Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.175 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:
88.16 mg/m³
Explanation for the modification of the dose descriptor starting point:

The starting point for DNEL derivation is the NOAEL of 100 mg/kg bw/d from the oral screening study.

For workers, the corrected inhalatory NOAEC is 100 mg/kg bw/d * sRVrat-1* Absoral rat/Absinh human* sRVhuman/wRV; i.e. 100 mg/kg bw/d * (0.38m3/kg bw/d)-1* (50/100) * (6.7 m3/10m3). This gives a modified inhalation starting point (NOAEC) of 88.16 mg/m3

AF for dose response relationship:
1
Justification:
Starting point is an adjusted NOAEC which was from a good quality modern study
AF for differences in duration of exposure:
6
Justification:
Extrapolation from a sub-acute study to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Use of an allometric scaling factor is not appropriate where route to route extrapolation is used since the species differences are accounted for in the breathing rate adjustments in the calculation.
AF for other interspecies differences:
2.5
Justification:
Default value for toxicokinetics and toxicodynamic interspecies differences
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:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.333 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:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The starting point for DNEL derivation is the NOAEL of 100 mg/kg bw/d from the oral screening study. In the absence of specific data and following the default assumption that dermal absorption is equal to oral absorption, the corrected dermal NOAEL is 100 mg/kg bw/d.

AF for dose response relationship:
1
Justification:
Starting point is a NOAEL from a good quality recent study
AF for differences in duration of exposure:
6
Justification:
Extrapolation from sub-acute study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Starting poitn is derived from a study in the rat
AF for other interspecies differences:
2.5
Justification:
Default value for toxicokinetics and toxicodynamic interspecies differences
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:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

The substance is not classified for acute toxicity but is classified for skin corrosion (Cat 1C) and serious eye damage (Cat 1). The substance is not classified for skin sensitisation and is not mutagenic based on in vitro data. There is no indication of developmental or reproductove toxicity from a screning study. The starting point for DNEL derivation is the NOAEL of 100 mg/kg bw/d from the oral OECD 422 screening study in rats, which is considered to be of sub-acute duration.

Inhalation DNELs

Systemic inhalation DNELs

The corrected starting point is an inhalation NOAEC of 88.16 mg/m3. Individual assessment factors of 1 (for dose-response relationship), 6 (for exposure duration), 1 (for allometric scaling), 2.5 (for other 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 overall assessment factor of 75 to the corrected inhalation NOAEC of 88.16 mg/m3 results in a long-term DNEL of 1.175 mg/m3. The substance is not classified for acute oral toxicity study; there are no data from an inhalation study. There is considered to be no hazard and a DNEL for acute/short-term systemic effects is not required. It is noted that the substance is classified as corrosive; therefore the potential for inhalation exposure will be limited through the use of engineering controls and suitable protective equipment.

Local inhalation DNELs

No data are available from studies using inhalation exposure. The substance is classified as a skin corrosive (Cat 1C) 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).

Dermal DNELs

Systemic dermal DNELs

The corrected starting point is a dermal NOAEL of 100 mg/kg bw/d. Individual assessment factors of 1 (for dose-response relationship), 6 (for exposure duration), 4 (for allometric scaling), 2.5 (for other 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 overall assessment factor of 300 to the corrected dermal NOAEL of 100 mg/kg bw/d results in a long-term DNEL of 0.333 mg/kg bw/d. The substance is not classified for acute oral toxicity; there are no data from a dermal study. There is considered to be no hazard and a DNEL for acute/short-term systemic effects is not required. It is noted that the substance is classified as corrosive; therefore the potential for dermal exposure will be limited through the use of engineering controls and suitable protective equipment.

Local dermal DNELs

The substance is classified as a skin corrosive (Cat 1C) 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).

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:
0.29 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:
43.48 mg/m³
Explanation for the modification of the dose descriptor starting point:

The starting point for DNEL derivation is the NOAEL of 100 mg/kg bw/d from the oral screening study.

For the general population, the corrected inhalation NOAEC is 100 mg/kg bw/d * (1/sRVrat) * (Oral absorbance in the rat/Inhalatory absorbance in human) i.e. 1235 mg/ kg bw/d * (1/1.15 m3/kg bw/d) * (50%/100%). This gives a modified starting point (inhalation NOAEC) of 43.48 mg/m3.

AF for dose response relationship:
1
Justification:
Starting point is a NOAEL from a good quality recent study
AF for differences in duration of exposure:
6
Justification:
Extrapolation from a sub-acute study to chronic exposure duration
AF for interspecies differences (allometric scaling):
1
Justification:
Use of an allometric scaling factor is not appropriate where route to route extrapolation is used since the species differences are accounted for in the breathing rate adjustments in the calculation.
AF for other interspecies differences:
2.5
Justification:
Default value for toxicokinetics and toxicodynamic interspecies differences
AF for intraspecies differences:
10
Justification:
Default value for 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:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.167 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:

The starting point for DNEL derivation is the NOAEL of 100 mg/kg bw/d from the oral screening study. In the absence of specific data and following the default assumption that dermal absorption is equal to oral absorption, the corrected dermal NOAEL is 100 mg/kg bw/d.

AF for dose response relationship:
1
Justification:
The starting point is a NOAEL from a good quality recent study
AF for differences in duration of exposure:
6
Justification:
Extrapolation from a sub-acute study to chronic exposure duration
AF for interspecies differences (allometric scaling):
4
Justification:
The starting point was from a rat study
AF for other interspecies differences:
2.5
Justification:
Default value for toxicokinetics and toxicodynamic interspecies differences
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:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.167 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:

Modification of the starting point is not required.

AF for dose response relationship:
1
Justification:
The starting point is based on good quality recent oral study.
AF for differences in duration of exposure:
6
Justification:
Extrapolation from a sub-acute study to chronic exposure duration
AF for interspecies differences (allometric scaling):
4
Justification:
Default value (starting point is a rat study)
AF for other interspecies differences:
2.5
Justification:
Default value for toxicokinetics and toxicodynamic interspecies differences
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 not classified for acute toxicity but is classified for skin corrosion (Cat 1C) and serious eye damage (Cat 1). The substance is not classified for skin sensitisation and is not mutagenic based on in vitro data. There is no indication of developmental or reproductove toxicity from a screning study. The starting point for DNEL derivation is the NOAEL of 100 mg/kg bw/d from the oral OECD 422 screening study in rats, which is considered to be of sub-acute duration.

Inhalation DNELs

Systemic inhalation DNELs

The corrected starting point is an inhalation NOAEC of 43.48 mg/m3. Individual assessment factors of 1 (for dose-response relationship), 6 (for exposure duration), 1 (for allometric scaling), 2.5 (for other 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 overall assessment factor of 150 to the corrected inhalation NOAEC of 43.48 mg/m3 results in a long-term DNEL of 0.29 mg/m3. The substance is not classified for acute oral toxicity study; there are no data from an inhalation study. There is considered to be no hazard and a DNEL for acute/short-term systemic effects is not required.

Local inhalation DNELs

No data are available from studies using inhalation exposure. The substance is classified as a skin corrosive (Cat 1C) 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).

Dermal DNELs

Systemic dermal DNELs

The corrected starting point is a dermal NOAEL of 100 mg/kg bw/d. Individual assessment factors of 1 (for dose-response relationship), 6 (for exposure duration), 4 (for allometric scaling), 2.5 (for other 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 overall assessment factor of 600 to the corrected dermal NOAEL of 100 mg/kg bw/d results in a long-term DNEL of 0.167 mg/kg bw/d. The substance is not classified for acute oral toxicity; there are no data from a dermal study. There is considered to be no hazard and a DNEL for acute/short-term systemic effects is not required.

Local dermal DNELs

The substance is classified as a skin corrosive (Cat 1C) 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).

Oral DNELs

Systemic oral DNELs

The starting point is an oral NOAEL of 100 mg/kg bw/d and does not therefore require correction. Individual assessment factors of 1 (for dose-response relationship), 6 (for exposure duration), 4 (for allometric scaling), 2.5 (for other 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 overall assessment factor of 600 to the oral NOAEL of 100 mg/kg bw/d results in a long-term DNEL of 0.167 mg/kg bw/d. The substance is not classified for acute oral toxicity. There is considered to be no hazard and a DNEL for acute/shor-term systemic effects 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).