Appendices Appendix 1 Points of departure — are generally three points of departure used for linear extrapolation or margin of exposure methods. The advantages/disadvantages of these methods are shown in Table 6. BMDx/BMDL10 BMDx/BMDLx values are not always available for chemicals and will generally need to be derived. The BMDx is defined as the dose that corresponds to a specific change (%) in response compared to the (modelled) response in control animals or subjects, the benchmark response (Crump et al., 1995). The BMD is determined by fitting a mathematical curve to the dose-response data over the range of observable responses from animal studies or human studies (if available). To take experimental uncertainty into account, the lower 95% confidence bound on the benchmark dose (BMDLx) is used as the point of departure by the US EPA. Prior to modelling, consideration should be given to the choice of data which would be used as the basis for the model. BMD analysis then involves model selection, model fit assessment and data reporting. There are various models for BMD determination with different software available to perform the calculation (Committee on Carcinogenicity, 2014; US EPA, 2012; EFSA, 2009; 2011; WHO/IPCS, 2009). BMDx/BMDLx values can differ depending on the data used for modelling and the method for modelling. These are potential sources of error and inaccuracy. The BMDx/BMDLx should only be determined by experts skilled in the interpretation of toxicological and epidemiological data (for the choice of data inputs)
Appendices Appendix 1 — Points of departure are generally three points of departure used for linear extrapolation or margin of exposure methods. The advantages/disadvantages of these methods are shown in Table 6. BMDx/BMDL10 BMDx/BMDLx values are not always available for chemicals and will generally need to be derived. The BMDx is defined as the dose that corresponds to a specific change (%) in response compared to the (modelled) response in control animals or subjects, the benchmark response (Crump et al., 1995). The BMD is determined by fitting a mathematical curve to the dose-response data over the range of observable responses from animal studies or human studies (if available). To take experimental uncertainty into account, the lower 95% confidence bound on the benchmark dose (BMDLx) is used as the point of departure by the US EPA. Prior to modelling, consideration should be given to the choice of data which would be used as the basis for the model. BMD analysis then involves model selection, model fit assessment and data reporting. There are various models for BMD determination with different software available to perform the calculation (Committee on Carcinogenicity, 2014; US EPA, 2012; EFSA, 2009; 2011; WHO/IPCS, 2009). BMDx/BMDLx values can differ depending on the data used for modelling and the method for modelling. These are potential sources of error and inaccuracy. The BMDx/BMDLx should only be determined by experts skilled in the interpretation of toxicological and epidemiological data (for the choice of data inputs)
non-threshold_based_genotoxic_carcinogen_-_accessory_document_to_recommending_health-based_workplace_exposure_standards_and_notations.docx