Benzene levels in benzoyl peroxide products may range from 0.19 to 35.3 parts per million, with formulation factors such as hot processing and antioxidant presence associated with these variations, according to a recent letter. 

In a study, published in JAMA Dermatology, researchers evaluated the role of formulation in benzene formation within benzoyl peroxide products. Given the widespread use of benzoyl peroxide for acne treatment and concerns regarding its degradation into benzene, a known human carcinogen, the researchers examined whether formulation characteristics could influence benzene concentrations in over-the-counter benzoyl peroxide products.

Led by John S. Barbieri, of Department of Dermatology at Brigham and Women’s Hospital, the researchers analyzed 111 benzoyl peroxide–containing products tested by Valisure, an independent laboratory specializing in pharmaceutical and consumer product safety. They then categorized the products by formulation type (leave-on vs wash), benzoyl peroxide concentration, days until expiration (as a proxy for product age), and specific formulation components, including the presence of excipients suggestive of high-temperature processing, antioxidants such as butylated hydroxytoluene (BHT), and benzoic acid, which may mitigate benzene formation. Multivariable linear regression was used to assess the association between these factors and benzene levels. Statistical analyses were conducted using Stata version 15.

The median benzene concentration across the 111 products was 0.89 parts per million (ppm) (range = 0.19–35.3 ppm, interquartile range = 0.39–2.48). Leave-on formulations were associated with lower benzene concentrations compared with wash-off products (coefficient = −5.83, 95% confidence interval [CI] = −8.15 to −3.51). No statistically significant association was observed between benzoyl peroxide concentration and benzene levels. A statistically significant but weak association was identified between benzene concentration and the number of days until expiration (coefficient = −0.010, 95% CI = −0.019 to −0.001).

In adjusted models, products containing excipients indicative of hot processing had higher benzene concentrations (coefficient = 7.34, 95% CI = 5.04–9.64), whereas the presence of BHT was associated with lower benzene concentrations (coefficient = −8.15, 95% CI = −13.03 to −3.26). Benzoic acid was also linked to lower benzene levels, though the association did not reach statistical significance (coefficient = −5.16, 95% CI = −10.54 to 0.23). Before incorporating formulation variables, product brand accounted for 32% of benzene level variance, which decreased to 15% after adjusting for formulation characteristics.

The study findings indicated that formulation characteristics may have a greater influence on benzene formation in benzoyl peroxide products than degradation over time at room temperature. The researchers noted that factors such as excipient selection and temperature control during manufacturing were associated with variations in benzene concentrations. They stated that further prospective studies are needed to confirm the findings.

Full disclosures can be found in the published letter.