Extrapolation of effects

The above example illustrates the inherent problems that can arise in the use of standardised protocols for assessing chemicals naturally occurring in the food chain. Had work on comparative metabolism and pharmacokinetics been undertaken before any animal bioassay work, it could have given more useful information. The extrapolation of effects obtained in high-dose animal studies to a large number of people exposed to a low dose is not the most effective use of resources. Nor are such experiments consistent with biological reality. There are few chemicals that would not cause illness or death if the daily intake was increased some 100-1000 fold as is the situation in many... 

Most commonly, bioassays for the evaluation of the acute toxic effects of pesticides are based on single aquatic species selected to be representative of a range of taxonomic and functional groups, i.e., bacteria, algae, invertebrates or fish [ 53,54]. Generally, toxicity evaluation using a single species is the alternative of choice rather than the use of multiple species, because extrapolation of effects to an ecosystem is more difficult and can often lead to incorrect conclusions. 

Reddy, J.K., Moody, D.E., Azamoff, D.L. Rao, M.S. (1976) Di-(2-ethylhexyl)phthalate an industrial plasticizer induces hypolipidemia and enhances hepatic catalase and carnitine acetyltransferase activities in rat and mice. Life Sci., 18, 941-945 Reddy, J.K., Reddy, M.K., Usman, M L, Lalwani, N.D. Rao, M S. (1986) Comparison of hepatic peroxisome proliferative effect and its implication for hepatocarcinogenicity of phthalate esters, di(2-ethylhexyl) phthalate, and di(2-ethylhexyl) adipate with a hypolipidemic drag. Environ. Health Perspect., 65, 317-327 Rexroat, M.A. Probst, GS. (1985) Mutation tests with Salmonella using the plate-incorporation assay. Prog. Mutat. Res., 5, 201-212 Rhodes, C., Orton, T.C., Pratt, I.S., Batten, P.L., Bratt, H., Jackson, S.J. Elcombe, C.R. (1986) Comparative pharmacokinetics and subacute toxicity of di(2-ethylhexyl) phthalate (DEHP) in rats and marmosets extrapolation of effects in rodents to man. Environ. Health Perspect., 65, 299-307... 

Ratte, H.T., Baird, D.J., Nahholz, J.V. and Sanderson, H. (2008) Extrapolation of effects measures across levels of biological organization in ecological risk assessment, in Extrapolation Practice for Ecotoxicological Effect Characterization of Chemicals, (eds K.R. Solomon, T.C.M. Brock, D. de Zwart, S.D. Dyer, L. Posfhuma, S.M. Richards, H. Sanderson, P.K. Sibley and P.J. van den Brink), CRC Press/Taylor and Francis/SETAC, Pensacola, FL,... 

Rhodes C, Orton TC, Pratt IS, et al. 1986. Comparative pharmacokinetics and subacute toxicity of di(2-ethylhexyl)phthalate in rats and marmosets Extrapolation of effects in rodents to man. Environ Health Perspect 65 299-308. 

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). 

A Extrapolation of Effects Measures across Levels of Biological Organization in Ecological Risk Assessment... 

Can extrapolation of effect measures across levels of biological organization be of help ... 

Extrapolations of the other significant components of risk assessment, measures of effects, are reviewed in Chapters 3 through 7, which present a hierarchical approach based on biological organization. Extrapolation of effect measures through (quantitative) structure-activity relationships (IQISARs) is often necessitated because... 

In general, selected tests should include responses that allow a prediction or extrapolation of effects to an assessment endpoint, which is usually at a higher... 

If and when consistent and robust responses to atrazine are identified in frogs, the mechanisms by which these effects are mediated should be elucidated. This will better allow the application of biomarkers to assess the significance of responses in the field situations and increase the precision and accuracy of extrapolation of effects to other an hibians and assessment of their relevance at the level of the population. 

---