Increased demand for e-cigarettes has led to a wide availability of refills containing nicotine-based e-liquids, so accurate communication of hazard to consumers is imperative. Nicotine itself has a harmonised classification, but classification of mixtures containing low concentrations has proved controversial, stimulating action to review the current classification.

For human health, nicotine is currently classified as toxic if swallowed (Category 3; H301) and fatal in contact with skin (Category 1; H310). The Dutch Competent Authority has an intention to submit a dossier proposing a change in the acute oral classification to fatal if swallowed (Category 1, H300), which would affect the classification of e-liquids, that typically contain nicotine at up to 40 mg/ml. The submitted dossier will be evaluated by ECHA, who may submit a final proposal to the Commission to decide whether new harmonised classification and labelling should be adopted.

A Category 3 oral classification implies an LD50 value (usually in rats) of 50 to 300 mg/kg bw. This fits with most of the available data on nicotine, including studies recorded in the relevant REACH dossier. No doubt the Dutch report will indicate what support there is for the more severe Category 1 classification. Possible candidates include mouse LD50 values of 3 and 18 mg/kg bw (presumably evaluated for the original harmonised classification; their study reliability/quality is unclear) or perhaps human data (an often-cited approximate lethal dose of 1 mg/kg bw was comprehensively demolished in 2014, potentially in favour of about 10 mg/kg bw).

In terms of health risk assessment (entirely separate from classification), the spilling of 10 ml of a 40 mg/ml solution onto the skin of a 20-kg child would provide a dermal dose of 20 mg/kg bw. This is close to the LD50 of ≤50 mg/kg bw implied by the Category 1 acute dermal classification; it would be highly undesirable, and highlights the importance of children not having access to e-liquids. Regarding oral exposure, a modern view on nicotine toxicity would be welcomed, as it should lead to consistency in the classification of mixtures (including e-liquids).

The toxicologists at bibra are highly experienced in the hazard and risk assessment of e-liquids and other chemical mixtures, and are well-versed in the classification and labelling of hazardous substances.

The above items were taken from the April 2015 issue of Toxicology and Regulatory News which is sent automatically to members of bibra (click here).

 

November update:

RAC agrees with a Dutch proposal that nicotine should be subject to harmonised classification and labelling as fatal if swallowed, inhaled or in contact with the skin, but recommends classification as Acute Tox. 2 for all routes rather than Acute Tox.1 for dermal and oral nicotine. RAC supports the application of acute toxicity estimates (ATEs) when nicotine is part of a mixture (e.g. in e-cigarettes), with ATEs of 5 mg/kg bw orally, 70.4 mg/kg bw dermally, and 0.19 mg/L by inhalation.

European Chemicals Agency (2015). Committee for Risk Assessment (RAC). Opinion proposing harmonised classification and labelling at EU level of nicotine (ISO); 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine. CLH-O-0000001412-86-68/F. Adopted 10 September 2015. http://echa.europa.eu/documents/10162/f9510930-4e5e-45ff-bb3a-888cefaf6592

 

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