Benzene in Benzoyl Peroxide Products: New Findings

The formulation of benzoyl peroxide (BP) products plays a role in the levels of benzene found, according to new research, with leave-on products found to have significantly lower concentrations of benzene.

Concerns about the potential for BP products to break down into benzene, a known carcinogen, have been ongoing.

In the new study, published in JAMA Dermatology on February 12, researchers examined the association of product formulation with benzene levels in 111 over-the-counter BP products. The findings are reassuring, said one of the study authors, John S. Barbieri, MD, MBA, assistant professor of dermatology at Harvard Medical School and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, both in Boston.

“The clinical data we have suggest it is unlikely to be a clinically meaningful issue,” he told Medscape Medical News. Even though he concluded in this study and in previous research that the benzene levels are not clinically meaningful, Barbieri said he sees the ongoing research as an important way to improve the products and thoroughly address safety concerns.

The production process and ingredient composition had a significant association with benzene levels, Barbieri found.

New Study, Recent Research

Barbieri and his colleagues evaluated the vehicles for the 111 products that had previously had their benzene levels evaluated by researchers at Valisure, an independent lab that tests the purity and safety of drugs and consumer products and reported its findings in 2024.

In that report, the Valisure researchers concluded: “Results suggest that potential benzene exposure from formation during BPO drug product use poses significant risks independent of the starting benzene concentration.”

In the new study, Barbieri found a median benzene concentration of 0.89 and a range of 0.19-35.3 parts per million (ppm); the US Food and Drug Administration (FDA) sets a limit of 2 ppm (interquartile range, 0.39-2.48). He cautioned, however, that concerns had been expressed about Valisure’s methodology, so replication of the findings is crucial.

Barbieri categorized products by use, such as leave-on or wash-on; concentration of BP; and days until expiration date (a measure of product age). They also looked at whether the product had a formulation, based on the ingredient list, which could indicate higher temperatures encountered by BP during formulation (such as hot processing), antioxidants (such as butylated hydroxytoluene [BHT]), and more acidity of the product (which could quench free radicals before they could turn into benzene).

Products included brands such as Clearasil, Neutrogena, Proactiv, Equate, Up&Up, Walgreens, CVS Health, and others.

Their findings were as follows:

• Leave-on products, which are often made in smaller batches and may cool more quickly, were associated with significantly lower concentrations of benzene.
• No significant association was found between BP and benzene concentrations.
• A weak but statistically significant association was found between days to expiration date and benzene concentration.
• In a regression model analyzed and adjusted for BP concentration, product type, and days until expiration, conditions consistent with hot processing were linked with increased benzene concentration and the use of antioxidants such as BHT with decreased benzene concentration.
• Each 100 days of storage at room temperature is linked with an increase of <1 ppm of benzene. “That suggests benzene is not forming at room temperature at any meaningful degree,” Barbieri said.

The findings could be of value to manufacturers, Barbieri said. Perhaps they would want to consider how to reduce or avoid heat during manufacturing to keep benzene levels as low as possible.

Expert Perspective

“There are multiple factors that could result in a slight increase of benzene levels in the products,” said Henry W. Lim, MD, former chair of dermatology and senior vice president for academic affairs at Henry Ford Health, Detroit. He reviewed the findings but wasn’t involved in the study. There is not a single factor, he said.

Also important to point out, he told Medscape Medical News, is that research has not found any clinical signal that anyone developed cancer because of these products.

“Most dermatologists are very, very comfortable to recommend these benzoyl peroxide products,” Lim said.

Perspective: Valisure

The new research finding about the importance of formulation “is very much in line with our results and what we have published multiple times,” said David Light, co-founder and president of Valisure, in a phone interview. “Benzoyl peroxide products are unstable and form benzene. Formulation is likely the strongest contributor to benzene content in benzoyl peroxide drug products.”

“The idea that formulation has a big impact on benzene formulation, we absolutely agree with,” he said. He believes manufacturers should reformulate with a goal of reducing benzene formulation but said he hasn’t seen substantiative action on that from them or the FDA.

While his lab doesn’t give an opinion on any clinically meaningful effects, his stand remains the same. “We think the presence of benzene is extremely concerning and should be eliminated or at least substantially reduced.”

Barbieri received consulting fees from Honeydew Care and Dexcel Pharma outside the submitted work. Lim had no disclosures. Valisure filed patents on shelf-stable formulations of BP and methods of producing them.

Kathleen Doheny is a freelance journalist in Los Angeles.