Benzene Update at AAD Discusses Both Regulations and Health Risks

Christopher Bunick, MD, PhD, FAAD, made waves at the 2024 American Academy of Dermatology (AAD) Annual Meeting with his presentation about benzene in benzoyl peroxide (BPO) products for acne treatments. At the 2025 AAD Annual Meeting in Orlando, Florida, Dr. Bunick provided an update on the research in this area—and a renewed plea for dermatologists to take it seriously.

After first noting that his work in this area stemmed from US Food and Drug Administration (FDA) activity involving benzene in hand sanitizers and sunscreens, Dr. Bunick emphasized the regulatory aspect. The FDA’s two-parts-per-million limit, he noted, is conditional. The FDA states that substances in benzene’s category “should not be employed in the manufacture of drug substances, excipients, and drug products because of their unacceptable toxicity or their deleterious environmental effect” and that “if their use is unavoidable in order to produce a drug product with a significant therapeutic advance, then their levels should be restricted [to two parts per million].”¹

“We have many other ways to treat acne,” Dr. Bunick said. “We don't need benzene or benzoyl peroxide to treat acne given these other options. Therefore, you cannot justify a therapeutic advance. This is commonly misunderstood. People often say, ‘The limit's two parts per million. It's OK if it's 1.5 ppm.’ Well, actually, no. The FDA says it should be zero and there's only conditional or emergency situations where it can exceed that up to 2 ppm.”

Dr. Bunick also disputed the notion that BPO should be considered harmless because of a lack of evidence indicating an association between BPO use and increased cancer risks.

“It has been said by others that any concentration of benzene greater than zero is not safe. There is probably no safe level of exposure to benzene,” he said. “And the early studies in people that were exposed to high levels, such as workers in the petroleum industry, at a benzene exposure level of 0.8 to 1.6 parts per million, a strong risk of leukemia was seen. Our regulatory agencies have come out with their own statements. The CDC: Benzene causes cancer in humans. The World Health Organization: Benzene is a known human carcinogen in the same category as asbestos, lead, formaldehyde. The National Institute for Occupational Safety and Health has actually set a limit of 0.1 parts per million for worker exposure. And the EPA has a federal limit of five parts per billion in drinking water, with the goal being zero. There's also an EPA limit for short-term drinking water exposure to children of 0.2 parts per million.”

Dr. Bunick cited a prospective study from the United Kingdom published in April 2024 indicating that long-term exposure to even benzene levels less than one part per million increases the risk of all mortality as well as cardiovascular disease, cancer, and more.²

He also cited a 2020 Journal of the American Medical Association article that found the ingredients in chemical sunscreens to be systemically absorbed with plasma concentrations that surpassed the FDA threshold for potentially waiving some of the additional safety studies for sunscreens.³ Importantly, this paper established a protocol or guide for rigorous assessment of blood concentrations of chemicals from topical products applied to the skin.

“Why is this important? Because these levels of the chemical ingredients in our chemical-based sunscreens exceeded the plasma concentration that the FDA has set to require additional safety studies. And if you didn't know this study in detail, you wouldn't realize that these sunscreens were actually skating by without doing additional safety studies at the FDA,” Dr. Bunick said. “Shortly after the benzene exposure from sunscreens was talked about, this paper came out in JAAD: Sunscreen use is not associated with increased blood concentrations of benzene among adults in the United States: Data from [the National Health and Nutrition Examination Survey 2003-2006 and 2009-2018].⁴ If you just read the title, you're going to assume, ‘Eh, this isn't a big deal; just use the sunscreens. Not a big deal.’ But let's look; the devil's in the details here. Look at the major limitations of this study. The limitations include a lack of respondent detail on the last application of sunscreen and total daily sunscreen use and unknown timing of blood draws relative to the sunscreen use. … They didn't even have the data in the database to make the conclusion in the title of the paper.”

Similarly, Dr. Bunick said, limitations should have been acknowledged in the October 2024 paper “No evidence for an association between benzoyl peroxide use and increased blood benzene levels in the National Health and Nutrition Examination Survey.”⁵

“The database doesn't know how much benzoyl peroxide is used, it doesn't know the skin area applied to, we don't have the BPO concentration, and we don't know the timing of the blood draws to the product application,” Dr. Bunick said. “Therefore, we have to take into context how these databases contain data before making strong conclusions.”

Finally, Dr. Bunick cited a new paper that he and co-authors from Canada published in the Journal of Investigative Dermatology just days earlier.⁶ The authors utilized a pharmacovigilance-based disproportionality analysis using the FDA Adverse Event Reporting System (FAERS) to unveil possible associations between BPO and cancer adverse event reporting, though they noted that the study was hypothesis-generating and that causality cannot be established or inferred.

“The methodology here is like this: You have a drug of interest, you have all other drugs in the database, you have an occurrence of the adverse event of interest—which is malignancy—and the occurrence of all other adverse events. And you have the reporting odds ratio: the odds of a particular adverse event for a particular drug compared to the odds of that adverse event for the entire database,” Dr. Bunick said. “So what was fact? First of all, the data in this analysis was from a 5-year period before the benzene news broke, chosen so that there was reduced bias. There were a number of benzoyl peroxide products in cases of neoplastic-related adverse events. … Neoplasm malignant as a category had about 5.6 more likelihood for benzoyl peroxide products to have this adverse event than all other drugs in the database. Skin cancer, about seven and breast cancer 0.83.”

Furthermore, the brand that had been found in previous studies to have the highest levels of benzene at room temperature showed a 63-fold higher likelihood of adverse event reporting of malignant neoplasm, 75-fold higher for skin cancer, and 8.8-fold higher for breast cancer.5

“What does this mean? … It does not prove causality,” Dr. Bunick emphasized. “It doesn't measure risk. It tells us there's a statistical signal in the database that warrants further evaluation about benzoyl peroxide and its connection to malignancy.”

1. US Food and Drug Administration. Q3C — Tables and List Guidance for Industry. Published August 2018. Accessed March 12, 2025. https://www.fda.gov/media/133650/download
2. Wang J, Ma Y, et al. Long-Term Exposure to Low Concentrations of Ambient Benzene and Mortality in a National English Cohort. Am J Respir Crit Care Med. 2024;209(8):987-994. doi: 10.1164/rccm.202308-1440OC.
3. Matta MK, Florian J, et al. Effect of Sunscreen Application on Plasma Concentration of Sunscreen Active Ingredients: A Randomized Clinical Trial. JAMA. 2020;323(3):256-267. doi: 10.1001/jama.2019.20747. Erratum in: JAMA. 2020 Mar 17;323(11):1098. doi: 10.1001/jama.2020.1950.
4. Chang MS, Moore KJ, Trepanowski N, Koru-Sengul T, Hartman RI. Sunscreen use is not associated with increased blood concentrations of benzene among adults in the United States: Data from the National Health and Nutrition Examination Survey 2003-2006 and 2009-2018. J Am Acad Dermatol. 2022;87(2):440-443. doi: 10.1016/j.jaad.2021.09.003.
5. Sadr N, Troger A, Chai PR, Barbieri JS. No evidence for an association between benzoyl peroxide use and increased blood benzene levels in the National Health and Nutrition Examination Survey. J Am Acad Dermatol. 2024;91(4):763-765. doi: 10.1016/j.jaad.2024.06.050.
6. Yang K, et al. A Disproportionality Analysis on Benzoyl Peroxide and its Risk of Malignancy using the FDA Adverse Event Reporting System. Journal of Investigative Dermatology. Published online March 7, 2025. https://www.jidonline.org/article/S0022-202X(25)00300-8/fulltext.

Dr. Bunick’s comments have been lightly edited for clarity, with his approval.