A repeated-dose dermal toxicity study of hydrophobically modified hydroxypropyl methylcellulose in rats.
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.
Obara
S
S
Specialty Chemicals Research Center, Shin-Etsu Chemical Co., Ltd., Niigata, Japan.
Muto
H
H
Ichikawa
N
N
Tanaka
O
O
Otsuka
M
M
Kawanabe
M
M
Ishii
H
H
Niikura
Y
Y
Komatsu
M
M
D000279:Administration, Cutaneous; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001772:Blood Cell Count / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D065347:Hypromellose Derivatives; D008297:Male; D008747:Methylcellulose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016482:Urinalysis
D065347:Hypromellose Derivatives; D008747:Methylcellulose; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase