Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.66 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
37.5
Dose descriptor starting point:
LOAEL
Value:
10 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
Value:
24.7 mg/m³
Explanation for the modification of the dose descriptor starting point:

The most appropriate endpoint for derivation of a DNEL is the oral LOAEL of 10 mg/kg bw/d taken from the rabbit developmental study (CIT, 2020) based on kidney observed fetal malformation.


 


Correction factor for differences in respiratory volume (rat/workers): 1/0.38


Correction factor for light activity at work : 6.7/10


Correction factor for difference between human and experimental exposure conditions : 7/5 (In the study, animals were exposed 7 days per week, and workers work 5 days per week).


Oral absorption = 100 % (see section 7.1 Toxicokinetics)


Inhalation absorption = 100% (see section 7.1 Toxicokinetics)


LOAEC = NOAEL x (1/0.38) x (6.7/10) x 7/5= 10 x (1/0.38) x (6.7/10) x 7/5 = 24.7 mg/m3


 

AF for dose response relationship:
3
Justification:
The Point of departure is the LOAEL.
AF for differences in duration of exposure:
1
Justification:
The key study is a rabbit developmental toxicity study, the study cover critical window during gestation.
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation. Allometric scaling is implicitly taken into account in the factor for remaining differences.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining differences.
AF for intraspecies differences:
5
Justification:
A factor of 5 is applied for worker DNELs.
AF for the quality of the whole database:
1
Justification:
The quality of the database is correct.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is applied.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
irritation (respiratory tract)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.56 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
140
Dose descriptor starting point:
LOAEL
Value:
10 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
140 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The most appropriate endpoint for derivation of a DNEL is the oral LOAEL of 10 mg/kg bw/d taken from the rabbit developmental study (CIT, 2020) based on kidney observed fetal malformation.


Based on the TK assessment, a dermal absorption of 10% was used.


Correction factor for difference between human and experimental exposure conditions : 7/5 (In the study, animals were exposed 7 days per week, and workers work 5 days per week).


Dermal LOAEL = oral LOAEL x 100/10 x 7/5= 10 x 100/10 x 7/5 = 140 mg/kg bw/day


 

AF for dose response relationship:
3
Justification:
The most appropriate endpoint for derivation of a DNEL is the oral LOAEL of 10 mg/kg bw/d taken from the rabbit developmental study (CIT, 2020) based on kidney observed fetal malformation.
AF for differences in duration of exposure:
1
Justification:
The key study is a rabbit developmental toxicity study, the study cover critical window during gestation.
AF for interspecies differences (allometric scaling):
2.4
Justification:
An allometric scaling factor of 2.4 must be applied because the key study was performed on rabbits.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining differences.
AF for intraspecies differences:
5
Justification:
A factor of 5 is applied for worker DNELs.
AF for the quality of the whole database:
1
Justification:
The quality of the database is considered to be correct.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is applied.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.12 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor starting point:
LOAEL
Value:
10 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
Value:
8.7 mg/m³
Explanation for the modification of the dose descriptor starting point:

The point of departure is the LOAEL of 10 mg/kg/day derived from the key developmental study (CIT, 2020).


Correction factor for differences in respiratory volume (rat/general population): 1/1.15


Oral absorption = 100 % (see section 7.1 Toxicokinetics)


Inhalation absorption = 100% (see section 7.1 Toxicokinetics)


LOAEC = LOAEL x (1/1.15) = 10 x (1/1.15) = 8.7 mg/m3

AF for dose response relationship:
3
Justification:
The POD is the LOAEL of 10mg/kg:day taken from the rabbit developmental study (CIT, 2020) based on fetal malformation.
AF for differences in duration of exposure:
1
Justification:
The key study is a rabbit developmental toxicity study, the study cover critical window during gestation.
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation. Allometric scaling is implicitly taken into account in the factor for remaining differences.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining differences.
AF for intraspecies differences:
10
Justification:
A factor of 10 is applied for the general population DNELs.
AF for the quality of the whole database:
1
Justification:
The quality of the database is considered to be correct.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is applied.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
irritation (respiratory tract)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.56 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
180
Dose descriptor starting point:
LOAEL
Value:
10 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The most appropriate endpoint for derivation of a DNEL is the oral LOAEL of 10 mg/kg bw/d taken from the rabbit developmental study (CIT, 2020) based on kidney observed fetal malformation.


Based on the TK assessment, a dermal absorption of 10% was used.


Dermal LOAEL = oral LOAEL x 100/10 = 10 x 100/10 = 100 mg/kg bw/day

AF for dose response relationship:
3
Justification:
Conversion from LOAEL to NOAEL: The POD is the LOAEL of 10 mg/kg:day taken from the rabbit developmental study (CIT, 2020) based on fetal malformation.
AF for differences in duration of exposure:
1
Justification:
The key study is a rabbit developmental toxicity study, the study cover critical window during gestation.
AF for interspecies differences (allometric scaling):
2.4
Justification:
An allometric scaling factor of 2.4 must be applied because the key study was performed on rabbits.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining differences.
AF for intraspecies differences:
10
Justification:
A factor of 10 is applied for the general population DNELs.
AF for the quality of the whole database:
1
Justification:
The quality of the database is considered to be correct.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is applied.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.06 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
180
Dose descriptor starting point:
LOAEL
Value:
10 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
10 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

General population long term exposure - systemic effects (oral) : DNELs were calculated from the LOAEL of 10 mg/kg/day, assuming a 100% absorption oral rate (worst case).

AF for dose response relationship:
3
Justification:
Conversion from LOAEL to NOAEL: The POD is the LOAEL of 10 mg/kg:day taken from the rabbit developmental study (CIT, 2020) based on fetal malformation.
AF for differences in duration of exposure:
1
Justification:
The key study is a rabbit developmental toxicity study, the study cover critical window during gestation.
AF for interspecies differences (allometric scaling):
2.4
Justification:
An allometric scaling factor of 2.4 must be applied because the key study was performed on rabbits.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining differences
AF for intraspecies differences:
10
Justification:
A factor of 10 is applied for the general population DNELs.
AF for the quality of the whole database:
1
Justification:
The quality of the database is considered to be correct.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is applied.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population