Risk assessment of titanium dioxide nanoparticles via oral exposure, including toxicokinetic considerations.
Titanium dioxide white pigment consists of particles of various sizes, from which a fraction is in the nano range (<100 nm). It is applied in food as additive E 171 as well as in other products, such as food supplements and toothpaste. Here, we assessed whether a human health risk can be expected from oral ingestion of these titanium dioxide nanoparticles (TiO2NPs), based on currently available information. Human health risks were assessed using two different approaches: Approach 1, based on intake, i.e. external doses, and Approach 2, based on internal organ concentrations using a kinetic model in order to account for accumulation over time (the preferred approach). Results showed that with Approach 1, a human health risk is not expected for effects in liver and spleen, but a human health risk cannot be excluded for effects on the ovaries. When based on organ concentrations by including the toxicokinetics of TiO2NPs (Approach 2), a potential risk for liver, ovaries and testes is found. This difference between the two approaches shows the importance of including toxicokinetic information. The currently estimated risk can be influenced by factors such as absorption, form of TiO2, particle fraction, particle size and physico-chemical properties in relation to toxicity, among others. Analysis of actual particle concentrations in human organs, as well as organ concentrations and effects in liver and the reproductive system after chronic exposure to well-characterized TiO2(NPs) in animals are recommended to refine this assessment.
a National Institute for Public Health and the Environment (RIVM) , Bilthoven , The Netherlands.
Minne B
MB
Heringa
a National Institute for Public Health and the Environment (RIVM) , Bilthoven , The Netherlands.
Liesbeth
L
Geraets
a National Institute for Public Health and the Environment (RIVM) , Bilthoven , The Netherlands.
Jan C H
JC
van Eijkeren
a National Institute for Public Health and the Environment (RIVM) , Bilthoven , The Netherlands.
Rob J
RJ
Vandebriel
a National Institute for Public Health and the Environment (RIVM) , Bilthoven , The Netherlands.
Wim H
WH
de Jong
a National Institute for Public Health and the Environment (RIVM) , Bilthoven , The Netherlands.
Agnes G
AG
Oomen
D065567:Absorption, Physiological; D000818:Animals; D019587:Dietary Supplements; D004435:Eating; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D010316:Particle Size; D018570:Risk Assessment; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D014025:Titanium / Q000737:chemistry / Q000633:toxicity*; D014100:Toothpastes / Q000737:chemistry; D066007:Toxicokinetics
D014100:Toothpastes; C009495:titanium dioxide; D014025:Titanium
TiO2; food; kinetic modeling; supplements; toothpaste