Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.7 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
Modified dose descriptor starting point:
other: NAEC human worker
Value:
52.5 mg/m³
Explanation for the modification of the dose descriptor starting point:
NAEC human worker=[(NOEL rep. oral tox / allometric scale) x standar human body weight ] / standard human worker brething volume (8h) = [(30 mg/kg bw day /4) x 70 kg]/10 m^3=52.5 mg/m^3
AF for dose response relationship:
1
Justification:
dose-response curve is consistent with toxicity behaviour
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
NAEC human worker
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
5
Justification:
NAEC human worker
AF for the quality of the whole database:
1
Justification:
GLP compliant with international guideline
AF for remaining uncertainties:
1
Justification:
assuming 100 % absorption
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
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:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Repeated oral study is the best way to assess the dermal route in absence of a repeated dermal study.

A correction of 10 for dermal adsorption from oral to dermal route is applied, due to the high molecular weight and the polarity of the substance.

AF for dose response relationship:
1
Justification:
dose-response curve is consistent with toxicity behaviour
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
5
Justification:
human worker
AF for the quality of the whole database:
1
Justification:
GLP compliant with international guideline
AF for remaining uncertainties:
1
Justification:
assuming 10 % dermal absorption
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.175 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
Modified dose descriptor starting point:
other: NAEC human g.p.
Value:
26.25 mg/m³
Explanation for the modification of the dose descriptor starting point:
NAEC human general population=[(NOEL rep. oral tox / allometric scale) x standar human body weight ] / standard human general population brething volume (24h) = [(30 mg/kg bw day /4)70 kg]/20 m^3=26.25 mg/m^3
AF for dose response relationship:
1
Justification:
dose-response curve is consistent with toxicity behaviour
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
NAEC general population
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
10
Justification:
NAEC general population
AF for the quality of the whole database:
1
Justification:
GLP compliant with international guideline
AF for remaining uncertainties:
1
Justification:
assuming 100 % absorption
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Repeated oral study is the best way to assess the dermal route in absence of a repeated dermal study.

A correction of 10 for dermal adsorption from oral to dermal route is applied, due to the high molecular weight and the polarity of the substance.

AF for dose response relationship:
1
Justification:
dose-response curve is consistent with toxicity behaviour
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
10
Justification:
human standard to human general population
AF for the quality of the whole database:
1
Justification:
GLP compliant with international guideline
AF for remaining uncertainties:
1
Justification:
assuming 10 % absorption
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.05 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
Modified dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
AF for dose response relationship:
1
Justification:
dose-response curve is consistent with toxicity behaviour
AF for differences in duration of exposure:
6
Justification:
sub acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
10
Justification:
human standard to human general population
AF for the quality of the whole database:
1
Justification:
GLP compliant with international guideline
AF for remaining uncertainties:
1
Justification:
assuming 100 % absorption
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population