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Cetylpyridinium chloride

Names
Preferred IUPAC name 1-Hexadecylpyridin-1-ium chloride
Other names Acetoquat CPC; Pyrisept EXADECYL-PYRIDINIUM, CHLORIDE
Identifiers
CAS Number	123-03-5 6004-24-6 (monohydrate) D08AJ03 (WHO), D09AA07 (WHO) (dressing), R02AA06 (WHO)
3D model (JSmol)	Interactive image
Beilstein Reference	3578606
ChEBI	CHEBI:32915
ChEMBL	ChEMBL34833
ChemSpider	28979
ECHA InfoCard	100.004.177
PubChem CID	31239
UNII	6BR7T22E2S D9OM4SK49P (monohydrate)
CompTox Dashboard (EPA)	DTXSID6041761
InChI InChI=1S/C21H38N.ClH/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-16-19-22-20-17-15-18-21-22;/h15,17-18,20-21H,2-14,16,19H2,1H3;1H/q+1;/p-1Key: YMKDRGPMQRFJGP-UHFFFAOYSA-M InChI=1/C21H38N.ClH/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-16-19-22-20-17-15-18-21-22;/h15,17-18,20-21H,2-14,16,19H2,1H3;1H/q+1;/p-1Key: YMKDRGPMQRFJGP-REWHXWOFAU
SMILES .1(ccccc1)CCCCCCCCCCCCCCCC
Properties
Chemical formula	C21H38ClN
Molar mass	339.99 g·mol
Appearance	Solid
Melting point	77 °C (171 °F; 350 K)
Pharmacology
ATC code	B05CA01 (WHO)
Hazards
Lethal dose or concentration (LD, LC):
LD50 (median dose)	36 mg/kg (rabbit, iv) 400 mg/kg (rabbit, oral) 6 mg/kg (rat, ip) 30 mg/kg (rat, iv) 200 mg/kg (rat, oral) 250 mg/kg (rat, sc) 10 mg/kg (mouse, ip) 108 mg/kg (mouse, oral)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). N verify (what is  ?) Infobox references

Cetylpyridinium chloride (CPC) is a cationic quaternary ammonium compound used in some types of mouthwashes, toothpastes, lozenges, throat sprays, breath sprays, and nasal sprays. It is an antiseptic that kills bacteria and other microorganisms. It has been shown to be effective in preventing dental plaque and reducing gingivitis. It has also been used as an ingredient in certain pesticides. Though one study seems to indicate cetylpyridinium chloride does not cause brown tooth stains, at least one mouthwash containing CPC as an active ingredient bears the warning label "In some cases, antimicrobial rinses may cause surface staining to teeth," following a failed class-action lawsuit brought by customers whose teeth were stained.

The name breaks down as:

1. cetyl- refers to the cetyl group, named for its relation to cetyl alcohol, which was first isolated from whale oil (Latin: cetus);
2. pyridinium refers to the cation , the conjugate acid of pyridine;
3. chloride refers to the anion Cl.

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 agency believes that the information contained in its adverse reaction files, 30 years of safe marketing of an OTC mouthwash containing cetylpyridinium chloride (NDA 14- 598), and the safety data evaluated by the Oral Cavity Panel are sufficient to conclude that 0.025 to 0.1 percent cetylpyridinium chloride is safe as an OTC oral antiseptic when labeled for short-term use (not to exceed 7 days).

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 LD₅₀ 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 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
• United States Pharmacopeia 31
• British Pharmacopoeia 1998

See also

• Mouthwash
• Oral-B
• Chlorhexidine
• Triclosan

References

1. ^ Lewis, Richard J. (1996). Sax's Dangerous Properties of Industrial Materials (9th ed.). New York, NY: Van Nostrand Reinhold. p. 691.
2. Asadoorian, Joanna; Williams, Karen (2008). "Cetylpyridinium chloride mouth rinse on gingivitis and plaque". Journal of Dental Hygiene. 82 (5).
3. ^ Haps, S.; Slot, D. E.; Berchier, C. E.; Van Der Weijden, G. A. (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. 6 (4): 290–303. doi:10.1111/j.1601-5037.2008.00344.x. PMID 19138180.
4. Rahman, B.; Alkawas, S.; Al Zubaidi, E. A.; Adel, O. I.; Hawas, N. (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 (4): 466–470. doi:10.4103/0976-237X.142813. PMC 4229754. PMID 25395761.
5. ^ Wintonyk, Darcy; Steele, Lynda (October 12, 2012). "Consumers spitting mad after mouthwash turns teeth brown". CTV British Columbia. Archived from the original on 6 June 2016. The product does have a small print warning on the back label that reads: "In some cases, antimicrobial rinses may cause surface staining to teeth," but consumers have complained the warning label is buried in the product information.
6. ^ White, Ed (August 6, 2009). "Mich. lawyer sues, claims mouthwash stained teeth". Associated Press. Archived from the original on 6 August 2016. Rossman's lawsuit seeks class-action status. It accuses P&G of violating the Michigan Consumer Protection Act by not putting a warning on the label.
7. Nordegren, Thomas (2002). The A-Z Encyclopedia of Alcohol and Drug Abuse. Universal Publishers. p. 165. ISBN 1-58112-404-X.
8. at least 125 OTC oral healthcare products containing CPC (as of September 2012)
9. For example, Kilcof Cough Mixture
10. FDA monograph on oral antiseptic drug products, p. 6094
11. ^ National Library of Medicine Toxicology Data Network
12. Winkel, E. G.; Roldán, S.; Van Winkelhoff, A. J.; Herrera, D.; Sanz, M. (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. 30 (4): 300–306. doi:10.1034/j.1600-051X.2003.00342.x. PMID 12694427.
13. d'Amico, F.; Moro, M.; Saracino, M.; Marmiere, M.; Cilona, M. B.; Lloyd-Jones, G.; Zangrillo, A. (2023). "Efficacy of Cetylpyridinium Chloride mouthwash against SARS-CoV-2: A systematic review of randomized controlled trials". Molecular Oral Microbiology. 38 (3): 171–180. doi:10.1111/omi.12408. PMID 36808889. S2CID 257068281.
14. Fasig, Lisa Biank (9 April 2007). "P&G hopes rinse effect won't wash away sales". Cincinnati Business Courier. The company's Crest Pro-Health Rinse, launched with much promise in April 2005, is discoloring the teeth of about 3 percent of its users, the company said, because it is doing its job.
15. "Does Crest Pro-Health Rinse stain teeth brown?". Crest. Archived from the original on 6 March 2016. Retrieved 6 June 2016. Tooth discoloration could actually be one indication, in some people, that the product is working: after the rinse kills germs in your mouth, the dead germs can collect on the tooth surface and create the appearance of a brown stain.
16. Sewell, Dan (May 7, 2008). "P&G's Pro-Health rinse draws complaints". Associated Press. Archived from the original on 30 June 2016. Brinker said P&G doesn't see a need for a warning label because the number of those affected is very small.
17. "Crest rinse fights off customer complaints". USA Today. 7 May 2008. But NBC's Today show reported Wednesday that the complaints have led to a consumer lawsuit alleging fraud and to further study by the Food and Drug Administration, which approved the product.
18. "Mouthwash staining lawsuit dismissed". DrBicuspid.com. July 26, 2010. Archived from the original on June 23, 2016. A U.S. District Court judge has dismissed a proposed class-action lawsuit filed against Procter and Gamble charging that the company's Crest Pro-Health mouthwash causes staining and browning of teeth
19. Lewis, R.J. (1996). Sax's Dangerous Properties of Industrial Materials. Vol. 1–3 (9th ed.). New York, NY: Van Nostrand Reinhold. p. 691.
20. Datta, Sandipan; He, Guochun; Tomilov, Alexey; Sahdeo, Sunil; Denison, Michael S.; Cortopassi, Gino (2017). "In Vitro Evaluation of Mitochondrial Function and Estrogen Signaling in Cell Lines Exposed to the Antiseptic Cetylpyridinium Chloride". Environmental Health Perspectives. 125 (8): 087015. doi:10.1289/ehp1404. PMC 5783672. PMID 28885978. S2CID 3647115.
21. "Effect of salt on the micelles of cetyl pyridinium chloride".
22. The United States Pharmacopeial Convention. "Revisions to FCC, First Supplement". Archived from the original on 5 July 2010. Retrieved 8 July 2009.
23. USP 31. "<1121> Nomenclature" (PDF). Archived from the original (PDF) on 9 January 2009. Retrieved 8 July 2009.{{cite web}}: CS1 maint: numeric names: authors list (link)
24. Therapeutic Goods Administration. "Chemical Substances" (PDF). Archived from the original (PDF) on 15 June 2009. Retrieved 8 July 2009.

External links

• Material Safety Data Sheet
• Chemical Information
• Sheen, S; Addy, M (2003). "An in vitro evaluation of the availability of cetylpyridinium chloride and chlorhexidine in some commercially available mouthrinse products". British Dental Journal. 194 (4): 207–10, discussion 203. doi:10.1038/sj.bdj.4809913. PMID 12627199. S2CID 39352250.

• Antiseptics
• Preservatives
• Chlorides
• Pyridinium compounds
• Cationic surfactants