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Acute Toxicity: inhalation

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acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted following guideline and good scientific practice.

Data source

Reference Type:

Materials and methods

Test guideline
according to guideline
EPA OTS 798.1150 (Acute inhalation toxicity)
GLP compliance:
not specified
Test type:
other: Acute Inhalation Toxicity
Limit test:

Test material

Constituent 1
Reference substance name:
Phosphorus tribromide
EC Number:
EC Name:
Phosphorus tribromide
Cas Number:
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: 270.686
- Substance type: inorganic
- Physical state: colorless or yellow liquid
- Analytical purity: 99.99 %
- Other: Source Sigma Aldrich Chemical Company
- Specific gravity: 2.850 g/mL
- Vapor pressure: 0.27 psi at 54 °C

Test animals

Fischer 344
Details on test animals or test system and environmental conditions:
See Repeated dose toxicity (Wolfe, R.E., et al., 1997)
- Source: Charles River Laboratories
- Weight at study initiation: Females: 75 to 100 grams
- Housing: two per cage, clear plastic cages with hardwood chip bedding
- Diet (e.g., ad libitum): ad lib except during exposure peroid
- Water (e.g., ad libitum): ad libitum
- Acclimation period: two week quarantine

- Temperature (°C): 21 to 25 °C
- Photoperiod (hrs dark / hrs light): 12 hours dark, 12 hours light

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Details on inhalation exposure:
- Exposure apparatus: Cannon 52 chambers
- Exposure chamber volume: housed within a 690 L inhalation exposure chamber
- Method of holding animals in test chamber: plexiglass restraining tubes
- Source and rate of air: 300 to 500 mL/min dry (< 3 % relative humidity) filtered house air supplied to each animal with a minimum of 10 L/min for each test group
- Method of conditioning air: filtered, dried
- System of generating particulates/aerosols: Sage syringe pumps delivered required mass of test material into air supply for Cannon 52 chambers.
- Treatment of exhaust air: vented through vacuum pump which delivered PBr3 vapor to water scrubber exhaust system

- Brief description of analytical method used: Analysis for bromide after reacting sample with water

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: Initially limit test at 5 mg/L (US EPA 1990). Subsequent concentrations at half, 20 % and 10 % of initial concentration
Analytical verification of test atmosphere concentrations:
Duration of exposure:
4 h
Initial test in 5 female rats: 5 mg/L. Followup exposures in groups of 5 male rats: 2.5, 1.0, and 0.5 mg/L.
No. of animals per sex per dose:
5 male or female rats per dose
Control animals:
Details on study design:
- Duration of observation period following administration: 14 days:
- Frequency of observations and weighing: Observations twice daily, weighing prior to exposure and post-exposure days 1, 2, 7, and 14.
- Necropsy of survivors performed: yes, all animals necropsied
- Other examinations performed: lungs taken for histopathology
Body weights were analyzed using repeated multivariate analysis of variance with Scheffe pairwise comparisons.

Results and discussion

Preliminary study:
The initial study exposed 5 female rats for 4 hours to a target concentration of 5.0 mg/L (4.09 mg/L measured). One animal died immediately post exposure. One animal was found dead on post exposure day 1, and the other three were euthanized in a moribund state on post exposure day 1.
Effect levelsopen allclose all
Dose descriptor:
Effect level:
4.09 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: The equivalent HBr concentration would be 3.66 mg/L
Dose descriptor:
Effect level:
> 0.42 - < 1.48 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Equivalent HBr concentrations would be 0.385 to 1.356 mg/L
Dose descriptor:
other: NOAEL
Effect level:
0.42 mg/L air (analytical)
Based on:
test mat.
Remarks on result:
other: Based on no clinical signs, gross lesions, or microscopic lesions
All rats exposed to 4.09 mg/L test article died or were euthanized by post exposure day 1. See attached Table 1. All animals in the 1.5 mg/L , 0.9 mg/L and 0.4 mg/L groups survived the 14 day recovery period.
Clinical signs:
other: In the preliminary study, observations during exposure included labored and mouth breathing. During the first hour of exposure, all animals tried to avoid breathing the exposure atmosphere by attempting to withdraw their noses and heads from the nose co
Body weight:
See Table 1 attached. There was a trend to lower mean body weights at day 14 in the male rat exposed groups.
Gross pathology:
In the female rats exposed to 5 mg/L for 4 hours, 4 of 5 animals had nares plugged with a black substance, and 1 of 5 animals had the epidermal layer of the nares missing. Gross findings in the 1.5 mg/l group were missing tips of nares and deep ulcerationof the external nares with exposure of underlying cartilage. There were no gross findings in animals of the 0.9 mg/L or 0.4 mg/L groups.
Other findings:
Histological findings in the female rats exposed to 1.5 mg/L test article were severe, diffuse, peracute necrosis of the lamina propria epitheliu of the nasal passages and moderate to severe, multifocal, acute necrosis of the turbinates epithelium. Male animals in the 1.5 mg/L group showed mild to moderate, suppartive to aubacute, multifocal, rhinitis of the lamina propria of the nasal passages in all animals. One of 5 animals also displayed squamous cell metaplasia of the nasal passages (most anterior regions). Pathology findings were normal in the 0.9 and 0.4 mg/L groups.

Applicant's summary and conclusion

The rat acute 4 hour LC100 of PBr3 is approximately 4 mg/L based a single nose only inhalation exposure. This corresponds to an HBr concentration of 3.664 mg/L. No mortality was seen in male rats exposed to 1.48 mg/L and below.
Executive summary:

In a 4-hour exposure to PBr3vapors in nose-only exposure chambers, mortality (100 % died or were euthanized moribund on day 1) was seen in female rats exposed to approximately 4 mg/L (equivalent to 3.664 mg/L). No mortality was seen in groups of male rats exposed under the same circumstances to analyzed concentrations of 1.48 mg/L and below. Pathology seen in the high dose animals and in those of the 1.48 mg/L group were corrosion or severe irritation of the upper respiratory tract.