EUROPEAN COMMISSION Brussels, 20.5.2016 COM(2016) 269 final REPORT FROM THE COMMISSION TO THE EUROPEAN PARLIAMENT AND THE COUNCIL on the potential risks to public health associated with the use of refillable electronic cigarettes



Background and context Article 20(10) of Directive 2014/40/EU (‘Tobacco Products Directive’ or ‘TPD’) requires the European Commission to submit a report to the European Parliament and the Council on the potential risks to public health associated with the use of refillable electronic cigarettes (‘e-cigarettes’). At the time of the adoption of the TPD, there were concerns about the risks of refillable e-cigarettes to users and consumers, due to their particular characteristics, which allow users to come into direct contact with refill liquids (‘e-liquids’) containing nicotine and other ingredients which may have adverse health effects. It should be noted that this report identifies the particular risks that may be associated with refillable e-cigarettes and their refill containers, as requested by the co-legislators. The report does not aim to make comparisons between refillable and other types of e-cigarettes, and does not consider the potential public health impact of e-cigarettes in general (such as initiation, cessation, dual use and long-term health effects). E-cigarettes are relatively new products on the EU market and evidence concerning their potential risks and benefits is only starting to emerge. At this stage, the Commission and Member States are monitoring scientific evidence, user profiles and market developments regarding all types of e-cigarettes. This evidence will also inform the report on the application of the Tobacco Products Directive to be submitted from the Commission to the European Parliament, the Council, the European Economic and Social Committee and the Committee of the Regions pursuant to Article 28 of the TPD. This report was prepared with input from the PRECISE study prepared by an external contractor. This study analysed the available scientific literature on health risks of refillable e-cigarettes, data from EU poison centres in eight Member States, and performed chemical analysis on e-cigarette samples. The contractor also conducted a survey amongst the e-cigarette industry to determine what they believed to be the main risks associated with refillable e-cigarettes. The Commission has carefully considered the risks of refillable e-cigarettes identified by Member States and has discussed this report with the Expert Group on Tobacco Policy and the Subgroup on Electronic cigarettes. Information based on discussions with international regulators has also been included in this report. Regulation of e-cigarettes under the Tobacco Products Directive Article 20 of the TPD sets down a number of safety and quality requirements for nicotine-containing e-cigarettes intended for the consumer market. These consumer e-cigarettes may be disposable, rechargeable with a cartridge or refillable by means of refill containers containing e-liquid. Manufacturers and importers must notify their products to Member State competent authorities (Article 20(2)). This notification must include information on ingredients and emissions, toxicological data, information on nicotine doses and uptake, and a description of the device and production processes. Manufacturers must also submit sales data and information on consumer preferences annually to Member States (Article 20(7)). Manufacturers and importers must collect information on suspected adverse effects on human health and take immediate corrective action if they believe their products to be unsafe (Article 20(9)). The TPD sets limits on the amount of nicotine in consumer e-cigarettes and refill containers. E-liquids must not contain more than 20 mg/ml nicotine (Article 20(3)(b)), tanks and cartridges must not be larger than 2 ml, and refill containers must not be larger than 10 ml (Article 20(3)(a)). Refill containers and e-cigarettes must also be child-resistant and tamper-proof, and sold with instructions for use and health warnings (Article 20 paragraphs 3(g), 4(a) and (b)). Potential risks to public health The Commission has identified four main risks related to the use of refillable e-cigarettes. These risks are: (1) poisoning from ingesting e-liquids containing nicotine (especially for young children), (2) skin reactions related to dermal contact with e-liquids containing nicotine and other skin irritants, (3) risks associated with home blending and (4) risks due to using untested combinations of e-liquid and device or hardware customisation. 1. Accidental ingestion of e-liquid Refillable e-cigarettes and refill containers are, in most cases, open systems that allow direct access to nicotine-containing liquids. Nicotine is an alkaloid found in tobacco plants. It is a stimulant that acts on the parasympathetic nervous system and is the primary cause of addiction to tobacco products. A highly addictive drug, nicotine is also acutely toxic (lethal) by all routes of exposure in high enough doses. In its opinion on the reclassification of nicotine, the European Chemical Agency’s Committee for Risk Assessment (RAC) considered that 5 mg per kg bodyweight was a justified estimate for the acute toxicity of nicotine through oral exposure. This Acute Toxicity Estimate (ATE) value is in the same order as outlined by Mayer (2014) who estimated the lower limit causing fatal outcomes as 0.5-1 g of ingested nicotine, corresponding to an oral LD50 of 6.5-13 mg per kg bodyweight for humans. This translates to 390-780 mg of nicotine for a 60 kg adult and 65-130 mg for a 10 kg child. Based on the limits set out in the TPD, refillable e-cigarette devices can contain up to 40 mg nicotine and refill containers can hold up to 200 mg nicotine. There is, therefore, a particular risk for young children if they accidently ingest e-liquid especially from a refill container. There have been media reports of lethal poisonings of young children in the US and Israel from e-liquids. The PRECISE study commissioned for DG Health and Food Safety analysed 277 cases of nicotine poisoning reported to poison centres in eight EU Member States (Austria, Hungary, Ireland, Lithuania, Netherlands, Portugal, Sweden and Slovenia) from January 2012 to March 2015. They found that 87.3% of cases were related to refill liquids, 0.7% to non-refillable e-cigarettes and 12% to unknown product types (which may partly be explained by their large market share). Of the cases studied, 71.3% related to unintentional poisoning. Overall, 67.5% of cases followed ingestion of e-liquids. In terms of demographics, 33.2% of cases related to children aged five or under, 9.7% related to 6-18 year olds and 57% related to adults over the age of 18. Regarding outcome, 23.7% of cases required hospitalisation and 6.8% had a moderate or major effect. These results are similar to data from US poison centres. Finally, it should also be noted that many different flavours are used in e-liquids; some of which are classified as hazardous to health under the CLP Regulation and warrant further investigation. How to mitigate risks?

In order to mitigate the risk of accidental ingestion of nicotine-containing e-liquids, refill containers and e-cigarette devices should be child-resistant as laid down in Article 20(3)(g). Refillable ecigarettes and their refill containers should also be sold with appropriate instructions for use and storage to prevent accidental ingestion of e-liquid by children or adults and warnings for specific risk groups (Article 20(4)(a)(i) and (iii)). They should also indicate a list of ingredients and be labelled with appropriate health warnings to communicate the potential health risks to consumers (TPD Article 20(4)(b) and the CLP Regulation). The rather high percentage of poisonings involving adults over the age of 18 (57%) also suggests the need to increase awareness amongst citizens on the toxicity of the e-liquids containing nicotine, perhaps through national educational campaigns. In addition to these precautionary requirements, it is also important that other requirements are set for e-cigarettes; such as those laid down in Article 20(3) paragraphs (a) and (b) that ensure that e-liquid containers do not contain excessive levels of nicotine (which could be lethal to children and adults). 2. Dermal contact Refillable e-cigarettes require users to refill the device directly with e-liquid, usually using a small bottle or refill container. There is a risk when opening or refilling that e-liquid from refillable e-cigarettes is spilled and comes into contact with the skin. E-liquids contain substances that are toxic through dermal exposure (nicotine) or may be irritating to the skin (propylene glycol and flavours). In its Opinion on the reclassification of nicotine, the European Chemicals Agency’s Committee for Risk Assessment considered that 70 mg per kg bodyweight was a justified estimate for the acute toxicity of nicotine through dermal exposure. This ATE value is identical to the LD50 derived from animal data, as the lethal dose of nicotine by the dermal route in humans is largely unknown. This would mean that at the concentrations allowed by the TPD, the amount of e-liquid needed to produce an acutely toxic effect through dermal exposure in humans is 35 ml for a small child and 210 ml for a 60kg adult. This is larger than the maximum size of a refill container allowed under the TPD. In their analysis of poison centre data, the PRECISE study also found that 10% of reported cases were related to dermal exposure. Propylene glycol, a large component of many e-liquids, also appears to have mild irritating and sensitising effects on the skin of humans. Some flavour components have also been self-reported as skin sensitizers or irritants in the European Chemicals Agency’s C&L inventory. How to mitigate risks? In order to mitigate the risk of dermal contact with nicotine-containing e-liquids, refill containers and e-cigarette devices should be child-resistant and protected against leakage (Article 20(3)(g)). They should also be refilled in a manner and be designed in a way that ensures refilling without leakage as laid down in Article 20(3)(g), and specified further by Commission Implementing Decision (EU) 2016/586. Refillable e-cigarettes and their refill containers should also be sold with appropriate instructions for use and storage to ensure that users and others do not accidently come into contact with the e-liquid when handling e-cigarettes and information on possible adverse effects (Article 20(4)(a)(i) and (iv)). E-cigarettes should also be labelled according to the requirements set out in the TPD (Article 20(4)(b)) and those specified under other relevant EU legislation (such as the CLP Regulation). 3. Mixing or customisation of liquids Unlike disposable or rechargeable e-cigarettes, refillable e-cigarettes allow users more flexibility to determine the e-liquid used in their devices. Although the majority of users purchase e-liquids pre-blended, some users prefer to blend their own e-liquid at home by purchasing ingredients separately (home blending or self-mixing). Refillable e-cigarettes may also allow users to ‘customise’ their e-liquid according to personal preferences by, for example, mixing flavours. There are a number of risks associated with these practices. Firstly, home blending requires that users purchase high-concentration nicotine. E-liquid is, for example, sold in 50 ml bottles containing 72 mg/ml nicotine (3.6g of nicotine per bottle). As outlined previously, there are risks to users and others if high concentrations of nicotine liquid are stored at home and handled inappropriately. There is also a risk that consumers do not dilute the solution correctly resulting in much higher nicotine concentrations than intended in the final e-liquids. Although the TPD introduces maximum nicotine concentration levels for e-cigarettes (e-liquids must not contain more than 20 mg/ml nicotine) and limits the volume of refill containers (they must not be larger than 10 ml), there is a risk that home blending may also allow users to circumvent the limits set for e-cigarettes in the TPD (through the purchase of high concentration nicotine or nicotine in powdered form if not adequately controlled by Member States). The TPD requires manufacturers or importers to submit data on toxicological studies (Article 20(2)(c)) and to ensure that only high-purity ingredients are used in e-liquids(Article 20(3)(d)). Home blending would mean that untested e-liquids with inappropriate ingredients could continue to be used by consumers. Secondly, many of the flavours currently in use in e-liquids have not been tested for use in e-liquids and it is not known if they are safe for inhalation. There is evidence emerging that some flavours are not safe when used in e-cigarettes. One concern is that refillable e-cigarettes will allow users to continue to use untested or unsafe flavours. Users could also potentially mix flavours with unknown effects (either through home-blending or adding additional flavours to purchased e-liquids (‘customising’)). The health risks of second-hand exposure of vapour from such self-mixed e-liquids are also unknown. An additional concern is that refillable e-cigarettes may be used with illegal substances such as tetrahydrocannabinol (THC). In a study of 3,847 students in the United States, 5.4% had used e-cigarettes to vaporise cannabis. Of those that had ever used e-cigarettes, 18% had used them to vaporise cannabis. How to mitigate risks? In order to mitigate the risks associated with home blending or e-liquid customisation, Member States should ensure that manufacturers and importers respect the limits on nicotine concentration set by the TPD. The TPD does not allow e-liquids of concentrations higher than 20 mg/ml or in containers larger than 10 ml. Similarly, high-concentration liquid or powdered nicotine for other purposes, such as industrial use, should not be easily accessible for consumer purchase. If they do not already do so, Member States should also consider regulating or limiting the sale of such solutions or powders. Authorities should also ensure that oils or liquids with THC or other illicit substances are not sold to consumers in Member States where they are not allowed. Member States should also monitor notifications and conduct research on the toxicological profile of e-liquids and emissions as regards flavours and the mixing of flavours in notified products. Member States should carefully monitor evidence on the health risks of flavours. As additional evidence emerges, it may be justified for Member States to prohibit certain flavours for use in e-liquids (as outlined in Recital 47 of the TPD, the responsibility for adopting rules on flavours remains with the Member States). 4. Use of e-liquids with untested devices and hardware customisation Refillable e-cigarettes allow users to mix and match e-liquid and devices and to customise their devices by purchasing components separately and ‘building’ their own device (also known as hardware customisation). Studies have also shown that if e-liquid is heated to higher temperatures, an increase in toxic emissions is observed.