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EC number: 421-450-8 | CAS number: 154702-15-5
- 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: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1997
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 997
- Report date:
- 1997
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- yes
Test material
- Reference substance name:
- -
- EC Number:
- 421-450-8
- EC Name:
- -
- Cas Number:
- 154702-15-5
- Molecular formula:
- C44H59N7O5
- IUPAC Name:
- 2-ethylhexyl 4-[(4-{[4-(tert-butylcarbamoyl)phenyl]amino}-6-[(4-{[(2-ethylhexyl)oxy]carbonyl}phenyl)amino]-1,3,5-triazin-2-yl)amino]benzoate
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Male (46) and female (46) Wistar rats were obtained from a colony maintained under SPF-conditions at Charles River Wiga GmbH, Sulzfeld Germany
- Age at study initiation: about 4 weeks old
- Weight at study initiation: 157.4 g - 189.1 g and 118.2 g - 145.2 g for males for females, respectively
- Housing: Housing conditions were conventional. From the start of the treatment period, the animals were housed in groups of five, separated by sex, in suspended stainless steel cages with wire mesh floor and front. During the acclimatisation period they were housed in similar cages in groups of five or six .
- Diet: feed (in powder) was provided ad libitum, from the arrival of the rats until the end of the study.
- Water: tap water was available, ad libitum, from the arrival of the rats until the end of the study.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 24. The temperature exceeded the upper value twice
- Humidity (%): 50 - 70. The humidity was lower than 50 % for two periods of a few hours and higher than 70 % for three such short periods. In addition, the humidity exceeded 70 % for about ten longer periods.
- Air changes (per hr): about 10
- Photoperiod (hrs dark / hrs light): lighting was artificial by fluorescent tubes, time switch controlled at a sequence of 12 h light (7.30-19.30), 12 h dark
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- The oral route was used because this route is recommended in the guidelines for testing of cosmetic ingredients for their safety evaluation. The TNO rodent diet was used as the carrier. The test substance was incorporated into this diet by mixing in a mechanical blender. Because the test substance contained particles of different sizes, the substance was ground in an electric coffee mill prior to diet mixing. Fresh batches of experimental diets were prepared at 2 - 3 week intervals and stored at about 20 °C in a freezer until use.
The doses were selected on the basis of the results of the 14 -day range-finding study. - Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 13 consecutive weeks.
- Frequency of treatment:
- Continuously
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0.15 other: % w/w
- Remarks:
- Basis: nominal in diet. Group 2
- Dose / conc.:
- 0.5 other: % w/w
- Remarks:
- Basis: nominal in diet. Group 3
- Dose / conc.:
- 1.5 other: % w/w
- Remarks:
- Basis: nominal in diet. Group 4: dietary intake corresponding to 831 and 963 mg/kg bw/day for male and female respectively
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent vehicle
Examinations
- Observations and examinations performed and frequency:
- - DETAILED CLINICAL OBSERVATIONS: Yes
- BODY WEIGHT: Yes
- FOOD CONSUMPTION AND COMPOUND INTAKE:: Yes
- FOOD EFFICIENCY: Yes
- WATER CONSUMPTION: Yes
- OPHTHALMOSCOPIC EXAMINATION: Yes
- HAEMATOLOGY: Yes
- CLINICAL CHEMISTRY: Yes
- URINALYSIS: Yes
- OTHER: Renal concentration test - Sacrifice and pathology:
- - GROSS PATHOLOGY: Yes
- HISTOPATHOLOGY: Yes
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Endocrine findings:
- not examined
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
Effect levels
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 831 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 963 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Any other information on results incl. tables
RESULTS
STABILITY, HOMOGENEITY AND ANALYIS OF THE TEST SUBSTANCE
The concentrations of the test substance found in diet samples analysed after storage in the animal room for 7 days or in a freezer for five weeks showed that the substance was stable under simulated experimental conditions. Analysis of 5 samples per diet, taken at different locations, showed that the test substance was homogeneously distributed in the diet at all dose levels. The content of the test substance was close to the intended level in all diets analysed.
GENERAL FINDINGS
The ingestion of the test substance was well tolerated, as evidenced by the absence of treatment-related changes in the appearance, general condition and behaviour of the animals, their growth, food and water consumption, red blood cell and clotting potential values, total white blood cell counts, clinical chemistry values, renal concentrating ability, composition of the urine, organ weights, gross necropsy findings and histopathological findings
In comparison with the controls, the mean percentage of neutrophils was higher and that of lymphocytes lower in all groups of female rats given test substance. The differences showed no dose-response relationship and probably resulted from the relatively low neutrophil and high lymphocyte count in the control group. Most importantly, the differences were not reflected in dose-related or significant changes in the absolute numbers of these cell types and are, therefore, regarded as chance findings, unrelated to treatment.
Applicant's summary and conclusion
- Conclusions:
- Since the ingestion of RA 3643 at dietary levels up to 1.5 % for 13 consecutive weeks was tolerated without signs of toxicity, the dietary concentration of 1.5 % was a no-observed-adverse-effect level of test substance under the conditions of this study. This dietary level provided a mean intake of 831 and 963 mg of test substance/kg bw/day in male and female rats, respectively.
- Executive summary:
The objective of this GLP compliant OECD TG 408 study was to examine the possible sub chronic oral toxicity of the test substance RA 3643 in rats. This substance was administered in the diet, at concentrations of 0, 0.15, 0.5 or 1.5 % w/w, to groups of 10 males and 10 female Wistar rats for 13 consecutive weeks. The ingestion of the test substance was well tolerated, as evidenced by the absence of treatment-related changes in the appearance, general condition and behaviour of the animals, their growth, food and water consumption, red blood cell and clotting potential values, total white blood cell counts, clinical chemistry values, renal concentrating ability, composition of the urine, organ weights, gross necropsy findings and histopathological findings
In comparison with the controls, the mean percentage of neutrophils was higher and that of lymphocytes lower in all groups of female rats given test substanct. The differences showed no dose-response relationship and probably resulted from the relatively low neutrophil and high lymphocyte count in the control group. Most importantly, the differences were not reflected in dose-related or significant changes in the absolute numbers of these cell types and are, therefore, regarded as chance findings, unrelated to treatment. The NOAEL was set at 831 and 963 mg/kg bw/day for male and female rats, respectively.
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