Benzene, a known human carcinogen that has been detected in consumer products like hand sanitizers, sunscreens, spray deodorants, and dry shampoos, has now been found in commonly used acne treatments.
The presence of benzene in those consumer products was the result of contamination. But in the case of benzoyl peroxide (BPO) acne treatments — both over-the-counter and prescription — the cause has been attributed to the drug itself degrading into benzene, according to the latest citizen petition filed by New Haven, Connecticut-based independent laboratory Valisure.
“It is a fundamental issue with the benzoyl peroxide formulations themselves,” David Light, president of Valisure, told MedPage Today, likening the situation to what was previously seen with ranitidine (Zantac).
Of 175 acne treatment products initially tested by Valisure, all 76 that contained other ingredients — most commonly salicylic acid or adapalene — had benzene levels that were either undetectable or below the FDA’s current limit of 2 parts per million (ppm), the company said in its citizen petition. However, 94 of the 99 BPO products contained benzene, often with values well above 2 ppm.
“This high prevalence of benzene in specifically BPO acne treatment products and discovering research in the academic literature as early as 1936 that concluded BPO can directly degrade into benzene, led Valisure to conduct a stability study at elevated temperatures on a diverse market sweep of BPO products and formulations,” the company wrote.
This consisted of testing at temperatures of 37°C/98.6°F (body temperature), 50°C/122°F (accepted pharmaceutical stability testing temperature), and 70°C/158°F (hot car temperature).
An initial stability study of five products revealed that dozens of ppm of benzene can form in just a few weeks at the lowest of the three temperatures, and that hundreds of ppm of benzene can form at the middle temperature, Valisure stated. At the highest of the three temperatures, the apparent degradation of BPO would often cause product packaging to burst.
Accordingly, the middle temperature was selected as a stability temperature for a broader study of 66 BPO products, the company stated. In 18 days of stability testing at this temperature, the company detected over 1,500 ppm of benzene produced in two products, over 100 ppm in 17 products, and over 10 ppm in 42 products.
“Even if a product is clean when purchased, it can form high levels of benzene over time, even sitting in a medicine cabinet,” Valisure said in a separate statement on stability testing.
“The purpose of stability studies is not to copy the conditions of an average consumer, rather, the purpose is to ensure the product is safe to use for the entire product’s life cycle, from manufacturing through distribution to its expiration date, often a total of 3 years for pharmaceutical products,” the company added. Furthermore, “according to publicly available calculators, 3 years of room temperature stability is equal to about 169 days at 50°C (122°F).”
The company reiterated that it “observed dramatically high levels of benzene in only 18 days at 50°C,” in the case of the BPO acne treatments tested.
The statement also pointed to the past example of ranitidine. In 2019, Valisure filed a citizen petition to the FDA “showing that the ranitidine molecule is fundamentally unstable and degrades to form high levels of the carcinogen NDMA,” it stated. By 2020, the FDA requested that manufacturers withdraw all ranitidine products from the market because NDMA had been found to “‘increase significantly in samples stored at higher temperatures, including temperatures the product may be exposed to during distribution and handling by consumers.'”
As for Valisure’s current citizen petition, the company further noted that high levels of benzene were found not only inside BPO acne treatments, but also in the air around incubated products.
This shows that benzene “can leak out of some product packages and pose a potentially serious inhalation risk,” the company wrote.
Valisure is requesting that the FDA take action in the wake of the company’s findings, including issuing a regulation, revising industry guidance, and requesting a recall and suspending sales of BPO products in the U.S. market.
The FDA said in an emailed statement to MedPage Today that it is “committed to ensuring drugs Americans use are safe, effective, and of high-quality.”
“The agency acts on information provided from a variety of sources, such as that provided by Valisure, but such data must be verified as accurate and reproducible before it can be utilized to make regulatory decisions such as recommending product sale suspensions and recalls,” the FDA said. “The agency will continue to provide updates to the public regarding benzene in drug products, as appropriate.”
The FDA acknowledged that it received the latest citizen petition from Valisure, but noted that it generally does not comment on pending petitions. When the FDA responds to the petition, it will respond directly to the petitioner and post the response in a public docket.
The agency added that it “reminds manufacturers both of drugs marketed under approved applications and of other drugs, including over-the-counter monograph drug products, of their obligation to ensure their products conform to appropriate quality specifications.”
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