Toxicology assessment methods

Dorato, M.A. and Vodicnik, M.J. (2001). The toxicological assessment of pharmaceutical and biotechnology products. In Principles and Methods of Toxicology, (Hayes, A.W., Ed.). Taylor Francis, Philadelphia, PA. 

The future of in vitro techniques in toxicological assessment takes us back to our introductory discussion of the philosophical and scientific considerations operating in the evolution of alternative methods. 

Tattersall, M.L., Dymond, M., Hammond, T., and Valentin, J.P., Correction of QT values to allow for increases in heart rate in conscious beagle dogs in toxicology assessment, /. Pharmacol. Toxicol. Method, 53, 11-19, 2006. 

The main emphasis is paid to the identification of the basic principles for combined actions and interactions of chemicals (Section 10.2), and to the current knowledge on effects of exposures to mixtures of industrial chemicals, including pesticides and environmental contaminants. Test strategies to assess combined actions and interactions of chemicals in mixtures (Section 10.3) as well as toxicological test methods (Section 10.4) are addressed, approaches used in the assessment of chemical mixtures are presented (Section 10.5), and examples of experimental studies using simple, well-defined mixtures are given (Section 10.6). 

Suter et al. 1993 Society of Environmental Toxicology and Chemistry [SETAC] 1994 European Union 1997 Ecological Committee on FIFRA Risk Assessment Methods [ECOFRAM] 1999 Campbell et al. 1999). The initial use of conservative assessment criteria (i.e., err on the side of caution) allows substances that do not present a risk to be eliminated from the risk assessment process early, thus allowing the focus of resources and expertise to be shifted to potentially more problematic substances or situations. As one ascends through the tiers, the estimates of exposure and effects become more realistic with the acquisition of more accurate and/or representative data, and uncertainty in the extrapolation of effects is thus reduced or at least better characterized. Likewise, the methods of extrapolation may become more sophisticated as one ascends through the tiers (Figure 1.2). 

Teuschler LK, Rice GE, Wilkes CR, Lipscomb JC, Power FW. 2004. A feasibility study of cumulative risk assessment methods for drinking water disinfection by-product mixtures. Journal of Toxicology and Environmental Health Part A 67 755-777. 

Probabilistic risk assessment methods are described herein for determining a popnlation s distribution of the dose from exposure and the combination of that exposnre characterization with appropriate toxicological information to form aggregate and cumulative risk assessments. An individual s dose from exposure is characterized as a set of chemical- and route-specific dose profiles over time. Toxic equivalence factors (TEFs) that reflect the toxic endpoint and exposure duration of concern are used to scale chemical- and route-specific doses to toxic equivalent doses (TEDs). The latter are combined in a temporally consistent manner to form a profile over time of the Total TED. For each individual, a Total MOE is calculated by dividing a toxicologically relevant benchmark dose (e.g. an EDio) by the individual s Total TED. The distribution of the Total MOE in a popnlation provides important information for risk management decisions. 

Extensions to the earlier chemometric approaches include a toxicological assessment approach based on neural network software to ascertain whether the methods provide a robust approach, which could lead to automatic toxin classification. The neural network approach to sample classification, based on NMR spectra of urine, was in general predictive of the sample class. It appears to be reasonably robust and once the network is trained, the prediction of new samples is rapid and automatic. However, the principal disadvantage is common to all neural network studies in that it is difficult to ascertain from the network which of the original sample descriptors are responsible for the classification. Although recently it has been suggested that probabilistic... 

This appendix is a source of methods and guidance to be used in environmental toxicology and risk assessment. Methods are periodically updated and the latest version should be used. Many of the methods are now available online from ASTM, USEPA, and other sources. 

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