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EC number: 701-337-2 | CAS number: -
- 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:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 9 December 2003 - 7 March 1994
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study was conducted according to OECD guideline 412 and under GLP conditions.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 994
- Report date:
- 1994
- Reference Type:
- publication
- Title:
- Twenty-eight day nose-only inhalation toxicity study of resorcinol bis-diphenylphosphate (Fyrolflex RDP) in rats
- Author:
- Henrich, R.T., Johnson, W.D., Rajendran, N., Freudenthal, R.I., Tomlinson, M.J., Aranyi, C.
- Year:
- 2 000
- Bibliographic source:
- International Journal of Toxicology, 19: 223-231 (2000)
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
- Deviations:
- yes
- Remarks:
- in addition, MNSE activity was determined to study neurotoxicity
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 3-[(diphenoxyphosphoryl)oxy]phenyl diphenyl phosphate
- EC Number:
- 701-337-2
- Cas Number:
- not available
- Molecular formula:
- C30H24O8P2
- IUPAC Name:
- 3-[(diphenoxyphosphoryl)oxy]phenyl diphenyl phosphate
- Details on test material:
- - Name of test material (as cited in study report): Fyrolflex RDP
- Physical state: Liquid
- Analytical purity: Confidential information
- Composition of test material, percentage of components: Confidential information
- Purity test date: Confidential information
- Lot/batch No.: Confidential information
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 Laboratories
- Age at study initiation: 8-9 weeks
- Weight at study initiation:
Males: 196-233 g
Females: 167-212 g
- Housing: According to guideline
- Diet (e.g. ad libitum): Ad libitum, rodent chow
- Water (e.g. ad libitum): Ad libitum, tap water
- Acclimation period: 3 days (of 15 days quaratine)
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-26
- Humidity (%): 32-60
- Air changes (per hr): 15 +/- 2
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- nose only
- Vehicle:
- other: unchanged (no vehicle)
- Remarks on MMAD:
- MMAD / GSD: By Quartz Crystal Microbalance (QCM)
MMAD: 1.39-1.70 um
GSD: 1.67-2.04 um - Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 52-port nose-only inhalation exposure chambers
- Method of holding animals in test chamber: Holding tubes
- Source and rate of air: Regulated compressed air source
- System of generating particulates/aerosols: nebulizers and regulated compressed air source
- Air flow rate: Adjusted to generate aerosol with particle size of <3 um MMAD
- Treatment of exhaust air: Moved through an inertial trap and a particulate filter by a ring compressor and exhausted outside the building
TEST ATMOSPHERE
- Brief description of analytical method used:
Aerosol mass concentraiton: Gravimetric analysis (filter), light scattering method (sensors) and chemical analysis (filter)
Aerosol particle size: Quartz Crystal Microbalance (QCM)
- Samples taken from breathing zone: no, only from filters and sensors - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Gravimetry and chemical analysis
- Duration of treatment / exposure:
- 4 weeks
- Frequency of treatment:
- 6 hours/day 5 days/week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0.1, 0.5, 2.0 mg/l
Basis:
nominal conc.
- No. of animals per sex per dose:
- Low- and mid-dose group: 10
High-dose group: 20 - Control animals:
- other: filtered air
- Details on study design:
- - Rationale for animal assignment: Random (constrained by body weight)
- Post-exposure recovery period in satellite groups: 60 days
- Section schedule rationale: Random - Positive control:
- Not relevant
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily
- Cage side observations: mortality and moribundity
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: at least weekly
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes, weekly
HAEMATOLOGY: Yes
- Time schedule for collection of blood: 7 days prior to exposure
- Anaesthetic used for blood collection: Yes (CO2 or sodium pentobarbital at termination)
- Animals fasted: Yes (overnight before termination)
- How many animals: All
- Parameters checked:
APTT
Erythrocyte count and morphology
Hematocrit
Hemoglobin concentration
Leukocyte count (total and differential)
Mean corpuscular hemoglobin
Mean corpuscular hemoglobin concentration
Mean corpuscular volume
Platelet count
Prothrombin time
Reticulocyte count
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood:
- Animals fasted: Yes (overnight before termination)
- How many animals: All
- Parameters checked:
Albumin
Albumin/globulin ratio (calculated)
Bilirubin (total)
Blood urea nitrogen
Calcium
Chloride
CPK
Cholesterol
Cholinesterase (plasma)
Cholinesterase (erythrocyte)
Creatinine
Gamma glutamyl transpeptidase
Globulin
Glucose
LDH
Monocyte non-specific esterase
Phosphorus
Potassium
Serum alanine aminotransferase
Serum alkaline phosphatase
Serum aspartase aminotransferase
Sodium
Total protein
Triglycerides - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes, examination of external surface and all orifices; external surfaces of brain and spinal cord; organs and tissues of cranial, thoracic, abdominal and pelvic cavities and neck; remainder of the carcass
ORGAN WEIGHTS: Yes, see below:
Liver
Kidney
Lungs
Spleen
Adrenal glands
Heart
Brain
Testes with epididymides or ovaries
Pituitary
Thymus
Thyroid/parathyroids
At recovery only lung weight determined
HISTOPATHOLOGY: Yes, microscopic examination of tissue of control and high-dose group (+ tissues with lesions and target organs from low- and mid-dose group):
Adrenal glands
Brain
Buccal mucosa
Epididymides
Esophagus
Eyes
Heart
Kidneys
Larynx
Liver
Lungs
Nose
Ovaries
Pancreas
Pituitary gland
Spinal cord
Spleen
Testes
Thymus
Thyroid gland
Trachea
Gross lesions
Target organs - Other examinations:
- Not relevant
- Statistics:
- ANOVA followed by Dunnett's test for comparison of multiple groups with a single control group
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- BODY WEIGHT AND WEIGHT GAIN
Mean body weight significantly decreased in high-dose males in weeks 1-3, and did not recover during the first 5 weeks of recovery. No effect were found in females, exept for a significant increase in mean body weight for high-dose females in week 4 of recovery.
FOOD CONSUMPTION
Food consumption significantly decreased in high dose males during weeks 1 and 3 of exposure
HEMATOLOGY
Low-dose female rats had significantly increased total erythrocyte counts, hemoglobin and hematocrit.
CLINICAL CHEMISTRY
No toxicologically significant effects on any clinical chemistry parameter during exposure.
Mean plasma cholinesterase activity levels significantly decreased in high-dose males and mid- and high-dose females at end of exposure period. Significant decrease was still present in high-dose females at end of recovery. No effects on erythrocyte cholinesterase levels.
MNSE activity levels increased in low- and mid-dose rats at end of exposure period. In high-dose animals this activity was comparable to controls, not indicating a dose related effect.
ORGAN WEIGHTS
Dose-related increase in absolute and relative lung weights in test group, significantly in mid and high dose animals at end of exposure period. This persisted in high-dose animals during recovery.
Mean absolute liver weights significantly increased in high-dose females, and mean relative liver weight significantly increased in mid- and high-dose females and high-dose males after exposure period.
GROSS PATHOLOGY
All animals of high-dose group had confluent white foci in the lungs. This effect was still apparent after recovery and not seen in the control group animals.
HISTOPATHOLOGY: NON-NEOPLASTIC
Alveolar histiocytosis observed in all mid- and high-dose animals at end of exposure period. According to the athors, these changes are consistent with a response to foreign material (water insoluble liquid aerosol) and they were not considered to be a response to chronic injury. Chronic foreign body inflammation was observed in high-dose animals at end of recovery.
Effect levels
- Dose descriptor:
- NOEL
- Effect level:
- 0.1 mg/L air (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: Lung effects, decrease in plasma cholinesterase (females)
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Not relevant
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of this study, a No Observed Effect Level (NOEL) of 0.1 mg/L was established for the inhalation of Fyroflex RDP in rats. This NOEL was based on the presence of lung effects, which persisted after recovery.
- Executive summary:
This study was performed to determine the ability of Fyroflex RDP to induce toxicity in rats by inhalation. The study was conducted according to OECD guideline 412 and under GLP conditions. Additionally, the Monocyte NonSpecific Esterase (MNSE) activity was evaluated to study neurotoxicity.
No deaths or toxicologically significant clinical signs were noted. In males of the high-dose group body weight and body weight gain was decreased. This returned to normal after recovery. Plasma cholinesterase activity was decreased in high-dose males and mid- and high-dose females, which persisted for high-dose females after recovery. No inhibition of erythrocyte cholinesterase acitivy levels was seen. MNSE activity levels were increased in low- and mid-dose rat, however, in high-dose animals this activity was comparable to that of controls. A dose-related increase in absolute and relative lung weights was seen in the test group, and was significant in mid- and high-dose animals. This persisted in high-dose animals during recovery. Mean absolute liver weights were significantly increased in high-dose females, and mean relative liver weight significantly increased in mid- and high-dose females and high-dose males. All animals of the high-dose group had confluent white foci in the lungs. This effect was still apparent after recovery and alveolar histiocytosis was observed in all mid- and high-dose animals. Chronic foreign body inflammation was observed in the high-dose animals at end of recovery.
Under the conditions of this study, a No Observed Effect Level (NOEL) of 0.1 mg/L was established for the inhalation of RDP in rats. This NOEL was based on the presence of lung effects, which persisted after recovery.
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