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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.1 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):
50
Modified dose descriptor starting point:
NOAEC
Value:
5.3 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAEL(oral) converted to NOAEC(inhal) (3 mg/kg x [1/0.38 x 100% oral absorption rat/100% inhalation absorption human x 6.7/10]) = 5.3 mg/m³

AF for dose response relationship:
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
AF for differences in duration of exposure:
2
Justification:
Extrapolation from subchronic study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
Justification:
Not applicable for inhalation. Differences in species addressed in calculation of dose descriptor starting point.)
AF for other interspecies differences:
2.5
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 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:
2
Justification:
Limited data on the substance itself / key values from read-across
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:
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):
3
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
other: DNEL for Inhalation Systemic effects – Long Term
Value:
0.1 mg/m³
Explanation for the modification of the dose descriptor starting point:

DNEL extrapolated from long term DNEL

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
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.06 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):
200
Modified dose descriptor starting point:
NOAEL
Value:
12 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Long-term: NOAEL (oral) converted to NOAEL (dermal): 3 mg/kg bw/day*100% ABS (oral)/25%ABS(dermal) = 12 mg/kg bw/day

AF for dose response relationship:
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
AF for differences in duration of exposure:
2
Justification:
Extrapolation from subchronic study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default value 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:
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 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:
2
Justification:
Limited data on the substance itself
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:
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):
3
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
other: DNEL for dermal systemic effects – long term.
Value:
0.06 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

DNEL extrapolated from long term DNEL

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

Sodium periodate is seen to be corrosive in an in-vitro assay, but no quantitative dose-response can be established; DNELs for acute exposure were established using a default 3-fold the long-term DNEL. DNELs for local effects could not be calculated.

The most sensitive endpoint was the NOAEL (3 mg/kg bw/day) obtained in an acceptable 90-day feeding study in rats, using potassium iodate. The study was performed in line with good scientific principles and reported to an adequate standard. In accordance with Klimisch (1997) the study was assigned a reliability score of 2. Sodium periodate may be expected to be reduced, under biological conditions, almost quantitatively to iodate and then to iodide. This NOAEL (3 mg/kg bw/day) was used as the starting point for the calculation of systemic DNELs. The reproductive and developmental toxicity was investigated in a study performed in accordance with standardised guidelines OECD 421 and EPA OPPTS 870.3550 using potassium iodide for read-across to support sodium periodate; this study showed no effect at the highest dose tested. No carcinogenicity study is available, although potassium iodate and iodide showed no evidence of genotoxicity. Iodine (and iodide), an essential mineral, is not known to be carcinogenic. The toxicity of iodate (the primary breakdown product of periodate) closely resembles that of iodine, for which a necessary daily intake is well understood. An additional factor of no more than 2 for completeness of the database is therefore applied.

For the purposes of human risk assessment there is sufficient information to consider that sodium periodate would be extensively absorbed (100%) by the oral route, and slowly metabolised and excreted. The consequences of slow metabolism and excretion are however adequately addressed within the NOAEL of a 90-day study. Human dermal absorption may be considered to be 25%; inhalation absorption is assumed to be complete.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.03 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):
100
Modified dose descriptor starting point:
NOAEC
Value:
2.6 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAEL(oral) converted to NOAEC(inhal) (3 mg/kg x [1/1.15 x 100% oral absorption rat/100% inhalation absorption human) = 2.6 mg/m³

AF for dose response relationship:
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
AF for differences in duration of exposure:
2
Justification:
Extrapolation from subchronic study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
Justification:
Not applicable for inhalation. Differences in species addressed in calculation of dose descriptor starting point.)
AF for other interspecies differences:
2.5
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 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:
2
Justification:
Limited data on the substance itself / key values from read-across
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:
DNEL (Derived No Effect Level)
Value:
0.09 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):
3
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
other: DNEL for Inhalation Systemic effects – Long Term
Value:
0.03 mg/m³
Explanation for the modification of the dose descriptor starting point:

DNEL extrapolated from long term DNEL

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
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.03 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):
400
Modified dose descriptor starting point:
NOAEL
Value:
12 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

NOAEL (oral) converted to NOAEL (dermal): 3 mg/kg bw/day*100% ABS (oral)/25%ABS(dermal) = 12 mg/kg bw/day

AF for dose response relationship:
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
AF for differences in duration of exposure:
2
Justification:
Extrapolation from subchronic study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default value 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:
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 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:
2
Justification:
Limited data on the substance itself
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:
DNEL (Derived No Effect Level)
Value:
0.09 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):
3
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
other: DNEL for dermal systemic effects – long term.
Value:
0.03 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

DNEL extrapolated from long term DNEL

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:
DMEL (Derived Minimum Effect Level)
Value:
0.01 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):
400
Modified dose descriptor starting point:
NOAEL
Value:
3 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

N/A oral study to oral DNEL derivation. Same oral absorption in rats and humans assumed

AF for dose response relationship:
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
AF for differences in duration of exposure:
2
Justification:
Extrapolation from subchronic study to chronic exposure value in line with Table R.8-5 of Chapter R.8 of Guidance on information requirements and chemical safety assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default value 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:
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 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:
2
Justification:
Limited data on the substance itself / key values from read-across
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:
DNEL (Derived No Effect Level)
Value:
0.03 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):
3
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
other: DNEL for oral systemic effects – long term.
Value:
0.01 mg/kg bw/day

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

Sodium periodate is seen to be corrosive in an in-vitro assay, but no quantitative dose-response can be established; DNELs for acute exposure were established using a default 3-fold the long-term DNEL. DNELs for local effects could not be calculated.

The most sensitive endpoint was the NOAEL (3 mg/kg bw/day) obtained in an acceptable 90-day feeding study in rats, using potassium iodate. The study was performed in line with good scientific principles and reported to an adequate standard. In accordance with Klimisch (1997) the study was assigned a reliability score of 2. Sodium periodate may be expected to be reduced, under biological conditions, almost quantitatively to iodate and then to iodide. This NOAEL (3 mg/kg bw/day) was used as the starting point for the calculation of systemic DNELs. The reproductive and developmental toxicity was investigated in a study performed using potassium iodide and used for read-across to support sodium periodate; this study showed no effect at the highest dose tested. No carcinogenicity study is available, although potassium iodate and iodide showed no evidence of genotoxicity. Iodine (and iodide), an essential mineral, is not known to be carcinogenic. The toxicity of iodate (the primary breakdown product of periodate) closely resembles that of iodine, for which a necessary daily intake is well understood. An additional factor of no more than 2 for completeness of the database is therefore applied.

 

The resulting oral long-term DNEL (0.01 mg/kg bw/day) at the same level as the tolerable upper intake level for iodide in adults as established by EFSA (2006).

The same endpoint used for workers was selected for setting the long-term DNELs for the general population. The larger assessment factor for intraspecies sensitivity was considered adequately protective for the more sensitive population.