Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.6 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
DNEL value:
88.2 mg/m³
Explanation for the modification of the dose descriptor starting point:
The REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) prescribes a default factor of 2 in case of dermal to inhalation extrapolation. Standard respiratory volume of a rat, corrected for 8 h exposure, as proposed in the REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) is considered to be 0.4 m³/kg bw. Correction for activity driven differences of respiratory volumes in workers compared to workers in rest was considered to be 6.7 m³/10 m³. Therefore the modified dose descriptor starting point is 88.2 mg/m³ (= 100 / 2 / 0.38 x (6.7/10)).
AF for differences in duration of exposure:
2
Justification:
Difference in duration of exposure extrapolating from subchronic to chronic
AF for other interspecies differences:
2.5
Justification:
Remaining difference
AF for intraspecies differences:
5
Justification:
Default value for workers
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:
1 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
DNEL value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route to route extrapolation is needed as the sub-chronic study was performed by dermal application
AF for differences in duration of exposure:
2
Justification:
Difference in duration from sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rats to humans
AF for other interspecies differences:
2.5
Justification:
Remaining differences
AF for intraspecies differences:
5
Justification:
Worker population
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:
no hazard identified

Additional information - workers

According to REACH guidance on information and requirements and chemical safety assessment , a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible.

Short-term toxicity

According to the REACH guideline (R8, Appendix R 8-8), a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential risk for high peak exposures. The substance is not classified for acute oral, dermal and inhalation toxicity, the DNELs derived for long term exposure are considered to be sufficient for protection of the workers, therefore no short-term DNELs are derived for these routes of exposure. The substance is also classified as irritating to the skin and as skin sensitizing but no DNELs could be derived. The test substance is classified as sensitizing, however, since only from a guinea pig maximization test results are available, no DNEL could be derived. No data is available whether the test substance could cause irritation to the respiratory track and therefore no DNEL could be derived.

Long-term toxicity

A sub-chronic (90-days) dermal toxicity study is available in rats. In this study a NOAEL of 100 mg/kg bw/day was established. Since only a sub-chronic dermal toxicity study is available a route-to-route extrapolation is needed to derive the DNELs for inhalation route.

 According to Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment, it is proposed in the absence of route-specific information on the starting route, to include a default factor of 2 in the case of oral-to-inhalation extrapolation. This approach will be taken forward to DNEL derivation. In the absence of route-specific information a ratio of 1 for oral to dermal absorption, considered as worst case scenario, is provisionally suggested for the risk assessment of the substance.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.87 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEC
DNEL value:
43.5 mg/m³
Explanation for the modification of the dose descriptor starting point:
The REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) prescribes a default factor of 2 in case of dermal to inhalation extrapolation. Standard respiratory volume of a rat, corrected for 24 h exposure, as proposed in the REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) is considered to be 1.15 m3/kg bw. Therefore the modified dose descriptor starting point is 43.5 m3/kg bw (= 100 / 2 / 1.15 ).
AF for differences in duration of exposure:
2
Justification:
Extrapolation to chronic exposure based on a sub-chronic toxicity study
AF for intraspecies differences:
10
Justification:
Default assessment factor for consumers.
AF for remaining uncertainties:
2.5
Justification:
Default assessment factor.
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:
0.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
DNEL value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route to route extrapolation is needed as the sub-chronic study was performed by dermal application
AF for differences in duration of exposure:
2
Justification:
Extrapolation to chronic exposure based on a sub-chronic toxicity study.
AF for interspecies differences (allometric scaling):
4
Justification:
Assessment factor for allometric scaling.
AF for intraspecies differences:
10
Justification:
Default assessment for consumers.
AF for remaining uncertainties:
2.5
Justification:
Default assessment factor.
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:
0.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
DNEL value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
On the assumption that, in general, dermal absorption will not be higher than oral absorption, no defaults factor should be introduced when performing oral-to-dermal extrapolation. The REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) prescribes a default factor of 1.
AF for differences in duration of exposure:
2
Justification:
Extrapolation to chronic exposure based on a sub-chronic toxicity study
AF for interspecies differences (allometric scaling):
4
Justification:
Assessment factor for allometric scaling.
AF for other interspecies differences:
2.5
Justification:
Remaining differences
AF for intraspecies differences:
10
Justification:
Default assessment factor for consumers.
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

According to REACH guidance on information and requirements and chemical safety assessment , a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible.

Short-term toxicity

According to the REACH guideline (R8, Appendix R 8-8), a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential risk for high peak exposures. The substance is not classified for acute oral, dermal and inhalation toxicity, the DNELs derived for long term exposure are considered to be sufficient for protection of the workers, therefore no short-term DNELs are derived for these routes of exposure. The substance is also classified as irritating to the skin and as skin sensitizing but no DNELs could be derived. The test substance is classified as sensitizing, however, since only from a guinea pig maximization test results are available, no DNEL could be derived. No data is available whether the test substance could cause irritation to the respiratory track and therefore no DNEL could be derived.

Long-term toxicity

A sub-chronic (90-days) dermal toxicity study is available in rats. In this study a NOAEL of 100 mg/kg bw/day was established. Since only a sub-chronic dermal toxicity study is available a route-to-route extrapolation is needed to derive the DNELs for inhalation route.

 According to Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment, it is proposed in the absence of route-specific information on the starting route, to include a default factor of 2 in the case of oral-to-inhalation extrapolation. This approach will be taken forward to DNEL derivation. In the absence of route-specific information a ratio of 1 for oral to dermal absorption, considered as worst case scenario, is provisionally suggested for the risk assessment of the substance.