Pulegone levels in e-liquids, smokeless tobacco products exceed FDA limits

A group of mint- and menthol-flavored e-liquids and smokeless tobacco products contained significantly more pulegone – a known carcinogen that causes hepatic carcinomas, pulmonary metaplasia, and other neoplasms – than the Food and Drug Administration considers acceptable, according to new findings.

Pulegone, an oil extract from mint plants such as peppermint, spearmint, and pennyroyal, was banned as a food additive by the agency in 2018, and the tobacco industry has taken steps to minimize pulegone levels in cigarettes because of the toxicity concerns.

Studies from the Centers for Disease Control and Prevention, however, have indicated that mint- and menthol-flavored e-cigarette liquids and smokeless tobacco products marketed in the United States contain substantial amounts of the substance, Sairam V. Jabba, DVM, PhD, and Sven-Eric Jordt, PhD, said in a research letter published in JAMA Internal Medicine.

Dr. Jabba and Dr. Jordt, both with the department of anesthesiology at Duke University, Durham, N.C., calculated the margin of exposure in five e-liquids (V2 Menthol, V2 Peppermint, Premium Menthol, South Beach Smoke Menthol, and South Beach Smoke Peppermint) and one smokeless tobacco product (Skoal Xtra Mint snuff) by dividing the no–observed adverse event level (13.39 mg/kg of bodyweight per day) by the mean human exposure to e-liquids or smokeless tobacco. The FDA considers margin-of-exposure values of 10,000 or less to require mitigation strategies.

The six products included in the analysis had pulegone concentration levels ranging from 25.7 to 119.0 mcg/g (a menthol cigarette has a pulegone concentration of 0.037-0.290 mcg/g). Based on those levels, light daily use (5 mL e-liquid, 10 g smokeless tobacco, half a pack of cigarettes) exposed e-cigarette users to 44-198 times more pulegone, compared with menthol cigarettes, and exposed smokeless tobacco users to 168-1,319 times as much pulegone. The margin of exposure ranged from 1,298 to 6,012, all below 10,000 threshhold the FDA deems acceptable.

For heavy daily use (20 mL e-liquid, 30 g smokeless tobacco, two packs of cigarettes), e-cigarette users were exposed to 282-1,608 times more pulegone, compared with menthol cigarettes; smokeless tobacco users were exposed to 126-990 times more pulegone. The margin of exposure ranged from 325 to 1,503.

The study findings “appear to establish health risks associated with pulegone intake and concerns that the FDA should address before suggesting mint- and menthol-flavored e-cigarettes and smokeless tobacco products as alternatives for people who use combustible tobacco products,” Dr. Jabba and Dr. Jordt concluded.

The study was funded by a grant from the National Institute of Environmental Health Sciences. Dr. Jordt reported receiving grants from the NIEHS and the National Institute on Drug Abuse, personal fees from Hydra Biosciences and Sanofi, and nonfinancial support from GlaxoSmithKline. Dr. Jabba reported no disclosures.

[email protected]

SOURCE: Jabba SV, Jordt S-E. JAMA Intern Med. 2019 Sep 16. doi: 10.1001/jamainternmed.2019.3649.

A group of mint- and menthol-flavored e-liquids and smokeless tobacco products contained significantly more pulegone – a known carcinogen that causes hepatic carcinomas, pulmonary metaplasia, and other neoplasms – than the Food and Drug Administration considers acceptable, according to new findings.

Pulegone, an oil extract from mint plants such as peppermint, spearmint, and pennyroyal, was banned as a food additive by the agency in 2018, and the tobacco industry has taken steps to minimize pulegone levels in cigarettes because of the toxicity concerns.

Studies from the Centers for Disease Control and Prevention, however, have indicated that mint- and menthol-flavored e-cigarette liquids and smokeless tobacco products marketed in the United States contain substantial amounts of the substance, Sairam V. Jabba, DVM, PhD, and Sven-Eric Jordt, PhD, said in a research letter published in JAMA Internal Medicine.

Dr. Jabba and Dr. Jordt, both with the department of anesthesiology at Duke University, Durham, N.C., calculated the margin of exposure in five e-liquids (V2 Menthol, V2 Peppermint, Premium Menthol, South Beach Smoke Menthol, and South Beach Smoke Peppermint) and one smokeless tobacco product (Skoal Xtra Mint snuff) by dividing the no–observed adverse event level (13.39 mg/kg of bodyweight per day) by the mean human exposure to e-liquids or smokeless tobacco. The FDA considers margin-of-exposure values of 10,000 or less to require mitigation strategies.

The six products included in the analysis had pulegone concentration levels ranging from 25.7 to 119.0 mcg/g (a menthol cigarette has a pulegone concentration of 0.037-0.290 mcg/g). Based on those levels, light daily use (5 mL e-liquid, 10 g smokeless tobacco, half a pack of cigarettes) exposed e-cigarette users to 44-198 times more pulegone, compared with menthol cigarettes, and exposed smokeless tobacco users to 168-1,319 times as much pulegone. The margin of exposure ranged from 1,298 to 6,012, all below 10,000 threshhold the FDA deems acceptable.

For heavy daily use (20 mL e-liquid, 30 g smokeless tobacco, two packs of cigarettes), e-cigarette users were exposed to 282-1,608 times more pulegone, compared with menthol cigarettes; smokeless tobacco users were exposed to 126-990 times more pulegone. The margin of exposure ranged from 325 to 1,503.

The study findings “appear to establish health risks associated with pulegone intake and concerns that the FDA should address before suggesting mint- and menthol-flavored e-cigarettes and smokeless tobacco products as alternatives for people who use combustible tobacco products,” Dr. Jabba and Dr. Jordt concluded.

The study was funded by a grant from the National Institute of Environmental Health Sciences. Dr. Jordt reported receiving grants from the NIEHS and the National Institute on Drug Abuse, personal fees from Hydra Biosciences and Sanofi, and nonfinancial support from GlaxoSmithKline. Dr. Jabba reported no disclosures.

[email protected]

SOURCE: Jabba SV, Jordt S-E. JAMA Intern Med. 2019 Sep 16. doi: 10.1001/jamainternmed.2019.3649.

A group of mint- and menthol-flavored e-liquids and smokeless tobacco products contained significantly more pulegone – a known carcinogen that causes hepatic carcinomas, pulmonary metaplasia, and other neoplasms – than the Food and Drug Administration considers acceptable, according to new findings.

Pulegone, an oil extract from mint plants such as peppermint, spearmint, and pennyroyal, was banned as a food additive by the agency in 2018, and the tobacco industry has taken steps to minimize pulegone levels in cigarettes because of the toxicity concerns.

Studies from the Centers for Disease Control and Prevention, however, have indicated that mint- and menthol-flavored e-cigarette liquids and smokeless tobacco products marketed in the United States contain substantial amounts of the substance, Sairam V. Jabba, DVM, PhD, and Sven-Eric Jordt, PhD, said in a research letter published in JAMA Internal Medicine.

Dr. Jabba and Dr. Jordt, both with the department of anesthesiology at Duke University, Durham, N.C., calculated the margin of exposure in five e-liquids (V2 Menthol, V2 Peppermint, Premium Menthol, South Beach Smoke Menthol, and South Beach Smoke Peppermint) and one smokeless tobacco product (Skoal Xtra Mint snuff) by dividing the no–observed adverse event level (13.39 mg/kg of bodyweight per day) by the mean human exposure to e-liquids or smokeless tobacco. The FDA considers margin-of-exposure values of 10,000 or less to require mitigation strategies.

The six products included in the analysis had pulegone concentration levels ranging from 25.7 to 119.0 mcg/g (a menthol cigarette has a pulegone concentration of 0.037-0.290 mcg/g). Based on those levels, light daily use (5 mL e-liquid, 10 g smokeless tobacco, half a pack of cigarettes) exposed e-cigarette users to 44-198 times more pulegone, compared with menthol cigarettes, and exposed smokeless tobacco users to 168-1,319 times as much pulegone. The margin of exposure ranged from 1,298 to 6,012, all below 10,000 threshhold the FDA deems acceptable.

For heavy daily use (20 mL e-liquid, 30 g smokeless tobacco, two packs of cigarettes), e-cigarette users were exposed to 282-1,608 times more pulegone, compared with menthol cigarettes; smokeless tobacco users were exposed to 126-990 times more pulegone. The margin of exposure ranged from 325 to 1,503.

The study findings “appear to establish health risks associated with pulegone intake and concerns that the FDA should address before suggesting mint- and menthol-flavored e-cigarettes and smokeless tobacco products as alternatives for people who use combustible tobacco products,” Dr. Jabba and Dr. Jordt concluded.

The study was funded by a grant from the National Institute of Environmental Health Sciences. Dr. Jordt reported receiving grants from the NIEHS and the National Institute on Drug Abuse, personal fees from Hydra Biosciences and Sanofi, and nonfinancial support from GlaxoSmithKline. Dr. Jabba reported no disclosures.

[email protected]

SOURCE: Jabba SV, Jordt S-E. JAMA Intern Med. 2019 Sep 16. doi: 10.1001/jamainternmed.2019.3649.