Registration Dossier

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
141 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Modified dose descriptor starting point:
NOAEC
Value:
1 763 mg/m³
Explanation for the modification of the dose descriptor starting point:
Convert oral NOAEL to inhalation NOAEC: 1000 mg/kg/day x [1/0.38 x 100/100 x 6.7/10] = 1763 mg/m3
AF for differences in duration of exposure:
1
Justification:
Although the duration of the OECD 421 study from which the starting point (NOAEL/NOEL 1000 mg/kg bw/day) was obtained is generally considered sub-acute, treatment for up to 6 months at the extremely high dosage of 7200 mg/kg bw/day resulted in no adverse effects but only adaptive changes in kidneys. On this basis it is considered appropriate to not apply any AF for duration of exposure at the much lower limit dose of 1000 mg/kg bw/day chosen as the worst-case starting point
Justification:
Not applicable for inhalation (differences in species addressed in calculation of dose descriptor starting point).
AF for other interspecies differences:
2.5
Justification:
Differences in species addressed in calculation of dose descriptor starting point.
AF for intraspecies differences:
5
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
AF for the quality of the whole database:
1
Justification:
Database appropriate for the tonnage.
AF for remaining uncertainties:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
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:
2 000 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEL
Value:
100 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Convert oral NOAEL to dermal NOAEL: 1000 mg/kg/day x [oral absorption 100% / dermal absorption 1%] = 100000 mg/kg/day
AF for differences in duration of exposure:
1
Justification:
Although the duration of the OECD 421 study from which the starting point (NOAEL/NOEL 1000 mg/kg bw/day) was obtained is generally considered sub-acute, treatment for up to 6 months at the extremely high dosage of 7200 mg/kg bw/day resulted in no adverse effects but only adaptive changes in kidneys. On this basis it is considered appropriate to not apply any AF for duration of exposure at the much lower limit dose of 1000 mg/kg bw/day chosen as the worst-case starting point.
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for rat in line with Table R.8-3 and Appendix R. 8-2, part 2, example B5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
AF for other interspecies differences:
2.5
Justification:
Differences in species addressed in calculation of dose descriptor starting point.
AF for intraspecies differences:
5
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
AF for the quality of the whole database:
1
Justification:
Database appropriate for the tonnage.
AF for remaining uncertainties:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
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

The substance is not acutely toxic following oral administration or dermal application and therefore acute DNELs for systemic effects are not required. The substance was not irritating either to the skin or eye and did not show any sensitising potential therefore DNELs for local effects are not required.

Based on the available studies used to support the registration, the substance is considered to not be genotoxic.

Treatment for up to 6 months at dosages as high as 7200 mg/kg bw/day resulted in no over toxicity and only in adaptive changes of the kidney to the constant high load of sodium. Similarly, no adverse effects were observed for any of the parameters examined in a fully compliant OECD 421 study, and the NOAEL for parental systemic toxicity, and reproductive and developmental toxicity was the set at the limit dose of 1000 mg/kg bw/day.

This value was chosen as the more appropriate starting point for systemic DNELs calculation however, as the longer-term studies demonstrated that increasing the exposure duration at extremely high doses does not increase the incidence or severity of adverse effects, an assessment factor of 1 has been applied to this lower NOAEL for duration of exposure.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
35 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
Value:
870 mg/m³
Explanation for the modification of the dose descriptor starting point:
Convert oral NOAEL to inhalation NOAEC: 1000 mg/kg/day x [1/1.15 x 100/100] = 870 mg/m3
AF for differences in duration of exposure:
1
Justification:
Although the duration of the OECD 421 study from which the starting point (NOAEL/NOEL 1000 mg/kg bw/day) was obtained is generally considered sub-acute, treatment for up to 6 months at the extremely high dosage of 7200 mg/kg bw/day resulted in no adverse effects but only adaptive changes in kidneys. On this basis it is considered appropriate to not apply any AF for duration of exposure at the much lower limit dose of 1000 mg/kg bw/day chosen as the worst-case starting point.
Justification:
Not applicable for inhalation (differences in species addressed in calculation of dose descriptor starting point).
AF for other interspecies differences:
2.5
Justification:
Differences in species addressed in calculation of dose descriptor starting point.
AF for intraspecies differences:
10
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
AF for the quality of the whole database:
1
Justification:
Database appropriate for the tonnage.
AF for remaining uncertainties:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
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:
1 000 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Value:
100 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Convert oral NOAEL to dermal NOAEL: 1000 mg/kg/day x [oral absorption 100% / dermal absorption 1%] = 100000 mg/kg/day
AF for differences in duration of exposure:
1
Justification:
Although the duration of the OECD 421 study from which the starting point (NOAEL/NOEL 1000 mg/kg bw/day) was obtained is generally considered sub-acute, treatment for up to 6 months at the extremely high dosage of 7200 mg/kg bw/day resulted in no adverse effects but only adaptive changes in kidneys. On this basis it is considered appropriate to not apply any AF for duration of exposure at the much lower limit dose of 1000 mg/kg bw/day chosen as the worst-case starting point.
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for rat in line with Table R.8-3 and Appendix R. 8-2, part 2, example B5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
AF for other interspecies differences:
2.5
Justification:
Differences in species addressed in calculation of dose descriptor starting point.
AF for intraspecies differences:
10
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
AF for the quality of the whole database:
1
Justification:
Database appropriate for the tonnage.
AF for remaining uncertainties:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
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:
10 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
AF for differences in duration of exposure:
1
Justification:
Although the duration of the OECD 421 study from which the starting point (NOAEL/NOEL 1000 mg/kg bw/day) was obtained is generally considered sub-acute, treatment for up to 6 months at the extremely high dosage of 7200 mg/kg bw/day resulted in no adverse effects but only adaptive changes in kidneys. On this basis it is considered appropriate to not apply any AF for duration of exposure at the much lower limit dose of 1000 mg/kg bw/day chosen as the worst-case starting point.
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for rat in line with Table R.8-3 and Appendix R. 8-2, part 2, example B5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
AF for other interspecies differences:
2.5
Justification:
Differences in species addressed in calculation of dose descriptor starting point.
AF for intraspecies differences:
10
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
AF for the quality of the whole database:
1
Justification:
Database appropriate for the tonnage.
AF for remaining uncertainties:
1
Justification:
Default value in line with Section R.8.4.3.1 of Chapter R.8 of Guidance on information requirements and chemical safety assessment.
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

The substance is not acutely toxic following oral administration or dermal application and therefore acute DNELs for systemic effects are not required. The substance was not irritating either to the skin or eye and did not show any sensitising potential therefore DNELs for local effects are not required.

Based on the available studies used to support the registration, the substance is considered to not be genotoxic.

Treatment for up to 6 months at dosages as high as 7200 mg/kg bw/day resulted in no over toxicity and only in adaptive changes of the kidney to the constant high load of sodium. Similarly, no adverse effects were observed for any of the parameters examined in a fully compliant OECD 421 study, and the NOAEL for parental systemic toxicity, and reproductive and developmental toxicity was the set at the limit dose of 1000 mg/kg bw/day.

This value was chosen as the more appropriate starting point for systemic DNELs calculation however, as the longer-term studies demonstrated that increasing the exposure duration at extremely high doses does not increase the incidence or severity of adverse effects, an assessment factor of 1 has been applied to this lower NOAEL for duration of exposure.