Sodium 4-chloro-3-nitrobenzenesulphonate

Endpoint summary

Description of key information

Skin Sensitization:

The skin sensitization potential of Sodium 4-chloro-3-nitrobenzenesulphonate was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. Sodium 4-chloro-3-nitrobenzenesulphonate was predicted to be non sensitizing to the skin of female Dunkin- Hartley guinea pigs.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation

Remarks:

in vivo

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 v3.3 and the QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3

GLP compliance:

not specified

Type of study:

other: Estimated data

Specific details on test material used for the study:

- Name of the test material: Sodium 4-chloro-3-nitrobenzenesulphonate
- IUPAC Name : sodium 4-chloro-3-nitrobenzene-1-sulfonate
- Molecular formula: C6H4ClNO5SNa
- Molecular weight: 259.601 g/mol
- Smiles: S(=O)(=O)([O-])c1cc([N+]([O-])=O)c(Cl)cc1.[Na+]
- InChI: 1S/C6H4ClNO5S.Na/c7-5-2-1-4(14(11,12)13)3-6(5)8(9)10;/h1-3H,(H,11,12,13);/q;+1/p-1
- Substance type: Organic
- Physical state: Solid powder (Off white to pale yellow)

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

no data available

Route:

epicutaneous, occlusive

Vehicle:

not specified

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

not specified

Adequacy of challenge:

not specified

No. of animals per dose:

10

Details on study design:

no data available

Challenge controls:

no data available

Positive control substance(s):

not specified

Reading:

1st reading

Group:

test chemical

No. with + reactions:

0

Clinical observations:

no effects observed

Remarks on result:

no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((("a" or "b" )  and ("c" and ( not "d") )  )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and "k" )  and "l" )  and "m" )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and "s" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups AND SN1 AND SN1 >> Nucleophilic attack after diazonium or carbenium ion formation AND SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups AND SN1 >> Nucleophilic attack after reduction and nitrenium ion formation AND SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups AND SN2 AND SN2 >> SN2 attack on activated carbon Csp3 or Csp2 AND SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic nitro by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic nitro by DNA binding by OECD

Domain logical expression index: "d"

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 OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR No alert found OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA binding by OECD

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as High reactive by DPRA Cysteine peptide depletion

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Moderate reactive by DPRA Cysteine peptide depletion

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Similarity boundary:Target: O=N(=O)c1cc(S(=O)(=O)O{-}.[Na]{+})ccc1Cl
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Similarity boundary:Target: O=N(=O)c1cc(S(=O)(=O)O{-}.[Na]{+})ccc1Cl
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Benzene/ Naphthalene sulfonic acids (Less susceptible) Rank C by Repeated dose (HESS)

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Chlorphentermine (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Benzene/ Naphthalene sulfonic acids (Less susceptible) Rank C by Repeated dose (HESS)

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Nitrobenzenes (Hemolytic anemia with methemoglobinemia) Rank A by Repeated dose (HESS)

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.13

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.53

Interpretation of results:

other: not sensitizing

Conclusions:

Sodium 4-chloro-3-nitrobenzenesulphonate was predicted to be non sensitizing to the skin of female Dunkin- Hartley guinea pigs.

Executive summary:

The skin sensitization potential of Sodium 4-chloro-3-nitrobenzenesulphonate was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. Sodium 4-chloro-3-nitrobenzenesulphonate was predicted to be non sensitizing to the skin of female Dunkin- Hartley guinea pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin Sensitization:

Various studies have been investigated for assessing the dermal sensitization potential of Sodium 4-chloro-3-nitrobenzenesulphonate to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs along with predicted data for target chemical and its structurally similar read across chemicals, Sodium toluene-4-sulphonate [CAS: 657-84-1] and 4-Hydroxpropylamino-3-nitrophenol[CAS: 92952-81-3]. The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

The skin sensitization potential of Sodium 4-chloro-3-nitrobenzenesulphonate was estimated by SSS (2017) using OECD QSAR toolbox v 3.3 with log kow as the primary descriptor. Sodium 4-chloro-3-nitrobenzenesulphonatewas predicted to be non sensitizing to the skin of female Dunkin- Hartley guinea pigs.

This result is supported by the experimental study summarized in International Journal of Toxicology; Vol 30, Issue 6_suppl, pp. 270S - 283S; 2011; for the structurally similar read across chemical, Sodium toluene-4-sulphonate [CAS: 657-84-1] .Guinea pigs were exposed dermally to a 42.8% solution of sodium toluene-4-sulphonate in deionized water under occlusive conditions (number of animals and duration not mentioned). The treated animals were observed for dermal irritation and sensitization effect at induction and challenge exposure. No irritation was observed at induction or at challenge exposure. Under the conditions of this study, it was considered that Sodium toluene-4-sulphonate was not a skin sensitizer.  

These results are also supported by the experimental study summarized in Scientific Committee on Consumer Products- SCCP, COLIPA n° B100, adopted on 18 December 2007; for thestructurally similar read across chemical, 4-Hydroxpropylamino-3-nitrophenol[CAS: 92952-81-3]. The study was performed as per OECD 429 “Mouse Local Lymphnode Assay” Guidelines. Five dose groups, two controls receiving vehicle alone consisting of 5 femaleCBA strain (inbred, SPF) mice were used.0.5, 1, 10, 25 and 50% in acetone : olive oil (4:1 v/v) were determined in a pretest with four mice. In parallel to both parts of the main study, control animals were treated with the vehicle alone.Each test group of mice was treated by topical (epidermal) application to the dorsal surface of each ear lobe (left and right) with the different test item concentrations. The application volume, 25 μl, was spread over the entire dorsal surface of each ear lobe once daily for three consecutive days. The control group was treated with the vehicle exclusively. Five days after the first topical application, all mice were administered with radio-labelled thymidine (³HTdR) by intravenous injection via the tail vein.Approximately five hours after ³HTdR application all mice were killed. The draining lymph nodes were excised and pooled for each experimental group. After preparation of the lymph nodes, disaggregation and overnight precipitation of macromolecules, these precipitations were re-suspended and transferred to scintillation vials. The level of ³HTdR incorporation was then measured by scintillation counting. The proliferative response of lymph node cells was expressed as the ratio of ³HTdR incorporation into lymph node cells of treated animals relative to that recorded in control mice (stimulation index).The positive control was α-hexylcinnamaldehyde and studies with this were undertaken in August 2003 and March 2004. EC3 values of 5.5 and 10.3% respectively were obtained. A test item is regarded as a sensitizer if the exposure to at least one concentration resulted in an at least 3-fold increase in incorporation of ³HTdR compared with concurrent controls, as indicated by the stimulation index (S.I.).No signs of skin irritation were noted on the ear dorsum of the treated mice at any concentration. Based on the criteria according to OECD 429, 4-Hydroxpropylamino-3-nitrophenol can be considered to be a non-sensitizer in mice at the highest achievable concentration of 50% (w/v) in acetone: olive oil.

Based on the available data for the target and read across substances and applying the weight of evidence approach, Sodium 4-chloro-3-nitrobenzenesulphonate can be considered to be not sensitizing to skin.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified.”

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Available data forSodium 4-chloro-3-nitrobenzenesulphonate suggests that it is not likely to cause any dermal sensitization to guinea pig skin.

Sodium 4-chloro-3-nitrobenzenesulphonate can be considered to be not sensitizer to skin and can be classified under the category “Not Classified” as per CLP regulation.