Study Supports News of Benzene in Benzoyl Peroxide Acne Products

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In 111 benzoyl-peroxide (BPO) drug products in major retailers within the US, new findings suggest significant contamination with benzene was uncovered when these products were tested shortly after acquisition off the shelf.¹

These findings were the conclusion of new research authored in part by Kaury Kucera, PhD, of Arnold & Marie Schwartz College of Pharmacy and Health Sciences at Long Island University in Connecticut. Kucera and colleagues conducted their research to assess BPO products for acne and rosacea and their potential inclusion of benzene, a known carcinogen.

This new research follows the March 2024 announcement by Valisure, the autonomous quality assurance organization, that their 8th US Food and Drug Administration (FDA) Citizen Petition would be filed due to ‘concerning’ levels of benzene in BPO acne treatment products and their fundamental instability.² The new analysis described here was both funded and resourced by Valisure, LLC.¹

“Since 2021, benzene contamination in consumer drug products including hand sanitizers (Valisure, 2021c), antifungal sprays (FDA, 2021b), sunscreens (Valisure, 2021b), antiperspirants (Valisure, 2021a), and dry shampoo products (Valisure, 2022) have led to global product recalls and FDA actions including industry guidance to reformulate some products to reduce the risk of benzene contamination,” Kucera et al. wrote.¹

Study Background

Prior academic literature has established that the decomposition of BPO into benzene is evident, though the investigators noted that despite FDA concerns the production of benzene from BPO found within drug products had not been documented widely until 2024. They cited long-term research which has linked even lower levels of exposure to cancer, in addition to warnings regarding hematotoxicity dating back to the 19th century.

The research team also added that there is not a safe level of benzene exposure for humans, further noting that FDA guidelines specify that drug products should not contain benzene due to its level of toxicity. Despite the presence of cases in which specific products may be exceptions due to their therapeutic benefits and the use of benzene in their manufacture, benzene content is still not permitted to exceed 2 parts per million (ppm).

The team expressed that Health Canada and the US Environmental Protection Agency (EPA) also caution against exposure, reporting that lifetime air exposure to only 0.4 ppb of benzene can raise risk of cancer. They highlighted the continued reinforcement of the position that no benzene exposure level is considered safe, affirmed by research conducted by the American Petroleum Institute in 1948 and more recent research in 2010.

Several product recalls have impacted products such as antifungal sprays, hand sanitizers, antiperspirants, sunscreens, and dry shampoos. These have also led FDA officials to issue guidance designed to diminish the risk of benzene in such products.

The aforementioned Valisure petition to the FDA touched upon the heat-induced instability of products made with BPO and the consequent formation of benzene. Tests were noted as having been conducted at temperatures of 50°C and 70°C, both commonly implemented for the purposes of stability testing and simulating an environment comparable to a ‘hot car.’

In addition to heat-induced benzene production, research also demonstrated that certain products were shown to have measurable levels of benzene at "Day 0," prior to exposure to temperature increases. Among 71 products tested, it was noted that 24 already contained more than 2 ppm of benzene, and 11 maintained concentrations higher than 10 ppm.

Design and Findings

Products in the latest study by Kucera and colleagues were found among major retail stores within up to 6 states in the US, spread across the entire country. Specifically, investigators looked at stores in Connecticut, California, Illinois, Floria, New York, and Texas.

The research team noted that in all situations in which duplicate lots were tested, sourcing of product samples from different states was conducted. They added that 2 products examined had expired by the time of the intake and testing.

The team reported that 111 drug products containing BPO which had been evaluated and sourced from American retailers were noted as having been contaminated substantially with benzene during tests shortly after being taken from the shelf.

The investigators noted that there was a range of averaged triplicate measurements which was 0.16 ± 6% ppm to 35.30 ± 2% ppm. They reported that 38 of the products, or 34% percent of products examined by the team, had contained levels of benzene above the conditionally restricted limits by FDA officials of 2 ppm in drug products.

The research team further found that the methods of analysis were more extensively summarized within the Valisure Citizen Petition on Benzene in Benzoyl Peroxide Drug Products from March 2024.

References

1. ^{Kucera K, Zenzola N, Hudspeth A, et al. Evaluation of benzene presence and formation in benzoyl peroxide drug products. J Invest Dermatol. October 7, 2024. https://www.jidonline.org/article/S0022-202X(24)02155-9/fulltext. Date accessed: October 7, 2024.}
2. ^{Smith T. Benzoyl Peroxide Acne Products Shown to Contain High Levels of Benzene. HCPLive. March 6, 2024. https://www.hcplive.com/view/benzoyl-peroxide-acne-products-shown-to-contain-high-levels-of-benzene. Date accessed: October 7, 2024.}