Acne medications containing benzoyl peroxide may be contaminated with the carcinogen benzene

Acne is a common skin condition that occurs when hair follicles, or pores, become clogged with oil, dead skin cells, and sometimes bacteria, leading to inflammation and characteristic lesions like pimples, blackheads, and whiteheads. It most often affects areas with many sebaceous (oil) glands, like the face, chest, and back, and is particularly common during adolescence, though it can occur at any age.

The causes of acne include the following:

• Excess Sebum Production: During puberty and other hormonal changes (like pregnancy), sebaceous glands produce more oil, or sebum. This excess oil can mix with dead skin cells, making it easier for pores to become clogged.
• Clogged Pores: Normally, dead skin cells are shed from the skin's surface, but in acne, they mix with excess oil and block pores. This creates an environment where acne-causing bacteria can thrive. Pores are small openings in the skin’s surface that serve as pathways for sweat and oils (sebum) to reach the outer layer of the skin.
• Bacterial Growth: Cutibacterium acnes is a bacterium that naturally resides on the skin. When it becomes trapped in clogged pores, it multiplies, triggering an immune response that leads to inflammation.

There are numerous medications for treating acne. Some of the most popular contain benzoyl peroxide as the active ingredient (Figure 1), and they are available both over-the-counter as well as by prescription. Benzoyl peroxide is able to generate free radicals which are capable of killing the acne-causing bacteria. By reducing the bacterial population, it helps prevent and treat inflamed pimples. In addition, benzoyl peroxide removes dead skin cells and excess oil from the skin’s surface, helping to prevent pores from clogging presumably through a mechanism that also involves free radicals (which may facilitate the removal of dead skin cells).

When benzoyl peroxide produces free radicals, it is converted into benzenoic acid which is harmless. However, there is an additional side reaction in which benzoyl peroxide under certain conditions can decompose into benzene which is not harmless (Figure 1). Two studies from an independent lab and private company called Valisure measured benzene levels in over 100 benzoyl peroxide-based acne products and found that a third contained high benzene levels, but there is an asterisk associated with this finding.

But first, benzene is classified as a carcinogen. It is well-documented to cause various forms of cancer, especially leukemia and other blood-related cancers such as lymphoma. Benzene exposure typically occurs through inhalation or skin contact, especially in industrial settings where benzene is used or produced, such as the manufacture of plastics and rubber, as well as crude-oil refining. The International Agency for Research on Cancer (IARC) and the U.S. Environmental Protection Agency (EPA) both classify benzene as a known human carcinogen.

Benzene causes cancer by disrupting the normal function of cells, particularly those in the bone marrow. When benzene is inhaled or absorbed, it is metabolized by the liver into toxic compounds (including those that generate free radicals) that can bind to and interfere with DNA and cellular repair mechanisms. This leads to mutations and genomic instability, increasing the risk of cancer, especially in blood-forming tissues. Unlike benzene, benzoyl peroxide cannot be inhaled or absorbed through the skin to gain access to the blood.

In the first study, the Valisure group subjected the acne medications to high temperatures, and found that the elevated temperatures significantly increased benzene levels in benzoyl peroxide products. Products stored above 150°F for extended periods (e.g., two weeks) showed particularly high benzene formation. For example, a commercial product from Proactiv stored at 158°F for almost 17 hours contained benzene levels 18 times higher than the FDA's safe limit for drugs (MSN). Importantly, acne treatments containing other active ingredients, such as salicylic acid or adapalene, did not exhibit elevated benzene levels, suggesting the issue is specific to benzoyl peroxide products.

Some brands, like Clearasil, rebutted these claims asserting that their products are safe when used as directed, and that Valisure’s findings reflected extreme conditions not typically experienced in normal use. The reaction in which benzoyl peroxide decomposes to benzene typically occurs at high temperatures or when benzoyl peroxide is exposed to intense UV light. In most topical skincare products, they argued that this reaction is unlikely because these conditions are avoided, and stabilizers are often added to prevent decomposition.

In a follow-up study, Valisure addressed these concerns by keeping the products at room temperature. Then they exposed the products to physiological conditions such as body temperature and ambient levels of UV light. In addition, their results were subjected to peer review and published in a medical journal. They found much lower levels of benzene with about 70 acne products not exceeding the US safety limit. The ones that did only slightly exceeded the limit such as some Clearasil products contained benzene just above the 2 parts per million (ppm) safety threshold.

In summary, storage of benzoyl peroxide containing acne medications at very high temperatures can result in the production of dangerous levels of the carcinogen benzene. Standard storage and application conditions can produce benzene at lower concentrations close to the safety limit. The Valisure research has been valuable in making the manufacturers and FDA aware of this problem. Since 2021, the FDA has recommended that the companies test products containing hydrocarbons, like benzoyl peroxide, for benzene contamination. Hopefully, the manufacturers take the findings and guidance seriously which would mitigate this potential threat. 

Figure 1. Chemical reactions involving the breakdown of benzoyl peroxide. Under standard conditions, benzoyl peroxide will split releasing a free radical which can help to kill bacteria and forming two molecules of benzoic acid which is relatively harmless. Under more extreme conditions, especially high temperatures, the benzoyl peroxide will split into a benzoyl radical species that releases carbon dioxide to form the carcinogen benzene.