New Valisure Scientific Paper on Benzene in Benzoyl Peroxide Products
Top Dermatology Journal Publishes New Valisure Research on Benzene Presence and Formation in Benzoyl Peroxide Drug Products
Building upon Valisure’s March, 2024 scientific study and FDA Citizen Petition, which showed for the first time that benzoyl peroxide (BPO) acne treatment drug products are fundamentally unstable and can degrade into the known human carcinogen benzene, on October 7, 2024, Valisure co-authored another study that published in the Journal of Investigative Dermatology titled, “Evaluation of Benzene Presence and Formation in Benzoyl Peroxide Drug Products.”
This study provides evidence for unacceptably high levels of benzene concentrations in dozens of BPO drug products maintained at room temperature, that encapsulated BPO drug product has similar instability and formation of benzene as other BPO products at elevated temperatures, refrigeration may help prevent BPO degradation, and UV exposure indicative of standard sunlight can also degrade BPO and generate high levels of benzene. The graphical abstract for the paper summarizes its findings below:
David Light, Valisure’s Co-Founder and President and lead investigator on the study stated: "The discovery of benzene formation in benzoyl peroxide acne treatments presents a potentially serious public health risk. Our research demonstrates that these products, widely used by consumers of all ages, can potentially contain or generate concerningly high levels of benzene, particularly under common environmental conditions. This issue highlights the critical importance of rigorous independent testing of drug products to help protect consumers from harmful contaminants."
Unacceptable Benzene Levels Found in Marketed Products
Valisure’s testing showed that a significant portion of BPO products currently on the market already contain unacceptably high levels of benzene when purchased from major retailers and stored at room temperature. The new study provides evidence for a wide range of benzene concentrations (0.16 ppm to 35.30 ppm) detected by GC-MS in 111 over-the-counter BPO drug products tested and maintained at room temperature. 38 products, representing 34% percent of products tested, contained benzene above the conditionally restricted FDA limit of 2 ppm for benzene for drug products.
It is important to note that 2 ppm is a conditionally restricted FDA limit and is not a level for which the FDA deems a product is safe. FDA guidance states that benzene “should not be employed in the manufacture of drug substances, excipients, and drug products because of [its] unacceptable toxicity” and only if benzene’s “use is unavoidable in order to produce a drug product with a significant therapeutic advance, then [its] levels should be restricted” to 2 ppm. Such conditions do not seem to apply to benzoyl peroxide; therefore, the FDA allowance of up to 2 ppm of benzene does not appear to be acceptable for BPO drug products. Scientific studies have concluded that “There is probably no safe level of exposure to benzene,” and the Canadian drug regulatory agency, Health Canada, has reinforced that “there is no safe level of benzene.”
Unlike the benzene contamination Valisure found in sunscreens, hand sanitizers and other consumer products, benzene concentrations in BPO drug products can increase over time, especially when exposed to higher temperatures or sunlight. As the benzoyl peroxide degrades, the likelihood of benzene formation increases, exacerbating the public health threat. This means that even if the BPO drug product has no benzene in it when used by an individual, research in the new study shows that substantial amounts of benzene can form within minutes when exposed to UV from sunlight.
"The potential harm posed by benzene exposure should not be ignored, and only underscores the critical need for independent quality assurance pioneered by Valisure," stated Chip Phillips, Chief Executive Officer of Valisure. "At Valisure, we're constantly expanding not only our technical capabilities but also the ways we collaborate with the industry to recognize and reward quality, ensuring the well-being of all stakeholders in healthcare."
Drug Instability Similar to Valisure's Prior Zantac Findings
This situation mirrors Valisure’s groundbreaking discovery in 2019, which revealed that the popular heartburn medication Zantac (ranitidine) degrades into NDMA, another potent carcinogen, when exposed to elevated temperatures over time. Following these findings, the FDA requested the withdrawal of all ranitidine products, stating that “NDMA has been found to increase significantly in samples stored at higher temperatures, including temperatures the product may be exposed to during distribution and handling by consumers.”
Valisure’s research indicates that BPO products pose an even more immediate risk, as they produce benzene at levels over 800 times the conditional regulatory limit in just two weeks at 50°C—lower than the reported 70°C conditions necessary to trigger NDMA formation in ranitidine at 1 times the regulatory limit in two weeks.
Toxicology and Clinical Implications
All of Valisure’s studies did not perform any toxicological or clinical analyses. Recently published studies have started to investigate these questions and the JID study discusses this topic in its conclusion:
“The toxicological and clinical implications of these findings are concerning and should be investigated. Future studies should consider and account for the substantial variability between BPO drug product formulations and between patients’ amount of use, especially for a drug product like BPO that is both over-the-counter and prescription (e.g., some patients may use a few milligrams as “spot treatments” only a few times per year and other patients may utilize many grams of prescription products for large areas of their bodies on a daily basis).
Standard, population-wide studies such as those recently performed regarding BPO use (Garate et al., 2024; Sadr et al., 2024), may not be meaningful without accounting for these substantive variations. Indeed, retrospective epidemiological studies of ranitidine, which was also available over-the-counter and prescription and possessed large variability in patient use, was shown by multiple population studies to have no detectable correlation to malignancies (You et al., 2023); however, when a population was adjusted to focus on high “defined daily dose” individuals, it revealed the strongest correlations to expected cancers in a dose-dependent manner (Wang et al., 2022). Future BPO research should consider such population adjustments and formulation-specific evaluations.”
New Valisure Scientific Paper on Benzene in Benzoyl Peroxide Products
October 7, 2024
Top Dermatology Journal Publishes New Valisure Research on Benzene Presence and Formation in Benzoyl Peroxide Drug Products
Building upon Valisure’s March, 2024 scientific study and FDA Citizen Petition, which showed for the first time that benzoyl peroxide (BPO) acne treatment drug products are fundamentally unstable and can degrade into the known human carcinogen benzene, on October 7, 2024, Valisure co-authored another study that published in the Journal of Investigative Dermatology titled, “Evaluation of Benzene Presence and Formation in Benzoyl Peroxide Drug Products.”
This study provides evidence for unacceptably high levels of benzene concentrations in dozens of BPO drug products maintained at room temperature, that encapsulated BPO drug product has similar instability and formation of benzene as other BPO products at elevated temperatures, refrigeration may help prevent BPO degradation, and UV exposure indicative of standard sunlight can also degrade BPO and generate high levels of benzene. The graphical abstract for the paper summarizes its findings below:
David Light, Valisure’s Co-Founder and President and lead investigator on the study stated: "The discovery of benzene formation in benzoyl peroxide acne treatments presents a potentially serious public health risk. Our research demonstrates that these products, widely used by consumers of all ages, can potentially contain or generate concerningly high levels of benzene, particularly under common environmental conditions. This issue highlights the critical importance of rigorous independent testing of drug products to help protect consumers from harmful contaminants."
Unacceptable Benzene Levels Found in Marketed Products
Valisure’s testing showed that a significant portion of BPO products currently on the market already contain unacceptably high levels of benzene when purchased from major retailers and stored at room temperature. The new study provides evidence for a wide range of benzene concentrations (0.16 ppm to 35.30 ppm) detected by GC-MS in 111 over-the-counter BPO drug products tested and maintained at room temperature. 38 products, representing 34% percent of products tested, contained benzene above the conditionally restricted FDA limit of 2 ppm for benzene for drug products.
It is important to note that 2 ppm is a conditionally restricted FDA limit and is not a level for which the FDA deems a product is safe. FDA guidance states that benzene “should not be employed in the manufacture of drug substances, excipients, and drug products because of [its] unacceptable toxicity” and only if benzene’s “use is unavoidable in order to produce a drug product with a significant therapeutic advance, then [its] levels should be restricted” to 2 ppm. Such conditions do not seem to apply to benzoyl peroxide; therefore, the FDA allowance of up to 2 ppm of benzene does not appear to be acceptable for BPO drug products. Scientific studies have concluded that “There is probably no safe level of exposure to benzene,” and the Canadian drug regulatory agency, Health Canada, has reinforced that “there is no safe level of benzene.”
Unlike the benzene contamination Valisure found in sunscreens, hand sanitizers and other consumer products, benzene concentrations in BPO drug products can increase over time, especially when exposed to higher temperatures or sunlight. As the benzoyl peroxide degrades, the likelihood of benzene formation increases, exacerbating the public health threat. This means that even if the BPO drug product has no benzene in it when used by an individual, research in the new study shows that substantial amounts of benzene can form within minutes when exposed to UV from sunlight.
"The potential harm posed by benzene exposure should not be ignored, and only underscores the critical need for independent quality assurance pioneered by Valisure," stated Chip Phillips, Chief Executive Officer of Valisure. "At Valisure, we're constantly expanding not only our technical capabilities but also the ways we collaborate with the industry to recognize and reward quality, ensuring the well-being of all stakeholders in healthcare."
Drug Instability Similar to Valisure's Prior Zantac Findings
This situation mirrors Valisure’s groundbreaking discovery in 2019, which revealed that the popular heartburn medication Zantac (ranitidine) degrades into NDMA, another potent carcinogen, when exposed to elevated temperatures over time. Following these findings, the FDA requested the withdrawal of all ranitidine products, stating that “NDMA has been found to increase significantly in samples stored at higher temperatures, including temperatures the product may be exposed to during distribution and handling by consumers.”
Valisure’s research indicates that BPO products pose an even more immediate risk, as they produce benzene at levels over 800 times the conditional regulatory limit in just two weeks at 50°C—lower than the reported 70°C conditions necessary to trigger NDMA formation in ranitidine at 1 times the regulatory limit in two weeks.
Toxicology and Clinical Implications
All of Valisure’s studies did not perform any toxicological or clinical analyses. Recently published studies have started to investigate these questions and the JID study discusses this topic in its conclusion:
“The toxicological and clinical implications of these findings are concerning and should be investigated. Future studies should consider and account for the substantial variability between BPO drug product formulations and between patients’ amount of use, especially for a drug product like BPO that is both over-the-counter and prescription (e.g., some patients may use a few milligrams as “spot treatments” only a few times per year and other patients may utilize many grams of prescription products for large areas of their bodies on a daily basis).
Standard, population-wide studies such as those recently performed regarding BPO use (Garate et al., 2024; Sadr et al., 2024), may not be meaningful without accounting for these substantive variations. Indeed, retrospective epidemiological studies of ranitidine, which was also available over-the-counter and prescription and possessed large variability in patient use, was shown by multiple population studies to have no detectable correlation to malignancies (You et al., 2023); however, when a population was adjusted to focus on high “defined daily dose” individuals, it revealed the strongest correlations to expected cancers in a dose-dependent manner (Wang et al., 2022). Future BPO research should consider such population adjustments and formulation-specific evaluations.”
New Valisure Scientific Paper on Benzene in Benzoyl Peroxide Products
Top Dermatology Journal Publishes New Valisure Research on Benzene Presence and Formation in Benzoyl Peroxide Drug Products
Building upon Valisure’s March, 2024 scientific study and FDA Citizen Petition, which showed for the first time that benzoyl peroxide (BPO) acne treatment drug products are fundamentally unstable and can degrade into the known human carcinogen benzene, on October 7, 2024, Valisure co-authored another study that published in the Journal of Investigative Dermatology titled, “Evaluation of Benzene Presence and Formation in Benzoyl Peroxide Drug Products.”
This study provides evidence for unacceptably high levels of benzene concentrations in dozens of BPO drug products maintained at room temperature, that encapsulated BPO drug product has similar instability and formation of benzene as other BPO products at elevated temperatures, refrigeration may help prevent BPO degradation, and UV exposure indicative of standard sunlight can also degrade BPO and generate high levels of benzene. The graphical abstract for the paper summarizes its findings below:
David Light, Valisure’s Co-Founder and President and lead investigator on the study stated: "The discovery of benzene formation in benzoyl peroxide acne treatments presents a potentially serious public health risk. Our research demonstrates that these products, widely used by consumers of all ages, can potentially contain or generate concerningly high levels of benzene, particularly under common environmental conditions. This issue highlights the critical importance of rigorous independent testing of drug products to help protect consumers from harmful contaminants."
Unacceptable Benzene Levels Found in Marketed Products
Valisure’s testing showed that a significant portion of BPO products currently on the market already contain unacceptably high levels of benzene when purchased from major retailers and stored at room temperature. The new study provides evidence for a wide range of benzene concentrations (0.16 ppm to 35.30 ppm) detected by GC-MS in 111 over-the-counter BPO drug products tested and maintained at room temperature. 38 products, representing 34% percent of products tested, contained benzene above the conditionally restricted FDA limit of 2 ppm for benzene for drug products.
It is important to note that 2 ppm is a conditionally restricted FDA limit and is not a level for which the FDA deems a product is safe. FDA guidance states that benzene “should not be employed in the manufacture of drug substances, excipients, and drug products because of [its] unacceptable toxicity” and only if benzene’s “use is unavoidable in order to produce a drug product with a significant therapeutic advance, then [its] levels should be restricted” to 2 ppm. Such conditions do not seem to apply to benzoyl peroxide; therefore, the FDA allowance of up to 2 ppm of benzene does not appear to be acceptable for BPO drug products. Scientific studies have concluded that “There is probably no safe level of exposure to benzene,” and the Canadian drug regulatory agency, Health Canada, has reinforced that “there is no safe level of benzene.”
Unlike the benzene contamination Valisure found in sunscreens, hand sanitizers and other consumer products, benzene concentrations in BPO drug products can increase over time, especially when exposed to higher temperatures or sunlight. As the benzoyl peroxide degrades, the likelihood of benzene formation increases, exacerbating the public health threat. This means that even if the BPO drug product has no benzene in it when used by an individual, research in the new study shows that substantial amounts of benzene can form within minutes when exposed to UV from sunlight.
"The potential harm posed by benzene exposure should not be ignored, and only underscores the critical need for independent quality assurance pioneered by Valisure," stated Chip Phillips, Chief Executive Officer of Valisure. "At Valisure, we're constantly expanding not only our technical capabilities but also the ways we collaborate with the industry to recognize and reward quality, ensuring the well-being of all stakeholders in healthcare."
Drug Instability Similar to Valisure's Prior Zantac Findings
This situation mirrors Valisure’s groundbreaking discovery in 2019, which revealed that the popular heartburn medication Zantac (ranitidine) degrades into NDMA, another potent carcinogen, when exposed to elevated temperatures over time. Following these findings, the FDA requested the withdrawal of all ranitidine products, stating that “NDMA has been found to increase significantly in samples stored at higher temperatures, including temperatures the product may be exposed to during distribution and handling by consumers.”
Valisure’s research indicates that BPO products pose an even more immediate risk, as they produce benzene at levels over 800 times the conditional regulatory limit in just two weeks at 50°C—lower than the reported 70°C conditions necessary to trigger NDMA formation in ranitidine at 1 times the regulatory limit in two weeks.
Toxicology and Clinical Implications
All of Valisure’s studies did not perform any toxicological or clinical analyses. Recently published studies have started to investigate these questions and the JID study discusses this topic in its conclusion:
“The toxicological and clinical implications of these findings are concerning and should be investigated. Future studies should consider and account for the substantial variability between BPO drug product formulations and between patients’ amount of use, especially for a drug product like BPO that is both over-the-counter and prescription (e.g., some patients may use a few milligrams as “spot treatments” only a few times per year and other patients may utilize many grams of prescription products for large areas of their bodies on a daily basis).
Standard, population-wide studies such as those recently performed regarding BPO use (Garate et al., 2024; Sadr et al., 2024), may not be meaningful without accounting for these substantive variations. Indeed, retrospective epidemiological studies of ranitidine, which was also available over-the-counter and prescription and possessed large variability in patient use, was shown by multiple population studies to have no detectable correlation to malignancies (You et al., 2023); however, when a population was adjusted to focus on high “defined daily dose” individuals, it revealed the strongest correlations to expected cancers in a dose-dependent manner (Wang et al., 2022). Future BPO research should consider such population adjustments and formulation-specific evaluations.”
Top Dermatology Journal Publishes New Valisure Research on Benzene Presence and Formation in Benzoyl Peroxide Drug Products
Building upon Valisure’s March, 2024 scientific study and FDA Citizen Petition, which showed for the first time that benzoyl peroxide (BPO) acne treatment drug products are fundamentally unstable and can degrade into the known human carcinogen benzene, on October 7, 2024, Valisure co-authored another study that published in the Journal of Investigative Dermatology titled, “Evaluation of Benzene Presence and Formation in Benzoyl Peroxide Drug Products.”
This study provides evidence for unacceptably high levels of benzene concentrations in dozens of BPO drug products maintained at room temperature, that encapsulated BPO drug product has similar instability and formation of benzene as other BPO products at elevated temperatures, refrigeration may help prevent BPO degradation, and UV exposure indicative of standard sunlight can also degrade BPO and generate high levels of benzene. The graphical abstract for the paper summarizes its findings below:
David Light, Valisure’s Co-Founder and President and lead investigator on the study stated: "The discovery of benzene formation in benzoyl peroxide acne treatments presents a potentially serious public health risk. Our research demonstrates that these products, widely used by consumers of all ages, can potentially contain or generate concerningly high levels of benzene, particularly under common environmental conditions. This issue highlights the critical importance of rigorous independent testing of drug products to help protect consumers from harmful contaminants."
Unacceptable Benzene Levels Found in Marketed Products
Valisure’s testing showed that a significant portion of BPO products currently on the market already contain unacceptably high levels of benzene when purchased from major retailers and stored at room temperature. The new study provides evidence for a wide range of benzene concentrations (0.16 ppm to 35.30 ppm) detected by GC-MS in 111 over-the-counter BPO drug products tested and maintained at room temperature. 38 products, representing 34% percent of products tested, contained benzene above the conditionally restricted FDA limit of 2 ppm for benzene for drug products.
It is important to note that 2 ppm is a conditionally restricted FDA limit and is not a level for which the FDA deems a product is safe. FDA guidance states that benzene “should not be employed in the manufacture of drug substances, excipients, and drug products because of [its] unacceptable toxicity” and only if benzene’s “use is unavoidable in order to produce a drug product with a significant therapeutic advance, then [its] levels should be restricted” to 2 ppm. Such conditions do not seem to apply to benzoyl peroxide; therefore, the FDA allowance of up to 2 ppm of benzene does not appear to be acceptable for BPO drug products. Scientific studies have concluded that “There is probably no safe level of exposure to benzene,” and the Canadian drug regulatory agency, Health Canada, has reinforced that “there is no safe level of benzene.”
Unlike the benzene contamination Valisure found in sunscreens, hand sanitizers and other consumer products, benzene concentrations in BPO drug products can increase over time, especially when exposed to higher temperatures or sunlight. As the benzoyl peroxide degrades, the likelihood of benzene formation increases, exacerbating the public health threat. This means that even if the BPO drug product has no benzene in it when used by an individual, research in the new study shows that substantial amounts of benzene can form within minutes when exposed to UV from sunlight.
"The potential harm posed by benzene exposure should not be ignored, and only underscores the critical need for independent quality assurance pioneered by Valisure," stated Chip Phillips, Chief Executive Officer of Valisure. "At Valisure, we're constantly expanding not only our technical capabilities but also the ways we collaborate with the industry to recognize and reward quality, ensuring the well-being of all stakeholders in healthcare."
Drug Instability Similar to Valisure's Prior Zantac Findings
This situation mirrors Valisure’s groundbreaking discovery in 2019, which revealed that the popular heartburn medication Zantac (ranitidine) degrades into NDMA, another potent carcinogen, when exposed to elevated temperatures over time. Following these findings, the FDA requested the withdrawal of all ranitidine products, stating that “NDMA has been found to increase significantly in samples stored at higher temperatures, including temperatures the product may be exposed to during distribution and handling by consumers.”
Valisure’s research indicates that BPO products pose an even more immediate risk, as they produce benzene at levels over 800 times the conditional regulatory limit in just two weeks at 50°C—lower than the reported 70°C conditions necessary to trigger NDMA formation in ranitidine at 1 times the regulatory limit in two weeks.
Toxicology and Clinical Implications
All of Valisure’s studies did not perform any toxicological or clinical analyses. Recently published studies have started to investigate these questions and the JID study discusses this topic in its conclusion:
“The toxicological and clinical implications of these findings are concerning and should be investigated. Future studies should consider and account for the substantial variability between BPO drug product formulations and between patients’ amount of use, especially for a drug product like BPO that is both over-the-counter and prescription (e.g., some patients may use a few milligrams as “spot treatments” only a few times per year and other patients may utilize many grams of prescription products for large areas of their bodies on a daily basis).
Standard, population-wide studies such as those recently performed regarding BPO use (Garate et al., 2024; Sadr et al., 2024), may not be meaningful without accounting for these substantive variations. Indeed, retrospective epidemiological studies of ranitidine, which was also available over-the-counter and prescription and possessed large variability in patient use, was shown by multiple population studies to have no detectable correlation to malignancies (You et al., 2023); however, when a population was adjusted to focus on high “defined daily dose” individuals, it revealed the strongest correlations to expected cancers in a dose-dependent manner (Wang et al., 2022). Future BPO research should consider such population adjustments and formulation-specific evaluations.”
