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Lack of Oncogenicity of Wood Creosote, the Principal Active Ingredient of Seirogan, an Herbal Antidiarrheal Medication, in Sprague-Dawley Rats

Taiko Pharmaceutical Company, Ltd., Suita, Osaka, Japan

Takashi Shibata

Taiko Pharmaceutical Company, Ltd., Suita, Osaka, Japan

Michael S. Willett

Advanced Biomedical Research, Inc., Pennington, New Jersey, USA

Patricia Turck

MPI Research, Inc., Mattawan, Michigan, USA

Karl A. Traul

Ingle and Traul Pharmaceutical Consulting, Inc., Princeton, New Jersey, USA

Seirogan, an herbal medicine containing wood creosote (tablets, 10.0% w/w), has been developed and marketed for almost a century in various countries for the control of acute diarrhea and treatment of associated symptoms, such as abdominal cramping. Wood creosote (CAS no. 8021–39–4) is a mixture of simple phenolic compounds, including guaiacol and creosol and related compounds, and is chemically distinct from, and should not be confused with, coal tar creosote, a known carcinogen. In the current study, the oncogenic potential of wood creosote was assessed in a 96/103-week oral gavage study in Sprague-Dawley rats. Groups of 60 rats/sex received wood creosote at dose levels of 20, 50, or 200 mg/kg body weight [bw]/day. An additional group of rats received the vehicle, 0.5% carboxymethylcellulose in deionized, distilled water, at the same dose volume as the treatment groups (10 ml/kg) and served as the controls. Treatment-related decreases in survival, body weight, and food consumption, as well as increased incidences of clinical signs that included rales, decreased activity, and salivation, were noted at 200 mg/kg bw/day when compared with the control group. There was an increased incidence of reddened and edematous lungs in rats from the 200 mg/kg bw/day group that died during the study. The lung findings were suggestive of test article aspiration during dose administration or agonal aspiration preceding and possibly resulting in death, especially because these observations were not seen in animals that survived to scheduled sacrifice. Additionally, phenols are generally recognized as having corrosive properties. There were no changes in clinical pathology and no increases in neoplastic or non-neoplastic lesions, excluding the lung findings, related to treatment with wood creosote at any dose level. Although the results of this study indicate that the maximum tolerated dose of wood creosote was met or exceeded at 200 mg/kg bw/day, there was no evidence of oncogenicity at any dose level. The lack of any evidence of oncogenicity supports the safety profile of the active ingredient in Seirogan, wood creosote.

Key Words: Antidiarrheal • Creosol • Guaiacol • Oncogenicity • Seirogan • Wood Creosote (CAS 8021–39–4)

International Journal of Toxicology, Vol. 20, No. 5, 297-305 (2001)
DOI: 10.1080/109158101753253036


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				T. Kuge, T. Shibata, and M. S. Willett Multiple-Dose Escalation, Safety, and Tolerability Study of Wood Creosote, the Principal Active Ingredient of Seirogan, an Herbal Antidiarrheal Medication, in Healthy Subjects J. Clin. Pharmacol., March 1, 2003; 43(3): 284 - 290. [Abstract] [Full Text] [PDF]