Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10.6 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: modified ECHA guidance
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
Value:
105.8 mg/m³
Explanation for the modification of the dose descriptor starting point:
The systemic NOAEL of 120 mg/kg bw/d from the OECD 408 study is corrected for breathing rate (/0.38 * 0.67) and the extent of absorption (*50%/100%)
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
extrapolation from sub-acute study to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
not required [accounted for in endpoint correction]
AF for other interspecies differences:
1
Justification:
additional factor not required according to ECETOC (2010). Although residual interspecies variability may remain following allometric scaling, this is largely accounted for in the default assessment factor proposed for intraspecies variability reflecting the inherent interdependency of inter- and intraspecies factors. Therefore, a separate residual AF for interspecies is unnecessary because it is already accounted for by the intraspecies assessment factor.
AF for intraspecies differences:
5
Justification:
default value [workers]
AF for the quality of the whole database:
1
Justification:
default value
AF for remaining uncertainties:
1
Justification:
default value
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
irritation (respiratory tract)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: modified ECHA guidance
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Value:
120 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No correction of the oral endpoint is required as oral and dermal absorption are considered to be comparable (worst-case assumption)
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
extrapolation from sub-acute study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
default value [rat study]
AF for other interspecies differences:
1
Justification:
additional factor not required according to ECETOC (2010). Although residual interspecies variability may remain following allometric scaling, this is largely accounted for in the default assessment factor proposed for intraspecies variability reflecting the inherent interdependency of inter- and intraspecies factors. Therefore, a separate residual AF for interspecies is unnecessary because it is already accounted for by the intraspecies assessment factor.
AF for intraspecies differences:
5
Justification:
default value [workers]
AF for the quality of the whole database:
1
Justification:
default value
AF for remaining uncertainties:
1
Justification:
default value
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)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

DNEL values are derived according to a modified REACH guidance and using standard assessment factors with the exception of the additional interspecies assessment factor. This additional factor is not required according to ECETOC (2010). Although residual interspecies variability may remain following allometric scaling, this is largely accounted for in the default assessment factor proposed for intraspecies variability reflecting the inherent interdependency of inter- and intraspecies factors. Therefore, a separate residual AF for interspecies is unnecessary because it is already accounted for by the intraspecies assessment factor.

The relevant starting point for the derivation of long-term systemic DNEL values is the NOAEL for systemic toxicity of 120 mg/kg bw/d from the OECD 408 study. The long-term systemic inhalation DNEL value for workers is derived following correction for breathing rate (/0.38 * 0.67) and the extent of absorption (*50%/100%) to give an oral NOAEC of 105.8 mg/m3. Application of an overall assessment factor of 10 [1 for dose-response relationship; 2 for exposure duration; 1 for allometric factors; 1 for other interspecies differences; 5 for intraspecies differences; 1 for database quality and 1 for remaining uncertainties] results in a long-term systemic inhalation DNEL of 10.6 mg/m3.

The long-term systemic dermal DNEL value for workers is derived from the systemic NOAEL of 120 mg/kg bw/d from the OECD 408 study; no correction of the oral endpoint is required as oral and dermal absorption are considered to be comparable (worst-case assumption). Application of an overall assessment factor of 40 [1 for dose-response relationship; 2 for exposure duration; 4 for allometric factors; 1 for other interspecies differences; 5 for intraspecies differences; 1 for database quality and 1 for remaining uncertainties] results in a long-term systemic dermal DNEL of 3 mg/kg bw/d.

Acute systemic (inhalation, dermal) DNEL values are not derived. The substance is classified (Category 3) for acute oral toxicity, however studies of repeated dose toxicity do not show clear evidence of systemic toxicity. The substance is corrosive and therefore it is concluded that the effects of acute exposure are primarily local.

DNELs for local effects are not derived. The substance is corrosive to skin. No data are available for the inhalation route of exposure; however it is prudent to assume that the substance may also cause local irritation/corrosion of the respiratory tract. In the absence of a quantitative endpoint, inhalation exposure must be avoided or minimised through the use of appropriate RMMs (engineering controls or RPE). In the absence of a quantitative endpoint, dermal exposure must similarly be avoided or minimised through the use of appropriate RMMs (engineering controls or PPE).  The substance is also assumed (in the absence of data) to be a severe eye irritant. Exposure should be avoided through the use of appropriate RMMs (engineering controls and/or PPE).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.6 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: modified ECHA guidance
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEC
Value:
52.2 mg/m³
Explanation for the modification of the dose descriptor starting point:
The systemic NOAEL of 120 mg/kg bw/d from the OECD 408 study is corrected for breathing rate (/1.15) and the extent of absorption (*50%/100%.)
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
extrapolation from sub-acute study to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
not required [accounted for in endpoint correction]
AF for other interspecies differences:
1
Justification:
additional factor not required according to ECETOC (2010). Although residual interspecies variability may remain following allometric scaling, this is largely accounted for in the default assessment factor proposed for intraspecies variability reflecting the inherent interdependency of inter- and intraspecies factors. Therefore, a separate residual AF for interspecies is unnecessary because it is already accounted for by the intraspecies assessment factor.
AF for intraspecies differences:
10
Justification:
default value [general population]
AF for the quality of the whole database:
1
Justification:
default value
AF for remaining uncertainties:
1
Justification:
default value
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
irritation (respiratory tract)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.5 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):
80
Modified dose descriptor starting point:
NOAEL
Value:
120 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No correction of the oral endpoint is required as oral and dermal absorption are considered to be comparable (worst-case assumption.)
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
extrapolation from sub-acute study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
default value [rat study]
AF for other interspecies differences:
1
Justification:
additional factor not required according to ECETOC (2010). Although residual interspecies variability may remain following allometric scaling, this is largely accounted for in the default assessment factor proposed for intraspecies variability reflecting the inherent interdependency of inter- and intraspecies factors. Therefore, a separate residual AF for interspecies is unnecessary because it is already accounted for by the intraspecies assessment factor.
AF for intraspecies differences:
10
Justification:
default value [general population]
AF for the quality of the whole database:
1
Justification:
default value
AF for remaining uncertainties:
1
Justification:
default value
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)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.5 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):
80
Modified dose descriptor starting point:
NOAEL
Value:
120 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not required (starting point is an oral study.
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
extrapolation from sub-acute study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
default value [rat study]
AF for other interspecies differences:
1
Justification:
default value
AF for intraspecies differences:
10
Justification:
default value [general population]
AF for the quality of the whole database:
1
Justification:
default value
AF for remaining uncertainties:
1
Justification:
default value
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

DNEL values are derived according to a modified REACH guidance and using standard assessment factors with the exception of the additional factor for interspecies differences. This factor is not required according to ECETOC (2010). Although residual interspecies variability may remain following allometric scaling, this is largely accounted for in the default assessment factor proposed for intraspecies variability reflecting the inherent interdependency of inter- and intraspecies factors. Therefore, a separate residual AF for interspecies is unnecessary because it is already accounted for by the intraspecies assessment factor.

The relevant starting point for the derivation of long-term systemic DNEL values is the NOAEL for systemic toxicity of 120 mg/kg bw/d from the OECD 408 study.

The long-term systemic inhalation DNEL value for the general population is derived following correction for breathing rate (/1.15) and the extent of absorption (*50%/100%) to give an inhalation NOAEC of 52.2 mg/m3. Application of an overall assessment factor of 20 [1 for dose-response relationship; 2 for exposure duration; 1 for allometric factors; 1 for other interspecies differences; 10 for intraspecies differences; 1 for database quality and 1 for remaining uncertainties] results in a long-term systemic inhalation DNEL of 2.6 mg/m3.

The long-term systemic dermal DNEL value for the general population is derived from the systemic NOAEL of 120 mg/kg bw/d from the OECD 408 study; no correction of the oral endpoint is required as oral and dermal absorption are considered to be comparable (worst-case assumption). Application of an overall assessment factor of 80 [1 for dose-response relationship; 2 for exposure duration; 4 for allometric factors; 1 for other interspecies differences; 10 for intraspecies differences; 1 for database quality and 1 for remaining uncertainties] results in a long-term systemic dermal DNEL of 1.5 mg/kg bw/d.

The long-term systemic oral DNEL value for the general population is derived from the systemic NOAEL of 120 mg/kg bw/d from the OECD 408 study; no correction of the oral endpoint is required. Application of an overall assessment factor of 80 [1 for dose-response relationship; 2 for exposure duration; 4 for allometric factors; 1 for other interspecies differences; 10 for intraspecies differences; 1 for database quality and 1 for remaining uncertainties] results in a long-term systemic dermal DNEL of 1.5 mg/kg bw/d.

Acute systemic (inhalation, dermal, oral) DNEL values are not derived. The substance is classified for acute oral toxicity (cat. 3), however studies of repeated dose toxicity do not show clear evidence of systemic toxicity. The substance is corrosive and therefore it is concluded that the effects of acute exposure are primarily local.

DNELs for local effects are not derived. The substance is corrosive to skin. No data are available for the inhalation route of exposure; however it is prudent to assume that the substance may also cause local irritation/corrosion of the respiratory tract. In the absence of a quantitative endpoint, inhalation exposure to high concentrations of the substance must be avoided or minimised. In the absence of a quantitative endpoint, dermal exposure to high concentrations of the substance must similarly be avoided or minimised.  The substance is also assumed (in the absence of data) to be a severe eye irritant. Exposure to high concentrations of the substance should be avoided.