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EC number: 401-680-5 | CAS number: 125304-04-3 TINUVIN 171; TINUVIN 571
- 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
Description of key information
In a subacute study with rats the test substance did not cause any adverse effects up to the highest dose tested (1000 mg/kg), therefore, the NOAEL was set at 1000 mg/kg bw.
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:
- 1986-06-03 - 1987-02-18
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- adopted May 12, 1981
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- yes
- Species:
- rat
- Strain:
- other: Crl:CD (SD) BR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Wiga, Sulzfeld, Germany
- Age at study initiation: 4 - 5 weeks/period
- Weight at study initiation: 90-100 g
- Fasting period before study: no
- Housing: individually in Makrolon type III cages on soft wood bedding (LIGNOCEL (R), type 3/4
- Diet: ALTROMIN(R) standard diet No. 1324, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 1 week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 10
- Air changes (per hr): 15 -20
- Photoperiod: 12 hrs dark / 12 hrs light
IN-LIFE DATES: 03-June - 09-July 1986 - Route of administration:
- oral: gavage
- Vehicle:
- olive oil
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
The dose formulations were prepared daily as follows: 250, 1250 and 5000 mg of the test item were weighed into volumetric flasks and filled up with the carrier to a final volume of 50 mL each. Subsequently the compound suspensions in the volumetric flasks were kept homogeneous by placing on magnetic stirrers till the end of dosing.
VEHICLE
- Justification for use and choice of vehicle: standard vehicle for studies of this type
- Concentration in vehicle: 5, 25 or 100 mg/mL
- Amount of vehicle: 10 mL/kg bw - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Prior to the start of the study, pretest samples from all dose levels of the test compound were analysed for stability, concentration and homogeneity. During the first week and the fourth week of the study samples from all dose levels were analysed for concentration and homogeneity. Concentration and homogeneity of all examined samples have been found to be acceptable. The test item has been proven stable.
- Duration of treatment / exposure:
- 28 d
- Frequency of treatment:
- Once daily, approximately the same time each day, 7 days per week.
- Dose / conc.:
- 50 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 250 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: The dose levels were based on the results of an acute toxicity study and the dosages were establishedin accordance with the sponsor.
- Positive control:
- None.
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: The animals were observed for clinical signs once before commencement of administration; twice daily on 7 days/week. Observations for mortality/viability were recorded twice daily on 7 days/week.
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
- Time schedule for examinations: Body weight was recorded before treatment and daily at the time the animals were dosed.
FOOD CONSUMPTION / FOOD EFFICIENCY: Yes
Individual food consumption was recorded before treatment and once every week during treatment.
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Before treatment and at the end of the treatment period all animals were subjected to an ophthalmologic examination. The eyes of the animals were examined with an ophthalmoscope and a slit-lamp. For exact examination of the lens, vitreous body and fundus of the eyes mydriasis was induced after installation of I % aqueous atropinesulfate into the conjunctival sac.
HAEMATOLOGY: Yes
- Time schedule for collection of blood: At the end of the study; blood samples were collected between 7.00 and 9.00 a.m. (24 hours after compound administration) to prevent chronobiologic variations.
- Anaesthetic used for blood collection: no data; blood collection for coagulation parameter assessment: CO2
- Animals fasted: Yes, overnight
- How many animals: all animals
- Parameters examined: Erythrocyte count, hemoglobin, hematocrit, mean cell volume, mean cell hemoglobin, mean cell hemoglobin concentration, reticulocyte count, red cell morphology, total leukocyte count, differential leukocyte count, platelet count, thromboplastin time, partial thromboplastin time, thrombin time
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Blood samples were collected at the end of the study between 7.00 and 9.00 a.m. (24 hours after compound administration) to prevent chronobiologic variations.
- Animals fasted: Yes
- How many animals: all animals
- Parameters examined: Glucose, urea, uric acid, creatinine, total bilirubin, total cholesterol, triglyceride, aspartate-aminotransferase, alanine-aminotransferase, lactate-dehydrogenase, gamma-glutamyl-transpeptidase, alkaline phosphatase, total protein (Biuret method and electrophoresis), inorganic phosphorus, chloride, sodium, potassium, calcium, albumin/globulin-ratio.
URINALYSIS: Yes
- Time schedule for collection of urine: Urinalyses were done at pretreatment period, week 2 and, week 4 (urine collected in 3 hours, 24 hours after compound administration, initial water supply: 2 mL/100 g bw).
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- Parameters examined: Volume, color, turbidity, specific gravity, blood, leukocytes, nitrite, pH, protein, glucose, ketone, urobilinogen, bilirubin, sediment, sodium, potassium, calcium, chloride
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
At autopsy the following weights were recorded from all animals: adrenals, brain, heart, kidneys, liver, ovaries, spleen, testes, thymus, thyroid glands with parathyroid glands
HISTOPATHOLOGY: Yes
Microscopical examinations:
Adrenal glands, aorta, brain, caecum, colon, duodenum, epididymides, esophagus, eyes with optic nerves, femur, heart, ileum, pituitary gland, prostate, rectum, salivary gland (mandibular), sciatic nerve, seminal vesicle, skeletal muscle, skin, spinal cord (thoracic), spleen, sternum, stomach, jejunum, kidneys, liver, lungs with bronchi, lymph nodes (cervical/mesentery), mammary gland, ovaries, pancreas, testes, thymus, thyroid glands with parathyroid glands, tongue, trachea, urinary bladder, uterus, all gross lesions - Statistics:
- Routine evaluation of the data was done by:
Student's t-test: Normal distributed values, single treatment groups were compared against the control group.
U-test: In not normal distributed values the U-test of Wilcoxon, Mann and Wliitney was employed to compare two autonomous random samples.
William's test: The control group was compared with treatment groups of constant increasing or decreasing dosage, to determine the lowest dosage, where a significant difference was apparent. The method used therefore was the Williams test (Trend test).
Bartlett's test: This test checks the homogeneity of variance in normal distributed data groups.
Global test: In biological datas mostly a sufficient normal distribution of values cannot be assumed. Therefore the H-test of Kruskal and Wallis was applied to compare several autonomous random samples. - Clinical signs:
- no effects observed
- Description (incidence and severity):
- No clinical signs of toxicity were observed.
- Mortality:
- no mortality observed
- Description (incidence):
- No animal died during the study.
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- A slight decrease in female rats and a slight increase in male rats were seen in relation to control, but no dose relation and no statistical significance were found.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- In food consumption no remarkable differences were found. In females of group 50 mg/kg bw and 1000 mg/kg bw a slight statistical significant increase of mean food consumption in g/day/kg bw was observed at week 4, but no dose relation was seen.
- Food efficiency:
- no effects observed
- Description (incidence and severity):
- In food efficiencies no remarkable differences were found.
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- no effects observed
- Description (incidence and severity):
- At ophthalmologic examinations no abnormal signs or pathologic symptoms were found.
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Differences of statistical significance between control and treated groups were found occasionally. All parameters were found to be in normal range and no dose relationship was seen, therefore the deviations were considered to be not of toxicological relevance.
- Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Differences of statistical significance between control and treated groups were found occasionally. All parameters were found to be in normal range and no dose relationship was seen, therefore the deviations were considered to be not of toxicological relevance.
- Urinalysis findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- In individual animals some parameters were observed slightly deviating from normal range, but no deviations related to the test substance were seen. Values slightly outside from normal range were found to be one time occurrences and therefore not considered to be compound related.
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No treatment related changes were observed. In males of group 50 mg/kg bw a statistical significant increase of the heart weight was found in relation to control (but only in absolute organ weight). In males of group 50 mg/kg bw a statistical significant decrease of the spleen was found (absolute and relative), but no dose relation was observed. In males of group 1000 mg/kg bw a statistical significant decrease of the thyroid glands was found (in relative organ weights). No dose relation was observed.
- Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The main lesions observed at gross observation were claycolored or mottled livers and alterations of thymus. Most of the observed lesions were found to be histologically normal. Therefore these lesions were considered to be not compound related.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No compound related lesions were found upon microscopic examinations of the tissues. The lesions most frequently seen included cytoplasmic vacuolation in the liver, hydronephrosis in the kidney, histiocytosis in the lungs, and posterior synechia in the eye. These lesions occurred with generally equal frequency in control and drug-treated groups, and therefore are considered not to be treatment-related. All other lesions observed occurred in one sex only, were one time occurrences and/or were seen in both control and treated groups and were therefore not considered to be treatment-related.
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No test-item related adverse effects up to and including the high dose level of 1000 mg/kg bw/d.
- Critical effects observed:
- not specified
- Conclusions:
- The repeated administration of the test article by gavage for 28 consecutive days to rats at doses of 50, 250 and 1000 mg/kg did not result in compound-related effects. The No Observed Effect Level was found to be 1000 mg/kg body weight.
- Executive summary:
In a 28-day repeated dose toxicity study according to OECD guideline 407 and in compliance with GLP, the test item in olive oil was administered daily to five rats/sex and dose level by gavage at dose levels of 0, 50, 250, and 1000 mg/kg body weight. Diet and water were provided ad libitum. All rats were observed at least twice daily for mortality and clinical signs of toxicity. Body weights were recorded daily, food consumption weekly. Ophthalmologic examinations were done during pretreatment and at week 4 of treatment. Hematology, blood chemistry evaluations and blood clotting investigations were conducted at termination of the study. Urinalyses were done during pretreatment and at week 2 and 4 of dosing. All rats were sacrificed after 4 weeks of treatment. Body weight of the exsanguinated animals and organ weights were taken and gross post mortem examinations were performed on all rats. A histopathological examination was done on all rats of the control and high-dose group and on all gross lesions seen at necropsy. No clinical signs of toxicity were observed and no animal died during the study. In body weight gain and food consumption no remarkable differences were seen between treated animals and control. At ophthalmologic examinations no abnormal signs or pathologic symptoms were found. In clinical laboratory investigations no deviations of toxicological relevance were seen, although differences of statistical significance between control and treated groups were found occasionally. The main lesions observed at gross observation were claycolored or mottled livers and alterations of thymus. The lesions are considered not to be compound related. No compound related lesions were found upon microscopic examinations of the tissues. As a result, the NO(A)EL was determined at 1000 mg/kg body weight in males/females.
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
In a GLP-compliant subacute rat gavage study (OECD 407), a total of 40 Sprague-Dawley rats (5 males and 5 females per dose group were dosed by gavage with 0, 50, 250 and 1000 mg/kg body weight daily for 28 consecutive days (Biomedizinische Forschungsanstalt, 1987). Controls received the vehicle (olive oil) alone. No relevant clinical signs and no mortalities related to administration of the test substance were observed during the treatment period. In body weight gain and food consumption no remarkable differences were seen between treated animals and control. At ophthalmologic examinations no abnormal signs or pathologic symptoms were found. In all examined parameters of clinical laboratory investigations no deviations of toxicological relevance were seen, although differences of statistical significance between control and treated groups were found occasionally. All rats were sacrificed after 4 weeks of treatment. Body weight of the exsanguinated animals and organ weights were taken and gross post mortem examinations were performed on all rats. The main lesions observed at gross observation were clay-colored or mottled livers and alterations of thymus. Most of these lesions were found to be histologically normal and therefore considered to be not compound related. Slight deviations in organ weights of heart, spleen and thyroid glands with parathyroid glands in males were identified, however these were not dose related and transient and therefore considered to be irrelevant No compound related lesions were found upon microscopic examinations of the tissues. The lesions most frequently seen included cytoplasmic vacuolation in the liver, hydronephrosis in the kidney, histiocytosis in the lungs, and posterior synechia in the eye. These lesions occurred with generally equal frequency in control and drug-treated groups, and therefore are considered not to be treatment-related. In conclusion, based on the lack of relevant signs of toxicity, the NOAEL was set at 1000 mg/kg/day.
Justification for classification or non-classification
Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008
The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the present data, classification for repeated dose toxicity is not warranted under Regulation (EC) No.1272/2008.
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