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EC number: 233-113-0 | CAS number: 10035-10-6
- 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:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study followed accepted scientific practice
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 997
- Report date:
- 1997
Materials and methods
Test guideline
- Guideline:
- other: US TSCA guidelines
- Principles of method if other than guideline:
- 28 day rat nose only inhalation test using vapor of phosphorus tribromide (PBr3) which rapidly forms hydrogen bromide (HBr) and phosporus acid (H3PO3).
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Phosphorus tribromide
- EC Number:
- 232-178-2
- EC Name:
- Phosphorus tribromide
- Cas Number:
- 7789-60-8
- IUPAC Name:
- phosphorus(3+) tribromide
- Details on test material:
- - Name of test material (as cited in study report): Phosphorus tribromide
- Molecular formula (if other than submission substance): PBr3
- Molecular weight (if other than submission substance): 270.686
- Substance type: inorganic
- Physical state: colorless to pale yellow liquid
- Analytical purity: 99.99 %
- Storage condition of test material: stored under nitrogen and used in hood
- Other: Specific gravity: 2.850 Vapor pressure: 0.27 psi at 54 °C
- Source: Aldrich Chemical Company
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River (CDF[F-344]/CrlBR)
- Weight at study initiation: Males 100 to 125 grams; females 75 to 100 grams
- Fasting period before study:
- Housing: two per cage in clear plastic cages with hardwood chip bedding, in laminar-flow rooms
- Diet (e.g., ad libitum): ad libitum except during exposure
- Water (e.g., ad libitum): ad libitum except during exposure
- Acclimation period: two week quarantine period
- Other: Animal care in acordance with Guide for the Care and Use of Laboratory Animals prepared by the Institute of Laboratory Animal Resources, National Research Council, National Academy Press, 1996 and the Animal Welfare Act of 1966 as amended
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 25 °C
- Photoperiod (hrs dark / hrs light): 12/12 hours
IN-LIFE DATES: Dates covered October, 1996 to May 1997 (acute through 28 day study).
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- nose only
- Vehicle:
- air
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Cannon 52 units within a set of Plexiglass boxes
- Method of holding animals in test chamber: Plexiglas restraining tubes
- Source and rate of air: dried laboratory air
- Method of conditioning air: Air dryer reduced humidity
- System of generating test substance: Gas tight syringes (1.0, 0.5, and 0.25 mL) used for direct delivery (needle tip evapoaration) into the10 L dried air stream. Sage syringe pumps used to control input of test article
- Temperature, humidity, pressure in air chamber: Humidity < 3 % as measured by HY-CAL detector.
- Air flow rate: minimum air flow delivery of 500 mL/animal
- Treatment of exhaust air: bypass and containment dump employed. Bypass air input used before and after the 4 hours exposures to supply clean air, and was used along with the PBr3 input carrier air to control the concentration of the exposure atmospheres. The Cannon chambers were vented through a vacuum pump which delivered the vapor to a water scrubber exhaust system. The containement areas were further isolated from the general laboratory area through use of a separate exhaust line which vented the enclosures.
TEST ATMOSPHERE
- Brief description of analytical method used: A bromide specific ion electrode permitted quantification of the test material through analysis of the bromide ion absorbed in an ionic strength buffer (pH 4.0). In order to monitor the lower concentrations, the ratio of vapor to buffer had to be increased from 10:1 air/absorber to 20:1 and 40:1. Sixty-mL plastic syringes containing 5.0 mL buffer were used to quantify the 50 mL vapor samples and acted as the reaction vessels for the absorption of test article. Multiple absorption samples were required to analyze the lower chamber concentrations.
- Samples taken from breathing zone: yes/no
VEHICLE (if applicable): not applicable - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analytical: The test material PBr3 reacts rapidly with water vapor present in air forming hydrogen bromide and phosphonic acid. It is also a good brominating agent. These properties prevented the usual methods for measuring exposure concentrations – IR absorbance or gas chromatography. The method used for analysis used water reactivity to free bromide ion for analysis, then use of a bromide combination specific ion electrode (ATI Orion) to determine bromide concentration. This was validated by quantitative addition of PBr3 and the formation of bromide ion – a set of three bubblers in series demonstrated that > 95 % was absorbed in the first tube. The rapid reactivity and sample line loss negated a continuous analysis. A direct method for analysis was chosen for confirming the nominal concentration by spot sampling every 20 minutes.
Bromide analysis: A separate syringe for each concentration was used and a double absorption for the mid chamber sample, and 4 x 50 mL samples for the low dose chamber. The probe was soaked in buffer (94 Series Ionic Strength adjuster, ATI Orion, pH to 4.0 for solution) at a concentration near that of the expected mid range level sample. An appropriate range of standards were made for the exposure set, bracketing low and high values. The standard 0.1 M sodium bromide from Orion was diluted to 1 uM in decade values. If the low end of the standard curve was non-linear with the log concentration, the standards were made between the decade vaules (such as 2, and 4.5 µM and 20 and 45 µM). PBr3 values were then calculated from the bromide ion concentration. Over 90 % of the samples were between 10 and 100 µM. - Duration of treatment / exposure:
- 4 hours per day, excluding weekends, for 28 days (total of 20 exposures).
- Frequency of treatment:
- Once daily, for 20 exposures (5 days per week over 28 days)
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0.3 mg/L
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
0.1 mg/L
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
0.03 mg/L
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
0.0 mg/L
Basis:
- No. of animals per sex per dose:
- 10 males and 10 females per treatment group
- Control animals:
- yes
- Details on study design:
- - Dose selection rationale: 5 day repeated dose preliminary showed differences between high dose (0.51 mg/L measured) and control animals in body weights on days 3 and 4, and gross and microscopic lesions of the anterior nasal passages, and in the trachea of one high dose animal. One rat in the mid dose group (0.16 mg/L) had minimal inflammation of anterior nasal passages. No microscopic lesions were seen in the low dose or the controls.
- Rationale for animal assignment: random
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes, on each exposure day
- Time schedule: daily, on exposure days
DETAILED CLINICAL OBSERVATIONS: Yes, on each exposure day
- Time schedule: daily, on exposure days
BODY WEIGHT: Yes
- Time schedule for examinations: Prior to initial exposure, then weekly
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data
WATER CONSUMPTION: No data
OPHTHALMOSCOPIC EXAMINATION: No data
HAEMATOLOGY: Yes
- Time schedule for collection of blood: At necropsy
- Anaesthetic used for blood collection: Yes, CO2 inhalation
- Animals fasted: Yes, 12 hours before necropsy
- How many animals: all animals
- Parameters checked in table [No.?] were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at necropsy
- Animals fasted: Yes, 12 hours before necropsy
- How many animals: all animals
- Parameters checked in table [No.?] were examined.
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No data
OTHER: - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see attached background document List of tissues
HISTOPATHOLOGY: Yes (see attached background document List of tissues - Statistics:
- Body weights were analyzed using the repeated multivariate analysis of variance with Scheffe pairwise comparisons (Barcikowski, R.J., 1983). Hematology, clinical chemistry, and organ weights were analyzed using a two-factorial analysis of variance with multivariate comparisons (Barcikowski, R.J., 1983). Histopathology data were analyzed with use of a Fischer Exact Test, or, if not valid, Yates' corrected Chi-square (Zar, J.R., 1974).
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- decreases in body weights in all treatment groups and controls
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- decreased platelets, increased monocyte and eosinophil %, increased mean corpuscular volume
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- decreased chloride, calcium, ALT, triglycerides
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- mild inflammation anterior nasal passages in high dose group
- Histopathological findings: neoplastic:
- no effects observed
Effect levels
open allclose all
- Dose descriptor:
- NOAEC
- Effect level:
- 0.1 mg/L air (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Microscopic findings of mild inflammation of the anterior nasal passages, minor serum chemistry and hematology effects seen in treated animals. Note: The NOAEC of PBr3 of 0.1 mg/L equates to 0.0916 mg/L HBr.
- Dose descriptor:
- LOAEC
- Effect level:
- 0.3 mg/L air (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Microscopic findings of mild inflammation of the anterior nasal passages seen in this concentration group. Note: This LOAEC value for PBr3 is equivalent to 0.2748 mg/L HBr.
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Attached tables:
Table 6 Body Weights of Male Rats Exposed for 28 days to Phosphorus Tribromide via Nose-only Inhalation
Table 7 Body Weights of Female Rats Exposed for 28 days to Phosphorus Tribromide via Nose-only Inhalation
Table 8 Mean Values of Serum Chemistries Parameters for Male Rats Exposed for 28 days to Phosphorus Tribromide via Nose-only Inhalation
Table 9 Mean Values of Serum Chemistry Parameters for Female Rats Exposed for 28 days to Phosphorus Tribromide via Nose-only Inhalation
Table 10 Blood Hematology Values for Male Rats Exposed for 28 days to Phosphorus Tribromide via Nose-only Inhalation
Table 11 Blood Hematology Values for Female Rats Exposed for 28 days to Phosphorus Tribromide via Nose-only Inhalation
Table 12 Absolute Organ Weights and Organ-To-Body Weight Ratios of Male Rats Exposed for 28 days to Phosphorus Tribromide via Nose-only Inhalation
Table 13 Absolute Organ Weights and Organ-To-Body Weight Ratios of Female Rats Exposed for 28 days to Phosphorus Tribromide via Nose-only Inhalation
Applicant's summary and conclusion
- Conclusions:
- The NOAEC of PBr3 when given by nose only exposure to male and female F-344 rats for 4 hours a day, 5 days per week for 20 exposures in 28 days is 0.1 mg/L (equivalent HBr exposure would be 0.0916 mg/L). The LOAEC, based on histopathology findings of mild inflammation in the anterior nasal passages was 0.3 mg/L (equivalent HBr exposure would be 0.274 mg/L). Decreased body weights were seen in treated and control groups and were thought to be due to restraint in the exposure chambers. Increased serum chloride levels in the exposed animals only was thought to be an artifact due to interference of ionized bromide in the test material with the serum chloride assay. There were no signs of toxic stress, or changes in organ weights in treated animals compared to control.
- Executive summary:
Phosphorus tribromide (PBr3) hydrolyzes into HBr and phosphonic acid. In a 28 day study in Fischer 344 rats exposed for 4 hours per day, five days per week, to 0.03, 0.1 or 0.3 mg/L PBr3 showed no signs of toxic stress, alterations of body weight, or changes in organ weights compared to control animals. Minor serum chemistry and hematology effects were seen in treated animals. Microscopic tissue findings were limited to rats of the 0.3 mg/L group and consisted of mild inflammation of the nasal passages. A concentration of 0.1 mg/L was the no observable adverse effect level (NOAEL) in a 28 day inhalation study.
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