Electronic cigarettes: overview of chemical composition and exposure estimation

Table 5 Toxicological thresholds selected for calculating the margin of exposure

Agent	Toxicological Endpoint^a	Value [mg/kg bw/day]	Type of endpoint^b	Reference
Nicotine	Heart rate acceleration in humans	0.008	LOAEL^c	EFSA [30] based on Lindgren et al. [42]
Nicotine	Heart rate acceleration in humans	0.0008	ADI	EFSA [30] based on Lindgren et al. [42]
Glycerol	2-year study in rats, no effects observed	10,000	NOAEL	OECD SIDS [31] based on Hine et al. [43]
1,2-Propanediol	2-year studies in rats and dogs, no effects observed in rats, increased erythrocyte destruction in dogs	2,500	NOAEL	JECFA [32] based on Gaunt et al. [44] and Weil et al. [45]
1,2-Propanediol		25	ADI	JECFA [32] based on Gaunt et al. [44] and Weil et al. [45]
Ethylene glycol	Developmental toxicity data in mice (total malformations and a skeletal variation)	76	BMDL₁₀	ATSDR [33] based on Neeper-Bradley et al. [46] and Tyl et al. [47]
Ethylene glycol		0.8	MRL
1,3-Propanediol	Developmental toxicity study in rats	1,000	NOAEL	EFSA Panel on Contaminants in the Food Chain [34] based on unpublished data
Thujone	Clonic seizures in rats	11	BMDL₁₀	Lachenmeier and Uebelacker [36] based on NTP [48]
Thujone	Clonic seizures in rats	0.11	ADI	Lachenmeier and Uebelacker [36] based on NTP [48]
Ethyl vanillin	13-week study in rats, no effects observed	500	NOEL	JECFA [35] based on unpublished data
Ethyl vanillin	13-week study in rats, no effects observed	3	ADI	JECFA [35] based on unpublished data

^aHuman data was preferred over animal data, if available. The most sensitive endpoint was chosen if dose–response data for several organ sites were available.
^bBMDL₁₀: lower one-sided confidence limit of the benchmark dose (BMD) for a 10% incidence of health effect. The No Effect Level (NOEL) or No Observed Adverse Effect Level (NOAEL) are used in cases when no usable BMD-modelling for oral exposure was identified in the literature. ADI: acceptable daily intake. MRL: minimal risk level.
^cThe lowest observed adverse effect level (LOAEL) is considered by EFSA [30] as close to the NOAEL. The values were derived from a study in humans who were injected nicotine intravenously assuming an oral bioavailability of 44%.

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