Potentiation of mortality by carbon tetrachloride during morphine pellet implantation in the mouse.
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Biomedical subjects
Publications and source records attributed to H M Mehendale.
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Hexachlorocyclopentadiene is eliminated from the body efficiently by urinary excretion. Although direct evidence is not available, it appears that expiration may be another important route of elimination. Of the administered dose 9% is excreted in the bile in 1 hr, approximately equal to the amount of fecal excretion in 7 days, suggesting enterohepatic circulation. After a single dose, HCPD decays from the blood biexponentially with a terminal phase half-life of 60 min. Of the tissues analyzed kidney, followed by liver, concentrate HCPD 1 hr or 7 days after exposure to any significant extent. Subcellularly, HCPD is predominantly associated with cytosol fractions of both kidney as well as liver, observations consistent with rapid elimination of HCPD after a single exposure. Preexposure to HCPD (50 mg/kg-day for 3 days) resulted in unaltered blood decay curves and biliary excretion, but increased the concentration in the kidneys after a single subsequent challenge.
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Female Sprague-Dawley rats (175-200 g) were maintained on a commercial powdered rat chow containing 0 or 10 ppm chlordecone (Kepone; CD). On day 15 of the dietary protocol, a single dose of CCl4 (5-100 microliters/kg) was administered i.p. in corn oil vehicle. Controls received corn oil vehicle only. Twenty-four hours after CCl4 administration, hepatotoxicity was assessed using biochemical, functional, and histopathological parameters. Serum enzymes (GPT, GOT, ICD and OCT) were elevated in a dose related manner in the animals receiving CD-CCl4 combination. CCl4 alone at the doses used had no marked effect. Centrilobular necrosis was observed in the animals receiving CD-CCl4 combination. Biliary excretion of phenolphthalein glucuronide (PG) and the rate of bile flow were decreased in a dose-dependent manner. Forty-eight hour LD50 of CCl4 was decreased 26-fold by CD pretreatment. These results indicate that CD potentiates CCl4 toxicity in female rats as well. Since the hepatic functional status is greatly compromised, the CD potentiated lethality is preceded by hepatic failure. Furthermore, female rats are sensitized to smaller doses of CCl4 in comparison to male rats.