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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
45
Dose descriptor starting point:
NOAEC
Value:
650 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
270 mg/m³
Explanation for the modification of the dose descriptor starting point:

The most relevant route of potential exposure to workers is the inhalation and dermal routes. Based on the available acute toxicity data (oral, dermal, inhalation) from read-across, fused tungsten carbide is not likely an acute toxicant, and therefore, derivation of DNEL long-term will be sufficient to control potential risks associated with short-term exposures. In addition, based on the available data from read-across, fused tungsten carbide is not likely irritating to either the eyes or skin, or sensitising to the skin. Therefore, based on the available data, fused tungsten carbide does not appear to elicit local toxicity effects. As such, derivation of a DNEL for local effects is not necessary. A 28-d inhalation toxicity study on tungsten oxide (also known as tungsten blue oxide or TBO) will be used for read-across as the key long-term study for derivation of the DNELs. Additional details of the read-across from TBO for fused tungsten carbide are described in the attached read-across document; where data for TBO as a more water soluble substance can be used for fused tungsten carbide as a less water-soluble substance. Based on in vitro bioaccessibility studies on both TBO and fused tungsten carbide, TBO is more bioaccessible in the various lung fluids, and would therefore likely be more bioavailable in the lung. As such, toxicity data on TBO administered via the inhalation route represent a conservative estimate of systemic toxicity effects for fused tungsten carbide. In the 28-d inhalation toxicity study with TBO, 5 rats/sex/dose were given TBO nose-only for 6 h per d, 7 d/week for 28 d at doses of 0 (control), 0.08, 0.325, and 0.65 mg TBO/L air. The NOAEL was deemed to be greater than 0.65 mg TBO/L air (650 mg TBO/m3).

The starting dose of 650 mg/m3needed to be modified, as the experimental animals were exposed for 6 h/d, whereas workers are exposed for 8 h/d. In addition, for occupational exposure, the starting point needs to be modified to correct for respiratory volume under standard conditions (6.7 m3/person) versus under conditions of light activity for workers (10 m3/person). Based on ECHA’s recommendations, it is assumed that respiratory absorption is equivalent between the animals and humans. Therefore, the corrected dose is 330 mg TBO/m3.

In addition, the starting dose was adjusted for the molecular weight of W since the bioavailable W is considered to be the toxic species and is the basis for the read-across approach. In order to be consistent with this approach, the DNEL value is derived in terms of the W concentration of the source read-across substance and then corrected for the molecular weight of the target read-across substance. Using the molecular formula and molecular weight for TBO and fused tungsten carbide, the corrected starting dose for calculation of the inhalation DNEL is 270 mg fused tungsten carbide/m3.

Per ECHA, the interspecies AF should include an allometric scaling (AS) factor plus an additional factor of 2.5. In the case of the rat, the ECHA-recommended AS factor is 4. However, when the starting point is an inhalation dose, an AS factor is not used. Therefore, for the inhalation route, only an interspecies factor of 2.5 is used. Eurometaux (2010) recommend an AF of 3 for intraspecies variability in workers, which is based on the ECETOC task force’s analysis of the intraspecies variability of toxicokinetic and toxicodynamic parameters from human data. Based on the recommendations of Eurometaux (2010), an intraspecies AF of 3 was used for workers. To account for extrapolation from a subacute study to chronic, ECHA recommend using an AF of 6.

The overall AF used to derive the systemic DNELlong-termfor the inhalation route for the worker was 45 (2.5 x 3 x 6).

AF for dose response relationship:
1
Justification:
No AF was considered as dose descriptor staring point was the NOAEC
AF for differences in duration of exposure:
6
Justification:
To account for extrapolation from a subacute study to chronic, ECHA recommends using an AF of 6
AF for interspecies differences (allometric scaling):
1
Justification:
In the case of the rat, the ECHA-recommended AS factor is 4. However, when the starting point is an inhalation dose, an AS factor is not used
AF for other interspecies differences:
2.5
Justification:
Per ECHA, the interspecies AF should include an allometric scaling (AS) factor plus an additional factor of 2.5. In the case of the rat, the ECHA-recommended AS factor is 4. However, when the starting point is an inhalation dose, an AS factor is not used. Therefore, for the inhalation route, only an interspecies factor of 2.5 is used.
AF for intraspecies differences:
3
Justification:
Eurometaux (2010) recommends an AF of 3 for intraspecies variability in workers, which is based on the ECETOC task force’s analysis of the intraspecies variability of toxicokinetic and toxicodynamic parameter s from human data. Based on the recommendations of Eurometaux (2010), an intraspecies AF of 3 was used for workers.
AF for the quality of the whole database:
1
Justification:
Quality of the data is properly assessed and found to be adequate
AF for remaining uncertainties:
1
Justification:
No additional uncertainties were considered
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.7 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
180
Dose descriptor starting point:
NOAEC
Value:
650 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
311 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For route-to-route extrapolation, to convert from an inhalation NOAEL/LOAEL (mg/m3) to a dermal dose (mg/kg bw/d), the inhalation NOAEL needs to be multiplied by the default respiratory volume of the rat. The default respiratory volume in the rat recommended by ECHA is 0.8 L/min/kg bw. 0.8 L/min/kg bw x (0.001 m3/1 L) x (1/min x 60 min/h x 24 h/1 d) = 1.152 m3/d/kg bw. The extrapolated NOAEL for the dermal route = 330 mg/m3x 1.152 m3/d/kg bw = 380 mg/kg bw/d. In the absence of specific data, as recommended by ECHA, the default is to assume the same bioavailability for experimental animals and humans for a particular exposure route. If substance-specific data are not available on the route-specific absorption values, default values may be used. Therefore, the dermal DNEL starting dose based on the NOAEL from the inhalation toxicity study is 380 mg TBO/kg bw/d.

In addition, the starting dose was adjusted for the molecular weight of tungsten since the tungsten ion is considered to be the toxic species and is the basis for the read-across approach. In order to be consistent with this approach, the DNEL value is derived in terms of the tungsten concentration of the source read-across substance and then corrected for the molecular weight of the target read-across substance. Using the molecular formula and molecular weight for tungsten blue oxide (TBO) and fused tungsten carbide, the corrected starting dose for calculation of the dermal DNEL is 311 mg fused tungsten carbide/kg bw/d.

Per ECHA, the interspecies AF should include an allometric scaling (AS) factor plus an additional factor of 2.5. In the case of the rat, the ECHA-recommended AS factor is 4. For the dermal route, the interspecies AF is equal to 4 x 2.5 = 10. Eurometaux (2010) recommend an AF of 3 for intraspecies variability in workers, which is based on the ECETOC task force’s analysis of the intraspecies variability of toxicokinetic and toxicodynamic parameters from human data. Based on the recommendations of Eurometaux (2010), an intraspecies AF of 3 was used for workers. To account for extrapolation from a subacute study to chronic, ECHA recommend using an AF of 6.

The overall AF used to derive the systemic DNELlong-termfor the dermal route for the worker was 180 (10 x 3 x 6).

AF for dose response relationship:
1
Justification:
No AF was considered as dose descriptor staring point was the NOAEC
AF for differences in duration of exposure:
6
Justification:
To account for extrapolation from a subacute study to chronic, ECHA recommends using an AF of 6.
AF for interspecies differences (allometric scaling):
4
Justification:
In the case of the rat, the ECHA-recommended AS factor is 4.

AF for other interspecies differences:
2.5
Justification:
For the inhalation route, only an interspecies factor of 2.5 is used

AF for intraspecies differences:
3
Justification:
Eurometaux (2010) recommends an AF of 3 for intraspecies variability in workers, which is based on the ECETOC task force’s analysis of the intraspecies variability of toxicokinetic and toxicodynamic parameters from human data
AF for the quality of the whole database:
1
Justification:
Quality of the data is properly assessed and found to be adequate
AF for remaining uncertainties:
1
Justification:
No additional uncertainities were considered
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Worker DNELlong-termfor the inhalation route = 270/45 = 6 mg fused tungsten carbide/m3(5.8 mg W/m3)

Worker DNELlong-termfor the dermal route = 311/180 = 1.7 mg fused tungsten carbide/kg bw/d (1.7 mg W/kg bw/d)

It should be noted that the inhalation DNELlong-termfor the worker of 5.8 mg W/m3is consistent with the current threshold limit value (TLV) for tungsten of 5 mg W/m3.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.75 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor starting point:
NOAEC
Value:
650 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
131 mg/m³
Explanation for the modification of the dose descriptor starting point:

The relevant routes of exposure for the general population are the oral, dermal, and inhalation routes. Based on the available acute toxicity data (oral, dermal, inhalation) from read-across, fused tungsten carbide is not likely an acute toxicant and therefore, derivation of DNELlong-termwill be sufficient to control potential risks associated with short term exposures. In addition, based on the available data from read-across, fused tungsten carbide is not likely irritating to either the eyes or skin, or sensitising to the skin. Therefore, based on the available data, fused tungsten carbide does not appear to elicit local toxicity effects. As such, derivation of a DNEL for local effects is not necessary. A 28-d inhalation toxicity study on tungsten oxide (also known as tungsten blue oxide or TBO) will be used for read-across as the key long-term study for derivation of the DNELs. Additional details of the read-across from TBO for fused tungsten carbide are described in the attached read-across document; where data for TBO as a more water soluble substance can be used for fused tungsten carbide as a less water-soluble substance. Based onin vitro bioaccessibility studies on both TBO and fused tungsten carbide, TBO is more bioaccessible in the various lung fluids, and would therefore likely be more bioavailable in the lung. As such, toxicity data on TBO administered via the inhalation route represent a conservative estimate of systemic toxicity effects for fused tungsten carbide. In the 28-d inhalation toxicity study with TBO, 5 rats/sex/dose were given TBO nose-only for 6 h/d, 7 d/week for 28 d at doses of 0 (control), 0.08, 0.325, and 0.65 mg TBO/L air. The NOAEL was deemed to be greater than 0.65 mg TBO/L air (650 mg TBO/m3).

The starting dose of 650 mg/m3needed to be modified, as the experimental animals were exposed for 6 h/d, whereas the general population may be exposed for 24 h/d. Therefore, the corrected dose is: NOAEL corrected = 650 mg/m3x 6/24 = 160 mg TBO/m3.

In addition, the starting dose was adjusted for the molecular weight of tungsten since the tungsten ion is considered to be the toxic species and is the basis for the read-across approach. In order to be consistent with this approach, the DNEL value is derived in terms of the W concentration of the source read-across substance and then corrected for the molecular weight of the target read-across substance. Using the molecular formula and molecular weight for TBO and fused tungsten carbide, the corrected starting dose for calculation of the inhalation DNEL is 131 mg fused tungsten carbide/m3.

Per ECHA, the interspecies AF should include an allometric scalling (AS) factor plus an additional factor of 2.5. In the case of the rat, the ECHA- recommended AS factor is 4. However, when the starting point is an inhalation dose, an AS factor is not used. Therefore, for the inhalation route, only an interspecies factor of 2.5 is used. Based on the recommendations of Eurometaux (2010), an intraspecies AF of 5 was used for the general population. Eurometaux (2010) recommend an AF of 5 for intraspecies variability in the general population, which is based on the ECETOC task force’s analysis of the intraspecies variability of toxicokinetic and toxicodynamic parameters from human data. Based on the recommendations of Eurometaux (2010), an intraspecies AF of 5 was used for the general population. To account for extrapolation from a subacute study to chronic, ECHA recommend using an AF of 6.The overall AF used to derive the systemic DNELlong-termfor the inhalation route for the general population was 75 (2.5 x 5 x 6).

AF for dose response relationship:
1
Justification:
No AF was considered as dose descriptor staritng point was the NOAEC
AF for differences in duration of exposure:
6
Justification:
To account for extrapolation from a subacute study to chronic, ECHA recommends using an AF of 6
AF for interspecies differences (allometric scaling):
1
Justification:
Per ECHA, the interspecies AF should include an allometric scaling (AS) factor plus an additional factor of 2.5. In the case of the rat, the ECHA- recommended AS factor is 4. So, the interspecies AF is equal to 4 x 2.5 = 10 for the oral route. However, when the starting point is an inhalation dose, an AS factor is not used. Therefore, for the inhalation route, only an interspecies factor of 2.5 is used
AF for other interspecies differences:
2.5
Justification:
Per ECHA, the interspecies AF should include an allometric scaling (AS) factor plus an additional factor of 2.5. In the case of the rat, the ECHA- recommended AS factor is 4. So, the interspecies AF is equal to 4 x 2.5 = 10 for the oral route. However, when the starting point is an inhalation dose, an AS factor is not used. Therefore, for the inhalation route, only an interspecies factor of 2.5 is used
AF for intraspecies differences:
5
Justification:
Eurometaux (2010) recommends an AF of 5 for intraspecies variability in the general population, which is based on the ECETOC task force’s analysis of the intraspecies variability of toxicokinetic and toxicodynamic parameters from human data. Based on the recommendations of Eurometaux (2010), an intraspecies AF of 5 was used for the general population
AF for the quality of the whole database:
1
Justification:
Quality of the data is properly assessed and found to be adequate
AF for remaining uncertainties:
1
Justification:
No additional uncertainities were considered
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.49 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEC
Value:
650 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
147 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For route-to-route extrapolation to convert from an inhalation NOAEL/LOAEL (mg/m3) to an oral dose (mg/kg/d), the inhalation NOAEL need to be multiplied by the default respiratory volume of the rat. The default respiratory volume in the rat recommended by ECHA is 0.8 L/min/kg bw. 0.8 L/min/kg bw x (0.001 m3/1 L) x (1/min x 60 min/h x 24 h/1 d) = 1.152 m3/d/kg bw. The extrapolated NOAEL for the oral and dermal routes = 160 mg TBO/m3x 1.152 m3/d/kg bw = 180 mg/kg bw/d. In the absence of specific data, as recommended by ECHA, the default is to assume the same bioavailability for experimental animals and humans for a particular exposure route. If substance-specific data are not available on the route-specific absorption values, default values may be used. In the case of extrapolation from inhalation-to-oral, no default factor (ie, a factor of 1) should be used in the extrapolation. Therefore, the oral and dermal DNEL starting dose based on the NOAEL from the inhalation toxicity study is 180 mg TBO/kg/d.

In addition, the starting dose was adjusted for the molecular weight of tungsten since the tungsten ion is considered to be the toxic species and is the basis for the read-across approach. In order to be consistent with this approach, the DNEL value is derived in terms of the W concentration of the source read-across substance and then corrected for the molecular weight of the target read-across substance. Using the molecular formula and molecular weight for tungsten blue oxide (TBO) and fused tungsten carbide, the corrected starting dose for calculation of the dermal DNELs is 147 mg fused tungsten carbide/kg/d.

Per ECHA, the interspecies AF should include an allometric scale (AS) factor plus an additional factor of 2.5. In the case of the rat, the ECHA- recommended AS factor is 4. So, the interspecies AF is equal to 4 x 2.5 = 10 for the oral and dermal routes. Based on the recommendations of Eurometaux (2010), an intraspecies AF of 5 was used for the general population. Eurometaux (2010) recommend an AF of 5 for intraspecies variability in the general population, which is based on the ECETOC task force’s analysis of the intraspecies variability of toxicokinetic and toxicodynamic parameters from human data. Based on the recommendations of Eurometaux (2010), an intraspecies AF of 5 was used for the general population. To account for extrapolation from a subacute study to chronic, ECHA recommend using an AF of 6.

AF for dose response relationship:
1
Justification:
No AF was considered as dose descriptor staritng point was the NOAEC
AF for differences in duration of exposure:
6
Justification:
To account for extrapolation from a subacute study to chronic, ECHA recommends using an AF of 6.
AF for interspecies differences (allometric scaling):
2.5
Justification:
In the case of the rat, the ECHA-recommended AS factor is 4. However, when the starting point is an inhalation dose, an AS factor is not used
AF for other interspecies differences:
4
Justification:
In the case of the rat, the ECHA- recommends AS factor of 4
AF for intraspecies differences:
5
Justification:
Eurometaux (2010) recommends an AF of 5 for intraspecies variability in the general population, which is based on the ECETOC task force’s analysis of the intraspecies variability of toxicokinetic and toxicodynamic parameters from human data
AF for the quality of the whole database:
1
Justification:
Quality of the data is properly assessed and found to be adequate
AF for remaining uncertainties:
1
Justification:
No additional uncertainities were considered.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.49 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEC
Value:
180 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
147 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For route-to-route extrapolation to convert from an inhalation NOAEL/LOAEL (mg/m3) to an oral dose (mg/kg/d), the inhalation NOAEL need to be multiplied by the default respiratory volume of the rat. The default respiratory volume in the rat recommended by ECHA is 0.8 L/min/kg bw. 0.8 L/min/kg bw x (0.001 m3/1 L) x (1/min x 60 min/h x 24 h/1 d) = 1.152 m3/d/kg bw. The extrapolated NOAEL for the oral and dermal routes = 160 mg TBO/m3x 1.152 m3/d/kg bw = 180 mg/kg bw/d. In the absence of specific data, as recommended by ECHA, the default is to assume the same bioavailability for experimental animals and humans for a particular exposure route. If substance-specific data are not available on the route-specific absorption values, default values may be used. In the case of extrapolation from inhalation-to-oral, no default factor (ie, a factor of 1) should be used in the extrapolation. Therefore, the oral and dermal DNEL starting dose based on the NOAEL from the inhalation toxicity study is 180 mg TBO/kg/d.

In addition, the starting dose was adjusted for the molecular weight of tungsten since the tungsten ion is considered to be the toxic species and is the basis for the read-across approach. In order to be consistent with this approach, the DNEL value is derived in terms of the W concentration of the source read-across substance and then corrected for the molecular weight of the target read-across substance. Using the molecular formula and molecular weight for tungsten blue oxide (TBO) and fused tungsten carbide, the corrected starting dose for calculation of the oral DNELs is 147 mg fused tungsten carbide/kg/d.

Per ECHA, the interspecies AF should include an allometric scalling (AS) factor plus an additional factor of 2.5. In the case of the rat, the ECHA- recommended AS factor is 4. So, the interspecies AF is equal to 4 x 2.5 = 10 for the oral and dermal routes. Based on the recommendations of Eurometaux (2010), an intraspecies AF of 5 was used for the general population. Eurometaux (2010) recommend an AF of 5 for intraspecies variability in the general population, which is based on the ECETOC task force’s analysis of the intraspecies variability of toxicokinetic and toxicodynamic parameters from human data. Based on the recommendations of Eurometaux (2010), an intraspecies AF of 5 was used for the general population. To account for extrapolation from a subacute study to chronic, ECHA recommend using an AF of 6.

AF for dose response relationship:
1
Justification:
No AF was considered as dose descriptor starting point was the NOAEC
AF for differences in duration of exposure:
6
Justification:
To account for extrapolation from a subacute study to chronic, ECHA recommends using an AF of 6.
AF for interspecies differences (allometric scaling):
4
Justification:
In the case of the rat, the ECHA- recommended AS factor is 4
AF for other interspecies differences:
5
Justification:
Eurometaux (2010) recommends an AF of 5 for intraspecies variability in the general population, which is based on the ECETOC task force’s analysis of the intraspecies variability of toxicokinetic and toxicodynamic parameters from human data
AF for intraspecies differences:
2.5
Justification:
Per ECHA, the interspecies AF should include an allometric scaling (AS) factor plus an additional factor of 2.5.
AF for the quality of the whole database:
1
Justification:
Quality of the data is properly assessed and found to be adequat
AF for remaining uncertainties:
1
Justification:
No additional uncertainities were considered
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

General population DNELlong-termfor the inhalation route = 131/75 = 1.75 mg fused tungsteb carbide/m3(1.7 mg W/m3)

General population DNELlong-termfor the dermal route = 147/300 = 0.49 mg fused tungsten carbide/kg bw/d (0.48 mg W/kg bw/d)

General population DNELlong-termfor the oral route = 147/300 = 0.49 mg fused tungsten carbide/kg bw/d (0.48 mg W/kg bw/d)