Registration Dossier
Registration Dossier
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 701-281-9 | CAS number: -
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 3.7 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):
- 75
- Dose descriptor starting point:
- NOAEL
- Value:
- 316 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 278.6 mg/m³
- Explanation for the modification of the dose descriptor starting point:
The dose descriptor starting point for 8 hours of exposure was calculated according to Ref Figure R.8-3:
Corrected inhalatory NOEC =oral NOEL * (1 / sRV, rat) * (ABSoral, rat / ABSinh-human) * (sRVhuman / wRV)
Where
- sRV, rat = standard Respiratory Volume, rat =m3/kg for 8 hours
- ABS = absorption
- ABSoral, rat / ABSinh-human = 1 / 2 (default factor for extrapolation from oral to inhalation)
- sRVhuman = standard Respiratory Volume, human = 6.7 m3/person for 8 hours
- wRV = standard Respiratory Volume, worker = 10 m3/person for 8 hours
Therefore the dose descriptor starting point is:
316 mg/kg bw * (1 /m3/kg bw) * 1/2 * (6.7 m3 / 10 m3) = 278.6 mg/m3
- AF for dose response relationship:
- 1
- Justification:
- Assessment factor for dose response (starting point is a NOAEL)
- AF for differences in duration of exposure:
- 6
- Justification:
- Assessment factors for exposure duration (sub-acute to chronic study)
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human) since this is already accounted for when obtaining the corrected NOEC
- AF for other interspecies differences:
- 2.5
- Justification:
- Assessment factors for remaining non-metabolic differences
- AF for intraspecies differences:
- 5
- Justification:
- Assessment factors for workers
- AF for the quality of the whole database:
- 1
- Justification:
- Good quality study
- AF for remaining uncertainties:
- 1
- Justification:
- No additional factors are required
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 70.5 mg/m³
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 125
- Dose descriptor starting point:
- other: LD50
- Value:
- 5 000 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 8 816 mg/m³
- Explanation for the modification of the dose descriptor starting point:
No acute inhalation study is available. Therefore the data of the acute oral toxicity study are used: LD50 oral, rat >5000 mg/kg bw.
The dose descriptor starting point for 4 hours of exposure was calculated according to Ref Figure R.8-3:
Corrected inhalatory NOEC =
= oral NOEL * (1 / sRV, rat) * (ABSoral, rat / ABSinh-human) * (sRVhuman / wRV)
Where
- sRV, rat = standard Respiratory Volume, rat =m3/kg bw for 4 hours
- ABS = absorption
- ABSoral, rat / ABSinh-human = 1 / 2 (default factor for extrapolation from oral to inhalation)
- sRVhuman = standard Respiratory Volume, human =m3/person for 4 hours
- wRV = standard Respiratory Volume, worker = 5 m3/person for 4 hours
Therefore the dose descriptor starting point is:
5000 mg/kg bw * (1 / 0,19 m3/kg bw) * 1/2 * (3.35 m3 / 5 m3) = 8816 mg/m3
- AF for dose response relationship:
- 10
- Justification:
- As some transient signs of toxicity were noted at that dose, a factor of 10 is therefore applied to cover the ratio of LD50/NOAEC
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human) since this is already accounted for when obtaining the corrected NOEC
- AF for other interspecies differences:
- 2.5
- Justification:
- Assessment factors for remaining non-metabolic differences
- AF for intraspecies differences:
- 5
- Justification:
- Assessment factors for workers
- AF for the quality of the whole database:
- 1
- Justification:
- Good quality study
- AF for remaining uncertainties:
- 1
- Justification:
- No additional factors are required
Local effects
Long term exposure
- Hazard assessment conclusion:
- no-threshold effect and/or no dose-response information available
Acute/short term exposure
- Hazard assessment conclusion:
- no-threshold effect and/or no dose-response information available
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.1 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:
- 316 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 316 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The dermal absorption is considered to be generally lower than the oral absorption. As a worst case it is therefore assumed that the NOAELdermal = NOAELoral.
- AF for dose response relationship:
- 1
- Justification:
- Assessment factor for dose-response (starting point is a NOAEL)
- AF for differences in duration of exposure:
- 6
- Justification:
- Assessment factors for exposure duration (sub-acute to chronic study)
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human)
- AF for other interspecies differences:
- 2.5
- Justification:
- Assessment factors for remaining non-metabolic differences
- AF for intraspecies differences:
- 5
- Justification:
- Assessment factors for workers
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 1
- Justification:
- No additional factors are required
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 40 mg/kg bw/day
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- Dermal
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 50
- Dose descriptor starting point:
- NOAEL
- Value:
- 2 000 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 2 000 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Not required; as acute dermal study was available.
- AF for dose response relationship:
- 1
- Justification:
- As no toxic signs were noted at the LD50, dermal, the dermal LD50 is considered to be also the NOAEL, dermal. A factor of 1 is therefore applied to cover the ratio of LD50/NOAEL.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human)
- AF for other interspecies differences:
- 2.5
- Justification:
- Assessment factor for any remaining non-metabolic differences
- AF for intraspecies differences:
- 5
- Justification:
- Assessment factor for workers
- AF for the quality of the whole database:
- 1
- Justification:
- Good quality study
- AF for remaining uncertainties:
- 1
- Justification:
- No additional assessment factors are required
Local effects
Long term exposure
- Hazard assessment conclusion:
- no-threshold effect and/or no dose-response information available
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- no-threshold effect and/or no dose-response information available
- Most sensitive endpoint:
- skin irritation/corrosion
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.92 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:
- 316 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 137.4 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Dose descriptor starting point:
The dose descriptor starting point for 24 hours of exposure was calculated according to Ref Figure R.8-3:
Corrected inhalatory NOEC= oral NOEL * (1 / sRV, rat) * (ABSoral, rat / ABSinh-human)
Where
- sRV, rat = standard Respiratory Volume, rat =m3/kg for 24 hours)
- ABS = absorption
- ABSoral, rat / ABSinh-human = 1 / 2 (default factor for extrapolation from oral to inhalation)
Therefore the starting dose descriptor is:
316 mg/kg bw * (1 /m3/kg bw) * 1/2 = 137.4 mg/m3
- AF for dose response relationship:
- 1
- Justification:
- Assessment factor for dose response (starting point is a NOAEL)
- AF for differences in duration of exposure:
- 6
- Justification:
- Assessment factors for exposure duration (sub-acute to chronic study)
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human) since this is already accounted for when obtaining the corrected NOEC
- AF for other interspecies differences:
- 2.5
- Justification:
- Assessment factor for any remaining non-metabolic differences
- AF for intraspecies differences:
- 10
- Justification:
- Assessment factor for general population
- AF for the quality of the whole database:
- 1
- Justification:
- Good quality study
- AF for remaining uncertainties:
- 1
- Justification:
- No additional assessment factors are required
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 21.1 mg/m³
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 250
- Dose descriptor starting point:
- other: LD50
- Value:
- 5 000 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 5 263 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Dose descriptor starting point:
No acute inhalation study is available. Therefore the data of the acute oral toxicity study are used: LD50 oral, rat >5000 mg/kg bw.
The dose descriptor starting point for 4 hours of exposure was calculated according to Ref Figure R.8-3:
Corrected inhalatory NOEC= oral NOEL * (1 / sRV, rat) * (ABSoral, rat / ABSinh-human)
Where
- sRV, rat = standard Respiratory Volume, rat =m3/kg bw for 4 hours
- ABS = absorption
- ABSoral, rat / ABSinh-human = 1 / 2 (default factor for extrapolation from oral to inhalation)
Therefore the starting dose descriptor is:
5000 mg/kg bw * (1 /m3/kg bw) * 1/2 = 5263 mg/m3
- AF for dose response relationship:
- 10
- Justification:
- As some transient signs of toxicity were noted at that dose, a factor of 10 is therefore applied to cover the ratio of LD50/NOAEC
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human) since this is already accounted for when obtaining the corrected NOEC)
- AF for other interspecies differences:
- 2.5
- Justification:
- Assessment factors for remaining non-metabolic differences
- AF for intraspecies differences:
- 10
- Justification:
- Assessment factors for general population
- AF for the quality of the whole database:
- 1
- Justification:
- Good quality study
- AF for remaining uncertainties:
- 1
- Justification:
- No additional factors are required
Local effects
Long term exposure
- Hazard assessment conclusion:
- no-threshold effect and/or no dose-response information available
Acute/short term exposure
- Hazard assessment conclusion:
- no-threshold effect and/or no dose-response information available
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.5 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):
- 600
- Dose descriptor starting point:
- NOAEL
- Value:
- 316 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 316 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The dermal absorption is considered to be generally lower than the oral absorption. As a worst case it is therefore assumed that the NOAELdermal = NOAELoral.
- AF for dose response relationship:
- 1
- Justification:
- Assessment factor fior dose-response (starting point is a NOAEL)
- AF for differences in duration of exposure:
- 6
- Justification:
- Assessment factors for exposure duration (sub-acute to chronic study)
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human)
- AF for other interspecies differences:
- 2.5
- Justification:
- Assessment factors for remaining non-metabolic differences
- AF for intraspecies differences:
- 10
- Justification:
- Assessment factors for general population
- AF for the quality of the whole database:
- 1
- Justification:
- Good quality study
- AF for remaining uncertainties:
- 1
- Justification:
- No additional factors are required
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 20 mg/kg bw/day
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- Dermal
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 100
- Dose descriptor starting point:
- NOAEL
- Value:
- 2 000 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 2 000 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Not required; as an acute dermal study was available
- AF for dose response relationship:
- 1
- Justification:
- As no toxic signs were noted at the LD50, dermal, the dermal LD50 is considered to be also the NOAEL, dermal. A factor of 1 is therefore applied to cover the ratio of LD50/NOAEL.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human)
- AF for other interspecies differences:
- 2.5
- Justification:
- Assessment factor for any remaining non-metabolic differences
- AF for intraspecies differences:
- 10
- Justification:
- Assessment factor for general population
- AF for the quality of the whole database:
- 1
- Justification:
- Good quality study
- AF for remaining uncertainties:
- 1
- Justification:
- No additional assessment factors are required
Local effects
Long term exposure
- Hazard assessment conclusion:
- no-threshold effect and/or no dose-response information available
Acute/short term exposure
- Hazard assessment conclusion:
- no-threshold effect and/or no dose-response information available
- Most sensitive endpoint:
- acute toxicity
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.5 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):
- 600
- Dose descriptor starting point:
- NOAEL
- Value:
- 316 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 316 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Not required; as an repeated dose oral toxicity study was available
- AF for dose response relationship:
- 1
- Justification:
- Assessment factor for dose-response (starting point is a NOAEL)
- AF for differences in duration of exposure:
- 6
- Justification:
- Assessment factors for exposure duration (sub-acute to chronic study)
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human)
- AF for other interspecies differences:
- 2.5
- Justification:
- Assessment factor for any remaining non-metabolic differences
- AF for intraspecies differences:
- 10
- Justification:
- Assessment factor for general population
- AF for the quality of the whole database:
- 1
- Justification:
- Good quality study
- AF for remaining uncertainties:
- 1
- Justification:
- No additional assessment factors are required
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 5 mg/kg bw/day
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 1 000
- Dose descriptor starting point:
- other: LD50
- Value:
- 5 000 mg/kg bw/day
- Modified dose descriptor starting point:
- other: LD50
- Value:
- 5 000 mg/kg bw/day
- AF for dose response relationship:
- 10
- Justification:
- As some transient signs of toxicity were noted at that dose, a factor of 10 is therefore applied to cover the ratio of LD50/NOAEC
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human)
- AF for other interspecies differences:
- 2.5
- Justification:
- Assessment factor for any remaining non-metabolic differences
- AF for intraspecies differences:
- 10
- Justification:
- Assessment factor for general population
- AF for the quality of the whole database:
- 1
- Justification:
- Good quality study
- AF for remaining uncertainties:
- 1
- Justification:
- No additional assessment factors are required
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - General Population
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
