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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