User safety assessment

Additionally, the test materials used in the validation process should be as closely related as possible to the characteristics of the unknowns to be tested. It is clear from the literature, for instance, that many cytotoxicity assays give good correlations with the in vivo ocular irritancy data for surfactants, but the correlations fail when compounds from other chemical classes are tested. Since any particular assay may be used differently by individual safety assessment programs, users must evaluate potential methods under conditions likely to be encountered in their own situations. 

Toxicologists must rely on results obtained from an alternative method if it is to serve as a replacement for an in vivo toxicity test. Two measures of alternative method performance must be known in order to define reliability from a test user s point of view. First, a toxicologist must know it is possible to consistently reproduce the data obtained from the alternative method over long periods of time. A test that does not provide the same results on the same test substance repeatedly would not be useful in the safety assessment process. Second, it must be possible to consistently predict in vivo toxicity endpoints at a known level of accuracy and precision. These measures of reliability are objective endpoints that can be measured experimentally. The part of the validation process that provides the data needed to confirm the reliability of an alternative method as proposed by its developers is the validation study. 

GLP embodies a set of principles that provide a framework within which studies are planned, performed, monitored, recorded, reported and archived. These studies are undertaken to generate data by which the hazards and risks to users, consumers, and third parties, including the environment, can be assessed for pharmaceuticals, agrochemicals, veterinary medicines, industrial chemicals, cosmetics, food and feed additives, and biocides. GLP helps assure regulatory authorities that the data submitted are a true reflection of the results obtained during the study and can therefore be relied upon when making risk/safety assessment decisions. 

The chemical safety assessment has to consider the manufacture or preparation of the substance as well as all identified uses. An identified use is a use of a substance or preparation containing it that is intended by a person involved in the supply chain or that is made known to him in writing by an immediate downstream user. The assessment shall consider all stages of the life cycle of the substance resulting from its manufacture and identified uses. The assessment has to be based on a comparison of the potential adverse effects of the substance with the known or reasonably foreseeable exposure of man or the environment, taking into account implemented and recommended risk management measures and operational conditions. 

Every user of a chemical is asked to communicate his special application of the supplied substance to the dehverer in order to make this an identified use. Therefore the necessary information for this exposure scenario should be provided to the manufacturer or importer. For registered substances, the manufacturer or importer shall prepare a chemical safety assessment and amend his chemical safety report before the next delivery in a time frame of 1 month. 

Within the safety context, an FME(C)A is generated to support the Safety Assessment, so it is important to understand the expectations and requiranents on the FMEA before any work on it commences. It is therefore important to coordinate the required scope of FMEA with the user requesting it. For instance,... 

Information acquired from the above items is not adaptable to any kind of numerical ranking for quantitative safety assessment purposes. However, the information can reveal the owner or user s apparent attention to good practice, careful operation, regular maintenance, and adherence to the recommendations and guidelines developed for susceptible applications. If the assessment indicates cracking and other serious damage problems, it is important that the inspector obtain qualified technical advice and opinion. After all, safety and health are of primary concern regarding pressure vessels. 

From the preceding, it is clear that SIS and reliability go hand-in-hand. A functional safety assessor (FSA) assesses the safety assessment/analysis report (SAR) after SIS is developed to check the system reliability and SIL. In order to achieve a tolerable risk level, the end-user, who needs to install SISs in the plant, initiates SIS projects. Detailed process outline for the same has heen elaborated as follows ... 

Cenfral to regisfration is fhe Chemical Safety Assessment (CSA), in which the registrant identifies and describes the conditions under which the manufacturing and use of a subsfance are considered to be safe. A CSA must be performed by registianfs for substances manufactured and imported in quantities at or above 10 tonnes per year and by downstream users if their uses are not addressed by their supplier. The CSA entails three major steps, hazard assessment, exposure assessment, and risk characterization, which are documented in the Chemical Safety Report (CSR). Figure 3.4 summarizes the process [95]. 

Both the Code of Practice and Competency Framework are considered to be good practice and consistent with the use of independent safety assessment in safety standards such as Def Stan 00-56 and lEC 61508. Both are voluntary. However, it is hoped and intended that they will be used by ISAs and users of ISAs as a basis for ensming that their responsibilities and reasonable expectations are met. 

User safety was assessed by FEEDAP. The results of acute inhalation studies in mice, rats and guinea pigs indicated that lasaloeid sodium dust has the potential to cause local toxicity to the respiratory tract and lungs and systemic toxicity to other organs. Acute dermal toxicity in rabbits was low, reflecting poor skin absorption. Lasaloeid sodium did not cause skin irritation in rabbits or skin sensitisation in guinea pigs, but did cause eye irritation in rabbits. 

Assessments of user safety indicated that salinomycin sodium biomass was irritant to skin and eyes and Bio-Cox 120 G caused skin sensitisation in miee. Sacox 120 microGranulate was slightly irritant to skin and eyes of rabbits and was a skin sensitiser in guinea-pigs. Neither Sacox microGranulate nor Bio-Cox 120G produce much dust when handled and none of the particles in Bio-Cox are of respirable size. However, about 10% of the Sacox product consisted of respirable particles (<10pm). No adverse effects were seen in an acute inhalation toxicity study of Sacox in rats, but the air concentration... 

K. N. Woodward, Assessment of user safety, exposure and risk to veterinary medicinal products in the European Union, Regul. Toxicol. Pharmacol., 2008, 50, 114-128. 

The safety/risk criteria. The safety/risk criteria establish the top-level system safety requirements, or objectives. Regulatory authorities may have different definitions for the various categories of hazards/accidents. To be able objectively to distinguish and evaluate the various hazards present, it is important to define the exact terminology and to allocate a measure of performance. This is an important (and arguably most neglected) topic as it is the safety acceptance criteria the system is expected to achieve, and hence the measure (or standard) the assessment will compare the system against. For more detail on safety criteria, see Appendix B. The system level. Define the systems level at which safety is to be assessed. The importance of this step is explained in Section 8.3 above. A safety assessment by a supplier of a component (e.g. a flare dispenser) will vastly differ in scope and approach to a safety assessment for a product (e.g. an aircraft) or user system (e.g. a facility). 

Starting from the principle that there is no one correct way of doing a safety assessment, I nevertheless endeavoured to compile my own user-guide (from which I could cut-and-paste definitions, approaches, templates, etc.), that would assist me to deliver consistently high-quality safety assessments efficiently. 

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