Registration Dossier
Registration Dossier
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EC number: 200-237-1 | CAS number: 55-55-0
- 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
Reproductive toxicity via oral route
NOAEL was estimated to be 740 mg/kg bw when Crj: CD(SD) male and female rats were exposed with p-Methylaminophenol sulphate orally.
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 from OECD QSAR toolbox v3.3 and the QMRF report has been attached.
- Qualifier:
- according to guideline
- Guideline:
- other: As mentioned below
- Principles of method if other than guideline:
- Prediction was done using OECD QSAR toolbox v3.3, 2017
- GLP compliance:
- not specified
- Limit test:
- no
- Justification for study design:
- not specified
- Specific details on test material used for the study:
- - Name of test material: p-Methylaminophenol sulfate- IUPAC name: Bis(4-hydroxy-N-methylanilinium) sulphate- Molecular formula: C14H20N2O6S- Molecular weight: 344.386 g/mole- Smiles:CNc1ccc(cc1)O.CNc1ccc(cc1)O.OS(=O)(=O)O- Inchl: 1S/2C7H9NO.H2O4S/c2*1-8-6-2-4-7(9)5-3-6;1-5(2,3)4/h2*2-5,8-9H,1H3;(H2,1,2,3,4)- Substance type: Organic- Physical state: Solid crystalline (off white - white)
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Details on species / strain selection:
- No data available
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- No data available
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- No data available
- Details on mating procedure:
- No data available
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- Treatment started 14 days prior to mating, and continued daily through the premating period, mating, gestation, and until lactation day 3.
- Frequency of treatment:
- Daily
- Details on study schedule:
- No data available
- Dose / conc.:
- 740 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 12
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data available
- Positive control:
- No data available
- Parental animals: Observations and examinations:
- No data available
- Oestrous cyclicity (parental animals):
- No data available
- Sperm parameters (parental animals):
- No data available
- Litter observations:
- No data available
- Postmortem examinations (parental animals):
- No data available
- Postmortem examinations (offspring):
- No data available
- Statistics:
- No data available
- Reproductive indices:
- No data available
- Offspring viability indices:
- No data available
- 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:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- No effect was observed on reproduction performance.
- Dose descriptor:
- NOAEL
- Effect level:
- 740 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reproductive performance
- Critical effects observed:
- no
- System:
- female reproductive system
- 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:
- 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
- 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:
- other: not specified
- Generation:
- other: not specified
- Based on:
- not specified
- Sex:
- not specified
- Basis for effect level:
- other: not specified
- Remarks on result:
- other: 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 740 mg/kg bw when male and female Crj: CD(SD) rats were exposed to p-Methylaminophenol sulphate orally.
- Executive summary:
In an prediction done by SSS (Nagpur, 2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for p-Methylaminophenol sulphate. No effect was estimated to be observed on the reproductive function. Hence, NOAEL was estimated to be 740 mg/kg bw when male and female Crj: CD(SD) rats were exposed to p-Methylaminophenol sulphate orally.
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" ) and "d" ) and "e" ) and "f" ) and "g" ) and "h" ) and ("i" and ( not "j") ) ) and ("k" and ( not "l") ) ) and ("m" and ( not "n") ) ) and ("o" and ( not "p") ) ) and ("q" and "r" ) )
Domain logical expression index: "a"
Referential boundary: The target chemical should be classified as Phenols (Acute toxicity) by US-EPA New Chemical Categories
Domain logical expression index: "b"
Referential boundary: The target chemical should be classified as Strong binder, NH2 group OR Very strong binder, OH group by Estrogen Receptor Binding ONLY
Domain logical expression index: "c"
Referential boundary: The target chemical should be classified as Phenols, Poly by Aquatic toxicity classification by ECOSAR
Domain logical expression index: "d"
Referential boundary: The target chemical should be classified as No alert found by Protein binding by OECD ONLY
Domain logical expression index: "e"
Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY
Domain logical expression index: "f"
Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (original) ONLY
Domain logical expression index: "g"
Similarity boundary:Target: CN{+}(c1ccc(O)cc1).O{-}S(=O)(=O)O{-}.N{+}(C)c1ccc(O)cc1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain logical expression index: "h"
Similarity boundary:Target: CN{+}(c1ccc(O)cc1).O{-}S(=O)(=O)O{-}.N{+}(C)c1ccc(O)cc1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain logical expression index: "i"
Referential boundary: The target chemical should be classified as o-/ p-Aminophenols (Hemolytic anemia with methemoglobinemia) Rank B AND Oxyphenistain (Hepatotoxicity) Alert AND p-Aminophenols (Renal toxicity) Rank B by Repeated dose (HESS)
Domain logical expression index: "j"
Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert by Repeated dose (HESS)
Domain logical expression index: "k"
Referential boundary: The target chemical should be classified as o-/ p-Aminophenols (Hemolytic anemia with methemoglobinemia) Rank B AND Oxyphenistain (Hepatotoxicity) Alert AND p-Aminophenols (Renal toxicity) Rank B by Repeated dose (HESS)
Domain logical expression index: "l"
Referential boundary: The target chemical should be classified as Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)
Domain logical expression index: "m"
Referential boundary: The target chemical should be classified as Aliphatic Amine, secondary AND Overlapping groups AND Precursors quinoid compounds by Organic Functional groups (nested)
Domain logical expression index: "n"
Referential boundary: The target chemical should be classified as Triazinetrione by Organic Functional groups (nested)
Domain logical expression index: "o"
Referential boundary: The target chemical should be classified as Aliphatic Amine, secondary AND Overlapping groups AND Precursors quinoid compounds by Organic Functional groups (nested)
Domain logical expression index: "p"
Referential boundary: The target chemical should be classified as Azomethine by Organic Functional groups (nested)
Domain logical expression index: "q"
Parametric boundary:The target chemical should have a value of log Kow which is >= 2.19
Domain logical expression index: "r"
Parametric boundary:The target chemical should have a value of log Kow which is <= 6.83
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 740 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- Data is Klimicsh 2 and from QSAR Toolbox 3.3. (2017)
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 11.47 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Data is Klimisch 2 and from a peer-reviewed publication
Additional information
Reproductive toxicity via oral route
In a prediction done by SSS (Nagpur, 2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for p-Methylaminophenol sulphate. No effect was estimated to be observed on the reproductive function. Hence, NOAEL was estimated to be 740 mg/kg bw when male and female Crj: CD(SD) rats were exposed to p-Methylaminophenol sulphate orally.
A reproductive and developmental toxicity study of p-Methylaminophenol sulphate was performed in female Sprague Dawley Crl CD (SD) IGS BR rats. The test material in a 0.5% suspension of carboxymethylcellulose were administered in dose concentration 0, 5, 25 or 125 mg/kg bw/day from day 6 through day 19 post-coitum by oral gavage. Animals were checked daily for clinical signs, and food consumption and body weight were recorded at designated intervals during pregnancy. On day 20 post-coitum, the dams were sacrificed and subjected to a macroscopic examination. The gravid uterus was weighed and the fetuses were removed by hysterectomy. The litter parameters like number of corpora lutea, implantation sites, early and late resorptions, dead and live fetuses were recorded. The fetuses were weighed, sexed and subjected to external, soft tissue or skeletal examinations. No treatment-related clinical signs and premature deaths were observed. Relevant maternal changes were only observed at 25 and 125 mg/kg/day where net body weight gain was slightly reduced when compared to controls. No relevant necropsy findings were noted. The litter parameters like number of corpora lutea, implantation sites, early and late resorptions, dead and live fetuses were not affected by treatment with the test item. Also, in fetuses there were no treatment-related malformations or variations in any groups at external, soft tissue or skeletal examinations. Therefore, LOEL for maternal toxicity was considered to be 25 mg/kg/day while the dose-level of 125 mg/kg/day was considered to be the NOAEL for embryo-fetal toxicity when pregnant female Sprague Dawley rats were treated with p-Methylaminophenol sulphate orally.
A combined repeated dose and reproductive/developmental toxicity study was performed to determine the toxic nature of N-Methyl-p-aminophenol sulfate when administered by a dermal route. The study was performed on female Charles River CD rats, where 2 ml/kg dye formulation 7404 or P-26 containing 1% and 0.05% N-methyl-p-aminophenol sulfate, respectively, was applied to the dorso-scapular area. These dye formulations contained other active ingredients in an aqueous solution and were mixed with an equal volume of 6% hydrogen peroxide prior to application. Application was made on gestation days 1, 4, 7, 10, 13, 16 and 19. The animals were observed for clinical signs, body weight changes, dermal irritation if any and food consumption. No dye formulation related toxicity was noted. Changes in female body weights and food consumption were similar for rats in the untreated controls and all dye-treated groups. No irritation or other changes in appearance were noted except for changes in skin and hair color at the site of topical application of the dye formulation. No significant differences in the mean number of corpora lutea, implantation sites and live fetuses, and the sex ratio were observed when compared with the control groups. No differences between groups were seen regarding the number of females exhibiting resorption sites or mean resorptions per pregnancy. No significant changes were observed regarding soft-tissue anomalies between the dye-treated groups and the untreated control groups. Normally occurring skeletal variations were present in all groups; the most frequent variation noted was accessory ribs. Therefore, NOAEL for N-Methyl-p-aminophenol sulfate in the maternal generation and the F1 generation of Charles River CD rats was considered to be 11.47 mg/kg for formulation 7404 and 0.5735 mg/kg for formulation P26, when both formulations contained the target compound.
Effects on developmental toxicity
Description of key information
Developmental toxicity
LOEL for maternal toxicity was considered to be 25 mg/kg/day, and the dose-level of 125 mg/kg/day was considered to be the NOAEL for embryo-fetal toxicity when female Sprague Dawley rats were treated with p-methylaminophenol sulphate orally.
Link to relevant study records
- Endpoint:
- developmental toxicity
- Remarks:
- (Prenatal Developmental Toxicity Study)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Justification for type of information:
- Data from secondary source
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Principles of method if other than guideline:
- A prenatal development toxicity study of p-methylaminophenol sulphate was performed in Sprague-Dawley rats.
- GLP compliance:
- not specified
- Limit test:
- no
- Specific details on test material used for the study:
- - Name of test material: p-Methylaminophenol sulfate- IUPAC name: Bis(4-hydroxy-N-methylanilinium) sulphate- Molecular formula: C14H20N2O6S- Molecular weight: 344.386 g/mole- Smiles:CNc1ccc(cc1)O.CNc1ccc(cc1)O.OS(=O)(=O)O- Inchl: 1S/2C7H9NO.H2O4S/c2*1-8-6-2-4-7(9)5-3-6;1-5(2,3)4/h2*2-5,8-9H,1H3;(H2,1,2,3,4)- Substance type: Organic- Physical state: Solid crystalline (off white - white)
- Species:
- rat
- Strain:
- Sprague-Dawley
- Remarks:
- Crl CD (SD) IGS BR)
- Route of administration:
- oral: gavage
- Vehicle:
- CMC (carboxymethyl cellulose)
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: p-methylaminophenol sulphate in a 0.5% suspension of carboxymethylcellulose was prepared prior to treatment.DIET PREPARATION- Rate of preparation of diet (frequency):No data available- Mixing appropriate amounts with (Type of food): No data available- Storage temperature of food: No data availableVEHICLE- Justification for use and choice of vehicle (if other than water): c
- Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- - M/F ratio per cage: No data available- Length of cohabitation: No data available- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy: The day of positive proof for sperm in the vaginal smear or sperm plug was designated as day 0 post coitum (p.c.) or gestation day 0. - After ... days of unsuccessful pairing replacement of first male by another male with proven fertility: No data available- Further matings after two unsuccessful attempts: No data available- After successful mating each pregnant female was caged (how): No data available- Any other deviations from standard protocol: No data available
- Duration of treatment / exposure:
- 14 days (from day 6 through day 19 post-coitum)
- Frequency of treatment:
- Daily from day 6 through day 19 post-coitum
- Duration of test:
- 20 days
- Remarks:
- Doses/Concentrations: 0, 5, 25 or 125 mg/kg bw/day
- No. of animals per sex per dose:
- Total: 96 ratsControl :24 females5 mg/kg bw/day: 24 females25 mg/kg bw/day: 24 females125 mg/kg bw/day: 24 females
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data available
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes - Time schedule: Daily- Cage side observations included: No data availableDETAILED CLINICAL OBSERVATIONS: Yes- Time schedule: DailyBODY WEIGHT: Yes - Time schedule for examinations: On designated intervals during prenancyFOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: On designated intervals during prenancy- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data availableWATER CONSUMPTION AND COMPOUND INTAKE(if drinking water study): No data availableOPHTHALMOSCOPIC EXAMINATION: No data availableHAEMATOLOGY: No data availableCLINICAL CHEMISTRY: No data availableURINALYSIS: No data availableNEUROBEHAVIOURAL EXAMINATION: No data availableOTHER: No data available
- Ovaries and uterine content:
- On day 20 post-coitum, the dams were sacrificed and subjected to a macroscopic examination. The gravid uterus was weighed and the fetuses were removed by hysterectomy.
- Fetal examinations:
- Upon necropsy, the fetuses were subjected to external, soft tissue or skeletal examinations.
- Statistics:
- No data available
- Indices:
- No data available
- Historical control data:
- No data available
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No treatment-related clinical signs were observed.
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- no mortality observed
- Description (incidence):
- There were no premature deaths during the study.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Relevant maternal changes were only observed at 25 and 125 mg/kg/day where net body weight gain was slightly reduced when compared to controls.
- 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
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- No relevant necropsy findings were recorded.
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- not specified
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not specified
- Dead fetuses:
- not specified
- Changes in pregnancy duration:
- not specified
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified- Changes in number of pregnant:
- not specified
- Other effects:
- not specified
- Dose descriptor:
- LOEL
- Effect level:
- 25 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- Abnormalities:
- not specified
- Fetal body weight changes:
- not specified
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not specified- Reduction in number of live offspring:
- not specified
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- not specified
- Changes in postnatal survival:
- not specified
- External malformations:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related malformations or variations in any groups at external examination.
- Skeletal malformations:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related malformations or variations in any groups at skeletal examinations.
- Visceral malformations:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related malformations or variations in any groups at soft tissue examinations.
- Other effects:
- not specified
- Dose descriptor:
- NOAEL
- Effect level:
- 125 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- external malformations
- skeletal malformations
- visceral malformations
- Abnormalities:
- not specified
- Developmental effects observed:
- no
- Lowest effective dose / conc.:
- 125 mg/kg bw/day (nominal)
- Treatment related:
- not specified
- Relation to maternal toxicity:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- LOEL for maternal toxicity was considered to be 25 mg/kg/day while the dose-level of 125 mg/kg/day was considered to be the NOAEL for embryo-fetal toxicity when pregnant female Sprague Dawley rats were treated with p-Methylaminophenol sulphate orally.
- Executive summary:
A reproductive and developmental toxicity study of p-Methylaminophenol sulphate was performed in female Sprague Dawley Crl CD (SD) IGS BR rats. The test material in a 0.5% suspension of carboxymethylcellulose were administered in dose concentration 0, 5, 25 or 125 mg/kg bw/day from day 6 through day 19 post-coitum by oral gavage. Animals were checked daily for clinical signs, and food consumption and body weight were recorded at designated intervals during pregnancy. On day 20 post-coitum, the dams were sacrificed and subjected to a macroscopic examination. The gravid uterus was weighed and the fetuses were removed by hysterectomy. The litter parameters like number of corpora lutea, implantation sites, early and late resorptions, dead and live foetuses were recorded. The fetuses were weighed, sexed and subjected to external, soft tissue or skeletal examinations. No treatment-related clinical signs and premature deaths were observed. Relevant maternal changes were only observed at 25 and 125 mg/kg/day where net body weight gain was slightly reduced when compared to controls. No relevant necropsy findings were noted. The litter parameters like number of corpora lutea, implantation sites, early and late resorptions, dead and live fetuses were not affected by treatment with the test item. Also, in fetuses there were no treatment-related malformations or variations in any groups at external, soft tissue or skeletal examinations. Therefore, LOEL for maternal toxicity was considered to be 25 mg/kg/day while the dose-level of 125 mg/kg/day was considered to be the NOAEL for embryo-fetal toxicity when pregnant female Sprague Dawley rats were treated with p-Methylaminophenol sulphate orally.
Reference
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 125 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Data is Klimisch 4 and from secondary source
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 11.47 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Data is Klimisch 2 and from a peer-reviewed publication
Additional information
Developmental toxicity
A reproductive and developmental toxicity study of p-Methylaminophenol sulphate was performed in female Sprague Dawley Crl CD (SD) IGS BR rats. The test material in a 0.5% suspension of carboxymethylcellulose were administered in dose concentration 0, 5, 25 or 125 mg/kg bw/day from day 6 through day 19 post-coitum by oral gavage. Animals were checked daily for clinical signs, and food consumption and body weight were recorded at designated intervals during pregnancy. On day 20 post-coitum, the dams were sacrificed and subjected to a macroscopic examination. The gravid uterus was weighed and the fetuses were removed by hysterectomy. The litter parameters like number of corpora lutea, implantation sites, early and late resorptions, dead and live foetuses were recorded. The fetuses were weighed, sexed and subjected to external, soft tissue or skeletal examinations. No treatment-related clinical signs and premature deaths were observed. Relevant maternal changes were only observed at 25 and 125 mg/kg/day where net body weight gain was slightly reduced when compared to controls. No relevant necropsy findings were noted. The litter parameters like number of corpora lutea, implantation sites, early and late resorptions, dead and live fetuses were not affected by treatment with the test item. Also, in fetuses there were no treatment-related malformations or variations in any groups at external, soft tissue or skeletal examinations. Therefore, LOEL for maternal toxicity was considered to be 25 mg/kg/day while the dose-level of 125 mg/kg/day was considered to be the NOAEL for embryo-fetal toxicity when pregnant female Sprague Dawley rats were treated with p-Methylaminophenol sulphate orally.
A combined repeated dose and reproductive/developmental toxicity study was performed to determine the toxic nature of N-Methyl-p-aminophenol sulfate when administered by an dermal route. The study was performed on female Charles River CD rats, where 2 ml/kg dye formulation 7404 or P-26 containing 1% and 0.05% N-methyl-p-aminophenol sulfate, respectively, was applied to the dorso-scapular area. These dye formulations contained other active ingredients in an aqueous solution and were mixed with an equal volume of 6% hydrogen peroxide prior to application. Application was made on gestation days 1, 4, 7, 10, 13, 16 and 19. The animals were observed for clinical signs, body weight changes, dermal irritation if any and food consumption. No dye formulation related toxicity was noted. Changes in female body weights and food consumption were similar for rats in the untreated controls and all dye-treated groups. No irritation or other changes in appearance were noted except for changes in skin and hair color at the site of topical application of the dye formulation. No significant differences in the mean number of corpora lutea, implantation sites and live fetuses, and the sex ratio were observed when compared with the control groups. No differences between groups were seen regarding the number of females exhibiting resorption sites or mean resorptions per pregnancy. No significant changes were observed regarding soft-tissue anomalies between the dye-treated groups and the untreated control groups. Normally occurring skeletal variations were present in all groups; the most frequent variation noted was accessory ribs. Therefore, NOAEL for N-Methyl-p-aminophenol sulfate in the maternal generation and the F1 generation of Charles River CD rats was considered to be 11.47 mg/kg for formulation 7404 and 0.5735 mg/kg for formulation P26, when both formulations contained the target compound.
Justification for classification or non-classification
Based on a (Q)SAR prediction and available experimental data of the target chemical, N-Methyl-p-aminophenol sulfate is not regarded as toxic for reproductive toxicity since no effects were noted on any reproductive parameters. In addition, no embryotoxicity or teratogenic effects were presented in the reviewed data and thus the target chemical is not regarded as toxic for developmental toxicity.
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