Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.933 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
LOAEC
DNEL value:
140 mg/m³
Modified dose descriptor starting point:
LOAEC
DNEL value:
140 mg/m³
Explanation for the modification of the dose descriptor starting point:

An inhalatory study is available; therefore DNEL is derived directly from inhalatory study route.

AF for dose response relationship:
3
Justification:
Starting point LOAEC
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Workers
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
2
Justification:
Read-across
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:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.132 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
LOAEC
DNEL value:
140 mg/m³
Modified dose descriptor starting point:
LOAEL
DNEL value:
79.403 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No available data on dermal study; therefore DNEL is derived from inhalation study route.

Dermal N(L)OAEC=inhalatory N(L)OAEL/(1/0.38 m3/kg/d)*0.67*(ABSdermal/ABSinh)

Absinhal/ABSdermal = 1

AF for dose response relationship:
3
Justification:
Starting point LOAEC
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
workers
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
2
Justification:
Read-across
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

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

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:
0.467 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
LOAEC
DNEL value:
140 mg/m³
Modified dose descriptor starting point:
LOAEC
DNEL value:
140 mg/m³
Explanation for the modification of the dose descriptor starting point:

An inhalatory study is available; therefore DNEL is derived from inhalation study route.

AF for dose response relationship:
3
Justification:
Starting point LOAEC
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
2
Justification:
Read-across
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:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.134 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1 200
Dose descriptor starting point:
LOAEC
DNEL value:
140 mg/m³
Modified dose descriptor starting point:
LOAEL
DNEL value:
161 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No available data on dermal study; therefore DNEL is derived from inhalation study route.

Dermal N(L)OAEL=Inhalatory N(L)OAEC/((1/1.15 m3/kg/d)*(ABSdermal/ABSinh))

Absinhal/ABSdermal = 1

AF for dose response relationship:
3
Justification:
Starting point LOAEC
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rat
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
2
Justification:
Read-across
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.134 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1 200
Dose descriptor starting point:
LOAEL
DNEL value:
0.152 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
DNEL value:
161 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No available data on oral study; therefore DNEL is derived from inhalation study route.

Oral N(L)OAEL=Inhalatory N(L)OAEC/((1/1.15 m3/kg/d)*(ABSoral/ABSinh))

Absinhal/ABSoral = 1

Dose descriptor starting point: 140 mg/m3 = 140/(13.2*70) = 0.1515151515 mg/kg/day

AF for dose response relationship:
3
Justification:
Starting point LOAEC
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rats
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
2
Justification:
Read-across
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population