title: An approach to ingredient screening and toxicological risk assessment of flavours in e-liquids.
abstract: Flavour ingredients are an essential part of e-liquids. Their responsible selection and inclusion levels in e-liquids must be guided by toxicological principles. We propose an approach to the screening and toxicological risk assessment of flavour ingredients for e-liquids. The screening involves purity requirements and avoiding ingredients that are carcinogenic, mutagenic or toxic to reproduction. Additionally, owing to the uncertainties involved in potency determination and the derivation of a tolerable level for respiratory sensitisation, we propose excluding respiratory sensitisers. After screening, toxicological data on the ingredients should be reviewed. Inhalation-specific toxicological issues, for which no reliable safe levels can currently be derived, can lead to further ingredient exclusions. We discuss the use of toxicological thresholds of concern for flavours that lack inhalation data suitable for quantitative risk assessment. Higher toxicological thresholds of concern are suggested for flavour ingredients (170 or 980μg/day) than for contaminant assessment (1.5μg/day). Analytical detection limits for measurements of potential reaction and thermal breakdown products in vaping aerosol, should be informed by the contaminant threshold. This principle leads us to recommend 5ng/puff as an appropriate limit of detection for untargeted aerosol measurements.
authors.affiliation: Nicoventures, Research & Development, Regents Park Road, Southampton, Hampshire SO15 8TL, United Kingdom. Electronic address: Sandra_Costigan@nicoventures.co.uk.
authors.forename: S
authors.initials: S
authors.lastname: Costigan
authors.affiliation: British American Tobacco, Group Research and Development, Regents Park Road, Southampton, Hampshire SO15 8TL, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Meredith
mesh_terms: D000818:Animals; D066300:Electronic Nicotine Delivery Systems; D005421:Flavoring Agents / Q000737:chemistry / Q000633:toxicity*; D006358:Hot Temperature; D006801:Humans; D018570:Risk Assessment / Q000379:methods
chemical_list: D005421:Flavoring Agents
keywords: Contaminants; E-cigarettes; E-liquid; Electronic cigarettes; Flavour ingredients; Ingredient screening; TTCs; Toxicological risk assessment; Toxicological thresholds of concern; Vaping