In vitro toxicological evaluation of a tobacco heating product THP COO and 3R4F research reference cigarette on human lung cancer cells

Toxicol In Vitro. 2021 Aug:74:105173. doi: 10.1016/j.tiv.2021.105173. Epub 2021 Apr 15.

Abstract

Cigarette smoking increases health risks, such as respiratory diseases and heart diseases. Despite the decline in smoking rates in some countries, millions of adults still choose to smoke cigarettes. The use of next-generation nicotine delivery devices, such as tobacco heating products (THPs), may become a potentially safer alternative to smoking. Here, we report on the development of an electrically heated THP, coded as THP COO, with three different flavored tobacco sticks. The purpose of the study was to measure the levels of a list of harmful and potentially harmful constituents (HPHCs) in the total particulate matter (TPM) generated and to conduct a set of toxicological assessments of THP COO as compared with 3R4F reference cigarette. For all 55 HPHCs identified, the levels generated by the THP tobacco sticks were significantly lower in comparison to those in 3R4F TPM. The rate of reduction of HPHCs was between 68.6% and 99.9% under Health Canada Intense (HCI) smoking regimen. Human lung cancer cells (NCI-H292) exposed to 3R4F TPM showed dose-dependent responses for most of the 15 in vitro toxicity endpoints, whereas those exposed to comparable doses of THP COO TPMs did not. Therefore, exclusive use of the THP COO products may reduce the exposure of those tested HPHCs and thus potentially reduce health risk of smoking.

Keywords: Cigarette smoke; Cytotoxicity; Genotoxicity; High content screening; In vitro; Tobacco heating products.

MeSH terms

  • Aerosols
  • Animals
  • CHO Cells
  • Cell Cycle / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Cricetulus
  • Cytokines / metabolism
  • Electronic Nicotine Delivery Systems*
  • Hazardous Substances / adverse effects*
  • Hazardous Substances / analysis
  • High-Throughput Screening Assays
  • Hot Temperature*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Micronuclei, Chromosome-Defective / chemically induced
  • Mutagenicity Tests
  • Mutagens / adverse effects
  • Mutagens / analysis
  • Reactive Oxygen Species / metabolism
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / genetics
  • Smoke / adverse effects*
  • Smoke / analysis
  • Tobacco Products*

Substances

  • Aerosols
  • Cytokines
  • Hazardous Substances
  • Mutagens
  • Reactive Oxygen Species
  • Smoke