title: A test strategy for the assessment of additive attributed toxicity of tobacco products.
abstract: The new EU Tobacco Product Directive (TPD) prohibits tobacco products containing additives that are toxic in unburnt form or that increase overall toxicity of the product. This paper proposes a strategy to assess additive attributed toxicity in the context of the TPD. Literature was searched on toxicity testing strategies for regulatory purposes from tobacco industry and governmental institutes. Although mainly traditional in vivo testing strategies have been applied to assess toxicity of unburnt additives and increases in overall toxicity of tobacco products due to additives, in vitro tests combined with toxicogenomics and validated using biomarkers of exposure and disease are most promising in this respect. As such, tests are needed that are sensitive enough to assess additive attributed toxicity above the overall toxicity of tobacco products, which can associate assay outcomes to human risk and exposure. In conclusion, new, sensitive in vitro assays are needed to conclude whether comparable testing allows for assessment of small changes in overall toxicity attributed to additives. A more pragmatic approach for implementation on a short-term is mandated lowering of toxic emission components. Combined with risk assessment, this approach allows assessment of effectiveness of harm reduction strategies, including banning or reducing of additives.
authors.affiliation: Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, The Netherlands. Electronic address: anne.kienhuis@rivm.nl.
authors.forename: Anne S
authors.initials: AS
authors.lastname: Kienhuis
authors.affiliation: Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, The Netherlands. Electronic address: yvonne.staal@rivm.nl.
authors.forename: Yvonne C M
authors.initials: YC
authors.lastname: Staal
authors.affiliation: Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, The Netherlands.
authors.forename: Lya G
authors.initials: LG
authors.lastname: Soeteman-Hernández
authors.affiliation: Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, The Netherlands.
authors.forename: Suzanne
authors.initials: S
authors.lastname: van de Nobelen
authors.affiliation: Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, The Netherlands.
authors.forename: Reinskje
authors.initials: R
authors.lastname: Talhout
mesh_terms: D006801:Humans; D018570:Risk Assessment; D014029:Tobacco Use Disorder; D018675:Toxicity Tests; D062789:Tobacco Products
keywords: In vitro toxicity methods; Mandated lowering; Risk assessment; Tobacco additives; Tobacco product directive