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Biomedical subjects

E R Adams

Publications and source records attributed to E R Adams.

10 recordsLinked to original sources
PubMed1992

Carcinogenicity studies of fluoxetine hydrochloride in rats and mice.

The antidepressant drug fluoxetine HCl was tested for carcinogenicity in three well designed and controlled studies in Fischer rats and C57BL/6 x C3H F1 mice. The compound was administered to the animals for 24 months at dietary doses of approximately 0, 0.5, 2.0, or 10.0 mg/kg body weight in rats and 1.0, 5.0, or 10.0 mg/kg in mice. The highest dose tested was a maximum tolerated dose for both species as evidenced by clinical signs (rats and mice) and some mortality (mice) referable to central nervous system pharmacological effects, decreased weight gain (rats), and histopathological changes of phospholipidosis (rats) and hepatic fatty change (mice). There was no evidence of an increased incidence of any type of unusual or commonly occurring spontaneous neoplasm in either rats or mice. There were statistically significant decreases in a few commonly occurring neoplasms. The data reported herein provide convincing evidence that fluoxetine is neither a complete carcinogen nor a tumor promoter.

Animals↗
PubMed1991

Oncogenicity study of trifluralin in B6C3F1 mice.

B6C3F1 mice were maintained for 24 months on diets containing 0, 563, 2250 or 4500 ppm trifluralin. These dietary concentrations corresponded to daily doses of approximately 70, 285 or 570 mg/kg body weight, respectively. The control group contained 120 mice/sex and treated groups consisted of 80 mice/sex. There were no treatment-related effects on the survival, appearance or behaviour of the mice. Survival at test termination was at least 67% in each group. Compared with controls, mean body weight was significantly reduced in a dose-related manner in mice of both sexes given the 2250 and 4500 ppm diets. At 21 months, the reduction in body weight was greater than or equal to 15 and greater than or equal to 30%, respectively. At study termination, dose-related decreases in erythrocytic and leucocytic values were also observed at dietary levels of 2250 and 4500 ppm. In clinical chemistry evaluations, blood urea nitrogen levels and alkaline phosphatase activity in mice of both sexes were significantly increased at trifluralin levels of 2250 and 4500 ppm. Blood urea nitrogen also showed a marginal increase in females given the low dose of trifluralin. Alanine aminotransferase activity was significantly increased in males at all treatment levels. Although there were a number of absolute and relative organ weight changes in all three treatment groups that were significantly different from the control values, the reduced relative kidney weights in males and the increased relative liver weights in both sexes at dietary levels of 2250 and 4500 ppm were the only changes that could be correlated with altered clinical chemistry values.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1989

Preclinical toxicology studies with nizatidine, a new H2-receptor antagonist: acute, subchronic, and chronic toxicity evaluations.

Nizatidine (NIZ), a new antiulcer drug, was evaluated for toxicity in acute, subchronic, and chronic tests. Acute toxicity studies were conducted in rats, mice, dogs, and monkeys. Median lethal doses (MLD) in rodents were greater than 1600, 230, and 1000 mg/kg by oral (po), iv, and sc administration, respectively. No deaths occurred in dogs given single doses of 800 mg/kg (po), 75 mg/kg (iv), or 225 mg/kg (im) or in monkeys given 1200 mg/kg (po) or 200 mg/kg (iv). Rats survived up to 1.0% dietary NIZ (daily intake ranging from 24 to 800 mg/kg/day) for 1 year. Slight decreases in body weight gain and increases in liver and kidney weights occurred. Slight decreases in erythrocytic parameters at 3 months were not present at 6 or 12 months. Mice survived up to 1.5% dietary NIZ for 3 months and effects were limited to slight decreases in body weight gain and increases in relative liver weight. Dogs survived oral doses up to 800 mg/kg/day for 3 months but had numerous clinical signs of toxicity and body weight loss. All dogs given oral NIZ doses up to 400 mg/kg/day survived except for one high-dose dog that was killed in a moribund condition following convulsions in the 41st week of treatment. Effects in dogs included miosis, body weight loss, increased thrombocyte counts, and decreased hepatic microsomal enzyme activity and P450 content. The increase in thrombocyte counts was unaccompanied by changes in thrombocyte function and did not reoccur in a subsequent study. A decrease in plasma testosterone in two of three surviving male dogs given 400 mg/kg/day for 1 year was unaccompanied by effects on the size or morphology of testes or prostate. Peak plasma levels of NIZ in all species tested were in excess of human plasma levels after therapeutic doses. In conclusion, there was no evidence of significant toxicity in organs or tissues including those sites (gastric mucosa, male sex organs, and liver) that have been affected by some agents of this therapeutic class.

Androgens↗
PubMed1987

One-dimensional and two-dimensional nuclear magnetic resonance studies of the reaction of phenyldichloroarsine with glutathione.

14C-labeled phenyldichloroarsine (PDA) enters the red blood cell and forms a 1:2 adduct with intracellular glutathione. Upon gel filtration of the hemolysate, [14C]PDA was recovered with the glutathione-containing fractions. One-dimensional and two-dimensional nuclear magnetic resonance spectroscopy were used to confirm the structure of the adduct and elucidate its stereochemistry, stability, and reactivity.

Arsenicals↗
PubMed1986

Studies to elucidate the mechanism of fenarimol-induced infertility in male rats.

Fenarimol (alpha-(2-chlorophenyl)-alpha-(4-chlorophenyl)-5- pyrimidinemethanol a pyrimidine carbinol fungicide, caused a dose-related decrease in male fertility in Wistar rats. The effect was particularly evident in the anatomically normal progeny of dams treated with fenarimol throughout gestation and lactation. Based on the observation that the infertility was associated with the absence of vaginal sperm at the time of mating, the effect appeared to be the result of an absence of male sexual behavior. Fenarimol does not readily cross the placenta but does concentrate in milk, reaching three- to fivefold higher concentrations than those observed in the maternal plasma. These results suggest that fenarimol might be acting to block the perinatal development of male patterns of sexual behavior which involves the action of gonadal steroids within the central nervous system (CNS). To test this hypothesis, [14C]fenarimol was administered to dams and the radioactivity measured in the brains of the neonates. Radioactivity in the hypothalamus was three- to fourfold higher and the half-life four times longer than that observed in the remainder of the brain. Since the hypothalamus is believed to play a key role in the development and expression of male sexual behavior, it appears likely that fenarimol is acting centrally to decrease male sexual behavior, thereby decreasing male fertility.

Administration, Oral↗
PubMedDate not supplied

Structure and dynamics of a lipoic acid-arsenical adduct.

The lipoic acid-phenyldichloroarsine adduct was prepared in methanol, and the structure and molecular motions of this adduct were studied. The results showed that a six-membered heteroatom adduct was formed. One-dimensional and two-dimensional NMR spectroscopy was used to confirm the structure and assign some of the resonances in the proton and carbon spectra. Spin-lattice relaxation times of the various carbon atoms indicated that the overall molecular reorientation time (tau R) of the molecule is 0.02 ns at 30 degrees C. An Arrhenius plot of the data showed that the activation energy (Ea) for molecular tumbling is 13.4 kJ/mol.

Arsenicals↗