In  vivo micronucleus studies with 6 @entity6701 materials (3  pigment-grade _ 3 nanoscale) in orally-exposed XXXX .

@entity137 @entity35295 @entity786 @entity6701 @entity35 @entity3759
UNASSIGNED: Six pigment-grade (pg) or ultrafine (uf)/nanoscale (anatase and/or rutile) @entity6701 ( @entity3759 ) particulates were evaluated for in  vivo genotoxicity (OECD 474 Guidelines) in male and female @entity35 by two different laboratories. All test materials were robustly characterized. The BET surface areas of the pg and uf samples ranged from 7 to 17  m(2)/g and 50 to 82  m(2)/g respectively. The materials were assessed for induction of micronuclei and @entity137 in bone marrow by analyzing peripheral blood reticulocytes (RETs) by flow cytometry. Single oral gavage doses of 500, 1000 or 2000  mg/kg body weight (bw) of each material were implemented with concurrent negative (water) and positive controls ( @entity786 ). Approximately 48 and 72  h after exposure, blood samples were collected and 20,000 RETs per animal were analyzed. For each of the six tests, there were no biologically or toxicologically relevant increases in the micronucleated @entity35295 frequency in any @entity3759 exposed group at either time point at any dose level. In addition, there were a lack of biologically relevant decreases in %RETs among total erythrocytes. All six @entity3759 test substances were negative for in  vivo genotoxicity effects; however, it is noted that the exposure to target tissues was likely negligible. One pigment grade and one ultrafine material each were evaluated for potential systemic exposure/uptake from the gastrointestinal tract by analysis of @entity3759 into blood and liver. No significant increases in @entity3759 over controls were measured in blood (48 or 72  h) or liver (72  h) following exposures to 2000  mg/kg bw @entity3759 . These data indicate that there was no absorption of the test material from the gastrointestinal tract into the blood circulation and the lack of genotoxic effects is therefore attributed to a lack of exposure due to the inability of the test material to migrate from the gastrointestinal tract into the blood and then into target tissues.
