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

The animals in the 14-day and the 90-day study were observed daily for clinical evidence of ill health and given physical exams weekly corresponding to body weight determinations. The physical exam included observing for changes in skin, fur, eyes, and mucous membranes, occurrence of secretions and excretions and autonomic activity (e.g., lacrimation, piloerection, pupil size and unusual respiratory pattern). The exam also included changes in gait, posture, and response to handling, as well as the presence of clonic or tonic movements, stereotypies (e.g., excessive grooming, repetitive circling), or bizarre behavior (e.g., self-mutilation, walking backwards). All abnormal observations were recorded. Rats in the 90-day study (during week 12) received a Functional Observation Battery in an open field for excitability, autonomic function, gait and sensorimotor coordination (open field and manipulative evaluations), reactivity and sensitivity (elicited behavior) and other abnormal clinical signs including, but not limited to convulsions, tremors, unusual or bizarre behavior, emaciation, dehydration and general appearance. Additionally, during week 12 rats in the 90-day study underwent a Motor Activity Assessment using a Photobeam Activity System [San Diego Instruments, Inc (San Diego, CA)] following recommended procedures. Investigators doing the physical examinations, Functional Observation Battery, and Motor Activity Assessment were blind to the treatments the rats were receiving.