2-aminobenzenesulphonic acid

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records

Reference

Endpoint:

toxicity to reproduction

Remarks:

other: screen test

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.1

GLP compliance:

no

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Route of administration:

oral: gavage

Type of inhalation exposure (if applicable):

not specified

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:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Histopathological findings: non-neoplastic:

not specified

Other effects:

not specified

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

Dose descriptor:

NOAEL

Effect level:

333.33 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Effects:No adversed effects observed on reproduction performance of parents.

Remarks on result:

other: not specified

Critical effects observed:

not specified

System:

other: not specified

Clinical signs:

not specified

Mortality / viability:

not specified

Body weight and weight changes:

not specified

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings:

not specified

Remarks on result:

not measured/tested

Reproductive effects observed:

not specified

Treatment related:

not specified

The prediction was based on dataset comprised from the following descriptors: NOAEL
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" )  )

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"

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

Domain logical expression index: "u"

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

Conclusions:

No observed adversed effect level (NOAEL) for reproductive toxicity to rat for 90 days was predicted to be 333.33 mg/kg bw/day.

Executive summary:

The reproductive toxicity by oral route NOAEL for CAS no. 88-21-1 is estimated to be1000mg/kg bw/day (when converted to sub-chronic become 333.33 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	-
88-44-8	NOAEL	1000 mg/kg bw/day	Rat	oral: feed	48 days	No effects were observed in copulation index, fertility index, gestation Iength, number of corpora Iutea, implantations, implantation index, gestation index, parturition or maternal behaviour.

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

CAS no.	End point	Value	Duration
Target 88-21-1	NOEL	333.33mg/kg bw/day	90 days
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 NOEL of analogues for 90 days for the species rat is 333.33 mg/kg bw /day. Thus the predicted NOEL 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 NOEL 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 NOEL for the purpose of weight of evidence

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

333.33 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.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

WoE Summary of 88-21-1 for toxicity to reproduction

Based on the studies available with Klimish rating 2 and 4 for the target as well as the read across substances for CAS: 88-21-1 based on the category approach of organic functional group along with similar mechanistic approach and having structural similarities defined by QSAR toolbox.

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

Sr. No	End point	Value	Species	Route	Effects	Remarks
1.	NOAEL	333.33 mg/kg bw/day	Rat (Crj: CD(SD))	oral: gavage	No adverse effects observed on reproduction performance of parents.	Predicted data from QSAR for target CAS: 88-21-1
2.	NOAEL	1000 mg/kg bw/day	Rat (Crj: CD(SD))	oral: gavage	No effects were observed in the copulation index, fertility index, gestation length, number of corpora lutea or implanations, implanation index,gestation index, parturition or maternal behavior.	Experimental data from study report for read across CAS:88-44-8

 

 

Based on the studies summarized in the above table it can be observed that the endpoint no observed effect value NOAEL = 333.33 mg/kg bw/day to 1000 mg/kg bw/day based on the data from prediction as well as publication for target &read across substance. The effect observed on the above doses are-

* No adverse effects observed on reproduction performance of parents.

* No effects were observed in the copulation index, fertility index, gestation length, number of corpora lutea or implanations, implanation index,gestation index, parturition or maternal behavior.

Thus based on the above results it can be concluded that substance CAS: 88-21-1 is expected to show the similar toxicological effect based on the effects observed on the other category members. Since no observed adverse effective dose value (NOAEL) is 333.33 mg/kg bw/day thus based on this value it can be concluded that substance CAS: 88-21-1 is considered to be not toxic to reproduction up to the dose level of 333.33 mg/kg bw/day as per the CLP criteria.

Short description of key information:

Study indicates that 2-aminobenzenesulphonic acid does not exhibit toxic effects to rat.

Justification for selection of Effect on fertility via oral route:

No observed adversed effect level (NOAEL) for reproductive toxicity to rat for 90 days was predicted to be 333.33 mg/kg bw/day.

Effects on developmental toxicity

Description of key information

2-aminobenzenesulphonic acid does not exhibit any teratogenic effects.

Link to relevant study records

Reference

Endpoint:

developmental toxicity

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.1

GLP compliance:

no

Species:

rat

Strain:

Sprague-Dawley

Route of administration:

oral: gavage

Type of inhalation exposure (if applicable):

not specified

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Frequency of treatment:

Daily

Duration of test:

90 days

Control animals:

not specified

Details on maternal toxic effects:

Maternal toxic effects:no data

Dose descriptor:

other: not specified

Based on:

not specified

Basis for effect level:

other: not specified

Remarks on result:

other: not specified

Abnormalities:

not specified

Localisation:

not specified

Description (incidence and severity):

not specified

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
No external anomalies were observed in newborns,overall no effects observed on fetus development.

Dose descriptor:

NOAEL

Effect level:

164.79 mg/kg bw/day

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: fetotoxicity

Remarks on result:

other: not specified

Abnormalities:

not specified

Localisation:

other: not specified

Description (incidence and severity):

not specified

Developmental effects observed:

not specified

Treatment related:

not specified

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

("a" and ("b" and "c" ) )

Domain logical expression index: "a"

Similarity boundary:Target: c1(S(=O)(=O)O)c(N)cccc1
Threshold=50%,
Dice(Atom centered fragments)

Domain logical expression index: "b"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.09

Domain logical expression index: "c"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.34

Conclusions:

The fetotoxicity NOAEL (No observable adverse effect level) of 2-aminobenzenesulphonic acid in Sprague-Dawley rats for 90 days was observed at a dose concentration of 164.79 mg/kg bw/day.

Executive summary:

The NOAEL for 2-aminobenzenesulphonic acid is estimated to be 494.399 mg/kg bw/day for Rat (when converted to sub-chronic study it become 164.79 mg/kg bw/day) using the toolbox version 3.2. The data is estimated to be based on the data summarized below

CAS no.	End point	Value	Species	Doses	Duration	Effects
121-57-3	NOAEL	1000mg/kg bw/day	Rat	62.5,250 and 1000 mg/kg bw/day	63 days	not produce any pathological evidence of local or systemic toxicity of the test item or any toxic effects on the development and reproduction
121-03-9	NOAEL	350 mg/kg bw/day	Rat	0, 175, 350, 700mg/kg bw/day	50 days	no external anomalies were observed in newborns
62-53-3	NOAEL	560 mg/kg bw/day	Rat	-	22 days	No apparent effect on the number of live litters produced and on liveborn pups per litter.
2243-62-1	NOAEL	2mg/kg bw/day	Rat	0, 2, 10 or 50 mg/kg bw/day	20 days	No effects observed on developmental toxicity

  

  All the values when equalized to 90 days duration by using conversion factor of 2 and 3

CAS no.	End point	Value	Duration
121-57-3	NOAEL	500 mg/kg bw/day	90 days
121-03-9	NOAEL	175 mg/kg bw/day	90 days
62-53-3	NOAEL	186.66 mg/kg bw/day	90 days
2243-62-1	NOAEL	0.666mg/kg bw/day	90 days

 

Thus the calculated NOAEL of analogues for 90 days for the species rat is within the range of0.666-500 mg/kg bw/day. Thus the predicted NOAEL value is (calculated to be) 215.58 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

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

164.79 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.

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

WoE Summary of 88-21-1 for developmental toxicity

Based on the studies available with Klimish rating 2 and 4 for the target as well as the read across substance for CAS: 88-21-1 based on the category approach of organic functional group along with similar mechanistic approach and having structural similarities defined by QSAR toolbox.

The results for target as well as analogues are summarized as follows

Sr. No	End point	Value	Species	Route	Effects	Remarks
1	NOAEL	164.79 mg/kg bw/day	Rat (Sprague-Dawley)	oral: gavage	No external anomalies were observed in newborns,overall no effects observed on fetus development.	Predicted data from QSAR for target CAS: 88-21-1
2	NOAEL	1000 mg/kg bw/day	Rat (Sprague-Dawley)	oral: gavage	There were no significant differences in number of offspring or live offspring, sex ratio, the live birth index, the viability index and the body weight. No abnormal findings related to the test substance were noted for external features, clinical signs, or on necropsy finding for the offspring. No pups with malformation were found in any group. No change in clinical signs and necropsy finding were observed in offspring.	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 found to vary between 164.79 mg/kg bw/day to 1000 mg/kg bw/day based on the data from prediction as well as publication for target &read across substance. The effect observed on the above doses are-

* No external anomalies were observed in newborns, overall no effects observed on fetus development.

* There were no significant differences in number of offspring or live offspring, sex ratio, the live birth index, the viability index and the body weight. No abnormal findings related to the test substance were noted for external features, clinical signs, or on necropsy finding for the offspring. No pups with malformation were found in any group. No change in clinical signs and necropsy finding were observed in offspring.

 

Thus based on the above results it can be concluded that substance CAS: 88-21-1 is expected to show the similar toxicological effect based on the effects observed on the other category members. Since no observed adverse effective dose value (NOAEL) is164.79 mg/kg bw/day thus based on this value it can be concluded that substance CAS: 88-21-1 is considered to be not toxic to fetus up to the dose level of 164.79 mg/kg bw/day as per the CLP criteria.

Justification for selection of Effect on developmental toxicity: via oral route:

The fetotoxicity NOAEL (No observable adverse effect level) of 2-aminobenzenesulphonic acid in Sprague-Dawley rats for 90 days was observed at a dose concentration of 164.79 mg/kg bw/day.

Justification for classification or non-classification

The chemical 2-aminobenzenesulphonic acid does not exhibit reproduction as well as developmental toxicity within the doses mentioned in the study end points thus not cosidered for further classification.