Cetylpyridinium chloride

Medical use

OTC (over the counter) products containing cetylpyridinium chloride include oral wash, oral rinse, and ingestable products, such as lozenges and over-the-counter cough syrup.

The United States' federal Food and Drug Administration's monograph on oral antiseptic drug products reviewed the data regarding CPC and made this conclusion:

The National Library of Medicine Toxicology Data Network (TOXNET) reviewed the range of toxicity of CPC and stated "Significant toxicity is rare after exposure to low concentration products that are typically available in the home."

The fatal dose in humans ingesting cationic detergents has been estimated to be 1 to 3 g. Therefore, a person using a typical oral ingestible product that provides 0.25 mg CPC per dose would need to take 4,000 doses at one time to reach the estimated fatal dose range.

A review found that mouthwashes containing CPC "provide a small but significant additional benefit when compared with toothbrushing only or toothbrushing followed by a placebo rinse" in reducing plaque and gingivitis-inflammation. In combination with chlorhexidine and zinc lactate, CPC has been found to be effective in treating halitosis.

CPC mouthwashes inactivate viruses, including the virus that causes COVID-19, by breaking their lipid envelope.

Side effects

Tooth staining

Cetylpyridinium chloride is known to cause tooth staining in approximately 3 percent of users. The Crest brand has noted that this staining is actually an indication that the product is working as intended, as the stains are a result of bacteria dying on the teeth. Crest stated that because of the low incidence of staining, there was no need to label Pro-Health mouthwash as a potential tooth stainer. However, after numerous complaints and a federal class-action lawsuit, which was later dismissed, the mouthwash now contains a label warning consumers of its potential to stain teeth.

Temporary loss of taste

In a small percentage of population, CPC can alter or eliminate the sense of taste. The effect generally goes away a few days after discontinuing use of the product.

Toxicology and pharmacology

The of cetylpyridinium chloride has been measured at 30 mg/kg in rats and 36 mg/kg in rabbits when the chemical is administered by intravenous infusion but 200 mg/kg in rats, 400 mg/kg in rabbits, and 108 mg/kg in mice when administered orally.

There is in-vitro evidence that cetylpyridinium chloride interferes with mitochondrial function at levels "that may be relevant to human exposures." The research was published in Environmental Health Perspectives" volume 125 no. 8.

Chemistry

The molecular formula of cetylpyridinium chloride is C21H38NCl. In its pure form it is a white solid at room temperature. It has a melting point of 77 °C when anhydrous or 80–83 °C as a monohydrate . It is soluble in water but insoluble in acetone, acetic acid, or ethanol. It has a pyridine-like odor. It is combustible. Concentrated solutions are destructive to mucous membranes. Its critical micelle concentration (CMC) is ~ 0.0009–0.0011M, and is strongly dependent on the salt concentration of the solution.

Some products are formulated instead with the bromide salt cetylpyridinium bromide, the properties of which are virtually identical.

Compendial status

• Food Chemicals Codex{{cite web |access-date=8 July 2009 |url-status=dead |archive-url=https://web.archive.org/web/20100705122159/http://www.usp.org/fcc/FCC61SBallotResultsWebPostingReport01.html |archive-date=5 July 2010
• United States Pharmacopeia 31
• British Pharmacopoeia 1998

References

References

1. Lewis, Richard J.. (1996). "Sax's Dangerous Properties of Industrial Materials". Van Nostrand Reinhold.
2. (2008). "Cetylpyridinium chloride mouth rinse on gingivitis and plaque". Journal of Dental Hygiene.
3. (2008). "The effect of cetylpyridinium chloride-containing mouth rinses as adjuncts to toothbrushing on plaque and parameters of gingival inflammation: A systematic review". International Journal of Dental Hygiene.
4. (2014). "Comparative antiplaque and antigingivitis effectiveness of tea tree oil mouthwash and a cetylpyridinium chloride mouthwash: A randomized controlled crossover study". Contemporary Clinical Dentistry.
5. (2012-10-12). "Consumers spitting mad after mouthwash turns teeth brown". [[CTV Television Network.
6. White, Ed. (2009-08-06). "Mich. lawyer sues, claims mouthwash stained teeth".
7. Nordegren, Thomas. (2002). "The A-Z Encyclopedia of Alcohol and Drug Abuse". Universal Publishers.
8. [https://dailymed.nlm.nih.gov/dailymed/search.cfm?startswith=CETYLPYRIDINIUM+CHLORIDE&x=20&y=6 at least 125 OTC oral healthcare products containing CPC (as of September 2012)]
9. For example, [http://www.conceptpharmacy.co.uk/kilkof-cough-mixture-150ml Kilcof Cough Mixture]
10. [https://web.archive.org/web/20090710142056/http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Over-the-CounterOTCDrugs/StatusofOTCRulemakings/ucm096101.pdf FDA monograph on oral antiseptic drug products], p. 6094
11. [https://web.archive.org/web/20190718135538/https://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+38 National Library of Medicine Toxicology Data Network]
12. (2003). "Clinical effects of a new mouthrinse containing chlorhexidine, cetylpyridinium chloride and zinc-lactate on oral halitosis. A dual-center, double-blind placebo-controlled study". Journal of Clinical Periodontology.
13. (2023). "Efficacy of Cetylpyridinium Chloride mouthwash against SARS-CoV-2: A systematic review of randomized controlled trials". Molecular Oral Microbiology.
14. Fasig, Lisa Biank. (2007-04-09). "P&G hopes rinse effect won't wash away sales". [[Cincinnati Business Courier]].
15. "Does Crest Pro-Health Rinse stain teeth brown?". Crest.
16. Sewell, Dan. (2008-05-07). "P&G's Pro-Health rinse draws complaints".
17. (2008-05-07). "Crest rinse fights off customer complaints". [[USA Today]].
18. (2010-07-26). "Mouthwash staining lawsuit dismissed". DrBicuspid.com.
19. Lewis, R.J.. (1996). "Sax's Dangerous Properties of Industrial Materials". Van Nostrand Reinhold.
20. (2017). "In Vitro Evaluation of Mitochondrial Function and Estrogen Signaling in Cell Lines Exposed to the Antiseptic Cetylpyridinium Chloride". Environmental Health Perspectives.
21. "Effect of salt on the micelles of cetyl pyridinium chloride".
22. USP 31. "<1121> Nomenclature".
23. Therapeutic Goods Administration. "Chemical Substances".