Technical Document Research Articles

KEY IMPACT PARAMETERS FOR APPLICATION OF ALTERNATIVE SOURCE TERM TO KORI UNIT 1

The object of this paper is to identify the key elements that impact a radiation dose at EAB (Exclusion Area Boundary). This study is based on the AST (Alternative Source Terms) as defined in Regulatory Guide 1.183. The LOCA (Loss of Coolant Accident) and the LRA (Locked Rotor Accident) are selected as limiting cases. A sensitivity analysis of accidental behavior with respect to various parameters during LOCA and LRA at Kori Unit 1 is also undertaken for the following objectives: to determine the limiting parameters, to find the impact trend of the radiation dose, and to find the safety margin between AST and TID (Technical Information Document) methodologies. This work confirms that key parameters are particulate removal rate, decontamination factor, iodine chemical form, gap fraction, partitioning factor, and the impact of isotopes group. Comparing TID with AST, the radiation dose of TID is about 80% greater than that of AST under a LOCA, and about 60% greater than that of AST for the case of a LRA; thus the safety margin is remarkably increased when the AST is used. In this work, the sensitivity analysis results are presented in terms of a sensitivity index called the “NDD (Normalized Dose Difference)”, which compares the impact of parameters with that of a reference case. These values are derived by using a combination of the leak rate (primary to secondary), iodine chemical form, gap fraction, partitioning factor, spray removal rate, source term, and other variables.

Combined environmental risk assessment for 5‐fluorouracil and capecitabine in Europe

An environmental risk assessment (ERA) was made for the old cytostatic active pharmaceutical ingredient 5-fluorouracil (5-FU) and for capecitabine (CAP), which is a prodrug of 5-FU. This ERA is based on published and company internal data as well as new test results for physicochemical, human metabolism, biodegradability, environmental partitioning and fate, and acute and chronic ecotoxicity properties of the active substance 5-FU as well as on use sales data for 5-FU and CAP in Europe. Predicted environmental concentrations (PECs) were extrapolated following the EMEA 2006 Guideline on ERA for human pharmaceuticals and the European Union 2003 Technical Guidance Document (TGD) for risk assessment as well as the TGD-based application EUSES v2.0. Actual amounts sold were taken from IMS Health Databases, in order to refine the default use and EMEA penetration factor as well as the PECs. Moreover, available measured environmental concentrations (MECs) were used to supplement PECs. A predicted no-effect concentration (PNEC) for 5-FU was derived from chronic ecotoxicity data. Except for the simplistic EMEA Phase I default PEC, the risk characterization by PEC:PNEC and MEC:PNEC ratios for various environmental compartments resulted in no significant risk. As the EMEA Phase I PEC does not integrate documented human metabolism and environmental degradation, in contrast to refined PEC derivations, it is inferred that the current use of CAP and 5-FU does not present any evident risk to the environment. An additional evaluation of persistence, bioaccumulation, and toxicity (PBT) properties supports the conclusion of no significant environmental risk for 5-FU and CAP.

Telemetry Via Wi-Fi: A Case Study

Telemetry Via Wi-Fi: A Case Study

Consumer exposure to biocides - identification of relevant sources and evaluation of possible health effects

BackgroundProducts containing biocides are used for a variety of purposes in the home environment. To assess potential health risks, data on products containing biocides were gathered by means of a market survey, exposures were estimated using a worst case scenario approach (screening), the hazard of the active components were evaluated, and a preliminary risk assessment was conducted.MethodsInformation on biocide-containing products was collected by on-site research, by an internet inquiry as well as research into databases and lists of active substances. Twenty active substances were selected for detailed investigation. The products containing these substances were subsequently classified by range of application; typical concentrations were derived. Potential exposures were then estimated using a worst case scenario approach according to the European Commission's Technical Guidance Document on Risk Assessment. Relevant combinations of scenarios and active substances were identified. The toxicological data for these substances were compiled in substance dossiers. For estimating risks, the margins of exposure (MOEs) were determined.ResultsNumerous consumer products were found to contain biocides. However, it appeared that only a limited number of biocidal active substances or groups of biocidal active substances were being used. The lowest MOEs for dermal exposure or exposure by inhalation were obtained for the following scenarios and biocides: indoor pest control using sprays, stickers or evaporators (chlorpyrifos, dichlorvos) and spraying of disinfectants as well as cleaning of surfaces with concentrates (hydrogen peroxide, formaldehyde, glutardialdehyde). The risk from aggregate exposure to individual biocides via different exposure scenarios was higher than the highest single exposure on average by a factor of three. From the 20 biocides assessed 10 had skin-sensitizing properties. The biocides isothiazolinone (mixture of 5-chloro-2-methyl-2H-isothiazolin-3-one and 2-methyl-2H-isothiazolin-3-one, CMI/MI), glutardialdehyde, formaldehyde and chloroacetamide may be present in household products in concentrations which have induced sensitization in experimental studies.ConclusionsExposure to biocides from household products may contribute to induction of sensitization in the population. The use of biocides in consumer products should be carefully evaluated. Detailed risk assessments will become available within the framework of the EU Biocides Directive.

PM 4/10(2): Certification scheme forRubus

Specific scopeThis standard describes the production of certified pathogen‐tested material ofRubus.Specific approval and amendmentFirst approved in 2004–09.Revised in 2009–09.

Guidance for Industry: Integrated Summaries of Effectiveness and Safety: Location Within the Common Technical Document

Biotechnology Law ReportVol. 28, No. 4 DOCUMENTSGuidance for Industry: Integrated Summaries of Effectiveness and Safety: Location Within the Common Technical DocumentPublished Online:30 Oct 2009https://doi.org/10.1089/blr.2009.9937AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byThree-Level Hepatotoxicity Prediction System Based on Adverse Hepatic Effects26 November 2018 | Molecular Pharmaceutics, Vol. 16, No. 1Tool selection method based on transfer learning for CNC machines27 February 2018 | Mechanical Sciences, Vol. 9, No. 1Optimal Control of Energy Storage Based on Fuzzy Dependent-Chance Programming1 February 2014 | Applied Mechanics and Materials, Vol. 530-531A Network-Based Multi-Dimensional Recommendation Algorithm1 September 2013 | Advanced Materials Research, Vol. 765-767 Volume 28Issue 4Aug 2009 Information© 2009 Mary Ann Liebert, Inc.To cite this article:Guidance for Industry: Integrated Summaries of Effectiveness and Safety: Location Within the Common Technical Document.Biotechnology Law Report.Aug 2009.532-536.http://doi.org/10.1089/blr.2009.9937Published in Volume: 28 Issue 4: October 30, 2009PDF download

Methods for estimating the bioconcentration factor of ionizable organic chemicals

The bioaccumulation potential is an important criterion in risk assessment of chemicals. Several regressions between bioconcentration factor (BCF) in fish and octanol-water partition coefficient (K(OW)) have been developed for neutral organic compounds, but very few approaches address the BCF of ionizable compounds. A database with BCFs of 73 acids and 65 bases was collected from the literature. The BCF estimation method recommended by the Technical Guidance Document (TGD) for chemical risk assessment in the European Union was tested for ionizing substances using log K(OW) (corrected for the neutral species, log[ f(n) x K(OW)]) and log D (sum of log K(OW) of neutral and ionic molecule, apparent log K(OW)) as predictors. In addition, the method of Meylan et al. (Environ Toxicol Chem 1999; 18:664-672) for ionizable compounds and a dynamic cell model based on the Fick- Nernst-Planck equation were tested. Moreover, our own regressions for the BCF were established from log K(OW) and pK(a). The bioaccumulation of lipophilic compounds depends mainly on their lipophilicity, and the best predictor is log D. Dissociation, the pH-dependent ion trap, and electrical attraction of cations impact the BCF. Several methods showed acceptable results. The TGD regressions gave good predictions when log( f(n) x K(OW)) or log D were used as a predictor instead of log K(OW). The new regressions to log K(OW) and pK(a) performed similarly, with mean errors of approximately 0.4. The method of Meylan et al. did not perform as well. The cell model showed weak results for acids but was among the best methods for bases.

Electronic Common Technical Document Implementation in Japan

The main missions of the Pharmaceuticals and Medical Devices Agency (PMDA) are the review of drug applications and also being in charge of the electronic common technical document (eCTD) regulations in the review process. However, we believe that we should consider enhancing eCTD implementation with other activities in electronic standardization of clinical trials. With this sense, the Ministry of Health, Labor and Welfare (MHLW) and PMDA are cooperating to enhance eCTD and e-clinical trials in Japan. This article introduces eCTD implementation in Japan, and also our concept for enhancing eCTD submissions in view of the Japanese government initiative for supporting the development of new drugs by the electronic standardization of clinical trials. PMDA is keen to have eCTD submissions and hopes these activities for eCTD will enhance the understanding of our concepts and support the activities of developing drugs in Japan.

Extending the environmental risk assessment for oseltamivir (Tamiflu ®) under pandemic use conditions to the coastal marine compartment

In case of an avian-influenza-derived human flu pandemic, an inordinately high use of medicines over several weeks is predicted, in particular for the recommended influenza antiviral oseltamivir (Tamiflu). While the risk of oseltamivir to sewage works and freshwater bodies has already been assessed, the fact that a large percentage of the human population worldwide lives relatively close to the sea raises concern for its environmental compatibility in coastal marine waters. The potential risk of high oseltamivir use to the marine compartment is assessed in this publication, based on the 2003 European Community Technical Guidance Document (TGD) for risk assessment. Subchronic embryo–larval ecotoxicity tests with three marine invertebrates ( Pomatoceros triqueter, Annelida; Mytilus edulis, Mollusca; Paracentrotus lividus, Echinodermata) and chronic growth inhibition tests with two different groups of marine microalgae ( Isochrysis galbana, Haptophyta; Skeletonema costatum, Heterokontophyta) were performed with the active substance oseltamivir carboxylic acid to derive a dependable marine predicted no-effect concentration (PNEC). This was compared to a predicted environmental concentration (PEC) for oseltamivir in coastal waters, based on the worst-case freshwater PEC. The PEC/PNEC risk characterisation ratio for the marine compartment is well below 1, which in the terminology of the TGD signifies no immediate concern. Further, while oseltamivir may be persistent (P), it is not bioaccumulative (B) nor highly ecotoxic (T) and therefore not a PBT substance. In conclusion, even a high pandemic use of oseltamivir would not lead to a significant risk for the marine compartment, in confirmation of the risk assessment for sewage works and freshwaters.

The usefulness of total concentrations and pore water concentrations of pesticides in soil as metrics for the assessment of ecotoxicological effects ‐ Scientific Opinion of the Panel on Plant Protection Products and their Residues (PPR)

The usefulness of total concentrations and pore water concentrations of pesticides in soil as metrics for the assessment of ecotoxicological effects ‐ Scientific Opinion of the Panel on Plant Protection Products and their Residues (PPR)

Modeling the exposure of children and adults via diet to chemicals in the environment with crop-specific models

Exposure to chemicals via diet is a major uptake pathway for many compounds but is often estimated in a rather generic way. We use a new model framework (NMF) with crop-specific models to predict the dietary intake by 4–5-year-old children and 14–75-year-old women of three environmental compounds from their background concentrations in soil and air. Calculated daily intakes of benzo(a)pyrene and 2,3,7,8-TCDD are in good agreement with measured results from diet studies. The major source of both compounds in human diet is deposition from air. Inhalation of air and ingestion of soil play a minor role. Children take up more than twice the amount than adults per kg bodyweight, due to higher consumption per kg bodyweight. Contrary, the methods for indirect human exposure suggested in the Technical Guidance Document (TGD) for chemical risk assessment in the EU lead to overprediction, due to unrealistic consumption data and a false root model.

Pathogen‐tested material of grapevine varieties and rootstocks

Pathogen‐tested material of grapevine varieties and rootstocks

Certification scheme for strawberry

Certification scheme for strawberry

Evolution and Implementation of the CDISC Study Data Tabulation Model (SDTM)

AbstractThe Clinical Data Interchange Standards Consortium (CDISC) Study Data Tabulation Model (SDTM) is a standard for submitting data tabulations to the FDA in support of marketing applications. In July 2004, this standard became part of the FDA Study Data Specification referenced in the electronic Common Technical Document (eCTD) Guidance. This article will provide an overview of evolution and status of the SDTM and the associated Implementation Guides, commonly referred to as the Study Data Tabulation Model Implementation Guide for Human Clinical Trials (SDTMIG) and the Standard for Exchange of Nonclinical Data (SEND).

NOAA operational sounding products for advanced TOVS

The National Oceanic and Atmospheric Administration (NOAA), National Environmental Satellite Data and Information Service (NESDIS) operates a fleet of civilian, polar‐orbiting, environmental satellites that provide users and researchers with a continuous suite of atmospheric and surface products on a global scale. The first advanced TIROS operational vertical sounder (ATOVS) radiometer configuration, onboard NOAA‐15, was successfully launched into an early evening orbit on 13 May 1998. The ATOVS featured the new 13 channel advanced microwave sounding unit (AMSU) module A1, the 2 channel AMSU‐A2 and 5 channel AMSU‐B radiometers, which replaced the MSU and SSU, along with a similar HIRS and AVHRR instrument payload (Goodrun G., Kidwell, K.B. and Winston, W., 2000, NOAA‐KLM users guide: September 2000 revision, Technical Document, National Oceanic and Atmospheric Administration, National Environmental Satellite Data and Information Service, National Climatic Data Center) that had been operational since 1979. The ATOVS onboard NOAA‐16 was successfully launched into an afternoon orbit on 21 September 2000, followed by NOAA‐17 into a late evening orbit on 24 June 2002, creating the first ever three‐satellite constellation of operational polar satellites (ATOVS). The following report summarizes the online and offline scientific processing systems, respectively, for deriving the NESDIS operational ATOVS sounding products and presents a series of results for the unique three‐operational‐satellite configuration of NOAA‐15, 16 and 17. Results focus on the value of the derived products in the analyses of global and regional scale weather, including direct comparisons against collocated numerical weather prediction (NWP) forecast and radiosonde data. The report is prefaced by a brief history of satellite weather products and concludes with future plans to meet expanding user requirements.

Toxicity on the luminescent bacterium Vibrio fischeri (Beijerinck). I: QSAR equation for narcotics and polar narcotics

Toxicity data on chemicals, supposed to have a narcotic or polar narcotic toxicological mode of action, have been produced on the luminescent bacterium Vibrio fischeri using the Microtox® test procedure. Advanced statistical methods have been used to calculate statistically sound values for ecotoxicological endpoints. Simple quantitative structure activity relationship (QSAR) equations were developed for narcotics and polar narcotics. These equations were compared with those proposed by the European Technical Guidance Document on Risk Assessment for other aquatic organisms (algae, Daphnia, and fish). Similarities and differences are discussed. The need for including the bacterial component in the ecotoxicological risk assessment for aquatic ecosystems is highlighted.

Sexual Health for the Millennium: An Introduction

ABSTRACT This special issue of the International Journal of Sexual Health is devoted to the issues of the United Nations Millennium Development Goals and the effort by the World Association for Sexual Health to argue that the promotion of sexual health is an essential strategy for attaining those goals. Recently, the World Association for Sexual Health has published Sexual Health for the Millennium: A Declaration and Technical Document (2008). This special issue of the IJSH contains the background papers which served as a foundation for the development of the declaration and technical document. These articles argue that sexuality is a fundamental aspect of being human, that human development must be premised on the promotion of sexual health and is a basic human right for all citizens. Public policies designed to promote human development must make the promotion of sexual health an essential strategy. This special issue is designed to stimulate more interest in the Sexual Health for the Millennium: A Declaration and Technical Document, encourage further analysis and research which will support the statements in the declaration, provoke more advocacy for sexual health, and, most importantly, to stimulate sound and effective public policies to create a sexually healthier world.

NOAA NATIONAL MARINE SANCTUARIES AS RESOURCE TRUSTEES IN THE UNIFIED COMMAND: GOOD OR BAD?

ABSTRACT The National Oceanic and Atmospheric Administration (NOAA) is a federal trustee within the National Contingency Plan (NCP) in addition to providing scientific and technical support to the Incident Command System (ICS) during a response. NOAA is also the home of the National Marine Sanctuary Program (NMSP), a system of 14 marine protected areas that encompass 150,000 square miles of coastal and oceanic waters. NOAA is increasing its capacity for addressing a significant incident through participating in and leading spill response exercises. One of the most intense aspects of those experiences is often the discussion of the role of NOAA as a trustee and whether they should be part of the Unified Command (UC). While the NCP outlines the expectations of Regional Response Team (RRT) members from the Department of the Interior and the Department of Commerce (NOAA), it provides the Federal On Scene Coordinator (FOSC) considerable flexibility in determining whether to include trustees within the UC or working with the Liaison or through the Environmental Unit. A recent Technical Assistance Document from the National Response Team speaks directly to this issue and provides RRT'S more specific guidance. There are some RRT'S that feel strongly that the only trustee in the UC should be the states. NOAA and the DOI believe that they should be afforded the same considerations in the marine and coastal environment as trustees or landowners in the terrestrial environment. Both the Safe Sanctuaries 2005 in Florida and the Safe Seas 2006 in California provided a forum for dialogue on this issue. In both instances, the FOSC did engage the trustees in the UC. It is not always necessary or appropriate for NOAA to participate as a member of the UC. In some situations it could be more effective to participate in other capacities within the ICS and NOAA may not be the trustee with the most significant resources at risk. When participating in a UC, it is incumbent upon the NOAA representative to work with other members of the UC to manage the response under a single, collaborative approach.

CreditRisk+ by Fast Fourier Transform

In this paper, we focus on the methodology applied in the CreditRisk + Technical Document. Its Appendix A gives analytical explanations of the technique used to generate the loss distribution arising from a credit portfolio. It is worth mentioning that although underlying concepts are easy to grasp for those with an intermediate mathematical knowledge, the technical methods employed in this paper may not be straightforward for those who are not fully familiar with the mathematics employed. First, we concentrate on the concepts of the Probability Generating Function and Convolution, and their application in CreditRisk + . Then, we explain, in practical terms, the use of the recurrence relation used by CreditRisk + . Last, we develop an alternative way to calculate CreditRisk + through the Fast Fourier Transform ( FFT ). In order to cover the gap between the theory and its practical implementation we provide VBA, MatLab and R codes that present step-by-step all the practical applications covered.

Approaches for derivation of environmental quality criteria for substances applied in risk assessment of discharges from offshore drilling operations

AbstractIn order to achieve the offshore petroleum industries “zero harm” goal to the environment, the environmental impact factor for drilling discharges was developed as a tool to identify and quantify the environmental risks associated with disposal of drilling discharges to the marine environment. As an initial step in this work the main categories of substances associated with drilling discharges and assumed to contribute to toxic or nontoxic stress were identified and evaluated for inclusion in the risk assessment. The selection were based on the known toxicological properties of the substances, or the total amount discharged together with their potential for accumulation in the water column or sediments to levels that could be expected to cause toxic or nontoxic stress to the biota. Based on these criteria 3 categories of chemicals were identified for risk assessment the water column and sediments: Natural organic substances, metals, and drilling fluid chemicals. Several approaches for deriving the environmentally safe threshold concentrations as predicted no effect concentrations were evaluated in the process. For the water column consensus were reached for using the species sensitivity distribution approach for metals and the assessment factor approach for natural organic substances and added drilling chemicals. For the sediments the equilibrium partitioning approach was selected for all three categories of chemicals. The theoretically derived sediment quality criteria were compared to field‐derived threshold effect values based on statistical approaches applied on sediment monitoring data from the Norwegian Continental Shelf. The basis for derivation of predicted no effect concentration values for drilling discharges should be consistent with the principles of environmental risk assessment as described in the Technical Guidance Document on Risk Assessment issued by the European Union.