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EC number: 209-711-2 | CAS number: 591-27-5
- 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
Repeated dose toxicity: dermal
Administrative data
- Endpoint:
- chronic toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Justification for type of information:
- Data is from study report
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 979
- Report date:
- 1979
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: Refer below principle
- Principles of method if other than guideline:
- Lifetime chronic toxicity/carcinogenisis study in rats were performed using the dermal application of test material m-aminophenol
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- 3-aminophenol
- EC Number:
- 209-711-2
- EC Name:
- 3-aminophenol
- Cas Number:
- 591-27-5
- Molecular formula:
- C6H7NO
- IUPAC Name:
- 3-aminophenol
- Reference substance name:
- m-aminophenol
- IUPAC Name:
- m-aminophenol
- Details on test material:
- - Name of test material (as cited in study report): formula P-25 and Formula P-26
- Substance type:organic
- Physical state:
P-25 : thick gray liquid
P-26 : Thick brown liquid
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- other: Charles river
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Details on test animal
TEST ANIMALS
- Source: Charles River
- Age at study initiation: No data available
- Weight at study initiation: Male weighing from 62 to 204 grams; Females weighing from 61 to 192 grams
- Fasting period before study: No data available
- Housing: The rats were housed individually in hanging wire mesh cages and maintained in a temperatures, humidity and light controlled environment.
- Diet (e.g. ad libitum): Ground Purinas Laboratory Chow, ad libitum
- Water (e.g. ad libitum): Water was available at libitum
- Acclimatization period: No data available
ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%): No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available
Administration / exposure
- Type of coverage:
- open
- Vehicle:
- other: No vehicle was used
- Details on exposure:
- TEST COMPOUND
The fully prepared formulas (P-25 and P-26) were recieved from Cosmair, Inc., New York.
TEST SITE
- Time intervals for shavings or clipplings: The hair on the neck and back of each rat was clipped with an electric clipper (at least 24 hours prior to compound administration) as necessary during the study
COMPOUND ADMINISTRATION
The dyes were applied as evenly as possible to assure skin contact and to avoid run off. - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 24 months (lifetime)
- Frequency of treatment:
- twice a week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
Each topical application (0.5 ml/rat) contained 3-aminophenol at approx. 0.59 mg/kg (P-26) or 2.65 mg/kg (P-25).
Basis:
- No. of animals per sex per dose:
- 600 rats in total, divided as below:
Control 1: 60 males, 60 females
Control 2: 60 males, 60 females
Control 3: 59 males, 60 females
P-25: 60 males, 60 females
P-26: 60 males, 60 females - Control animals:
- other: Yes, untreated but clipped on the same regime as the treated rats but no compund was added.
- Details on study design:
- No data
- Positive control:
- No data
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Weekly
BODY WEIGHT: Yes
- Time schedule for examinations:Individual body weights were recorded weekly for the first 14 weeks and monthly thereafter
FOOD CONSUMPTION:
Sex group food consumption was recorded weekly.
FOOD EFFICIENCY: No
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data available
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
- Time schedule for examinations: No data available
OPHTHALMOSCOPIC EXAMINATION: No
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
HAEMATOLOGY: Yes
- Time schedule for collection of blood: At 3, 12, 18 and 24 months
- Anaesthetic used for blood collection: No data available
- Animals fasted: Yes
- How many animals: 5 males and 5 females in each group.
- Parameters examined: Hemoglobin, hematocrit, total erythrocyte, total and differential leucocyte counts, total platelet and reticulocyte count.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At 3, 12, 18 and 24 months
- Animals fasted: Yes
- How many animals: 5 males and 5 females in each group.
- Parameters examined: Fasting glucose, urea nitrogen, serum alkaline phosphate, serum glutamic oxalacetic, pyruvic transaminase activities and serum creatinine.
URINALYSIS: Yes
- Time schedule for collection of urine: At 3, 12, 18 and 24 months
- Metabolism cages used for collection of urine: No data available
- Animals fasted: Yes
- Parameters examined: Volume, pH, specific gravity, description of color and appearance, and qualitative test for albumin, glucose, bilirubin and occult blood. Microscopic examinations of sediment was also performed.
NEUROBEHAVIOURAL EXAMINATION: No
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
OTHER: no data availble - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
After twelve months of treatment, five male and five female rats from each group were sacrificed by decapitation and necropsied. At necropsy, representative tissues from each rat were collected in buffered neutral 10% .formalin. All~ rats of a sex were sacrificed and necropsied when the survival for that sex reached 20%.. Any rats which died or were sacrificed in extremis during the course of the study also were necropsied and, unless precluded by autolysis, representative tissues were retained in formalin.
HISTOPATHOLOGY: Yes
The following tissues from all rats sacrificed after twelve months of treatment and at study termination were sectioned and stained with hematoxylin and eosin, and were then examined microscopically: skin neck (thyroid level), lung, gastrointestinal tract , spleen, pancreas, liver, pituitary, kidneys, urinary bladder, ureters, bone marrow, lymph node, adrenalsgonads ,brain, skeletal muscle, eyes and all tumor masses. - Other examinations:
- No data
- Statistics:
- All statistical analyses compared the treatment groups with each control group. The body weights and hematological and biochemical parameters were compared by analysis of variance (one-way classification). Then Bartlett's test for hemogeneity of variance was applied to the respective parameters. The appropiate t-test (for equal or unequal variance) was used to judge the significance of differences between the means, based upon Dunnett's multiple comparison tables.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- The most common incidental finding noted for some control and treated rats were localized hair loss, ocular discharge, and masses.
- Dermal irritation:
- no effects observed
- Mortality:
- mortality observed, non-treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- The terminal body weight was marginally lower (9.4% lower) among females in the 2.65 mg/kg dose group compared to control group.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Food consumption was slightly higher at 0.59 and 2.65 mg/kg compared to concurrent control groups.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- At 2.65 mg/kg, one male rat at 12 months of study showed slight decrease in total erythrocytes, hemoglobin and hematocrit with increases in reticulocytes, neutrophils and platelets compared to control group. Also at 2.65 mg/kg, one female rat at 24 months of study showed moderate increases in total leukocytes and a marked decrease in lymphocytes. At 0.59 mg/kg, two male and two females at 24 months of study showed slight to moderate decreases in total erythrocytes, hemoglobin and hematocrit. Two of these four animals also showed moderate increases in reticulocyte counts.
Based on the low incidences and the lack of a dose-related trend, these effects are not attributed to 3-aminophenol exposure. - Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- At 2.65 mg/kg, one female at 24 months of study showed slight urea nitrogen and a marked increase in alkaline phosphatase activity and another female at 24 months of study showed moderate increases in the urea nitrogen level, serum glutamic-oxaloacetic transaminase and alkaline phosphatase activities.
At 0.59 mg/kg, one male rat at 18 months of study showed slight increases in urea nitrogen levels and a moderate increase in serum glutamic-oxaloacetic transaminase activity. At 0.59 mg/kg at 24 months of study, one male showed slight increases urea nitrogen levels and serum glutamic-oxaloacetic transaminase acitivty and a moderate increase in alkaline phosphatase activity whereas another male at 24 months of study showed a moderate increase in urea nitrogen level and a slight increase in the creatinine level.
Based on the low incidences and the lack of a dose-related trend, these effects are not attributed to 3-aminophenol exposure - Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- There were no gross lesions attributed to the compound at necropsy in any experimental rats at the 12 or 24 months of study or in rats which died or were sacrificed extremis during the course of the study.
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Non-neoplastic lesions were observed in various organs and tissues of rats from the control and experimental groups. These changes appeared to reflect normal background incidence of histopathology for rats of this strain and age routinely observed at this laboratory and were not considered to be compound related.
- Histopathological findings: neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The most common neoplasm or neoplasm-like lesion observed in rats from all sex groups was pituitary adenoma, the incidence of the neoplasm was generally greater in female rats then in males in the control and experimental groups. However, statistically significant variations of the tumor did occur in males between various control and experimental groups. The incidence of the tumor was significantly greater in male rats from groups Control 2, Control 3 and at 2.65 mg/kg than in males from group Control 1. Conversely, the incidence of the tumor was significantly less in male rats treated at 0.59 mg/kg than in males from groups Control 2 and Control 3. The statistically significant variations in incidence of pituitary adenomas between rats of different control groups as well as their statistically significant decrease in an experimental group when compared with two ontrol groups tended to discount in aging rats of this strain at this laboratory. The incidence of mammary lobular hyperplasia was statistically significantly greater in female rats from group Control 3 at 0.59 mg/kg when compared with group Control 1 females. Again, the occurrence of statistically significant variations between control groups as well as between a control and an experimental group discounted the biological significance of these findings. The incidence of skin fibromas in female rats fram groups Control 2, Control 3 at 0.59 mg/kg was statistically significantly less than those of group Control 1 females. This finding was considered to be of no biological significance but demonstrated the variations in incidence of neoplasms that may occur between rats of a given group. No other statistically significant variations in neoplasms or neoplasm-like lesions occurred. Actuarial (life table) analyses did not show significant variations in incidences of tumor bearing animals in either of the treated groups when compared with each of the three control groupa by sex. A number of other neoplasms or neplasm-like lesions of relatively low incidences were observed in various organs and tissues of rats from the control and experimental groups. These changes appeared to reflect normal background incidence of histopathology for rats of this strain and age routinely observed at this laboratory and were not considered to be compound related.
- Other effects:
- not specified
- Details on results:
HISTOPATHOLOGY: NEOPLASTIC
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 0.59 other: mg/kg bw per week
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- behaviour (functional findings)
- body weight and weight gain
- clinical biochemistry
- clinical signs
- dermal irritation
- food consumption and compound intake
- haematology
- histopathology: neoplastic
- histopathology: non-neoplastic
- mortality
- urinalysis
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- NOAEL for the test chemical was found at the 0.59 mg/kg when rats were exposed to the test chemical by the dermal route two times per week for 2 years.
- Executive summary:
In this study by L’Oreal (1979) male and female Charles river rats were exposed by dermal route two times per week for 24 months to hair dye formulations P-26 or P-25. Each topical application contained a 3-aminophenol concentration of approximately 0.59 mg/kg (for P-26) and 2.65 mg/kg (for P-25). The terminal body weight was marginally lower (9.4% lower) in the females in the P-25 treatment group as compared to the controls. Food consumption was slightly higher in the treated rats as compared to the controls. No gross lesions were considered to be compound-related. In the P-25 treatment group, hyperkeratosis and/or acanthosis of the stomach mucosa was considered to be possibly compound-related. Hepatocellular hypertrophy/hyperplasia or formation of hyperplastic/hypertrophic nodules in the livers of the rats in the P-25 treatment group (most notably in males) was also considered to be possibly compound-related. The incidence of liver hematopoiesis in both sexes in the P-25 treatment group was moderately higher as compared to the controls. This effect was of doubtful clinical significance due to absence of increased incidence of hematopoiesis in other blood forming organs. The incidence of testicular seminiferous tubular atrophy or degeneration in male rats in the P-25 and P-26 treatment groups was also of doubtful clinical significance due to historical control data of the laboratory. There were no significant changes in hematology parameters, blood biochemistry or in urine. There were also no significant changes in general behavior or food intake. NOAEL for the test chemical was found at the 0.59 mg/kg dose level.
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