bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of fermentation conditions on content of phenolic compounds in red wine
Authors: Puskas Vladimir , Kovac Vladimir , Dodic Jelena , Dodic Sinisa
Published: November 2007

The evidence of compounds that increase the nutritive value of red wines has been presented in a number of papers. These compounds include catechins and proanthocyanidins among others. Their protective effect on the cardiovascular system and anticarcinogenic properties has been proved. The effect of maceration conditions and increased solid grape parts content, seed in the first place, on the content of phenolic compounds of wine was investigated. Several micro-trials were performed with Cabernet sauvignon sort; in some variants time and temperature of maceration were varied, while the ratio of residual stem and content of seed was increased several times, resulting in a significant change of phenolic compounds content in the obtained wine samples. The presence of ripe stem yielded good results, but only during six days of maceration, while in the case of longer maceration, the change of colour quality was negative. Supplementary quantities of seeds during maceration resulted in an increase of total phenols and catechins. A significant influence on colour of wines was also observed, especially in wines obtained applying shorter maceration.
Determination of polycyclic aromatic hydrocarbons in soil by gas chromatography-mass spectrometry
Authors: Kravic Snezana , Marjanovic Nikola , Pucarevic Mira , Suturovic Zvonimir , Svarc-Gajic Jaroslava
Published: November 2007

Polycyclic aromatic hydrocarbons (PAHs) were determined in soil samples from forty different locations in Vojvodina. The samples were Soxhlet extracted cleaned-up and analyzed using gas chromatography-mass spectrometry (GC-MS) in the selected ion monitoring mode (SIM). Each PAH was separately quantified using an eight-point calibration of mixed standard solutions in the range between 0.25 and 10 ?g/cm3. The sum of the 16 US Environmental Protection Agency PAHs analyzed in the soil samples varied from 0.043 to 1.362 mg/kg of dry soil.
Low-temperature tension properties of glass-epoxy composite materials
Authors: Putic Slavisa , Stamenovic Marina , Bajceta Branislav , Stajcic Predrag , Bosnjak Srdjan
Published: November 2007

The aim of this paper was to present the determination of tensile strength Rm and modulus of elasticity Et of glass-epoxy composites at two different temperatures (at room temperature t=20?C, and at t =?50?C). Standard mechanical testing was carried out on glass woven-epoxy composite material with different structures (two specific weights of reinforcement, 210 g/m2 and 550 g/m2) and orientations (0?/90? and ?45?). Micromechanical analysis of failure was performed on a stereo microscope and SEM in order to determine real models and mechanisms of crack.
Covalent immobilization of lipase from Candida rugosa on Eupergit®
Authors: Bezbradica Dejan , Corovic Jasmina , Prodanovic Radivoje , Milosavic Nenad , Knezevic Zorica
Published: November 2007

An approach is presented for the stable covalent immobilization of Upase from Candida rugosa on Eupergit? with a high retention of hydrolytic activity. It comprises covalent bonding via lipase carbohydrate moiety previously modified by periodate oxidation, allowing a reduction in the involvement of the enzyme functional groups that are probably important in the catalytic mechanism. The hydrolytic activities of the lipase immobilized on Eupergif1 by two conventional methods (via oxirane group and via glutaralde-hyde) and with periodate method were compared. Results of lipase assays suggest that periodate method is superior for lipase immobilization on Eupergit? among methods applied in this study with respect to both, yield of immobilization and hydrolytic activity of the immobilized enzyme.
Extraction and partial purification of coagulation active components from common bean seed
Authors: Sciban Marina , Antov Mirjana , Klasnja Mile
Published: November 2007

An active coagulation component was extracted from common bean seed by NaCl solution and the obtained crude extract was partially purified through a sequence of steps that included precipitation of protein by ammonium sulphate, desalting by dialysis and anion exchange. A turbid water was treated by protein fractions obtained in the anion- exchange elution process by stepwise increase in NaCl concentration. The jar tests were conducted at various dosages of eluates. Different mode of relation between coagulation activity and applied coagulant dose for each protein fraction indicated the existence of different mechanisms of coagulation/flocculation, depending of characteristics of different proteins in the fractions.
Relishes: The new pickled vegetables
Authors: Tepic Aleksandra , Vujicic Biserka , Andric Aleksandra , Milatovic Snezana
Published: November 2007

There have been an increasing interest of consumers for a \ride variety of pickled vegetable products worldwide. Regarding the regional vegetable supplies and relatively poor assortment of ready-to-use products, the need to broaden the offer of domestic pickled vegetables at the market came out. In this work recipes for different vegetables, spices and condiments were developed. The best graded samples were analyzed for their main chemical composition (dry matter, proteins, oils and fats, total acidity, total sugars, sucrose, starch, cellulose, pH) and energy- values.
Comparison of mentha extracts obtained by different extraction methods
Authors: Milic Slavica , Lepojevic Zika , Adamovic Dusan , Mujic Ibrahim , Zekovic Zoran
Published: November 2007

The different methods of mentha extraction, such as steam distillation, extraction by methylene chloride (Soxhlet extraction) and supercritical fluid extraction (SFE) by carbon dioxide (CO J were investigated. SFE by CO, was performed at pressure of 100 bar and temperature of40?C. The extraction yield, as well as qualitative and quantitative composition of obtained extracts, determined by GC-MS method, were compared.
Trafficking in women in Serbia and neighboring countries: Scope, characteristics and causes
Authors: Nikolic-Ristanovic Vesna
Published: November 2007

In this paper scope, characteristics and causes of sex trafficking in women are analyzed. The analysis considers trafficking in women in Serbia and in its direct and indirect surrounding. Available data about distribution and channels of trafficking in women, as well as about methods of recruitment, transfer and victimization of women are analyzed. Also, some of characteristics of traffickers are considered. The special chapter deals with factors that contribute to sex trafficking in women. These factors are classified in three groups: push factors, pull factors and facilitating factors. In the conclusion, the author points out the importance of data exposed in this paper for building efficient system of struggle against as well as prevention of trafficking of human beings in general, and, of sex trafficking in women, in particular.
Criminal offense of trafficking in human beings: International documents, contemporary solutions in national legislations and Criminal Code of Federal Republic of Yugoslavia
Authors: Copic Sanja , Nikolic-Ristanovic Vesna
Published: November 2007

Due to its high social danger and far-reaching consequences, trafficking in human beings, as a form of transnational crime, needs an all-inclusive international approach in countries of origin, transit and destination. That means the use of effective measures concerning prevention, punishment of perpetrators and protection of victims. In connection with that, intensive efforts of the international community in stamping out this phenomenon marked the end of 20? century. They are incarnated in a numerous of international documents and other activities, which particular emphasize the need of criminalization of trafficking in human beings in national legislation. In the paper, authors are analyzing international documents that are both directly or indirectly dealing with this topic, as well as criminal law provisions of a number of countries (USA, Western Europe, Central and Eastern Europe, Southern Europe). The aim of such an approach is to perceive our legislation though the prism of the contemporary tendencies, as well as to point out certain shortages and the importance of harmonizing our legislature with the international standards and demands of the international community. The first step toward that should be inclusion of trafficking in human beings as a separate criminal offence in the Criminal Code of Federal Republic of Yugoslavia. Victimology Society of Serbia drafted such criminal law provision, which is presented in this paper.
Safe Horizon: Victim support service in New York
Authors: Milivojevic Sanja
Published: November 2007

This article contains analysis of history and development of the victim support movement in United States of America, with particular focus on New York City. The analysis includes the causes of establishment, the history of the victim support services as well as today?s situation in the movement for helping victims of crime. Specific part of the article is dedicated to Safe Horizon, victim support service in New York, and programs this organization, known also under old name - Victim Services, Inc., is running today.
Zrtve kriminaliteta, emocionalna reakcija i proces oporavka
Authors: Vidakovic Ivana
Published: November 2007

The article is based on the experiences of the European services that provide assistance for the victims of criminality. It describes characteristics of the emotional reactions and recovery process of both the victim and his/her surrounding. Some factors of risk are explored that make certain categories of people especially vulnerable after the criminal incident. A crime victim may have certain difficulties in dealing with the unpleasant experience in cases when he/she is hurt on purpose, intentionally by another person. As a result of that many victims lose the sense of interior control over the things that happen to them, lose self-respect, faith in other people and the community. Therefore, the task of the whole community is to actively contribute to the process of victim's recovery and restitution of self-confidence as well as the confidence in other people and institutions that provide protection and aid.
Albert R. Roberts: Helping crime victims: Research, policy and practice, Sage publications, London, Newberry park and New Delhi,1990, str. 277.
Authors: Lukic Marija
Published: November 2007

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Kak pomocja zertve prestuplenija, Drustvo za pomoc zrtvama kriminala, Ohvriabi, Estonija, 2001, str. 65
Authors: Nikolic Jasmina
Published: November 2007

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11. Septembar - od soka do “projekta sloboda”
Authors: Milivojevic Sanja
Published: November 2007

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O ocu mom/tvom/njenom/njegovom - tresak koji cujem posle pedeset godina
Authors: Radovic Nadezda
Published: November 2007

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Istina i pomirenje - analiza slucaja - moguci put razumijevanja
Authors: Knezic Branislava
Published: November 2007

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Gerry Johnstone: Restorative justice ideas, values, debates, Willan publishing, Devon, U.K., 2002, str.190
Authors: Copic Sanja
Published: November 2007

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Domestic violence
Authors: Kiurski Jasmina
Published: November 2007

In this article author examines a definition of a family, the role of a family as a social and legal institution as well as state reaction in a situation of mal function of a family. Special attention is given to a definition of a family, its protective function and criminal law in modern legal systems. Author also analyzes recent reform of our legislation firstly new criminal offence (Article 118a of the Criminal Code of Republic of Serbia) - Domestic Violence - and its relation to other similar criminal offences. Finally, author gives an overview of up-to-now practice from District and Municipal Prosecutors Offices in Belgrade and suggestions for solving observed problems in implementation of this criminal offence.
Practice of the city magistrates in Belgrade regarding domestic violence
Authors: Andjelkovic Marija
Published: November 2007

In this paper author analyzes all cases of the city magistrates in Belgrade in 2002 which went into effect. The goal of this analysis is to determine how many cases are related to domestic violence and to define sentencing policy applied in these cases. In this analysis author pointed out problems and needs which exist in the work of the city magistrates. Also, some suggestions and recommendations for overcoming these problems are underlined.
Implementation of the Domestic Violence Law in the Republika Srpska
Authors: Markovic Ivanka
Published: November 2007

In this paper author analyzes criminal offence "Violence in family or extended family". This criminal offence was introduced for the first time in the new Criminal Code of the Republika Srpska in 2000 (article 198). In the first part of the paper author exposes characteristics of legal provisions regarding criminal offence "Violence in family or extended family". In the second part practical implementation of this criminal offence is analyzed. For doing that analyzes, the author uses the interviews carried out with representatives of the police, prosecutors judges and representatives of non-governmental organizations. At the end author suggests introduction of certain measures for victim protection such as mandatory arrest of a perpetrator, the increased efficiency of the criminal procedure, restraining orders (regarding communication and contact between perpetrator and victim) and other measures, which should provide adequate implementation of this incrimination and optimal protection of victims of this crime.
The response of the modern legal systems to domestic violence: Comparative analysis of some of the European countries and New York State, USA
Authors: Milivojevic Sanja
Published: November 2007

In the last few years of XX century domestic violence was in focus of interest in majority of European countries and worldwide. The severity of consequences that this type of violence generates to victims and other members of their families (indirect victims), the development of women's rights movement, large number of research and scholars papers that warn about danger from this violence, led to the criminal prosecution of domes tic violence and establishment of large scale of measures for victims protection, prevention of further victimization, punishment of perpetrators and minimization of negative consequences of violence. The aim of this paper is to compare modern European legislations as well as the legislation of New York State, USA, in order to consider possible further development in fighting this complex social problem in our society and practice.
Lode Walgrave (ur): Restorative justice and the law, Willan publishing, Devon UK, 2002
Authors: Stevanovic Ivana
Published: November 2007

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Prostitution and (il)legal migration as possible hidden forms of trafficking in human beings: The analyses of the practice of the Magistrate Court in Belgrade
Authors: Andjelkovic Marija
Published: November 2007

In this paper the author analyses all the cases from the 2002 practice of Magistrate Court in Belgrade, which relate to prostitution and illegal migration. The main aim of this paper is to show who are the women and men who are accused and punished for prostitution and illegal migration, as well as to argue that the part of them are in fact victims of trafficking in human beings. In conclusion, the author suggests the necessity for training of magistrate judges in order to be able to recognize victims of trafficking and, consequently, to be able to treat them as victims rather than as offenders.
Social construction of victim’s blame, with special emphasis on criminal procedure against accused for the assassination of Zoran Djindjic, the prime minister of Serbia
Authors: Nikolic-Ristanovic Vesna
Published: November 2007

In this paper, the problem of victim blaming is analyzed, in general, and particularly, in the criminal procedure and through the media. Also, the attention is paid to the secondary victimization of family members of murder victims in general, and, especially, in criminal procedure, and when there is the tendency of blaming direct victim. In the first part of the paper the overview of existing theoretical knowledge is given. In the second part, the analyses of social construction of victim?s blame in the case of criminal procedure for the assassination of Zoran Djindjic, the prime minister of Serbia, before and during the starting phase of the trial is done. Additionally, the impact that the entire social climate which accompany the trial can have on the victim?s family members as indirect victims is analyzed.
Zoran Kanduc: Onkraj zlocina in kazni (S one strane zlocina i kazni), Studentska zalozba, Ljubljana, 2003
Authors: Simeunovic-Patic Biljana
Published: November 2007

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SOS hotline for women victims of discrimination at the workplace
Authors: Dobrosavljevic-Grujic Ljiljana
Published: November 2007

SOS hotline for women victims of discrimination at the workplace offers free legal assistance to women, whenever their labor rights are endangered. If the dispute cannot be resolved peacefully by mediation between employer and employees, female lawyer skilled for the labor law starts up judicial proceedings. Some characteristic cases of discrimination of women from the practice of SOS telephone, such as dismissal from the work, physical violence and sexual blackmail, are presented in the paper.
New Macedonian legislation which improves the position of the injured party
Authors: Lazetic-Buzarovska Gordana
Published: November 2007

This article deals with newly adopted provisions in the Macedonian criminal legislation, that are affecting the position and status of injured party in the criminal procedure, with special attention to alternative measures as new criminal sanctions and new opportunities for realization of compensation request on time and in effective way. As author says, with extending the grounds for submitting compensation request the legislator have introduced provisions that contribute toward improving the position of the injured party during the criminal procedure and even after its termination. Beside already strengthened position of public prosecutor, there are new provisions regarding widening of possibilities for injured party when he is in the role of subsidiary prosecutor. Having in mind European countries? experiences regarding witness protection, Republic of Macedonia has created legislative framework for combating most difficult types of organized crime. However, practical implementation of newly adopted Law on witness protection depends a lot on successful establishment and functioning of authorities responsible for caring out witness protection Programs, providing enough financial resources and intensive and direct interstate co-operation. Hence, it is obvious that the legislative provisions are just the first step among necessary activities for accomplish witness protection programs.
Characteristics of peer violence in schools
Authors: Sinobad Sandra
Published: November 2007

In this paper the author analyses types and main characteristics of peer violence in schools as well as forms of their manifestation. The analysis refers to data about the prevalence of peer violence in schools in Serbia, and in particular to forms of peer violence within our country as well as in the world. The part of the text refers to characteristics of perpetrators and their victims as well as on consequences that spring up from long term exposure to violence. Finally, the article has been pointed out an importance of introducing intervention programs in schools, by which use peer violence could be significantly decreased.
Mobbing prevention and types of assistance to the victims
Authors: Kostelic-Martic Andreja
Published: November 2007

Mobbing - psychological abuse at workplace is a phenomenon perpetually existing in the work organizations. Exceedingly important is to detect mobbing in the work organizations before it educe wide and severe effects not only on the victim, but also on the work organization itself. In this article, the mobbing prevention at the level of work organization, health and legal system is discussed. The types of victim assistance are also addressed. Moreover, the author?s experience in working with mobbing victims at the Work Clinic in Milan, i.e. in the ?Center for prevention, diagnosis, treatment and rehabilitation of occupational maladjustment, is briefly described. .
Association joint action for truth and reconciliation: Activities in 2006 and plans for the future
Authors: Nikolic-Ristanovic Vesna , Bjelic Danijela
Published: November 2007

In this paper the detailed overview of 2006 activities of Association Joint action FOR truth and reconciliation, as well as main directions of its expected actions in 2007, is given. During 2006 the activities of the Association were primarily oriented toward its own development, including defining aims and basic values, as well as empowerment and mutual support of its members. The second part of activities was oriented to the public promotion of the idea of "third way" and the Association itself. Activities in 2006 included: activities oriented toward development of Association, development of resource center and research, activities in direction of increasing social visibility of Association, as well as activities oriented toward development of cooperation and promotion of "third way" in other parts of the former Yugoslavia. .
New solutions in the juvenile criminal law in the light of the restorative justice
Authors: Jovasevic Dragan
Published: November 2007

New criminal legislation got into force in Serbia at the beginning of 2006. In that way, Serbia got unique Criminal Code which includes all provisions of material criminal law except provisions related to the criminal position of juveniles. System of criminal sanctions for juvenile off enders, procedure for their imposition and the way, procedure and terms for their execution are regulated by the provisions of the separate law - the Law on juvenile off enders and criminal protection of juveniles. Some of the most important novelties introduced by new juvenile criminal law are system of diversion, i.e. system of diversion orders, which aim at excluding the imposition of criminal sanctions in the cases when criminal sanction is not necessary from the perspective of crime suppression. Bearing that in mind, this paper is dedicated to forms of diversion orders as a form of measures that lead to more efficient system of restorative justice within our new juvenile criminal legislation. .
Pardon in the light of restorative justice
Authors: Miladinovic Dusica
Published: November 2007

The main aim of this paper is to consider pardon in the restorative justice context. Beginning from the basic standpoint that restorative justice imposes request for interests-balancing of different subjects connected by criminal act, the author tries to examine the articulation of the aforementioned standpoint through the pardon concept, accepted in domestic positive law. There is no doubt that the institute is designed in favour of the crime perpetrator, which is confirmed by the analysis of different legal effects produced by its content, while the victim- and society interests remained, at least, insufficiently protected. Therefore, the author points to some positive examples from comparative law and poses certain suggestions, that can be of use for eventual reforming of the institute, in order to achieve values of restorative justice. .
Victim support services in Serbia: Survey results
Authors: Copic Sanja
Published: November 2007

From September 1, 2006 to June 1, 2007, within the project "Development of victim support services in Serbia", Victimology Society of Serbia has conducted a survey on organizations in Serbia that are offering support to victims of crime. Aims of the survey were: to identify organizations that are supporting victims of crime either within state institutions and non-governmental organizations; to collect and analyze the data that might be useful for victims, and also to make directory of victim support services in Serbia. The sample encompassed 188 organizations from 55 towns in Serbia. The aim of this paper is point out, through the analysis of the data obtained through the survey, to which extent victims of crime in general, and of some forms of crime in particular can get support in Serbia, which organizations are offering support, what form of support and in which way. .
Victims and the criminal justice system in India: Need for a paradigm shift in the justice system
Authors: Srinivasan Murugesan , Eyre Mathew
Published: November 2007

Until 1970s the victims of crime were a forgotten entity in the criminal justice system. The attitude began to change as the discipline of victimology came into its own. The past few decades have witnessed a revolution in the way society deals with victims of crime. Many countries have now recognized the need to provide services to victims to help them recover from the effects of crime and assist them in their dealings with the criminal justice system. But in India, there has not been any significant improvement in the position of victims in the criminal justice system. The present paper has attempted to examine the position of victims of crime in India and the criminal justice system. The paper also emphasizes the need to provide assistance to crime victims. The authors of the present paper have also suggested some of the immediate steps that are to be implemented by the law enforcement agencies in India to improve the position of victims in the criminal justice system. .
The Acute and Subchronic Toxicity in Rats of Trans-1,2-Dichloroethylene in Drinking Water
Authors: Hayes J. R. , Condie L. W. , Egle J. L. , Borzelleca J. F.
Published: November 2007

Trans-1,2-dichloroethylene was administered either by gavage (acute studies) or in drinking water (subchronic studies) to male and female Sprague-Dawley derived Charles River rats. The acute oral LD50 was 7902 mg/kg for males and 9939 mg/kg for females. Decreased activity, ataxia, and depressed respiration preceded death. In the subchronic study, rats received theoretical daily doses of 500, 1500, and 3000 mg trans-1,2-dichloroethylene/kg body weight/day for 90 consecutive days. The actual daily doses were 402, 1314, and 3114 mg/kg for males and 353, 1257, and 2809 mg/kg for females. There were no compound-related deaths. There were no consistently significant compound-related dose-dependent adverse effects on any of the hematological, serological, or urinary parameters evaluated. There were dose-dependent increases in kidney weights and ratios in treated females. There were no compound-related gross or histological effects. No specific organ site toxicity could be identified in these studies. These data suggest that the toxicity from exposure to trans-1,2-dichloroethylene in drinking water apparently is low and probably does not constitute a serious health hazard.
Significance of Neoplastic and Nonneoplastic Changes in Female C3H/HeN-MTV—Mice Fed Diethylstilbestrol Continuously
Authors: Greenman D. L. , Sheldon W. , Highman B. , Amini S. , Norvell M. J.
Published: November 2007

Female C3H/HeN-MTV—mice were fed DES (0, 10, 40, 160, 640, or 1280 ppb) continuously. They were palpated weekly for mammary tumors and killed when masses reached a 1 cm diameter or at scheduled periods of 6, 12, 18, 24, or 30 months of exposure. Dead and moribund mice were examined histologically. In scheduled-sacrifice animals, mammary tumors were more prevalent than in controls at 640 and 1280 ppb. Time-to-removal with palpable tumors was reduced at and above 40 ppb. Pituitary adenomas, endometrial and cervical adenocarcinomas, and peritoneal mesotheliomas were more frequent and occurred earlier than in controls at 160 ppb or above. In scheduled-sacrifice animals fed 40 ppb, prevalences of several nonneoplastic findings were increased, including uterine grandular hyperplasia, cervical adenosis, splenic hypererythropoiesis, osseous trabecular proliferation, and mammary hyperplastic alveolar nodules. Corpora luteal depletion, pituitary cystoid degeneration, and sternal osteofibrosis were more prevalent at or above 160 ppb than in controls. Among mice removed at unscheduled periods, mammary tumors and nonneoplastic changes tended to be more frequent than in controls, even at 10 ppb DES. This study shows that exposure of mice to DES levels causing nonneoplastic alterations is also likely to increase neoplastic effects with time and suggests that any efficacious use of DES as a human drug increases the probability of cancer to an extent related to the drug-induced increase in estrogenic body burden.
Case History. Pheochromocytomas and Reserpine: Review of Carcinogenicity Bioassay
Authors: Diener R. M.
Published: November 2007

The results of the reserpine bioassay (DHHS Publication Nos. NIH 70-1749 and 80-1749) were published more than 7 years ago. Yet many of the controversies emanating from that bioassay remain unresolved. Uniform diagnostic criteria and terminology still are not applied consistently in rodent toxicity studies, and the word “pheochromocytoma” is still used in some of these studies despite the availability of more appropriate terminology. However, increased incidences of rat adrenal medullary tumors now have been observed with a wide variety of pharmacologically unrelated and diverse agents. An analysis of these data make it evident that the proliferative lesions in the aged rat adrenal medulla are of no carcinogenic relevance to man.
Oncogenic Evaluation of 3,3′-Dimethoxybenzidine Dihydrochloride in BALB/c Mice
Authors: Schieferstein G. J. , Sheldon W. G. , Allen R. R. , Greenman D. L. , Allaben W. T.
Published: November 2007

3,3′-Dimethoxybenzidine, a congener of the known carcinogen benzidine, is carcinogenic in the rat and possibly the hamster. This study was undertaken to assess carcinogenicity in an inbred mouse strain. Male and female (840 each) BALB/c mice were given 0, 20, 40, 80, 160, 315, or 630 ppm of 3,3′-dimethoxybenzidine dihydrochloride in their drinking water. At the serial sacrifices (13, 26, 39, 52, 78, or 112 weeks on dose), detailed necropsies and histopathologic examinations were performed. There was a decrease in water consumption at the 630 ppm dose level. Compared with controls, the 630 ppm dose produced a decrease in body weight gain of 10.7 and 13.3% in males and females, respectively, at 48 to 52 weeks on test. These weight decrements may be related to low water palatability at the 630 ppm dose level and may not reflect toxicity induced by 3,3′-dimethoxybenzidine itself. There was no treatment-related effect upon mortality or pathology. In summary, 3,3′-dimethoxybenzidine dihydrochloride was not carcinogenic in the mouse in the current investigation.
Developmental Toxicology Assessment of 1-Octanol, 1-Nonanol, and 1-Decanol Administered by Inhalation to Rats
Authors: Nelson B. K. , Brightwell W. S. , Khan A. , Krieg E. F. , Hoberman A. M.
Published: November 2007

As part of a large study evaluating the developmental toxicology of industrial alcohols administered by inhalation, groups of approximately 15 pregnant female Sprague-Dawley rats were exposed for 7 h/day on gestation days 1-19 (sperm = 0) to one of three long-chain alcohols at the maximum concentrations that could be generated as a vapor. These concentrations were 400 mg/m3 1-octanol, 150 mg/m3 1-nonanol, and 100 mg/m3 1-decanol. Dams were weighed daily for the first week of exposure, and weekly thereafter. On gestation day 20, rats were sacrificed. Fetuses were serially removed, blotted dry, examined for external malformations, sexed, weighed, placed in appropriate fixatives, and subsequently examined for visceral or skeletal abnormalities. No treatment-related effects were observed in pregnant females, frequency of resorptions, fetal weights, or skeletal/visceral malformations. Thus, long-chain alcohols at these vapor concentrations appear not to be toxic as evidenced by these fetal and maternal parameters.
GLP Studies: Special Considerations for Auditing/Inspecting in an Academic Environment
Authors: Goeke Jane E.
Published: November 2007

This presentation provides information to the quality assurance professional that will enable him or her to conduct GLP audits/inspections in an academic environment that are efficient and constructive. This includes information about academic self-perceptions, academic organizational structure, academic organizational practices, and academic research formats. GLP audits/inspections conducted in academic toxicology laboratories are not merely inconveniences to be tolerated, but useful tools, especially if the GLP auditor/inspector is used as an educator and resource.
The Impact of the FDA GMP Regulation
Authors: Borghese Robert N.
Published: November 2007

The impact of the Food and Drug Administration's Good Manufacturing Practice Regulation for Medical Devices is explored ten years after its promulgation. The main purpose of the regulation was never to be specific and exacting in interpretation, but rather to serve as a framework for the development of individualized quality assurance programs. The manufacturer is ultimatelly responsible for implementation. The role of the quality assurance professional is to be a persuasive advocator of compliance. Issues which were emphasized in the past are noted. What we can expect in the future is explored.
Model Selection in Toxicology: Principles and Practice
Authors: Gad Shayne C.
Published: November 2007

The key assumptions underlying modern toxicology are that (1) animals can serve as accurate predictive models of toxicity in humans, (2) that selection of an appropriate model to use is the key to accurate prediction in humans, and (3) that understanding the strengths and weaknesses of any particular model is essential to understanding the relevance of specific findings to humans. It must first be made clear, however, that the term model encompasses more than a test organism. Then the basic principles underlying these assumptions and the general limitations of models (both in vivo and in vitro) can be critically examined. The actual practice of model selection and why it deviates from the generally accepted principles are overviewed, along with the issue of errors induced by the “high-class model” problem. Historical results as to the accuracy of prediction of human effects are summarized. Finally, the reasons that models fail to predict effects in humans in some cases are examined, along with methods and problems in cross-species extrapolation and the issue of species peculiarities.
New Technologies for Use in Toxicology Studies: Monitoring the Effects of Xenobiotics on Immune Function
Authors: Robinson J. Paul , Pfeifer R.W.
Published: November 2007

New developments in flow cytometry are now being applied in toxicology studies. There are several reasons for using this technology. First, techniques are well characterized to measure functional parameters of single cells. Such measurements can be directly related to perturbations by xenobiotics, cell-mediated immune responses, or trauma. Second, there is a clear indication for movement toward in vitro systems as highly objective assessments of toxicologic interactions. By measuring specific cell functions at the single cell level, it is possible to define a range of normal responses. More importantly, a multiparametric analysis can be performed with flow cytometry and parameters can be directly related to one another. Furthermore, kinetic measurements can be made, providing vital clues to the mechanisms of actions of drugs or chemicals on functions of specific cell populations. Major advantages of this approach are that studies can be performed on very small volumes of blood, body fluid, or cell culture lines and it is not necessary to isolate pure populations of cells to perform these assays. We believe that this alternative approach in toxicology will provide valuable information unobtainable by traditional means.
Developmental Toxicity Evaluation of Several Cosmetic Ingredients in the Hydra Assay
Authors: Newman L.M. , Giacobbe R.L. , Fu L-J. , Johnson E.M.
Published: November 2007

The developmental toxicity hazard potential of six cosmetic products was determined in the in vitro Hydra assay. These studies were conducted to supplement available toxicological information and provide an indication of the priority of these compounds for higher level (in vivo) developmental toxicity testing. All but one ingredient, potassium sorbate, was predicted by the assay to be generally equally or more toxic to adults than to embryos and, therefore, to be low-priority chemicals for more elaborate tests. In contrast, assay results suggest that potassium sorbate is a prime candidate for higher-level animal developmental toxicology testing. The endpoints for this in vitro prescreen were ‘set’ some years ago to avoid false negatives as much as possible, but approximately 7% false positives result. Therefore, it is premature to consider sorbate as being uniquely hazardous to in utero development until this is established by testing in pregnant laboratory mammals.
Developmental Toxicity Study of Orally Administered Lithium Hypochlorite in Rats
Authors: Hoberman Alan M. , Deprospo John R. , Lochry Elizabeth A. , Christian Mildred S.
Published: November 2007

The purpose of this study was to examine the developmental toxicity of lithium hypochlorite in Sprague-Dawley rats. Groups of 25 pregnant rats received lithium hypochlorite at dosages of 0 (vehicle-reverse osmosis deionized water), 10, 50, 100, or 500 mg/kg/day, via oral gavage once daily on days 6 through 15 of gestation. The test solution was not adjusted for ion concentration. All dosages were given at a volume of 10 m/kg per day, adjusted daily for body weight. The rats were given RO deionized water for drinking, to prevent ingestation of chlorine or any other ions except those provided by the test substance. Clinical signs, body weight, and feed consumption were recorded daily during the dosage and postdosage periods. Caesarean-sectioning of the rats occurred on day 20 of gestation. Evaluations were made for pregnancy, number and placement of implantations, early and late resorptions, fetal viability, and number of corpora lutea. Fetuses were subsequently examined for gender, body weight, and gross external, soft tissue, and skeletal alterations. Significant (p ≤ 0.05 to p ≤ 0.01) maternal toxicity was observed in the 500 mg/kg per day dosage group, which included maternal death, clinical signs, gross necropsy findings, and inhibited maternal body weight gain and feed consumption. These effects were consistent with those expected from chlorine toxicity. The only effects of this dosage on embryo-fetal development were small reversible delays in growth (decreased fetal body weight, wavy ribs and delayed ossification of the thoracic vertebrae (bifid centra), forepaw and hindpaw phalanges, and metatarsal and metacarpal bones). Average values for corpora lutea, implantation sites, litter sizes, live and dead fetuses, and resorptions were comparable in the five dosage groups andlor were within the range observed historically. On the basis of these data, both the maternal no-observable-adverse-effect level (NOAEL) and the developmental NOAEL for lithium hypochlorite were 100 mg/kg per day. These data are in agreement with other studies and demonstrate that developmental toxicity of lithium hypochlorite does not occur in the absence of overt maternal toxicity.
Measurement of Respiration and Respiratory Responses During Inhalation Exposures
Authors: Mauderly Joe L.
Published: November 2007

This report reviews approaches for making measurements of the respiration of subjects during inhalation exposures. Respiration is measured to quantitate the volume of exposure material inhaled, to evaluate the normalcy and steadiness of respiration during exposure, to relate breathing pattern to deposition or uptake of inhaled materials, to detect physiological responses to inhaled materials, and to monitor respiration during controlled breathing. A small number of basic devices are commonly used during exposures, including nonrebreathing valves, pneumotachographs, spirometers, and plethysmographs. Less frequently used devices adaptable for use during exposures include hot wire anemometers, respiratory-inductive plethysmographs, and impedance pneumographs. These devices, some of their potential uses, and their advantages and disadvantages are described and useful references are given. Several useful combinations of respiratory measurement devices are suggested for low-volume, bag-to-bag, and immersion exposure systems.
Modernization of Nose-Only Smoking Machines for Use in Animal Inhalation Studies
Authors: Ayres P.H. , Mosberg A.T. , Coggins C.R.E.
Published: November 2007

Several modifications to a continuous-smoking inhalation machine for exposing animals to cigarette smoke are described. The improvements to the original machine provide a much more efficient method of exposing animals to cigarette smoke, and improve substantially the simplicity of operation and maintenance. The changes include a simplified pump for extracting puffs from the cigarettes, computerized control and display of exposure conditions, improved structure of the cigarette holders, and addition of a second puffing port to allow preignition of the cigarettes. The modifications were part of an overall modernization of the original design, as well as to allow the use of cigarettes which do not decrease in length as they are smoked (cigarettes which heat rather than burn tobacco).
Triethylene Glycol Ethers: Evaluations of In Vitro Absorption Through Human Epidermis, 21-Day Dermal Toxicity in Rabbits, and a Developmental Toxicity Screen in Rats
Authors: Leber A. Philip , Scott R.C. , Hodge M.C.E. , Johnson D. , Krasavage W.J.
Published: November 2007

The methyl, ethyl, and butyl ethers of triethylene glycol (TM, TE, and TB, respectively) were evaluated in three screening studies to assess their potential hazards to humans. The assessments included (1) an in vitro procedure to determine the ability of the materials to penetrate human skin, (2) a 21-day dermal limit test in rabbits to determine potential systemic toxicities, and (3) a screening procedure to evaluate the chemicals' potentials to induce developmental toxicity. In the in vitro dermal absorption procedure, the three test materials crossed human epidermis at molar rates 170-330 times more slowly than the lower molecular weight homolog ethylene glycol methyl ether (EM), a chemical known to induce systemic effects following skin application. In the 21-day dermal study, daily applications of 1000 mg/kg TM, TE, or TB did not produce systemic toxicity in male or female rabbits, including hematologic or testicular effects. The low dermal penetration rate of the triethylene glycol ethers may have played a role in this outcome. In the developmental toxicity screening test, oral doses of 1000 mg/kg given on Days 6-15 of gestation did not produce maternal toxicity in rats and had no effect on viability or growth of offspring, pre-or postnatally, indicating low developmental toxic potential for these compounds. The results of these studies indicate that triethylene glycol methyl, ethyl, and butyl ethers have very low capacities to be absorbed through the skin of exposed individuals, low potentials to produce systemic toxicity following oral or dermal exposures, and do not appear to be selectively toxic to the developing conceptus. The data clearly indicate that triethylene glycol ethers do not exhibit toxicologic profiles comparable to those of the methyl and ethyl ethers of ethylene glycol.
Fourteen-and Ninety-Day Oral Toxicity Studies of Methyl Tertiary-Butyl Ether in Sprague-Dawley Rats
Authors: Robinson M. , Bruner R.H. , Olson G.R.
Published: November 2007

Male and female Sprague-Dawley rats were gavaged with methyl tertiary-butyl ether (MtBE) for 14 or 90 days to evaluate subacute and subchronic toxicity. Five daily dose levels ranged from 0 to 1428 mg/kg body weight for the 14 day study and 0 to 1200 mg/kg body weight for the 90-day exposure. Controls received the corn oil vehicle. At or above dose levels of 1200 mg/kg, MtBE-induced anesthesia lasted about 2 h, followed by uneventful recovery. Diarrhea was common in all treatment groups, but no deaths were attributed to MtBE toxicity. In the subacute study, lung weights were reduced in high-dose females. Trends in the 14-day exposure also included increased cholesterol in both females and males and decreased blood-urea nitrogen (BUN) and creatinine in females. In the 90-day study, females exhibited elevated cholesterol and decreased BUN, while creatinine was decreased in high-dose males. Microscopic findings in most organs were unremarkable, except for high-dose males where renal changes were compatible with alpha 2-globulin nephropathy and were considered to have little toxicologic significance for humans. Both studies indicated that dose levels below those which induce anesthesia (1200 mg/kg) do not result in significant pathophysiologic changes.
Precision-Cut Rat Liver Slices in Dynamic Organ Culture for Structure-Toxicity Studies
Authors: Brendel Klaus , Fisher Robyn L. , Krumdieck Carlos L. , Gandolfi A. Jay
Published: November 2007

We describe a novel in vitro mammalian liver system, which simplifies both metabolism and hepatotoxicity studies in a multitude of species. This system is based on mechanical cutting of slices with high precision and culture of such slices under dynamic organ culture conditions. This system permits study of intoxication or metabolism for many hours to days and is suitable for integrative biochemical assays as well as histological and morphological evaluation. We report the toxicity exhibited by the isomeric dichlorobenzenes, which in Sprague-Dawley rat liver slices is M>O>P. We also compared a series of bromobenzene analogs, which in Sprague-Dawley rat liver slices are toxic in the following sequence DBB > BB > BBN > BA > BBT > BT. The toxicity of medium chain length branched-chain fatty acids related to valproic acid also was evaluated in this system. Results show that toxicity increased with chain length in α-methyl fatty acids and depended on the location of the carboxyl group in branched-chain octanoic acids. These examples serve to illustrate the utility of precision-cut rat liver slices in dynamic organ culture for structure—toxicity studies.
Repeated-Dose and Subchronic Toxicity Studies of 2,2,2-Trichloroethanol in Sprague-Dawley Rats
Authors: Bercz J. Peter , Robinson Merrel , Garner Lucille M. , Page Norbert P. , Olson Greg R.
Published: November 2007

Male and female Sprague-Dawley rats were administered 2,2,2-trichloroethanol (TCE) by gavage for 14 or 90 consecutive days. The gavage solution consisted of TCE dissolved in distilled water, containing 10% Emulphor. Doses of 37.5, 75, 150, and 300 mg/kg/day in the 14-day study and 40, 80, 160, and 320 mg/kg/day for the 90-day study were employed. Evaluation of clinical symptoms, clinical chemistry, and pathology examinations did not reveal a specific toxic effect or identify a target organ. In male rats an increase of red blood cells (RBCs) and hematocrit (Hct) in both 14- and 90-day studies, as well as increased hemoglobin (Hgb) in the 90-day study was observed at the highest dose level. In the high-dose females only increase of Hgb was seen in the 14-day study. These hematopoietic indices were not accompanied by commensurate changes in reticulocytes, mean corpuscular volumes or spleen weights. Serum lactic dehydrogenase (LDH) levels were increased in males at the two highest dose levels of both studies. Other changes in chemistries were sporadic in nature and did not appear to be dose related. Collectively, there was no basis to identify a target organ. The RBC and LDH levels did not correlate with other biochemical or pathology results and did not support the hypothesis that they represent a specific toxic effect. Based on the lack of detectable toxicity of TCE at the highest doses tested in rats, the following lowest observed adverse effect levels (LOAEL) were assigned for this chemical: in the 14-day exposure, 300 mg/kg/day for both sexes; in the 90-day protocol, 320 mg/kg/day for female; and 160 mg/kg/day for male rats.