Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

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