Import Alert 66-74

"Detention Without Physical Examination Of Dentifrice Products Containing Diethylene Glycol(DEG)"

Diethylene glycol (DEG) is a glycol compound possessing toxicity similar to ethylene glycol. It is a Central Nervous System depressant and potent kidney and liver toxin when ingested. It is commonly used in industry as a solvent, a thickening agent, a humectant, and as a component in antifreeze and gas conditioning formulations.

DEG has been improperly used as a low cost substitute for glycerin and propylene glycol in pharmaceutical preparations resulting in various lethal poisoning incidents in humans worldwide. Among these incidents are, elixir sulfanilamide in the U.S., sedative mixtures in South Africa, paracetamol elixirs in Bangladesh and Nigeria, acetaminophen syrup in Haiti, and a cough expectorant product in India. Most recently, a cough syrup resulted in serious man injury and over 40 deaths in Panama in September 2006. These recent DEG poisoning incidents involved a "glycerin" product manufactured in China that was a mixture of sorbitol and DEG and less than one percent glycerin.

In May 2007, FDA received accounts that toothpaste from China shipped to Panama, Australia, and the Dominican Republic was found to contain DEG. A significant amount of toothpaste from China is imported into the United States. FDA is presently sampling dentifrice products manufactured in China to determine potential contamination with DEG.

To date, FDA has found DEG in three products manufactured by Goldcredit International Trading, China. The products are Cooldent Fluoride, Cooldent Spearmint, and Cooldent ICE. Analysis of these products has revealed that they contain between 3 and 4 percent diethylene glycol. FDA has also found DEG in one product manufactured by Suzhou City Jinmao Daily Chemicals Co., China. Analysis of that product, Shir Fresh Mint Fluoride Paste, found that it contained approximately 1% DEG. These products have been included in the DPWE list attachment of this alert. As the agency identifies other toothpaste products containing DEG, these products and their manufacturers will also be added to the Import Alert.

The products were labeled as containing diglycol. Diglycol is one of many synonyms of diethylene glycol. According to REPROTEXT ® System, diethylene glycol may be also known as:

1. Brecolane ndg
2. Carbitol
3. Deactivator E
4. Deactivator H
5. DEG
6. Degrees
7. Dicol
8. Diethylene ether
9. Diethylene glycol
10. Diethylenglykol (Czech)
11. Digenos
12. Diglycol
13. Digol
14. Dihydroxydiethyl ether
15. 2,2' Dihydroxydiethyl ether
16. beta,beta' Dihydroxydiethyl ether
17. Dihydroxyethylether
18. 2,2' Dihydroxyethyl ether
19. Dissolvant APV
20. Ethanol, 2,2' oxybis
21. Ethanol, 2,2' oxydi
22. Ethylene diglycol
23. Glycol ether
24. Glycol ethyl ether
25. 2 Hydroxyethyl ether
26. bis(2 Hydroxyethyl)ether
27. 3 Oxapentane 1,5 diol
28. 3 Oxa 1,5 pentanediol
29. 2,2' Oxybisethanol
30. 2,2' Oxybis ethanol
31. 2,2' Oxydiethanol
32. 2,2' Oxyethanol
33. TL4N

FDA has also identified a number of other dentifrice products manufactured by Goldcredit that are labeled as containing DEG (or a synonym thereof). These products have also been included in the DWPE list on this alert.

Dentifrice products may be marketed in the United States as drugs or cosmetics. Dentifrice products intended to prevent or mitigate dental cavities/decay (anticaries toothpaste) are regulated as over the counter (OTC) drugs. OTC anticaries toothpaste containing diethylene glycol cannot be marketed in the U.S. without an approved new drug application (NDA). DEG can be toxic and even fatal in humans and FDA is not aware of DEG having been used for a material extent and time in formulating OTC anticaries drug products. Thus, FDA regards any OTC anticaries drug product containing DEG to be a "new drug" as defined by section 201(p) of the Federal Food, Drug, and Cosmetic Act (the Act). "New drugs" must be the subject of an approved NDA under section 505 of the Act to be legally marketed in the United States . Presently, there are no OTC anticaries drug products containing DEG approved for marketing in the U.S.

The use of DEG in OTC anticaries drug products causes them to be adulterated under section 501(a)(2)(B) of the Act because of the toxicity of DEG when ingested, and therefore, the methods or controls used to manufacture the anticaries drug containing the DEG do not conform to current Good Manufacturing Practices to assure the drug meets the requirements of the Act regarding safety.

Non fluoride dentifrices products that are not drugs are ordinarily marketed as cosmetics, as their intended use is for oral hygienic cleansing.

At this time, the only DEG containing dentifrice products identified by FDA as being offered for import into the U.S. are from China. However, no DEG containing dentifrice products manufactured in China or any other country may be imported into the U.S. Therefore, this alert covers dentifrice products containing DEG from any source.

Districts may detain without physical examination all shipments of dentifrice products identified in the attachment to this alert.

Districts may detain without physical examination any shipment of dentifrice products labeled as containing diethylene glycol or any of its synonyms.

Districts may detain without physical examination all shipments of dental hygiene kits which contain dentifrice products identified in the Red List or which contain dentifrice products labeled as containing diethylene glycol or any of its synonyms.

For questions regarding dentifrice product marketed as drugs please contact ***the CDER Imports Exports Compliance Branch at cderimportsexports@fda.hhs.gov.***

For questions regarding dentifrice product marketed as cosmetics please contact, CFSAN, Labeling Compliance Team Richard.jewell@fda.hhs.gov.

For questions or issues concerning science, science policy, sample collection, analysis, preparation, or analytical methodology, contact the Division of Field Science at (301) 796-6600.

All dentifrice products, including aerosols, liquids, toothpastes, and tooth powders with or without fluoride containing DEG as identified in the Red List for specific product and manufacturers

For fluoride containing dentifrice drug products: "The article is subject to refusal of admission pursuant to Section 801(a)(3) in that it appears to be a new drug within the meaning of Section 201(p) without an effective new drug application (NDA) [Unapproved New Drug, Section 505(a)]."

OASIS charge code: UNAPPROVED

and

"The article is subject to refusal of admission pursuant to Section 801(a)(3) in that it appears that the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice to assure that such drug meets the requirements of this Act as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess [Adulterated Drugs, Section 501(a)(2)(B)]."

OASIS charge code: DRUG GMPS

For non fluoride containing dentifrice cosmetic products: "The article is subject to refusal of admission pursuant to section 801(a)(3) in that it appears to be adulterated in that it contains a poisonous or deleterious substance, namely diethylene glycol, which may render it injurious to users under such conditions of use as are customary or usual [Adulterated Cosmetic, Section 601(a)]."

OASIS charge code: POISONOUS