Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.8 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:
262 mg/m³
Explanation for the modification of the dose descriptor starting point:

The most relevant routes of potential exposure to workers would be the dermal and inhalation routes. Based on the available acute toxicity data (oral, dermal, inhalation), tungsten metal is not likely an acute toxicant, and therefore, derivation of DNELlong-term will be sufficient to control potential risks associated with shortterm exposures. In addition, based on the available data, tungsten metal is not likely irritating to either the eyes or skin, or sensitizing to the skin. Therefore, based on the available data, tungsten metal does not appear to elicit local toxicity effects. As such, derivation of a DNEL for local effects is not necessary. No repeat-dose toxicity data are available for tungsten metal; however, a 28-day inhalation toxicity study is available on TBO, which will be used for read-across and is considered the key long-term study for derivation of the DNELs. In this study, 5 rats/sex/dose were given TBO nose-only for 6 hours per day, 7 days/week, for 28 days 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/L air (650 mg TBO/m3). The starting dose of 650 mg/m3needed to be modified, as the experimental animals were exposed for 6 hrs per /day, whereas workers are exposed for 8 hrs per /day. 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 tungsten since the bioavailable tungsten is considered to be the toxic species and is the basis for the readacross 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 TBO and tungsten metal, the corrected starting dose for calculation of the inhalation DNEL is 262 mg W/m3.

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 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

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:
301 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/day), 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/hr x 24 hrs/1 day) = 1.152 m3/day/kg bw. The extrapolated NOAEL for the dermal route = 330 mg/m3x 1.152 m3/day/kg bw = 380 mg/kg/day. 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/day. 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 TBO and tungsten metal, the corrected starting dose for calculation of the dermal DNEL is 301 mg W/kg/day.

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

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) 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. 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 recommends using an AF of 6.

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

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

- Worker DNELlong-term for the inhalation route = 262/45 = 5.8 mg W/m3 Worker DNELlong-term for the dermal route = 301/180 = 1.7 mg W/kg/day It should be noted that the inhalation DNELlong-term for the worker of 5.8 mg W/m3 is 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:
1.7 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:
127 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), tungsten is not likely an acute toxicant and therefore, derivation of DNELlong-term will be sufficient to control potential risks associated with short term exposures. In addition, based on the available data, tungsten metal is not likely irritating to either the eyes or skin, or sensitizing to the skin. Therefore, based on the available data, tungsten metal does not appear to elicit local toxicity effects. As such, derivation of a DNEL for local effects is not necessary. No repeat-dose toxicity data are available for tungsten metal; however, a 28-day inhalation toxicity study is available on TBO, which will be used for read-across and is considered the key long-term study for derivation of the DNELs. In this study, 5 rats/sex/dose were given TBO nose-only for 6 hours per day, 7 days/week, for 28 days at doses of 0 (control), 0.08, 0.325, and 0.65 mg/L air. The NOAEC was deemed to be greater than 0.65 mg/L air (650 mg/m3).

The starting dose of 650 mg/m3needed to be modified, as the experimental animals were exposed for 6 hrs/day, whereas the general population may be exposed for 24 hours/day. Therefore, the corrected dose is 160 mg TBO/m3. In addition, the starting dose was adjusted for the molecular weight of tungsten since the bioavailable tungsten 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 TBO and tungsten metal, the corrected starting dose for calculation of the inhalation DNEL is 127 mg W/m3.

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:
0.48 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:
143 mg/kg bw/day
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), tungsten is not likely an acute toxicant and therefore, derivation of DNELlong-term will be sufficient to control potential risks associated with short term exposures. In addition, based on the available data, tungsten metal is not likely irritating to either the eyes or skin, or sensitizing to the skin. Therefore, based on the available data, tungsten metal does not appear to elicit local toxicity effects. As such, derivation of a DNEL for local effects is not necessary. No repeat-dose toxicity data are available for tungsten metal; however, a 28-day inhalation toxicity study is available on TBO, which will be used for read-across and is considered the key long-term study for derivation of the DNELs. In this study, 5 rats/sex/dose were given TBO nose-only for 6 hours per day, 7 days/week, for 28 days at doses of 0 (control), 0.08, 0.325, and 0.65 mg/L air. The NOAEC was deemed to be greater than 0.65 mg/L air (650 mg/m3).

The starting dose of 650 mg/m3 needed to be modified, as the experimental animals were exposed for 6 hrs/day, whereas the general population may be exposed for 24 hours/day. Therefore, the corrected dose is 160 mg TBO/m3. In addition, the starting dose was adjusted for the molecular weight of tungsten since the bioavailable tungsten 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 TBO and tungsten metal, the corrected starting dose for calculation of the inhalation DNEL is 127 mg W/m3.

For route-to-route extrapolation to convert from an inhalation NOAEL/LOAEL (mg/m3) to an oral dose (mg/kg/day), 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/hr x 24 hrs/1 day) = 1.152 m3/day/kg bw. The extrapolated NOAEL for the oral and dermal routes = 160 mg/m3x 1.152 m3/day/kg bw = 180 mg/kg/day. 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 (i. e., 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/day. 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 TBO and tungsten metal, the corrected starting dose for calculation of the dermal DNEL is 143 mg W/kg/day.

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:
0.48 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:
143 mg/kg bw/day
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), tungsten is not likely an acute toxicant and therefore, derivation of DNELlong-term will be sufficient to control potential risks associated with short term exposures. In addition, based on the available data, tungsten metal is not likely irritating to either the eyes or skin, or sensitizing to the skin. Therefore, based on the available data, tungsten metal does not appear to elicit local toxicity effects. As such, derivation of a DNEL for local effects is not necessary. No repeat-dose toxicity data are available for tungsten metal; however, a 28-day inhalation toxicity study is available on TBO, which will be used for read-across and is considered the key long-term study for derivation of the DNELs. In this study, 5 rats/sex/dose were given TBO nose-only for 6 hours per day, 7 days/week, for 28 days at doses of 0 (control), 0.08, 0.325, and 0.65 mg/L air. The NOAEC was deemed to be greater than 0.65 mg/L air (650 mg/m3).

The starting dose of 650 mg/m3needed to be modified, as the experimental animals were exposed for 6 hrs/day, whereas the general population may be exposed for 24 hours/day. Therefore, the corrected dose is 160 mg TBO/m3. In addition, the starting dose was adjusted for the molecular weight of tungsten since the bioavailable tungsten 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 TBO and tungsten metal, the corrected starting dose for calculation of the inhalation DNEL is 127 mg W/m3.

For route-to-route extrapolation to convert from an inhalation NOAEL/LOAEL (mg/m3) to an oral dose (mg/kg/day), 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/hr x 24 hrs/1 day) = 1.152 m3/day/kg bw. The extrapolated NOAEL for the oral and dermal routes = 160 mg/m3x 1.152 m3/day/kg bw = 180 mg/kg/day. 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 (i. e., 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/day. 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 TBO and tungsten metal, the corrected starting dose for calculation of the dermal DNEL is 143 mg W/kg/day.

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

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. Based on the recommendations of Eurometaux (2010), an intraspecies AF of 5 was used for the general population. 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.  To account for extrapolation from a subacute study to chronic, ECHA recommends using an AF of 6.

The overall AF used to derive the systemic DNELlong-term for the inhalation route for the general population was 75 (2.5 x 5 x 6).

The overall AF used to derive the systemic DNELlong-term for the oral and dermal routes for the general population was 300 (10 x 5 x 6).

General population DNELlong-term for the inhalation route = 127/75 = 1.7 mg W/m3

General population DNELlong-term for the dermal route = 143/300 = 0.48 mg W/kg/day

General population DNELlong-term for the oral route = 143/300 = 0.48 mg W/kg/day