OECD 488 transgenic rodent mutation assay (TGRA) using the Big Blue® rat

The conduct of an OECD 488 transgenic rodent mutation assay (TGRA) using the Big Blue® rat using cII mutant selection for the University of Sheffield. Studies will be conducted to GLP, and are based on the following preliminary study design:

1. Breeding of target cohort of 46 Big Blue male rats, with delivery of a target of 44 rats to Charles River Laboratories (CRL) facility, Ashland Ohio, USA.
2. Transfer of HPLC analytical method for dose formulation analysis (DFA) and method transfer summary performed by CRL.
3. Method validation, homogeneity, solubility and stability work to enable GLP dose formulation analysis during Big Blue® TGRA main study, performed by CRL.
4. 7-day dose-range finding study (DRF), wild type Fischer F344 male and female rats, to determine limit dose of 1000 mg / kg body weight /day or MTD, performed by CRL.
5. Big Blue® TGRA rat main study, male only, using vehicle, 3 dose groups and concurrent positive control conducted at CRL. Each group will contain at least 6 male rats, conducted in accordance with OECD 488; daily test item administration by oral gavage for 28 days (positive control will be dosed days 1, 3, 10, 17 & 24 only); termination and schedule necropsy on day 31 with duodenum, liver and bone marrow removed from all animals, flash frozen and stored prior to shipment to Gentronix.