13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies to evaluate the carcinogenic potential of epinephrine have not been conducted.
Epinephrine and other catecholamines have been shown to have mutagenic potential in vitro. Epinephrine was positive in the Salmonella bacterial reverse mutation assay, positive in the mouse lymphoma assay, and negative in the in vivo micronucleus assay. Epinephrine is a mutagen based on the E. coli WP2 Mutoxitest bacterial reverse mutation assay.
The potential for epinephrine to impair reproductive performance has not been evaluated, but epinephrine has been shown to decrease implantation in female rabbits dosed subcutaneously with 1.2 mg/kg/day (15-fold the highest human intramuscular or subcutaneous daily dose) during gestation days 3 to 9.
13.2 Animal Toxicology and/or Pharmacology
Epinephrine was associated with metabolic effects, decreased mesentery, coronary and renal conductance in a sheep model of septic shock. Data from hemolysis study have shown that epinephrine at 1:1000 dilution is non-hemolytic. Epinephrine infusion significantly increased the MAP (69 vs. 86 mmHg) and cardiac output (6.4 vs. 7.1 L/min) and decreased renal blood flow (330 vs. 247 mL/min).