New substances: organisms, risk assessment summary 16936

Regulatory Decision

Under Part 6 of the Canadian Environmental Protection Act, 1999 (CEPA 1999) and its New Substances Notification Regulations (Organisms) [NSNR (O)], the Minister of the Environment and the Minister of Health have assessed information in respect of the notified organism, and determined that the organism is not suspected of being harmful to the Canadian environment or human health as defined in section 64 of the CEPA 1999Footnote[1], when imported for introduction into the environment anywhere in Canada. Therefore, the importation of Finalyse™ EC for this purpose may proceed after December 28, 2012.

NSNR (O) Schedule: 1
Organism Identity: Finalyse™ EC (product containing the notified micro-organism); Genus and species names are confidential
Notifier: Elanco Canada, 150 Research Lane, Guelph, ON, Canada
Date of decision: December 28, 2012
Proposed use(s): Processing aid for an in-plant, pathogen-reduction system designed to reduce pathogenic Escherichia coli (E. coli) on cattle hides

Questions & Answers Summary

Identity / Strain History / Genetic Modification

The notified micro-organism which is present in the Finalyse™ EC product is a naturally occurring bacteriophage. Bacteriophages are viruses that infect bacteria by recognizing and binding to specific receptors on the cell wall, injecting their DNA into the cell and inducing the replication of viral particles and subsequent cell lysis. The notified organism was isolated from recycled waste water from a beef processing plant in Arkansas USA using E.coli active culture.

Identification of the notified micro-organism was performed using full-length genome sequencing by the notifier. The classification of the notified strain was assigned based on distinguishing features of this bacteriophage.

Hazard Considerations

Environmental Hazard

Bacteriophages in general are widespread in nature and are present in sewage and marine waters (Zhao et al, 2009). The biosphere is estimated to sustain approximately greater than or equal to 1030 phage particles. In 2006, the United States Department of Agriculture, Food Safety and Inspection Service (USDAFSIS) issued a no objection letter for E. coli-targeting bacteriophages for use at beef processing facilities on hides of live animals prior to slaughter. Finalyse™ EC has been used in the USA since 2009 for this purpose without any reports of adverse effects.

The environmental hazard of the notified micro-organism was assessed based on multiple factors including its biological and ecological properties, history of safe use, horizontal gene transfer, pathogenicity/toxicity and other ecological effects. The notified bacteriophage is a naturally occurring organism without any subsequent genetic modifications. It has a narrow host range of bacteria and its hosts have been fully identified; it is exclusively lytic (incapable of lysogeny) and carries no known sequences of concern. It is not shown to be pathogenic or toxic to animals, fungi or plants and it is not expected to have any other type of harmful effect to the environment other than killing certain bacteria.

The potential for the notified micro-organism to cause adverse effects on the environment, its conservation or its biological diversity was therefore, considered low.

Human Health Hazard

In general, bacteriophages have a very restricted host range, and the phage found in Finalyse™ EC was shown to infect only particular pathogenic serotypes of E. coli. Despite bacteriophages being omnipresent in the environment and in the human micro flora, no incidents of infection or toxicity have been reported in the literature. No adverse effects were reported in bacteriophage clinical trials, in the decades-long history of use of phage in human as antimicrobial therapy or in standard toxicity tests in animal models using Finalyse™ EC (Summers, 2001; Merril et al, 2003; Sulakvelidze and Kutter, 2005; Burrowes et al, 2011).

Since bacteriophages affect bacteria, they have the potential to disrupt the normal human microflora. Clinical studies in the literature report that oral administration of bacteriophages has no effect on human microflora including commensal E. coli. In addition, notifier provided test data to show that the predominant human commensal gut bacteria are not susceptible to the notified bacteriophage.

As such, the use of the notified micro-organism is not expected to cause adverse effects to the general population. Its potential hazard to human health was considered to be low.

Exposure Considerations

Finalyse™ EC will be imported from USA into a location in Canada, which serves as the distribution point for Canada

Environment Canada has assessed the environmental exposure potential and has deemed it as high given that: (i) the product containing the notified bacteriophage is marketed with the potential for use in any slaughterhouse or abattoir in Canada. The notified use at specific locations indicates a release pattern of moderate to high quantity with high frequency and duration; (ii) the potential for persistence of the notified strain in the environment is unknown. Conservative assumptions for potential persistence have been applied and (iii) other potential uses, such as wastewater treatment, would not require re-notification since the notified strain is eligible for listing on the Domestic Substances List; and thus, have been assessed during this notification. These uses could also lead to a high exposure scenario, in particular in the aquatic environment.

Given the proposed use, Health Canada's assessment has deemed the potential human exposure as low for the following reasons: (i) the notifier provided evidence that the bacteriophages applied to the hide before slaughter will not contaminate the skinned carcass, and the salt curing effectively eliminates the bacteriophages from the hides. Furthermore, Finalyse™ EC bacteriophages was shown not to penetrate the hide; (ii) bacteriophages in run-off from sprayed animals will enter the wastewater stream, but sewage treatment facilities are expected to effectively eliminate the phages, so exposure to drinking water is unlikely; (iii) in the absence of a viable host, phages are highly susceptible to environmental conditions such as ultraviolet light, extreme temperatures, desiccation and predation by protozoa and bacterial enzymatic digestion. As such, they are not expected to persist at levels to cause adverse human health effects.

Other potential uses such as a food additive, disinfectant or in pharmaceutical products intended for homes as well as public institutions were also considered. Although large quantities would likely be applied in food safety scenarios, exposure might be limited because the bacteriophage would not be expected to persist in food in the absence of a viable host, and cooking and refrigeration would be expected to effectively eliminate phages from treated foods. The indirect human exposure from the potential uses was considered to be medium, since the bacteriophage is not likely to persist in the environment in the absence of the viable host. The direct human exposure from the potential uses of the notified organism could be high; such exposure would be assessed under the Food and Drugs Act.

Risk Assessment Conclusion / Regulatory Outcome

Based on the hazard and exposure considerations described above, the risk assessment conducted by Environment Canada and Health Canada concluded that the notified micro-organism found in the Finalyse™ EC product is not expected to cause harm to the Canadian environment or human health as described in section 64 of the CEPA 1999.

The substance is eligible for addition to the Domestic Substances List on the basis of this risk assessment.


Please note that the following is only a partial reference list due to confidentiality reasons.

Burrowes, B., Harper, D.R., Andersen, J., McConville, M., and Enright, M.C. 2011. Bacteriophage therapy: potential uses in the control of antibiotic-resistant pathogens. Expert Rev Anti Infect Ther 9, 775-85.

Denis, F. A., 1975. Contamination of shellfish with strains of Pseudomonas aeruginosa and specific bacteriophages, Can J Microbiol 21, 1055-1057.

Merril, C.R., Scholl, D., and Adhya, S.L. 2003. The prospect for bacteriophage therapy in Western medicine. Nat. Rev. Drug Discov. 2, 489-497.

Sulakvelidze, A., and Kutter, E. 2005. Bacteriophage therapy in humans. In Bacteriophages: biology and applications, Kutter, Elizabeth, and Sulakvelidze, Alexander eds., (Boca Raton, FL: CRC Press) pp. 381-436.

Summers, W.C.2001. Bacteriophage therapy. Annu. Rev. Microbiol. 55, 437-451.

Whitman, P.A. and Marshall R.T. 1971. Isolation of psychrophilic bacteriophage host systems from refrigerated food products. Appl Microbiol 22, 220-223.

Zhao, Y., Wang, K., Jiao, N., and Chen, F. 2009. Genome sequences of two novel phages infecting marine roseobacters. Environ. Microbiol. 11, 2055-2064.

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