Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
9.9 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor starting point:
NOAEL
Value:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
740 mg/m³
Explanation for the modification of the dose descriptor starting point:

Figure R.8-3 of ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health (Version 2.1; November 2012).

AF for dose response relationship:
1
Justification:
Default assessment factor applied because starting point for DNEL calculation is a NOAEL.
AF for differences in duration of exposure:
6
Justification:
Default conversion factor for sub-acute to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling not required because differences in breathing between rat and human already accounted for during modification of starting point.
AF for other interspecies differences:
2.5
Justification:
Default correction for other interspecies differences to allow for variation in toxicokinetics and toxicodynamics.
AF for intraspecies differences:
5
Justification:
Default assessment factor for workers.
AF for the quality of the whole database:
1
Justification:
The starting point NOAEL was obtained from a GLP guideline study.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is considered necessary.
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:
4 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEL
Value:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Modification based on 50% absorption through skin for high molecular weight substance

AF for dose response relationship:
1
Justification:
Default assessment factor applied because starting point for DNEL calculation is a NOAEL.
AF for differences in duration of exposure:
6
Justification:
Default conversion factor for sub-acute to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling to correct for differences in metabolic rate (rat to human).
AF for other interspecies differences:
2.5
Justification:
Default correction for other interspecies differences to allow for variation in toxicokinetics and toxicodynamics.
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
Justification:
The starting point NOAEL was obtained from a GLP guideline study.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is considered necessary.
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:
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:
0.46 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
NOAEL
Value:
160 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
68.8 mg/m³
Explanation for the modification of the dose descriptor starting point:

Figure R.8-3 of ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health (Version 2.1; November 2012).

AF for dose response relationship:
1
Justification:
Default assessment factor applied because starting point for DNEL calculation is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Default conversion factor for sub-acute to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling not required because differences in breathing between rat and human already accounted for during modification of starting point.
AF for other interspecies differences:
2.5
Justification:
Default correction for other interspecies differences to allow for variation in toxicokinetics and toxicodynamics
AF for intraspecies differences:
10
Justification:
Default assessment factor for general population.
AF for the quality of the whole database:
1
Justification:
The starting point NOAEL was obtained from a GLP guideline study
AF for remaining uncertainties:
1
Justification:
No other assessment factor is considered necessary
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:
0.13 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
160 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
80 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Example B.5 of ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health (Version 2.1; November 2012).

AF for dose response relationship:
1
Justification:
Default assessment factor applied because starting point for DNEL calculation is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Default conversion factor for sub-acute to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling to correct for differences in metabolic rate (rat to human).
AF for other interspecies differences:
2.5
Justification:
Default correction for other interspecies differences to allow for variation in toxicokinetics and toxicodynamics.
AF for intraspecies differences:
10
Justification:
Default assessment factor for general population.
AF for the quality of the whole database:
1
Justification:
The starting point NOAEL was obtained from a GLP guideline study.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is considered necessary.
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:
0.26 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
160 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
160 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation not required.

AF for dose response relationship:
1
Justification:
Default assessment factor applied because starting point for DNEL calculation is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Default conversion factor for sub-acute to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling to correct for differences in metabolic rate (rat to human).
AF for other interspecies differences:
2.5
Justification:
Default correction for other interspecies differences to allow for variation in toxicokinetics and toxicodynamics.
AF for intraspecies differences:
10
Justification:
Default assessment factor for general population.
AF for the quality of the whole database:
1
Justification:
The starting point NOAEL was obtained from a GLP guideline study.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is considered necessary.
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