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EC number: 204-171-4 | CAS number: 117-08-8
- 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: inhalation
Administrative data
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline with acceptable restrictions
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 979
- Report date:
- 1979
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
- Deviations:
- yes
- Remarks:
- No functional observations and ophthalmological examinations; fluctuations in chamber concentrations
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Tetrachlorophthalic anhydride
- EC Number:
- 204-171-4
- EC Name:
- Tetrachlorophthalic anhydride
- Cas Number:
- 117-08-8
- Molecular formula:
- C8Cl4O3
- IUPAC Name:
- tetrachloro-1,3-dihydro-2-benzofuran-1,3-dione
- Details on test material:
- - Name of test material (as cited in study report): Tetrathal
- Supplier: Monsanto Chemical Company
- Physical state: fines-dust form
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Age at study initiation: 53 days
- Weight at study initiation: males 271 g (244-295), females 170 g (138-194)
- Diet (e.g. ad libitum): Purina Laboratory Rodent Chow 5001
- Water (e.g. ad libitum): tap water
- Acclimation period: 2 weeks
Administration / exposure
- Route of administration:
- inhalation: dust
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: unchanged (no vehicle)
- Remarks on MMAD:
- MMAD / GSD: 0.5 mg/m3 dose group: 2.69 µm/1.90-11.58 (The range of geometric standard deviation for 11 of the 13 samlples was 1.90 to 4.99, the other two value of 10.69 and 11.58 may have resulted from a sampling error);
5.0 mg/m3 dose group: 3.34 µm/2.07-4.53
50 mg/m3 dose group: 3.45 µm/1.80-4.25 - Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel and glass chambers in which the animals were exposed had a total volume of one cubic meter with an effective exposure volume of 760 liters.
- Source and rate of air: operated dynamically at an air flow rate of approximately 288 liters per minute. This flow rate provided one complete air change every 3.6 minutes and a 99% equilibrium time (T99) of 16.1 minutes.
- System of generating particulates/aerosols: The test material Fines Dust Form, was sieved through a 60-mesh sieve and hand packed into a cylinder of a Wright dust-feed mechanism. Appropriate exposure concentrations were achieved by adjusting the gear ratios of the dust-feed mechanism and by varying the air flow through the dust-feed mechanism.
- Method of particle size determination: Particle size distribution assessment was made once a week using a Batelle cascade impactor.
TEST ATMOSPHERE
- Brief description of analytical method used: The initial method selected to analyze chamber concentrations was to utilize the GCA Respirable Dust Monitor (Model 201). A different method was initiated on Week 6. The test material was collected on a glass fiber filter, extracted with hot water, an alliquot was taken and the absorbance measured at 213 nm on the Hitachi Model 110-40 uV/Vis spectrophotometer. A calibration curve, comparing known concentrations of the test material in water versus absorbance, was prepared. Chamber concentrations beginning with Week 6 were calculated by comparing the total amount of material collected to the total volume of air sampled. Exposure levels for the first five weeks of the study have been extlapolated based on a regression analysis comparing daily nominal concentration and daily average concentrations from Weeks 6 through 13.
- Samples taken from breathing zone: yes - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Chamber concentrations were analyzed using a GCA Respirable dust monitor for the first 5 weeks and then spectrophotometrically during the remainder of the study. Analytical exposure levels for the first 5 weeks were calculated by extrapolation based on regression analysis of daily nominal concentrations. Daily analytical concentrations were used for the last 8 weeks of the study. Correlation coefficients for regression analysis of analytical and nominal concentrations was 0.97 for the low, mid and high doses combined, and was 0.90 for the high and mid dose, but only 0.50 for the low dose; hence the low dose level may not be accurately described.
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- 6 hours/day, 5 days/week
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0, 0.5, 5 and 50 mg/m3
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
0, 0.73, 4.15 and 36.3 mg/m3
Basis:
analytical conc.
- No. of animals per sex per dose:
- 15
- Control animals:
- yes, concurrent vehicle
Examinations
- Observations and examinations performed and frequency:
- DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice daily
BODY WEIGHT: Yes
- Time schedule for examinations: weekly from 12 days prior to exposure through termination
HAEMATOLOGY: Yes
- Time schedule for collection of blood: week 7 and 13
- Anaesthetic used for blood collection: No, collected by venipuncture of the orbital sinus
- Animals fasted: Yes
- How many animals: 15/sex
- Parameters checked: hemoglobin, hematocrit, erythrocyte count, clotting time, total and differential leukocytes
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: week 7 and 13
- How many animals: 15/sex for the control and high dose group
- Parameters checked: alkaline phosphatase, blood urea nitrogen, serum glutamic pyruvic transminase and blood glucose
URINALYSIS: Yes
- Time schedule for collection of urine:
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked: appearance, bilirubin, ketones, glucose, occult blood, pH, protein, specific gravity, microscopic examination - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
15 animals/sex/group were sacrificed by exsanguination under ether anesthesia. The organ weight of liver, lungs, pituitary and spleen were measured. Tissues fixed and histopathologically examined were: adrenals (2), bone marrow (sternal), brain (3 sections including frontal cortex and basal ganglia, parietal cortex and thalamus; cerebellum and pons), eyes (2), gonads (ovaries, testes and epididymides), mammary gland (right inguinal), pancreas, pituitary, salivary gland (right submaxillary), skeletal muscle (right biceps femoris), skin (right inguinal), spinal cord, spleen, stomach, heart (with coronary vessels), intestine (colon, duodenum, ileum), kidneys (2), liver (2 sections), lung and mainstem bronchi, lymph node (mesenteric), thyroid/parathyroid, urinary bladder, uterus/prostrate, gross lesions, tissue masses. - Statistics:
- Mean group values for body weights, organ weights and weight ratios were evaluated statistically using Dunnett's test. The F-test and Student’s t-test were used to compare group means for hematology and clinical chemistry parameters. When variances were observed in the F-test, a Student’s t-test, as modified using Cochran's approximation test was employed. All comparisons were made at both the 5% and 10% level of significance.
Results and discussion
Results of examinations
- Details on results:
- CLINICAL SIGNS AND MORTALITY: All animals survived the study duration. Physical observations were limited to the high dose group, and consisted of increased nasal discharge, ano-genital staining and excessive lacrimation.
BODY WEIGHT AND WEIGHT GAIN: Body weight gains for all levels for both sexes were considered comparable to controls.
HAEMATOLOGY: no treatment related effects were observed.
CLINICAL CHEMISTRY: no treatment related effects were observed.
URINALYSIS: High dose males exhibited slight proteinuria at 7 weeks and 13 weeks. Microscopic examination of the urine revealed a slight increase in the amount of amorphous matter in the urine after 13 weeks.
ORGAN WEIGHTS: An significant increase in absolute and relative lung weights (p ≤ 0.01) in the mid-dose & high-dose males, and high-dose females were considered treatment-related. The percentage increase in the relative lung weight in the mid and high dose males were 24 and 62, respectively. Similarly, the percentage increase in the relative lung weight in the mid and high dose females were 7 and 25, respectively. The several other small changes in organ weights or ratios were considered unrelated to treatment since there was no dose-response evident.
GROSS PATHOLOGY: The only gross pathological observation attributable to treatment was the appearance of petechial hemorrhages in the lungs of several treated rats.
HISTOPATHOLOGY: NON-NEOPLASTIC: Histopathological changes in the lungs were also noted in all doses groups. Irregular thickening of the alveolar septa, noted in all dose groups. Irregular thickening of the alveolar septa, scattered pigmented macrophages and multinucleate giant cells, multifocal accumulation of alveolar macrophages and multifocal alveolar hemorrhages were noted. High dose animals also exhibited mild centrilobular hepatocellular hypertrophy.
Effect levels
open allclose all
- Dose descriptor:
- NOAEC
- Effect level:
- 0.73 mg/m³ air (analytical)
- Sex:
- male/female
- Dose descriptor:
- LOAEC
- Effect level:
- 4.15 mg/m³ air (analytical)
- Sex:
- male/female
- Basis for effect level:
- other: lung weight and histological changes
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Cumulative mean analytical concentrations were 0.73, 4.15, and 36.3 mg/m3 respectively based on spectrophotometric analysis of chamber samples. Although the mean analytical chamber concentrations for the low and mid level appear close to target levels, extreme variations in chamber concentrations were observed from day to day and also during any given day. At the high dose level, similar daily excursions occurred. In general, during weeks 2 through 5, animals appeared to have been exposed to concentrations well below the target levels.
Applicant's summary and conclusion
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.
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