New Study Explores Benzoyl Peroxide-Related Adverse Events and Potential Neoplasm Signals

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A new paper published in the Journal of Investigative Dermatology (JID) analyzed benzoyl peroxide (BPO) and its potential for adverse events (AEs) and malignancies, with strong signals suggesting increased reporting of malignancies in users of BPO.¹

To investigate potential associations between BPO use and potential cancer risk, researchers conducted a pharmacovigilance-based disproportionality analysis utilizing the US Food and Drug Administration’s Adverse Event Reporting System (FAERS) public dashboard. They examined quantities of BPO-related AEs and neoplasm cases, which include malignant neoplasms and cases of skin and breast cancer, among others.

“We note this study is hypothesis-generating, and causality cannot be established or inferred,” according to authors Yang et al.

Background

Within the past year, the subject of benzene contamination in BPO-containing products has been explored in numerous studies and academic papers. In March 2024, independent testing laboratory Valisure LLC shared a citizen petition³ to the FDA requesting a recall after their research reported that numerous BPO products contained up to 12 times the FDA’s allowable conditionally allowed limit of 2 parts per million of benzene.²

Later, Kucera et al published research in JID reporting testing of BPO products at room temperature, citing that "111 BPO drug products tested from major US retailers appear to be substantially contaminated with benzene when tested shortly after being acquired off the shelf."³

Earlier this year, a new study published in JAMA Dermatology examined how the formulation of BPO products affects benzene levels, particularly under high temperatures.⁴ Researchers found that hot processing increases benzene concentrations, while antioxidants like BHT help reduce them, reinforcing the importance of formulation, production, and distribution controls in minimizing benzene formation in BPO products.

“The chemical formation of benzene from benzoyl peroxide is well established. Recent research has demonstrated many benzoyl peroxide products have benzene concentrations exceeding the emergency or conditional FDA limit of 2 ppm benzene," said study investigator, associate professor of dermatology and physician-scientist at Yale School of Medicine in New Haven, Connecticut, and editor in chief of Dermatology Times, Christopher Bunick, MD, PhD. "While these products are not in line with FDA regulatory policy, the health implications of benzene exposure from BPO products on consumers and patients is less understood. This new research in JID does not establish causality or potential for risk, but does identify a malignancy signal in the FDA’s own adverse event reporting database that warrants further studies into BPO.”

The newly published AE report in JID includes collected data that predates the initial Valisure report in an effort to minimize bias and offer additional context.² Using the FAERS database to examine AEs from BPO has also been demonstrated in similar research, including a paper published earlier this year in the Journal of Cosmetic Dermatology.⁵

Data

From Q1 2019 to Q1 2024, FAERS recorded 452 AE cases associated with BPO use. Of these, 23 cases (5.09%) were classified under neoplasms, including benign, malignant, and unspecified tumors. The mean age of BPO users reporting AEs was 31.87 years, while the mean age of those reporting neoplasms was higher at 51.54 years. The study's population had a higher proportion of women than men, possibly reflecting acne’s greater prevalence among women.⁶ Notably, a significant portion of neoplasm-related cases were reported in the past 2 years.

A statistical disproportionality analysis revealed strong signals suggesting increased reporting of malignancies in BPO users. The reporting odds ratio (ROR) for malignant neoplasms was 5.59 (95% CI: 10.11, 3.09) with a chi-squared value of 36.65. For skin cancer specifically, the ROR was 6.94 (95% CI: 16.70, 2.88), meeting the threshold for a strong signal. Among Proactiv products containing BPO, the signals were even stronger, notably in line with previous research on the topic.³ The ROR for malignant neoplasms reached 63.31 (95% CI: 117.26, 34.18), while skin cancer had an ROR of 75.39 (95% CI: 184.17, 30.86). Breast cancer also showed a strong signal, with an ROR of 8.85 (95% CI: 27.79, 2.82). These findings highlight potential safety concerns that warrant further investigation.

The study aligns with existing literature indicating potential health risks associated with benzene exposure. Previous research has linked benzene derivatives to genetic mutations that may contribute to cancer development. Moreover, skin cancer associations have been noted in occupational settings where dermal absorption of aromatic hydrocarbons occurs.

Clinical Implications

Recent studies have reinforced concerns about benzene formation in BPO-containing products, particularly under standard storage conditions. Investigations have identified benzene in various acne treatments, prompting increased scrutiny from regulatory and public health entities. The findings in this analysis suggest a potential association between BPO use and reported malignancies, though causality remains unproven.

Although this study contributes valuable insights, it is important to recognize its limitations, including the potential for reporting bias and the inability to establish direct causation. “We believe this study to be hypothesis-generating and warrants further research investigating the relationship between BPO drug products and malignancies,” researchers wrote. Further research, including controlled clinical studies and formulation assessments, will be crucial to determining the long-term safety of BPO products. In the meantime, consumers and health care providers should remain informed about best practices for product storage and use while regulatory bodies continue to assess potential for AEs.

References

1. Yang K, Czyz S, Zuberi R, et al. A disproportionality analysis on benzoyl peroxide and its risk of malignancy using the FDA adverse event reporting system. J Invest Dermatol.

2. Valisure citizen petition on benzene in benzoyl peroxide drug products. Valisure. March 5, 2024. Accessed March 5, 2025. https://assets-global.website-files.com/6215052733f8bb8fea016220/65e8560962ed23f744902a7b_Valisure%20Citizen%20Petition%20on%20Benzene%20in%20Benzoyl%20Peroxide%20Drug%20Products.pdf

3. Kucera K, Zenzola N, Hudspeth A, et al. Evaluation of benzene presence and formation in benzoyl peroxide drug products. J Invest Dermatol. 2024 Oct 7:S0022-202X(24)02155-9. : 10.1016/j.jid.2024.09.009

4. Barbieri JS, Rubin CB, Pham JP, Wong M. The role of formulation in benzene formation in benzoyl peroxide products. JAMA Dermatol. 2025 Feb 12. doi: 10.1001/jamadermatol.2024.6443

5. Zhou S, Yan S, Ming S. A comprehensive study on adverse reactions of benzoyl peroxide (BPO) in dermatological aesthetics utilizing the FAERS database. J Cosmet Dermatol. 24: e16787. https://doi.org/10.1111/jocd.16787

6. Collier CN, Harper JC, Cafardi JA, et al. The prevalence of acne in adults 20 years and older. 2008 May;58(5):874. J Am Acad Dermatol. 2008;58(1):56-59. doi:10.1016/j.jaad.2007.06.045