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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 56 (1984), S. 117-122 
    ISSN: 1432-0738
    Keywords: Rat ; Retinoids ; Bone alterations ; Adverse effects ; Arotinoid ethylsulfone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Repeated ingestion of high doses of retinoids cause the so-called hypervitaminosis A syndrome. In rats the main symptoms are weight loss, alopecia, erythema, desquamation of the skin, and alterations of the skeletal system, including bone fractures. In the present study, three retinoids (Ro 15-1570, arotinoid ethylsulfone, 6 mg/kg; retinoic acid, 100 mg/kg and etretinate, 50 mg/kg) were administered orally to rats for 1 and 2 weeks, respectively, to six male and six female rats/group. All the above changes were induced by all three retinoids, with the exception that the arotinoid ethylsulfone Ro 15-1570 did not cause bone alterations. The absence of toxic effects on the bones by Ro 15-1570 was confirmed by X-ray-film examinations, densitometry of the X-rayed femora and tibiae, examination of the thickness of the femoral and tibial compacta in histological slides plus the determination of the femoral ash weight and its main inorganic constituents (calcium, magnesium, sodium, and potassium). The present demonstration that the arotinoid ethylsulfone Ro 15-1570 was devoid of bone toxicity constitutes major progress in the pharmacologic development of retinoids with a better balance between therapeutic and adverse effects.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 59 (1986), S. 195-200 
    ISSN: 1432-0738
    Keywords: Recombinant DNA products ; Species-specific proteins ; Adverse effects ; Safety testing ; Human and animal toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Preclinical toxicity studies in animals with species-specific recombinant DNA products have now been performed for several years. An interim statement on the significance of these animal tests and their ability to predict adverse effects in humans therefore appears indicated, with the aim of deducing future testing strategies. The experience accumulated so far shows that the animal models have failed to predict adverse effects subsequently observed in man. Immunogenicity of these proteins further restricted the usefulness of standard toxicity tests. There is also increasing evidence that animal tests on the toxic potential of impurities contained in the products are markedly inferior in sensitivity to analytical and quality control methods. Thus, modified testing programs are proposed to demonstrate safety rather than target organ toxicity using rodents and small non-rodent species and restricted dosing; furthermore the study duration should be limited by the detection of immunogenic responses.
    Type of Medium: Electronic Resource
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