according to results from an analysis that used gas chromatography–mass spectrometry and other methods.
The analysis, which was published in the Journal of Investigative Dermatology and expands on a similar study released more than 6 months ago, also found that encapsulated BPO products break down into benzene at room temperature but that refrigerating them may mitigate this effect.
“Our research provides the first experimental evidence that cold storage can help reduce the rate of benzoyl peroxide breakdown into benzene,” said one of the study authors, Christopher G. Bunick, MD, PhD, associate professor of dermatology at Yale University, New Haven, Connecticut. “Therefore, cold storage throughout the entire supply chain — from manufacturing to patient use — is a reasonable and proportional measure at this time for those continuing to use benzoyl peroxide medicine.” One acne product, the newer prescription triple-combination therapy (adapalene-clindamycin-BPO) “already has a cold shipping process in place; the patient just needs to continue that at home,” he noted.
For the study — which was funded by an independent lab, Valisure — researchers led by Valisure CEO and founder David Light, used gas chromatography-mass spectrometry to detect benzene levels in 111 BPO drug products from major US retailers and selected ion flow tube mass-spectrometry to quantify the release of benzene in real time. Benzene levels ranged from 0.16 ppm to 35.30 ppm, and 38 of the products (34%) had levels above the FDA limit of 2 ppm for drug products. “The results of the products sampled in this study suggest that formulation is likely the strongest contributor to benzene concentrations in BPO drug products that are commercially available, since the magnitude of benzene detected correlates most closely with specific brands or product types within certain brands,” the study authors wrote.
When the researchers tested the stability of a prescription encapsulated BPO drug product at cold (2 °C) and elevated temperature (50 °C), no apparent benzene formation was observed at 2 °C, whereas high levels of benzene formed at 50 °C, “suggesting that encapsulation technology may not stabilize BPO drug products, but cold storage may greatly reduce benzene formation,” they wrote.
In another component of the study, researchers exposed a BP drug product to a UVA/UVB lamp for 2 hours and found detectable benzene through evaporation and substantial benzene formation when exposed to UV light at levels below peak sunlight. The experiment “strongly justifies the package label warnings to avoid sun exposure when using BPO drug products,” the authors wrote. “Further evaluation to determine the influence of sun exposure on BPO drug product degradation and benzene formation is warranted.”
In an interview, John 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, Boston, Massachusetts characterized the findings as “an important issue that we should take seriously.” However, “we also must not overreact.”
BPO is a foundational acne treatment without any clear alternative, he said, pointing out that no evidence currently exists “to support that routine use of benzoyl peroxide–containing products for acne is associated with a meaningful risk of benzene in the blood or an increased risk of cancer.”
And although it is prudent to minimize benzene exposure as much as possible, Barbieri continued, “it is not clear that these levels are a clinically meaningful incremental risk in the setting of an acne cream or wash. There is minimal cutaneous absorption of benzene, and it is uncertain how much benzene aerosolizes with routine use, particularly for washes which are not left on the skin.”
Bunick said that the combined data from this and the study published in March 2024 affected which BPO products he recommends for patients with acne. “I am using exclusively the triple combination therapy (adapalene-clindamycin-benzoyl peroxide) because I know it has the necessary cold supply chain in place to protect the product’s stability. I further encourage patients to place all their benzoyl peroxide–containing products in the refrigerator at home to reduce benzene formation and exposure.”
Bunick reported having served as an investigator and/or a consultant/speaker for many pharmaceutical companies, including as a consultant for Ortho-Dermatologics; but none related to this study. Barbieri reported having no relevant disclosures.
A version of this article first appeared on Medscape.com.