Weight-of-evidence assessment

There are adopted in vitro test methods (Section 4.5.3.2) under which a substance can be identified as corrosive. A negative result in these tests should, however, be supported by a weight of evidence assessment using other data. It should be noted that these tests do not provide information on skin irritation. 

Clinical pathology plays a prominent role in the weight of evidence assessment of immunotoxic potential of pharmaceutical entities and identifying means of monitoring clinical patients. Tlie routine parameters should be evaluated as a whole, since individual parameters are extremely dynamic, interrelated, and rarely interpretable out of context. Furthermore, individual clinical pathology... 

Mf this writing, recognized and validated animal models for the testing of respiratory hypersensitivity are not available. Under certain circumstances, data h-om animal studies may provide valuable information in a weight of evidence assessment. 

This section describes how the tj pes of to.xicity inforniation arc considered in the to.xicity assessment for carcinogenic effects. A slope factor and the accompanying weight of evidence determination are the toxicity data most commonly used to evaluate potential human carcinogenic risks. The methods the USEPA uses to derive these values arc outlined below. 

Generally, the slope factor is a plausible upper bound estimate of the probability of a response per unit intake of a ehemieal over a lifetime. The slope factor is used in risk assessments to estimate an upper-bound lifetime probability of an individual developing cancer as a result of e.xposure to a particular level of a potential carcinogen. Slope factors should always be accompanied by the weight-of-evidence classification to indicate the strength of the evidence that the agent is a human carcinogen. Calculational details are presented below. 

How will the data from these assays be incorporated into any weight-of-evidence approach to assessing human health risk ... 

The purpose of the hazard identification is to evaluate the weight of evidence of adverse effects in humans based on assessment of all available data on toxicity and toxicological mode(s)... 

Positive carcinogenic findings in animals require careful evaluation to determine their relevance to humans. Of key importance is the mechanisms/mode(s) of action of tumor induction. The WHO/IPCS has developed a conceptual framework to provide a strucmred and transparent approach for the assessment of the overall weight of evidence for a posmlated mode of induction for each mmor type observed (Sonich-Mullin et al. 2001). The framework promotes confidence in... 

The WHO/IPCS international workshop on skin sensitization in chemical risk assessment (WHO/IPCS 2007) concluded (Q)SARs and expert systems for identification of sensitizing capacity have not been vahdated to date, but may be used as part of a weight of evidence approach for identifying the sensitizing capacity of chemicals. There are certain local (Q)SARs that can be used for a small range of chemicals. However, these are currently insufficient to cover the full range of chemicals. The Workshop recommended that QSAR models need to be further developed, and the apphcabihty domain of each model needs to be established. ... 

An alternative approach to a quantitative assessment is to divide the highest dose at which there is no observed increase in tumor incidence in comparison with controls by a large composite UF, for example 5000 as suggested by Wed (1972). The magnimde of the factor could be a function of the weight of evidence, e.g., numbers of species in which the mmors have been observed or namre of the mmors (WHO/IPCS 1994). The adequacy of this approach, which is sometimes used when data on dose-response are limited, must be judged by criteria similar to those used in developing a tolerable intake for threshold effects this is addressed in detail in Chapter 5. 

Mumtaz, M.M. and P.R. Durkin. 1992. A weight-of-evidence approach for assessing interactions in chemical mixtures. Toxicol. Ind. Health 8 377M-06. 

Usually, some lines of evidence will not be suitable for direct incorporation into quantitative analysis. Semiquantitative or qualitative methods will then be needed to weigh the different lines of evidence, including the quantitative assessment, and integrate them for decision making. Methods for assessing weight of evidence were outside the scope of the workshop that developed this book but are discussed by Suter et al. (2000) and were recently the focus of another workshop (Chapman et al. 2002). Whatever method is used for weighing different lines of evidence, it will be important to characterize uncertainties in each line of evidence and show their effect on the overall assessment outcome. 

Chapman PM, McDonald BG, Lawrence GS. 2002. Weight-of-evidence issues and frameworks for sediment quality (and other) assessments. Human Ecol Risk Assess 8 1489-1515. 

Central to any risk assessment is a model of causality. At the onset, a conceptual model is needed that identifies a plausible cause-effect relationship linking stressor exposure to some effect. Most ecological risk assessments rely heavily on weight-of-evidence or expert opinion methods to foster plausibility of the causal model. Unfortunately, such methods are prone to considerable error (Lane et al. 1987 Hutchinson and Lane 1989 Lane 1989), and attempts to quantify that error are rare. Although seldom used in risk assessment, Bayesian methods can explicitly quantify the plausibility of a causal model. 

Regardless of the method used, the basis of the final risk characterization must be explicit. All components and sources of evidence should be described. The explicit linkage between the analysis results and the assessment endpoints must be clearly but adequately stated. Tandem presentation of conventional methods (e.g., ad hoc weight of evidence) and formal methods (e.g., Bayesian, meta-anal-ysis) are recommended to enhance understanding. This is intended to facilitate acceptance of unfamiliar approaches, not to imply that the conventional methods are a touchstone. 

In the present study a weight-of-evidence approach derived on the basis of three LOEs has been evaluated in order to better assess the risk from TBT in Dutch harbours and open waters. Based on chemical data, risk values were determined according to Aldenberg et al. (2002) and ISI values were calculated based on the dose-response curve reported by Oehlmann (2002). Actual ISI observations were made in the field and the presence of gastropods was recorded. In the overall approach evidence from the different LOEs was combined. 

Smith, E.P., Lipkovich, L, Ye, K. (2002). Weight of Evidence (WOE) Quantitative Estimation of Probability of Impact. Human and Ecological Risk Assessment, 8, 1585-1596. 

In assessing the potential for a chemical to produce heritable mutations in humans, it is necessary to examine the weight of evidence obtained from in vitro tests for mutations in microorganisms and cultured mammalian cells, from in vivo tests of mutations in animals, and from in vitro and in vivo tests for chromosome aberrations in mammalian cells. The strongest evidence would come from the demonstration that a chemical causes mutations or chromosome aberrations in human cells. As no studies were located that tested isophorone in cultured human cells or examined the cells of people with known exposure, this evidence is lacking. Of the five experiments that tested whether isophorone caused mutations or chromosome aberration in cultured mammalian cells, only two were positive a weak mutagenic response in mouse lymphoma cells and a positive test for sister... 

The purpose of hazard identification is to evaluate the weight of evidence for adverse effects in humans based on assessment of all available data, ranging from observations in humans and animal data to an analysis of mechanisms of action and structure-activity relationships. Each source of information has its advantages and limitations, which determine the weight of that evidence collectively, the evidence permits a scientific judgement as to whether the chemical can cause adverse effects. 

A weight of evidence approach to assessing reproductive toxicity requires rigorous evaluation of all available data. However, often only limited information is available, and default assumptions must be made because of uncertainties in understanding mechanisms, dose-response relationships at low dose levels and human exposure patterns. Several of these assumptions are basic to the extrapolation of toxicity data from animals to humans, while others are specific to reproductive toxicity. The general default assumptions for reproductive toxicity stated in the IPCS (1995) report are summarized as follows ... 

The RCEP considered that the current risk assessment approach has the advantage of being evidence-based and transparent, but that a new approach, one that balances precaution with an evidence-based approach is needed (RCEP, 2003, p96). This suggests that precaution disregards evidence, which is not the case. Rather, it is more open to different types of evidence than the often narrow view taken by risk assessment. It considers the weight of evidence , the evidence from differ-... 

REACH (Annex XI) recommends that a weight of evidence approach is used for deciding whether or not a chemical has a particular dangerous property. See also De Rosa et al (1996) on the use of a weight of evidence approach in the assessment of the effects of chemicals. 

Risk assessment being by nature imprecise must consist to a substantial degree of scientific judgment, and the weight of evidence must constantly be the guide. All of the assumptions and uncertainties in these assessments must be made clear to the decision maker and the public. 

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