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In vitro bioavailability studies in artificial body fluids were conducted with WO2 and other tungsten oxides providing the base for read-across of toxicological endpoints. In addition basic toxicokinetic was assessed according to OECD 417 on tungsten oxide (TBO) and in a non-guideline inhalation study in beagles .

The solubility of tungsten dioxide was determined in artificial body fluids (gastric fluid, interstitial fluid, lysosomal fluid, and artificial perspiration; KMHC 2012). Results were reported as µg W/g sample, % W/g sample and as % of total available W released. The bioavailability ranged from 0.23 % (5h, gastric fluid) to 4.52 % (12h, artificial perspiration). Based on the results, the bioavailability of tungsten dioxide would be expected to be low for all routes of administration and best at slightly acidic to neutral pH.

Similar data are available for other tungsten oxides (IITRI, 2010) that were used to verify the applicability of each read across.The bioavailability of tungsten trioxide was determined in artificial gastric, alveolar, lysosomal, interstitial fluids, and sweat. The bioavailability ranged from 0.0055% (gastric fluid) to 39% (interstitial fluid). The maximum bioavailability of tungsten from tungsten trioxide was determined at 72 hours for the simulated alveolar, lysosomal and interstitial fluids (34, 38 and 39%, respectively). Based on the results, the bioavailability of tungsten from tungsten trioxide would be expected to be low for the oral route of administration, but moderate for the inhalation route. 

The bioaccessibility of tungsten from WO3 and WO2 is the basis for read-across. The release was consistently lower for WO2 compared to WO3. Only at very low pH WO3 was virtually not soluble (5h simulated gastric fluid; 0.0055%) compared to 0.23% for WO2. The value of 0.23% is rather low. As a potential oral toxicity would be elicited by the combined gastro-intestinal release, the higher solubility of WO3 in the gut (pH 5-8.3) is assumed to result in a significant higher total release of tungsten ions. Therefore the oral toxicity studies conducted with WO3 are considered to be protective when reading across to WO2.

In an in vivo study, tissue distribution, retention, and excretion were determined following administration of tungsten oxide after a single nose-only exposure to six beagle dogs. 60% of the inhaled activity was deposited in the respiratory tract. Removal of the inhaled activity from the body was quite rapid, with approximately 90% of the activity removed with a biological half-time of 14 hours.

In addition a toxicokinetic study conducted according to OECD 417 on TBO was used for read-across. When TBO was administered via inhalation, tungsten was absorbed systemically. Cmax and AUC increased proportionally with increasing TBO dose level: Cmax was 0.819 ± 0.215 and 10.9 ± 4.7 fig/g, and AUC was 11.8 ± 3.29 and 148 ± 33.7 hr*Rg/g for the 0.08 and 0.65 mg/L dose groups, respectively. The systemic elimination half-life was 23 ± 4.3 and 154 ± 92.8 hours for the 0.08 and 0.65 mg/L dose groups, respectively, and the clearance rate was 1.24 ± 0.39 and 0.78 ± 0.18 L/hr/kg for the 0.08 and 0.65 mg/L dose groups, respectively. The majority of the inhaled TBO was excreted through the gastrointestinal tract. Tungsten concentration in lung tissue was at least one order of magnitude greater than in any other organ collected. In general, the femur and kidney ranked second and third highest, respectively, in tungsten concentration on a per organ weight basis. In terms of total tungsten burden in the organs, the lung, femur and liver ranked first, second and third, respectively. Tungsten distribution in tissue and organs reached steady-state on study Day 14. With the exception of the femur, the functional elimination half-life of tungsten in most organs was less than 24 hours.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential

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