Winter 2025

Benzene: Everywhere You Look

By Caroline B. Tuit, Ph.D.

A rash of reports in recent years have found benzene at elevated concentrations in personal care products, including hand sanitizers, aerosol products (i.e., antiperspirants, sunscreens, antiseptics, antifungals, dry shampoos), after-sun care gels, acne medications made with benzoyl peroxide, and, recently, generic cold medicines (Light et al., 2021a,b,c, 2022, 2024; US FDA, 2023).  Much of this discovery is the work of a single laboratory, Valisure, which has submitted five citizen petitions to the US Food and Drug Administration (US FDA) in the past three years regarding benzene contamination in products (see Chart).  These efforts have been followed by considerable media attention and, in some cases, product recalls and class action lawsuits.  Given this intense focus on benzene, manufacturers may want to consider reviewing and testing their product portfolios to identify any potential vulnerabilities.  However, identifying the right method for product testing can be difficult and may depend on the product composition, potential routes of exposure, and regulatory limits, among other factors.

Identifying the right method for product testing can be difficult and may depend on the product composition, potential routes of exposure, and regulatory limits, among other factors.”

The methods used by Valisure are not significant technological leaps; they are built on established US FDA and US Pharmecopeia (USP) headspace gas chromatography (GC) methods (USP, 2007; US FDA, 2020).  The focus on personal care products regulated by US FDA means the relevant regulatory criteria is the 2 parts per million (ppm) benzene limit US FDA has placed on Class I solvents in drugs.  This is a relatively low bar to meet.  For comparison, the US FDA method for benzene in soft drinks and other beverages has a quantification limit of approximately 1 part per billion (ppb), while the US Environmental Protection Agency (US EPA) drinking water maximum contaminant limit is 5 ppb (US FDA, 2006).  The Valisure methods for benzene are based on “USP <467> Residual Solvents Procedure A,” modified from flame ionization detection (FID) to mass spectrometry (MS) detection (USP, 2007).  These methods use selected ion monitoring (SIM), which increases the sensitivity of the MS, but quantification is typically based on external standard curve, with only the most recent method employing internal standard quantification.  In contrast, methods meeting sub-ppb detection limits for benzene generally use isotope dilution quantification methods and cryo-concentration, in addition to SIM (US FDA, 2006).

US FDA validated a method for benzene in sunscreen by headspace gas chromatography-mass spectrometry (GC-MS) (US FDA, 2024) very similar to the Valisure method, with a notable exception that US FDA uses internal standard quantification and a headspace incubation temperature of 90°C.  Valisure uses a temperature of 37°C (98.6°F) for the headspace incubation to limit the formation of benzene from thermal degradation during analysis to only that which could be expected at body temperatures (Light et al., 2024).  The potential for thermal generation of benzene was considered in the US FDA soft drink method (US FDA, 2006), which did not find any formation of benzene from common preservatives, particularly benzoate salts and ascorbic acid.  This issue, however, was not evaluated during the sunscreen method validation despite the presence of potential precursors, such as avobenzone and oxybenzone (US FDA, 2024).  The potential impact of thermal generation has been demonstrated by Valisure’s recent studies on benzoyl peroxide products, which have shown no benzene generation at 2°C compared to rapid generation of benzene at elevated temperatures (50°C/122°F) (Light et al., 2024).  When benzene precursors are known to be present in a product, it may be more prudent to adopt a lower incubation temperature as a precaution or to perform thermal degradation testing.

Indeed, whether these elevated temperatures are relevant for consumer exposure, or the concentrations measured in any of these products will result in significant increases in consumer exposure to benzene compared to more common sources (e.g., gasoline, cigarette smoke), is currently the subject of considerable debate.  However, it seems likely that efforts by independent labs and nongovernmental organizations (NGOs) may continue to drive product testing and potential regulations.  US FDA met recently with Valisure to “hear about Valisure’s business and future plans and to share information about appropriate analytical testing approaches for the work that Valisure does” (US FDA, 2024).  Prudent manufacturers may want to take steps to understand their potential vulnerabilities now.