2-aminobenzenesulphonic acid

Endpoint summary

Description of key information

The substance 2-aminobenzenesulphonic acid does not exhibit repeated dose toxicity by any of the route.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.1

GLP compliance:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

not specified

Route of administration:

oral: gavage

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

90 days

Frequency of treatment:

Daily

Control animals:

not specified

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Dose descriptor:

NOEL

Effect level:

331.33 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: Effects:no effects observed on clinical sign,body weight and haematology.

Critical effects observed:

not specified

The prediction was based on dataset comprised from the following descriptors: NOEL,LOEL
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

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

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 Aniline AND Aryl AND Sulfonic acid by Organic functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aniline AND Overlapping groups AND Sulfonic acid by Organic functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Nitrogen, one aromatic attach [-N] AND Aromatic Carbon [C] AND Hydroxy, sulfur attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Suflur {v+4} or {v+6} AND Sulfinic acid [-S(=O)OH] AND Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Amine AND Aromatic compound AND Primary amine AND Primary aromatic amine AND Sulfonic acid AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Radical AND Radical >> ROS formation after GSH depletion AND Radical >> ROS formation after GSH depletion >> Aromatic and Heterocyclic Primary Amines AND SN1 AND SN1 >> Nitrenium ion formation AND SN1 >> Nitrenium ion formation >> Aromatic and Heterocyclic Primary Amines by DNA binding by OASIS v.1.1 ONLY

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Aniline AND Aryl AND Sulfonic acid by Organic functional groups

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Aniline AND Overlapping groups AND Sulfonic acid by Organic functional groups (nested)

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Aliphatic Nitrogen, one aromatic attach [-N] AND Aromatic Carbon [C] AND Hydroxy, sulfur attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Suflur {v+4} or {v+6} AND Sulfinic acid [-S(=O)OH] AND Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA)

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Amine AND Aromatic compound AND Primary amine AND Primary aromatic amine AND Sulfonic acid AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Aniline AND Aryl AND Sulfonic acid by Organic functional groups

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Aniline AND Overlapping groups AND Sulfonic acid by Organic functional groups (nested)

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Aliphatic Nitrogen, one aromatic attach [-N] AND Aromatic Carbon [C] AND Hydroxy, sulfur attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Suflur {v+4} or {v+6} AND Sulfinic acid [-S(=O)OH] AND Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA)

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Amine AND Aromatic compound AND Primary amine AND Primary aromatic amine AND Sulfonic acid AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.1

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Carbamates OR Acylation >> Direct acylation involving a leaving group >> N-acylamides OR Acylation >> Direct acylation involving a leaving group >> N-acylsulphonamides OR Acylation >> Direct acylation involving a leaving group >> Sulphonyl halides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated alkyl or aryl esters OR Acylation >> Ester aminolysis or thiolysis >> Diarylesters OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> Active cyclic agents OR Michael addition 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 >> Michael addition on conjugated systems with electron withdrawing group >> Cyanoalkenes OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Nitroalkenes OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> N-sulfonylazomethyne compounds OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Vinyl sulfonyl compounds OR Michael addition >> Michael type addition on vinyl pirydines and activated ethenylarenes OR Michael addition >> Michael type addition on vinyl pirydines and activated ethenylarenes >> Activated electrophilic ethenylarenes OR Michael addition >> Michael type addition on vinyl pirydines and activated ethenylarenes >> Vinyl pyridines OR Michael addition >> Michael-type addition on azoxy compounds OR Michael addition >> Michael-type addition on azoxy compounds >> Azoxy compounds OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Naphtoquinone and naphtoquinone imines OR Michael addition >> Quinone type compounds >> Quinone (di)imines OR Michael addition >> Quinone type compounds >> Quinone methide imines OR Nucleophilic addition OR Nucleophilic addition >> Addition to Carbon-hetero double/triple bond OR Nucleophilic addition >> Addition to Carbon-hetero double/triple bond >> Azomethyne type compounds OR Nucleophilic addition >> Addition to Carbon-hetero double/triple bond >> Ketones OR Nucleophilic addition >> Addition to Carbon-hetero double/triple bond >> Thiocyanates OR Nucleophilic addition >> Nucleophilic addition at polarized N-functional double bond OR Nucleophilic addition >> Nucleophilic addition at polarized N-functional double bond >> C-Nitroso compounds OR Radical OR Radical >> Free radical formation OR Radical >> Free radical formation >> Organic peroxy compounds OR Schiff base formation OR Schiff base formation >> Pyrazolones and pyrazolidinones derivatives OR Schiff base formation >> Pyrazolones and pyrazolidinones derivatives >> Pyrazolones and pyrazolidinones OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Azoxy compounds-forming carbenium ion OR SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Activated alkyl esters OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> alpha-haloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Phosphonates OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Thiophosphates OR SN2 >> Nucleophilic substitution at sulfur atom OR SN2 >> Nucleophilic substitution at sulfur atom >> Thiosulfate compounds OR SN2 >> Nucleophilic substitution on heterocyclic sulfenamides OR SN2 >> Nucleophilic substitution on heterocyclic sulfenamides >> Heterocyclic sulfenamides OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Isothiazolones derivatives OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated halogens OR SNAr >> Nucleophilic aromatic substitution on activated halogens >> Activated haloarenes by Protein binding by OASIS v1.1

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Amine AND Aromatic compound AND Primary amine AND Primary aromatic amine AND Sulfonic acid AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "u"

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

Domain logical expression index: "v"

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

Conclusions:

The 90 days sub-chronic repeated dose study on rat by oral route indicated that no effects observed on clinical sign,body weight and haematology.
Thus, on the basis of study results the NOAEL (No observed adverse effect level) was observed to be 331.33 mg/kg/day

Executive summary:

The repeated dose toxicity by oral route NOAEL for CAS no. 88-21-1 is estimated to be 994mg/kg bw/day (when converted to sub-chronic become 331.33 mg/kg bw/day) for rat using the toolbox version 3.2. The data is estimated to be based on the data summarized below:

CAS no.	End point	Value	Species	Route	Duration	Effects
121-47-1	NOAEL	1000 mg/kg bw/day	Rat	oral: feed	48 days	Body weight increased
88-44-8	NOAEL	1000 mg/kg bw/day	Rat	oral: feed	48 days	Food consumption increased

 

All the values when equalized to 90 days duration by using conversion factor of 3.

CAS no.	End point	Value	Duration
121-47-1	NOEL	333.33mg/kg bw/day	90 days
88-44-8	NOEL	333.33mg/kg bw/day	90 days

 

Thus the calculated NOAEL of analogues for 90 days for the species rat is 333.33 mg/kg bw /day. Thus the predicted NOAEL value is (calculated to be) 333.33 mg/kg bw/d with 90 days for rat (harmonized using assessment factors) falls within the domain using Log Kow as the descriptor and justified to be used as NOAEL for further DNEL calculation for the purpose of risk assessment. Also it does not impact the classification of the substance thus the predicted value considered to be acceptable. 

Justified to be used as NOAEL for the purpose of weight of evidence

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

331.33 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

The data is K2 level as the data has been obtained from QSAR model considered by OECD.

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

other:

Critical effects observed:

not specified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: dermal

Data waiving:

other justification

Justification for data waiving:

other:

Critical effects observed:

not specified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose toxicity oral:

No. of studies were reviewed for repeated dose oral toxicity with Klimish rating 2 and 4 of the target (2-aminobenzenesulphonic acid) and read across substances.

The results for target and read across substances are summarized as follows

Sr. No	End point	Value	Species/strain	Route	Effects	Remarks
1.	NOEL	331.33 mg/kg/day	Rat (Sprague-Dawley)	oral: gavage	No effects observed on clinical sign, body weight and haematology.	Predicted data from QSAR for target CAS:88-21-1
2.	NOAEL	300mg/kg/day bw	Rat (Sprague-Dawley)	oral: gavage	No change in mortality and behavior were observed in any groups.body weight and food consumption: No toxic effect was observed in any groups.	Experimental data from study report for read across CAS:88 -44 -8

 

Based on the studies summarized in the above table with oral routes it can be observed that the endpoint No observed adverse effect value (NOAEL) varies from 300mg/kg/day bw to 331.33 mg/kg/day based on the data from prediction for target substance and from publication for read across. The effect observed on the above doses are-

 * No effects observed on clinical sign, body weight and haematology.

* No change in mortality and behavior were observed in any groups.body weight and food consumption: No toxic effect was observed in any groups.

 

Based on the above results it can be concluded that the no observed effect level (NOEL) for target substance is 331.33 mg/kg/day and no observed adverse effect level (NOAEL) for read across substance is 300mg/kg/day bw, thus based on this value it can be concluded that substance CAS: 88-21-1(2-aminobenzenesulphonic acid) is considered to be not toxic to repeated dose via oral route up to the above mentioned doses as per the CLP criteria.  

Repeated dose toxicity: inhalation

For 2-aminobenzenesulphonic acid, repeated dose toxicity testing by the inhalation route was considered for waiver given that the substance has low vapour pressure of 0.000027 at 25 degC as well as the particle size distribution indicates that the majority particle size is 150 (62.80%) - 300 (17.83%) micro meter. Thus, exposure by inhalation route is also unlikely for 2-aminobenzenesulphonic acid given the comparatively larger size of the particulates.

Repeated dose toxicity: dermal

Repeated dermal toxicity is unlikely to occur since dermal absorption of 2-aminobenzenesulphonic acid is very low based on the value 0.00027 mg/cm2/event. Thus, given considerations, it is assumed that 2-aminobenzenesulphonic acid shall not exhibit repeated dose toxicity by the dermal route.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:

The 90 days sub-chronic repeated dose study on rat by oral route indicated that no effects observed on clinical sign,body weight and haematology.

Thus, on the basis of study results the NOAEL (No observed adverse effect level) was observed to be 331.33 mg/kg/day bw.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:

For 2-aminobenzenesulphonic acid, repeated dose toxicity testing by the inhalation route was considered for waiver given that the substance has low vapour pressure of 0.000027 at 25 degC as well as the particle size distribution indicates that the majority particle size is 150 (62.80%) - 300 (17.83%) micro meter. Thus, exposure by inhalation route is also unlikely for 2-aminobenzenesulphonic acid given the comparatively larger size of the particulates.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:

Repeated dermal toxicity is unlikely to occur since dermal absorption of 2-aminobenzenesulphonic acid is very low based on the value 0.00027 mg/cm2/event. Thus, given considerations, it is assumed that 2-aminobenzenesulphonic acid shall not exhibit repeated dose toxicity by the dermal route.

Justification for classification or non-classification

The substance 2-aminobenzenesulphonic acid do not show repeated dose toxicity effect for oral,dermal and inhalation route and thus will not be considered for further classification.

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