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Hydrocortisone-induced embryotoxicity and embryonic drug disposition in H-2 congenic mice

Thesis/Dissertation ·
OSTI ID:6583866
Congenic mouse strains C57BL/10Sn (B10) and B10.A/SgSn(B10A), genetically different only at the H-2 complex, were compared for sensitivity to glucocorticoid-induced embryotoxicity and embryonic drug disposition. B10A mice dosed intramuscularly with 0, 100, 150 and 200 mg hydrocortisone/kg body weight on gestational day twelve, and B10 mice injected with 0, 200, 400, 600, and 800 mg/kg, were evaluated at dissection on gestational day eighteen for signs of toxicity. In both strains, probit analysis of cleft palate production demonstrated a linear dose response. The ED50 for cleft palate production demonstrates a linear dose response. The ED50 for cleft palate production in B10A mice was 143.6 mg/kg and 512.0 mg/kg for the B10 strain. Embryonic exposure was evaluated by administration of /sup 3/H-hydrocortisone (5 uCi/mouse) to pregnant mice on day twelve of gestation, at the ED50 for cleft palate production in B10A strain. The purposes of the experiment were to quantify the difference in susceptibility to steroid-induced cleft palate, determine if a milder manifestation of embryotoxicity, fetal growth retardation, occurred at sub-clefting dosages, and determine if the difference in sensitivity to hydrocortisone-induced embryotoxicity was the result of an underlying difference in embryonic exposure to the teratogen.
Research Organization:
California Univ., Davis (USA)
OSTI ID:
6583866
Country of Publication:
United States
Language:
English

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Related Subjects

550501 -- Metabolism-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADRENAL HORMONES
ANIMALS
BIOLOGICAL VARIABILITY
CORTICOSTEROIDS
DOSE-RESPONSE RELATIONSHIPS
EMBRYOS
GENETIC VARIABILITY
GLUCOCORTICOIDS
HORMONES
HYDROCORTISONE
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KETONES
LABELLED COMPOUNDS
MAMMALS
MICE
ORGANIC COMPOUNDS
PREGNANES
RODENTS
SENSITIVITY
STEROID HORMONES
STEROIDS
TERATOGENESIS
TOXICITY
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES