3-amino-5-hydroxynaphthalene-2,7-disulphonic acid

Endpoint summary

Description of key information

The skin sensitization potential of3-amino-5-hydroxynaphthalene-2,7-disulfonic acid(90-40-4)was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances of3-amino-5-hydroxynaphthalene-2,7-disulfonic acid(90-40-4)was predicted to be not sensitizing to the skin of female CBA mouse .

 

 

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

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 from OECD QSAR toolbox v3.4 and the QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.4, 2017

GLP compliance:

not specified

Type of study:

mouse local lymph node assay (LLNA)

Justification for non-LLNA method:

No data available

Specific details on test material used for the study:

- Name of the test material: 3-amino-5-hydroxynaphthalene-2,7-disulfonic acid
- IUPAC name: 3-amino-5-hydroxynaphthalene-2,7-disulfonic acid
- Molecular formula: C10H9NO7S2
- Molecular weight: 319.3131 g/mol
- Substance type: Organic
- Smiles: c1c2cc(c(cc2c(cc1S(=O)(=O)O)O)N)S(=O)(=O)O

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

No data available

Vehicle:

propylene glycol

Concentration:

5, 10, 25%

No. of animals per dose:

4

Details on study design:

No data available

Statistics:

No data available

Positive control results:

No data available

Parameter:

SI

Remarks on result:

other: other: 5%: 0.84 10%: 0.98 25%: 0.79

Cellular proliferation data / Observations:

No data available

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes mode 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 "j" )  and "k" )  and ("l" and ( not "m") )  )  and ("n" and "o" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anilines (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines AND Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines AND SN1 AND SN1 >> Nucleophilic attack after metabolic nitrenium ion formation AND SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines by DNA binding by OASIS v.1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Strong binder, NH2 group OR Strong binder, OH group by Estrogen Receptor Binding ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines by Protein binding by OASIS v1.4

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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 >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Lysine peptide depletion

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Low reactive OR Low reactive >> N-substituted aromatic amides by DPRA Lysine peptide depletion

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "j"

Similarity boundary:Target: Nc1cc2c(cc1S(O)(=O)=O)cc(S(O)(=O)=O)cc2O
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "k"

Similarity boundary:Target: Nc1cc2c(cc1S(O)(=O)=O)cc(S(O)(=O)=O)cc2O
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Aromatic amines AND Phenols AND Sulfonic acids or their salts by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Ketones by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.21

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= -1.42

Interpretation of results:

other: not sensitising

Conclusions:

The skin sensitization potential of 3-amino-5-hydroxynaphthalene-2,7-disulfonic acid (90-40-4) was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances of 3-amino-5-hydroxynaphthalene-2,7-disulfonic acid (90-40-4) was predicted to be not sensitizing to the skin of female CBA mouse

Executive summary:

The skin sensitization potential of 3-amino-5-hydroxynaphthalene-2,7-disulfonic acid (90-40-4) was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances of 3-amino-5-hydroxynaphthalene-2,7-disulfonic acid (90-40-4) was predicted to be not sensitizing to the skin of female CBA mouse .

 

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization 

In different studies, 3-amino-5-hydroxynaphthalene-2,7-disulfonic acid (90-40-4) has been investigated for potential of skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in mouse for target chemical 3-amino-5-hydroxynaphthalene-2,7-disulfonic acid (90-40-4) and its structurally similar read across substancesD and C red 33 (3567-66-6)andCurry Red(25956-17-6) , the predicted data using the OECD QSAR toolbox has also been compared with the experimental data of read across.

The skin sensitization potential of 3-amino-5-hydroxynaphthalene-2,7-disulfonic acid (90-40-4) was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances of 3-amino-5-hydroxynaphthalene-2,7-disulfonic acid (90-40-4) was predicted to be not sensitizing to the skin of female CBA mouse .

 Supported by experimental study conducted by European Commission (Opinion of the Scientific Committee on Consumer Products on Acid Red 33 (C22), 2007) to evaluate the skin sensitizing potential of read across substance D and C red 33 (3567-66-6) in guinea pig . In Guinea pig maximization test of D and C red 33 (3567-66-6) was performed in 15 female SPF guinea pig(10 test group and 5 in control group) also 2-mercaptobenzothiazole used as positive control. In induction phase, intradermal induction given as5% dilution of test item in 1% CMC and in an emulsion of FCA/physiological saline to nuchal region of left flank, then after one week epidermal induction of 25% dilution in 1% CMC given in same region for 18hr, before that pre-treatment of the test areas with 10%s odium-laureth-sulfate (SLS), 24 hours prior to application of the test item given. The animals of the control group were intradermally induced with 1% CMC and FCA/physiological saline and epidermally induced with 1% CMC under occlusion following pre-treatment with 10% SLS. In challenge phase, test material 25% dilution in 1% CMC was applied epidermally on left flank and evaluated after 24hr and 48hr.No indication of skin sensitization was noted. Hence it is considered that D and C red 33 (3567-66-6) was not skin sensitizing in guinea pig by Guinea pig maximization test.

Also it is further Supported by experimental study conducted by European Commission (EC)( Evaluation and opinion on Curry Red, 2004) to evaluate the skin sensitizing potential of read across substanceCurry Red(25956-17-6) in mouse . Local lymph node assay (LLNA) of Disodium6-hydroxy-5-[(2-methoxy-4-sulphonato-m-tolyl)azo]naphthalene-2-sulphonate (25956-17-6) was performed on female mice CBA/J by measuring the cell proliferation in the draining lymph nodes after topical application onto the ears. In control group only 25µl of vehicle while in test group , 0.5, 1, 2, 4 % (w/v) test substance dissolved in DMSO and 0.5, 1, 2, 4 % in aqua/acetone (1:1) mixed with olive oil (4:1).Positive control p-phenylenediamine at 1 % in DMSO was applied on three consecutive days to the surface of the ear of 5 female CBA/J mice per group. After application, the ears were dried for about 5 minutes by means of a hair dryer.

All the animals were observed twice daily for any clinical signs and morbidity/mortality before and after given dose. Body weight was determined on day 1 and 5.On day 5 the mice received an intravenous injection of 250 μl phosphate buffered saline containing 20.8 μCi of [H3] methyl thymidine. After 5hr animals were died by giving CO2-inhalation and the draining auricular lymph node was removed and weighed. The cell suspension for each animal prepared. The cells were predicated by TCA. The liquid scintillation counting as disintegration per minute (dpm) was used to determined radioactivity due to incorporation of [H3] methyl thymidine in the pellets. The stimulation index was calculated by comparing test material with concurrent vehicle control.Result was noted using mean stimulation index ,test substance in concentration 0.5, 1, 2, 4 % (w/v) in DMSO mean stimulation indices of 0.6, 0.7, 0.9 and 0.9 were obtained while test substance as 0.5, 1, 2, 4 % in aqua/acetone (1:1) mixed with olive oil (4:1).The mean stimulation indices of1.2, 1.0, 0.9 and 0.9 were obtained. The positive control (PPD, 1 % in DMSO) caused an increase in the stimulation index by a factor of 7.8.As no relevant increase in the mean stimulation indices was observed (all figures were well below the trigger value of three), Hence it is considered thatDisodium6-hydroxy-5-[(2-methoxy-4-sulphonato-m-tolyl)azo]naphthalene-2-sulphonate (25956-17-6) was not skin sensitizer in mice by using Local lymph node assay (LLNA)

Thus based on the above predictions on 3-amino-5-hydroxynaphthalene-2,7-disulfonic acid (90-40-4) as well as its read across and applying weight of evidence, it can be concluded that 3-amino-5-hydroxynaphthalene-2,7-disulfonic acid (90-40-4) is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, 3-amino-5-hydroxynaphthalene-2,7-disulfonic acid (90-40-4) can be considered as not classified for skin sensitization

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Thus comparing the above studies with the criteria of CLP regulation, 3-amino-5-hydroxynaphthalene-2,7-disulfonic acid (90-40-4) can be considered as not classified for skin sensitization.