title: 14-day repeat-dose oral toxicity evaluation of oxazyme in rats and dogs.
abstract: 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.
authors.affiliation: Captozyme LLC, Gainesville, FL, USA.
authors.forename: Aaron B
authors.initials: AB
authors.lastname: Cowley
authors.forename: Duane W
authors.initials: DW
authors.lastname: Poage
authors.forename: Robin R
authors.initials: RR
authors.lastname: Dean
authors.forename: Carol L
authors.initials: CL
authors.lastname: Meschter
authors.forename: Majid
authors.initials: M
authors.lastname: Ghoddusi
authors.forename: Qing-Shan
authors.initials: QS
authors.lastname: Li
authors.forename: Harmeet
authors.initials: H
authors.lastname: Sidhu
mesh_terms: 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
chemical_list: D011994:Recombinant Proteins; D002262:Carboxy-Lyases; C021915:oxalate decarboxylase