Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.6 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
Modified dose descriptor starting point:
NOAEC
Value:
141 mg/m³
Explanation for the modification of the dose descriptor starting point:
Available data do not suggest a pronounced difference between oral and inhalation route. Based on physicochemical properties absorption is considered equal for inhalation and oral exposure.
AF for dose response relationship:
1
Justification:
default
AF for differences in duration of exposure:
2
Justification:
default for sub-chronic > 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:
default for worker
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
0.8 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:
80 mg/kg bw/day
AF for dose response relationship:
1
Justification:
default
AF for differences in duration of exposure:
2
Justification:
default for sub-chronic > chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default for rat > human
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
default for worker
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Worker DNEL dermal

Starting point NOAEL 80 mg/kg bw/d (90d rat oral, OECD 408)

Dermal absorption is expected to be low because of the nature of the substance and its log Kow. The substance is dry and poorly soluble in water (0.5 mg/l). The experimental log Kow is 5.5; therefore, the rate of penetration may be limited by the rate of transfer between the stratum corneum and the epidermis, but uptake into the stratum corneum will be high. The molecular weight is 270.37 g/mol

The substance is not a skin irritant; therefore, no increase of skin absorption is expected due to damage to the skin surface.

In conclusion, oral absorption (100%) is supposed to be higher than dermal absorption, but it is not possible to derive a factor for this difference. Therefore, in line with the ECHA guidance R.7.c, a route specific adaptation of absorption is NOT applied.

Starting point: 80 mg/kg bw/d

Assessment factors (according to ECHA Guidance):

Interspecies: rat to human 10 (4 allometric scaling, 2.5 remaining differences)

Intraspecies: 5 worker

Time extrapolation from sub-chronic to chronic: 2

Correction for dose-response or quality of data-set: 1

Overall assessment factor: 100

80 mg/kg bw/100 = 0.8 mg/kg bw/d

 

Worker DNEL dermal, long-term, systemic: 0.8 mg/kg bw/d

 

Worker DNEL inhalative

starting point NOAEL 80 mg/kg bw/d (90d rat oral, OECD 408)

Corrected inhalatory NOAEC = oral NOAEL × 1/sRVrat x ABSoral-rat/ABSinh-human × sRVhuman/wRV

Correction for absorption ABSoral-rat/ABSinh-human: equal absorption based on physic-chemical properties = factor of 1

80 mg/kg/day × 1/0.38 m³/kg/day × 6.7 m³ (8h)/10 m³ (8h) = 141 mg/m³

Assessment factors (according to ECHA guidance):

Interspecies: rat to human 2.5 for remaining differences

Intraspecies: 5 worker

Time extrapolation from sub-chronic to chronic: 2

Correction for dose-response or quality of data-set: 1

Overall assessment factor: 25

141 mg/m³/25 = 5.6 mg/m³

Worker DNEL inhalative, long-term, systemic: 5.6 mg/m³

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.4 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
Modified dose descriptor starting point:
NOAEC
Value:
69.6 mg/m³
Explanation for the modification of the dose descriptor starting point:
Available data do not suggest a pronounced difference between oral and inhalation route. Based on physicochemical properties absorption is considered equal for inhalation and oral exposure.
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
0.4 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:
80 mg/kg bw/day
AF for dose response relationship:
1
Justification:
default
AF for differences in duration of exposure:
2
Justification:
default for sub-chronic > chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
default
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.4 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:
80 mg/kg bw/day
AF for dose response relationship:
1
Justification:
default
AF for differences in duration of exposure:
2
Justification:
default for sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default for rat to human
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
default
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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

General population DNEL dermal

Starting point: NOAEL 80 mg/kg bw/d (90-d rat oral)

Assessment factors (according to ECHA Guidance):

Interspecies: rat to human 10 (4 allometric scaling, 2.5 remaining differences)

Intraspecies: 10 general population

Time extrapolation from sub-chronic to chronic: 2

Correction for dose-response or quality of data set: 1

Overall assessment factor: 200

80 mg/kg bw/d/200 = 4 mg/kg bw/d

General population DNEL dermal long-term systemic: 0.4 mg/kg bw/d

General population DNEL inhalative

Starting point NOAEL 80 mg/kg bw/d (90-d rat oral)

Corrected inhalatory NOAEC = oral NOAEL × 1/sRVrat x ABSoral-rat/ABSinh-human

Correction for absorption ABSoral-rat/ABSinh-human: equal absorption based on physic-chemical properties = factor of 1

80 mg/kg/day × 1/1.15 m³/kg/day = 69.6 mg/m³

Assessment factors (according to ECHA Guidance):

Interspecies: 2.5 for remaining differences

Intraspecies: 10 general population

Time extrapolation from subacute to chronic: 6

Correction for dose-response or quality of data-set: 1

Overall assessment factor: 50

69.6 mg/m³/50 = 1.4 mg/m³

General population DNEL inhalative long-term systemic: 1.4 mg/m³

General population DNEL oral

Starting point NOAEL 80 mg/kg bw/d (90d rat oral)

No correction necessary

Using ECHA guidance factors:

Assessment factors

Interspecies: rat to human 10 (4 allometric scaling, 2.5 remaining differences)

Intraspecies: 10 general population

Time extrapolation from sub-chronic to chronic: 2

Correction for dose-response or quality of data-set: 1

Overall assessment factor: 200

General population DNEL oral long-term systemic: 0.4 mg/kg bw/d