A subchronic toxicity study in rats and genotoxicity tests with an aqueous ethylcellulose dispersion.
Surelease Aqueous Ethylcellulose Dispersion is an excipient used as a modified release coating for beads, granules, non-pariels, drug crystals and tablets and for taste masking applications for drug products and dietary supplement products. A study was conducted to assess the toxicity of spray-dried Surelease when administered orally, via dietary admixture, to Sprague-Dawley CD rats (20/sex/group) at dose levels of 0, 2000, 3500, and 5000 mg/kg/day for a period of at least 3 months. After 3 months of treatment, all rats scheduled for terminal sacrifice were killed and selected organs were weighed. Complete macroscopic examinations and histopathological evaluation of selected tissues were conducted on all animals. Neuropathological evaluations were performed on 5 animals/sex/group. No mortality occurred during the study. Clinical observations, ophthalmology, body weight and food consumption, hematology, coagulation, clinical chemistry, urinalysis, functional observational assessments, motor activity, organ weights and ratios and macroscopic and microscopic observations did not reveal any significant, consistent, dose-dependent test article-related adverse effects. The NOAEL (no-observed-adverse-effect-level) is 5000 mg/kg/day, the highest dose tested. A series of genotoxicity tests were conducted with Surelease. Surelease showed no evidence of mutagenic activity in the bacterial reverse mutation test with and without metabolic activation and in the in vitro cell mutation assay under the experimental conditions employed. Surelease did not show any evidence of causing chromosome damage or bone marrow cell toxicity when administered by gavage in the mouse micronucleus in vivo test procedure. These findings support the safety of Surelease for use as an excipient.
DeMerlis
C C
CC
Colorcon, West Point, PA, USA. cdemerlis@colorcon.com
Schoneker
D R
DR
Borzelleca
J F
JF
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001777:Blood Coagulation / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002482:Cellulose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D002626:Chemistry, Pharmaceutical; D004032:Diet; D004435:Eating / Q000187:drug effects; D005079:Excipients / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D008223:Lymphoma / Q000473:pathology; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009422:Nervous System Diseases / Q000139:chemically induced / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
D005079:Excipients; D009153:Mutagens; C013517:ethyl cellulose; D002482:Cellulose