Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.56 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
30
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:
12.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
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

1. Relevant Toxicology Data, exposure pattern and route

The calculation of the DNEL is based on the results of a 28 day repeated dose toxicity study in rats (OECD 407).

The oral administration of the test material resulted in microscopic changes in the mid- and high-dose groups in the adrenals, kidneys, and stomach/forestomach. The effects on the adrenals were accompanied by an increased organ weight. The FOB (functional observational battery) identified decreased landing foot splay in the mid- and high-dose females, and also decreased rectal temperature in the high-dose females. A NOAEL for systemic toxicity was established at 150 mg/kg bw.

2. Mode of action

No non-threshold mode of action is associated with this 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.

NOAEL (oral) = 150 mg/kg/d

NOAEL(corrected)= 1500 mg/kg/d for dermal exposure, dermal absorption less than 10% was justified.

NOAEL(corrected)=NOAELrat-oral÷0.38 m3/kg*(ABSrat-oral÷ ABShuman-inhalation)*6.7÷10.3 (sRV human 8h/wRV 8h)= 256.8 mg/m3for inhalation exposure

 

4. Application of assessment factors

Dermal route: The following assessment factors were chosen: interspecies difference (4 for allometric scale, 1 for remaining difference), intraspecies difference (5 for workers), duration extrapolation (6 for subacute to chronic exposure duration), and quality of the data (1 for a reliable study).

Inhalation route: The following assessment factors were chosen: interspecies difference (1), intraspecies difference (5 for workers), duration extrapolation (6 for subacute to chronic exposure duration), and quality of the data (1 for a reliable study).

 

 

 

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):
60
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:
6.25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
240
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:
0.024 mg/cm²
Most sensitive endpoint:
sensitisation (skin)

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
DNEL related information
Overall assessment factor (AF):
600
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

1. Relevant Toxicology Data, exposure pattern and route

The calculation of the DNEL is based on the results of a 28 day repeated dose toxicity study in rats (OECD 407).

The oral administration of the test material resulted in microscopic changes in the mid- and high-dose groups in the adrenals, kidneys, and stomach/forestomach. The effects on the adrenals were accompanied by an increased organ weight. The FOB (functional observational battery) identified decreased landing foot splay in the mid- and high-dose females, and also decreased rectal temperature in the high-dose females. A NOAEL for systemic toxicity was established at 150 mg/kg bw.

2. Mode of action

No non-threshold mode of action is associated with this 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.

NOAEL (oral) = 150 mg/kg/d

NOAEL(corrected)= 1500 mg/kg/d for dermal exposure, dermal absorption less than 10% was justified.

NOAEL(corrected)== NOAELrat-oral÷1.15 m3/kg*(ABSrat-oral÷ ABShuman-inhalation) = 130.4 mg/ m3for inhalation exposure

4. Application of assessment factors

The following assessment factors were chosen:

Dermal route: interspecies difference (4 for allometric scale; for remaining difference 1 was used), intraspecies difference (10 for general population), duration extrapolation (6 for subacute to chronic exposure duration), and quality of the data (1 for a reliable study).

Inhalation route: interspecies difference (1), intraspecies difference (10 for general population), duration extrapolation (6 for subacute to chronic exposure duration), and quality of the data (1 for a reliable study).

Oral route: interspecies difference (4 for allometric scale; for remaining difference 2.5 was used), intraspecies difference (10 for general population), duration extrapolation (6 for subacute to chronic exposure duration), and quality of the data (1 for a reliable study).