September 26, 2024

IARC Publishes Monographs on Aspartame, Two Flavoring Substances

The International Agency for Research on Cancer (IARC) has published volume 134 of its monograph series, which evaluates the carcinogenicity of the artificial sweetener aspartame and the flavoring compounds methyleugenol and isoeugenol.

Aspartame has been used in foods and beverages for decades. Currently, its highest concentrations are found in tabletop sweeteners, chewing gum, and food supplements, according to IARC. An IARC working group classified aspartame as group 2B, possibly carcinogenic to humans, based on limited evidence for an association between aspartame consumption and liver cancer. This conclusion was based on three studies of consumption of artificially sweetened beverages. The working group also found limited evidence for a link between aspartame and cancer in experimental animals and limited mechanistic evidence for aspartame’s carcinogenicity. In occupational environments, the highest potential exposures occur for workers who manually handle aspartame powder.

IARC classified isoeugenol, a fragrance and flavoring compound used in food, cosmetics, household products, and veterinary medicines, as group 2B based on sufficient evidence for cancer in experimental animals and inadequate evidence for cancer in humans. No studies on the effects of isoeugenol on humans were available.

Methyleugenol, like isoeugenol, is a fragrance and flavoring compound. Methyleugenol is used in cosmetics and personal care products, and—in combination with insecticides—as an insect attractant. Neither the United States nor the European Union allows the use of methyleugenol as a flavoring agent, but it occurs naturally in many herbs and spices. IARC classified methyleugenol as group 2A, probably carcinogenic to humans, based on sufficient evidence in experimental animals and strong mechanistic evidence.

A NIOSH survey in the early 1980s identified potential occupational exposures to isoeugenol and methyleugenol for hairdressers, cosmetologists, janitors, machine operators, and packaging and filling machine operators. A later study of wildland firefighters found significant increases in the concentration of isoeugenol in urine following smoke exposure. Aromatherapists may be exposed to methyleugenol, a constituent of essential oils, through dermal contact when giving massages. Workers who handle insect traps may also have dermal exposure to methyleugenol.

When IARC first announced its aspartame classification in July 2023, it noted that no recommendation was made to lower the acceptable daily intake (ADI) of aspartame from its current level of 0–40 milligrams per kilogram of body weight. A news release accompanying the announcement clarified that an adult weighing 70 kg—about 154 pounds—would need to consume more than 9–14 cans of diet soft drinks per day to exceed the ADI, assuming the beverages contained between 200 and 300 mg of aspartame.

“The assessments of aspartame have indicated that, while safety is not a major concern at the doses which are commonly used, potential effects have been described that need to be investigated by more and better studies,” said Dr. Francesco Branca of the World Health Organization.

Following IARC’s 2023 announcement, the U.S. Food and Drug Administration stated that it “disagrees with IARC’s conclusion that these studies support classifying aspartame as a possible carcinogen to humans.”

Volume 134 of IARC’s monograph series is available from the organization’s website. For more information, see IARC’s news release, its 2023 statement on aspartame, and FDA’s webpage on aspartame and other sweeteners.