BACKGROUND: In vaccines/biologics, preservatives are used to prevent microbial growth. MATERIAL/ METHODS: The present study examined: (1) the comparative toxicities of commonly used preservatives in US licensed vaccines to human neurons; and (2) the relative toxicity index of these compounds to human neurons in comparison to bacterial cells. RESULTS: Using human neuroblastoma cells, the relative cytotoxicity of the levels of the compounds commonly used as preservative in US licensed vaccines was found to be phenol <2-phenoxyethanol < benzethonium chloride < Thimerosal. The observed relative toxicity indices (human neuroblastoma cells/bacterial cells) were 2-phenoxyethanol (4.6-fold) < phenol (12.2-fold) < Thimerosal (>330-fold). In addition, for the compounds tested, except for 2-phenoxyethanol, the concentrations necessary to induce significant killing of bacterial cells were significantly higher than those routinely present in US licensed vaccine/biological preparations. CONCLUSIONS: None of the compounds commonly used as preservatives in US licensed vaccine/biological preparations can be considered an ideal preservative, and their ability to fully comply with the requirements of the US Code of Federal Regulations (CFR) for preservatives is in doubt. Future formulations of US licensed vaccines/biologics should be produced in aseptic manufacturing plants as single dose preparations, eliminating the need for preservatives and an unnecessary risk to patients.
BACKGROUND: In vaccines/biologics, preservatives are used to prevent microbial growth. MATERIAL/ METHODS: The present study examined: (1) the comparative toxicities of commonly used preservatives in US licensed vaccines to human neurons; and (2) the relative toxicity index of these compounds to human neurons in comparison to bacterial cells. RESULTS: Using humanneuroblastoma cells, the relative cytotoxicity of the levels of the compounds commonly used as preservative in US licensed vaccines was found to be phenol <2-phenoxyethanol < benzethonium chloride < Thimerosal. The observed relative toxicity indices (humanneuroblastoma cells/bacterial cells) were 2-phenoxyethanol (4.6-fold) < phenol (12.2-fold) < Thimerosal (>330-fold). In addition, for the compounds tested, except for 2-phenoxyethanol, the concentrations necessary to induce significant killing of bacterial cells were significantly higher than those routinely present in US licensed vaccine/biological preparations. CONCLUSIONS: None of the compounds commonly used as preservatives in US licensed vaccine/biological preparations can be considered an ideal preservative, and their ability to fully comply with the requirements of the US Code of Federal Regulations (CFR) for preservatives is in doubt. Future formulations of US licensed vaccines/biologics should be produced in aseptic manufacturing plants as single dose preparations, eliminating the need for preservatives and an unnecessary risk to patients.