Following a request from the European Commission, the Panel on Biological Hazards (BIOHAZ Panel) and the Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF Panel) of the European Food Safety Authority (EFSA) were asked to deliver a Scientific Opinion on an application dossier submitted by the company Safe Foods Corporation for approval of the use of the preparation Cecure® for removal of microbial surface contamination on raw poultry products.
More specifically, the approval was sought for treatments using an aqueous solution of Cecure® consisting of cetylpyridinium chloride (CPC) as the active ingredient and food-grade propylene glycol (PG). Cecure® should be applied by drenching at a concentration of less than 1.0% CPC, at room temperature, and the solution should be recycled for reuse.
The Commission asked EFSA to issue a Scientific Opinion on the assessment of the safety and efficacy of Cecure® when used to reduce microbial surface contamination on raw poultry products (defined as skin-on whole chicken carcasses or parts). Specifically, the task was to consider the toxicological safety of the substance, its antimicrobial efficacy, the potential emergence of reduced microbial susceptibility to biocides and/or resistance to therapeutic antimicrobials linked to the use of the substance, and any risk related to the release of effluents containing the substance from the slaughterhouse and/or processing plant into the environment. The assessment was based on the guidance document on the submission of data for the evaluation of the safety and efficacy of substances for the removal of microbial surface contamination of foods of animal origin intended for human consumption published by EFSA.
The available data indicate that CPC, formulated as a diluted solution in Cecure®, is not mutagenic in bacteria and not clastogenic in cultured mammalian cells. Negative results were also obtained in a gene mutation assay with CPC in mouse lymphoma cells and in limited tests in Aspergillus, Tradescantia and Drosophila. The CEF Panel also noted that, in addition to these consistently negative results, the substance does not contain structural alerts for genotoxicity. Thus, based on the available evidence, the CEF Panel considered that there is no concern for genotoxicity.
The CEF Panel had access to information on subchronic toxicity studies on CPC. From a recent 90-day toxicity study in Sprague-Dawley rats, the CEF Panel could identify a No-Observable-Adverse-Effect-Level (NOAEL) of 18 mg/kg bw/day in rats, based on increased caecum weights noted in males. The CEF Panel considered the increase in caecum weight as relevant for risk characterisation of Cecure® since CPC has been suggested to decrease the total number of microorganisms in the caecal contents of rats of both sexes. This led to an increase in caecum to body weight ratios, which was positively correlated with dietary levels of CPC. The CEF Panel considered thus that a potential similar effect of CPC on human gastrointestinal microflora should not be disregarded.
The data presented by the applicant allowed the CEF Panel to perform a very conservative risk assessment. The potential exposure to CPC was estimated to be up to 5.7 µg/kg bw/day at the mean and 17.8 µg/kg bw/day at the 95th percentile of poultry consumption. The potential exposure to PG by mean and high level consumers, such as young children would be up to 0.5 µg/kg bw/day at the mean and 1.4 µg/kg bw/day at the 95th percentile of treated poultry consumption. These exposure estimates are worst cases since they assumed that all poultry carcasses which are going to be consumed have been treated with Cecure®.
Taking into account the highest calculated potential conservative exposure estimates to CPC from treated poultry consumption, the margins of safety for CPC would be more than 3000 at the mean and more than 1000 at the 95th percentile, when compared to the NOAEL of 18 mg CPC/kg bw/day, identified by the CEF Panel in a 13-week toxicity study in Sprague-Dawley rats. For PG, the margins of safety would be 22000 at the mean and 7000 at the 95th percentile, when compared to the Acceptable Daily Intake (ADI) of 0 - 10 mg/kg bw/day allocated by the Joint FAO/WHO Expert Committee on Food Additives (JECFA). Furthermore, they would be 3500 times below the TDI of 5 mg/kg bw/day established by the Scientific Committee on Food (SCF) for PG.
Therefore based on the toxicological data available, the estimated margins of safety (going from three orders of magnitude for CPC to four orders of magnitude for PG) and the conservative exposure estimates used to assess CPC exposure from consumption of poultry carcasses, the CEF Panel considers that there are no safety concerns for humans from the proposed use of Cecure® for removal of microbial surface contamination from raw poultry under the usage conditions specified in this opinion.
A total of 15 peer reviewed published papers and 13 in-house studies dealing with testing of CPC or Cecure® for decontamination efficacy were submitted. Based on selection criteria, five peer-reviewed published papers and eleven in-house studies were selected and used in the assessment of the efficacy of Cecure® by the BIOHAZ Panel.
The selected studies were classified as high, medium or low strength of evidence, based on the experiment setting (industrial scale, pilot plant or laboratory) and on the type of microbial contamination of the analysed samples (naturally contaminated or inoculated).
Based on results published in peer-reviewed papers and in-house conducted studies, mostly performed at industrial scale and on naturally contaminated samples, both Cecure® and its active ingredient CPC were found to be efficacious in reducing contamination with pathogenic microorganismson fresh broiler carcasses or chicken skin. The microbial reductions achieved on pre- and post-chill treated samples were in the range of <1.0 to 5.0 log units over untreated and water-treated controls. The lower reductions were generally associated with lower concentrations of CPC (e.g., 0.1% or 1 mg/ml CPC) applied to samples of low initial contamination, while the higher reductions were achieved with inoculated samples.
The BIOHAZ Panel further concluded that the efficacy appeared to be influenced more by the concentration of the active ingredient than by the volume of solution applied, flow rate, spraying pressure, rate of carcass processing, and time of exposure within the ranges examined. Since the Cecure® solution is to be recycled after use, the BIOHAZ Panel assessed the level of efficacy of the recycled solution, and concluded that there is inadequate evidence to support that the recycled Cecure® solution is as efficacious as the fresh solution and that it does not accumulate resistant bacterial cells and/or spores.
Data to address the issue of the potential emergence and selection of isolates with reduced susceptibility to biocides and/or resistance to therapeutic antimicrobials linked to the use of CPC were not provided. Moreover, no tests were undertaken by the applicant to test for the potential development of resistance of the target organisms either under the conditions of use, or in wastewater. The data provided were not considered useful to support the absence of antimicrobial activity of CPC in organic material. Further, evidence was not provided about testing potential microbial contamination of Cecure® solution in the recycling process for all bacterial species.
Concerning the risk related to the release of CPC into the environment as a result of use of Cecure®, basic data necessary for an assessment of the environmental compartments surface water, sediment and soil, as well as for evaluation of the function of sewage treatment plants, were not submitted or could not be validated. Therefore, data on the toxicity, fate and behaviour of CPC found in the open literature were used to perform a preliminary risk assessment.
The predicted environmental concentrations (PECs) and predicted no-effect concentrations (PNECs) for protection of the function of sewage treatment plants (STP) for surface water, as well as for sediment and soil, were derived using the software system EUSES 2.1.1 which has been developed for quantitative assessment of the risks of biocides and industrial chemicals to man and the environment. This system is fully based on the EU Technical Guidance Documents (TGD) for the risk assessment of these chemicals.
A comparison of PECs with the PNECs suggests that the use of CPC in poultry slaughterhouses does not pose a risk for the function of sewage treatment plants. As there are no indications of a high bioaccumulation potential, no risk for birds and mammals in the environment via indirect exposure through the food-chain (secondary poisoning) has to be expected. In view of the low vapour pressure, low bioaccumulation potential and the high adsorptive properties of CPC, indirect exposure of man via groundwater (as a source for drinking water), air and fish is expected to be negligible.
Despite the fact that it is assumed that a large proportion of the active ingredient is recycled and that the product is assumed to be used in a specific application system claimed by the applicant, risks for the environmental compartments surface water, sediment and soil are apparent.
It is recommended that, as requested in the EFSA guidance (EFSA, 2010), data addressing the potential emergence of and selection for reduced susceptibility to biocides and or resistance to therapeutic antimicrobials linked to the use of CPC should be provided by the applicant. Moreover the minimum CPC concentration applied for should be specified, and data about possible accumulation of bacterial spores, as well as data to support continuous efficacy of the recycled solution should be collected.
In order to improve the robustness and reduce the uncertainty of the assessment, the CEF Panel recommends to the applicant to provide more reliable data on the environmental fate and behaviour of CPC and to provide (long-term) tests relevant for the compartments surface water, sediment and soil. However, considering the high level of potential risk indicated by the present assessment, it is the opinion of the CEF Panel that the attainment of safe environmental levels would be highly unlikely without suitable measures to reduce environmental emissions. An option would be to reduce exposure by achieving a high proportion of recycling during treatment in poultry slaughterhouses.