mixtures Using the Toxic Equivalency Factor Approach. Environmental Health Perspectives, 106(Suppl. 4), 1051-1058. 

Witzmann FA et al. Toxicity of chemical mixtures proteomic analysis of persisting liver and kidney protein alterations induced by repeated exposure of rats to... 

For many, familiarity with the TSCA generally stems from its specific reference to polychlorinated biphenyls, which raise a vivid, deadly characterization of the harm caused by them. But the TSCA is not a statute that deals with a single chemical or chemical mixture or product. In fact, under the TSCA, the EPA is authorized to institute testing programs for various chemical substances that may enter the enviromnent. Under the TSCA s broad authorization, data on the production and use of various chemical substances and mixtures may be obtained to protect public health and the environment from the effects of harmful chemicals. In actuality, the TSCA supplements the appropriate sections dealing with toxic substances in other federal stamtes, such as the Clean Water Act (Section 307) and the Occupational Safety and Health Act (Section 6). 

Environmental contamination usually consists of a mixture of pollutants and their partially degraded derivatives. Such an ill-defined chemical mixture will eventually lead to the formation of an ecosystem of microbes. The individual member species cannot survive in the toxic and hostile environment. Effective bioremediation technologies should therefore invoke a mixture of microorganisms forming synergistic consortia. Any realistic bioremediation concept is based on the recognition that it is the concerted action of various species, which may bring about the desired clean-up effect. 

Stacey NH. 1987b. Assessment of the toxicity of chemical mixtures with isolated rat hepatocytes Cadmium and chloroform. Fundam Appl Toxicol 9 616-622. 

Broderius, S. and Kahl, M. Acute toxicity of organic chemical mixtures to the fathead minnow, Aquat. Toxicol, 6(4) 307-322. 1985... 

At present the risk assessment of contaminated objects is mainly based on the chemical analyses of a priority list of toxic substances. This analytical approach does not allow for mixture toxicity, nor does it take into account the bioavailability of the pollutants present. In this respect, bioassays provide an alternative because they constitute a measure for environmentally relevant toxicity, that is, the effects of a bioavailable fraction of an interacting set of pollutants in a complex environmental matrix [9-12]. 

W. K. Lutz, S. Vamvakas, A. Kopp-Schneider, J. Schlatter and H. Stopper, Deviation from additivity in mixture toxicity relevance of nonlinear dose-response relationships and cell line differences in genotoxicity assays with combinations of chemical mutagens and g-radiation. Environmental Health Perspectives Supplements, 2002,110(6), 915-918. 

As has already been outlined in the introduction, one of the main points to consider is whether there will be no interaction or interaction in the form of either synergism or antagonism. These three basic principles of combined actions of chemical mixtures are purely theoretical and one often has to deal with two or all three concepts at the same time, especially when mixtures consist of more than two compounds and when the toxicity targets are more complex. 

Testing of the whole mixture as such has been recommended for mixtures that are not well characterized (Mumtaz et al. 1993), and has successfully been applied for assessing the combined toxicity of simple, defined chemical mixtures where the toxicological properties of the individual components were also investigated, see Section 10.6. 

Approaches for Assessment of Joint Toxic Action of Chemical Mixtures Suggested by ATSDR... 

ATSDR. 2004. Guidance manual for the assessment of joint toxic action of chemical mixtures. Atlanta, U.S.A. U.S. Department of Health and Human Services, Public Health Service, Agency of Toxic Substances and Disease Registry, Division of Toxicology, http //www.atsdr.cdc.gov/interactionprofiles/ipga.html... 

Limited information is available regarding the influence of other chemicals on the toxicity of 1,3-DNB or 1,3,5-TNB. One study reported that a chemical mixture containing 1,3-DNB was not toxic and did not induce methemoglobin formation. The mixture contained 1,3-DNB (0.5%), ethylene glycol (77.5% or less), and diethylene glycol (15% or more) (Ishihara and Ikeda 1979). As the mixture was made more polar either by adding water or short-chain dicarboxylic acids, methemoglobin formation was favored. The specific mechanism of this interaction is not known. 

Altenburger R., T. Backhaus, W. Boedeker, M. Faust, M. Scholze, and L. H. Grimme (2000). Predictabihty of the toxicity of multiple chemical mixtures to Vibrio fischeri Mixtures composed of similarly acting chemicals. Environmental Toxicology and Chemistry 19 2341-2347. 

For the purposes of estimating the potential toxicity of the chemical mixture, it is assumed the toxicity of the individual component compounds is additive. Data from the Registry of Toxic Effects of Chemical Substances (RTECS) and from the Hazardous Substances Data Bank will be accepted, as well as peer-reviewed primary data. 

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