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Administrative data

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records
Reference
Endpoint:
one-generation reproductive toxicity
Remarks:
based on test type (migrated information)
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data is from QSAR Toolbox 3.4.
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.4
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
No data avaialble
Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
not specified
Vehicle:
water
Details on exposure:
No data avaialble
Details on mating procedure:
No data avaialble
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data avaialble
Duration of treatment / exposure:
54 days
Frequency of treatment:
daily
Details on study schedule:
No data avaialble
Remarks:
Doses / Concentrations:No data avaialble Basis:
No. of animals per sex per dose:
No data avaialble
Control animals:
not specified
Details on study design:
No data avaialble
Positive control:
No data avaialble
Parental animals: Observations and examinations:
No data avaialble
Oestrous cyclicity (parental animals):
No data avaialble
Sperm parameters (parental animals):
No data avaialble
Litter observations:
No data avaialble
Postmortem examinations (parental animals):
No data avaialble
Postmortem examinations (offspring):
No data avaialble
Statistics:
No data avaialble
Reproductive indices:
No data avaialble
Offspring viability indices:
No data avaialble
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 examined
Reproductive function: oestrous cycle:
not examined
Reproductive function: sperm measures:
not examined
Reproductive performance:
not specified
No data avaialble
Dose descriptor:
NOAEL
Effect level:
691.8 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No effect on reproductive performance
Remarks on result:
other: not specified
Critical effects observed:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified
Dose descriptor:
other: not specified
Based on:
test mat.
Sex:
not specified
Remarks on result:
other: not specified
Critical effects observed:
not specified
System:
other: not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified
Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Sexual maturation:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not specified
Histopathological findings:
not examined
No data avaialble
Dose descriptor:
other: not specified
Generation:
other: not specified
Based on:
not specified
Sex:
not specified
Remarks on result:
other: not specified
Critical effects observed:
not specified
System:
other: not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified
Dose descriptor:
other: not specified
Generation:
other: not specified
Based on:
not specified
Sex:
not specified
Remarks on result:
other: not specified
Critical effects observed:
not specified
System:
other: not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified
Reproductive effects observed:
not specified
Treatment related:
not specified
Relation to other toxic effects:
not specified
Dose response relationship:
not specified
Relevant for humans:
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 ( not "g") )  )  and ("h" and "i" )  )

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 Aminoaniline, meta AND Aniline AND Aryl AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aminoaniline, meta 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 No alert found by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael addition to activated double bonds in heterocyclic ring systems OR AN2 >> Michael addition to activated double bonds in heterocyclic ring systems >> Pyrazolone and Pyrazolidine Derivatives OR AN2 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> Substituted Anilines OR AN2 >> Shiff base formation with carbonyl compounds OR AN2 >> Shiff base formation with carbonyl compounds >> Pyrazolone and Pyrazolidine Derivatives by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of logP Multicase which is >= -7.14

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of logP Multicase which is <= 4.24

Conclusions:
estimated NOAEL was considered to be 691.8 mg/kg bw when Wistar male and female rats were treated with 2,4-diaminobenzenesulfonic acid orally by gavage for 54 days.
Executive summary:
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Reproductive toxicity was estimated using QSAR Toolbox 3.4.(2016) in Wistar male and female rats by using 2,4-diaminobenzenesulfonic acid orally by gavage. No effects on reproductive performance of treated male and female rats were observed. Therefore, estimated NOAEL was considered to be 691.8 mg/kg bw when Wistar male and female rats were treated with 2,4-diaminobenzenesulfonic acid orally by gavage for 54 days.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
691.8 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Data is Klimisch 2 and from QSAR Toolbox 3.4
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Reproductive toxicity:

Based on the data available for target 2,4-diaminobenzenesulphonic acid (CAS no 88-63-1) and its read across 2- Amino-5-Methylbenzenesulfonic Acid (CAS no 88-44-8) are summarized below

Based on the prediction done by using QSAR Toolbox 3.4.(2016), reproductive toxicity was estimated in Wistar male and female rats by using 2,4-diaminobenzenesulfonic acid orally by gavage. No effects on reproductive performance of treated male and female rats were observed. Therefore, estimated NOAEL was considered to be 691.8 mg/kg bw when Wistar male and female rats were treated with 2,4-diaminobenzenesulfonic acid orally by gavage for 54 days.

In a study given by Ministry of Health, Labour, Welfare and Environment J-CHECK - (2016) for read across,reproductive toxicity was evaluated in Crj: CD (SD) male and female rats by using2- Amino-5-Methylbenzenesulfonic Acid in the concentration of0, 100, 300 and 1000 mg/kg/bw/day orally by gavage in Sesame oil. No effect on survival of treated male and female rats were observed. In amle rats, ocular secretion in 1 rat at 100 mg /kg, hair loss in 1 rat at 300 mg /kg and Crust and hair loss were observed in 1 in case at 1000 mg/kg. In female rats, hair removal was observed in 100 mg/kg group through pregnancy and nursing periods, and in the control group, all the dead animals were found in 2 cases. No clinical signs were observed in treated male and female rats due to treatment as compared to control.In female rats, at 100 and 1000 mg / kg, statistically significant decrease in body weight only at 4th day of nursing was observed as compared to the control. However, since there was no obvious difference on the other measurement days and it was a change only for 1 day, and since there was no obvious change in body weight gain during the nursing period, the influence of administration of the test substance It was not thought to be an accidental change.In male rats, statistically significant increase in food consumption from 8 to 15 days cumulative food intake from 1 to 15 days were observed at 1000 mg / kg bw and in female rats, no significant effect was observed as compared to control. Similarly, no reproductive toxic effect were observed onestrous cycle, corpus luteums, number of implantation traces, number of births and number of stillborn, gestation index, implantation rate, delivery rate, livebirth rate and mating rate of treated rats as compared to control. In addition,statistically significant decrease in absolute weights of epididymiswere observedin male rats but no effect on relative weight of epididymis were observed at 300 and 1000 mg/kg bw as compared to contorl.No significant changes were observed intesticular weigth of treated male rats as compared to control. In male rats, black lesions on lung in 1 animal, red spots of the liver, testis, epididymis and thinning of the coat in 1 case of the same individual gropue were observed at 300 mg/kg bw and thinning of the coat 1 case of the same individual gropue were observed at 1000 mg/kg bw. In female rats, black spots in lung stomach ulcers and white spots of the adrenal glands in 1 case each at 1000 mg/kg bw and ovary cyst and coat thinning were observed in 1 case each at 100 mg/kg bw. No findings that could be attributed to administration of the test substance were observed in any of the animals. In male rats, one case skin erosion and squamous epithelium hyperplasia and cell infiltration of epididymis at 1000 mg / kg, seminiferous tubular, testicular and epididymal atrophy of testes, stromal cell proliferation, spermatozoa of epididymis, lung inflammation and liver necrosis at 300 mg / kg were observed. However, since it is low frequency expression, it was not considered to be influence of the test substance. In female rats, 1 case of the lung inflammation, 1 case of the stomach ulcer, 1 part of the adrenal cortex and atrophy of the thymus at 1000 mg/kg bw, 1 case of atrophy of the thymus at 300 mg/kg bw and Young yolk sac cysts in one case, inflammatory infiltration of the skin and squamous epithelium proliferation were observed in one at 100 mg/kg bw, spontaneously delivered, so it was considered that there was no effect on the ovaries of the test substance. Atrophy of the thymus and purulent inflammation of the uterus were observed in one case in all the dead animals. No abnormal findings were observed in the other case. Therefore, NOAEL was considered to be 1000 mg/kg bw for P and F1 generation when Crj: CD (SD) male and female rats were treated with2- Amino-5-Methylbenzenesulfonic Acid orally by gavage inSesame oil for 28 days.

In a similar source study given for read across, repeated dose oral toxicity was evaluated in Crj: CD (SD) male and female rats by using 2- Amino-5-Methylbenzenesulfonic Acid in the concentration of 0, 100, 300 and 1000 mg/kg/bw/day orally by gavage in Sesame oil for 28 days. No effect on survival and clinical signs were observed in treated male and female rats as compared to control. No significant effects on body weight and body weight gain and food consumption were observed in treated male and female rats as compared to control. Significant decrease in white blood cell count was observed in males as compared to control. Decrease in white blood cell count was mainly due to the decrease in lymphocytes in view of the percentage of white blood cells at 1000 mg/kg bw. Significant decrease in total cholesterol in male, and significant increase in GPT and significant decreases in blood glucose were observed in female at 1000 mg/kg bw and significant decreases in blood glucose were observed in female rats at 100 mg/kg bw. Reduction in blood glucose was not observed in the 300 mg / kg bw and was a lack of dose correlation, but the value in the 1000 mg / kg group was clearly lower than that in the control group. Significant increase in specific gravity and decrease in pH were observed in male rats at 1000 mg/kg bw as compared to control. No significant change in hematology, clinical chemistry and Urinanalysis was observed in recovery group at 1000 mg/kg bw. Similarly, significant decrease in absolute and relative weights of thymus and significant increase in relative weight of spleen were observed in female rats at 100 mg/kg bw and significant increase in relative weight of spleen were observed in female rats at 300 and 1000 mg/kg bw, but the observed effects were dose dependent and considered as non significant. No significant changes were observed in testis, epididymis, and prostate and ovaries weigth of treated male and femlae rats as compared to control. In addition, Mild dilatation due to cecal contents retention was observed in each male and female rats but in recovery, no change in the cecum were observed at 1000 mg/kg bw. Mild changes in the lung, liver, pancreas, kidney and prostate were observed in the control group and 1000 mg / kg bw group, but findings that were sporadic and did not show dose correlation and were judged to be accidental changes. No gross pathological and histopathological changes were observed in testicle, epididymis, seminal vesicle, ovary and vagina of 1000 mg/kg bw treated male and female rats were observed as compared to control. Therefore, NOAEL was considered to be 1000 mg/kg bw for P generation when Crj: CD (SD) male and female rats were treated with 2- Amino-5-Methylbenzenesulfonic Acid orally by gavage in Sesame oil for 28 days.

Thus, based on weight of evidence for target 2,4-diaminobenzenesulphonic acid (CAS no 88-63-1) and its read across and 2- Amino-5-Methylbenzenesulfonic Acid (CAS no 88-44-8) is likely to be non hazardous as reproductive toxicant.

Short description of key information:

2,4-diaminobenzenesulphonic acid (CAS no 88-63-1) is likely to be non hazardous as reproductive toxicant.

Justification for selection of Effect on fertility via oral route:

estimated NOAEL was considered to be 691.8 mg/kg bw when Wistar male and female rats were treated with 2,4-diaminobenzenesulfonic acid orally by gavage for 54 days.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on weight of evidence for target 2,4-diaminobenzenesulphonic acid (CAS no 88-63-1) and its read across and 2- Amino-5-Methylbenzenesulfonic Acid (CAS no 88-44-8) is likely to be non hazardous as reproductive toxicant.