Safety Assessment of a Hemp Extract using Genotoxicity and Oral Repeat-Dose Toxicity Studies in Sprague-Dawley Rats

Dziwenka, Margitta; Coppock, Robert; Alexander, McCorkle; Palumbo, Eddie; Ramirez, Carlos; Lermer, Stephen

A board-certified veterinary pathologist (DACVP) evaluated the tissues for histopathology. In the 14-day study, centrilobular hepatocellular hypertrophy (increased cell size) in Groups 3 (3/10) and 4 (5/ 10) was seen that correlated with an increase in liver weights. Adrenal cortical vacuolation was observed and was mild in all Group 4 animals, minimal to mild in 3/5 of the Group 3 males and 4/5 of the Group 3 females and minimal in 1/5 for the Group 2 males. For the 90-day study, test article related histopathology changes were limited to hepatocellular hypertrophy of centrilobular hepatocytes. This lesion was seen in the male and female animals in Groups 2 to 4. The hepatocellular hypertrophy was associated with dose-dependent increases in absolute liver weight for Group 2 to 4 females, liver-to-body weight ratios for Group 3 females, and liver-to-body/brain weight ratios for Group 4 females. Significant (p < 0.05) increase in liver-to-body weight ratios for Group 3 females and liver-to-body/brain weight ratios for Group 4 females were seen. The increases in liver weight and ratios correlated with the microscopic finding of hepatocellular hypertrophy at all dose levels. Non-significant (p > 0.05) dose-dependent increase in absolute liver weight was observed for Group 2-4 females. The centrilobular hepatocellular hypertrophy and increased liver weights were not seen in recovery groups at the end of the 28-day recovery period indicating the hepatocellular hypertrophy was reversible.