Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11.2 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:
280 mg/m³
Explanation for the modification of the dose descriptor starting point:

DNEL for systemic effects via inhaled route determined from 90-day inhalation NOAEC = 557 mg/m3. Following corrections made: correction for exposure duration, 6 hour rat/8 hour worker; correction for respiratory  volume (worker) 6.7 m3/day/10m3/day; therefore corrected NOAEC = 557*(6/8)*(6.7/10) = 280 mg/m3

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default (subchronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (inhaled rat to inhaled human)
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:
Default (guideline study)
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11.2 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
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.6 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:
40 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

DNEL for systemic effects via dermal route determined from 90-day inhalation NOAEC = 557 mg/m3. Following corrections made: correction for exposure duration, 6 hour rat/8 hour worker; correction for respiratory  volume 0.38 m/kg (default, rat, 8 hour); Assessment Factor allometric scaling 4 (rat to human); therefore corrected NOAEL (dermal) = 557*(6/8)*0.38/4 = 40 mg/kg/day

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default (subchronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (inhaled rat to dermal human)
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:
Default (guideline study)
AF for remaining uncertainties:
1
Justification:
Default (no remaining uncertainties)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.6 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
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
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:
2 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:
99.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

DNEL for systemic effects via inhaled route determined from 90-day inhalation NOAEC = 557 mg/m3. Following corrections made: correction for expsoure duration, 6 hour to 24 hour; correction for number of exposures per week 5 days/7 days; therefore corrected NOAEC = 557*(6/24)*(5/7) =  99.5 mg/m3

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default (subchronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (inhaled rat to inhaled human)
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:
Default (guideline study)
AF for remaining uncertainties:
1
Justification:
Default (no remaining uncertainties)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 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
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.6 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:
28.6 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

DNEL for systemic effects via dermal route determined from 90-day inhalation NOAEC = 557 mg/m3. Following corrections made: correction for expsoure duration 6 hour to 24 hour; correction for number of exposures per week 5 days/7 days; correction for respiratory  volume 1.15 m/kg (default, rat, 24 hour); Assessment Factor allometric scaling 4 (rat to human); therefore corrected NOAEL (dermal) = 557*(6/8)*(5/7)*1.15/4 = 28.6 mg/kg/day

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
2
Justification:
Default (subchronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (inhaled rat to dermal human)
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:
Default (guideline study)
AF for remaining uncertainties:
1
Justification:
Default (no remaining uncertainties)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.6 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
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
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:
0.08 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:
12.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

DNEL for systemic effects via oral route determined from 28-day oral NOAEL = 50 mg/kg/day. Following corrections made: Assessment Factor allometric scaling 4 (rat to human); therefore corrected NOAEL (oral) = 50/4 = 12.5 mg/kg/day

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
6
Justification:
Default (subacute to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (oral rat to oral human)
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:
Default (guideline study)
AF for remaining uncertainties:
1
Justification:
Default (no remaining uncertainties)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.08 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
DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population