Development and Validation of a High- Throughput Method for the Determination of Titanium Dioxide in Rodent Lung and Lung-Associated Lymph Node Tissues

Abstract

There is a need to determine the tissue burdens of inhaled titanium dioxide due to the widespread industrial use of this compound. A high-throughput method for the determination of TiO₂ as titanium in rodent lung and lung-associated lymph node tissues by inductively coupled plasma optical emission spectrometry (ICP-OES) was developed and validated. Samples were digested in open-vessel, disposable centrifuge tubes in the presence of nitric and hydrofluoric acids. The determined method quantitation limit (MQL) was 4.2 µg TiO₂/g tissue. Replicate control samples prepared at this level were determined with a high level of accuracy (100%) and precision (2% RSD). After validation, the described method was applied to determine the concentration of TiO₂ (as titanium) in 600 rodent tissue samples spanning a 16-month time period. During this time period, laboratory control samples (n = 48) were analyzed to assess the long-term precision and accuracy of the method. The average recovery of titanium in these samples was 102±4.8%.

Keywords:

• Titanium dioxide
• Inductively coupled plasma optical emission spectrometry
• Open-vessel microwave digestion
• High-throughput
• Rodent tissues
• Lung tissue
• Lymph node tissue

Acknowledgment

The authors would like to thank the CIIT Centers for Health Research for their support of this effort by providing resources from the TiO₂ panel of the American Chemistry Council and the European Chemical Industry Council. The authors also acknowledge Dr. Barbara Kuyper for her editorial assistance in the preparation of this manuscript.