Profile of incidental exposures to e-cigarette liquids in Europe,2018

Abstract

Background:

Following the implementation of the European Union Tobacco Product Directive (EU TPD) regulations on e-cigarette products in 2016, we assessed the current profile of e-cigarette liquid exposure incidents and their associated health outcomes.

Methods:

De-identified data were received from poison centers in eight EU Member States (Sweden, the Netherlands, Italy, Hungary Austria, Finland, Spain and Croatia) reporting on e-cigarette liquid exposure incidents between August 2018 to December 2019. Descriptive analysis was conducted to present incident characteristics and health outcomes. Chi-square tests and multivariable logistic regression analysis were used to test associations.

Results:

Of the 223 e-liquid exposure incidents recorded by poison centers in multiple EU MS, 64.7% of the cases were unintentional exposures, ranging from 48.4% among adults aged ≥19 years to 100.0% among children aged 0–5 years (p < 0.05). The most frequent route of exposure was ingestion (73.5%) while55.2% experienced any clinical symptoms, including nausea (16.6%), vomiting (11.1%), and dizziness (9.0%). 57.8% of the cases were treated at the residence or on-site.

Conclusion:

Further monitoring is warranted, using uniform reporting requirements, to ensure the continued compliance to the EU TPD and assess its long-term impact on related incident characteristics.

Keywords

Poisoning e-cigarettes e-liquid poison centers Europe

Introduction

As the popularity and availability of e-cigarettes have grown across European Union Member States (EU MS),^1
–3 it is important to monitor potential exposure incidents related to e-cigarette liquid use and misuse. An assessment of incidental exposures to e-cigarette liquids in 10 EU MS had noted that the number of reported incidents substantially rose during 2012 to 2014, highlighting the fact that the majority (71.3%) of incidents were unintentional exposures involving e-cigarette refill vials, and that ingestion of e-liquids was more frequent among young children compared to adults.⁴

To protect consumers from any adverse health effects that may be caused by accidental exposures, the EU Tobacco Products Directive (TPD) 2014/40/EU,⁵ along with the Commission Implementing Decision EU 2016/586 (2016),⁶ set forth technical standards for the e-cigarette refill vials in the EU. The requirements enumerated in the EU TPD Article 20 include, but not limited to, a maximum volume for e-liquid refill vials (≤10 mL), a maximum nicotine content of the vial (≤20 mg/mL), and the existence of child-resistant fastening and a tamper-proof system. These requirements were developed with the aim to mitigate the following four major risks associated with the use of e-cigarettes as outlined by the European Commission Report to the EU Council and Parliament: 1) poisoning from ingesting e-liquids containing nicotine, especially for young children; 2) skin reactions through 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 customization.⁷

Following the implementation of the above regulations, it is of importance to monitor the current profile of the e-cigarette liquid exposure incidents. The objective of this study was to provide a profile of the e-cigarette liquid exposure incidents and their associated health outcomes across multiple EU MS after the implementation of the EU TPD.

Methods

Data collection

De-identified data were received from poison centers in eight EU MS (Sweden [SE], the Netherlands [NL], Italy [IT], Hungary [HU], Austria [AT], Finland [FI], Spain [ES] and Croatia [HR]) reporting on e-cigarette liquid exposure incidents between August 2018 to December 2019. Data were obtained independently from each poison center due to the lack of a functional unified reporting system across the EU. Data on the case’s age (≤18, and ≥19 years); gender (male, female); route of exposure (ingestion, respiratory, dermal and ocular); type of exposure source (e-cigarette refill liquid-, e-cigarette non-refillable cartridge-, unknown—as per the definitions of the Tobacco Products Directive⁵); management of the incident (managed on-site, hospital, other); reported symptoms (vomiting, dizziness, nausea, throat conditions, eye conditions, headache, diarrhea, breathing conditions, tremor, or any other symptoms), reported clinical outcome (minor/moderate/major outcomes and death); and reason of exposure (unintentional, intentional, abuse, misuse, or suspected suicidal attempt) were collected from the archive of each center. For the purpose of our analysis, abuse, misuse, and suspected suicidal attempt cases were grouped as intentional exposures. As this was a secondary analysis of de-identified data, ethics review by an institutional review board (IRB) was not required. However, the study was conducted with respect to the confidentiality of the records.

Statistical analyses

Descriptive analysis was conducted to present frequencies and percentages of characteristics of exposure incidents. Fisher’s exact tests were used to examine bivariate associations between exposure characteristics. We also conducted a multivariable Poisson regression analysis to investigate associations between the presence of any symptoms and age, sex, the intentionality of exposure, and management of the incident. The level of significance was set at p < 0.05. Data were analyzed using R statistical package version 3.6.1.

Results

Characteristics of exposure incidents

During 2018–2019, a total of 223 incidents were reported to the participating poison centers across eight EU MS (77 NL; 45 SE; 45 FI; 21 ES; 15 AT; 10 IT; 8 HU; 2 HR). By the type of the exposure source, 162 incidents were reported as exposures to e-cigarette refill liquids, only one incident was from a non-refillable e-cigarette, and the remaining 60 incidents were from an unknown type of e-liquid. While 96 incidents resulted in no clinical outcome, 119 reported the presence of any clinical outcomes (96 minor, 16 moderate, 5 major clinical outcomes, and 1 death).

The majority of cases were adults aged ≥19 years (61.9%), male (57.1%), and exposed unintentionally (64.7%). Among all the incidents reported, the most common route of exposure was ingestion (73.5%) followed by respiratory intake (15.2%) (Table 1). 55.2% of the incidents reported the presence of any symptoms. The most common symptoms reported were nausea (16.6%), followed by vomiting (11.7%), and dizziness (9.0%). More than half the incidents were managed at the residence or on-site (57.8%).

Table 1.

Incidents of exposure to e-liquids reported to poison centers in 8 European Union Member States,¹ 2018–2019 (n = 223).

				Age group							Intentionality					Presence of symptom
		All		0–5 yo		6–18 yo		≥19 yo		p-value	Unintentional		Intentional		p-value	No		Yes		p-value
		n	%	n	%	n	%	n	%		n	%	n	%		n	%	n	%
Age	0–5 yo	63	29.3	—	—	—	—	—	—	—	63	45.3	0	0.0	<0.05	50	52.6	13	10.8	<0.05
	6–18 yo	19	8.8	—	—	—	—	—	—	—	10	7.2	8	10.7		6	6.3	13	10.8
	≥19 yo	133	61.9	—	—	—	—	—	—	—	66	47.5	67	89.3		39	41.1	94	78.3
Gender	Female	98	45.8	24	42.9	4	21.1	67	50.8	0.06	60	44.1	37	47.4	0.88	45	48.4	53	43.8	0.58
	Male	116	54.2	32	57.1	15	78.9	65	49.2		76	55.9	41	52.6		48	51.6	68	56.2
Intentionality	Unintentional	143	64.7	63	100.0	10	58.8	66	51.6	<0.05	—	—	—	—	—	84	86.6	59	50.9	<0.05
	Intentional	78	35.3	0	0.0	7	41.2	62	48.4							13	13.4	57	49.1
	(Abuse)	7	3.2	0	0.0	1	5.9	6	4.7	0.23	—	—	—	—	—	2	2.1	5	4.3	0.46
	(Misuse)	9	4.1	0	0.0	2	11.8	5	3.9	<0.05	—	—	—	—	—	1	1.0	8	6.9	<0.05
	(Suspected suicidal attempt)	8	3.6	0	0.0	2	11.8	6	4.7	0.06	—	—	—	—	—	0	0.0	8	6.9	<0.05
Exposure route	Ingestion	164	73.5	61	96.8	15	78.9	85	63.9	<0.05	115	80.4	48	61.5	<0.05	82	82.0	82	66.7	<0.05
	Respiratory	34	15.2	1	1.6	5	26.3	25	18.8	<0.05	3	2.1	31	39.7	<0.05	8	8.0	26	21.1	<0.05
	Dermal	16	7.2	3	4.8	0	0.0	12	9.0	0.40	16	11.2	0	0.0	<0.05	12	12.0	4	3.3	<0.05
	Ocular	14	6.3	0	0.0	0	0.0	13	9.8	<0.05	14	9.8	1	1.3	<0.05	3	3.0	11	8.9	0.09
	Other	3	1.3	2	3.2	0	0.0	1	0.8	0.43	2	1.4	1	1.3	1.00	2	2.0	1	0.8	0.58
Presence of any symptom	No	100	44.8	50	79.4	6	31.6	39	29.3	<0.05	84	58.7	15	19.2	<0.05	—	—	—	—	—
	Yes	123	55.2	13	20.6	13	68.4	94	70.7		59	41.3	63	80.8
	(Vomiting)	26	11.7	7	11.1	2	10.5	17	12.8	0.98	15	10.5	11	14.1	0.48	—	—	—	—	—
	(Dizziness)	20	9.0	0	0.0	2	10.5	17	12.8	<0.05	8	5.6	12	15.4	<0.05	—	—	—	—	—
	(Nausea)	37	16.6	3	4.8	1	5.3	32	24.1	<0.05	15	10.5	23	29.5	<0.05	—	—	—	—	—
	(Throat conditions)	7	3.1	0	0.0	1	5.3	6	4.5	0.22	3	2.1	4	5.1	0.26	—	—	—	—	—
	(Abdominal conditions)	13	5.8	2	3.2	1	5.3	10	7.5	0.49	8	5.6	5	6.4	0.90	—	—	—	—	—
	(Eye conditions)	14	6.3	0	0.0	0	0.0	13	9.8	<0.05	12	8.4	3	3.8	0.21	—	—	—	—	—
	(Headache)	12	5.4	0	0.0	2	10.5	9	6.8	0.07	3	2.1	9	11.5	<0.05	—	—	—	—	—
	(Diarrhea)	1	0.4	1	1.6	0	0.0	0	0.0	0.29	1	0.7	0	0.0	0.44	—	—	—	—	—
	(Breathing conditions)	10	4.5	1	1.6	1	5.3	7	5.3	0.48	1	0.7	1	1.3	<0.05	—	—	—	—	—
	(Tremor)	7	3.1	0	0.0	1	5.3	6	4.5	0.22	3	2.1	4	5.1	0.26	—	—	—	—	—
	(Other)	64	28.7	6	9.5	10	52.6	47	35.3	<0.05	27	18.9	35	44.9	<0.05	—	—	—	—	—
Management of incident	On-site	129	57.8	36	57.1	9	47.4	78	58.6	0.63	99	69.2	30	38.5	<0.05	74	74.0	55	44.7	<0.05
	Hospital	91	40.8	28	44.4	10	52.6	52	39.1	0.46	44	30.8	46	59.0	<0.05	24	24.0	67	54.5	<0.05
	Other	6	2.7	1	1.6	0	0.0	3	2.3	1.00	2	1.4	3	3.8	0.35	3	3.0	3	2.4	1.00

1: Data were from poison centers in the Netherland (n = 77), Sweden (n = 45), Finland (n = 45), Spain (n = 21), Austria (n = 15), Italy (n = 10), Hungary (n = 8), and Croatia (n = 2). Differences in distributions within subgroups were tested with chi-square tests. For exposure route, presence of any symptoms, and management incident, response categories are not mutually exclusive as respondents could choose multiple items.

At the bivariate level, age was associated with the intentionality of exposure, the exposure route, and the presence of symptoms such as dizziness, nausea, and eye conditions (p < 0.05). All 63 incidents among children aged 0–5 years were unintentional exposures to e-liquids. The proportions of intentional exposures were 41.2% and 48.4% among those aged 6–18 years and ≥19 years, respectively. The vast majority (96.8%) of the incidents among children aged 0–5 years were through ingestion, higher than that of older age groups. The presence of any symptom was lower among children aged 0–5 years (20.6%), and more than threefold among children aged 6–18 years (68.4%) and ≥19 years (70.7%).

The intentionality of exposure and the presence of any symptoms were also significantly associated at the bivariate level. The presence of symptoms was reported more frequently for intentional incidents (80.8%) in comparison to those that were unintentional (41.3%).

Associations between exposure characteristics and presence of symptoms

Compared to adults aged ≥19 years, children aged 0–5 years were less likely to report any symptoms (adjusted Prevalence Ratio [aPR] = 0.31, 95%CI = 0.19–0.52) (Table 2). The presence of any symptoms was 1.64 (95%CI = 1.31–2.06) times higher among incidents managed at hospitals than those maintained at other sites (residence, on-site, or other).

Table 2.

Associations between exposure characteristics and presence of symptoms reported to poison centers in 8 EU MS¹ in 2018–2019 (n = 214).

		Presence of any sypmtom² aPR (95%CI)
Age	0–5 yo	0.31 (0.19–0.52)
	6–18 yo	0.91 (0.65–1.27)
	≥19 yo	Ref.
Gender	Female	Ref.
	Male	1.13 (0.91–1.39)
Intentionality	Unintentional	Ref.
	Intentional	1.12 (0.89–1.40)
Management of incident	Residence/on-site/other only	Ref.
	Hospital	1.64 (1.31–2.06)

1: Data were from poison centers in the Netherland (n = 77), Sweden (n = 45), Finland (n = 36), Spain (n = 21), Austria (n = 15), Italy (n = 10), Hungary (n = 8), and Croatia (n = 2). Results in bold type imply statistical significance.

2: Reported symptoms include vomiting, dizziness, nausea, throat conditions, abdominal conditions, eye conditions, headache, diarrhea, breathing conditions, tremor, and/or any other symptoms.

Discussion

Of the 223 e-liquid exposure incidents recorded by poison centers in multiple EU MS, two in three cases were unintentional exposures, although with a wide range across age groups. The most frequent route of exposure was ingestion, resulting in various symptoms, including nausea, vomiting, and dizziness. More than half the cases were treated at the residence or on-site and experienced any clinical symptoms.

The profile of incident characteristics was mostly consistent with those identified before the implementation of the EU TPD Article 20, using data from ten EU MS during 2012–2015.⁴ Our analysis revealed that nearly one-third of the reported incidents were among children under 6 years old. This is different to the US, in which a high occurrence of child exposures was noted, as children under 5 years accounted for 63.3% of all domestic cases during 2018.⁸ It is also noteworthy that, in our study, all of the reported incidents among children under 6 years were unintentional exposures. Unintentional exposures also accounted for more than 50% of the incidents among older children and adults. To protect both adults and children from unintentional poisoning exposures, the EU TPD has set the specific requirements on e-cigarette product designs such as child-resistant fastening and tamper-proof packaging. A recent study evaluating product compliance to these regulations found that there were substantial improvements after the implementation of the EU TPD, achieving nearly a complete compliance among the most commonly used e-cigarette refill products in nine EU MS.⁹ However, another post-TPD study had recently indicated that e-cigarette users perceive that e-liquids are easy for a child to open, and experienced undesirable events such as e-liquid spilling during refill and leaking during use.¹⁰ Considering together with these, our findings support the maintained monitoring of design features of e-cigarettes and refill vials to ensure continued compliance with the regulations coupled with an assessment of consumers’ behaviors.

Of the 78 intentional exposure incidents reported in our study, an overwhelming majority (89.3%) was among adults aged 19 years or older. This is supported by the findings from a previous systematic literature review that intentional exposure to e-liquids is strongly predicted by age, and that suicide attempts are the primary cause of intoxication for those older than ten years in Europe and globally.¹¹ There were eight cases of suspected suicidal attempt in our data, accounting for 3.6% of the total incidents reported. Although our analysis did not show significant associations between the intentionality of exposure and adverse health outcomes after controlling for other exposure characteristics, this should be cautiously interpreted considering the small data size of the study, and that intentional use is often accompanied by a higher level of exposure that may consequently result in worse outcomes.¹¹

As was reported by the pre-TPD profile assessment in Europe and other studies,^4,12,13 we identified vomiting, nausea and dizziness as the most frequent symptoms from e-liquid exposure incidents, all of which are major symptoms of nicotine poisoning.¹⁴ Nevertheless, we cannot rule out the possibility that ingredients other than nicotine, including those the effects of which on human health have been understudied, or the combinations of chemical substances would cause or enhance adverse health outcomes.^11,15,16 As data on poisoning effects accumulate, it is important to continue close monitoring of ingredients of e-liquid products that are sold on the market.

The present study provides a multinational profile of e-cigarette exposure incidents across eight EU MS after the implementation of the EU TPD regulations. However, the study is subject to the following limitations. First, although we used pooled data from eight EU MS for the analysis, the majority of reported incidents were from a few countries such as NL (n = 77), SE (n = 45), and FI (n = 45), and did not include other e-cigarette related incidents, such as EVALI.¹⁷ Hence, the numbers of incidents reported to national poison centers were not proportional to either the country’s population size and may reflect differences in e-cigarette prevalence, quality control in the internal market or differences at the reporting level and might reflect reporting procedures or differences in the e-cigarette products used in each country and may not be generalizable to specific EU MS. Second, as the level of clinical outcomes was determined by each poison center individually, there may be inconsistencies in the classification across EU MS. To alleviate this limitation we used a common reporting format and asked each poison center to complete their data according to our predefined fields, so as to improve data harmonization. To this extent a common reporting format, and reporting process for use across EU MS would improve the quality of data reporting at the EU level. Continued monitoring with a standardized reporting format and process is warranted for the assessment of more generalizable long-term trends.

Conclusions

In eight EU MS during 2018–2019, almost two in three (64.7%) of the reported e-cigarette liquid exposure incidents were involuntary exposures. Children under 6 years old accounted for one-third of the total incidents. A majority of exposures occurred unintentionally, through ingestion, and resulted in various symptoms such as dizziness, vomiting and nausea. Further monitoring is warranted, using uniform reporting requirements, to ensure the continued compliance with the EU TPD and assess its long-term impact on related incident characteristics.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Constantine I Vardavas

Charis Girvalaki

Maria Caterina Grassi

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Profile of incidental exposures to e-cigarette liquids in Europe,2018–2019

Abstract

Background:

Methods:

Results:

Conclusion:

Keywords

Introduction

Methods

Data collection

Statistical analyses

Results

Characteristics of exposure incidents

Associations between exposure characteristics and presence of symptoms

Discussion

Conclusions

Footnotes

Declaration of conflicting interests

Funding

ORCID iDs

References