Abstract
The effects of seven nanomaterials (four amorphous silicon dioxides with or without surface functionalization, two surface-functionalized zirconium dioxides, and barium sulfate) upon 28-day oral exposure to male or female rats were investigated. The studies were performed as limit tests in accordance with OECD Test Guideline 407 applying 1,000 mg test substance/kg body weight/day. Additionally, the acute phase proteins haptoglobin and α2-macroglobulin as well as cardiac troponin I were determined, and metabolome analysis was performed in plasma samples. There were no test substance-related adverse effects for any of the seven nanomaterials. Moreover, metabolomics changes were below the threshold of effects. Since test substance organ burden was not analyzed, it was not possible to establish whether the lack of findings related to the absence of systemic exposure of the tested nanomaterials or if the substances are devoid of any potential for toxicity. The few published subacute oral or short-term inhalation studies investigating comparable nanomaterials (SiO2, ZrO2, and BaSO4) also do not report the occurrence of pronounced treatment-related findings. Overall, the results of the present survey provide a first indication that the tested nanomaterials neither cause local nor systemic effects upon subacute oral administration under the selected experimental conditions. Further investigations should aim at elucidating the extent of gastrointestinal absorption of surface-functionalized nanomaterials. Electronic supplementary materialThe online version of this article (doi:10.1007/s00204-014-1337-0) contains supplementary material, which is available to authorized users.
Highlights
Due to the well-known effects of generic particulate dusts on the human lung and its thin air–blood barrier, uptake by inhalation is expected to be the critical route of exposure for most nanomaterials (NMs) (Hankin et al 2011)
An overview of the primary and secondary physico-chemical properties of the test substances is provided in Table 1, which has been adapted from Wohlleben et al (2013) and Landsiedel et al (2014)
Under the experimental conditions of the present study, neither the 4 SiO2 NMs, nor the 2 surface-functionalized ZrO2 NMs or BaSO4 NM-220, elicited any effects upon 28-day oral exposure to rats that were assessed as test substance-related and adverse
Summary
Due to the well-known effects of generic particulate dusts on the human lung and its thin air–blood barrier, uptake by inhalation is expected to be the critical route of exposure for most nanomaterials (NMs) (Hankin et al 2011). Information on in vitro and in vivo pulmonary effects of NMs is increasingly becoming available (Landsiedel et al 2012a). NMs may be taken up orally, when they are used in the pharmacological context, e.g., to increase oral drug bioavailability or to promote applicability of drugs (Bouwmeester et al 2011; Fröhlich and Roblegg 2012). Inhaled NMs may be translocated into the pharynx by the mucociliary clearance system of the respiratory tract and be swallowed into the gastrointestinal tract (Landsiedel et al 2012b)
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