Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
133 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
333 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
169 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
other: See justification and comments below
Overall assessment factor (AF):
1.2
Modified dose descriptor starting point:
NOAEL
Value:
203 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Based on a NOAEL.
AF for differences in duration of exposure:
1
Justification:
No factor is used for study length as the data shows that the severity of key haemotoxic effect does not increase from 90 days to lifetime exposure (see information on repeat dose oral NTP studies in chapter 7.5.3 of IUCLID dossier)
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human extrapolation.
AF for other interspecies differences:
0.1
Justification:
An interspecies toxicodynamic factor is 0.1 is applied based on the much lower sensitivity of humans to haemotoxicity compared to rodents (see section 7.9.3 of IUCLID dossier).
AF for intraspecies differences:
3
Justification:
Proposed factor for workers. See detailed justification in document attached to this record.
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
default
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
120 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: See justification and comments below
Overall assessment factor (AF):
9
Modified dose descriptor starting point:
LOAEL
Value:
1 080 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Assuming 50% absorption the oral NOAEL translates to a dermal NOAEL of 1080mg/kg.
AF for dose response relationship:
3
Justification:
Extrapolation from a LOAEL to a NOAEL. Default factor
AF for interspecies differences (allometric scaling):
1
Justification:
Human data
AF for other interspecies differences:
1
Justification:
Human data
AF for intraspecies differences:
3
Justification:
Proposed factor for workers. See detailed justification in document attached to this record.
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
default

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Dose descriptor:
other: NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

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:
80 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
200 mg/m³
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
102 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
other: See justification and comments below
Overall assessment factor (AF):
2
Modified dose descriptor starting point:
NOAEL
Value:
203 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Based on a NOAEL.
AF for differences in duration of exposure:
1
Justification:
No factor is used for study length as the data shows that the severity of key haemotoxic effect does not increase from 90 days to lifetime exposure (see information on repeat dose oral NTP studies in chapter 7.5.3 of IUCLID dossier)
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human extrapolation.
AF for other interspecies differences:
0.1
Justification:
An interspecies toxicodynamic factor is 0.1 is applied based on the much lower sensitivity of humans to haemotoxicity compared to rodents (see section 7.9.3 of IUCLID dossier).
AF for intraspecies differences:
5
Justification:
Proposed factor for general population. See detailed justification in document attached to this record.
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
default
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
72 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: See justification and comments below.
Overall assessment factor (AF):
15
Modified dose descriptor starting point:
NOAEL
Value:
1 080 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Assuming 50% absorption the oral NOAEL translates to a dermal NOAEL of 1080mg/kg.
AF for dose response relationship:
3
Justification:
Extrapolation from a LOAEL to a NOAEL. Default factor
AF for interspecies differences (allometric scaling):
1
Justification:
Human data
AF for other interspecies differences:
1
Justification:
Human data
AF for intraspecies differences:
5
Justification:
Proposed factor for general population. See detailed justification in document attached to this record.
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
default

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.6 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: See justification and comments below
Overall assessment factor (AF):
1.5
Modified dose descriptor starting point:
LOAEL
Value:
12.9 mg/kg bw/day
AF for dose response relationship:
3
Justification:
LOAEL to NOAEL default factor
AF for differences in duration of exposure:
1
Justification:
No factor is used for study length as the data shows that the severity of key haemotoxic effect does not increase from 90 days to lifetime exposure (see information on repeat dose oral NTP studies in chapter 7.5.3 of IUCLID dossier)
AF for interspecies differences (allometric scaling):
1
Justification:
LOAEL is a factor derived for humans by PBPK modelling so no additional allometric factor required.
AF for other interspecies differences:
0.1
Justification:
An interspecies toxicodynamic factor is 0.1 is applied based on the much lower sensitivity of humans to haemotoxicity compared to rodents (see section 7.9.3 of IUCLID dossier).
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
default
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
36 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
other: See justification and comments below.
Overall assessment factor (AF):
15
Modified dose descriptor starting point:
NOAEL
Value:
540 mg/kg bw/day
AF for dose response relationship:
3
Justification:
LOAEL to NOAEL extrapolation
AF for interspecies differences (allometric scaling):
1
Justification:
Human data
AF for other interspecies differences:
1
Justification:
Human data
AF for intraspecies differences:
5
Justification:
Proposed factor for general population. See detailed justification in document attached to this record.
AF for the quality of the whole database:
1
Justification:
default
AF for remaining uncertainties:
1
Justification:
default

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population