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: 601-141-6 | CAS number: 111937-03-2
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 51.5 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: following ECHA guidance and Literature
- Overall assessment factor (AF):
- 3.4
- Dose descriptor starting point:
- NOAEL
- Value:
- 100 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 175 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Starting point correction NOAEL oral -> NOAEC human (8h worker): NOAEC human (8h worker) = oral NOAEL rat 100 / sRVrat (AS) 4 x bw human 70 / 8h Volume 10 = 175,0 mg / m3 / 24h
- AF for dose response relationship:
- 1
- Justification:
- according to ECHA guideance
- AF for differences in duration of exposure:
- 1.4
- Justification:
- subchronic -> chronic, Batke et al. Toxicology Letters 205 (2011) 122– 129
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- allready considered in starting point correction
- AF for other interspecies differences:
- 1
- Justification:
- Escher et al. Toxicology Letters 218 (2013) 159– 165
- AF for intraspecies differences:
- 2.4
- Justification:
- Schneider et al. Regul Toxicol Pharmacol 44, (2006) 172-181
- AF for the quality of the whole database:
- 1
- Justification:
- key study with KL 1
- AF for remaining uncertainties:
- 1
- Justification:
- no remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- By inhalation
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 74.6 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA guidance and Literature
- Overall assessment factor (AF):
- 13.4
- Dose descriptor starting point:
- NOAEL
- Value:
- 100 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 000 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Based on Kreos et al. 2007 (Food Chem Toxicol.2007 Dec;45(12):2533-62) taking molecular weight of 382.66-410.72 g/mol and log Pow > 6 a flux jmax<0.1 can be anticipiated.
Hence low dermal absorption is anticipated which can be adressed by 10% dermal absorption.
Therefore factor 10 modification for dermal dose descriptor is necessary (assumed that worst case 10% is absorbed). Hence the NOAEL systemic dermal is assumed to be 10 times NOAEL systemic oral. NOAEL (dermal, rat) = 10 * NOAEL (oral, rat)
- AF for dose response relationship:
- 1
- Justification:
- according to ECHA guideance
- AF for differences in duration of exposure:
- 1.4
- Justification:
- subchronic -> chronic, Batke et al. Toxicology Letters 205 (2011) 122– 129
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- rat, according to ECHA guideance
- AF for other interspecies differences:
- 1
- Justification:
- Escher et al. Toxicology Letters 218 (2013) 159– 165
- AF for intraspecies differences:
- 2.4
- Justification:
- Schneider et al. Regul Toxicol Pharmacol 44, . (2006) 172-181
- AF for the quality of the whole database:
- 1
- Justification:
- key study with KL 1
- AF for remaining uncertainties:
- 1
- Justification:
- no remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- 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:
- 15.6 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: following ECHA guidance and Literature
- Overall assessment factor (AF):
- 5.6
- Dose descriptor starting point:
- NOAEL
- Value:
- 100 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 87.5 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Starting point correction NOAEL oral -> NOAEC human (24h): NOAEC human (24h) = oral NOAEL rat 100 / sRVrat (AS) 4 x bw human 70 / 24h Volume 20 = 87,5 mg / m3 / 24h
- AF for dose response relationship:
- 1
- Justification:
- according to ECHA guideance
- AF for differences in duration of exposure:
- 1.4
- Justification:
- subchronic -> chronic, Batke et al. Toxicology Letters 205 (2011) 122– 129
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- already considered in starting point correction
- AF for other interspecies differences:
- 1
- Justification:
- Escher et al. Toxicology Letters 218 (2013) 159– 165
- AF for intraspecies differences:
- 4
- Justification:
- general pop., Batke et al. Toxicology Letters 205 (2011) 122– 129
- AF for the quality of the whole database:
- 1
- Justification:
- key study with KL 1
- AF for remaining uncertainties:
- 1
- Justification:
- no remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- By inhalation
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 44.6 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: following ECHA guidance and Literature
- Overall assessment factor (AF):
- 22.4
- Dose descriptor starting point:
- NOAEL
- Value:
- 100 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 000 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Based on Kreos et al. 2007 (Food Chem Toxicol.2007 Dec;45(12):2533-62) taking molecular weight of 382.66-410.72 g/mol and log Pow > 6 a flux jmax<0.1 can be anticipiated.
Hence low dermal absorption is anticipated which can be adressed by 10% dermal absorption.
Therefore factor 10 modification for dermal dose descriptor is necessary (assumed that worst case 10% is absorbed). Hence the NOAEL systemic dermal is assumed to be 10 times NOAEL systemic oral. NOAEL (dermal, rat) = 10 * NOAEL (oral, rat)
- AF for dose response relationship:
- 1
- Justification:
- according to ECHA guideline
- AF for differences in duration of exposure:
- 1.4
- Justification:
- subchronic -> chronic, Batke et al. Toxicology Letters 205 (2011) 122– 129
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- rat, according to ECHA guideline
- AF for other interspecies differences:
- 1
- Justification:
- Escher et al. Toxicology Letters 218 (2013) 159– 165
- AF for intraspecies differences:
- 4
- Justification:
- general pop., Batke et al. Toxicology Letters 205 (2011) 122– 129
- AF for the quality of the whole database:
- 1
- Justification:
- key study with KL 1
- AF for remaining uncertainties:
- 1
- Justification:
- no remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- 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:
- 4.5 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: following ECHA guidance and Literature
- Overall assessment factor (AF):
- 22.4
- Dose descriptor starting point:
- NOAEL
- Value:
- 100 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 100 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Oral NOAEL value can be directly derived from a 90d rodent study. As no differences in absorption to human are know, no starting point correction is done.
- AF for dose response relationship:
- 1
- Justification:
- according to ECHA guideline
- AF for differences in duration of exposure:
- 1.4
- Justification:
- subchronic -> chronic, Batke et al. Toxicology Letters 205 (2011) 122– 129)
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- rat, according to ECHA guideline
- AF for other interspecies differences:
- 1
- Justification:
- Escher et al. Toxicology Letters 218 (2013) 159– 165
- AF for intraspecies differences:
- 4
- Justification:
- general pop., Batke et al. Toxicology Letters 205 (2011) 122– 129
- AF for the quality of the whole database:
- 1
- Justification:
- key study with KL 1
- AF for remaining uncertainties:
- 1
- Justification:
- no remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- Oral
DNEL related information
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.
