Guideline studies

For certain unusual effects such as, e.g., some types of malformations in the fetus or rare tumors, the number of animals usually included in the various dose groups in test guideline studies is generally too low in order for the incidence of such an effect in treated group(s) to achieve statistical significance from that in the control group. 

Data from studies in animals according to test guideline methods, particularly if conducted in accordance with principles of GLP, will usually give very good information in order to identify whether a substance would be considered to be, or not to be, corrosive or irritant to the skin or eye in the test species. In general, it is assumed that substances, which are irritant in test guideline studies in animals will be skin and/or eye irritants in humans, and those which are not irritant in test guideline studies will not be irritant in humans. 

Repeated dose toxicity studies differ with respect to duration. In principle, any duration is possible, but for the sake of harmonization it has become necessary to limit the study durations to a number of standard durations in the test guideline studies. 

Table 4.12 summarizes the various OECD test guideline studies for repeated dose toxicity in more detail, including the parameters examined in each test, in order to provide a brief overview of the similarities and differences between the various repeated dose toxicity studies. 

The test guideline studies for repeated dose toxicity are comprehensive and basically include all target organs. In addition, for certain targets, more specific test guidelines have been developed. These targets include the immune system and the nervous system. 

Overview of In Vivo Repeated Dose Toxicity OECD Test Guideline Studies... 

The standard repeated dose toxicity guideline studies include a number of parameters relevant for the evaluation of a substance s neurotoxic potential. In addition to these standard... 

The number of repeated dose toxicity studies available for a substance under evaluation is likely to be variable, ranging from none to the 28-day repeated dose toxicity guideline study, to a series of guideline studies for some substances, including subchronic and/or chronic studies. There may also... 

The neurotoxicity studies will provide information on major neurobehavioral and neuropatho-logical effects in adult rodents. The protocol for the OECD/EU test guideline studies has been developed so that it can be tailored to meet particular needs to confirm the specific histopathological and behavioral neurotoxicity of a substance as well as to provide a characterization and quantification of the neurotoxic responses, and can thus form the basis for an estimate of a NOAEL for neurotoxicity. See also Section 4.7.7. 

The first phase of ToxCast profiled a chemical library of 320 environmental chemicals (309 unique structures and 11 replicates), which are mostly pesticidal actives and inerts having rich in vivo data from guideline studies. ToxCast is now in Phase II, bringing to 1060 the number of unique chemicals tested across nearly 650 diverse assays. The additional Phase II chemicals include a number of reference chemicals, consumer products, food additives, failed pharmaceuticals, data-poor chemicals being screened for potential endocrine... 

In a few cases, studies to evaluate developmental neurotoxicity or other postnatal functions may have been conducted, and these can provide amore complete evaluation of potential developmental effects. In addition to the standard guideline studies, data from experimental studies on mechanisms of action, etc., can provide useful data for consideration in the risk assessment process. 

ToxRefDB actor.epa.gov/toxrefdb Contains in vivo toxicity study data, mostly from EPA guideline studies of pesticides... 

Study Design Factors Affecting Exposure Variability 33 Specific Requirements for Guideline Studies 34 Label Compliance 34 Sample Size 34 Observational Bias 35 Motivational Bias 35... 

Recommendations for Improvements in the Design of Guideline Studies 36 Population Selection 36 Sampling Location 36 Sampling Season 36 Duration of Measurements 37 Post-Registration Studies 37 CONCLUSIONS AND RECOMMENDATIONS 37 ACKNOWLEDGEMENTS 38 REFERENCES 38... 

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