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Acute Toxicity Evaluation of Proliferol: A Dose-Escalating, Placebo-Controlled Study in RatsCAM Research Institute, Irvine, California, USA; Division of Orthopaedic Surgery and Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Canada
CAM Research Institute, Irvine, California, USA; U.S. Spine & Sport Foundation, San Diego, California, USA; and School of Physical Therapy and Rehabilitation Sciences, College of Medicine, University of South Florida, Tampa, Florida, USA
CAM Research Institute, Irvine, California, USA
Department of Neurology, University of California Irvine, Irvine, California, USA; Department of Epidemiology, University of California Los Angeles, Los Angeles, California, USA; Southern California University of Health Sciences, Whittier, California, USA
Consultant Toxicologist, Blue Bell, Pennsylvania, USA Correspondence: Address correspondence to Simon Dagenais, DC, PhD, CAM Research Institute, 27 Peters Canyon Road, Irvine, CA 92606, USA. E-mail:simon{at}camresearch.com Proliferol is an investigational new drug containing lidocaine hydrochloride 0.25%, dextrose 12.5%, glycerin 12.5%, and phenol 1.0% in aqueous solution. Despite extensive human experience with similar drugs administered by intraligamentous injection for chronic musculoskeletal disorders, little is known concerning preclinical toxicity. The purpose of this study was to assess the acute toxicity of intramuscular Proliferol in 96 (48 male, 48 female) Charles River strain rats, which were randomly assigned to low-(1x), medium- (5x), or high- (10x) dose Proliferol (derived from a human dose of 20 ml on a volume per bodyweight basis), or high-dose saline placebo. Observations included clinical observations, biochemistry, hematology, urinalysis, and full histopathology after 24 h or 14 days. There were no signs of ill health or reaction to treatment, and gait and body temperature were within normal limits. Biochemistry findings at 24 h included elevated aspartate aminotransferase, alanine aminotransferase, and haptoglobin; at 14 days all values were within normal ranges. Urinalysis findings at 24 h included increased urobilinogen and blood in all dose groups compared with placebo. Urine concentrations of phenol and lidocaine were greatest at 2 h and absent at 24 h. Histopathology findings included localized acute inflammatory soft tissue changes at the injection sites at 24 h and skeletal muscle regeneration at 14 days, which were consistent with the anticipated mechanism of action of Proliferol. There was no evidence of systemic toxicity from intramuscular injection of Proliferol in rats at up to 10x the human dose.
Key Words: Intraligamentous • Local Inflammation • Prolotherapy • Sclerosing Injections • Toxicity
International Journal of Toxicology, Vol. 26, No. 5,
451-463 (2007) This article has been cited by other articles:
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