A REPEATED-DOSE DERMAL TOXICITY STUDY OF HYDROPHOBICALLY MODIFIED HYDROXYPROPYL METHYLCELLULOSE IN RATS

• Published in: Journal of toxicological sciences 1997/08/10, Vol.22(3), pp.255-280
• Main Authors: OBARA, Sakae, MUTO, Hiroaki, ICHIKAWA, Naoto, TANAKA, Osamu, OTSUKA, Michio, KAWANABE, Mikiko, ISHII, Hiroyuki, NIIKURA, Yoshiyuki, KOMATSU, Masahiko
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Alanine Transaminase - blood; Animals; Aspartate Aminotransferases - blood; Biological and medical sciences; Blood Cell Count - drug effects; Body Weight - drug effects; Drug toxicity and drugs side effects treatment; Eating - drug effects; Female; Hypromellose Derivatives; Male; Medical sciences; Methylcellulose - administration & dosage; Methylcellulose - analogs & derivatives; Methylcellulose - toxicity; Pharmacology. Drug treatments; Rat; Rats; Rats, Sprague-Dawley; Time Factors; Toxicity: skin, dermoskeleton; Urinalysis
• ISSN: 0388-1350; 1880-3989
• DOI: 10.2131/jts.22.3_255

A six-month repeated-dose dermal toxicity study followed by a 30-day recovery test of hydrophobically modified hydroxypropyl methylcellulose (HM-HPMC), a new cellulose derivative used as a thickener for topical pharmaceuticals, was conducted using rats. Aqueous paste of HM-HPMC was applied to the skin of rats once daily at dose levels up to 60 mg/kg/day, which was the highest dose that could be administered. Items checked included general signs, urinalysis, hematology, ophthalmology, and histopathology. One rat died during the administration period owing to a malignant tumor in the hemopoietic system, which was not attributed to the test substance. Statistically significant differences were found in some test results, but those were not dose-dependent and were considered to be incidental or spontaneous. It was concluded that the test substance was not toxic upon chronic dermal administration at dose levels up to 60 mg/kg/day.