1,4-diamino-2,3-dichloroanthraquinone

Endpoint summary

Description of key information

The skin sensitization potential of 1,4-diamino-2,3-dichloroanthraquinone (81-42-5) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances 1,4-diamino-2,3-dichloroanthraquinone (81-42-5) was predicted to be not sensitizing to the skin of female Dunkin-Hartley guinea pig.

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:

equivalent or similar to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3, 2017

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

No data available

Specific details on test material used for the study:

Name of the test chemical: 1,4-diamino-2,3-dichloroanthraquinone
Molecular formula: C14H8Cl2N2O2
Molecular weight: 307.135 g/mol
Smiles Notation: c1cc2c(cc1)C(=O)c1c(c(c(c(c1N)Cl)Cl)N)C2=O
InChI: 1S/C14H8Cl2N2O2/c15-9-10(16)12(18)8-7(11(9)17)13(19)5-3-1-2-4-6(5)14(8)20/h1-4H,17-18H2
Substance Type: Organic
Physical State: Solid crystal powder (purple-black)

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

No data available

No. of animals per dose:

No data available

Details on study design:

No data available

Challenge controls:

No data available

Positive control substance(s):

not specified

Statistics:

No data available

Positive control results:

No data available

Reading:

1st reading

Group:

test chemical

No. with + reactions:

0

Clinical observations:

No skin sensitization reaction was 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 6 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aminoaniline, para OR Anthracenone/ Antracendione OR Aryl halide OR Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Amine OR Aromatic compound OR Aryl chloride OR Aryl halide OR Carbonyl compound OR Halogen derivative OR Ketone OR Primary amine OR Primary aromatic amine by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "c"

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

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for skin sensitization by OASIS v1.3

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Michael Addition OR Michael Addition >> alpha,beta-Unsaturated carbonyl compounds OR Michael Addition >> alpha,beta-Unsaturated carbonyl compounds >> alpha,beta-Aldehydes  OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  OR Michael Addition >> Polarised Alkenes OR Michael Addition >> Polarised Alkenes >> Polarised Alkene - alkenyl pyridines, pyrazines, pyrimidines or triazines  OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Schiff base formation OR Schiff base formation >> Direct acting Schiff base formers OR Schiff base formation >> Direct acting Schiff base formers >> 1,2-Dicarbonyls and 1,3-Dicarbonyls  OR SN2 OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Epoxides, Aziridines and Sulfuranes  OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds OR SNVinyl OR SNVinyl >> SNVinyl at a vinylic (sp2) carbon atom OR SNVinyl >> SNVinyl at a vinylic (sp2) carbon atom >> Vinyl type compounds with electron withdrawing groups  by Protein binding alerts for skin sensitization by OASIS v1.3

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CNHal Lipid Solubility < 400 g/kg AND Group All Melting Point > 200 C AND Group CNHal Aqueous Solubility < 0.004 g/L AND Group CNHal Aqueous Solubility < 0.1 g/L AND Group CNHal log Kow > 3.8 by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Aqueous Solubility < 0.0005 g/L OR Group C Melting Point > 55 C OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CNS log Kow > 1.5 OR Group CNS Melting Point > 50 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (with extensions) ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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 SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Canada DSL AND ECHA PR AND EINECS AND METI Japan AND NICNAS AND REACH ECB AND TSCA AND US HPV Challenge Program by Inventory Affiliation

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as DSSTOX by Inventory Affiliation

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= 3.02

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.63

Interpretation of results:

other: not sensitizing

Conclusions:

The skin sensitization potential of 1,4-diamino-2,3-dichloroanthraquinone (81-42-5) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances 1,4-diamino-2,3-dichloroanthraquinone (81-42-5) was predicted to be not sensitizing to the skin of female Dunkin-Hartley guinea pig.

Executive summary:

The skin sensitization potential of 1,4-diamino-2,3-dichloroanthraquinone(81-42-5)was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances 1,4-diamino-2,3-dichloroanthraquinone(81-42-5)was predicted to be not sensitizing to the skin of female Dunkin-Hartley guinea pig.

 

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization 

In different studies, 1,4-diamino-2,3-dichloroanthraquinone(81-42-5)has been investigated for potential of skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pig and human for target chemical 1,4-diamino-2,3-dichloroanthraquinone(81-42-5) and its structurally similar read across substances1,4-bis(p-tolylamino)anthraquinone(128-80-3)andD&C Violet 2(81-48-1),the predicted data using the OECD QSAR toolbox has also been compared with the experimental data of read across.

The skin sensitization potential of 1,4-diamino-2,3-dichloroanthraquinone(81-42-5)was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances 1,4-diamino-2,3-dichloroanthraquinone(81-42-5)was predicted to be not sensitizing to the skin of female Dunkin-Hartley guinea pig.

 

 Also these results are further supported by the experimental study conducted in an OECD GLP laboratory (Sustainability Support Services (Europe) AB has the letter of access) for the structurally similar read across substance,1,4-bis(p-tolylamino)anthraquinone(128-80-3). The contact allergenic potential of SANDOPLAST GREEN GSB (1,4-bis(p-tolylamino)anthraquinone) was studied by LLNA method in three groups each of four female mice were treated daily with the test item at concentrations of 2.5 %, 5% and 10% (w/v) in acetone/olive oil (4/1, v/v) by topical application to the dorsum of each ear lobe (left and right) for three consecutive days. 10 % was the highest technically applicable concentration in the vehicle.A control group of four mice was treated with the vehicle (acetone/olive oil (4/1, v/v)) only.Five days after the first topical application the mice were injected intravenously into a tail vein with radio-labelled thymidine (3H-methyl thymidine). Approximately five hours after intravenous injection, the mice were sacrificed, the draining auricular lymph nodes excised and pooled per group. Single cell suspensions of lymph node cells were prepared from pooled lymph nodes which were subsequently washed and incubated with trichloroacetic acid overnight. The proliferative capacity of pooled lymph node cells was determined by the incorporation of 3H-methyl thymidine measured in a ß-scintillation counter. All treated animals survived the scheduled study period. No clinical signs were observed in any animals of the control group. After the first application, both ears of all test item groups of mice (Groups 2-4) showed black at dosing sites, persisting for the remainder of the in-life phase of the study. In this study STIMULATION INDICES of 1.8, 0.8 and 1.2 were determined with the test item at concentrations of 2.5 %, 5 % and 10 % (w/v) , respectively, in acetone/olive oil (4/1 (v/v). Hence the test item SANDOPLAST GREEN GSB (1,4-bis(p-tolylamino)anthraquinone) was considered to be a non-sensitizer when tested at up to the highest applicable concentration of 10 % (w/v) in acetone/olive oil (4/1 (v/v).

Supported by experimental study conducted by Guin JD(Contact Dermatitis 2003: 49: 217–218) to evaluate the skin sensitizing potential of read across substance D&C Violet 2(81-48-1)in human. The sensitization potential of D&C Violet was determined by performing patch tests on humans. The dye was applied as 2%concentration in petrolatum in Finn Chambers and read first at 2 or (more commonly) 3 days and again at 4–7 days. The reactions of the patients were graded as ‘?+ ‘ , ‘+’ and ‘++’ categories. 27 patients were tested with the dye. None of the patients showed any reactions to dye.  The sensitizing potential of D&C Violet 2(81-48-1) can be considered non- sensitizing to humans.

 Thus based on the above predictions on 1,4-diamino-2,3-dichloroanthraquinone(81-42-5)as well as its read across and applying weight of evidence, it can be concluded that 1,4-diamino-2,3-dichloroanthraquinone(81-42-5) is not a skin sensitizer. Thus comparing the above studies with the criteria of CLP regulation, 1,4-diamino-2,3-dichloroanthraquinone(81-42-5)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, 1,4-diamino-2,3-dichloroanthraquinone(81-42-5)can be considered as not classified for skin sensitization.