Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.82 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):
25
Modified dose descriptor starting point:
NOAEC
Value:
70.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

Absorption is considered to be comparable via all routes, therefore no modification of the starting dose descriptor (oral route) is considered appropriate.

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
corrected NOAEL worker: 40 mg/kg bw / 0.38*0.67
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
5
Justification:
worker
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.4 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):
100
Modified dose descriptor starting point:
NOAEL
Value:
40 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The substance causes no local effects and systemic uptake is considered comparable for all routes of exposure.
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
5
Justification:
worker
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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

1. Identification of relevant dose descriptor

In a combined OECD 414/415 study the test item caused maternal toxicity and influenced fertility of the dams. The NOAEL for the parental generation is considered to be 40 mg/kg bw.

2. Mode of action

No non-threshold mode of action is associated with the test substance. In particular, the test substance has no genotoxic potential.

3. Application of assessment factors

Allometric scaling: rat to human = 4

Interspecies factor (remaining differences): 2.5

Intraspecies factor: worker = 5, general population = 10

Exposure duration subacute to chronic: 6

Quality of data base: 1

Dose response: 1

4. Daily exposure

Worker: exposed for 8h

General population: exposed for 24h

Calculation of DNEL bases upon Guidance Document on Dermal Absorption, European Commission, 2004 and Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health, may 2008

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.7 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):
50
Modified dose descriptor starting point:
NOAEC
Value:
34.8 mg/m³
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
NOAEL to NOAEC: 40 mg/kg bw / 1.15
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
0.2 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):
200
Modified dose descriptor starting point:
NOAEL
Value:
40 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
0.2 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):
200
Modified dose descriptor starting point:
NOAEL
Value:
40 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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

1. Identification of relevant dose descriptor

In a combined OECD 414/415 study the test item caused maternal toxicity and influenced fertility of the dams. The NOAEL for the parental generation is considered to be 40 mg/kg bw.

2. Mode of action

No non-threshold mode of action is associated with the test substance. In particular, the test substance has no genotoxic potential.

3. Application of assessment factors

Allometric scaling: rat to human = 4

Interspecies factor (remaining differences): 2.5

Intraspecies factor: worker = 5, general population = 10

Exposure duration subacute to chronic: 6

Quality of data base: 1

Dose response: 1

4. Daily exposure

Worker: exposed for 8h

General population: exposed for 24h

Calculation of DNEL bases upon Guidance Document on Dermal Absorption, European Commission, 2004 and Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health, may 2008