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Teratogenic and Mutagenic Potential of Triethylenemelamine, Ethyl Methanesulfonate, and N-Ethyl-N-Nitrosourea for Causing Fetal Anomalies in Mus Musculus

Description: In five separate experiments, weight-adjusted doses of TEM, EMS, and ENU were injected intraperitoneally into twelve week-old female mice six hours after mating. On day seventeen of gestation, the females were sacrificed and their uterine contents were examined. The effect of each agent was determined by its ability to cause malformations and death to the developing embryos. All treatment groups showed statistically significant elevated levels of malformations in comparison to their corresponding control groups. The reproductive damage induced in these experiments cannot be singularly attributed to teratogenesis or mutagenesis but a combination of the two.
Date: December 1987
Creator: Gans, Murry J. (Murry Joe)
Partner: UNT Libraries

Gordon Research Conference on Genetic Toxicology

Description: Genetic toxicology represents a study of the genetic damage that a cell can incur, the agents that induce such damage, the damage response mechanisms available to cells and organisms, and the potential consequences of such damage. Genotoxic agents are abundant in the environment and are also induced endogenously. The consequences of such damage can include carcinogenesis and teratogenesis. An understanding of genetic toxicology is essential to carry out risk evaluations of the impact of genotoxic agents and to assess how individual genetic differences influence the response to genotoxic damage. In recent years, the importance of maintaining genomic stability has become increasingly recognized, in part by the realization that failure of the damage response mechanisms underlies many, if not all, cancer incidence. The importance of these mechanisms is also underscored by their remarkable conservation between species, allowing the study of simple organisms to provide significant input into our understanding of the underlying mechanisms. It has also become clear that the damage response mechanisms interface closely with other aspects of cellular metabolism including replication, transcription and cell cycle regulation. Moreover, defects in many of these mechanisms, as observed for example in ataxia telangiectasia patients, confer disorders with associated developmental abnormalities demonstrating their essential roles during growth and development. In short, while a decade ago, a study of the impact of DNA damage was seen as a compartmentalized area of cellular research, it is now appreciated to lie at the centre of an array of cellular responses of crucial importance to human health. Consequently, this has become a dynamic and rapidly advancing area of research. The Genetic Toxicology Gordon Research Conference is biannual with an evolving change in the emphasis of the meetings. From evaluating the nature of genotoxic chemicals, which lay at the centre of the early conferences, the emphasis has moved ...
Date: February 15, 2003
Creator: Jeggo, Project Director Penelope
Partner: UNT Libraries Government Documents Department

Statistical analysis of litter experiments in teratology

Description: Teratological data is binary response data (each fetus is either affected or not) in which the responses within a litter are usually not independent. As a result, the litter should be taken as the experimental unit. For each litter, its size, n, and the number of fetuses, x, possessing the effect of interest are recorded. The ratio p = x/n is then the basic data generated by the experiment. There are currently three general approaches to the analysis of teratological data: nonparametric, transformation followed by t-test or ANOVA, and parametric. The first two are currently in wide use by practitioners while the third is relatively new to the field. These first two also appear to possess comparable power levels while maintaining the nominal level of significance. When transformations are employed, care must be exercised to check that the transformed data has the required properties. Since the data is often highly asymmetric, there may be no transformation which renders the data nearly normal. The parametric procedures, including the beta-binomial model, offer the possibility of increased power.
Date: November 1, 1982
Creator: Williams, R. & Buschbom, R.L.
Partner: UNT Libraries Government Documents Department

2004 Annual Meeting - Genes, Mutations and Disease: The Environmental Connection

Description: The Meeting consisted of 9 Symposia, 4 Keynote Lectures, 3 Platform Sessions and 4 Poster Sessions. In addition there were Breakfast Meetings for Special Interest Groups designed to inform attendees about the latest advances in environmental mutagenesis research. Several of the topics to be covered at this broad meeting will be of interest to the Department of Energy, Office of Science. The relevance of this meeting to the DOE derives from the fact that low dose radiation may represent one of the most significant sources of human mutations that are attributable to the environment. The EMS membership, and those who attended the EMS Annual Meeting were interested in both chemical and radiation induced biological effects, such as cell death, mutation, teratogenesis, carcinogenesis and aging. These topics thate were presented at the 2004 EMS Annual meeting that were of clear interest to DOE include: human variation in cancer susceptibility, unusual mechanisms of mutation, germ and stem cell mutagenesis, recombination and the maintenance of genomic stability, multiple roles for DNA mismatch repair, DNA helicases, mutation, cancer and aging, Genome-wide transcriptional responses to environmental change, Telomeres and genomic stability: when ends don?t meet, systems biology approach to cell phenotypic decision processes, and the surprising biology of short RNAs. Poster and platform sessions addressed topics related to environmental mutagen exposure, DNA repair, mechanisms of mutagenesis, epidemiology, genomic and proteomics and bioinformatics. These sessions were designed to give student, postdocs and more junior scientists a chance to present their workl.
Date: August 23, 2004
Creator: Samson, Leona D.
Partner: UNT Libraries Government Documents Department

Toxicology and metabolism of nickel compounds: comprehensive report of overall activities during the three-year period from December 1, 1977 to November 30, 1980

Description: The main research accomplishments during the past three years are summarized. The principle areas of investigation are: 1. embryotoxicity, teratogenicity, and mutagenicity of nickel carbonyl; 2. metabolism, detoxification, and excretion of nickel compounds; 3. studies of nickel carcinogenesis; 4. nickel analysis in body fluids and tissues to monitor occupational exposures; 5. nephrotoxicity of nickel compounds; and 6. hematological effects of nickel compounds. (ACR)
Date: August 15, 1980
Creator: Sunderman, Jr, F W
Partner: UNT Libraries Government Documents Department

Biology Division progress report, June 1, 1980-July 31, 1982

Description: Highlights of progress for the period June 1980 through July 1982 are summarized. Discussions of projects are presented under the following headings: molecular and cellular sciences; cellular and comparative mutagenesis; mammalian genetics and teratology; toxicology; and carcinogenesis. In addition this report includes an outline of educational activities. Separate abstracts have been prepared for individual technical reports for inclusion in the Energy Data Base. (RJC)
Date: December 1, 1982
Partner: UNT Libraries Government Documents Department

Utilization of critical periods during development to study the effects of low levels of environmental agents

Description: Careful definition of critical periods in the development of selected characters can result in experimental systems that may be highly useful in studying risk at low levels of exposure. Three examples are presented. Epidemiological investigations can lose much of their value unless critical periods are known for the end points being studied.
Date: January 1, 1980
Creator: Russell, L.B.
Partner: UNT Libraries Government Documents Department

Inhalation developmental toxicology studies: Teratology study of acetone in mice and rats: Final report

Description: Acetone, an aliphatic ketone, is a ubiquitous industrial solvent and chemical intermediate; consequently, the opportunity for human exposure is high. The potential for acetone to cause developmental toxicity was assessed in Sprague-Dawley rats exposed to 0, 440, 2200, or 11000 ppm, and in Swiss (CD-1) mice exposed to 0, 440, 2200, and 6600 ppm acetone vapors, 6 h/day, 7 days/week. Each of the four treatment groups consisted of 10 virgin females (for comparison), and approx.32 positively mated rats or mice. Positively mated mice were exposed on days 6-17 of gestation (dg), and rats on 6-19 dg. The day of plug or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 46 refs., 6 figs., 27 tabs.
Date: November 1, 1988
Creator: Mast, T.J.; Evanoff, J.J.; Rommereim, R.L.; Stoney, K.H.; Weigel, R.J. & Westerberg, R.B.
Partner: UNT Libraries Government Documents Department

Bilogical effects of ionizing radiation: epidemiological surveys and laboratory animal experiments. Implications for risk evaluation and decision processes

Description: General background is given for an understanding of the potential health effects in populations exposed to low-level ionizing radiations. The discussion is within the framework of the scientific deliberations and controversies that arose during preparation of the current report of the committee on the biological effects of ionizing radiation of the National Academy of Science - National Research Council (1980 Beir-III Report). (ACR)
Date: April 1, 1981
Creator: Fabrikant, J.I.
Partner: UNT Libraries Government Documents Department

Mouse models for understanding human developmental anomalies

Description: The mouse experimental system presents an opportunity for studying the nature of the underlying mutagenic damage and the molecular pathogenesis of this class of anomalies by virtue of the accessibility of the zygote and its descendant blastomeres. Such studies could contribute to the understanding of the etiology of certain sporadic but common human malformations. The vulnerability of the zygotes to mutagens as demonstrated in the studies described in this report should be a major consideration in chemical safety evaluation. It raises questions regarding the danger to human zygotes when the mother is exposed to drugs and environmental chemicals.
Date: January 1, 1989
Creator: Generoso, W.M.
Partner: UNT Libraries Government Documents Department

Inhalation developmental toxicology studies: Teratology study of n-hexane in mice: Final report

Description: Gestational exposure to n-hexane resulted in an increase in the number of resorbed fetuses for exposure groups relative to the control group; however, the increases were not directly correlated to exposure concentration. The differences were statistically significant for the 200-ppM with respect to total intrauterine death (early plus late resorptions), and with respect to late resorptions for the 5000-ppM group. A small, but statistically significant, reduction in female (but not male) fetal body weight relative to the control group was observed at the 5000-ppM exposure level. There were no exposure-related increases in any individual fetal malformation or variation, nor was there any increase in the incidence of combined malformations or variations. Gestational exposure of CD-1 mice to n-hexane vapors appeared to cause a degree of concentration-related developmental toxicity in the absence of overt maternal toxicity, but the test material was not found to be teratogenic. This developmental toxicity was manifested as an increase in the number of resorptions per litter for all exposure levels, and as a decrease in the uterine: extra-gestational weight gain ratio at the 5000-ppM exposure level. Because of the significant increase in the number of resorptions at the 200-ppM exposure level, a no observable effect level (NOEL) for developmental toxicity was not established for exposure of mice to 200, 1000 or 5000-ppM n-hexane vapors. 21 refs., 3 figs., 9 tabs.
Date: May 1, 1988
Creator: Mast, T.J.; Decker, J.R.; Stoney, K.H.; Westerberg, R.B.; Evanoff, J.J.; Rommereim, R.L. et al.
Partner: UNT Libraries Government Documents Department

Development of critical life stage assays: Teratogenic effects of SRS effluent components on freshwater fish, gambusia

Description: The final report of the research carried out at Voorhees College contains a composite compilation of the last two years work. The data note variation in the number of young fish delivered per female vary markedly between several ponds on the SRS and of SRS ponds. The reasons for this are unknown at present. Initial research was carried out on the effects on the developing fish fetus of various substances that may have produced these variations. Further study is necessary to identify the factors that produce the observed alterations. 7 figs., 5 tabs.
Date: November 1, 1990
Creator: Guram, M.S.
Partner: UNT Libraries Government Documents Department

Inhalation developmental toxicology studies: Teratology study of 1,3-butadiene in mice: Final report

Description: Maternal toxicity, reproductive performance and developmental toxicology were evaluated in CD-1 mice following whole-body, inhalation exposures to 0, 40, 200 and 1000 ppM of 1,3-butadiene. The female mice, which had mated with unexposed males were exposed to the chemical for 6 hours/day on 6 through 15 dg and sacrificed on 18 dg. Maternal animals were weighed prior to mating and on 0, 6, 11 and 18 dg; the mice were observed for mortality, morbidity and signs of toxicity during exposure and examined for gross tissue abnormalities at necropsy. Live fetuses were weighed and subjected to external, visceral and skeletal examinations to detect growth retardation and morphologic anomalies. Significant concentration-related decreases were detected in a number of maternal body weight measures. There was a significant concentration-related depression of fetal body weights and placental weights. Body weights of male fetuses of all exposed groups were significantly lower than values for control fetuses; weights of female fetuses were significantly depressed in the mice exposed to 200 and 1000 ppM. In the 200- and 1000-ppM exposure groups, weights of placentas of male fetuses were significantly decreased, but placental weights of female fetuses were significantly affected only in litters exposed to the highest 1,3-butadiene concentration. This exposure regimen produced significant signs of maternal toxicity at concentrations of 200 and 1000 ppM 1,3-butadiene.
Date: November 1, 1987
Creator: Hackett, P.L.; Sikov, M.R.; Mast, T.J.; Brown, M.G.; Buschbom, R.L.; Clark, M.L. et al.
Partner: UNT Libraries Government Documents Department

Inhalation developmental toxicology studies: Teratology study of n-hexane in rats: Final report

Description: The straight chain hydrocarbon, n-hexane, is a volatile, ubiquitous solvent used in industrial, academic, and smaller commercial environments. The significant opportunity for women of child-bearing age to be exposed to this chemical prompted the undertaking of a study to assess the developmental toxicity of n-hexane in an animal model. Timed-pregnant (30 animals per group) and virgin (10 animals per group) Sprague-Dawley rats were exposed to 0 (filtered air), 200, 1000, and 5000 ppM n-hexane (99.9% purity) vapor in inhalation chambers for 20 h/day for a period of 14 consecutive days. Sperm-positive females were exposed for 6 to 19 days of gestation (dg) and virgins were exposed concurrently for 14 consecutive days. The day of sperm detection was designated as 0 dg for mated females. Adult female body weights were monitored prior to, throughout the exposure period, and at sacrifice. Uterine, placental, and fetal body weights were obtained for gravid females at sacrifice. Implants were enumerated and their status recorded as live fetus, early or late resorption, or dead. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 16 refs., 3 figs., 7 tabs.
Date: December 1, 1987
Creator: Mast, T.J.
Partner: UNT Libraries Government Documents Department

Inhalation developmental toxicology studies of 1,3-butadiene in the rat: Final report

Description: Maternal toxicity, reproductive performance and developmental toxicology were evaluated in Sprague-Dawley-derived rats during and following 6 hours/day, whole-body, inhalation exposures to 0, 40, 200, and 1000 ppM of 1,3-butadiene. The female rats (Ns = 24 to 28), which had mated with unexposed males, were exposed to the chemical from 6 through 15 dg and sacrificed on 20 dg. Maternal animals were weighed prior to mating and on 0, 6, 11, 16 and 20 dg; the rats were observed for mortality, morbidity and signs of toxicity during exposure and examined for gross tissue abnormalities at necropsy. Live fetuses were weighed and subjected to external, visceral and skeletal examinations to detect growth retardation and morphologic anomalies. There were no significant differences among treatment groups in maternal body weights or extragestational weights of rats exposed to 1,3-butadiene concentrations of 40 or 200 ppM, but, in animals exposed to 1000 ppM, significantly depressed body weight gains were observed during the first 5 days of exposure and extragestational weight gains tended to be lower than control values. These results, and the absence of clinical signs of toxicity, were considered to indicate that there was no maternal toxicity at exposure levels of 200 ppM or lower. The percentage of pregnant animals and the number of litters with live fetuses were unaffected by treatment. Under the conditions of this exposure regimen, there was no evidence for a teratogenic response to 1,3-butadiene exposure.
Date: November 1, 1987
Creator: Hackett, P.L.; Sikov, M.R.; Mast, T.J.; Brown, M.G.; Buschbom, R.L.; Clark, M.L. et al.
Partner: UNT Libraries Government Documents Department

Inhalation developmental toxicology studies: Teratology study of methyl ethyl ketone in mice: Final report

Description: Methyl ethyl ketone (MEK) is a widely used industrial solvent which results in considerable human exposure. In order to assess the potential for MEK to cause developmental toxicity in rodents, four groups of Swiss (CD-1) mice were exposed to 0, 400, 1000 or 3000 ppM MEK vapors, 7 h/day, 7 dy/wk. Ten virgin females and approx.30 plug-positive females per group were exposed concurrently for 10 consecutive days (6--15 dg for mated mice). Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice on 18 dg. Uterine implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. Exposure of pregnant mice to these concentrations of MEK did not result in apparent maternal toxicity, although there was a slight, treatment-correlated increase in liver to body weight ratios which was significant for the 3000-ppM group. Mild developmental toxicity was evident at 3000-ppM as a reduction in mean fetal body weight. This reduction was statistically significant for the males only, although the relative decrease in mean fetal body weight was the same for both sexes. 17 refs., 4 figs., 10 tabs.
Date: February 1, 1989
Creator: Mast, T.J.; Dill, J.A.; Evanoff, J.J.; Rommereim, R.L.; Weigel, R.J. & Westerberg, R.B.
Partner: UNT Libraries Government Documents Department

Inhalation developmental toxicology studies: Teratology study of isoprene in mice and rats: Final report

Description: Isoprene, a reactive, branched diene, is used in large quantities in the manufacture of polyisoprene and as a copolymer in the synthesis of butyl rubber. The potential for isoprene to cause developmental toxicity was assessed in rodents, by exposing four groups each of Sprague-Dawley rats and Swiss (CD-1) mice to 0, 280, 1400, or 7000 ppM isoprene vapors, 6 h/day, 7 day/wk. Each treatment group consisted of 10 virgin females (for comparison), and approx.30 positively mated rats or mice. Positively mated mice were exposed on days 6-17 of gestation (dg), and rats on 6-19 dg. The day of plug or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 31 refs., 6 figs., 19 tabs.
Date: January 1, 1989
Creator: Mast, T.J.; Evanoff, J.J.; Stoney, K.H.; Westerberg, R.B.; Rommereim, R.L. & Weigel, R.J.
Partner: UNT Libraries Government Documents Department

Embryo culture in teratological surveillance and serum proteins in development. Progress report, 1978-1979

Description: Two initial studies on the use of cultured rat embryos for teratological surveillance have been completed using cadmium and cyclophosphamide teratogens. It was found that rat embryos could be cultured successfully on human serum supplemented with glucose, allowing testing to extend to human subjects. Tests using energy-related fuel substances (petroleum crude; shale oil; two coal-derived oils) implied possible long-term growth-inhibition effects for petroleum and coal but not for shale oil which was only shown to be teratogenic. (PCS)
Date: January 1, 1979
Creator: Klein, N.W.
Partner: UNT Libraries Government Documents Department

Solvent-refined-coal (SRC) process: health programs. Research and development report No. 53, Interim report No. 39. Volume III. Pilot plant development work. Part 4: Industrial hygiene, clinical and toxicological programs. Final report of subcontract No. 10, June 1, 1976-June 9, 1978

Description: This report summarizes the toxicological studies on SRC-I materials completed under Subcontract No. 10 as part of the Health Programs under the Solvent Refined Coal (SRC) Process Contract during the total period of the subcontract, June 1, 1976 through June 9, 1978. The studies were conducted by Industrial Bio-Test Laboratories (IBT) as the subcontractor. A number of acute studies were completed on the products and intermediate streams as well as several subchronic studies. In addition, preliminary dose-ranging, or pilot, studies were completed. None of the materials exhibited high toxicities when administered orally, dermally, or by the inhalation route. Three of the materials proved to be severely or extremely irritating to the eyes. The pilot dermal and teratogenesis studies revealed some evidence of decreased viability in offspring and reduced fetal body weights. The subcontract was terminated for convenience on June 9, 1978 when it became apparent that IBT could not satisfactorily continue the studies.
Date: November 1, 1981
Partner: UNT Libraries Government Documents Department

BEIR-III report and the health effects of low-level radiation

Description: The present BEIR-III Committee has not highlighted any controversy over the health effects of low-level radiation. In its evaluation of the experimental data and epidemiological surveys, the Committee has carefully reviewed and assessed the value of all the available scientific evidence for estimating numerical risk coefficients for the health hazards to human populations exposed to low levels of ionizing radiation. Responsible public awareness of the possible health effects of ionizing radiations from medical and industrial radiation exposure, centers on three important matters of societal concern: (1) to place into perspective the extent of harm to the health of man and his descendants to be expected in the present and in the future from those societal activities involving ionizing radiation; (2) to develop quantitative indices of harm based on dose-effect relationships; such indices could then be used with prudent caution to introduce concepts of the regulation of population doses on the basis of somatic and genetic risks; and (3) to identify the magnitude and extent of radiation activities which could cause harm, to assess their relative significance, and to provide a framework for recommendations on how to reduce unnecessary radiation exposure to human populations. The main difference of the BEIR Committee Report is not so much from new data or new interpretations of existing data, but rather from a philosophical approach and appraisal of existing and future radiation protection resulting from an atmosphere of constantly changing societal conditions and public attitudes. (PCS)
Date: January 1, 1980
Creator: Fabrikant, J.I.
Partner: UNT Libraries Government Documents Department