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EC number: 202-957-1 | CAS number: 101-59-7
- 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
Carcinogenicity
Administrative data
Description of key information
Key value for chemical safety assessment
Carcinogenicity: via oral route
Link to relevant study records
- Endpoint:
- carcinogenicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- 4-(p-nitrophenylthio)aniline - DAPEA (chemical target) and 4,4'-Thiodianiline - TDA (chemical source) share the larger part of the chemical structure, included the main structural alerts for DNA binding and getotoxicity.
- Reason / purpose for cross-reference:
- read-across source
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- All high-dose animals died by week 77, and all low-dose animals died by week 79.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Body weight was significantly reduced in both sexes; however, the high and low doses caused about the same reduction in body weight.
- Histopathological findings: neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- The liver and thyroid gland were the primary target tissues in both sexes.
The time to the first observed liver tumor in mice exposed to TDA at 5,000 ppm was 40 weeks in female mice and 50 to 54 weeks in male mice. At the low dose (2,500 ppm), liver tumors appeared at 54 weeks in both sexes. Spontaneous liver tumors occurred at 88 weeks in male controls. The first thyroid tumors appeared at 40 weeks in high-dose females, 54 weeks in high-dose males, 59 weeks in low-dose females, and 63 weeks in low-dose males.
The incidence of hepatocellular carcinoma was significantly increased in both sexes at both dose levels. These tumors were metastatic to the lungs and kidney. The incidence of thyroid follicular-cell carcinoma was significantly increased at both dose levels in males, but only at the high dose in females. These tumors were metastatic to the lungs. In addition, two unspecified thyroid adenomas occurred in the high-dose females. The incidences of total tumors of the thyroid gland (follicular-cell adenoma or carcinoma combined) and liver (hepatocellular adenoma or carcinoma combined) were significantly increased in both sexes at both dose levels. - Remarks on result:
- not determinable
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 2 500 ppm
- System:
- hepatobiliary
- Organ:
- liver
- thyroid gland
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- not specified
- Conclusions:
- The NCI concluded that TDA was carcinogenic in B6C3F1 mice.
Based on the similarity between the chemical source (TDA) and the chemical target (DAPEA), study results can be reliably extrapolated to DAPEA. - Endpoint:
- carcinogenicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- 4-(p-nitrophenylthio)aniline - DAPEA (chemical target) and 4,4'-Thiodianiline - TDA (chemical source) share the larger part of the chemical structure, included the main structural alerts for DNA binding and getotoxicity.
- Reason / purpose for cross-reference:
- read-across source
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- A significant (P ≤ 0.001, Tarone test) dose-related trend in mortality was observed. All animals in the control groups survived as long as week 52, and 6 males (40%) and 5 females (33%) survived until the end of the study (104 weeks). Among TDA-exposed males, 23 (66%) in the low-dose group and 18 (51%) in the high-dose group survived to week 52. Survival of females was a little higher, with 32 (91%) in the low-dose group and 21 (60%) in the high-dose group surviving to week 52. However, all high-dose rats died by week 69, and all low-dose rats died by week 72.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Throughout the study, body weight was significantly lower in all exposed groups than in the control group.
- Histopathological findings: neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- All TDA-exposed rats except one had tumors at one or more sites, including the ear canal, lung, liver, and thyroid gland. Additionally, skin and colon tumors occurred in males, and uterine tumors in females. Tumor incidences were signficantly increased in at least one sex. The times to the first observed tumors in TDA-exposed rats were 25 weeks for ear-canal tumors in males, 32 weeks for thyroid tumors in males, 44 weeks for liver and colon tumors in males and thyroid and uterine tumors in females, 46 weeks for ear-canal tumors in females, and 61 weeks for liver tumors in females. Liver and colon tumors appeared earlier in the lowdose groups than in the high-dose groups, as did ear-canal tumors in females. Skin tumors occurred only in low-dose males and were observed at 48 weeks. Lung tumors were observed at 50 weeks in low-dose males and 63 weeks in low-dose females.
The incidences of liver, thyroid, and ear-canal tumors were significantly increased in male rats, and the incidences of thyroid and uterine tumors were significantly increased in female rats. Although the increased incidences of colon tumors in males and ear-canal tumors in females were not statistically significant, they were considered to be related to TDA administration because they were not observed in the concurrent controls or in 235 historical control animals. For similar reasons, the increased incidence of skin tumors in male rats may have been associated with TDA exposure (tumors were not observed in concurrent controls and were observed in only 1 of 235 historical controls).
All tumors were epithelial in origin, and most of them were malignant. These included squamous-cell papilloma and carcinoma of the skin; squamous-cell papilloma and carcinoma of the external ear canal and adjacent subcutaneous tissues; squamous-cell carcinoma, alveolar-cell carcinoma, and bronchiolar adenoma of the lungs; hepatocellular adenoma and carcinoma; adenocarcinoma of the colon; follicular-cell adenoma and carcinoma of the thyroid; and adenocarcinoma of the uterus. Many of these tumors had invaded surrounding tissue or metastasized to the lungs, lymph nodes, liver, or spleen. The ear-canal tumors currently are classified as Zymbal gland tumors. - Remarks on result:
- not determinable
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 1 500 ppm
- Organ:
- liver
- lungs
- thyroid gland
- zymbal gland
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- not specified
- Conclusions:
- TDA was carcinogenic in rats.
Based on the similarity between the chemical source (TDA) and the chemical target (DAPEA), study results can be reliably extrapolated to DAPEA.
Referenceopen allclose all
In addition to the neoplastic lesions, several degenerative, proliferative, and inflammatory changes occurred in mice of the TDA-exposed and control groups. Although most of these lesions are typical for aged mice, follicular-cell hyperplasia of the thyroid was observed only in the TDA-exposed mice and was believed to be exposure-related. This lesion occurred in 29 of 33 males and 31 of 33 females in the low-dose groups and in 4 of 23 males and 26 of 30 females in the high-dose groups.
In addition to the neoplastic lesions, a number of chemically induced degenerative, proliferative, and inflammatory lesions were observed. These included lesions in the lung (epidermal inclusion cyst formation, alveolar-cell hyperplasia, and alveolar and bronchiolar squamous metaplasia), liver (hepatocellular nodular hyperplasia and bile duct hyperplasia), and thyroid gland (follicular-cell hyperplasia). These lesions were not observed in any of the control animals. Epidermal inclusion cysts, alveolar-cell hyperplasia, and alveolar and bronchiolar squamous metaplasia were observed, respectively, in 5, 15, and 12 of 33 low-dose males and 2, 13, and 4 of 32 low-dose females. Thyroid follicular-cell hyperplasia occurred in 1 of 33 low-dose males and 7 of 33 low-dose females. Thyroid and lung lesions were not observed in the high-dose groups. Liver nodular hyperplasia occurred in 4 of 33 low-dose and 10 of 33 high-dose males and 1 of 32 low-dose and 9 of 33 high-dose females. Bile-duct hyperplasia occurred in 8 of 33 low-dose and 25 of 33 high-dose males and in 6 of 33 low-dose and 12 of 33 high-dose females.
Justification for classification or non-classification
Since 4-(p-nitrophenylthio)aniline is structurally similar to 4,4'-Thiodianiline (which has a harmonized classification as Carc 1B, H351) and considering the positive results revealed by the bacterial revers mutation assays, 4-(p-nitrophenylthio)aniline is suspected to be carcinogen. Therefore, classification as Carc. 2 H351 applies, in accordance with CLP Regulation.
Additional information
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