VALISURE DETECTS KNOWN HUMAN CARCINOGEN BENZENE IN SEVERAL HAND SANITIZER PRODUCTS AND REQUESTS FDA ACTIONS

Samples from 44 hand sanitizer products contained benzene, an industrial chemical known to cause leukemia and carry other serious health risks  

NEW HAVEN, CT – MARCH 24, 2021 – Valisure has tested and detected benzene, a known human carcinogen, in several batches across multiple brands of hand sanitizer, which are considered drug products regulated by the Food and Drug Administration (FDA). Benzene is known to cause cancer in humans according to the U.S. Centers for Disease Control and Prevention (CDC), the International Agency for Research on Cancer (IARC), the World Health Organization (WHO), and other regulatory agencies. The National Institute for Occupational Safety and Health (NIOSH) defines benzene as a carcinogen and lists “inhalation, skin absorption, ingestion, skin and/or eye contact” as exposure routes. The FDA states that benzene should not be used in the manufacture of any component of a drug product because of its unacceptable toxicity; however, to meet the high demand for hand sanitizer during the COVID-19 public health emergency, FDA has allowed an interim limit of 2 parts per million (ppm) for benzene only in aqueous solution (liquid) hand sanitizers. Of the 260 hand sanitizer products tested by Valisure, including liquid and non-liquid products, 44 batches (17%) contained benzene with the highest level of benzene detected of 16.1ppm, which is over eight times this interim limit.

Valisure is asking FDA to request an immediate recall of the contaminated batches and to update its guidance to include an exposure limit for benzene in addition to a concentration. Also, Valisure is requesting FDA further investigate batches of hand sanitizer that, in addition to being  contaminated, are inconsistent with FDA guidance to not add inactive ingredients, such as those that improve smell, taste or appearance, that could increase the risk of ingestion from children. Some of the highly contaminated batches Valisure analyzed appear to be specifically formulated and marketed for children.

More Information: Valisure’s FDA Citizen Petition on Hand Sanitizer

Certified Products: List of hand sanitizer products that are batch-certified and where they are sold

Product Testing: Individuals or organizations can submit hand sanitizer samples for analysis at no cost

In June 2020, FDA updated their guidelines for the production of liquid hand sanitizer to temporarily allow for the presence of benzene of up to 2.0 ppm “to reflect data submitted by fuel ethanol manufacturers producing ethanol via fermentation and distillation, indicating that at least some of their fuel ethanol products have harmful chemicals, including gasoline and benzene, which are known human carcinogens (cancer-causing agents).”

Although hand sanitizers with unacceptable levels of benzene have not previously been identified, since mid-2020, FDA has issued warnings on hand sanitizer products that have been contaminated with methanol, which can lead to serious adverse events if the contaminated products are swallowed. The CDC has issued warnings regarding individuals ingesting hand sanitizer and has stated that, “Young children might unintentionally swallow these products [hand sanitizers], whereas adolescents or adults with history of alcohol use disorder might intentionally swallow these products as an alcohol (ethanol) substitute.”

The FDA also recognizes the danger of children ingesting hand sanitizer, and, in FDA’s guidance for the manufacture of hand sanitizer during the declared COVID-19 Public Health Emergency, the agency states that firms producing hand sanitizer should “not add other active or inactive ingredients, such as ingredients to improve the smell or taste, due to the risk of accidental ingestion in children.” Out of the 44 batches of hand sanitizer containing benzene, at least 20 (45%) have product labels that indicate the use of additional ingredients to improve the smell, taste, or appearance, which do not adhere to FDA guidance, and could make such products more appealing to children, thereby increasing the risk of ingestion of specifically contaminated products.

Although considerations for ingestion of hand sanitizer should be undertaken, hand sanitizer products are not intended to be swallowed and are labeled only for topical use. Therefore, a contaminant such as benzene that can harm individuals through dermal absorption or inhalation is of great concern for public health as it can potentially affect individuals that properly use hand sanitizer on exposed skin or breath its fumes.

Beginning in January of this year, FDA placed all alcohol-based hand sanitizers from Mexico on a countrywide import alert to help stop products that contain methanol from entering the U.S. As of March 9, 2021, 83% of the 231 FDA product warnings are for products manufactured in Mexico, 7% in China, and 3% in the United States. Of the 44 hand sanitizer products Valisure independently sourced and are contaminated with benzene, 2% are manufactured in Mexico, 50% in China, and 34% in the United States. This underscores the need for further action from FDA beyond the current import alerts.

“Consumer use of hand sanitizers has increased significantly during the coronavirus pandemic and while it is important that consumers have access to products that help ensure personal and public safety, it is of utmost importance that consumers have access to products that are safe and not contaminated,” stated David Light, Founder & CEO of Valisure. “The detection of hand sanitizer products that contain high levels of benzene is cause for significant concern as these products are potentially being used in high volumes several times daily by adults and children alike. We urge FDA and manufacturers to act expeditiously to remove the contaminated lots from the market. It is also important for consumers to understand that uncontaminated hand sanitizer products are available and should continue to be used.”

Benzene Toxicity

The toxicity of benzene in humans has been well established for over 120 years. The hematotoxicity of benzene has been described as early as 1897. A study from 1939 on benzene stated that “exposure over a long period of time to any concentration of benzene greater than zero is not safe,” which is a comment reiterated in a 2010 review of benzene research specifically stating “There is probably no safe level of exposure to benzene, and all exposures constitute some risk in a linear, if not supralinear, and additive fashion.”  Benzene is specifically associated with blood cancers such as leukemia, making absorption through the skin particularly concerning as there have been multiple FDA studies showing that structurally similar chemicals in sunscreen products are found in the blood at high levels after application to exposed skin.

There is a recent history of broad drug product recalls due to contamination with probable human carcinogens. Specifically, there have been a multitude of manufacturer recalls of medications, such as valsartan, irbesartan, losartan,  ranitidine, nizatidine,  and metformin,  due to the detection of the Group 2A “probable human carcinogen” N-Nitrosodimethylamine (NDMA) in excess of FDA limits. FDA limits for NDMA are defined in both (ppm) and permissible daily intake, which is held constant at a specified nanogram level (ng) per day for all drug products.  Having a constant permissible daily intake or exposure is critical when there is variability in drug product size and exposures per day, a situation particularly relevant to an individual’s application of hand sanitizer. Valisure is not aware of any FDA guidance on a permissible daily exposure for benzene in any drug product, including hand sanitizer, and is requesting urgent action from FDA to issue guidance to fill this gap.

Table of limits set for NDMA and benzene in drug products:

 NDMA –   Standard Drugs  Benzene – Special   Circumstances**  Benzene –   Standard Drugs
Concentration limit  (parts per million)  0.3 – 3.0 ppm*  2.0 ppm  Not specified***
Daily limit (nanograms)  96 ng  Not specified  Not specified***

*Dependent on the drug product. These numbers refer to guidance specifically for -sartan medications.
**A drug product constituting a “significant therapeutic advance” where the use of benzene for manufacturing is unavoidable or for hand sanitizer products during the declared COVID-19 Public Health Emergency.
***FDA states that benzene should not be employed in the manufacture of drug substances because of its unacceptable toxicity, but does not specifically define limits.

“With this discovery, we have potentially identified a new and very concerning category of contamination in drug products. To properly address this problem, we need better-defined regulatory parameters that must include exposure limits and not just concentration limits,” said David Light.  “As an example, when you’re on a diet you may need to keep track of the total amount of sugar that you consume in a day. Having one small slice of cake with a high ‘concentration’ of sugar might be fine. Eating the whole cake would amount to a very different total ‘exposure’ of sugar, even though each individual serving would have the same ‘concentration’ of sugar. Hand sanitizer products are typically used in many times greater volume than standard drug products like tablets or capsules, so even a relatively low concentration limit can result in very high total exposure. This strongly underscores the need for a daily limit in addition to a concentration limit.”

Valisure’s Findings

Valisure analyzed 260 unique batches from 168 different brands. Significant variability from batch to batch was observed, even within a single brand. Twenty-one batches of hand sanitizer were found to contain benzene above the 2.0 ppm FDA interim limit for the COVID-19 Public Health Emergency, with an additional 23 batches of hand sanitizer containing between 0.1 ppm – 2.0 ppm of benzene. Benzene was not detected in an additional 216 batches of hand sanitizer from 152 brands through initial analysis of at least one sample (see detailed tables in Valisure’s FDA Citizen Petition).

“Benzene has many industrial uses and, much like other toxic materials including lead and asbestos, regulators recognized the dangers of exposure to it and have tried to limit or eliminate its use. FDA makes it clear that benzene should not be used in drug manufacturing, except where required in situations involving a significant therapeutic advance or in special circumstances,” said Kaury Kucera, Chief Scientific Officer for Valisure. “We at Valisure recognize the importance of constant vigilance and not taking drug quality for granted, which is why we continuously expand our testing capabilities to investigate impurities that could be of potential concern. The safety of all consumers is the cornerstone of our mission at Valisure.”

In its testing of hand sanitizer products, Valisure also detected unacceptably high levels of methanol, and acetaldehyde, a Group 2B carcinogen defined by the WHO and IARC as “possibly carcinogenic to humans.” These results are also included in Valisure’s FDA Citizen Petition.

Valisure’s independent chemical testing has identified several serious drug quality issues, which have resulted in global recalls of ranitidine, a once common antacid medication, and metformin, a top diabetes drug with roughly 90 million prescriptions written per year in the United States.

Complete Valisure Citizen Petition Documents:

Full Petition – Contains lists of products where benzene was detected at 0.1 ppm or above.

Attachment A – Contains list of products where benzene was not detected at 0.1 ppm or above.

Attachment B – Resolution from the American College of Cardiology regarding independent testing.

Attachment C – Contains images of all products tested by Valisure. (File size: 75 MB)

About Valisure:

Valisure’s core mission is to independently check the chemical composition of medications before they reach consumers and deliver that transparency and visible quality assurance to patients, doctors, and the broader healthcare ecosystem. Valisure accomplishes this mission through partnerships with healthcare stakeholders engaged in patient care. In response to rising concerns about counterfeit medications, generics, and overseas manufacturing, Valisure’s team of Harvard- and Yale-trained scientists developed proprietary analytical technologies to screen out poor-quality batches. Every medication or supplement Valisure analyzes comes with a certificate of analysis listing important chemical properties of the samples analyzed at Valisure’s lab. Valisure has ISO 17025 accreditation and is DEA and FDA registered. For more information, please visit valisure.com and follow @Valisure on Twitter.