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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
24.7 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):
25
Dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
616.7 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:
2
Justification:
DNEL is based on administration of test material to the rat for 90 days (sub-chronic 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:
350 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):
100
Dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
35 000 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:
2
Justification:
DNEL is based on administration of test material to the rat for 90 days (sub-chronic 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
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The substance is not acutely toxic via the oral or dermal routes (LD50 > 2000 mg/kg), has a low vapour pressure at ambient temperature and no evidence of skin irritation, eye irritation or skin sensitisation have been reported. Furthermore, no adverse effects leading to classification were reported in a sub-chronic (90-day) repeat dose oral study via the oral route. Nevertheless, long-term systemic DNELs have been derived for the inhalation and dermal routes as a precaution.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.35 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):
50
Dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
217.5 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:
2
Justification:
DNEL is based on administration of test material to the rat for 90 days (sub-chronic 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:
125 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):
200
Dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
25 000 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:
2
Justification:
DNEL is based on administration of test material to the rat for 90 days (sub-chronic 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:
2.5 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):
200
Dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
500 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:
2
Justification:
DNEL is based on administration of test material to the rat for 90 days (sub-chronic 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:
no hazard identified

Additional information - General Population

The substance is not acutely toxic via the oral or dermal routes (LD50 > 2000 mg/kg), has a low vapour pressure at ambient temperature and no evidence of skin irritation, eye irritation or skin sensitisation have been reported. Furthermore, no adverse effects leading to classification were reported in a sub-chronic (90-day) repeat dose oral study via the oral route. Nevertheless, long-term systemic DNELs have been derived for the inhalation, dermal and oral routes as a precaution.