Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
9.7 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
Dose descriptor starting point:
NOAEL
Value:
275 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
242 mg/m³
Explanation for the modification of the dose descriptor starting point:

The starting point is the oral NOAEL of 275 mg/kg bw/d from the 90 -day rat study. This is corrected for the duration of exposure, breathing rate and relative absorption (1/0.38*6.7/10*100/50) to give a corrected inhalation NOAEC of 242 mg/m3.

AF for dose response relationship:
1
Justification:
Default factor
AF for differences in duration of exposure:
2
Justification:
Default factor for extrapolating from a subchronic study to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Not required; already taken into account
AF for other interspecies differences:
2.5
Justification:
Default factor
AF for intraspecies differences:
5
Justification:
Default factor for workers
AF for the quality of the whole database:
1
Justification:
Default factor
AF for remaining uncertainties:
1
Justification:
Default factor; no significant remaining uncertainties
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:
2.8 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:
275 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
275 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

 The starting point is the oral NOAEL of 275 mg/kg bw/d from the 90 -day rat study. Based on the conservative (default) assumption that dermal absorption is equivalent to oral absorption, the corrected starting point is a dermal NOAEL of 275 mg/kg bw/d.

AF for dose response relationship:
1
Justification:
Default factor
AF for differences in duration of exposure:
2
Justification:
Default factor for extrapolating from subchronic study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor (rat study)
AF for other interspecies differences:
2.5
Justification:
Default factor
AF for intraspecies differences:
5
Justification:
Default factor for workers
AF for the quality of the whole database:
1
Justification:
Default factor
AF for remaining uncertainties:
1
Justification:
Default factor (no signficant remaining uncertainties)
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

Based on read-across data, the submission substance is considered to be of low acute toxicity and is not an irritant or sensitiser. The key study is an oral 90 -day study with the submission which reports a NOAEL of 275 mg/kg bw/d. This provides the starting point for systemic DNEL derivation.

Inhalation DNELs

Systemic

The starting point is the oral NOAEL of 275 mg/kg bw/d from the 90 -day rat study. This is corrected for the duration of exposure, breathing rate and relative absorption (1/0.38*6.7/10*100/50) to give a corrected inhalation NOAEC of 242 mg/m3. Individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 1 (for allometric scaling), 2.5 (for other interspecies differences), 5 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) result in an overall assessment factor of 25. Applying the overall assessment factor to the corrected starting point results in a long-term DNEL of 9.7 mg/m3. The substance is of low acute toxicity and is not classified for acute toxicity.  A short-term systemic DNEL is therefore not proposed.

Local

No hazard is identified. The substance is not a skin or eye irritant or skin sensitiser and is not classified for irritation or sensitisation. Local DNELs are therefore not proposed.

Dermal DNELs

Systemic

The starting point is the oral NOAEL of 275 mg/kg bw/d from the 90 -day rat study. Based on the conservative (default) assumption that dermal absorption is equivalent to oral absorption, the corrected starting point is a dermal NOAEL of 275 mg/kg bw/d. Individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 4 (for allometric scaling), 2.5 (for other interspecies differences), 5 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) result in an overall assessment factor of 100. Applying the overall assessment factor to the corrected starting point results in a long-term DNEL of 2.8 mg/kg bw/d. The substance is of low acute toxicity and is not classified for acute toxicity.  A short-term systemic DNEL is therefore not proposed.

Local

No hazard is identified. The substance is not a skin or eye irritant or skin sensitiser and is not classified for irritation or sensitisation. Local DNELs are therefore not proposed.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.4 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
Dose descriptor starting point:
NOAEL
Value:
275 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
120 mg/m³
Explanation for the modification of the dose descriptor starting point:

The starting point is the oral NOAEL of 275 mg/kg bw/d from the 90 -day rat study. This is corrected for breathing rate and relative absorption (1/1.15*100/50) to give a corrected inhalation NOAEC of 120 mg/m3.

AF for dose response relationship:
1
Justification:
Default factor
AF for differences in duration of exposure:
2
Justification:
Default factor for extrapolating from subchronic study to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Not required: already taken into account
AF for other interspecies differences:
2.5
Justification:
Default factor
AF for intraspecies differences:
10
Justification:
Default factor for general population
AF for the quality of the whole database:
1
Justification:
Default factor
AF for remaining uncertainties:
1
Justification:
Default factor (no significant remaining uncertainties)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Justification:
No hazard is identified. The substance is not a skin or eye irritant or skin sensitiser and is not classified for irritation or sensitisation. A local DNEL is therefore not proposed
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:
1.4 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:
275 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
275 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The starting point is the oral NOAEL of 275 mg/kg bw/d from the 90 -day rat study. Based on the conservative (default) assumption that dermal absorption is equivalent to oral absorption, the corrected starting point is a dermal NOAEL of 275 mg/kg bw/d.

AF for dose response relationship:
1
Justification:
Default factor
AF for differences in duration of exposure:
2
Justification:
Default factor for extrapolating from subchronic study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor (starting point is a rat study)
AF for other interspecies differences:
2.5
Justification:
Default factor
AF for intraspecies differences:
10
Justification:
Default factor for general population
AF for the quality of the whole database:
1
Justification:
Default factor
AF for remaining uncertainties:
1
Justification:
Default factor (no significant remaining uncertainties)
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:
1.4 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:
275 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
275 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Correction of the starting point is not required.

AF for dose response relationship:
1
Justification:
Default factor
AF for differences in duration of exposure:
2
Justification:
Default factor for extrapolating from subchronic study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor (starting point is a rat study)
AF for other interspecies differences:
2.5
Justification:
Default factor
AF for intraspecies differences:
10
Justification:
Default factor for general population
AF for the quality of the whole database:
1
Justification:
Default factor
AF for remaining uncertainties:
1
Justification:
Default factor (no significant remaining uncertainties)
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

Based on read-across data, the submission substance is considered to be of low acute toxicity and is not an irritant or sensitiser. The key study is an oral 90 -day study with the submission which reports a NOAEL of 275 mg/kg bw/d. This provides the starting point for systemic DNEL derivation.

Inhalation DNELs

Systemic

The starting point is the oral NOAEL of 275 mg/kg bw/d from the 90 -day rat study. This is corrected for breathing rate and relative absorption (1/1.15*50/100) to give a corrected inhalation NOAEC of 434.8 mg/m3. Individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 1 (for allometric scaling), 2.5 (for other interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) result in an overall assessment factor of 50. Applying the overall assessment factor to the corrected starting point results in a long-term inhalation DNEL of 2.9 mg/m3. The substance is of low acute toxicity and is not classified for acute toxicity.  A short-term systemic DNEL is therefore not proposed.

Local

No hazard is identified. The substance is not a skin or eye irritant or skin sensitiser and is not classified for irritation or sensitisation. Local DNELs are therefore not proposed.

Dermal DNELs

Systemic

The starting point is the oral NOAEL of 275 mg/kg bw/d from the 90 -day rat study. Based on the conservative (default) assumption that dermal absorption is equivalent to oral absorption, the corrected starting point is a dermal NOAEL of 275 mg/kg bw/d. Individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 4 (for allometric scaling), 2.5 (for other interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) result in an overall assessment factor of 200. Applying the overall assessment factor to the corrected starting point results in a long-term dermal DNEL of 1.4 mg/kg bw/d. The substance is of low acute toxicity and is not classified for acute toxicity.  A short-term systemic DNEL is therefore not proposed.

Local

No hazard is identified. The substance is not a skin or eye irritant or skin sensitiser and is not classified for irritation or sensitisation. Local DNELs are therefore not proposed.

Oral DNELs

The starting point is the oral NOAEL of 275 mg/kg bw/d from the 90 -day rat study; correction of the starting point is not required. Individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 4 (for allometric scaling), 2.5 (for other interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) result in an overall assessment factor of 200. Applying the overall assessment factor to the corrected starting point results in a long-term oral DNEL of 1.4 mg/kg bw/d. The substance is of low acute toxicity and is not classified for acute toxicity.  A short-term systemic DNEL is therefore not proposed.