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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
78 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
Value:
1 945 mg/m³
Explanation for the modification of the dose descriptor starting point:

The DNEL for repeated dose effects via the inhalation route is determined on the basis of the 90-day inhalation study. In this study a NOAEC of 3870 mg/m³ was derived based on adverse effects on the liver.  NOAEC: 3870 mg/m³ The following correction was made to the NOAEC: Correction for exposure duration: 6 h/8 h (default for workers). Correction for respiratory rate and volume (human worker): (6.7 m³/d/10 m³/d) (default) Therefore the corrected NOAEC for the inhalation route is: 3870*(6/8)*(6.7 m³/d /10 m³/d) = 1945 mg/m³.

AF for dose response relationship:
1
Justification:
A clear NOAEC was established
AF for differences in duration of exposure:
2
Justification:
Default (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (inhalation route)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Guideline, GLP study
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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:
1 103 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Value:
110 300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The DNEL for repeated dose effects via the dermal route is determined on the basis of route-to-route extrapolation from the 90-day inhalation study. In this study a NOAEC of 3870 mg/m³ was derived based on adverse effects on the liver. The following correction was made to the NOAEC(inhalation) to derive a NOAEL(dermal): Correction for exposure duration: 6h / 8h (default for workers) Correction for respiratory volume: 0.38 m³/kg (default, rat, 8 hour). Therefore, the corrected NOAEL for effects via the dermal route is: 3870*(6/8)*0.38 = 1103 mg/kg bw/day. In practice, the dermal absorption of this substance is very limited. A further correction for the known dermal absorption of 1% has been made, with the additional factor of 100: 1103 mg/kg bw/day x 100 = 110300 mg/kg bw/day

AF for dose response relationship:
1
Justification:
A clear NOAEC was established
AF for differences in duration of exposure:
2
Justification:
Default (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Guideline, GLP study
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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

Short-term high exposures are considered unlikely given the high levels of control in place at sites producing and using the substance. DNELs for long-term exposure are therefore adequate to protect against short-term exposures and no separate short-term DNELs are calculated.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
19 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEC
Value:
968 mg/m³
Explanation for the modification of the dose descriptor starting point:

The DNEL for repeated dose effects via the inhalation route is determined on the basis of the 90-day inhalation study. In this study a NOAEC of 3870 mg/m³ was derived based on adverse effects on the liver.  NOAEC: 3870 mg/m³ The following correction was made to the LOAEC: Correction for exposure duration: 6/24 (default for consumers) Therefore the corrected NOAEC for effects via the inhalation route is: 3870 mg/m³*(6/24) = 968 mg/m³.

AF for dose response relationship:
1
Justification:
A clear NOAEC was established
AF for differences in duration of exposure:
2
Justification:
Default (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (inhalation route)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Guideline, GLP study
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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:
556.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Value:
111 300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The DNEL for repeated dose effects via the dermal route is determined on the basis of route-to-route extrapolation from the 90-day inhalation study. In this study a NOAEC of 3870 mg/m3 was derived based on adverse effects on the liver. The following correction was made to the NOAEC(inhalation) to derive a NOAEL(dermal): Correction for exposure duration: 6h / 24h (default for consumers) Correction for respiratory volume: 1.15 m³/kg (default, rat). Therefore the corrected NOAEL for effects via the dermal route is: 3870*(6/24)*1.15 = 1113 mg/kg bw/day. In practice, the dermal absorption for this substance is very limited. A further correction for the known dermal absorption of 1% has been made, with the additional factor of 100: 1113 mg/kg bw/day x 100 = 111300 mg/kg bw/day 

AF for dose response relationship:
1
Justification:
A clear NOAEC was established
AF for differences in duration of exposure:
2
Justification:
Default (sub-chronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Guideline, GLP study
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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:
0.04 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
Modified dose descriptor starting point:
NOAEL
Value:
25 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The DNEL for the oral route is based on the 28-day oral study and no route to route extrapolation is required.

AF for dose response relationship:
1
Justification:
A clear NOAEL was established
AF for differences in duration of exposure:
6
Justification:
Default (sub-acute to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Guideline, GLP study
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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