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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Risk analysis 5 (1985), S. 0 
    ISSN: 1539-6924
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Risk analysis 16 (1996), S. 0 
    ISSN: 1539-6924
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: The decision-making process used by the National Toxicology Program (NTP) in its evaluation of long-term rodent carcinogenicity studies was investigated to determine whether or not this procedure resulted in an excessive number of false positive or false negative outcomes. All site-specific tumor incidences that were found to be significantly (p 〈 0.05) increased either by a trend test or by pairwise comparisons of each dosed group against the controls in 218 NTP 2-year studies with Fischer 344 rats and/or B6C3F1 mice were tabulated and compared to the number of statistically significant tumor increases expected to occur by chance. Our evaluation suggests that false positive rates are fairly low in NTP long-term studies. Assessing false negative rates is more difficult because of the limited sensitivity of the bioassay for detecting subtle carcinogenic effects. Moreover, reduced body weights frequently occur in dosed animals, and the positive correlation between the incidences of certain site-specific tumors and body weight may mask the detection of carcinogenic effects. Despite these difficulties, our analysis did identify one tumor showing evidence of false negative outcomes: interstitial cell tumors of the testis in male Fischer 344 (F344) rats. This tumor showed considerably more significant (p 〉 0.05) increased incidences than expected by chance, yet none were considered to be chemically-related. However, the biological significance of interstitial cell tumor increases in F344 rats is uncertain because of the high background rate of neoplasia (〉90%) for this target site.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 534 (1988), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 534 (1988), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0738
    Keywords: Doxorubicin ; Immature testes ; Puberty ; Spermatogenesis ; Leydig cell ; Sertoli cell ; Fertility ; ABP ; Sperm counts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The toxic effects of doxorubicin on the reproductive system of the male rat were studied at different susceptible stages of postnatal development. A multidisciplinary approach including the assessment of histopathological, functional and biochemical parameters was chosen. Groups of male rats were treated once with the compound (3 mg/kg) on postnatal day 6, 16, 24 or 45. Both the onset of reproductive capacity and fertility were determined by serially mating ten animals per group for 12 weeks beginning at the age of 45 days. Reproductive organ weights, sperm counts and epididymal androgen binding protein (ABP) were measured at intermediate (80-day-old rats) or terminal sacrifice (129-day-old rats). Age dependent differential doxorubicin toxicity was evident. Treatment of 6-day-old animals with doxorubicin severely impaired development of reproductive functions. Treatment of 16-dayold animals reduced fertility throughout the mating study, as well as body and reproductive organ weights and sperm counts. Initial toxicity was observed in the group treated at 24 days of age; particularly, low reproductive organ weights and low sperm counts were found. These findings proved reversible towards the end of the study. Neither biochemical nor functional impairment of the reproductive system could be observed in the group treated at 45 days of age.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Cancer and metastasis reviews 8 (1989), S. 1-21 
    ISSN: 1573-7233
    Keywords: benign neoplasms ; chemical carcinogenesis ; long-term studies ; National Toxicology Program
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recent carcinogenicity studies conducted and evaluated by the National Toxicology Program/National Institute of Environmental Health Sciences were examined to determine the frequency of chemically increased incidences of neoplasia. Many of the chemicals originally selected for study were chosen because of an a priori suggestion that they might be carcinogens. Of the 143 chemical studies evaluated, usually involving male and female rats and mice, 42 (29%) did not induce any neoplasms, 20 (14%) gave marginal or equivocal neoplastic responses, and 81 (57%) showed positive neoplastic responses in one or more of the 524 species-gender experiments. Of these 81 positive studies, 60 (74%) were considered positive based on malignant neoplasia, 16 (20%) were positive due primarily to benign neoplasia, but hd supporting evidence of malignant neoplasia in the same organ/tissue, and 5 (6%) were positive based only on benign neoplasia. These five chemicals are a) allyl isothiocyanate (transitional cell papillomas of the urinary bladder in male rats), b) 2-amino-4-nitrophenol (tubular cell adenomas of the kidney in male rats), c) asbestos intermediate range chrysotile (adenomatous polyps of the large intestine in male rats), d) decabromodiphenyl oxide (neoplastic nodules of the liver in male and female rats), and e) nitrofurazone (fibroadenomas of the mammary gland in female rats and benign mixed tumors and granulosa cell tumors of the ovary in female mice). For all but one of these lesions (mammary gland), the occurrence in historic controls is low. Thus, only 5 of the 143 chemicals studied (3.5%) induced benign neoplasia alone, and those observed benign neoplasms are known to progress to malignancy. Accordingly, we consider chemically induced benign neoplasia to be an important indicator of a chemical's carcinogenic potential in rodents, and believe it should continue to be made an integral part of the overall weight-of-the evidence evaluation process for identifying potential human health hazards.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Behavior genetics 2 (1972), S. 3-19 
    ISSN: 1573-3297
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Psychology
    Notes: Abstract Procedures are given, using sib pairs, for estimating linkage between a knownm-allele locus and a hypothesized two-allele locus that governs a quantitative trait. Random mating and linkage equilibrium are assumed. Also given are parametric and nonparametric methods for detecting linkage when the trait in question is governed by several two-allele loci, provided there is no epistasis.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Behavior genetics 1 (1970), S. 11-19 
    ISSN: 1573-3297
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Psychology
    Notes: Abstract Methods are presented for estimating genetic variance simultaneously from monozygotic and dizygotic twin data, care being taken to clarify the necessary underlying assumptions. Testing for the presence of genetic variance is also considered, by both parametric and non-parametric means.
    Type of Medium: Electronic Resource
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