In vitro Toxicity Testing in the Twenty-First Century

The National Research Council (NRC) article “Toxicity Testing in the 21st Century: A vision and A Strategy” (National Research Council, 2007) was written to bring attention to the application of scientific advances for use in toxicity tests so that chemicals can be tested in a more time and cost efficient manner while providing a more relevant and mechanistic insight into the toxic potential of a compound. Development of tools for in vitro toxicity testing constitutes an important activity of this vision and contributes to the provision of test systems as well as data that are essential for the development of computer modeling tools for, e.g., system biology, physiologically based modeling. This article intends to highlight some of the issues that have to be addressed in order to make in vitro toxicity testing a reality in the twenty-first century

alternative approach for potency assessment in vitro methods

Over the last decade, incredible progress has been made in the development of non-animal tests to assess contact hypersensitivity. Four methods have been successfully validated and Organisation for Economic Co-operation and Development (OECD) guidelines are available or soon will be. Currently validated methods are useful for hazard identification, classification and labeling. However, to achieve a complete replacement of animals in skin sensitization assessment, dose-response information and evaluation of relative skin sensitizing potency to support effective risk assessment are necessary. In this context, potency is based on the concentration of chemicals needed to induce a positive response. This will require a better understanding of the mechanisms determining potency, including pathway analysis and marker signature identification (selection of an appropriate immune-mediated response to serve as the basis), together with quantitative and qualitative correlations between marker signatures and potency of chemicals in relation with T cell responses. This review aims to discuss the state-of-the-art in the field of in vitro assessment of the no induction sensitization level of contact sensitizers

Applying the adverse outcome pathway (AOP) for food sensitization to support in vitro testing strategies

Background Before introducing proteins from new or alternative dietary sources into the market, a compressive risk assessment including food allergic sensitization should be carried out in order to ensure their safety. We have recently proposed the adverse outcome pathway (AOP) concept to structure the current mechanistic understanding of the molecular and cellular pathways evidenced to drive IgE-mediated food allergies. This AOP framework offers the biological context to collect and structure existing in vitro methods and to identify missing assays to evaluate sensitizing potential of food proteins. Scope and approach In this review, we provide a state-of-the-art overview of available in vitro approaches for assessing the sensitizing potential of food proteins, including their strengths and limitations. These approaches are structured by their potential to evaluate the molecular initiating and key events driving food sensitization. Key findings and conclusions The application of the AOP framework offers the opportunity to anchor existing testing methods to specific building blocks of the AOP for food sensitization. In general, in vitro methods evaluating mechanisms involved in the innate immune response are easier to address than assays addressing the adaptive immune response due to the low precursor frequency of allergen-specific T and B cells. Novel ex vivo culture strategies may have the potential to become useful tools for investigating the sensitizing potential of food proteins. When applied in the context of an integrated testing strategy, the described approaches may reduce, if not replace, current animal testing approaches

Анализ методов вибродиагностики металлорежущих станков

Цель работы - выработка рекомендаций по применению методов вибродиагностики металлорежущих станков в конкретной задаче. Объект исследования - методы и комплексы вибродиагностики металлорежущих станков. Предмет исследования – систематизация и обобщение методов вибродиагностики металлорежущих станков. Актуальность - отсутствие простой для реализации методики виброиспытаний. В процессе работы были рассмотрены различные методы вибродиагностики металлорежущих станков, сделаны предложения по применению методов вибродиагностики металлорежущих станков в каждой конкретной задаче, создана универсальная методика проведения вибродиагностики металлорежущих станков диагностическим комплексом "Виброрегистратор-М2".The aim of the work is to develop recommendations on the application of vibration diagnostics methods for metal-cutting machine tools in a specific task. The object of research is methods and complexes of vibration diagnostics of metal cutting machines. The subject of the study is the systematization and generalization of methods of vibration diagnostics of metal-cutting machines. Actuality is the absence of a simple vibration testing technique. In the course of the work various methods of vibration diagnostics of metal cutting machines were considered, suggestions were made on the application of vibration diagnostics methods for metal cutting machines in each specific task, a universal technique for performing vibration diagnostics of metal cutting machines with the Vibroregistrator-M2

Prevalence and significance of sexually transmitted diseases among Ethiopian women attending antenatal clinics in Addis Ababa

Abstract: To determine the prevalence of sexually transmitted diseases (STDs) and the risk for (i) the mother regarding pregnancy wastage and puerperal sepsis and (ii) the child with regard to congenital and neonatal infection, 342 routine antenatal clinic (ANC) at tenders were investigated. The prevalence of antibodies showing exposure to specific STD pathogens in pregnant women attending ANC was: syphilis (TPHA) 27%, (VDR:) 28%, gonorrhoea 43%, genital chlamydiae 54%, HBV 37%, HSV-2 35 %, H ducreyi 10%. High titre seropositivity suggestive of active infection was: gonorrhoea 10%, genital chlamydiae 31 %, HSV2 19%; with HBV SAg 5% -all of which are likely to be transmitted to the foetus in utero or during delivery. Only 10% of ANC at tenders had no serological evidence of any STD: 72% had serological evidence for two or more STDs. Among conditions requiring treatment vaginitis was the most important, 20% having a severe trichomonal infection. Despite the frequency of this condition it was noted that few women (4%) complained of vaginal discharge. Thus women attending the ANC revealed a high prevalence of STD. Consequently the foetus and neonate are put at risk because of intrauterine or intrapartum transmission of infection. The high prevalence among ANC at tenders also reflects the relative prevalence of STDs in the community. Measures such as screening at ANC and information and education regarding prevention are required to reduce STDs in pregnant women and their sexual partners. Prophylaxis for the neonate can be considered until this goal is achieved. [Ethiop. J. Health Dev. 1995;9(1):31-40

A sociological and serological study of at tenders of family planning clinics in Addis Ababa

Abstract: A study of 542 women attending family planning clinics (FPC) and 1568 women attending obstetric and gynaecologic clinics in Addis Ababa showed utilisation of FPC was highest in those with a family income of 100-500 EB per month (36%), in women who were: Tigrawi (33%) or Amara (31 %), aged 20-34 years (30%), age 16 or older at first marriage/coitus (28%), parity of 2... 2 children (35%), > 5 lifetime husbands/sexual partners (39%), or were bargirls (73%) or prostitutes (43%). FPC attendance was lowest among the nulliparous (2.3%), women from rural areas (10%), the Guragie (10%) and Oromo women (19%), Moslem women 14(%), those of subsistence income ( < 10EB per month) (14%). The seroprevalence rates indicative of exposure to STD pathogens were high as was the prevalence of essentially asymptomatic pelvic inflammatory disease (PID). Only 4% of FPC at tenders had no serological evidence of STD: 64% had 3 or more different STD. Specific present or active STD infection prevalence for syphilis (VDRL) 28%, Neisseria gonorrhoea 31 %, genital chlamydia 46% and HSV-2 21% was higher in FPC at tenders than among women attending other clinics. Clinical evidence of PID was also more common in the FPC at tenders (54%), 37% having evidence of salpingitis. Thus FPCs provide a useful setting for screening women particularly at risk. Because of lack of symptoms, these women are unlikely to attend either an STDs clinic or a hospital for routine check up, and as such are not treated and represent a population from which STDs can spread into the population. Measures to screen, treat and educate FPC at tenders, their partners and their clients, are recommended in an attempt to Control STDs and ultimately HIV in the community. [Ethiop. J. Hea/th Dev. 1995;9(1):19-30

ESAC Opinion on the BASF-coordinated Performance Standards-based validation of the LuSens test method for skin sensitisation testing

ESAC, the EURL ECVAM Scientific Advisory Committee, advises EURL ECVAM on scientific issues. Its main role is to conduct independent peer review of validation studies of alternative test methods and to assess their scientific validity for a given purpose. The committee reviews the appropriateness of study design and management, the quality of results obtained and the plausibility of the conclusions drawn. ESAC peer reviews are formally initiated with a EURL ECVAM Request for ESAC Advice, which provides the necessary background for the peer-review and establishes its objectives, timelines and the questions to be addressed. The peer review is normally prepared by specialised ESAC Working Groups. These are typically composed of ESAC members and other external experts relevant to the test method under review. These experts may be nominated by ESAC, EURL ECVAM and partner organisations within the International Cooperation on Alternative Test Methods (ICATM). ESAC ultimately decides on the composition of these Working Groups. ESAC's advice to EURL ECVAM is formally provided as 'ESAC Opinions' and 'Working Group Reports' at the end of the peer review. ESAC may also issue Opinions on other scientific issues of relevance to the work and mission of EURL ECVAM but not directly related to a specific alternative test method. The ESAC Opinion expressed in this report relates to the peer-review of the BASF-coordinated Performance Standards-based validation of the LuSens test method for skin sensitisation testing.JRC.F.3-Chemicals Safety and Alternative Method

An Adverse Outcome Pathway for Sensitization of the Respiratory Tract by Low-Molecular-Weight Chemicals: Building Evidence to Support the Utility of In Vitro and In Silico Methods in a Regulatory Context

Sensitization of the respiratory tract is an important occupational health challenge, and understanding the mechanistic basis of this effect is necessary to support the development of toxicological tools to detect chemicals that may cause it. Here we use the adverse outcome pathway (AOP) framework to organize information that may better inform our understanding of sensitization of the respiratory tract, building on a previously published skin sensitization AOP, relying on literature evidence linked to low-molecular-weight organic chemicals and excluding other known respiratory sensitizers acting via different molecular initiating events. The established key events (KEs) are as follows: (1) covalent binding of chemicals to proteins, (2) activation of cellular danger signals (inflammatory cytokines and chemokines and cytoprotective gene pathways), (3) dendritic cell activation and migration, (4) activation, proliferation, and polarization of T cells, and (5) sensitization of the respiratory tract. These events mirror the skin sensitization AOP but with specific differences. For example, there is some evidence that respiratory sensitizers bind preferentially to lysine moieties, whereas skin sensitizers bind to both cysteine and lysine. Furthermore, exposure to respiratory sensitizers seems to result in cell behavior for KEs 2 and 3, as well as the effector T cell response, in general skewing toward cytokine secretions predominantly associated with T helper 2 (Th2) response. Knowledge gaps include the lack of understanding of which KE(s) drive the Th2 polarization. The construction of this AOP may provide insight into predictive tests that would in combination support the discrimination of respiratory-sensitizing from non- and skin-sensitizing chemicals, a clear regulatory need