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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
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):
25
Modified dose descriptor starting point:
NOAEC
Value:
176 mg/m³
Explanation for the modification of the dose descriptor starting point:
The oral NOAEL of 200 mg/kg bw/d is corrected for the extent of oral absorption (50%) and inhalation absorption (100%), for breathing rate (/0.38) and activity (*0.67). The corrected inhalation starting point is therefore 176 mg/m3.
AF for dose response relationship:
1
Justification:
Default value
AF for differences in duration of exposure:
2
Justification:
Extrapolation from subchronic to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling required where route to route extrapolation is used
AF for other interspecies differences:
2.5
Justification:
Default value for remaining interspecies difference
AF for intraspecies differences:
5
Justification:
Default value for intraspecies value (workers)
AF for the quality of the whole database:
1
Justification:
Default value for quality database
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14 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):
12.5
Modified dose descriptor starting point:
NOAEC
Value:
176 mg/m³
Explanation for the modification of the dose descriptor starting point:
The oral NOAEL of 200 mg/kg bw/d is corrected for the extent of oral absorption (50%) and inhalation absorption (100%), for breathing rate (/0.38) and activity (*0.67). The corrected inhalation starting point is therefore 176 mg/m3.
AF for dose response relationship:
1
Justification:
Default value
AF for interspecies differences (allometric scaling):
1
Justification:
Default value - no allometric scaling required where route to route extrapolation is used
AF for other interspecies differences:
2.5
Justification:
Default value for remaining interspecies difference
AF for intraspecies differences:
5
Justification:
Default value for intraspecies value (workers)
AF for the quality of the whole database:
1
Justification:
Default value for quality database
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties

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:
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
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
In the absence of data, dermal absorption is considered to be equivalent to oral absorption.
AF for dose response relationship:
1
Justification:
Default value
AF for differences in duration of exposure:
2
Justification:
Default value for extrapolation from subchronic to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for allometric scaling between rat and humans
AF for other interspecies differences:
2.5
Justification:
Default value for remaining interspecies difference
AF for intraspecies differences:
5
Justification:
Default value for intraspecies differences
AF for the quality of the whole database:
1
Justification:
Default value for quality database
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
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):
50
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
In the absence of data, dermal absorption is considered to be equivalent to oral absorption.
AF for dose response relationship:
1
Justification:
Default value
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for allometric scaling between rats and humans
AF for other interspecies differences:
2.5
Justification:
Default value for remaining interspecies difference
AF for intraspecies differences:
5
Justification:
Default value for intraspecies value
AF for the quality of the whole database:
1
Justification:
Default value for quality database
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties

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

The relevant endpoint for DNEL derivation is the NOAEL of 200 mg/kg bw/d from the 90 -day oral gavage study in the rat.

Inhalation DNEL values

Systemic inhalation DNEL values

The oral NOAEL of 200 mg/kg bw/d is corrected for the extent of oral absorption (50%) and inhalation absorption (100%), for breathing rate (/0.38) and activity (*0.67). The corrected inhalation starting point is therefore 176 mg/m3.

Long-term

Individual assessment factors of 1 (for dose-response relationship), 2 (for exposure duration), 1 (for allometric scaling), 2.5 (for interspecies differences), 5 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) give an overall assessment factor of 25. Application of this overall assessment factor to the corrected starting point gives a DNEL value of 7 mg/m3.

Short-term

Individual assessment factors of 1 (for dose-response relationship), 1 (for allometric scaling), 2.5 (for interspecies differences), 5 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) give an overall assessment factor of 12.5. Application of this overall assessment factor to the corrected starting point gives a DNEL value of 14 mg/m3.

Local inhalation DNEL values

The substance is not classified as a skin irritant, eye irritant or skin sensitiser; no local effects are predicted. The systemic inhalation DNELs are protective for local effects.

Dermal DNEL values

Systemic dermal DNEL values

In the absence of data, dermal absorption is considered to be equivalent to oral absorption.

Long-term

Individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 4 (for allometric scaling), 2.5 (for interspecies differences), 5 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) give an overall assessment factor of 100. Application of this overall assessment factor to the corrected starting point gives a DNEL value of 2 mg/kg bw/d.

Short-term

Individual assessment factors of 1 (for dose-response relationship), 4 (for allometric scaling), 2.5 (for interspecies differences), 5 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) give an overall assessment factor of 50. Application of this overall assessment factor to the corrected starting point gives a DNEL value of 4 mg/kg bw/d.

Local dermal DNEL values

The substance is not classified as a skin irritant, eye irritant or skin sensitiser; no local effects are predicted. The systemic inhalation DNELs are protective for local effects.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.7 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
Modified dose descriptor starting point:
NOAEC
Value:
87 mg/m³
Explanation for the modification of the dose descriptor starting point:
The oral NOAEL of 200 mg/kg bw/d is corrected for the extent of oral absorption (50%) and inhalation absorption (100%), for breathing rate (/1.15). The corrected inhalation starting point is therefore 87 mg/m3.
AF for dose response relationship:
1
Justification:
Default value
AF for differences in duration of exposure:
2
Justification:
Default value for extrapolation from subchronic to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling required where route to route extrapolation is used
AF for other interspecies differences:
2.5
Justification:
Default value for remaining interspecies difference
AF for intraspecies differences:
10
Justification:
Default value for intraspecies value (general population)
AF for the quality of the whole database:
1
Justification:
Default value for quality database without data gaps
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.5 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:
348 mg/m³
AF for dose response relationship:
1
Justification:
Default value
AF for interspecies differences (allometric scaling):
1
Justification:
Default value - no allometric scaling required where route to route extrapolation is used
AF for other interspecies differences:
2.5
Justification:
Default value for remaining interspecies difference
AF for intraspecies differences:
10
Justification:
Default value for intraspecies value (general population)
AF for the quality of the whole database:
1
Justification:
Default value for quality database without data gaps
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties

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:
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
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
In the absence of data, dermal absorption is considered to be equivalent to oral absorption.
AF for dose response relationship:
1
Justification:
Default value
AF for differences in duration of exposure:
2
Justification:
Default value for extrapolation from subchronic to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for allometric scaling between rat and human
AF for other interspecies differences:
2.5
Justification:
Default value for remaining interspecies difference
AF for intraspecies differences:
10
Justification:
Default value for intraspecies value (general population)
AF for the quality of the whole database:
1
Justification:
Default value for quality database without data gaps
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short 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
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
In the absence of data, dermal absorption is considered to be equivalent to oral absorption.
AF for dose response relationship:
1
Justification:
Default value
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for allometric scaling between rat and human
AF for other interspecies differences:
2.5
Justification:
Default value for remaining interspecies difference
AF for intraspecies differences:
10
Justification:
Default value for intraspecies value (general population)
AF for the quality of the whole database:
1
Justification:
Default value for quality database without data gaps
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties

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:
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
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not required
AF for dose response relationship:
1
Justification:
Default value
AF for differences in duration of exposure:
2
Justification:
Default value for extrapolation from subchronic to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for allometric scaling between rat and human
AF for other interspecies differences:
2.5
Justification:
Default value for remaining interspecies difference
AF for intraspecies differences:
10
Justification:
Default value for intraspecies value (general population)
AF for the quality of the whole database:
1
Justification:
Default value for quality database
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short 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
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not required
AF for dose response relationship:
1
Justification:
Default value
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for allometric scaling between rat and human
AF for other interspecies differences:
2.5
Justification:
Default value for remaining interspecies difference
AF for intraspecies differences:
10
Justification:
Default value for intraspecies value (general population)
AF for the quality of the whole database:
1
Justification:
Default value for quality database without data gaps
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

The relevant endpoint for DNEL derivation is the NOAEL of 200 mg/kg bw/d from the 90 -day oral gavage study in the rat.

Inhalation DNEL values

Systemic inhalation DNEL values

The oral NOAEL of 200 mg/kg bw/d is corrected for the extent of oral absorption (50%) and inhalation absorption (100%), for breathing rate (/1.15). The corrected inhalation starting point is therefore 87 mg/m3.

Long-term

Individual assessment factors of 1 (for dose-response relationship), 2 (for exposure duration), 1 (for allometric scaling), 2.5 (for interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) give an overall assessment factor of 50. Application of this overall assessment factor to the corrected starting point gives a DNEL value of 1.7 mg/m3.

Short-term

Individual assessment factors of 1 (for dose-response relationship), 1 (for allometric scaling), 2.5 (for interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) give an overall assessment factor of 12.5. Application of this overall assessment factor to the corrected starting point gives a DNEL value of 3.5 mg/m3.

Local inhalation DNEL values

The substance is not classified as a skin irritant, eye irritant or skin sensitiser; no local effects are predicted. The systemic inhalation DNELs are protective for local effects.

Dermal DNEL values

Systemic dermal DNEL values

In the absence of data, dermal absorption is considered to be equivalent to oral absorption.

Long-term

Individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 4 (for allometric scaling), 2.5 (for interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) give an overall assessment factor of 200. Application of this overall assessment factor to the corrected starting point gives a DNEL value of 1 mg/kg bw/d.

Short-term

Individual assessment factors of 1 (for dose-response relationship), 4 (for allometric scaling), 2.5 (for interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) give an overall assessment factor of 100. Application of this overall assessment factor to the corrected starting point gives a DNEL value of 2 mg/kg bw/d.

Local dermal DNEL values

The substance is not classified as a skin irritant, eye irritant or skin sensitiser; no local effects are predicted. The systemic inhalation DNELs are protective for local effects.

Oral DNEL values

The starting point does not need correction for the derivation of oral DNEL values.

Long-term

Individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 4 (for allometric scaling), 2.5 (for interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) give an overall assessment factor of 200. Application of this overall assessment factor to the corrected starting point gives a DNEL value of 1 mg/kg bw/d.

Short-term

Individual assessment factors of 1 (for dose-response relationship), 4 (for allometric scaling), 2.5 (for interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) give an overall assessment factor of 100. Application of this overall assessment factor to the corrected starting point gives a DNEL value of 2 mg/kg bw/d.