Test Endpoints

Positive results from the in vitro mammalian cell transformation test indicate that the test substance produces phenotypic changes in cultured mammalian cells associated with malignant transformation in vivo. None of the in vitro test endpoints has an established mechanistic link with cancer. Some of the test systems are capable of detecting tumor promoters. 

A Bayesian hierarchical modeling framework was used to evaluate the effects data for each species and test endpoint (Figure 7.4). Hierarchical models reduce the effect of incomplete data sets, small numbers of tests, inconsistent information on effects among species, and other issues that lend uncertainty to the risk characterization results. 

Test endpoint Category Validation transfer Application Throughput... 

Table 3. Endpoints of the different tests. Endpoints of survival and reproduction were recorded for the 7-d Ceriodaphnia dubia test and population growth was also included since it is possible to calculate a growth rate using reproduction and survival across the age...

Hazard potential for each effluent was calculated using a mathematical formula (the PEEP index) proposed by Costan et al. (1993). This formula integrates the ecotoxic responses of the battery of tests before and after a biodegradation step. Toxicity test endpoint responses are first transformed to toxic units. The product of effluent toxicity and effluent flow (m3/h) gives the toxic loading value. The log 10 value of an effluent s toxic loading corresponds to its PEEP index. In order to rank the effluents a toxicity classification scale is generated (Tab. 11). 

Data from the reconnaissance survey indicated that bulk sediment concentrations of all COPCs were greater than apparent effect levels (AELs Environment Canada, 1995), indicating that contamination was widespread. A 20% reduction in toxicity test endpoint performance (relative to the negative control) was used to evaluate toxicity data. Such a reduction typically indicates real differences from the control. All samples demonstrated greater than a 20% reduction in bivalve normal development, however, similar reductions in amphipod survival were not observed, with the exception of one marginal hit for a single sample. As a result of the bivalve toxicity and elevated COPC concentrations observed in the reconnaissance survey, a full SQT was considered necessary for the site. 

Reductions in toxicity test endpoint performance (e.g., amphipod survival, polychaete growth) of greater than 20% (relative to the negative control) were considered indicative of moderate effects, while reductions greater than 50% were considered indicative of severe effects. Results of the toxicity testing were as follows ... 

Assumption 5 states that the endpoints measured in the toxicity tests on which the SSD is based must be ecologically relevant. Mortality is the most frequently studied endpoint in laboratory tests. In chronic tests, endpoints such as reproduction and inhibition of growth are also studied. Forbes et al. (2001a) argued that individual-level endpoints like survival, fecundity, and growth may not reflect effects at the population level (Assumption 5). They recommended that additional consideration be given to the relative frequency of different life cycle types, to the proportion of sensitive and insensitive taxonomic groups in communities, and to the role of density-dependent influences on population dynamics (see also Forbes and Calow 2002). 

Is the organization level of the test endpoint equal to the level of the... 

Have clear dose-response relationships (except for tests in which the substance s water solubility does not permit the testing of higher concentrations and consequently the test endpoint is equal to or higher than the highest test concentration or in cases of a limit test for which only 1 relatively high concentration was tested and no effects were found)... 

The toxic pressure of each of the compounds in a mixture is calculated using the species sensitivity distribution (SSD) concept. In this concept, laboratory toxicity data for various species are collected from a database, for example, the USEPA s Ecotox database (USEPA 2005) or the RIVM e-toxBase (Wintersen et al. 2004), and compiled for each compound. A statistical distribution of these data, called the SSD, is derived. Each SSD describes the relationship between exposure concentration (X) and toxic pressure (Y), whereby the latter is expressed as the probably affected fraction (PAF, %) per compound (Posthuma et al. 2002). Depending on the test endpoint chosen for deriving SSDs, there is the option to derive chronic and acute toxic pressures, based on SSDN0ECs and SSDEC50s, respectively. 

The aim of the mixture assessment should include a specihcation of the relevant effect endpoints and exposure durations. This is particularly important because empirical studies have shown that the results of mixture tests are dependent on the endpoints considered (Chapter 4) and the duration of a mixture test (Chapter 2). It should be carefully evaluated whether the tested endpoints and exposure durations are relevant for the assessment at hand. 

Test endpoint A response measure in a toxicity test, that is, the values derived from a toxicity test that characterize the results of the test (e.g., NOEC or LC50). 

A9.3.3.2.1 Chronic toxicity, for purposes of classification, refers to the potential or actual properties of a substance to cause adverse effects to aquatic organisms during exposures which are determined in relation to the life-cycle of the organism. Such chronic effects usually include a range of sublethal endpoints and are generally expressed in terms of a No Observable Effect Concentration (NOEC), or an equivalent ECx. Observable endpoints typically include survival, growth and/or reproduction. Chronic toxicity exposure durations can vary widely depending on test endpoint measured and test species used. 

Problem formulation. Within this process all available information about a contaminated site is collected including the nature of the contaminants and their sources, obvious effects and potential receptors as well as environmental recipients. Within this very first stage of the risk assessment procedure, an assessment endpoint has to be determined. Assessment endpoints are the expression of an environmental value (represented by an ecological entity) that is at risk, e.g. a distinct population that faces harm due to pollution. It has to be emphasised that toxicity-test endpoints or other measurement endpoints (in general, measured effects under test conditions) in most cases do not represent assessment endpoints (response of population or ecosystem in the field). Measurement endpoints should be representative for assessment endpoints or have a known relationship to the assessment endpoint allowing the extrapolation of data. 

Survival. The extent of mortality amongst test organisms due to toxicant exposure is used frequently to describe the level of effect. Mortality may be measured after acute or chronic exposure. However, mortality is commonly associated with acute lethality after short-term toxicity testing. If a concentration series of the toxicant is tested, results are usually expressed as LC50, the concentration that is lethal to 50% of tested organisms (Gaudet 1994). Mortality may be difficult to verify, particularly in case of small organisms. For example, in the acute Daphnia test, immobility is used as test endpoint instead of mortality. 

Accuracy criteria are not applicable to toxicity testing endpoints, because there are no standard organism responses against which to compare test results. In place of... 

With regard to standard test endpoints, the differences between fish species may be smaller than is sometimes supposed (Sprague, 1970). The various LC50 test procedures for fish generally result in a coincident relative ranking of the toxicants that is, the most toxic compound is always the most toxic, intermediates remain the intermediates and the least-toxic compound is always the least toxic, provided that the physical and chemical test parameters are kept constant. Absolute LC50 values are generally more dependent on the specific test set-up than on the inherent sensitivity of the fish species. Various factors may influence the absolute values of the observed toxic concentrations ... 

Experimental Animal Pb Exposure Test Endpoint Results References... 

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