Case histories toxic release

Hazard assessment. A hazard assessment is required to assess the potential effects of an accidental (or intentional) release of a covered chemical/material. This RMP element generally includes performing an off-site consequence analysis (OCA) and the compilation of a five-year accident history. The OCA must include analysis of a least one worst-case scenario. It must also include one alternative release scenario for the flammables class as a whole also each covered toxic substance must have an alternative release scenario. USEPA has summarized some simplified consequence modeling... 

In the case of noncompendial materials, specifications and complete descriptions of the test methodologies to be used for quality control release purposes by the sponsor should be included. In addition, it may be necessary for the sponsor to obtain a letter authorizing reference to a DMF from the supplier concerning the manufacturing and controls procedures used to make these materials, such as mixtures of colorants or flavors. It may be necessary to obtain toxicity data if the mixture or component has little or no history of human use (e.g., new polymers). If it is anticipated that an untried component will be used, it is recommended that discussions be initiated with the FDA s reviewing chemist and pharmacologist. These sessions should be scheduled as soon as possible to minimize the possibility of delays in NDA approval caused by inadequate information to support use of the material. 

The available evidence for PbBO as a dose metric in Pb toxicology and epidemiology documents that it (1) is a cumulative but not inert dose/exposure metric which both serves to quantify stored Pb and, in metabolicaUy diverse settings, released Pb as an endogenous source of systemic Pb exposure (2) may be a better Pb exposure correlate with various toxic effects than PbB in settings where resorptive releases are significant or long term, e.g., in retired Pb workers or in children, older children, or adults whose Pb-exposure histories foretell sizeable stores of bone Pb and (3) is likely a measure of the source of much of the Pb that is released on provocative chelation and that better reflects potential toxicity risk than PbB. However, the relative robustness of PbBO in dose—response relationships versus other measures of toxic dose, e.g., PbB or chelatable Pb, wiU vary case to case. 

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