Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.8 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.8 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC

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:
1.2 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.2 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL

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)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

1. Identification of relevant dose descriptor

The 90-day oral toxicity study in rats with the test substance was the most representative repeat-dose study performed and is considered as appropriate for DNEL derivation.

2. Mode of action

No non-threshold mode of action is associated with the test substance. In particular, the test substance has no genotoxic potential.

3. Correction of dose descriptor

NOAEL (oral) is converted into a NOAEL(corrected)in accordance toGuidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose[concentration]-response for human health, ECHA, May 2008.

Workers: NOAEL (oral) = 50 mg/kg bw =>NOAEL(corrected)=88 mg/m3

4. Application of assessment factors

The following assessment factors were choosen: A correction for differences in metabolic rate per body weight was made by an allometric scaling factor of 4 (except for inhalation). Intraspecies differences account for a factor of 5. For exposure duration a factor of 2 is employed. Overall, an assessment factor of 40 was employed.

5.Selection of the critical DNEL(s)/DMELs and/or qualitative/semi-quantitative descriptor for critical health effects

 

DNEL- acute, inhalation, systemic:The acute DNELs could not be calculated directly but the long-term DNELs are sufficient to ensure that acute effects do not occur, provided high-peak acute exposure (especially for inhalation) can be avoided.

DNEL- acute, inhalation, local:

Not quantifiable. The long-term DNEL was considered appropriate to apply.

DNEL- acute, dermal, systemic: Not quantifiable; The acute DNELs could not be calculated directly but the long-term DNELs are sufficient to ensure that acute effects do not occur, provided high-peak acute exposure can be avoided. The skin irritation and sensitization potential supposed to be covered by the oral DNEL derived, in addition to the appropriate risk management measures to minimize skin contact.

DNEL- acute, dermal, local:

Not quantifiable

The long-term DNEL was considered appropriate to apply.

DNEL- long-term, inhalation, local:

Not quantifiable and not considered applicable.

 DNEL- long-term, inhalation, systemic:

NOAEL (corrected) / Sum of assessment factors applicable

88 mg/kg bw / 10 = 8.8 mg/m3

DNEL- long-term, dermal, systemic:

NOAEL (oral) / Sum of assessment factors applicable

50 mg/kg bw / 40 = 1.25 mg/kg bw

The dermal route is typically covered by oral route information in the absence of data for this administration route.

DNEL- long-term, dermal, local:

Not quantifiable and not considered applicable.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.2 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.2 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEC

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:
0.6 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
80
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.6 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
80
Modified dose descriptor starting point:
NOAEL

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)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.6 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
80
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.6 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
80
Modified dose descriptor starting point:
NOAEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

1. Identification of relevant dose descriptor

The 90-day oral toxicity study in rats with the test substance was the most representative repeat-dose study performed and is considered as appropriate for DNEL derivation.

2. Mode of action

No non-threshold mode of action is associated with the test substance. In particular, the test substance has no genotoxic potential.

3. Correction of dose descriptor

NOAEL (oral) is converted into a NOAEL(corrected)in accordance to Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose[concentration]-response for human health, ECHA, May 2008.

General population: NOAEL (oral) = 50 mg/kg bw =>NOAEL(corrected)= 43.5 mg/m3

4. Application of assessment factors

The following assessment factors were choosen: A correction for differences in metabolic rate per body weight was made by an allometric scaling factor of 4 (except for inhalation). Intraspecies differences account for a factor of 10. For exposure duration a factor of 2 is employed. . Overall, an assessment factor of 80 was employed.

5.Selection of the critical DNEL(s)/DMELs and/or qualitative/semi-quantitative descriptor for critical health effects

 

DNEL- acute, inhalation, systemic:The acute DNELs could not be calculated directly but the long-term DNELs are sufficient to ensure that acute effects do not occur, provided high-peak acute exposure (especially for inhalation) can be avoided.

DNEL- acute, inhalation, local:

Not quantifiable. The long-term DNEL was considered appropriate to apply.

DNEL- acute, dermal, systemic: Not quantifiable; The acute DNELs could not be calculated directly but the long-term DNELs are sufficient to ensure that acute effects do not occur, provided high-peak acute exposure can be avoided.

DNEL- acute, dermal, local:

Not quantifiable.

The long-term DNEL was considered appropriate to apply.

DNEL- long-term, inhalation, local:

Not quantifiable and not considered applicable.

 DNEL- long-term, inhalation, systemic:

NOAEL (corrected) / Sum of assessment factors applicable

43 mg/kg bw / 20 = 2.2 mg/m3

DNEL- long-term, dermal, systemic:

NOAEL (oral) / Sum of assessment factors applicable

50 mg/kg bw / 80 = 0.6 mg/kg bw

The dermal route is typically covered by oral route information in the absence of data for this administration route.

DNEL- long-term, dermal, local:

Not quantifiable and not considered applicable.