Toxicological interactions

Levin, B.C. Paabo, M. Gurman, J.L. Harris, S.E. Braun, E. Toxicological Interactions Between Carbon Monoxide and Carbon Dioxide, Toxicology 1987, 47, 135-164. 

Information is also needed on the toxicological interactions of groups of polychlorinated chemicals (such as certain biphenyls, biphenylenes, and dibenzofurans) known to be isosteric with 2,3,7,8-TCDD and that frequently coexist with 2,3,7,8-TCDD in environmental samples. Acquisition of these data should provide the basis of a risk assessment analysis for dioxin and fishery and wildlife resources. 

Jakab, G.J., The toxicologic interactions resulting from inhalation of carbon black and acrolein on pulmonary antibacterial and antiviral defenses, Toxicol. Appl. Pharmacol. 121, 2, 167, 1993. 

In the natural environment, organisms are exposed to mixtures of compounds. Therefore toxicological interactions such as competitive... 

For experimental studies of mixtmes, consideration is given to the possibility of changes in the physicochemical properties of the test substance during collection, storage, extraction, concentration and delivery. Chemical and toxicological interactions of the components of mixtmes may result in nonlinear dose-response relationships. 

Soni MG, Mehendale HM. Role of tissue repair in toxicological interactions among hepatotoxic organics. 

B.C. Levin, M. Paabo, J.L. Gurman, S.E. Harris, E. Braun, Toxicological interactions between carbon monoxide and carbon dioxide. Toxicology 47 135, 1987. 

For noncancer effects the use of PBTD models has elucidated the fundamental mechanisms of toxicological interactions. Such mechanistic knowledge linked with Monte Carlo simulations has initially been employed in in silico toxicology to develop models that predict the toxicity of mixtures in time. The combination of PBTK/TD models for individual compounds with binary PBTK/TD models can be achieved by incorporating key mechanistic knowledge on metabolism inhibitions and interactions through shared enzyme pathways. Simulations of such models can then be compared to experimental data and allow conclusions to be reached about their pharmacokinetics and the likelihood of effects being dose additive. 

Component-Based Methods. Component-based approaches (Figure 5.5) are generally used to evaluate human health risks from exposure to a limited number of chemicals as a mixture. Key issues for component-based assessments include similarity in dose-response curves and similar vs. independent toxic modes of action (MOAs) among mixture components. A distinction can be made between 1) assessments using relatively simple additivity methods without the consideration of potential interaction effects, and 2) assessments that include data on toxicological interactions. Both types of assessments are discussed in more detail below. 

Figure 5.9 A limited array of possible (dis)similar actions of compounds at the target site of intoxication, including the relationship between the toxicological interaction and the final effect that is observed. In this figure, a and b are compounds, A1 and A2 are sites of action, SI and S2 are affected subsystems, and Eff is an effect that can be observed (e.g., reproduction).

Interaction Chemicals influence each other by physical, chemical, or biological means before or after reaching the molecular site of toxic action. Toxicological interactions are responses that deviate from those expected under some definition of additivity (e.g., following the concepts of IA or CA). The most commonly used terms for interaction are synergism and antagonism. ... 

El-Masri HA, Thomas RS, Sabados GR, Phillips JK, Constan AA, Benjamin SA, Andersen, ME, Mehendale HM, Yang RSH. 1996a. Physiologically based pharmacokinetic/phar-macodynamic modeling of the toxicologic interaction between carbon tetrachloride and kepone. Arch Toxicol 70 704-713. 

Gennings C, Carter WH Jr, Carchman RA, Teuschler LK, Simmons JE, Carney EW. 2005. A unifying concept for assessing toxicological interactions changes in slope. Toxicol Sci 88 287-297. 

Steevens JA, Benson WH. 1999. Toxicological interactions of chlorpyrifos and methyl mercury in the amphipod, Hyalella azteca. Toxicol Sci 52 168-177. 

Yang RSH. 1997. Toxicologic interactions of chemical mixtures. In Bond IA, editor, Comprehensive toxicology. Vol. 1. Oxford (UK) Elsevier Science Ltd. p 189-203. 

To highlight the importance of trace metals in biological systems, we ll first move across the periodic table of the elements, providing examples of essential metal functions. This is intended to provide a brief overview into the variety of functions that metals can play. In part, this wide range of critical essential metal functions provides the basis for the wide range of toxicological interactions that metals can have with biological systems. 

Yang, R.S.H. Colorado State University Toxicological interaction studies in chemical mixtures-pharmacokinetics NIEHS... 

The toxicological interactions among chemical substances depend on the chemicals present, their mode of action, and their concentrations. Of the four types of interactions, additive effects are the most plausible. This requires that the chemicals act through similar mechanisms and affect the same target tissue. For instance, the (combined) action of two or more chemicals causing irritation effects is often an added effect rather than attributable to any one candidate chemical substance. 

Cohen SD (1984) Mechanisms of toxicological interactions involving organophosphate insecticides. Fundamental and Applied Toxicology 4 315-324. 

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