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Male Sprague-Dawley rats were injected with either a single subcutaneous dose of 75 mg of secobarbital, or once daily injections of 20 mg of secobarbital for 7 days. Plasma was collected prior to treatment and 18 hours later (75 mg) or 8 and 15 days later (20 mg). Plasma was analyzed for the platelet count (PLT), prothrombin time (PT), fibrinogen (FIB), and coagulation factor activities for factors II, V, VII, IX, and X. Treatment with a single subcutaneous injection of 75 mg of secobarbital caused statistically significant alterations in every clotting activity measured whereas 7 days of treatment with 20 mg once daily resulted in only 2 clotting factors being abnormal. These two factors returned to pretreatment levels following 7 days of withdrawal of secobarbital. The data indicates that a single larger dose of secobarbital is more influential on hepatic synthesized clotting factor activity than is longer treatment with a lesser dose.

Female Sprague-Dawley rats were placed on a drinking solution of 1 ppm Diazinon or malathion dissolved in water for 6 months. At the conclusion of the experiment liver tissue and plasma were examined. Clotting studies included the prothrombin time (PT), partial thromboplastin time (APTT), fibrinogen, and factors II, V, VII, X, plus the platelet count. Hepatic morphology, basically hepatocyte degeneration, was altered by malathion while diazinon had no notable effect. Likewise, malathion prolonged both the PT and APTT, the only changes in clotting activity.

Adult male and female rats were subjected to gonadectomy by means of surgical removal of the gonads. In the male, castration resulted in a significant decrease in both body and liver weights compared to intact controls, which persisted for at least 3 weeks. Conversely, ovariectomy was associated with a significant enhancement in both growth rate and liver weight from intact controls. Castration of male rats resulted in induction of hepatic L-ADH (cytosolic alcohol dehydrogenase) and L-ALDH (cytosolic aldehyde dehydrogenase) as contrasted with inhibition of mitochondrial ALDH which was evident in the enzyme with the apparent high Km. Kinetic studies indicate that there was an increase in apparent Km of L-ADH, and hence reduced affinity to hepatic metabolism of ethanol as a consequence of castration in the male rat. This is compared with few changes occurring in the apparent Km value of L-ALDH. Ovariectomy did not alter endogenous L-ADH or L-ALDH. Short-term administration of a synthetic estrogenic steroid ethinyl estradiol, inhibited liver mitochondrial ALDH in the intact female rat but not in the ovariectomized female. Short-term administration of the same dose of an androgen, testosterone, did not alter specific activities of the liver enzymes measured in the intact or in the castrated male rat. Administration of both components of OCs (oral contraceptives) combined or the estrogen alone in behavioral experiments profoundly reduced ethanol drinking by voluntary intake of diluted ethanol solution by the intact female rat. These results suggest a hepatic-gonadal link may exist and that a toxic interaction between the OCs and alcohol drinking is definitely possible.