Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.2 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):
75
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
88 mg/m³
Explanation for the modification of the dose descriptor starting point:

The oral NOAEL of 100 mg/kg bw/d from the OECD 422 screening study is corrected for respiratory volume (*1/0.38), working rate (*6.7/10) and relative oral and inhalation absorption (*50/100), resulting in a corrected inhalation NOAEC of 88 mg/m3.

AF for dose response relationship:
1
Justification:
The starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
The starting point is a NOAEL from a sub-acute toxicity study.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric factors are already accounted for in derivation of the corrected starting point.
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
5
Justification:
Default value for workers
AF for the quality of the whole database:
1
Justification:
Default value: good quality database
AF for remaining uncertainties:
1
Justification:
Default value: 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:
1.7 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):
300
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Based on its physicochemical properties, dermal absorption of the substance is assumed to be 10%; oral absorption is assumed to be 50%. The corrected dermal NOAEL is therefore 500 mg/kg bw/d.

AF for dose response relationship:
1
Justification:
The starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
The starting point is a NOAEL from a sub-acute toxicity study.
AF for interspecies differences (allometric scaling):
4
Justification:
The starting point is derived from a study in the rat
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
5
Justification:
Default value for workers
AF for the quality of the whole database:
1
Justification:
Default value: good quality database
AF for remaining uncertainties:
1
Justification:
Default value: 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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

The substance is of low acute oral toxicity, is not classified as a skin irritant or sensitiser but is classified for eye irritation in CLP Category 1. The critical starting point for DNEL derivation is the NOAEL of 100 mg/kg bw/d derived from an oral OECD 422 screening study (considered to be of subacute derivation).

DNEL derivation

Inhalation DNELS

Long-term systemic DNEL

The oral NOAEL of 100 mg/kg bw/d from the OECD 422 screening study is corrected for respiratory volume (*1/0.38), working rate (*6.7/10) and relative oral and inhalation absorption (*50/100), resulting in a corrected inhalation NOAEC of 88 mg/m3.

Individual assessment factors of 1 (for dose-response relationship), 6 (for duration of exposure), 1 (for allometric scaling), 2.5 (for remaining interspecies differences), 5 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) are combined to give an overall assessment factor of 75. Applying the assessment factor of 75 to the corrected starting point of 88 mg/m3 results in a DNEL of 1.2 mg/m3.

Short-term systemic DNEL

The substance is of low acute toxicity and is not classified for acute toxicity. In the absence of any identified hazard, an acute/short-term DNEL is not required.

Local DNELs

There are no data on local effects following inhalation. In the absence of any identified hazard, local inhalation DNELs are not derived.

Dermal DNELs

Long-term systemic DNEL

Dermal absorption is considered to be 10% based on the physicochemical properties of the substance; oral absorption is assumed to be 50%. The corrected dermal NOAEL is therefore 500 mg/kg bw/d. Individual assessment factors of 1 (for dose-response relationship), 6 (for duration of exposure), 4 (for allometric scaling), 2.5 (for remaining interspecies differences), 5 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) are combined to give an overall assessment factor of 300. Applying the assessment factor of 300 to the corrected starting point of 500 mg/kg bw/d results in a DNEL of 1.7 mg/kg bw/d.

Short-term systemic DNEL

The substance is of low acute toxicity and is not classified for acute toxicity. In the absence of any identified hazard, an acute/short-term DNEL is not required

Local DNELs

The substance is not classified for skin irritation or skin sensitisation. In the absence of any identified hazard, a local dermal DNEL is not required.

Hazard for the eyes

Hazard for the eyes

The substance is classified for eye damage (Cat 1) and is therefore considered to represent a moderate hazard according to the ECHA Guidance on Information Requirements and Chemical Safety Assessment Part E: Risk Characterisation (version 3.0, May 2016).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.3 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):
150
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
43 mg/m³
Explanation for the modification of the dose descriptor starting point:

The oral NOAEL of 100 mg/kg bw/d from the OECD 422 screening study is corrected for respiratory volume (*1/1.15) and relative oral and inhalation absorption (*50/100), resulting in a corrected inhalation NOAEC of 43 mg/m3.

AF for dose response relationship:
1
Justification:
The starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
The starting point is a NOAEL from a sub-acute toxicity study.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric factors are already accounted for in derivation of the corrected starting point.
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
10
Justification:
Default value for the general population
AF for the quality of the whole database:
1
Justification:
Default value: good quality database
AF for remaining uncertainties:
1
Justification:
Default value: 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

General Population - 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):
600
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dermal absorption is considered to be 10% based on the physicochemical properties of the substance. Oral absorption is assumed to be 50%. The corrected dermal NOAEL is therefore 500 mg/kg bw/d.

AF for dose response relationship:
1
Justification:
The starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
The starting point is a NOAEL derived from a sub-acute toxicity study
AF for interspecies differences (allometric scaling):
4
Justification:
The starting point is derived from a study in the rat
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
10
Justification:
Default value for the general population
AF for the quality of the whole database:
1
Justification:
Default value: good quality database
AF for remaining uncertainties:
1
Justification:
Default value: 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:
0.2 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):
600
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The starting point is derived from an oral study and does not therefore need correction.

AF for dose response relationship:
1
Justification:
The starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
The starting point is a NOAEL from a sub-acute toxicity study.
AF for interspecies differences (allometric scaling):
4
Justification:
The starting point is derived from a rat study
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
10
Justification:
Default value for the general population
AF for the quality of the whole database:
1
Justification:
Default value: good quality database
AF for remaining uncertainties:
1
Justification:
Default value: 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:
medium hazard (no threshold derived)

Additional information - General Population

The substance is of low acute oral toxicity, is not classified as a skin irritant or sensitiser but is classified for eye irritation in CLP Category 1. The critical starting point for DNEL derivation is the NOAEL of 100 mg/kg bw/d derived from an oral OECD 422 screening study (considered to be of subacute derivation).

DNEL derivation

Inhalation DNELS

Long-term systemic DNEL

The oral NOAEL of 100 mg/kg bw/d from the OECD 422 screening study is corrected for respiratory volume (*1/1.15), relative oral and inhalation absorption (*50/100), resulting in a corrected inhalation NOAEC of 43 mg/m3.

Individual assessment factors of 1 (for dose-response relationship), 6 (for duration of exposure), 1 (for allometric scaling), 2.5 (for remaining interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) are combined to give an overall assessment factor of 150. Applying the assessment factor of 150 to the corrected starting point of 88 mg/m3 results in a DNEL of 0.3 mg/m3.

Short-term systemic DNEL

The substance is of low acute toxicity and is not classified for acute toxicity. In the absence of any identified hazard, an acute/short-term DNEL is not required.

Local DNELs

There are no data on local effects following inhalation. In the absence of any identified hazard, local inhalation DNELs are not derived.

Dermal DNELs

Long-term systemic DNEL

Dermal absorption of 10% is assumed based on the physicochemical properties of the substance; oral absorption is assuemd be 50%. The corrected dermal NOAEL is therefore 500 mg/kg bw/d. Individual assessment factors of 1 (for dose-response relationship), 6 (for duration of exposure), 4 (for allometric scaling), 2.5 (for remaining interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) are combined to give an overall assessment factor of 600. Applying the assessment factor of 600 to the corrected starting point of 500 mg/kg bw/d results in a DNEL of 0.8 mg/kg bw/d.

Short-term systemic DNEL

The substance is of low acute toxicity and is not classified for acute toxicity. In the absence of any identified hazard, an acute/short-term DNEL is not required

Local DNELs

The substance is not classified for skin irritation or skin sensitisation. In the absence of any identified hazard, a local dermal DNEL is not required.

Oral DNELs

Long-term systemic DNEL

The starting point is derived from an oral study and does not therefore need correction. Individual assessment factors of 1 (for dose-response relationship), 6 (for duration of exposure), 4 (for allometric scaling), 2.5 (for remaining interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) are combined to give an overall assessment factor of 600. Applying the assessment factor of 600 to the starting point of 100 mg/kg bw/d results in a DNEL of 0.2 mg/kg bw/d.

Short-term systemic DNEL

The substance is of low acute toxicity and is not classified for acute toxicity. In the absence of any identified hazard, an acute/short-term DNEL is not required

Hazard for the eyes

The substance is classified for eye damage (Cat 1) and is therefore considered to represent a moderate hazard according to the ECHA Guidance on Information Requirements and Chemical Safety Assessment Part E: Risk Characterisation (version 3.0, May 2016).