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

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Toxicity to reproduction:

The NOAEL was estimated to be 865 mg/kg bw when Sprague- Dawley male and female rats were orally exposed with Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-). 

Thus, as per criteria of CLP regulation, Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-) can be not classified for reproductive toxicity.    

Link to relevant study records

Reference

Endpoint:

toxicity to reproduction

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

Limit test:

no

Justification for study design:

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

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

Type of inhalation exposure (if applicable):

not specified

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

not specified

Frequency of treatment:

not specified

Details on study schedule:

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

Parental animals: Observations and examinations:

not specified

Oestrous cyclicity (parental animals):

not specified

Sperm parameters (parental animals):

not specified

Litter observations:

not specified

Postmortem examinations (parental animals):

not specified

Postmortem examinations (offspring):

not specified

Statistics:

not specified

Reproductive indices:

not specified

Offspring viability indices:

not specified

Clinical signs:

not specified

Dermal irritation (if dermal study):

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

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

Key result

Dose descriptor:

NOAEL

Effect level:

865 mg/kg bw/day

Based on:

test mat.

Sex:

not specified

Basis for effect level:

reproductive performance

Remarks on result:

other: no significant changes estimated at mentioned dose level

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality / viability:

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

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings:

not specified

Other effects:

not specified

Behaviour (functional findings):

not specified

Developmental immunotoxicity:

not specified

Dose descriptor:

other: not specified

Generation:

other: not specified

Based on:

not specified

Sex:

not specified

Basis for effect level:

other: not specified

Remarks on result:

other: not specified

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Reproductive effects observed:

not specified

Treatment related:

not specified

Relation to other toxic effects:

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 6 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 ( not "p") )  )  and ("q" and ( not "r") )  )  and "s" )  and ("t" and "u" )  )

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 Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Inorganic chemical by DART scheme v.1.0

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Toluene and small alkyl toluene derivatives (8a) by DART scheme v.1.0

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Organophosphorus compounds (1b) by DART scheme v.1.0

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No alert found by DNA alerts for AMES, MN and CA by OASIS v.1.3

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Michael addition by DNA alerts for AMES, MN and CA by OASIS v.1.3

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg AND Group All Aqueous Solubility < 0.000005 g/L AND Group All Aqueous Solubility < 0.00002 g/L AND Group All Melting Point > 200 C AND Group CN Aqueous Solubility < 0.1 g/L AND Group CN log Kow > 4.5 AND Group CN Molecular Weight > 290 g/mol by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Group All log Kow < -3.1 by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg AND Group All Aqueous Solubility < 0.000005 g/L AND Group All Aqueous Solubility < 0.00002 g/L AND Group All Melting Point > 200 C AND Group CN Aqueous Solubility < 0.1 g/L AND Group CN log Kow > 4.5 AND Group CN Molecular Weight > 290 g/mol by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Group All Molecular Weight > 650 g/mol by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Subststituted pyrazoles by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Not bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is >= 6.11

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is <= 9.17

Conclusions:

The NOAEL was estimated to be 865 mg/kg bw when Sprague- Dawley male and female rats were orally exposed with Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-).

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-). The NOAEL was estimated to be 865 mg/kg bw when Sprague- Dawley male and female rats were orally exposed with Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-). 

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

865.36 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.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Reproductive toxicity:

In different studies, Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-) has been investigated for reproductive toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimation in rodents, i.e. most commonly in rats for Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-) along with the study available on structurally similar read across substance Barium lithol red (CAS no 1103-38-4) andTerphenyl (CAS no 26140-60-3).The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-). The NOAEL was estimated to be 865 mg/kg bw when Sprague- Dawley male and female rats were orally exposed with Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-). 

In another experimental study given by HPVIS (High Production Volume Information System (HPVIS), OPPT, US EPA (Uniteted State environment protction agency), 2017) on structurally similar read across substance Barium lithol red (CAS no 1103-38-4), CD male and female rats were treated with Barium lithol red in the concentration of 0 and 10,000 mg/kg bw/day orally in diet for 30 month. No mortality, Clinical signs, changes in Body weight and Food consumption of treated rats were observed as compared to control. Similarly, No significant effect on reproductive performance of treated rat were observed as compared to control rats. In addition, no effect on reproductive parameters and gross pathological of treated rats were observed in treated rat as compared to control. No effect on viability, sex ratio and body weight of pups were observed as compared to control. No external abnormality was observed in pups as compared to control. Therefore, NOAEL was considered to be 10,000 mg/kg bw for P and F1 generation when CD male and female rats were treated with Barium lithol red orally in diet for 30 month.

Further supported byexperimental study given by HPVIS (High Production Volume Information System (HPVIS), OPPT, US EPA (Uniteted State environment protction agency), 2017) on structurally similar read across substanceTerphenyl (CAS no 26140-60-3),Long-Evansmale and female rats were treated withTerphenylin the concentration of 0, 3, 31 and 350 mg/kg for male and 0, 3.5, 37 and 409 mg/kg for female orally in diet for 235 Days.No effect onHistopathology of reproductive organ such as testes or ovaries after 130, 188 and 235 days of treated male and female rats were observed as compared to control. Therefore, NOAEL was considered to be 350 mg/kg bw for male and 409 mg/kg bw for female whenLong-Evans maleand female rats were treated withTerphenylorally in diet for 235 Days.

Thus, based on the above study and predictions on Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-) and its read across substances, it can be concluded that NOAEL value is 865 mg/kg bw with no effect on reproduction. Thus, as per criteria of CLP regulation, Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-) can be not classified for reproductive toxicity.  

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the above study and predictions on Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-) and its read across substances, it can be concluded that NOAEL value is 865 mg/kg bw with no effect on reproduction. Thus, as per criteria of CLP regulation, Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-) can be not classified for reproductive toxicity.