Tungsten carbide

Endpoint summary

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2009-01-28 to 2009-06-01

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP in-vitro bioaccessability study performed according to the "Draft Guidance for RIP 3.6: Bioavailability and Read-Across for Metals and Minerals".

Reason / purpose for cross-reference:

reference to other study

Objective of study:

absorption

Qualifier:

according to guideline

Guideline:

other: Draft Guidance for RIP 3.6: Bioavailability and Read-Across for Metals and Minerals

Deviations:

no

GLP compliance:

yes

Radiolabelling:

no

Species:

other: Human simulated fluids

Strain:

not specified

Sex:

not specified

Route of administration:

other: In vitro study

Duration and frequency of treatment / exposure:

Single application of tungsten with fluids. Simulated Gastric Fluid was sampled for the determination of tungsten at 5 hours. Simulated Interstitial, Alveolar and Lysosomal Fluids were sampled for the determination of tungsten at 2, 5, 24, and 72 hours. Simulated Sweat was sampled for the determination of tungsten after 12 hours.

Remarks:

Doses / Concentrations:
0.1 g of test substance in 50 mL of simulated fluid

Control animals:

no

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: Simulated gastric fluid, Simulated interstititial fluid, Simulated alveolar fluid, Simulated lysosomal fluid and Simulated sweat
- Time and frequency of sampling: Simulated gastric fluid sampled at 5 hours, Simulated interstititial fluid sampled at 2, 5, 24, and 72 hours, Simulated alveolar fluid sampled at 2, 5, 24, and 72 hours, Simulated lysosomal fluid sampled at 2, 5, 24, and 72 hours and Simulated sweat sampled after 12 hours.

Sample analysis: Samples were diluted (if necessary), spiked with an internal standard [bismuth (Bi) at 1,000 pg/mL, prepared from dilution of a 1,000 ug/mL Certified Standard; Ultra Scientific, North Kingston, RI and analyzed directly on a Perkin Elmer Elan DRC II ICP-MS equipped with a dynamic reaction cell (DRC) and PerkinElmer AS-93 Plus autosampler instrument, according to methods established at IITRI for this study. A standard curve (prepared from dilutions of a 10,000 5%HNO3/6% HF; inorganic Ventures, Lakewood, NJ] was analyzed along with samples on each day of analysis. Instruments calibrators were prepared by diluting Certified Standard with 0.5% nitric acid to concentrations of approximately 200; 400; 800; 1,600; 3,200; 6,400; 13,000; and 25,000 pg/mL.

Statistics:

Calibration curves, regression coefficients and r-squared values were calculated using PerkinElmer ICP-MS software and Microsoft Excel software. Concentration values of tungsten in the study samples were calculated from linear regression coefficients derived from calibration standards that bracketed the expected concentration levels of tungsten in the study samples.

Transfer type:

other: not applicable as it is an in vitro study

Toxicokinetic parameters:

other: not applicable as it is an in vitro study

Metabolites identified:

no

Bioaccessibility (or Bioavailability) testing results:

The fluid extracts were diluted 1:250 to 1:2500 for analysis. The average amount of tungsten found in the extracts was in the 0.019 to 0.48% range. The maximum solubility was determined at 72 hours for the simulated alveolar and lysosomal fluids (0.48 and 0.41%, respectively). Percent relative standard deviations (%RSDs) ranged from 2 to 74%.

Gastric Fluid: The percent of available tungsten in simulated gastric fluid sampled at 5 hours was 0.035 +/- 0.00071% (2.0 % relative standard deviation).
Sweat Fluid: The percent of available tungsten in simulated sweat fluid sampled at 12 hours was 0.076 +/-0.0030 % (4.0% relative standard deviation).
Alveolar Fluid: The percent of available tungsten in simulated alveolar fluid sampled at 2, 5, 24, and 72 hours was 0.019 +/- 0.0022%, 0.033 +/- 0.0012%, 0.089 +/- 0.0070%, and 0.48 +/-0.057 %, respectively; with percent relative standard deviations of 12, 3.7, 7.9, and 12 %RSD, respectively.
Lysosomal Fluid: The percent of available tungsten in simulated lysosomal fluid sampled at 2, 5, 24, and 72 hours was 0.078 +/- 0.047%, 0.092 +/- 0.059%, 0.20 +/- 0.15%, and 0.41 +/- 0.28 %, respectively with percent relative standard deviations of 60, 64, 74, and 68 %RSD, respectively.
Interstitial Fluid: The percent of available tungsten in simulated interstitial fluid sampled at 2, 5, 24, and 72 hours was 0.045 +/- 0.020%, 0.037 +/- 0.0089%, 0.065 +/- 0.010%, and 0.13 +/- 0.053 %, respectively with percent relative standard deviations of 44, 24, 15, and 41 %RSD, respectively.

Conclusions:

The average amount of tungsten found in the extracts was in the 0.019 to 0.48% range. The maximum solubility was determined at 72 hours for the simulated alveolar and lysosomal fluids (0.48 and 0.41%, respectively).

The percent of available tungsten in simulated gastric fluid sampled at 5 hours was 0.035 +/- 0.0071% (2.0 % relative standard deviation). The percent of available tungsten in simulated sweat fluid sampled at 12 hours was 0.076 +/-0.0030 % (4.0% relative standard deviation). The percent of available tungsten in simulated alveolar fluid sampled at 2, 5, 24, and 72 hours was 0.019 +/- 0.0022%, 0.033 +/- 0.0012%, 0.089 +/- 0.0070%, and 0.48 +/-0.057 %, respectively; with percent relative standard deviations of 12, 3.7, 7.9, and 12 %RSD, respectively. The percent of available tungsten in simulated lysosomal fluid sampled at 2, 5, 24, and 72 hours was 0.078 +/- 0.047%, 0.092 +/- 0.059%, 0.20 +/- 0.15%, and 0.41 +/- 0.28 %, respectively with percent relative standard deviations of 60, 64, 74, and 68 %RSD, respectively. The percent of available tungsten in simulated interstitial fluid sampled at 2, 5, 24, and 72 hours was 0.045 +/- 0.020%, 0.037 +/- 0.0089%, 0.065 +/- 0.010%, and 0.13 +/- 0.053 %, respectively with percent relative standard deviations of 44, 24, 15, and 41 %RSD, respectively. Based on the results, the bioavailability of tungsten carbide would be expected to be low for the oral, dermal, and inhalation routes of administration.

Reference 2

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

Low number of animals tested. Reliability assigned by secondary source. Only secondary source reviewed.

Objective of study:

excretion

Qualifier:

no guideline followed

Principles of method if other than guideline:

Method: the bioavailability based on excretion route was investigated.

GLP compliance:

not specified

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Animals were 8-12 weeks old and weighed 216-217 g

Route of administration:

oral: gavage

Vehicle:

other: 1 % methyl cellulose

Duration and frequency of treatment / exposure:

24 hour(s)

Remarks:

Doses / Concentrations:
2000 mg/kg bw

No. of animals per sex per dose / concentration:

Females: 3

Control animals:

yes, concurrent vehicle

Positive control reference chemical:

no

Details on study design:

no data

Details on dosing and sampling:

Urine and faeces were collected for 24 hours after application and then the animals were sacrificed. The tungsten content in urine and faeces as well as in shaved dorsal skin, gastrointestinal tract and carcass (without skin) was determined. Tungsten was analysed by ICP-OES (Inductive coupled plasma-optical emission spectroscopy).

Statistics:

no data

Details on excretion:

More than 98 % of the applied total tungsten found was in the faeces, about 1 % in the gastrointestinal tract, and only 0.04-0.05 % was found in the urine; this shows that after oral application of tungsten carbide to rats only a very minor part (< 0.1 %) becomes bioavailable and is excreted in urine.

The treatment was tolerated without clinical signs and at
necropsy no pathological changes were observed. The results
of the tungsten determinations are presented in the table.

Parameter   Tungsten content in milligrams (% of W found)
            /Contr.      /  No. 2 WC       /   No. 3 WC
Skin        /0.0017      /  0.0011 (.0003) /  0.0008 (.0002)
GIT         /0.0673      /  4.0887 (.9805) /  2.3216 (.5900)
Carcass     /0.0853      /  0.0401 (.0100) /  0.0557 (.0100)
Faeces      /0.1407      /412.6830 (98.97) /393.0240 (99.36)
Urine       /0.0005      /  0.2100 (.0500) /  0.1500 (.0400)
Total W     /0.2955      /417.0229         /395.5521
Total WC    /0.3150      /444.1294         /421.2630
WC dose     /0           /432.0000         /434.0000
% WC dose   /-           /103              /97
GIT= Gastrointestinal Tract

Conclusions:

More than 98 % of the applied total tungsten found was in the faeces, and only 0.04-0.05 % was found in the urine; this shows that after oral application of tungsten carbide to rats only a very minor part (< 0.1 %) becomes bioavailable and is excreted in urine.

Reference 3

Endpoint:

basic toxicokinetics

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

2010-08-31 to 2010-01-29

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The reliability of this study for the substance tested is a K1, but in application of read-across to a different substance ECHA’s guidance specifies that the score can be a maximum of K2. Due to higher water solubility and greater in vitro bioaccessibility in synthetic alveolar, lysosomal, and interstitial fluids simulating inhalation exposure for the source substance (TBO) as compared to the target substance (tungsten carbide) and lack of toxicity from acute toxicity studies for the target and source substances, toxicity data on the source substance is expected to represent a worse case, so read-across is appropriate between these substances. In addition, read-across is appropriate for this endpoint because the classification and labelling for human health toxicity endpoints is the same for the source and target substances, the PBT/vPvB profile is the same, and the dose descriptors are, or are expected to be, sufficiently similar or lower for the source substance. For more details, refer to the attached description of the read-across approach.

Justification for type of information:

1. HYPOTHESIS FOR THE CATEGORY APPROACH: The hypothesis is that properties are likely to be similar or follow a similar pattern because of the presence of a common metal ion, in this case tungstate.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES):
Source: Tungsten Oxide
Target: Tungsten Carbide
3. CATEGORY APPROACH JUSTIFICATION: See Annex 3 in CSR
4. DATA MATRIX: See Annex 3 in CSR

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

read-across: supporting information

Objective of study:

toxicokinetics

Qualifier:

according to guideline

Guideline:

OECD Guideline 417 (Toxicokinetics)

Principles of method if other than guideline:

The experimental design included toxicokinetic (TK) animals for analysis of TBO content during the 28 days of exposure (TK Sets 1-4) and to assess the elimination phase of the test substance after one day of exposure (TK Set 5).

GLP compliance:

yes

Radiolabelling:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, (St. Constant, Canada)
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: One day following receipt, body weight ranges of the first shipment of rats 226 to 279 g (males). One day following receipt, body weight range of the second shipment of male rats was 207 to 234 g.
- Fasting period before study: no food or water was provided during exposures.
- Housing: At the start of food consumption measurements, the rats were individually housed in clear polycarbonate rodent cages (Allentown Caging Equipment Co., Allentown, NJ) equipped with an automatic watering system.
-Diet: Certified Rodent Chow 5002 meal (PMI Nutrition International, Inc., Brentwood, MO) was provided ad libitum, except during inhalation exposures and scheduled fasting periods. Diet analysis reports received from the supplier are maintained with facility records. The diet contained no known contaminants at levels that would be expected to interfere with the test substance or the animals or confound interpretation of the study.
- Water (eg ad libitum): Each rodent cage was provided with an automatic watering system (Edstrom Industries, Inc, Waterford, WI) supplying fresh city of Chicago water without additional treatment ad libitum, except during inhalation exposures.
- Acclimation period: The animals were quarantined for 2 weeks; To condition the animals for placement and restraint in the nose-only exposure tubes, and reduce stress during the exposure phase, the animals were acclimated to the restraining tubes during a three-day acclimation period. Animals were restrained for 1/4 (1.5 hours), 1/2 (3 hours), and 3/4 (4.5 hours) of the daily exposure duration (6 hours) on three non-holiday weekdays before the animals were exposed.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.6 to 23.0 °C
- Humidity (%): 25.1-64.6%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): automatic 12-hour light/dark cycle was maintained in the exposure and housing chamber laboratories.

IN-LIFE DATES: From: 2010-09-09 To: 2010-10-21

Route of administration:

inhalation: dust

Vehicle:

unchanged (no vehicle)

Duration and frequency of treatment / exposure:

Set 1: 6 hours/day, 7 days/week for 28 days
Set 2: 6 hours/day for 3 days
Set 3: 6 hours/day for 7 days
Set 4: 6 hours/day for 14 days
Set 5: 6 hours with 7 day recovery

Remarks:

Doses / Concentrations:
0.08 and 0.65 mg/L (Target TBO concentration); 15.2 and 123.6 mg/kg/day (Target Inhaled Dose)

No. of animals per sex per dose / concentration:

Animals designated for toxicokinetic analysis were divided into five sets consisting of 4 males/set (time point) in each of the Low and High dose groups.

Control animals:

no

Positive control reference chemical:

no

Details on dosing and sampling:

PHARMACOKINETIC STUDY
- Tissues and body fluids sampled: at necropsy the brain, lungs, bone (femur), liver, kidney, spleen and reproductive organs were collected for analysis of TBO concentration. All toxicokinetic-designated animals were euthanized using sodium pentobarbital and exsanguinated from the abdominal aorta. Toxicokinetic animals were bled and necropsied as follows:

Set 1: Blood collection for the Low and High dose groups was performed on TK Day 0 [study Day 1 (pre-exposure)], and after the daily exposure on TK Days 1, 2, 3, 7, 14 and 28 (study Days 2, 3, 4, 8, 15 and 29); feces and urine were also collected from these animals overnight starting on TK Days 0, 1, 2, 3, 7, 14 and 28 (collection occurred the next day). These animals were necropsied on study Day 29. Blood was also collected on study Day 29, but was not chemically analyzed.

Set 2: Blood collection for the Low and High dose groups was performed on TK Day 3 (study Day 4) after the daily exposure and preserved for future evaluation. These animals were necropsied on TK Day 3.

Set 3: Blood collection for the Low and High dose groups was performed on TK Day 7 (study Day 8) after the daily exposure and preserved for future evaluation. These animals were necropsied on TK Day 7.

Set 4: Blood collection for the Low and High dose groups was performed on TK Day 14 (study Day 15) after the daily exposure and preserved for future evaluation. These animals were necropsied on TK Day 14.

Set 5: Blood collection for the Low and High dose groups was performed on this group on TK Day 0 [study Day 28 (pre-exposure)], after the exposure on TK Day 1 (study Day 29), and recovery Days 2, 3, 4, 5, 6 and 7) (study Days 30, 31, 32, 33, 34 and 35); feces and urine were also collected from these animals overnight starting on TK Days 0, 1, 2, 3, 4, 5, 6 and 7 (collection occurred the next day). These animals were necropsied on TK Day 8 (study Day 36) after the final urine and feces collection. Blood was also collected on TK Day 8, but was not chemically analyzed.

Statistics:

no data

Details on absorption:

In the single dose experiment, tungsten was absorbed systemically and blood tungsten concentration reached maximum (Tmax) at 0 hours post-exposure.

Details on distribution in tissues:

Repeat dose experiment:

From the repeat dose experiments, tungsten concentration in lung tissue was at least one order of magnitude greater than in any other organ collected, the lung being the primary organ for tungsten oxide (aka tungsten blue oxide or TBO) exposure via inhalation. In general, the femur and kidney ranked second and third highest in tungsten concentration on a per organ weight basis, respectively. The results indicated that the lung, femur and liver ranked first, second and third for total tungsten burden, respectively. The study day appeared to have little or no effect on the rank of tungsten distribution in tissue and organs. Tungsten concentration in tissue and organs increased with increasing dose, but not in a dose-proportionate manner.
Tungsten concentration in each organ increased with increasing inhalation exposure time for the lung, liver, kidney, spleen, testes, brain and femur, respectively. The increment was not significantly different between study Days 7 and 14, suggesting that steady-state absorption of inhaled TBO was reached on study Day 14. Compared with the steady-state concentration on study Day 14, tungsten in liver, kidney, testes and brain decreased at least 50% on study Day 29; however, unlike toxicokinetic Set 2 to 4 animals (necropsied immediately following termination of inhalation exposure on study Day 3, 7 or 14, respectively), the Set 1 animals were necropsied 24 hours after termination of exposure on study Day 29 to allow for overnight urine and feces collection. The results suggest that the functional elimination half-life of tungsten in those organs was less than 24 hours. On the contrary, tungsten in femur on study Day 29 was no different as compared to study Day 14, indicating that elimination of tungsten from femur was relatively slow as compared to other organs. The results were consistent with the Set 5 results (animals necropsied on Recovery Day 8 following a single inhalation exposure). Tungsten in femur on Recovery Day 8 (Set 5) was approximately one third as compared to that on study Day 3 (Set 2 animals) following multiple inhalation exposure, while tungsten concentration in the rest of organs was at least one order of magnitude lower.

Single administration experiment:

Following inhalation exposure of TBO, tungsten was absorbed systemically, as indicated by maximum blood concentration at 0 hour post-exposure. At 48 hours post-exposure, there was a slow elimination phase following an initial fast elimination phase for the 0.65 mg/L dose group (High). However, the second slow elimination phase was not evident for the 0.08 mg/L dose group (Low), which may be due to background noise of tungsten concentration. Based on the concentrations in the blood, the terminal phase half-life values were determined to be 23 ± 4.3 and 154 ± 92.8 hours for the 0.08 and 0.65 mg/L dose groups, respectively. Maximum blood tungsten concentration was 0.819 ± 0.215 and 10.9 ± 4.7 1.1g/g and area under the blood concentration-time curve extrapolated to infinity was 11.8 ± 3.29 and 148 ± 33.7 hr*i.tg/g for the 0.08 and 0.65 mg/L dose groups, respectively. These two exposure parameters increased proportionally with increasing TBO dose level. The systemic clearance based on the concentrations in the blood 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.

Details on excretion:

Repeat dose experiment:

The results from the repeat dose experiments indicate that the amount of tungsten excreted from feces was approximately three orders of magnitude greater than from urine. Since the nasal cavities are the major deposition site for inhaled particles in the rate, the study results suggest that most of the inhaled TBO was deposited in the nasal passages and subsequently ingested into the gastrointestinal tract and excreted with the feces. The study results also indicate that the excretion rate of tungsten from feces and urine and tungsten concentration in blood increased with increasing TBO dose level; however, the effect of study day was sporadic and a discernible trend was not observed.

Single administration experiment:

From the single dose experiment, the results indicate that excretion of tungsten from the gastrointestinal tract was negligible after post-exposure Day 2 and 3 for Groups 2 (Low) and 4 (High), respectively. The results are consistent with the general consensus that insoluble particles deposited in the nasal and tracheobronchial airways would be cleared within 24 hours through mucus escalator followed by ingestion into gastrointestinal tract and excretion with the feces. In contrast, there was still detectable tungsten in urine on post-exposure Day 7.

Toxicokinetic parameters:

AUC: 11.8 ± 3.29 hr ug/g for the 0.08 mg/L dose group

Toxicokinetic parameters:

Cmax: 0.819 ± 0.215 ug/g for the 0.08 mg/L dose group

Toxicokinetic parameters:

half-life 1st: 23 ± 4.3 hours for the 0.08 mg/L dose group

Toxicokinetic parameters:

AUC: 148 ± 33.7 hr ug/g for the 0.65 mg/L dose group

Toxicokinetic parameters:

Cmax: 10.9 ± 4.7 ug/g for the 0.65 mg/L dose group

Toxicokinetic parameters:

half-life 1st: 154 ± 92.8 hours for the 0.65 mg/L dose group

Metabolites identified:

not measured

The mean MMADs of the test atmosphere were 2.63 and 2.74 um with GSDs of 1.89 and 1.92 for the low and high dose groups, respectively.

Overall means for tungsten oxide (aka tungsten blue oxide or TBO) concentrations were determined gravimetrically to be 0.081and 0.652 mg/L for the low and high dose groups, respectively. The TBO % recovery ranged from 100.83-102.38%. Small amounts of TBO in the chemically-analyzed filters for the Filtered Air Control group were attributed to contamination during the filter analysis processing and/or the calibration curve. The Filtered Air Control group filter-collected mean gravimetric value was 0.000 mg/L. The particle size distribution of the test atmosphere was within the respirable range. The overall mean TBO inhaled dose levels were 14.8 and 118.8 mg/kg/day for the lowand high dose groups, respectively. The overall mean male TBO inhaled dose levels were 13.7 and 110.2 mg/kg/day for the low and high dose groups, respectively. The overall mean female TBO inhaled dose levels were 15.8 and 127.3 mg/kg/day for the low and high dose groups, respectively. The male inhaled dose levels were 10-11% below the target levels for all groups, while the female inhaled dose levels were 3-5% above the target levels for all groups. Prior to exposure initiation, the homogeneity of the test atmosphere in each TBO exposure chamber was confirmed.

Conclusions:

Following inhalation exposure to TBO, tungsten was absorbed systemically with blood tungsten concentrations reaching maximum at 0 hours post-exposure. The exposure parameters of 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.

Executive summary:

No toxicokinetics data of sufficient quality are available for tungsten carbide (target substance). However, toxicokinetics data are available for tungsten oxide (source substance), which will be used for read-across. Due to lower water solubility for the target substance compared to the source substance, the resulting read-across from the source substance to the target substance is appropriate. In addition, read-across is appropriate because the classification and labelling is similar for the source substance than the target substance, the PBT/vPvB profile is the same, and the dose descriptors are, or are expected to be, lower for the source substance. For more details, refer to the read-across category approach included in the Category section of this IUCLID submission on Annex 3 in the CSR.

Description of key information

In an in vivo toxicokinetic study in which tungsten carbide (WC) was administered to female rats by oral gavage, feces and urine were collected 24 hours after dosing. More than 98% of the total tungsten found was in the faeces, and only 0.04-0.05% was found in the urine; which indicated that after oral administration of WC to rats, the bioavailability of tungsten was low. In a GLP in vitro study conducted according to Draft Guidance for RIP 3.6: Bioavailability and Read-Across for Metals and Minerals (Eurometaux 2008), the bioavailability of WC was determine in simulated human gastric, sweat, alveolar, lysosomal, and interstitial fluids. The average amount of W found in the extracts was in the 0.0192 to 0.485% range. The maximum solubility was determined at 72 hours for the simulated alveolar and lysosomal fluids (0.4852 and 0.414%, respectively). The percent of available W in simulated gastric fluid sampled at 5 hours was 0.0357 +/- 0.000716% (2.0 % relative standard deviation (RSD)). The percent of available W in simulated sweat fluid sampled at 12 hours was 0.07681 +/-0.00302 % (4.0% relative standard deviation). The percent of available W in simulated alveolar fluid sampled at 2, 5, 24, and 72 hours was 0.01920 +/- 0.00224%, 0.0335 +/- 0.00123%, 0.08995 +/- 0.00705%, and 0.4852 +/-0.05762%, respectively; with percent relative standard deviations of 12, 3.7, 7.9, and 12% RSD, respectively. The percent of available W in simulated lysosomal fluid sampled at 2, 5, 24, and 72 hours was 0.07884 +/- 0.04751%, 0.0929 +/- 0.05963%, 0.202 +/- 0.156%, and 0.414 +/- 0.2830%, respectively with percent RSDs of 60, 64, 74, and 68% RSD, respectively. The percent of available W in simulated interstitial fluid sampled at 2, 5, 24, and 72 hours was 0.0458 +/- 0.0201%, 0.03740 +/- 0.008996%, 0.06570 +/- 0.0101%, and 0.134 +/- 0.0537 %, respectively with percent relative standard deviations of 44, 24, 15, and 41% RSD, respectively.

 

In addition a toxicokinetic study conducted according to OECD 417 on tungsten oxide was used for read across. When tungsten oxide was administered via the inhalation route, W was absorbed systemically with blood W concentrations reaching maximum at 0 hours post-exposure. Cmax and AUC increased proportionally with increasing tungsten oxide 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 tungsten oxide 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 W concentration on a per organ weight basis. In terms of total W 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 W in most organs was less than 24 hours.

 

Based on the available data, the bioavailability of tungsten carbide would be expected to be low for the oral, dermal, and inhalation routes of administration.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential