Safety Assessment Studies Research Articles

Physico-chemical characteristics of graphite aerosols generated during postulated air ingress accident

Graphite is used as a structural material, neutron moderator and reflector in some designs of nuclear reactors. The core of a prismatic or pebble bed type High Temperature Reactor (HTR) is also comprised of graphite components. In addition to HTRs, it is also used as a structural material in the Molten Salt Breeder Reactor (MSBR). It’s response to postulated accidental condition is a critical aspect of probabilistic safety assessment studies for such futuristic reactor designs. Generation of graphite aerosol particles has been shown as a possible hazard in the case of an air ingress accident for HTRs. These aerosol particles act as a carrier for radioactive source term and their characteristics decide the impact of accident. This study aims to measure and interpret number and mass characteristics of graphite particles generated by exposing graphite to varying high temperature conditions. An exclusive sophisticated facility is developed, tuned and employed for measuring the aerosol characteristics at extreme temperature and concentration conditions. Apart from measuring number and mass size distributions of generated particles at different temperatures and flows, emission of CO and CO2 was also monitored. Particle concentration and CO gas concentration was found to be maximum at 700 °C, the transition temperature for the generation process. Evaporation-condensation and transport of unburnt carbon particles could be linked to the observed particles in nucleation and accumulation mode size ranges, respectively. Mechanism of particle generation and graphite particle transformation at different temperatures is also discussed.

Exemplification of AC2’s multidimensional capabilities to the application of large pools within the frame of the German EASY project

Realistic numerical predictions of dynamic, complex, multidimensional flow scenarios occurring in light water reactors are vital prerequisites for every reliable safety assessment study. System analysis codes employing only one-dimensional fluid-mechanics models may fail to realistically capture the complex flow conditions in large scale passive components of light water reactors.Even though today’s CFD codes are capable of accurately representing multidimensional flow behaviour, they require huge computational efforts to simulate long-term transients. The German thermal-hydraulic system code (THS) ATHLET (Analysis of Thermal-hydraulics of LEaks and Transients) part of the AC2 simulation environment, is being developed by GRS (Gesellschaft für Anlagen- und Reaktorsicherheit gGmbH) for the analysis of the whole spectrum of operational transients, design-basis accidents and beyond design-basis accidents anticipated for nuclear energy facilities. The code provides a wide range of specific models for several light water reactor designs of Generation II, III+ and IV. Currently, the code’s one-dimensional six-equation two-fluid model, is being extended towards a fully three-dimensional set of thermal-hydraulic conservation equations. Until now ATHLET’s ability to capture multidimensional flow behaviour has mainly been assessed for the flow mixing behaviour in the reactor pressure vessel. Within this work, ATHLET’s capabilities to capture the multidimensional flow behaviour will be assessed for the flow within large scale passive components of light water reactors.These analyses highlight the advantages of ATHLET’s newly developed 3D model for the simulation of large scale passive systems.

562 - Vacuum physiotherapy after first stage buccal mucosa graft (BMG) urethroplasty in proximal hypospadias: A feasibility, safety and protocol compliance assessment study

562 - Vacuum physiotherapy after first stage buccal mucosa graft (BMG) urethroplasty in proximal hypospadias: A feasibility, safety and protocol compliance assessment study

Pesticides Evaluation in Egyptian Fruits and Vegetables: A Safety Assessment Study

Pesticides Evaluation in Egyptian Fruits and Vegetables: A Safety Assessment Study

Evaluation of Occupational Safety of Pre-hospital Emergency Personnel in Traffic Accidents: A Qualitative Study in Isfahan City

Background: Traffic incidents are the first service provided by pre-hospital emergency staff. The existence of occupational safety for this cortex increases the efficiency and quality of service. This research was conducted to evaluate the occupational safety of pre-hospital emergency personnel in Isfahan by examining their experiences. Methods: This study was a qualitative study and its purposeful sampling. The degree of entry of individuals into the study of work experience over 3 years as a technician in urban and road bases in the emergency medical section. In this research, 15 people were interviewed and the framework analysis was used to analyze the data. Results: The findings of the occupational safety assessment study of the pre-hospital emergency staff with their experiences of four main axes and 16 sub-axes. The four main axes of personnel experience in occupational safety included: individual problems, organizational problems, inadequate coordination and community-related problems. Personnel 115 considered major issues and problems that led to an increase in job insecurity in people s lack of awareness of 115 emergency tasks. Relief from 115 personnel in cases of assault, psychiatric disorders and anger in the patient s companions, in turn, compromise the safety of 115 personnel. The failure of equipment and vehicles and the lack of recognition of some natural and chemical and microbial incidents before deployment lead to increased incidents and deaths for personnel. Conclusion: According to the findings of the study, the preparation of a joint message center between the relief agencies, the psychotherapy team and the rapid reaction teams for the relief of particular cases, the coordinated system of payment of salaries, the creation of job rotation between urban and road bases, in Considering the amenities and the non-material needs of the constructive suggestions for improving the personnel performance and improving the job safety of the city of Isfahan.

Preliminary analysis of gaseous radiocarbon behavior in a geological repository hosted in salt rock

ABSTRACTA preliminary evaluation of gaseous radiocarbon (14C) behavior under geological repository conditions for Italian radioactive high level waste-long-lived and intermediate level waste disposal has been performed. Although in Italy there is still no defined project for a geological disposal facility, current work may support future safety assessment studies for a hypothetical future repository in deep salt rock. In the Italian context of radioactive waste, the percentage of 14C bearing waste to be disposed in a possible geological repository is low; irradiated graphite is the most important radiological source. Data about the radiological inventory has been collected to simulate production and migration of gaseous 14C in a hypothetical geological repository. Three different conceptual models have been developed and simulated. The first model has considered a preliminary evaluation of the radiological impact referred to the whole inventory; the second and third model have evaluated the impact only due to the irradiated graphite. A preliminary sensitivity analysis has been carried out, highlighting the importance of geometry and of distribution coefficients (Kd) in materials used to seal the disposal underground facility. Results show the possibility to correlate the Kd values, the volume and the location of the sealing materials to the amount of 14C migrating toward the surface.

Development of a Seismic Probabilistic Safety Assessment Quantification Tool

Shanghai Nuclear Engineering Research and Design Institute (SNERDI) has been studying seismic risk analysis for nuclear power plant for a long time, and completed seismic margin analysis for several plants. After Fukushima accident, seismic risk has drawn an increasing attention worldwide, and the regulatory body in China has also required the utilities to conduct a detailed analysis for seismic risk. So, we turned our focus on a more intensive study of seismic probabilistic safety assessment (PSA/PRA) for nuclear power plant in recent years. Since quantification of seismic risk is a key part in Seismic PSA, lots of efforts have been devoted to its research by SNERDI. The quantification tool is the main product of this research, and will be discussed in detail in this paper. First, a brief introduction to Seismic PSA quantification methodology is presented in this paper, including fragility analysis on system or plant level, convolution of seismic hazard curves and fragility curves, and uncertainty analysis as well. To derive more accurate quantification results, the binary decision diagram (BDD) algorithm was introduced into the quantification process, which effectively reduces the deficiency of the conventional method on coping with large probability events and negated logic. Finally, this paper introduced the development of the seismic PSA quantification tool based on the algorithms discussed in this paper. Tests and application have been made for this software based on a specific nuclear power plant seismic PSA model.

Engineering a Next-Generation Glycoconjugate-Like Streptococcus pneumoniae Vaccine.

We detail the development of a next-generation Streptococcus pneumoniae liposomal encapsulation of polysaccharides (LEPS) vaccine, with design characteristics geared toward best-in-class efficacy. The first generation LEPS vaccine, which contained 20 encapsulated pneumococcal capsular polysaccharides (CPSs) and two surface-displayed virulence-associated proteins (GlpO and PncO), enabling prophylactic potency against 70+ serotypes of Streptococcus pneumoniae (the causative agent of pneumococcal disease), was rationally redesigned for advanced clinical readiness and best-in-class coverage. In doing so, the virulent-specific GlpO protein antigen was removed from the final formulation due to off-target immunogenicity toward bacterial species within the human microbiome, while directed protection was maintained by increasing the dose of PncO from 17 to 68 μg. LEPS formulation parameters also readily facilitated an increase in CPS valency (to a total of 24) and systematic variation in protein-liposome attachment mechanisms in anticipation of clinical translation. An additional safety assessment study demonstrated that LEPS does not exhibit appreciable toxicological effects even when administered at ten times the effective dose. In summary, this new design offers the broadest, safest, and most-complete protection while maintaining desirable glycoconjugate-like features, positioning the LEPS vaccine platform for clinical success and a global health impact.

Conceptual model development using a generic Features, Events, and Processes (FEP) database for assessing the potential impact of hydraulic fracturing on groundwater aquifers

Abstract. Hydraulic fracturing for natural gas extraction from unconventional reservoirs has not only impacted the global energy landscape but has also raised concerns over its potential environmental impacts. The concept of “features, events and processes” (FEP) refers to identifying and selecting the most relevant factors for safety assessment studies. In the context of hydraulic fracturing we constructed a comprehensive FEP database and applied it to six key focused scenarios defined under the scope of FracRisk project (http://www.fracrisk.eu, last access: 17 August 2018). The FEP database is ranked to show the relevance of each item in the FEP list per scenario. The main goal of the work is to illustrate the FEP database applicability to develop a conceptual model for regional-scale stray gas migration.

Scientific and Regulatory Policy Committee Points to Consider: Histopathologic Evaluation in Safety Assessment Studies for PEGylated Pharmaceutical Products.

Colorless, intracytoplasmic vacuoles occur in multiple tissues in animals following repeated administration of polyethylene glycol (PEG)-conjugated molecules. The extent of vacuolation depends on physical characteristics and molecular backbone of the PEG and the dose, product, drug target/pharmacology, and duration of exposure. The collective experience gathered from multiple nonclinical toxicology studies of PEGylated biopharmaceuticals indicates that in general, PEG-related vacuolation is not associated with demonstrable cell and tissue damage or dysfunction and is reversible with sufficient duration of drug-free periods. Existing data are insufficient to predict whether nonclinical animal species differ in their sensitivity to develop PEG-associated vacuoles; however, recent data suggest that there may be species differences. Recent comprehensive reviews have addressed the basic challenges in developing PEGylated pharmaceutical products, including general reference to and description of PEG-associated tissue findings. These manuscripts have identified gaps in our current understanding of PEG-associated vacuolation, including the lack of a widely accepted standardized histological terminology and criteria to record and grade the severity of vacuolation as well as insufficient knowledge regarding the nature of the contents of these vacuoles. The goal of this article is to help address some of the gaps identified above by providing points to consider, including a pictorial review of PEG-associated microscopic findings, when evaluating and reporting the extent, severity, and significance (adversity or lack of adversity) of PEG-associated cytoplasmic vacuolation in safety assessment studies. [Box: see text].

PEGylated lipid microspheres loaded with cabazitaxel for intravenous administration: stability, bioavailability, antitumor efficacy, and toxicity.

This paper aimed to develop a novel lipid microsphere delivering cabazitaxel (CTX) using phosphatidylcholine combined with DSPE-PEG2000 as emulsifier, and evaluate its stability, pharmacokinetics, antitumor efficacy, and toxicity. The pegylated cabazitaxel-loaded lipid microspheres (CTX-PLMs) were prepared by high-pressure homogenization methods; the biological samples were analyzed by the UPLC-MS/MS method. CTX-PLMs had a drug concentration of 1.2mg/ml and a mean particle size of 180.0 ± 51.119nm. CTX-PLMs showed a superior physical stability as it could remain nearly intact after 1-year storage. The AUC0-t of the CTX-PLMs was 1562.6 ± 520.1μghL-1 compared with the CTX-solution of 860.734 ± 312.4μghL-1. CTX-PLMs exhibited a strong antitumor efficacy against NCI-N87 and DU145 tumor models with tumor growth inhibition rates of 93.5 and 88.5%, respectively. The LD50 of CTX-PLMs in rats was 20.89mg/kg. As for the long-term toxicity, the thymus, mesenteric lymph nodes, and bone marrow were the main toxic target organs and systemic toxicity induced by CTX-PLMs was alleviated relative to that of the CTX-solution. Safety assessment studies including hemolysis test, dermal sensitization test, systemic anaphylaxis, and vascular stimulation test indicated that CTX-PLMs is safe enough for intravenous administration. In a word, CTX-PLMs are a promising carrier for intravenous administration with satisfactory stability, stronger tumor inhibition, and superior safety profile.

Nutritional Assessment of Dietary Bt and Cp4EPSPS Proteins on the Serum Biochemical Changes of Rabbits at Different Developmental Stages.

In recent years, the influence of genetically modified (GM) cotton expressing different types of Bt and EPSPS genes has been attested in term of reduced application of pesticides and insecticides coupled with improved cotton production. Although the cultivation of GM cotton has been authorized by the regulatory authorities of various countries in the world, based on the biosafety studies reported by most of the GM cotton producers, yet the information on its safe use are inadequate. In order to support the issues on food safety, it is therefore mandatory to conduct further safety assessment studies on GM cotton for each independent transgenic event on the basis of case assessment rule. In the present study, the effects of different doses of dietary GM cotton seed expressing Bt and EPSPS genes were studied on the level of serum biochemical in albino rabbits (Oryctolagus cuniculus). The rabbits were fed a diet containing different levels of GM cotton seeds (i.e., 20, 30, and 40% w/w) respectively mixed with standard diet for 180 days. During the course of the study, various serum enzymes, electrolytes, proteins, glucose and serum total cholesterol were examined at specific time intervals (0, 45, 90, 135, and 180) days. The results showed non-significant (P > 0.05) dose dependent effects in most of the evaluated serum biochemical parameters. Although, the results in some of the serum biochemistry were significantly different (P < 0.05) among the groups, however, they were not biologically significant, since all the differences were within the normal physiological range. These results thus, suggested that the GM cotton seed meal could be considered as safe as other conventional feed ingredients. The experimental evidence for the safe usage of GM cotton was highlighted in this study.

Mine safety assessment using gray relational analysis and bow tie model.

Mine safety assessment is a precondition for ensuring orderly and safety in production. The main purpose of this study was to prevent mine accidents more effectively by proposing a composite risk analysis model. First, the weights of the assessment indicators were determined by the revised integrated weight method, in which the objective weights were determined by a variation coefficient method and the subjective weights determined by the Delphi method. A new formula was then adopted to calculate the integrated weights based on the subjective and objective weights. Second, after the assessment indicator weights were determined, gray relational analysis was used to evaluate the safety of mine enterprises. Mine enterprise safety was ranked according to the gray relational degree, and weak links of mine safety practices identified based on gray relational analysis. Third, to validate the revised integrated weight method adopted in the process of gray relational analysis, the fuzzy evaluation method was used to the safety assessment of mine enterprises. Fourth, for first time, bow tie model was adopted to identify the causes and consequences of weak links and allow corresponding safety measures to be taken to guarantee the mine’s safe production. A case study of mine safety assessment was presented to demonstrate the effectiveness and rationality of the proposed composite risk analysis model, which can be applied to other related industries for safety evaluation.

Safety assessment study of a planned offshore floating platform pipelaying test

ABSTRACTServing as the most important component of a subsea production system, marine risers are one of the weakest and vulnerable marine structures. Therefore, the offshore pipelaying installation operation has been drawing more and more attention. In this paper, a safety assessment study of a planned offshore floating platform pipelaying test by reel-lay method is put forward. First, the real marine environment data and platform motion are collected in the field from the sea area. Then, tensile and bending tests of a flexible pipe are conducted to acquire its nonlinear tension-strain and moment-curvature mechanical properties. Later, based on the improved rod theory, the analyses of the flexible pipe's motion response under the offshore pipelaying operation are carried out by fully taking account of the irregular platform motion and hydrodynamic loadings caused by wave and current. Finally, a methodology for the flexible pipe offshore laying operation could be established.

Biochemical Alterations Following Repeated Intramuscular Administration of Cefquinome in Cow Calves during its Safety Assessment

The present study was carried out to investigate biochemical alterations induced after repeated intramuscular administration of cefquinome at the dose rate of 2 mg.kg -1 body weight in five healthy cow calves during its safety assessment study. Blood samples were collected before administration of the drug which served as control (day 0). After administration of drugs, blood samples were collected at day 1 st , 2 nd , 3 rd , 4 th , 5 th and 6 th from jugular vein into vacutainers without K 3 EDTA for serum biochemical parameters (serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), serum lactate dehydrogenase (LDH), serum alkaline phosphatase (AKP), serum acid phosphatase (ACP) and serum bilirubin) analysis. The results of the study clearly demonstrated that repeated intramuscular administration of cefquinome in therapeutic dose produced non-significant (p<0.05) difference in values of serum biochemical parameters in cow calves when compared with control values (0 day). Lack of clinical signs of adverse reactions and absence of significant difference in serum biochemical parameters following intramuscular administration of cefquinome, may open a new avenue for insight into the strategy for clinical treatment of various bacterial diseases in cow calves.

Sodium cholate-enhanced polymeric micelle system for tumor-targeting delivery of paclitaxel.

PurposePolymeric micelles are attractive nanocarriers for tumor-targeted delivery of paclitaxel (PTX). High antitumor efficacy and low toxicity require that PTX mainly accumulated in tumors with little drug exposure to normal tissues. However, many PTX-loaded micelle formulations suffer from low stability, fast drug release, and lack of tumor-targeting capability in the circulation. To overcome these challenges, we developed a micellar formulation that consists of sodium cholate (NaC) and monomethoxy poly (ethylene glycol)-block-poly (d,l-lactide) (mPEG-PDLLA).MethodsPTX-loaded NaC-mPEG-PDLLA micelles (PTX-CMs) and PTX-loaded mPEG-PDLLA micelles (PTX-Ms) were formulated, and their characteristics, particle size, surface morphology, release behavior in vitro, pharmacokinetics and in vivo biodistributions were researched. In vitro and in vivo tumor inhibition effects were systematically investigated. Furthermore, the hemolysis and acute toxicity of PTX-CMs were also evaluated.ResultsThe size of PTX-CMs was 53.61±0.75 nm and the ζ-potential was −19.73±0.68 mV. PTX was released much slower from PTX-CMs than PTX-Ms in vitro. Compared with PTX-Ms, the cellular uptake of PTX-CMs was significantly reduced in macrophages and significantly increased in human cancer cells, and therefore, PTX-CMs showed strong growth inhibitory effects on human cancer cells. In vivo, the plasma AUC0−t of PTX-CMs was 1.8-fold higher than that of PTX-Ms, and 5.2-fold higher than that of Taxol. The biodistribution study indicated that more PTX-CMs were accumulated in tumor than PTX-Ms and Taxol. Furthermore, the significant antitumor efficacy of PTX-CMs was observed in mice bearing BEL-7402 hepatocellular carcinoma and A549 lung carcinoma. Results from drug safety assessment studies including acute toxicity and hemolysis test revealed that the PTX-CMs were safe for in vivo applications.ConclusionThese results strongly revealed that NaC-mPEG-PDLLA micelles can tumor-target delivery of PTX and enhance drug penetration in tumor, suggesting that NaC-mPEG-PDLLA micelles are promising nanocarrier systems for anticancer drugs delivery.

Contribution of mouse carcinogenicity study for safety assessment of pesticide approved in Japan

Contribution of mouse carcinogenicity study for safety assessment of pesticide approved in Japan

人体の衝突・転倒時の安全評価に関する基礎的研究 : 第1報 ダミーの衝突・転倒実験による現象の把握

人体の衝突・転倒時の安全評価に関する基礎的研究 : 第1報 ダミーの衝突・転倒実験による現象の把握

Testicular Fibrous Hypoplasia in Cynomolgus Monkeys ( Macaca fascicularis): An Incidental, Congenital Lesion.

Testicular fibrous hypoplasia is an incidental lesion characterized by replacement of the testicular parenchyma by mature collagen. A retrospective survey of hematoxylin and eosin-stained testicular sections from 722 purpose-bred Asian and 90 Mauritian cynomolgus monkeys from 56 safety assessment studies conducted between 1999 and 2011 was performed. The incidence of the lesion increased markedly over time. No cases occurred between 1999 and 2004. Between 2005 and 2009, the incidence ranged between 8.1% and 11.0% of the monkeys examined and then rose to 26.1% in 2010 and 30.9% in 2011. Overall, the lesion was identified in 10.94% of Asian monkeys with the highest incidence in animals originating from China and Vietnam; severity ranged from minimal to severe and it occurred unilaterally (38.5%) and bilaterally (61.5%). In Mauritian monkeys, the lesion was predominantly minimal in severity, bilateral in distribution, and affected 6.6% of the animals examined. The lesion occurred regardless of sexual maturation status but when present in mature monkeys was often associated with cystic tubular atrophy of the seminiferous epithelium. Based on the morphological characteristics of the lesion and the unilateral/bilateral distribution, the lesion is considered to be a congenital or developmental abnormality.

Capillary microsampling in nonclinical safety assessment: practical sampling and bioanalysis from a CRO perspective.

Microsampling has the 3R benefits of refining blood collection techniques while reducing the number of animals required for rodent safety assessment studies. There are significant scientific benefits of correlating study findings with systemic exposure and consequently, there is an industry drive to utilize microsampling in regulatory toxicology studies. This article will focus on capillary microsampling and will discuss the initial considerations before using capillary microsampling, study design and some practicalities of sample collection. From a bioanalytical perspective, the impact of different sample collection and storage workflows on the design of method validation experiments, the suitability of using microsampling for unstable analytes and aspects supporting analysis of peptides, large molecules and for biomarker applications will be discussed.