Toxicological Evaluation of Electronic Nicotine Delivery Systems and E-Liquids

What are ENDS?

Electronic Nicotine Delivery Systems (ENDS), also known as e-cigarettes, are tobacco products that use electronic systems to deliver nicotine to the user. They heat a nicotine-containing liquid to vaporize it so that it can be inhaled. They are considered an alternative to traditional tobacco products and have become extremely popular in many countries. The nicotine-containing liquids, which are called e-liquids, can come in many flavors in addition to the excipients propylene glycol (PG) and vegetable glycerol (VG). Both PG and VG belong to the alcohol class of molecules and together they act as solvents for the nicotine and flavor molecules. The greater the VG amount in the e-liquid, the greater the amount of “white cloud” of vapor that can be formed that ENDS users like to inhale and see. 

ENDS come in two main types, an open system and closed “pod”-like systems. The open system has an atomizer unit comprising controls, battery, and heating coils along with a user-fillable tank. A pod ENDS system has an atomizer unit like the open ENDS devices, but it uses prefilled and sealed e-liquid tanks, which are often referred to as pods. Both open and pod ENDS are consumer devices that can have modifiable settings such as power and voltage to enable users to consume different vape amounts in a single puff. Today, manufacturers are designing and producing 4th generation devices for consumers and consideration as prescription smoking cessation devices.

In most countries, the regulation and sale of ENDS devices and e-liquids are strictly controlled. A few countries have banned the use of ENDS devices outright. However, in other countries, regulatory authorities have taken a positive stance toward ENDS products, viewing them as a way to reduce harm to smokers. Accordingly, those countries have developed regulatory pathways for their approval and sale.

Who Uses ENDS?

Most users of ENDS devices with nicotine-containing e-liquids are adults, many of whom still smoke tobacco products or consume other nicotine products. In 2019, 4.5% of U.S. adults were current e-cigarette users. However, some adult users of ENDS devices have never smoked other tobacco products. Among current adult e-cigarette users in the U.S., the percentage who have never smoked cigarettes is highest among those aged 18–24 years (56.0%) and is lower in older age groups. In 2019, among current adult e-cigarette users overall, 36.9% also currently smoked cigarettes, 39.5% formerly smoked cigarettes, and 23.6% had never smoked cigarettes.

Additionally, and of great concern to regulatory and health bodies, are the number of children trying ENDS devices and becoming regular ENDS users. In 2021, an estimated 2.06 million U.S. middle and high school students were current e-cigarette users. This number includes 11.3% of high school students and 2.8% of middle school students.

In England, the current use of ENDS among adults has remained stable since 2014, and in 2019 was between 5% and 7%. Current ENDS prevalence among smokers there varied between 14% and 20% across surveys, again showing little change since 2014. Kapan et al. conducted a “narrative review” of ENDS use in European populations and found that males, adolescents, young adults, smokers of conventional cigarettes, and former smokers are all more likely to use ENDS. The prevalence of current e-cigarette use ranged from 0.2% to 27%, and daily use ranged from 1% to between 2.9% and 4%. The percentage of the population that has ever used ENDS ranged from 5.5% to 56.6%.

ENDS - assessing their toxicity

Are ENDS harmful?

The answer to this question is yes, but they are considered less harmful than regular cigarettes. Many governments actively promote a smoke-free health policy framework. In recent years, the tobacco industry has been promoting a harm reduction agenda that involves finding and developing products that will cause less harm than regular cigarettes. They aim to improve health outcomes for both smokers and society at large. In partnership with regulatory assessors, analytical chemists, and ENDS producers, toxicologists conduct risk assessments of ENDS devices.

ENDS products can and usually do contain nicotine, a highly addictive substance and one that is toxic to developing fetuses. Nicotine exposure has also been shown to impair adolescent and young brain development. Other chemicals that can be present in the vapor of ENDS devices are also known to cause harm to the lungs and body. These chemicals include metals like lead, nickel, and chromium, as well as toxic volatile organic compounds, which include cancer-causing chemicals. However, the number of and exposure to toxic chemicals is much reduced for ENDS devices compared to the over 7,000 toxic chemicals present in cigarette smoke. Leading U.K. health and public health organizations including the Royal College of Physicians, the British Medical Association, and Cancer Research UK now agree that, while not risk-free, e-cigarettes are far less harmful than smoking.

How can Evalueserve Help You Risk-Assess Your ENDS and e-Liquid Products?

Chemicals in the vapor of ENDS devices can originate in the materials of the device itself, the ingredients in the e-liquid, or thermal transformation during the heating process. Our toxicologists search and retrieve all relevant and publicly available knowledge on these chemicals to identify known hazards. Our digital solutions offer insights and risk assessment process enhancements. The solutions comprehensively search and retrieve information from up to 70 databases in a fast and efficient manner, giving the toxicologist more time to evaluate the information. 

Our experts summarize data on chemical properties, use cases, and toxicological findings, such as acute and general toxicity, irritation and sensitization potential, reproductive and development toxicities, carcinogenicity, and mutagenicity. We also collate expert review analysis and regulatory health values to protect the general population. Our toxicological profiles support risk assessments of human exposure predictions of these chemicals in acute, chronic, and lifetime settings. 

We can provide you with a toxicological repository of your profiles and data, connecting product use, material choice, and supplier information to information on the regulatory framework. This gives you an understanding of chemical safety in your portfolio of products.

Case Study

A client needed to submit regulatory risk assessments for a U.S. Premarket Tobacco Product Application for an ENDS device and associated e-liquid. To meet their deadline, they enlisted Evalueserve. We helped the client complete toxicological evaluations and toxicological profile updates for over 50 chemicals. We complemented the client’s toxicological capacity for completing the profiles and solved their capability gaps in data collation and analysis.

Our toxicology consultants put together a pilot program in partnership with the client to establish technical requirements for delivering these complex profiles. This program was eventually turned into a full-time equivalency relationship in which dedicated toxicologists were assigned to deliver the client program of work. We accelerated the delivery of these complex toxicological reports with our domain expertise and technology solutions. The reports had comprehensive search and analysis with high accuracy, relevancy, and quality.

Evalueserve Capabilities

Our Chemical Safety & Regulatory Affairs team is a global team of toxicologists, regulatory scientists, chemists, project managers, and solution architects that delivers a broad range of toxicology and risk assessment services in multiple industry domains. We cover everything from materials and environmental assessments to guidance value derivations and clinical use data analysis. 

We are knowledgeable about chemical safety and risk assessment evaluation in cosmetics, personal care products, home care products, agrochemicals, ENDS & oral nicotine products, food and nutritional products, and medical devices. We also offer bespoke digital solutions in toxicology information retrieval, management, and updating.


Talk to One of Our Experts

Connect with us to find out how we can help with your chemical safety and risk assessment needs. 

Alex Bell
Associate Director, Chemical Safety and Regulatory Affairs at Evalueserve Posts

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