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Genotoxicity of Aluminum and Aluminum Oxide Nanomaterials in Rats Following Oral Exposure.

ABSTRACT: Due to several gaps remaining in the toxicological evaluation of nanomaterials (NMs), consumers and public health agencies have shown increasing concern for human health protection. In addition to aluminum (Al) microparticles, Al-containing nanomaterials (Al NMs) have been applied by food industry as additives and contact materials. Due to the limited amount of literature on the toxicity of Al NMs, this study aimed to evaluate the in vivo genotoxic potential of Al0 and Al2O3 NMs after acute oral exposure. Male Sprague-Dawley rats were administered three successive gavages at 6, 12.5 and 25 mg/kg bw. A comparison with AlCl3 was done in order to assess the potential effect of dissolution into Al ions. Both DNA strand breaks and oxidative DNA damage were investigated in six organs/tissues (duodenum, liver, kidney, spleen, blood and bone marrow) with the alkaline and the Fpg-modified comet assays. Concomitantly, chromosomal damage was investigated in bone marrow and colon with the micronucleus assay. The comet assay only showed DNA damage with Al2O3 NMs in bone marrow (BM), while AlCl3 induced slight but non-significant oxidative DNA damage in blood. No increase of chromosomal mutations was observed after treatment with the two Al MNs either in the BM or in the colons of rats.

SUBMITTER: Jalili P

PROVIDER: S-EPMC7075173 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Genotoxicity of Aluminum and Aluminum Oxide Nanomaterials in Rats Following Oral Exposure.

Jalili Pégah P Huet Sylvie S Lanceleur Rachelle R Jarry Gérard G Le Hegarat Ludovic L Nesslany Fabrice F Hogeveen Kevin K Fessard Valérie V

Nanomaterials (Basel, Switzerland) 20200211 2

Due to several gaps remaining in the toxicological evaluation of nanomaterials (NMs), consumers and public health agencies have shown increasing concern for human health protection. In addition to aluminum (Al) microparticles, Al-containing nanomaterials (Al NMs) have been applied by food industry as additives and contact materials. Due to the limited amount of literature on the toxicity of Al NMs, this study aimed to evaluate the in vivo genotoxic potential of Al<sup>0</sup> and Al<sub>2</sub>O ...[more]

PMID: 32053952

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Project description:The toxicokinetics of nanomaterials are an important factor in toxicity, which may be affected by slow clearance and/or distribution in the body.Four types of nickel oxide (NiO) nanoparticles were single-administered intratracheally to male F344 rats at three doses of 0.67-6.0 mg/kg body weight. The rats were sacrificed under anesthesia and the lung, thoracic lymph nodes, bronchoalveolar lavage fluid, liver, and other organs were sampled for Ni burden measurement 3, 28, and 91 days post-administration; Ni excretion was measured 6 and 24 h after administration. Solubility of NiO nanoparticles was determined using artificial lysosomal fluid, artificial interstitial fluid, hydrogen peroxide solution, pure water, and saline. In addition, macrophage migration to trachea and phagosome-lysosome-fusion rate constants were estimated using pulmonary clearance and dissolution rate constants.The wire-like NiO nanoparticles were 100% dissolved by 24 h when mixed with artificial lysosomal fluid (dissolution rate coefficient: 0.18/h); spherical NiO nanoparticles were 12% and 35% dissolved after 216 h when mixed with artificial lysosomal fluid (1.4?×?10-3 and 4.9?×?10-3/h). The largest irregular-shaped NiO nanoparticles hardly dissolved in any solution, including artificial lysosomal fluid (7.8?×?10-5/h). Pulmonary clearance rate constants, estimated using a one-compartment model, were much higher for the NiO nanoparticles with a wire-shape (0.069-0.078/day) than for the spherical and irregular-shaped NiO nanoparticles (0-0.012/day). Pulmonary clearance rate constants of the largest irregular-shaped NiO nanoparticles showed an inverse correlation with dose. Translocation of NiO from the lungs to the thoracic lymph nodes increased in a time- and dose-dependent manner for three spherical and irregular-shaped NiO nanoparticles, but not for the wire-like NiO nanoparticles. Thirty-five percent of the wire-like NiO nanoparticles were excreted in the first 24 h after administration; excretion was 0.33-3.6% in that time frame for the spherical and irregular-shaped NiO nanoparticles.These findings suggest that nanomaterial solubility differences can result in variations in their pulmonary clearance. Nanoparticles with moderate lysosomal solubility may induce persistent pulmonary inflammation.

Dataset Information

Genotoxicity of Aluminum and Aluminum Oxide Nanomaterials in Rats Following Oral Exposure.

Publications

Genotoxicity of Aluminum and Aluminum Oxide Nanomaterials in Rats Following Oral Exposure.

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