14-day repeat-dose oral toxicity evaluation of oxazyme in rats and dogs.
Oxazyme (OC4) is an orally administered formulation that has as an active component a recombinant mutant form of Bacillus subtilis oxalate decarboxylase (OxDC) enzyme C383S, designed to degrade dietary oxalate in the stomach. Fourteen-day repeat-dose studies were conducted in rats and dogs to evaluate toxicity and determine a no observed adverse effect level (NOAEL). Animals were administered OC4 by oral gavage twice daily for 14 consecutive days. Reversibility, progression, and delayed appearance of any observed changes were evaluated in a subset of animals that underwent a recovery of 7 days following 14 days of control or test-article. There were no test-article-related adverse effects or deaths in either species. Results indicate that the NOAEL under the conditions used in the studies was 720.8 mg/kg/d in rats and 187.2 mg/kg/d in dogs, the high dose tested in each species.
Cowley
Aaron B
AB
Captozyme LLC, Gainesville, FL, USA.
Poage
Duane W
DW
Dean
Robin R
RR
Meschter
Carol L
CL
Ghoddusi
Majid
M
Li
Qing-Shan
QS
Sidhu
Harmeet
H
D000284:Administration, Oral; D000818:Animals; D001774:Blood Chemical Analysis; D002262:Carboxy-Lyases / Q000008:administration & dosage / Q000633:toxicity*; D004285:Dogs; D005260:Female; D006403:Hematologic Tests; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000633:toxicity*; D018675:Toxicity Tests; D016482:Urinalysis
D011994:Recombinant Proteins; D002262:Carboxy-Lyases; C021915:oxalate decarboxylase