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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.47 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
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
61.71 mg/m³
Explanation for the modification of the dose descriptor starting point:




























Bioavailability: animal experiment (oral)



50% (default)



Bioavailability human route



100% (default inhalation)



Exposure in animal study/exposure in humans



7/5 (default worker)



RVrat/RVhuman



0,38 (default)



Light activity in worker



6,7/10 (default)



Corrected human NOAEC



61.71 mg/m³ (50 x 1/0,38 x7/5 x50/100 x 6.7/10)



 


 

AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for differences in duration of exposure:
2
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
5
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
Guideline study
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
12.35 mg/m³
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
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:
0.7 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):
200
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
AF for differences in duration of exposure:
2
Justification:
ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
Guideline study
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.5 mg/kg bw/day
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
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

Systemic toxicity (long-term):


Starting point: NOAEL 50 mg/kg; OECD TG 408


Once daily (gavage) for 13 consecutive weeks.


ECHA REACH Guidance factors are used for derivation of the DNELs


 


Systemic toxicity (short-term):


Short-term toxicity is derived from long-term toxicity (factor 5).


 


Local toxicity (long- and short-term):


Classification: Skin Corr. 1B; H314 -> medium hazard band (ECHA REACH Guidance).


Classification: H314: Causes severe skin burns and eye damage -> medium hazard band (ECHA REACH Guidance).


 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.43 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):
50
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
21.74 mg/m³
Explanation for the modification of the dose descriptor starting point:
























Bioavailability: animal experiment (oral)



50% (default)



Bioavailability human route



100% (default inhalation)



Exposure in animal study/exposure in humans



7/7 (default general population)



RVrat/RVhuman



1,15 (default)



Corrected human NOAEC



21.74 mg/m³ (50 x 1/1,15 x 50/100)


AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for differences in duration of exposure:
2
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
Guideline study
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.15 mg/m³
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
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:
0.25 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):
200
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for differences in duration of exposure:
2
Justification:
ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
Guideline study
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.25 mg/kg bw/day
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
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:
0.25 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):
200
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for differences in duration of exposure:
2
Justification:
ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
Guideline study
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.25 mg/kg bw/day
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
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

Systemic toxicity (long-term):


Starting point: NOAEL 50 mg/kg; OECD TG 408


Once daily (gavage) for 13 consecutive weeks.


ECHA REACH Guidance factors are used for derivation of the DNELs


 


Systemic toxicity (short-term):


Short-term toxicity is derived from long-term toxicity (factor 5).


 


Local toxicity (long- and short-term):


Classification: Skin Corr. 1B; H314 -> medium hazard band (ECHA REACH Guidance).


Classification: H314: Causes severe skin burns and eye damage -> medium hazard band (ECHA REACH Guidance).