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EC number: 240-834-4 | CAS number: 16803-97-7
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Description of key information
The NOAEL was estimated to be 605 mg/kg bw when Crl:CD(SD)IGS BR VAF/Plus female rats were orally exposed with 4-amino-N-(4-aminophenyl)benzene-1-sulfonamide.
Thus, as per criteria of CLP regulation, 4-amino-N-(4-aminophenyl)benzene-1-sulfonamide can be Not classified for reproductive toxicity.
Link to relevant study records
- Endpoint:
- toxicity to reproduction
- 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 predicted using OECD QSAR toolbox version 3.4 and the supporting QMRF report has been attached
- Qualifier:
- according to guideline
- Guideline:
- other: as below
- Principles of method if other than guideline:
- Prediction is done using QSAR Toolbox version 3.4
- GLP compliance:
- not specified
- Limit test:
- no
- Specific details on test material used for the study:
- - Name of test material : 4-amino-N-(4-aminophenyl)benzenesulphonamide
- Molecular formula : C12H13N3O2S
- Molecular weight : 263.32 g/mol
- Smiles notation : O=S(=O)(c1ccc(cc1)Nc1ccc(cc1)N)N
- InChl : 1S/C12H13N3O2S/c13-9-1-3-10(4-2-9)15-11-5-7-12(8-6-11)18(14,16)17/h1-8,15H,13H2,(H2,14,16,17)
- Substance type : Organic
- Physical state : Solid - Species:
- rat
- Strain:
- other: Crl:CD(SD)IGS BR VAF/Plus
- Sex:
- female
- Route of administration:
- oral: gavage
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- CMC (carboxymethyl cellulose)
- Remarks:
- 0.5%
- Details on exposure:
- not specified
- Details on mating procedure:
- not specified
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 15 days prior mating and for 17 days thereafter.
- Frequency of treatment:
- Daily
- Details on study schedule:
- not specified
- Dose / conc.:
- 605 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 25 females
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- not specified
- Positive control:
- not specified
- Parental animals: Observations and examinations:
- not specified
- Oestrous cyclicity (parental animals):
- not specified
- Sperm parameters (parental animals):
- not specified
- Litter observations:
- not specified
- Postmortem examinations (parental animals):
- not specified
- Postmortem examinations (offspring):
- not specified
- Statistics:
- not specified
- Reproductive indices:
- not specified
- Offspring viability indices:
- not specified
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- not specified
- Dose descriptor:
- NOAEL
- Effect level:
- 605 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- histopathology: non-neoplastic
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- 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
- Other effects:
- not specified
- Behaviour (functional findings):
- not specified
- Developmental immunotoxicity:
- not specified
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 605 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- mortality
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- 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
- Conclusions:
- NOAEL was estimated to be 605 mg/kg bw when Crl:CD(SD)IGS BR VAF/Plus female rats were orally exposed with 4-amino-N-(4-aminophenyl)benzene-1-sulfonamide.
- Executive summary:
In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 4-amino-N-(4-aminophenyl)benzene-1-sulfonamide. The NOAEL was estimated to be 605 mg/kg bw when Crl:CD(SD)IGS BR VAF/Plus female rats were orally exposed with 4-amino-N-(4-aminophenyl)benzene-1-sulfonamide.
Reference
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 SN1 AND SN1 >> Nitrenium Ion
formation AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine
by DNA binding by OECD
Domain
logical expression index: "c"
Referential
boundary: The
target chemical should be classified as Strong binder, NH2 group by
Estrogen Receptor Binding
Domain
logical expression index: "d"
Referential
boundary: The
target chemical should be classified as Acylation AND Acylation >>
Acylation involving an activated (glucuronidated) sulfonamide group AND
Acylation >> Acylation involving an activated (glucuronidated)
sulfonamide group >> Arenesulfonamides AND AN2 AND AN2 >> Michael-type
addition to quinoid structures AND AN2 >> Michael-type addition to
quinoid structures >> Substituted Anilines AND AN2 >> Nucleophilic
addition at polarized N-functional double bond AND AN2 >> Nucleophilic
addition at polarized N-functional double bond >> Arenesulfonamides by
Protein binding by OASIS v1.4
Domain
logical expression index: "e"
Referential
boundary: The
target chemical should be classified as Amides AND Anilines (Unhindered)
by Aquatic toxicity classification by ECOSAR
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as Strong binder, NH2 group by
Estrogen Receptor Binding
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as Moderate binder, NH2 group OR
Non binder, MW>500 OR Weak binder, NH2 group by Estrogen Receptor Binding
Domain
logical expression index: "h"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= -1.43
Domain
logical expression index: "i"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 6.84
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 605 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- Data is Klimisch 2 and OECD QSAR toolbox
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:
In different studies, 4-amino-N-(4-aminophenyl) benzene-1-sulfonamide has been investigated for reproductive toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for 4-amino-N-(4-aminophenyl)benzene-1-sulfonamide along with the study available on structurally similar read across substance 4,4'-Diamino-2,2'-stilbenedisulfonic acid (CAS no 81-11-8) and 1,3-Benzenediol (108-46-3). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.
In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 4-amino-N-(4-aminophenyl)benzene-1-sulfonamide. The NOAEL was estimated to be 605 mg/kg bw when Crl:CD(SD)IGS BR VAF/Plus female rats were orally exposed with 4-amino-N-(4-aminophenyl)benzene-1-sulfonamide.
In another experimental study conducted by J-Check (Ministry of Health, Labour and Welfare", "Ministry of the Environment" and "National Institute of Technology and Evaluation, J-Check, 2010) on structurally similar read across substance 4,4'-Diamino-2,2'-stilbenedisulfonic acid (CAS no 81-11-8), Crj:CD (SD) male and female rats were treated with 4,4'-Diamino-2,2'-stilbenedisulfonic acid in the concentration of 0 (vehicle), 40, 200, 1000 mg/kg/day orally by gavage. At 200 mg / kg, one male died after the start of administration on the fourth day. At necropsy, perforation was found in the lung, so it was judged to be death due to administration error. No change was observed in general condition and body weight and weight gain were observed in treated rats as compared to control. In male rat at 1000 mg / kg, from the start of administration to the 14th day a significant increase in food consumption were observed, but after that, the values were similar to those of the control group, and no significant difference was observed. In females, no significant change was observed throughout the entire period. Similarly, No effect was observed on estrous cycle, copulation index, fertility index, gestation length, number of corpora lutea or implantations, implantation index, gestation index, delivery index, parturition or maternal behavior were observed as compared to control of P generation. No significant change in both the actual weight and the body weight ratio in testis and epididymis were observed. Miniaturization of bilateral testes was observed in each case of 40 and 1000 mg / kg, but it was judged as random change from the expression frequency did. No histological changes were found in the epididymal, non-mating and non-pregnant animal ovaries of p generation rats were observed as compared to control. In addition, No significant differences in numbers of offspring or live offspring, sex ratio, live birth index, viability index and body weight of pups were observed as compared to control. No abnormalities were observed in both surviving animals and dead animals as compared to control. Therefore, NOAEL was considered to be 1000 mg/kg/day for P and F1 generation when Crj:CD (SD) male and female rats treated with 4,4'-Diamino-2,2'-stilbenedisulfonic acid orally by gavage.
Further supported by another experimental study given by United States Environmental Protection Agency (High Production Volume Information System (HPVIS)| OPPT | US EPA, 2017) on structurally similar read across substance 1,3-Benzenediol (108-46-3), Crj:CD (SD) male and female rats were treated with1,3-Benzenediolin the concentration of 0,12, 36, 100 and 300 mg/kg orally in drinking water. No mortality and change in general condition of P, F1 and F2 rats were observed as compared to control. Decreased in mean cumulative body weight gains were observed in P female during the pre-mating period or the entire generation in males at 300 mg/kg. There were no clear trends in mean weekly body weight gains in these males and females; however, mean body weights were decreased by up to 6.3% in P females from study day 56 through 70. Mean body weights in the 300 mg/kg P females were also decreased during the first week of gestation (up to 5.5%), throughout lactation (up to 8.4%) and after the lactation period ended (6.3%). Decreased mean cumulative body weight gains were observed in F1 males during the entire generation at 300 mg/kg. While there were no clear trends for weekly mean body weight gains, mean body weights in these males were decreased by up to 7.1% during the entire generation. Mean body weights were also reduced in the 300 mg/kg F1 females during lactation (up to 6.1%) and after the lactation period ended (up to 7.0%). Mean body weights and body weight gains were unaffected in the 12, 36 and 100 mg/kg P and F1 males and females. Similarly, Decreased mean water consumption was observed at 300 mg/kg F0 and F1 parental animals during the pre-mating period in females or the entire generation in males. Decreased mean water consumption of F1 pups gang housed by litter from PND 21 28. Water consumption was also often decreased in the 100 mg/kg males and females, although the decreases were less severe and the onset was later in the 300 mg/kg group. Mean water consumption in the 100 mg/kg was consistently reduced compared to the control beginning on study days 21-24; however, slight decreases were also noted inconsistently earlier in the pre-mating period. The decreased water consumption in the 100 mg/kg continued through the first week of gestation while the decreased water consumption in the 300 mg/kg females continued throughout gestation and lactation. Decreases in water consumption were not considered an adverse change due to the lack of associated effects on food intake and food utilization. No statistically significant effects on concentrations of T3, T4 or TSH were observed in P and F1 parental animals. No statistically significant effects on concentrations of T3, T4 or TSH were observed in F1 and F2 pups (PND 4 or PND 21). The higher TSH values were observed in the P males at the scheduled necropsy were not considered test article-related in the absence of effects on T3 or T4, organ weights or adverse macroscopic or microscopic findings. Test article-related decreased colloid within the thyroid glands of the 300 mg/kg P males was not considered adverse due to the lack of associated functional effects. In addition, no reproductive toxic effect were observed in P and F1 parental animals such as on estrous cycle, mean testicular and epididymal sperm numbers and sperm production rate, motility, progressive motility and morphology, mating and fertility indices, number of days between pairing and coitus, gestation length and parturition of treated rats were observed as compared to control. No significant change in organ weight of P and F1 parental animals. No gross pathological changes were observed in treated P, F1 and F2 male and female rats as compared to control. No histological changes were observed in treated male and female P and F1 rats. Therefore, NOAEL was considered to be 300 mg/kg for P, F1 and F2 generation when Crj:CD (SD) male and female rats treated with 1,3-Benzenediolorally in drinking water for 70 Days.
Thus, based on the above studies and predictions on 4-amino-N-(4-aminophenyl)benzene-1-sulfonamide and its read across substances, it can be concluded that NOAEL value is 605 mg/kg bw with no effect on reproduction. Thus, as per criteria of CLP regulation, 4-amino-N-(4-aminophenyl)benzene-1-sulfonamide can be Not classified for reproductive toxicity.
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 the above studies and predictions on 4-amino-N-(4-aminophenyl)benzene-1-sulfonamide and its read across substances, it can be concluded that NOAEL value is 605 mg/kg bw with no effect on reproduction. Thus, as per criteria of CLP regulation, 4-amino-N-(4-aminophenyl)benzene-1-sulfonamide can be Not classified for reproductive toxicity.
Additional information
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