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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:
37.7 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
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:
4 015 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
2 825 mg/m³
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an inhalation NOAEC observed in a developmental toxicity study in mice (OECD 414; 1986).

Conversion of an inhalatory mouse NOAEC into a corrected inhalatory NOAEC in case of differences between experimental and human exposure condition has to be performed.

Corrected starting point for the inhalative route for workers:

= NOAEC (inhalation) * exposure condition mouse / exposure condition human

= 4015 mg/m³ * (6h/day / 8h/day) * (6.7 m³ (8h) /10 m³ (8h) )* (7 days exposure mouse/5 days exposure worker)

= 4015 mg/m³ * 0.75 * 0.67 m³ * 1.4 = 2825 mg/m³

 

Thus, the corrected starting point for workers was 2825 mg/m³ for inhalation.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEC.
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a subacute study.
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
5
Justification:
Default value for workers according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on high-quality studies.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties as the lowest NOAEC was used.
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:
5.01 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
525
Dose descriptor starting point:
NOAEC
Value:
4 015 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
2 631 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an inhalation NOAEC observed in a developmental toxicity study in mice (OECD 414; 1986).

Conversion of an inhalatory mouse NOAEC into a corrected dermal NOAEL in case of differences between experimental and human exposure condition and interspecies differences between mouse and human has to be performed.

Corrected starting point for the inhalative route for workers:

To correct the interspecies difference between rat and human the no observed effect level has to be corrected as follows:

Corrected starting point for the inhalative route for workers:

= NOAEC (inhalation) * sRV(mouse) * exposure condition mouse / exposure condition human * (ABSinh-mouse/ABSdermal-human) * (7 days exposure mouse/5 days exposure worker)

= 4015 mg/m³ * 0.624 m³/kg bw* (6h/day / 8h/day) * (1/1) * 1.4 = 2631 mg/kg bw/day

It is assumed that dermal absorption and inhalation absorption rates are equal.

(ABSdermal-human = dermal absorption in humans, ABSinh-mouse = inhalation absorption rate in mice)

Thus, the corrected starting point for workers is 2631 mg/kg bw/day for dermal exposure.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a subacute study.
AF for interspecies differences (allometric scaling):
7
Justification:
Default value for mice according to ECHA REACH Guidance.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
5
Justification:
Default value for workers according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on high-quality studies.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.7 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
NOAEC
Value:
4 015 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
1 004 mg/m³
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an inhalation NOAEC observed in a developmental toxicity study in mice (OECD 414; 1986).

Conversion of an inhalatory mouse NOAEC into a corrected inhalatory NOAEC in case of differences between experimental and human exposure condition has to be performed.

Corrected starting point for the inhalative route for workers:

= NOAEC (inhalation) * exposure condition mouse / exposure condition human

= 4015 mg/m³ * (6h/day / 24h/day)

= 4015 mg/m³ * 0.25 = 1004 mg/m³

 

Thus, the corrected starting point for workers was 1004 mg/m³ for inhalation.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a subacute study.
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used used for inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guida
AF for intraspecies differences:
10
Justification:
Default value general population.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on a high-quality data set.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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:
1.79 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1 050
Dose descriptor starting point:
NOAEC
Value:
4 015 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
1 877 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an inhalation NOAEC observed in a developmental toxicity study in mice (OECD 414; 1986).

Conversion of an inhalatory mouse NOAEC into a corrected dermal NOAEL in case of differences between experimental and human exposure condition and interspecies differences between mouse and human has to be performed.

Corrected starting point for the inhalative route for workers:

To correct the interspecies difference between rat and human the no observed effect level has to be corrected as follows:

Corrected starting point for the inhalative route for workers:

= NOAEC (inhalation) * sRV(mouse) * exposure condition mouse / exposure condition human * (ABSinh-mouse/ABSdermal-human) * (7 days exposure mouse/5 days exposure worker)

= 4015 mg/m³ * 1.87 m³/kg bw* (6h/day / 24h/day) * (1/1) = 1877 mg/kg bw/day

It is assumed that dermal absorption and inhalation absorption rates are equal.

(ABSdermal-human = dermal absorption in humans, ABSinh-mouse = inhalation absorption rate in mice)

Thus, the corrected starting point for general population is 1877 mg/kg bw/day for dermal exposure.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a subacute study.
AF for interspecies differences (allometric scaling):
7
Justification:
Default value for mice according to ECHA REACH Guidance.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
Default value for general population according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is base on a set of high-quality studies.
AF for remaining uncertainties:
1
Justification:
No remaining uncertaintie.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.79 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1 050
Dose descriptor starting point:
NOAEC
Value:
4 015 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 877 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an inhalation NOAEC observed in a developmental toxicity study in mice (OECD 414; 1986).

Conversion of an inhalatory mouse NOAEC into a corrected dermal NOAEL in case of differences between experimental and human exposure condition and interspecies differences between mouse and human has to be performed.

Corrected starting point for the inhalative route for workers:

To correct the interspecies difference between rat and human the no observed effect level has to be corrected as follows:

Corrected starting point for the inhalative route for workers:

= NOAEC (inhalation) * sRV(mouse) * exposure condition mouse / exposure condition human * (ABSinh-mouse/ABSdermal-human) * (7 days exposure mouse/5 days exposure worker)

= 4015 mg/m³ * 1.87 m³/kg bw* (6h/day / 24h/day) * (1/1) = 1877 mg/kg bw/day

It is assumed that oral absorption and inhalation absorption rates are equal.

(ABSdermal-human = dermal absorption in humans, ABSinh-mouse = inhalation absorption rate in mice)

Thus, the corrected starting point forgeneral population is 1877 mg/kg bw/dayfordermal exposure.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a subactue study.
AF for interspecies differences (allometric scaling):
7
Justification:
Default value for mice according to ECHA REACH Guidance.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default value for general population according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The DNEL is based on a set of high-quality studies.
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population