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EC number: 226-970-7 | CAS number: 5580-57-4
- 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
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Endpoint summary
Administrative data
Description of key information
oral:
subacute (28-days): NOAEL = 1000 mg/kg bw/day (OECD 407)
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2008-05-06 to 2008-10-29
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- yes
- Limit test:
- no
- Specific details on test material used for the study:
- - Lot/batch No.: 7218
- Expiration date of the lot/batch: 02/2023
- Stability under test conditions: 15 years
- Storage condition of test material: the test substance was stored at the labotarory temperature during the study - Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source:SPF breeding, VELAZ s.r.o.., Kolec u Kladna, Czech Republic, RCH CZ 21760152
- Age at study initiation: 6 -7 weeks
- Weight at study initiation: ca. 130 g (females) and 170 g (males)
- Fasting period before study: no information
- Housing: 2-3 rats of the same sex in one plastic cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 16.09.2008 To: 16.10.2008 - Route of administration:
- oral: gavage
- Vehicle:
- olive oil
- Details on oral exposure:
- The application form (test substance suspension in olive oil) was prepared daily just before administration.
- Analytical verification of doses or concentrations:
- no
- Details on analytical verification of doses or concentrations:
- The test substance is insoluble in many solvents. Low solubility of the test substance is declared by the sponsor and it was also checked up within the substance identity verification. In this study the substance was found also insoluble in olive oil. Therefore the test substance was administered as an olive oil suspension. A suitable analytical method was not found for homogeneity and stability testing. Since undissolved particles of the test substance are easily visible in the application form, homogeneity was checked by eye (suspension were mixed for 15 minutes by magnetic stirrer).
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- daily
- Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 160 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 400 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Range-finder study
- Rationale for selecting satellite groups: Reversibility of potential effects at the top dose.
- Post-exposure recovery period in satellite groups: 14 days - Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Mortality, general health condition and general clinical symptoms were observed daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly
At the first part of observation behaviour of animals in the cage was monitored: posture, position of eyelids, tonic or clonic movements, piloerection, stereotypes or bizarre behaviour. The second part was the observation during removal from cage: reaction to handling, elasticity of skin, colour of mucous membranes, salivation, lacrimation, cleanliness of fur around foramina.
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION:
- Food consumption: weekly
WATER CONSUMPTION : Yes
- Time schedule for examinations: twice per week
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: day 28 and day 42 (for recovery animals)
- Anaesthetic used for blood collection: Yes (light ether narcosis)
- Animals fasted: 18h
- How many animals: all
- Parameters: total erythrocytes count, mean corpuscular volume, haematocrit, haemoglobin concentration, total leucocytes count, total platelets count, partial thromboplastin time, prothrombin time, fibrinogen, granulocytes, lymphocytes, monocytes
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: day 28 and day 42 (for recovery animals)
- Animals fasted: 18h
- How many animals: all
- Parameters checked in table 1 were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: day 28 and day 42 (for recovery animals)
- Metabolism cages used for collection of urine: Yes
- Animals fasted: No
- Parameters checked in table 2 were examined.
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: once during the last week of treatment and the last week of the recovery time.
- Dose groups that were examined: all
- Battery of functions tested: During functional examination, the sensory reactivity on auditory, visual, proprioceptive stimuli and pupillary reflex were evaluated and motor activity assessment was conducted. Moreover the individual observations of grip strength were performed using dynamometer. Measurements were made on: 1) pectoral legs, 2) pelvis legs, 3) all four legs. Grip power was expressed in Newtons. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
At the end of study the experimental animals were narcotised and sacrificed by cutting the neck spine and medulla. After the gross necropsy of the cranial, thoracic and abdominal cavities the organs for weighing and further histological examination were collected. The absolute weights of liver, kidneys, adrenals, testes or ovaries, epididymides or uterus, thymus, spleen, brain, pituitary gland and heart were recorded.
HISTOPATHOLOGY: Yes (see table 4) - Statistics:
- The ANOVA test - Analysis of Variance (QC.Expert 2.5) at significance level 0.05 was used for the statistical analysis. This statistical analysis was used for the results of haematology, blood chemistry, urinalysis, biometry of organs and body weight. Control group with vehicle was compared with three treated groups and satellite control with vehicle was compared with satellite treated group.
The results statistically significant on probability level 0.05 are indicated by figures with asterisk in the tables of medians or averages. - Clinical signs:
- no effects observed
- Description (incidence and severity):
- No clinically observed signs of toxicity were detected. The animal' s health condition was very good during whole study and functional observation evidenced no effect of the test substance.
- Mortality:
- no mortality observed
- Description (incidence):
- There were no unscheduled deaths during the test.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No adverse effect on body weight development was detected. The body weight of all treated and control groups were well-balanced without statistically significant difference during the whole application and recovery period. The intergroup differences were minimal and isolated, therefore they were regarded as fortuitous. No significant differences of average body weight increment were recorded in treated groups of males and females (in comparison with control).
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- No adverse effect on dietary intake or food conversion was detected. Food consumption of all groups was well-balanced. Sporadic slight intergroup reduction or increasing of food consumption and food conversion of males were considered to be a result of normal variation, which could not be related with administration of the test substance. Inspection of water consumption revealed no significant intergroup differences during the application period.
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The haemocoagulation examination detected statistically significant changes only in males. Shortening of protrombine time and prolongation of partial thromboplastin time were recorded at all dose levels but without dose-response relationship. These changes were not recorded in satellite treated males after 14-day recovery period - the effect of the test substance on this blood component was reversible. All changed parameters were within historical control range. These intergroup differences were considered to be adaptative response of a living organism to stress without toxicological significance.
The haematology parameters of red blood cells were without significant changes. Decreased value of haematocrite was measured in males of the lowest dose level only at the end of application period, but expected related changes of total erythrocyte count, mean corpuscular volume or haemoglobin volume were not detected. Changes of differential leucocyte count were recorded in both sexes but with statistical significance only in males at the middle dose level at the end of application period. Increased total leucocyte count was found out at the end of recovery period. These differences of haematological parameters were considered to be adaptative response to stress without toxicological significance. - Urinalysis findings:
- no effects observed
- Description (incidence and severity):
- Urinalysis detected no treatment-related effects in males and females.
- Behaviour (functional findings):
- no effects observed
- Description (incidence and severity):
- unctional observation evidenced no effect of the test substance. All inter and intra group differences in behavioural scores (upstanding, emiction, defecation) and sensory reactivity were considered to be a result of normal variation for rats of the strain and age used and were no toxicological importance. There were no treatment-related changes in functional performance parameters measured (grip strength).
- Description (incidence and severity):
- Biometry of organs detected intergroup difference in absolute and relative weight of thymus in males but statistically significant increase was found only in absolute weight in the middle dose level. Slight intergroup difference of uterus weight was recorded at treated females. These morphological changes are commonly observed in employed strain of females and are considered to be not of toxicological significance.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- Pathology examination revealed yellowish colour of chyme and coloured mucous membrane in digestive system at the end of application period with dose-related response. Other macroscopic findings were found out in stomach of treated males and females: congestion of mucous membrane, dilatation or focal changes on mucous membrane. These changes were not recorded at the end of recovery period - the effect of the test substance was reversible. Application of the test substance caused temporary colouring of the chyme but without marked effect on function of digestive tract.
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Metastatic mineralization in kidneys of females at the middle and highest dose levels were found out at the end of the application period. Due to absence of changed urinary parameters, this was considered to be no toxicological importance. Further sporadic pathologic changes were recorded: inflammation in prostate gland in males and hydrometra of uterus or cyst on ovaries in females. Frequencies of these microscopic findings in genital tract were similar in treated and control groups. This was considered to be of no toxicological importance.
- Histopathological findings: neoplastic:
- no effects observed
- Description (incidence and severity):
- No neoplastic findings were recorded by histopathological examination.
- Other effects:
- effects observed, treatment-related
- Description (incidence and severity):
- Other findings: Yellowish colour of excrement in the treated animals was recorded from the 1st week of application to the 1st week of the recovery period. As the pigment is of yellow color, this intakes passage of the test item through the gastrointestinal tract.
Biochemical Examination:
Statistical analysis of parameters revealed one significant difference in males (decreased calcium concentration against control at the lowest dose level). This variable factor was not important toxicologically because its fluctuation was within historical control range. - Details on results:
- CLINICAL SIGNS AND MORTALITY: There were no unscheduled deaths during the test. No clinically observed signs of toxicity were detected. The animal' s health condition was very good during whole study and functional observation evidenced no effect of the test substance.
BODY WEIGHT AND WEIGHT GAIN: No adverse effect on body weight development was detected. The body weight of all treated and control groups were well-balanced without statistically significant difference during the whole application and recovery period. The intergroup differences were minimal and isolated, therefore they were regarded as fortuitous. No significant differences of average body weight increment were recorded in treated groups of males and females (in comparison with control).
FOOD/WATER CONSUMPTION AND COMPOUND INTAKE: No adverse effect on dietary intake or food conversion was detected. Food consumption of all groups was well-balanced. Sporadic slight intergroup reduction or increasing of food consumption and food conversion of males were considered to be a result of normal variation, which could not be related with administration of the test substance. Inspection of water consumption revealed no significant intergroup differences during the application period.
HAEMATOLOGY: The haemocoagulation examination detected statistically significant changes only in males. Shortening of protrombine time and prolongation of partial thromboplastin time were recorded at all dose levels but without dose-response relationship. These changes were not recorded in satellite treated males after 14-day recovery period - the effect of the test substance on this blood component was reversible. All changed parameters were within historical control range. These intergroup differences were considered to be adaptative response of a living organism to stress without toxicological significance.
The haematology parameters of red blood cells were without significant changes. Decreased value of haematocrite was measured in males of the lowest dose level only at the end of application period, but expected related changes of total erythrocyte count, mean corpuscular volume or haemoglobin volume were not detected. Changes of differential leucocyte count were recorded in both sexes but with statistical significance only in males at the middle dose level at the end of application period. Increased total leucocyte count was found out at the end of recovery period. These differences of haematological parameters were considered to be adaptative response to stress without toxicological significance.
CLINICAL CHEMISTRY: Statistical analysis of parameters revealed one significant difference in males (decreased calcium concentration against control at the lowest dose level). This variable factor was not important toxicologically because its fluctuation was within historical control range.
URINALYSIS: Urinalysis detected no treatment-related effects in males and females.
NEUROBEHAVIOUR: Functional observation evidenced no effect of the test substance. All inter and intra group differences in behavioural scores (upstanding, emiction, defecation) and sensory reactivity were considered to be a result of normal variation for rats of the strain and age used and were no toxicological importance.There were no treatment-related changes in functional performance parameters measured (grip strength).
ORGAN WEIGHTS: Biometry of organs detected intergroup difference in absolute and relative weight of thymus in males but statistically significant increase was found only in absolute weight in the middle dose level. Slight intergroup difference of uterus weight was recorded at treated females. These morphological changes are commonly observed in employed strain of females and are considered to be not of toxicological significance.
GROSS PATHOLOGY: Pathology examination revealed yellowish colour of chyme and coloured mucous membrane in digestive system at the end of application period with dose-related response. Other macroscopic findings were found out in stomach of treated males and females: congestion of mucous membrane, dilatation or focal changes on mucous membrane. These changes were not recorded at the end of recovery period - the effect of the test substance was reversible. Application of the test substance caused temporary colouring of the chyme but without marked effect on function of digestive tract.
HISTOPATHOLOGY: Metastatic mineralization in kidneys of females at the middle and highest dose levels were found out at the end of the application period. Due to absence of changed urinary parameters, this was considered to be no toxicological importance. Further sporadic pathologic changes were recorded: inflammation in prostate gland in males and hydrometra of uterus or cyst on ovaries in females. Frequencies of these microscopic findings in genital tract were similar in treated and control groups. This was considered to be of no toxicological importance. No neoplastic findings were recorded by histopathological examination.
OTHER FINDINGS: Yellowish colour of excrement in the treated animals was recorded from the 1st week of application to the 1st week of the recovery period. As the pigment is of yellow color, this intakes passage of the test item through the gastrointestinal tract. - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- >= 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Key result
- Critical effects observed:
- no
- Conclusions:
- The NOAEL (No Observed Adverse Effect Level) for males and females in this study is equal to 1000 mg/kg/day.
- Executive summary:
The test substance, was tested for subacute toxicity using the method B.7. Repeated Dose (28 days) Toxicity (Oral), Council Regulation (EC) No. 440/2008, Published in O.J. L142, 2008 in compliance with GLP.
Wistar rats of SPF quality were used for testing. The test substance was administered as suspension in olive oil using a stomach tube; oral application of rats was made daily. The study includes four main groups and two satellite groups of animals. Each main group consisted of 5 males and 5 females; each satellite group consisted of 5 males and 5 females. Main groups contained 3 treated groups (doses 160, 400, 1000 mg/kg of body weight /day) and one control group (vehicle only). The satellite groups contained one control group (vehicle only) and one treated group (1000 mg/kg/day). The administration period lasted 28 days. After that animals of main groups were sacrificed and satellite animals were observed for the next 14 days without treatment.
Doses for the main study - 160, 400, 1000 mg/kg/day were chosen on the basis of results of dose-range finding experiment.
During the 28-day study clinical observation and health status control were performed daily. The body weight, food consumption were measured weekly and the detailed clinical observation was carried out in the same time interval. Water consumption was measured twice a week. Before the end of study the functional observation was accomplished. The study was finished by urinalysis, haematological and biochemical analysis, and gross necropsy of animals. The selected organs for weighing and histopathology examination were removed.
There were no unscheduled deaths during the test. No clinically observed signs of toxicity were detected. The animal's health condition was very good during whole study and functional observation evidenced no effect of the test substance. No adverse effect on body weight development was detected. The body weight and body weight increment of all test groups was relatively well-balanced during whole application and recovery period. No adverse effect on dietary intake, food conversion or water consumption was detected. The haemocoagulation examination detected significant changes only in males but these changes were not recorded in satellite treated males after 14-day recovery period. Changes of differential leucocyte count were recorded in both sexes but with statistical significance only in males at the end of application. Increased total leucocyte count was measured at the end of recovery period. Statistical analysis of parameters revealed one significant difference in males ( decreased calcium concentration against control at the lowest dose level). All these intergroup differences were considered to be adaptative response to stress without toxicological significance.
Application of the test substance caused temporary colouring of chyme but without marked effect on function of digestive tract. Metastatic mineralization in kidneys of females at the middle and highest dose levels were found out at the end of the application period. Due to absence of changed urinary parameters, this was considered to be no toxicological importance.Based on the results of laboratory investigations in clinical biochemistry, haematology and urinalysis and with respect to the results of histopathological examination the following conclusion about NOAEL can be suggested in this study: The NOAEL (No Observed Adverse Effect Level) for males and females in this study is equal to 1000 mg/kg/day.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
With C. I. Pigment Yellow 93 (CAS number 5580-57-4) a GLP subacute toxicity study according to OECD 407 (Synthesia, 2009) has been performed. The oral administration of Pigment Yellow 93 to rats (5/sex) by gavage for a period of twenty-eight consecutive days at dose levels 160, 400 and 1000 mg/kg/day produced no toxicologically significant changes in the parameters measured. No major functional changes in any organ systems or severe organ dysfunction were detected. Consistent changes in clinical biochemistry, haematology and urinalysis parameters, which indicate organ dysfunction, were not recorded at any dose level. Histopathological examination revealed no pathological changes, which could be related with administration of the test substance. Based on the results of laboratory investigations in clinical biochemistry, haematology and urinalysis and with respect to the results of histopathological examination the following conclusion about NOAEL can be suggested in this study:
The NOAEL (No Observed Adverse Effect Level) for males and females in this study is equal to 1000 mg/kg/day.
Justification for classification or non-classification
Classification, Labelling, and
Packaging Regulation (EC) No 1272/2008
The available experimental test
data are reliable and suitable for classification purposes under
Regulation (EC) No 1272/2008. Based on available data on repeated dose
toxicity, the test item is not classified according to Regulation (EC)
No 1272/2008 (CLP) as
amended for the thirteenth time in Regulation (EC) No. 2018/1480.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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