Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-)

Endpoint summary

Description of key information

Repeated dose toxicity: oral

The No Observed Adverse Effect Level (NOAEL) for Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-) in rats is estimated to be 1092.0 mg/Kg bw/day after repeated exposure via oral route.

Repeated dose toxicity: inhalation

According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-), which is reported as 1.6132E-24 Pa. Thus, exposure to inhalable dust, mist and vapour of the chemical Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-) is highly unlikely. Therefore this study is considered for waiver.

Repeated dose toxicity: dermal

The acute toxicity value for Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-) (as provided in section 7.2.3) is >2000 mg/kg body weight. Also, given the use of the chemical; repeated exposure by the dermal route is unlikely since the use of gloves is common practice in industries. Thus, it is expected that Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-) shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-) shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is predicted by OECD QSAR Toolbox version 3.3. The supporting QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

The data is predicted using the OECD QSAR toolbox version 3.3 with log Kow as the primary descriptor.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material : Sodium tris (1, 2-naphthoquinone 1-oximato-O, O’) ferrate (1- )
- Molecular formula : C30H18FeN3O6.Na
- Molecular weight : 595.3222 g/mol
- Smiles notation : [Na+].[Fe+2].[O-]\N=C\1/C(=O)C=Cc2ccccc12.[O-]\N=C\3/C(=O)C=Cc4ccccc34.[O-]\N=C\5/C(=O)C=Cc6ccccc56
- InChl : HWLCXJRHGUPXJZ-ZHJLFMMCSA-K
- Substance type: Organic
- Physical state: Solid

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

oral: unspecified

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

not specified

Frequency of treatment:

not specified

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Positive control:

not specified

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Key result

Dose descriptor:

NOAEL

Effect level:

1 092 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: no significant changes estimated at mentioned dose level

Remarks on result:

other: No toxic effect were observed

Critical effects observed:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

The prediction was based on dataset comprised from the following descriptors: NOAEL
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and "o" )  and "p" )  and "q" )  and "r" )  and "s" )  and "t" )  and "u" )  and "v" )  and ("w" and ( not "x") )  )  and ("y" and ( not "z") )  )  and ("aa" and ( not "ab") )  )  and ("ac" and "ad" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anion OR Aromatic compound OR Cation by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aromatic Carbon [C] OR Carbonyl, olefinic attach [-C(=O)-] OR Carbonyloxime derivative [C(=O)C=NO-] OR Iron [Fe] OR Ketone in a ring, olefinic aromatic attach OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Oxygen, nitrogen attach [-O-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Diketone OR Fused carbocyclic aromatic OR Ketoxime derivatives OR Overlapping groups OR Quinoid compounds by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aryl OR Cycloketone OR Diketone OR Fused carbocyclic aromatic OR Ketoxime derivatives OR Quinoid compounds by Organic Functional groups ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone methides OR Radical OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Quinone methides by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Aliphatic nitriles (Hepatotoxicity) Rank B OR Oximes (Hemolytic anemia with methemoglobinemia) Rank B by Repeated dose (HESS)

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Aryl AND Cycloketone AND Diketone AND Fused carbocyclic aromatic AND Ketoxime derivatives AND Quinoid compounds by Organic Functional groups ONLY

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Diketone AND Fused carbocyclic aromatic AND Ketoxime derivatives AND Overlapping groups AND Quinoid compounds by Organic Functional groups (nested) ONLY

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aromatic Carbon [C] AND Carbonyl, olefinic attach [-C(=O)-] AND Carbonyloxime derivative [C(=O)C=NO-] AND Iron [Fe] AND Ketone in a ring, olefinic aromatic attach AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Oxygen, nitrogen attach [-O-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Aromatic Carbon [C] AND Carbonyl, olefinic attach [-C(=O)-] AND Carbonyloxime derivative [C(=O)C=NO-] AND Iron [Fe] AND Ketone in a ring, olefinic aromatic attach AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Oxygen, nitrogen attach [-O-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Aromatic Carbon [C] AND Carbonyl, olefinic attach [-C(=O)-] AND Carbonyloxime derivative [C(=O)C=NO-] AND Iron [Fe] AND Ketone in a ring, olefinic aromatic attach AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Oxygen, nitrogen attach [-O-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Aromatic Carbon [C] AND Carbonyl, olefinic attach [-C(=O)-] AND Carbonyloxime derivative [C(=O)C=NO-] AND Iron [Fe] AND Ketone in a ring, olefinic aromatic attach AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Oxygen, nitrogen attach [-O-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Aromatic Carbon [C] AND Carbonyl, olefinic attach [-C(=O)-] AND Carbonyloxime derivative [C(=O)C=NO-] AND Iron [Fe] AND Ketone in a ring, olefinic aromatic attach AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Oxygen, nitrogen attach [-O-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Aromatic Carbon [C] AND Carbonyl, olefinic attach [-C(=O)-] AND Carbonyloxime derivative [C(=O)C=NO-] AND Iron [Fe] AND Ketone in a ring, olefinic aromatic attach AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Oxygen, nitrogen attach [-O-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Not categorized by US-EPA New Chemical Categories

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Lanthanides or Rare Earth Metals by US-EPA New Chemical Categories

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Canada DSL AND ECHA PR AND EINECS AND NICNAS AND TSCA by Inventory Affiliation

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as (N/A) by Inventory Affiliation

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as (N/A) by Database Affiliation

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as Bioconcentration NITE by Database Affiliation

Domain logical expression index: "ac"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.522

Domain logical expression index: "ad"

Parametric boundary:The target chemical should have a value of log Kow which is <= 8.7

Conclusions:

The No Observed Adverse Effect Level (NOAEL) for Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-) in rats is estimated to be 1092.0 mg/Kg bw/day after repeated exposure via oral route.

Executive summary:

Repeated dose oral toxicity was evaluated for Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-) using SSS QSAR prediction database.

The study assumed the use of rats in a subacute study. Since no significant changes were noted, the No Observed Adverse Effect Level (NOAEL) for Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-) in rats is estimated to be 1092.0 mg/Kg bw/day after repeated exposure via oral route. Based on this the test substance is estimated to be not toxic after Repeated exposure via oral route as per CLP classification criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 092 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Data is of K2 reliability and is predicted from OECD QSAR toolbox.

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: dermal

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose toxicity: oral

The predicted data for target Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-) (CAS 16143 -80 -9) and its structurally read across substance Acid green 1 (CAS 19381 -50 -1) were reviewed to determine the toxic nature of the test compound upon repeated application and is summarised below as weight of evidence approach:

Repeated dose oral toxicity was evaluated forSodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-)using SSS QSAR prediction database.

The study assumed the use of rats in a subacute study. Since no significant changes were noted, the No Observed Adverse Effect Level (NOAEL) for Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-) in rats is estimated to be 1092.0 mg/Kg bw/day after repeated exposure via oral route. Based on this the test substance is estimated to be not toxic after Repeated exposure via oral route as per CLP classification criteria.

The above result was supported by the read across data obtained from the Report of the Scientific Committee on Cosmetology (seventh series) by Commission of the European Communities, in which the substance Ferric Complex of trisodium tris[5,6-dihydro-5-(hydroxyimino)-6-oxonaphthalene-2-sulphonato(2-)-N5,O6]ferrate(3 -) (CAS No. 19381-50-1) was tested for its potential toxic effects after repeated exposure via oral route of administration. The test animal considered for the study was rats. The test substance was exposed via gavage route at concentration of 1000 or 2000 mg/kg bw/day at frequency of 5 days/week for 13 weeks. Treatment of rats with the test chemical did not induce any deleterious effects. Hence, the No Observed Adverse Effect Level (NOAEL) for trisodium tris[5,6-dihydro-5-(hydroxyimino)-6-oxonaphthalene-2-sulphonato(2-)-N5,O6]ferrate(3-) in rats is considered to be 2000 mg/kg bw/day after repeated exposure via oral route.

Based on the above data and by applying weight of evidence approach, it can be concluded that the chemical Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-) (CAS 19381 -50 -1) is not likely to cause repeated dose toxicity by the oral route of exposure. Thus, the chemical is not likely to be considered for classification under Repeated dose toxicity as per CLP classification criteria.

Repeated dose toxicity: inhalation

According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-), which is reported as1.6132E-24 Pa. Thus, exposure to inhalable dust, mist and vapour of the chemical Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-)is highly unlikely. Therefore this study is considered for waiver.

Repeated dose toxicity: dermal

The acute toxicity value for Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-)(as provided in section 7.2.3) is >2000 mg/kg body weight. Also, given the use of the chemical; repeated exposure by the dermal route is unlikely since the use of gloves is common practice in industries. Thus, it is expected thatSodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-)shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-) shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.

Justification for classification or non-classification

Based on the above data and the applicable waivers, it can be concluded that the chemical Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-) (CAS 16143 -80 -9)

is not likely to cause repeated dose toxicity by the oral, inhalation and dermal route of exposure. Thus, the chemical is not likely to be considered for classification under Repeated dose toxicity as per CLP classification criteria.