Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.82 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:
NOAEC
Value:
50 ng/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
70.5 mg/m³
Explanation for the modification of the dose descriptor starting point:
There is a key oral repeated dose toxicity study; no inhalation toxicity study present.
AF for dose response relationship:
1
Justification:
Start from NOAEC
AF for differences in duration of exposure:
3
Justification:
ECHA default factor for subchronic toxicity
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling already in route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
ECHA default factor for remaining differences
AF for intraspecies differences:
5
Justification:
ECHA default factor
AF for the quality of the whole database:
1
Justification:
High quality study
AF for remaining uncertainties:
1
Justification:
No other 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:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 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):
100
Dose descriptor starting point:
NOAEL
Value:
50 ng/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
There is a key oral repeated dose toxicity study; no repeated dermal toxicity study present.
AF for dose response relationship:
1
Justification:
Start from NOAEL
AF for differences in duration of exposure:
3
Justification:
ECHA default factor for subchrinic toxicity
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default factor for toxicokinetic differences
AF for other interspecies differences:
2.5
Justification:
ECHA default factor for remaining differences
AF for intraspecies differences:
5
Justification:
ECHA default factor
AF for the quality of the whole database:
1
Justification:
High quality study
AF for remaining uncertainties:
1
Justification:
No other uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

A key study repeated dose toxicity study (90 day oral gavage) in Wistar rats was performed by oral gavage at the doses of 50, 200 and 350 mg/kg b.w. marked changes to haematological parameters beyond historical control data in at 200 and 350 mg/kg body weight/day in terms of reduced blood cell mass, regenerative processes and other associated changes to red blood cell parameters were considered as test item related, adverse effects. Thus, the NOAEL of this study was considered to be 50 mg/kg body weight/day.

General Population - 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):
50
Dose descriptor starting point:
NOAEL
Value:
50 ng/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
34.8 mg/m³
Explanation for the modification of the dose descriptor starting point:
There is a key oral repeated dose toxicity study; no inhalation toxicity study present.
AF for dose response relationship:
1
Justification:
Start from NOAEC
AF for differences in duration of exposure:
3
Justification:
ECHA default factor for subchronic toxicity
AF for interspecies differences (allometric scaling):
2.5
Justification:
ECHA default factor for remaining differences
AF for other interspecies differences:
1
Justification:
Allometric scaling already in route-to-route extrapolation
AF for intraspecies differences:
10
Justification:
ECHA default factor
AF for the quality of the whole database:
1
Justification:
High quality study
AF for remaining uncertainties:
1
Justification:
No other 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:
hazard unknown (no further information necessary)
DNEL related information

General Population - 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):
200
Dose descriptor starting point:
NOAEL
Value:
50 ng/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
There is a key oral repeated dose toxicity study; no repeated dermal toxicity study present.
AF for dose response relationship:
1
Justification:
Start from NOAEL
AF for differences in duration of exposure:
3
Justification:
ECHA default factor for subchronic toxicity
AF for interspecies differences (allometric scaling):
2.5
Justification:
ECHA default factor for remaining differences
AF for other interspecies differences:
4
Justification:
ECHA default factor for toxicokinetic differences
AF for intraspecies differences:
10
Justification:
ECHA default factor
AF for the quality of the whole database:
1
Justification:
High quality study
AF for remaining uncertainties:
1
Justification:
No other uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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

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 ng/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Start from NOAEL
AF for differences in duration of exposure:
3
Justification:
ECHA default factor for subchronic toxicity
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default factor
AF for other interspecies differences:
2.5
Justification:
ECHA default factor
AF for intraspecies differences:
10
Justification:
ECHA default factor
AF for the quality of the whole database:
1
Justification:
High quality study
AF for remaining uncertainties:
1
Justification:
No other uncertainties
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

A key study repeated dose toxicity study (90 day oral gavage) in Wistar rats was performed by oral gavage at the doses of 50, 200 and 350 mg/kg b.w. Marked changes to haematological parameters beyond historical control data in at 200 and 350 mg/kg body weight/day in terms of reduced blood cell mass, regenerative processes and other associated changes to red blood cell parameters were considered as test item related, adverse effects. Thus, the NOAEL of this study was considered to be 50 mg/kg body weight/day.