Genotoxicity and sub-chronic oral toxicity of a blend of bacteriophage for animal feeds.

Bacteriophage (phage) are naturally occurring viruses which infect bacteria. They exhibit high host specificity and can be used to selectively control bacterial pathogens. Phage offer the potential of reducing pathogen contamination directly in foods or in feeds for livestock, thereby lowering the likelihood of infectious pathogens entering the food chain. A preparation consisting of a blend of phages targeting Salmonella spp., Escherichia coli strains and Clostridium perfringens has been created for application in animal feeds. A series of GLP-compliant studies was carried out to help establish the safety of the phage preparation in order to assess its suitability for use in animal feed. In vitro mammalian cell gene mutation testing using the Thymidine Kinase gene (OECD TG 490) established no significant increase in mutation frequency at dose levels up to 2000 μg/ml. In vitro mammalian cell micronucleus testing (OECD TG 487) showed no significant changes in micronuclei at dose levels up to 2000 μg/ml compared to the vehicle control. In vivo mammalian bone marrow chromosomal aberration testing (OECD TG 475) demonstrated that the phage preparation did not induce structural chromosomal aberrations or cytotoxicity at dose levels up to 80 mg/kg body weight. A sub-chronic oral toxicity study conducted using Sprague-Dawley rats (OECD TG 408), including an additional recovery phase, established a No Observed Adverse Effect Level (NOAEL) of 2.0 × 109 PFU/kg BW/day (200 mg/kg BW/day).