Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented publication which meets basic scientific principles

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1995
Report date:
1995

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Oxalyl dichloride
EC Number:
201-200-2
EC Name:
Oxalyl dichloride
Cas Number:
79-37-8
Molecular formula:
C2Cl2O2
IUPAC Name:
ethanedioyl dichloride

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, Inc. in Portage, Mich.; USA
- Weight at study initiation: males: 223-275 g; females: 159-199 g
- Acclimation period: at least seven days

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 160-L stainless steel and glass exposure chamber
- Exposure chamber volume: 160 L
- System of generating aerosols: The exposure concentrations were generated via a Harvard syringe drive model 22 and a Meinhard all-glass nebulizer TR-30-Al. Compressed air drove the nebulizer at 20 psig, which resulted in an airflow of 0.85 L/min.
- Method of particle size determination: Anderson Cascade Impactor

TEST ATMOSPHERE
- Brief description of analytical method used: The concentration of the test substance was determined electrochemically using an Orion model 94-17 chloride electrode. It was drawn through fritted bubblers containing 100 mL of distilled water. Following reaction with water to yield hydrogen chloride, the chloride ion concentration was analyzed with the ion-specific electrode, and oxalyl chloride concentration was calculated mathematically based on the molecular weight of each.

TEST ATMOSPHERE
- Particle size distribution: The small amount of particles collected during the cascade impactor sampling indicated that greater than 95% of the vapor/aerosol mixture was in the vapor phase.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.6 - 8.0 µm / 3.03 - 4.25 µm
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
1 h
Concentrations:
462 ± 115 ppm, 866 ± 173 ppm, 1694 ± 135 ppm, 2233 ± 404 ppm, 1232 ± 135 ppm (conisted of six males in order to examine lungs and trachea on post exposure day 1)
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed for pharmacotoxic signs during exposure. They were observed 2 times daily during the 14 day post-exposure period for mortality, one of which also served for notation of pharmacotoxic signs. Body weight was recorded for all animals pre-exposure and 7 and 14 days postexposure.
- Necropsy of survivors performed: yes

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
1 850 ppm
Based on:
test mat.
95% CL:
1 531 - 2 210
Exp. duration:
1 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
462.5 ppm
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: calculated from 1 hour value using Haber's law
Sex:
male/female
Dose descriptor:
LC50
Effect level:
2.45 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: calculated from ppm value
Mortality:
462 ppm: all animals survived
866 ppm: 2/5 males died within 9 days after exposure
1694 ppm: 3/5 males and 2/5 females died within 11 days after exposure
2233 ppm: all males and 2/5 females died within 7 days after exposure
1232 ppm: 2/6 males died within one day after exposure (only males were tested at this dose group)
Clinical signs:
other: The significant pharmacotoxic signs noted immediately post-exposure and during the 14-day observation period were dyspnea with gasping, increased salivation, and necrotic areas on forefeet and nose. These signs were qualitatively similar in all groups, al
Body weight:
Body weight gain was normal for all animals in group with 462 ppm during the entire post-exposure period. Body weight gain was decreased during the first week for both males and females in groups with 866 ppm, 1694 ppm, and 2233 ppm but returned to normal for both sexes during the second week for those animals that survived.
Gross pathology:
Gross pathological changes included cloudiness of the eye with erosion and/or red discoloration of the cornea in all treated groups and red or dark red discoloration and red foci in the lungs in animals from groups with 2233 ppm, 1694 ppm and 1232 ppm. The increased lung-trachea weight from animals in group with 1232 ppm suggested the presence of pulmonary edema. This was confirmed on microscopic examination. Microscopically, the lungs from the treated animals exhibited acute bronchiolitis, exudate within the alveoli, and congestion. The bronchiolitis involved terminal and respiratory bronchioles. The exudate in the alveoli contained fibrin, neutrophils, macrophages, and red blood cells. This observation is indicative of an acute inflammatory reaction occurring in the alveolar walls. The affected alveoli were frequently located around the terminal bronchioles. These histopathological changes were multifocal and involved all lobes of the lungs.

Any other information on results incl. tables

LC50 of 1850 ppm corresponds to 9759.4 mg/m³ (9.8 mg/L) at 1013 hPa and 20°C and 126.93 g/mol.

Applicant's summary and conclusion

Interpretation of results:
moderately toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU

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