• Alberto Oviedo, Stefan Lebrun, Ulrike Kogel, Jenny Ho, Wei Teck Tan, Bjoern Titz, Patrice Leroy, Gregory Vuillaume, Monali Bera, Florian Martin, Gregory Rodrigo, Marco Esposito, Ruth Dempsey, Nikolai V Ivanov, Julia Hoeng, Manuel C Peitsch, and Patrick Vanscheeuwijck.
• Philip Morris International Research Laboratories Pte Ltd, 50 Science Park Road #02-07, The Kendall, Science Park II, Singapore 117406, Singapore(2).
• Regul. Toxicol. Pharmacol. 2016 Nov 30; 81 Suppl 2: S93-S122.

AbstractThe toxicity of a mentholated version of the Tobacco Heating System (THS2.2M), a candidate modified risk tobacco product (MRTP), was characterized in a 90-day OECD inhalation study. Differential gene and protein expression analysis of nasal epithelium and lung tissue was also performed to record exposure effects at the molecular level. Rats were exposed to filtered air (sham), to THS2.2M (at 15, 23 and 50 μg nicotine/l), to two mentholated reference cigarettes (MRC) (at 23 μg nicotine/l), or to the 3R4F reference cigarette (at 23 μg nicotine/l). MRCs were designed to meet 3R4F specifications. Test atmosphere analyses demonstrated that aldehydes were reduced by 75%-90% and carbon monoxide by 98% in THS2.2M aerosol compared with MRC smoke; aerosol uptake was confirmed by carboxyhemoglobin and menthol concentrations in blood, and by the quantities of urinary nicotine metabolites. Systemic toxicity and alterations in the respiratory tract were significantly lower in THS2.2M-exposed rats compared with MRC and 3R4F. Pulmonary inflammation and the magnitude of the changes in gene and protein expression were also dramatically lower after THS2.2M exposure compared with MRCs and 3R4F. No menthol-related effects were observed after MRC mainstream smoke-exposure compared with 3R4F.Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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