2-chlorobenzene-1,4-diammonium sulphate

Endpoint summary

Description of key information

The skin senitization potential of 2-chlorobenzene-1,4-diammonium sulphate was estimated using OECD QSAR toolbox v3.3 with log Pow as the primary descriptor. 2-chlorobenzene-1,4-diammonium sulphate was estimated to be sensitizing to the skin of  guinea pigs. Based on the estimated results, 2-chlorobenzene-1,4-diammonium sulphate can be considered to be sensitizing to skin and can be classified under the category “ Category 1 (skin sensitising) based on GHS criteria” as per CLP regulation.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

(Q)SAR

Adequacy of study:

other information

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 using OECD QSAR toolbox version 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

OECD QSAR toolbox v3.3

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Not specified

Specific details on test material used for the study:

IUPAC name: 2-chlorobenzene-1,4-diammonium sulphate
Molecular formula: C6H7ClN2.xH2O4S
Molecular weight:240.6661
substance type: organic
physical state: light grey colored solid powder.
InChI:1S/C6H7ClN2.H2O4S/c7-5-3-4(8)1-2-6(5)9;1-5(2,3)4/h1-3H,8-9H2;(H2,1,2,3,4)
Smiles:S(=O)(=O)(O)O.c1(c(ccc(c1)N)N)Cl

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

No data available

Route:

other: Not specified

Vehicle:

not specified

Concentration / amount:

Not specified

Day(s)/duration:

Not specified

Adequacy of induction:

not specified

No.:

#1

Route:

other: Not specified

Vehicle:

not specified

Concentration / amount:

Not specified

Day(s)/duration:

Not specified

Adequacy of challenge:

not specified

No. of animals per dose:

Not specified

Details on study design:

No data available

Challenge controls:

Not specified

Positive control substance(s):

not specified

Reading:

1st reading

Group:

test chemical

Dose level:

Not specified

Clinical observations:

Not specified

Remarks on result:

positive indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "S M W N"
Estimation method: Takes highest mode value from the 9 nearest neighbours
Domain  logical expression:Result: In Domain

((((((("a" or "b" or "c" or "d" or "e" )  and "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" )  )

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 Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines by DNA binding by OASIS v.1.3 ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Weak binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Anilines (amino-para) OR Anilines (Unhindered) OR Inorganic Compound by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found AND Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines AND SN1 AND SN1 >> Nucleophilic attack after metabolic nitrenium ion formation AND SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines by DNA binding by OASIS v.1.3 ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Aminoaniline, para AND Aniline AND Aryl AND Aryl halide AND No functional group found AND Precursors quinoid compounds by Organic Functional groups

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Aminoaniline, meta by Organic Functional groups

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Aminoaniline, para AND Aniline AND Aryl AND Aryl halide AND No functional group found AND Precursors quinoid compounds by Organic Functional groups

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Carboxylic acid by Organic Functional groups

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Aminoaniline, para AND Aniline AND Aryl AND Aryl halide AND No functional group found AND Precursors quinoid compounds by Organic Functional groups

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Aromatic amine by Organic Functional groups

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Aromatic amines AND Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.08

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.8

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Conclusions:

2-chlorobenzene-1,4-diammonium sulphate was considered to be sensitizing to skin of guinea pigs.

Executive summary:

The skin sensitization potential of 2-chlorobenzene-1,4-diammonium sulphate was estimated using OECD QSAR toolbox v3.3 with log Pow as the primary descriptor. 2-chlorobenzene-1,4-diammonium sulphate was estimated to be sensitizing to the skin of  guinea pigs. Based on the estimated results, 2-chlorobenzene-1,4-diammonium sulphate can be considered to be sensitizing to skin and can be classified under the category “ Category 1 (skin sensitizing) based on GHS criteria” as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Skin sensitization:

In different studies, 2-chlorobenzene-1,4-diammonium sulphate has been investigated for potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs along with human data for target chemical 2-chlorobenzene-1,4-diammonium sulphate and its structurally similar read across substances 2-methyl-p-phenylenediamine sulphate (CAS:615-50-9 ) and 2-Chloro-1,4-phenylenediamine (CAS: 615-66-7).

The predicted data using the OECD QSAR toolbox has also been compared with the experimental data. The skin sanitization potential of 2-chlorobenzene-1,4-diammonium sulphate was estimated using OECD QSAR toolbox v3.3 with log Pow as the primary descriptor. 2-chlorobenzene-1,4-diammonium sulphate was estimated to be sensitizing to the skin of  guinea pigs. Based on the estimated results, 2-chlorobenzene-1,4-diammonium sulphate can be considered to be sensitizing to skin and can be classified under the category “ Category 1 (skin sensitizing) based on GHS criteria” as per CLP regulation.

The above predicted data was supported by experimental study conducted by Christina L. Burnett et.al in International Journal of Toxicology 29 ( supplement 2) 2010 for the structurally similar read across substance 2-methyl-p-phenylenediamine sulphate (CAS:615-50-9 )

2-methyl-p-phenylenediamine sulphate was used as attest material to evaluate skin sensitization potential on the Hartley albino guinea pigs skin

  In the induction treatment the test material was applied in the concentration 1% in white petrolatum under occlusive patch to the nape of 10 guinea pigsfor 48 hrs three times per week for 2 weeks.The animals were given 2 weeks non treatment period after the induction treatment and before challenge treatment .

  The challenge treatment was givenunder occlusive patch to the flanks of the test animals for 48 hrs and the animals were observed for 24 and 48 hrs after the removal of test material. Sensitization rate for 0.1% test solution was 10% and 1% test solution was 40%. Positive skin sensitization reactions were observed. Hence,2-methyl-p-phenylenediamine sulphate  was considered to be sensitizing to guinea pig’s skin.

 The above experimental result was further supported by experimental study conducted by Lynn Willis in Journal of the American college of Toxicology Volume 11, Number 4,1992 for the structurally similar read across substance 2-Chloro-1,4-phenylenediamine (CAS: 615-66-7).

2-Chloro-1,4-phenylenediamine was used as a test material to evaluate its skin sensitization potential on fifteen Pirbright white guinea pigs using the maximization test of Magnusson and Kligman.

In induction period the test material was subjected in to the test animal by 5 intracutaneous injections of 0.3% in distilled water over a period of 5 days.Ten female Pirbright white guinea pigs, which received no injections, served as controls. Challenge was proceeded after 4 weeks of resting period.

In challenge treatment animal were applied with subcutaneous patch of test material in the concentration 0.003, 0.006, 0.03, and 0.3% ,and their reactions were scored after 24 and 48 h. A Student’s t-test was used to compare the skin reaction scores of the test and control animals.

Positive skin allergic reactions were observed. Hence,2-Chloro-1,4-phenylenediamine was considered to be skin sensitizing.

Based on the available data for the target as well as it read across substances and applying the weight of evidence approach, it can be concluded that 2-chlorobenzene-1,4-diammonium sulphate was sensitizing to skin. Itcan be classified under the category “Category 1 (skin sensitising) based on GHS criteria” as per CLP regulation

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available data for the target as well as it read across substances and applying the weight of evidence approach, it can be concluded that 2-chlorobenzene-1,4-diammonium sulphate was sensitizing to skin. Itcan be classified under the category “Category 1 (skin sensitising) based on GHS criteria” as per CLP regulation