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 Al 0 and Al 2 O 3 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 AlCl 3 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 Al 2 O 3 NMs in bone marrow (BM), while AlCl 3 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.

Genotoxic Impact of Aluminum-containing Nanomaterials in Human Intestinal and Hepatic Cells.

“…Nevertheless, the induction of MN formation in liver was shown to decrease with an antioxidant treatment [18,19]. Consistent with these results, a slight oxidative DNA damage was observed in blood after a shortterm oral exposure [16].…”

“…Nevertheless, in our recent in vivo study investigating the genotoxicity of Al NMs, only a very limited genotoxic response was observed. In fact, only a cross-linking effect was suggested in the rat duodenum with Al 0 NMs [16]. As the in vivo treatment duration was rather short (3 administrations over 2 days), and that it cannot be excluded that the level of NMs in the organs would be low, we chose to complete our study by investigating the in vitro genotoxicity of Al NMs in human intestinal Caco-2 and hepatic HepaRG cells using complementary tests.…”

“…Genotoxic effects were observed in bone marrow, but not in other organs, after a short-term treatement with lower doses of Al 2 O 3 NMs [16]. In vivo effects of Al 0 NMs following oral exposure are mostly lacking, although one study suggested cross-linking effects on DNA in the duodenum of rats [16]. Following oral exposure of rodents with ionic forms of Al, an increase in MN frequency was reported in bone marrow after a single oral administration [17] and in liver after a 30 day oral treatment [18].…”

“…AlCl 3 (hexahydrate) was purchased from Sigma Aldrich (Saint Louis, USA). NM dispersion was performed according to the NANOGENOTOX protocol [39], as described in [16].…”

“…DNA damage was reported in erythrocytes of rats after a single oral treatment with Al 2 O 3 NMs, although at high doses (≥1,000 mg/kg) [14,15]. Genotoxic effects were observed in bone marrow, but not in other organs, after a short-term treatement with lower doses of Al 2 O 3 NMs [16]. In vivo effects of Al 0 NMs following oral exposure are mostly lacking, although one study suggested cross-linking effects on DNA in the duodenum of rats [16].…”