Chemistry and Safety of Triclosan, and Its Use as an Antimicrobial Coating on Coated VICRYL~* Plus Antibacterial Suture (Coated Polyglactin 910 Suture with Triclosan)

摘要

Background: The safety of the antimicrobial agent triclosan was reviewed, and the biocom-patibility of coated polyglactin 910 suture with triclosan was evaluated. Methods: Acute single exposure LD_(50) values for triclosan were determined in multiple species by several routes of administration. Subacute to chronic toxicity for dermal and oral exposure to triclosan was determined in multiple species in studies of up to one year's duration. Chronic oral toxicity/carcinogenicity potential was determined in 2-year studies in rodents and non-rodents. The genotoxicity potential of triclosan was determined using a battery of standard assays. Reproductive toxicity and teratology studies were conducted in rodents and non-rodents. Immunotoxicity studies in guinea pigs and the repeat-insult patch test in humans were conducted to assess the potential for sensitization reactions. Pharmaco-kinetic studies were conducted in animals and humans to understand the metabolic profile of triclosan. Preclinical biocompatibility studies conducted on coated polyglactin 910 suture with triclosan included in vitro cytotoxicity, in vivo intracutaneous reactivity, material-mediated pyrogenicity, and intramuscular tissue reaction/absorption studies. Results: The oral LD_(50) values for triclosan ranged from 3,750 to 5,000 mg/kg, whereas the LD_(50) after subcutaneous injection was >14,600 mg/kg. Safety factors calculated from repeated daily dosing studies ranged from 1,000 to 25,000 times the no-observed-effect levels. There was no evidence of carcinogenic potential in either species, and genotoxicity studies were negative. Reproductive toxicity studies did not reveal any evidence of teratogenic potential. There was no evidence of skin sensitization potential in controlled studies. Pharmacokinetic studies in animals and humans have shown that triclosan is rapidly absorbed, well distributed in the body, metabolized in the liver, and excreted by the kidneys, with no indication of accumulation over time. Biocompatibility studies showed that coated polyglactin 910 suture with triclosan was non-cytotoxic, non-irritating, and not a chemical pyrogen. In addition, an intramuscular implantation study demonstrated a tissue reaction, a healing response, and an absorption profile comparable to current polyglactin 910 suture. Conclusion: The extensive toxicology database supporting the safety of triclosan and the biocompatibility studies conducted on coated polyglactin 910 suture with triclosan demonstrate the safety of this suture for clinical use. Considering the clinical relevance of surgical site infections and the relatively low level of triclosan required to inhibit bacterial colonization of the suture, the use of this antimicrobial technology is well suited to this application.