Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.33 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:
LOAEC
Value:
5 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
Value:
12.3 mg/m³
Explanation for the modification of the dose descriptor starting point:

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 = LOAEL x (1/0.38) x (6.7/10) x 7/5= 5 x (1/0.38) x (6.7/10) x 7/5 = 12.3 mg/m3

AF for dose response relationship:
3
Justification:
This factor is applied because the dose-descriptor starting point is a LOAEC.
AF for differences in duration of exposure:
1
Justification:
DNEL is based on a reprotoxic effect. Assessment factor for duration exposure is not relevant.
AF for interspecies differences (allometric scaling):
1
Justification:
AF not relevant for inhalation.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining difference.
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 key study is considered as a reliable study with a klimisch score of 1.
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
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:
0.47 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):
150
Dose descriptor starting point:
LOAEL
Value:
5 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
70 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

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= 5 x 100/10 x 7/5 = 70 mg/kg bw/day

AF for dose response relationship:
3
Justification:
This factor is applied because the dose-descriptor starting point is a LOAEL.
AF for differences in duration of exposure:
1
Justification:
DNEL is based on a reprotoxic effect. Assessment factor for duration exposure is not relevant.
AF for interspecies differences (allometric scaling):
4
Justification:
An allometric scaling factor of 4 must be applied because the key study was performed on rats.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining difference.
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 key study is considered as a reliable study with a klimisch score of 1.
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

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:
0.06 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:
5 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
Value:
4.3 mg/m³
Explanation for the modification of the dose descriptor starting point:

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) = 5 x (1/1.15) = 4.3 mg/m3

AF for dose response relationship:
3
Justification:
This factor is applied because the dose-descriptor starting point is a LOAEC.
AF for differences in duration of exposure:
1
Justification:
DNEL is based on a reprotoxic effect. Assessment factor for duration exposure is not relevant.
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining difference.
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 key study is considered as a reliable study with a klimisch score of 1.
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:
0.17 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):
300
Dose descriptor starting point:
LOAEL
Value:
5 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

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


Dermal LOAEL = oral LOAEL x 100/10 = 5 x 100/10 = 50 mg/kg bw/day

AF for dose response relationship:
3
Justification:
This factor is applied because the dose-descriptor starting point is a LOAEL.
AF for differences in duration of exposure:
1
Justification:
DNEL is based on a reprotoxic effect. Assessment factor for duration exposure is not relevant.
AF for interspecies differences (allometric scaling):
4
Justification:
An allometric scaling factor of 4 must be applied because the key study was performed on rats.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining difference.
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 key study is considered as a reliable study with a klimisch score of 1.
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:
0.017 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):
300
Dose descriptor starting point:
LOAEL
Value:
5 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No difference of oral absorption is expected between rat and human.
AF for dose response relationship:
3
Justification:
This factor is applied because the dose-descriptor starting point is a LOAEL.
AF for differences in duration of exposure:
1
Justification:
DNEL is based on a reprotoxic effect. Assessment factor for duration exposure is not relevant.
AF for interspecies differences (allometric scaling):
4
Justification:
An allometric scaling factor of 4 must be applied because the key study was performed on rats.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining difference.
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 key study is considered as a reliable study with a klimisch score of 1.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is applied.
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population