The organ-tissue distribution and clearance of Degussa P25 TiO2 nanoparticles were determined after intravenous administration to rats (0.95 mg/kg bodyweight) using an inductively coupled plasma sector field mass spectrometer. The detection limits of Ti analysis, 0.54 and 1.4 ng/mL for blood and urine and 0.35-2.0 ng/g tissue for several organ tissues, enabled determination of tissue distribution and clearance for organs in which Ti content could not be previously determined due to low concentrations. Blood concentrations of TiO2 were 420 and 19 ng/mL at 5 and 15 min after administration, which were equivalent of only 2.8% and 0.13% of the administration dose, respectively. At 6 h, 94%, 2.0%, 0.17%, 0.023%, 0.014% and 0.026% of administered TiO2 was found in the liver, spleen, lung, kidney, heart and blood, respectively. Liver and spleen TiO2 burden was significantly higher in the administration than control group (p < 0.01) and did not decrease up to 30 days after administration, while TiO2 burden in the lung, kidney, heart and blood decreased over time. A two-step decay model was more suitable than a one-step decay model for the decay curves of pulmonary TiO2 burden but did not improve fitting to the decay curves of kidney TiO2 burden. No translocation to the brain was confirmed at a lower detection limit than was applied in previous studies. Ti content in faeces and urine in the TiO2 administration group did not differ from that in the control group.

We have examined potential changes in the isotopic compositions of Fe, Cu and Zn (using multi-collector inductively coupled plasma-mass spectrometry) and the corresponding concentrations (using inductively coupled plasma-atomic emission spectrometry) in plasma from hematological malignancy (HM) patients and assessed their prognostic capability. Together with clinical laboratory test values, data were examined in view of a 5-years survival prediction. Plasma Cu and Zn isotope ratios and their concentrations were significantly different in HM patients compared to matched controls (P < 0.05). Both δ65Cu and δ66Zn values showed significant mortality hazard ratios (HRs) in HM. The group of patients with decreased δ65Cu and increased δ66Zn values showed significantly poorer survival from the early phase (HR 3.9; P = 0.001), forming a unique cohort not identified based on laboratory test values. Well-known prognostic factors for HM, such as the creatinine level, and anemia-related values were highly correlated with the δ66Zn value (P < 0.05). Time-dependent ROC curves based on the δ65Cu or δ66Zn value were similar to that based on the creatinine concentration (a well-known prognostic factor in HM), indicating that δ65Cu or δ66Zn values are useful for prognosis of HM. Variations in stable isotope ratios of essential mineral elements have thus been shown to reflect alterations in their homeostasis due to physiological changes in malignancies with higher sensitivity than concentrations do.

AEROSIL(®) P25 titanium dioxide (TiO2) nanoparticles dispersed in 0.2% disodium phosphate solution were intratracheally administered to male F344 rats at doses of 0 (control), 0.375, 0.75, 1.5, 3.0, and 6.0 mg/kg. The rats were sacrificed under anesthesia at 1 day, 3 days, 7 days, 4 weeks, 13 weeks, and 26 weeks after administration. Ti levels in various pulmonary and extrapulmonary organs were determined using sensitive inductively coupled plasma sector field mass spectrometry. One day after administration, the lungs contained 62-83% of TiO2 administered dose. Twenty-six weeks after administration, the lungs retained 6.6-8.9% of the TiO2 administered at the 0.375, 0.75, and 1.5 mg/kg doses, and 13% and 31% of the TiO2 administered at the 3.0 and 6.0 mg/kg doses, respectively. The pulmonary clearance rate constants from compartment 1, k1, were estimated using a 2-compartment model and were found to be higher for the 0.375 and 0.75 mg/kg doses of TiO2 (0.030/day for both) than for TiO2 doses of 1.5-6.0 mg/kg (0.014-0.022/day). The translocation rate constants from compartment 1 to 2, k12, were estimated to be 0.015 and 0.018/day for the 0.375 and 0.75 mg/kg doses, and 0.0025-0.0092/day for doses of 1.5-6.0mg/kg. The pulmonary clearance rate constants from compartment 2, k2, were estimated to be 0.0086 and 0.0093/day for doses of 0.375 and 0.75 mg/kg, and 0-0.00082/day for 1.5-6.0 mg/kg doses. Translocation of TiO2 from the lungs to the thoracic lymph nodes increased in a time- and dose-dependent manner, accounting for 0.10-3.4% of the administered dose at 26 weeks. The measured thoracic lymph node burdens were a much better fit to the thoracic lymph node burdens estimated assuming translocation from compartment 1 to the thoracic lymph nodes, rather than those estimated assuming translocation from compartment 2 to the thoracic lymph nodes. The translocation rate constants from the lungs to the thoracic lymph nodes, kLung→Lym, were 0.000037-0.00081/day, and these also increased with increasing doses of TiO2. Although a small amount of TiO2 had translocated to the liver by 3 days after the administration (0.0023-0.012% of the highest dose administered, 6.0 mg/kg), translocation to the other extrapulmonary organs was not detected.

We evaluated and compared the pulmonary clearance kinetics and extrapulmonary translocations of seven titanium dioxide (TiO2) nano- and submicron particles with different characteristics, including size, shape and surface coating. Varying doses of TiO2 nano- and submicron particles dispersed in 0.2% disodium phosphate solution were intratracheally administered to male F344 rats. The rats were euthanized under anesthesia for 3, 28 and 91 days after administration. Ti levels in pulmonary and various extrapulmonary organs were determined using inductively coupled plasma-sector field mass spectrometry (ICP-SFMS). The lungs, including bronchoalveolar lavage fluid (BALF), contained 55-89% of the administered TiO2 dose at 3 days after administration. The pulmonary clearance rate constants, estimated using a one-compartment model, were higher after administration of 0.375-2.0 mg/kg body weight (bw) (0.016-0.020/day) than after administration of 3.0-6.0 mg/kg bw (0.0073-0.013/day) for six uncoated TiO2. In contrast, the clearance rate constant was 0.011, 0.0046 and 0.00018/day following administration of 0.67, 2.0 and 6.0 mg/kg bw TiO2 nanoparticle with Al(OH)3 coating, respectively. Translocation of TiO2 from the lungs to the thoracic lymph nodes increased in a time- and dose-dependent manner. Furthermore, the translocation of TiO2 from the lungs to the thoracic lymph nodes after 91 days was higher when Al(OH)3 coated TiO2 was administered (0.93-6.4%), as compared to uncoated TiO2 (0.016-1.8%). Slight liver translocation was observed (<0.11%), although there was no clear trend related to dose or elapsed time. No significant translocation was observed in other organs including the kidney, spleen and brain.

Background Occupational exposure to chemotherapeutic agents in hospitals is a critical issue. Here, we focused on occupational exposure to platinum-based anti-cancer drugs (PDs) by evaluating platinum concentrations in hair and environmental workplace samples to monitor the risk among workers. Methods Hospital workers who dealt with or without PDs, patients treated with PDs, and non-medical office workers outside the hospital donated hair samples and completed a questionnaire regarding their history of handling PDs, including any incidents. Hair samples were collected and surface wipe sampling was performed in July 2010 and April 2015, before and after moving to a new building and introducing a revised safety program in August 2010. Samples were analyzed by inductively coupled plasma-mass spectrometry. Results Platinum concentrations in hair from PDs-handling workers was significantly higher than in non-PDs-handling workers (P = 0.045), although 50 times lower than that from PDs-treated patients. Platinum concentrations in the hospital environment had decreased at the second survey 5 years later but had not changed significantly in the hair samples from hospital workers. Conclusion Platinum concentrations in hair are likely dependent on the frequency of handling PDs. Reduced environmental contamination from PDs did not influence platinum levels in hospital workers’ hair. Continuous monitoring by measuring platinum concentrations in the environment and in hair would provide information regarding these issues.