Reproductive, Developmental and General Toxicity Study of 3'-Azido-3'-Deoxythymidine (CAS No. 30516-87-1) and Ethanol (CAS No. 64-17-5) Combinations in Swiss MiceReport Date: Feb. 1, 1994
The toxicity of AZT/ethanol combination therapy was assessed in Swiss mice. Oral doses of AZT (100, 200, 400 mg/kg/day) were given alone or in combination with ethanol (0, 10% in water). Male mice (10/group) were dosed from study day 5 until the day prior to sacrifice on study day 25 or 26. Prior to dosing (study days 0-4), the male mice were cohabited with a group of female mice (20/dose group), hereafter referred to as females (b). The sperm-positive female mice were dosed on days 6 through 15 of gestation and sacrificed on scheduled day 4 of lactation. A second group of female mice (20/dose group), hereafter referred to as females (a), were dosed from study day 0 throughout mating on study days 9 to 13 until sacrifice on day 18 of gestation. Adult mice were evaluated for clinical signs, body weight, water consumption, hematology, clinical chemistry parameters, gross necropsy, and histopathology evaluations of specified lesions, and offspring were evaluated for viability, external anomalies, and weight.
Administration of ethanol alone did not produce toxicity in male mice. The most significant alteration encountered in male mice treated with AZT alone consisted of a dose related anemia. Administration of combinations of ethanol and AZT to male mice did not exacerbate the-anemia produced by AZT alone.
Administration of ethanol alone did not produce measurable toxicity in female mice. The most significant alterations detected subsequent to the administration of AZT alone to female (a) mice were a mild anemia and leukopenia. Administration of AZT alone to female (b) mice resulted in only a mild decrease in RBC counts. AZT and ethanol administered together to female (a) and female (b) mice did not exacerbate the hematological toxicity of AZT administration alone.
In female mice, the 100 and 200 mg/kg/day dosages of AZT alone and in combination with 10% ethanol in the drinking water produced minimal if any maternal toxicity. The 400 mg/kg/day dosage of AZT produced both maternal and developmental toxicity. AZT appeared more toxic to the developing conceptus and pup than the adult animal. Dosages of 100, 200, and 400 mg of AZT/kg/day alone or with 10% ethanol in the drinking water produced developmental toxicity.
Ten percent ethanol in the drinking water alone did not produce any maternal or developmental toxicity and when administered in combination, AZT and ethanol did not increase either maternal or developmental toxicity.