Registration Dossier

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: see 'Remark'
Remarks:
Reliable with restrictions: 1) There is no data about GLP. 2) The study parameter "duration of exposure" was only 1 h instead of 4 hours (according to EC testing guideline B.2). 3) It is not documented how often the exposure concentration was measured during the exposure. Nevertheless the study is sufficient to accept the data, is scientifically acceptable and a well documented publication.

Data source

Reference
Reference Type:
publication
Title:
Acute Inhalation Toxicology of oxalyl chloride
Author:
S.J. Barbee, J.J. Stone, R.J. Hilaski
Year:
1995
Bibliographic source:
Am. Ind. Hyg. Assoc. J. 56(1):74-76 (1995)

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
yes
Remarks:
exposure duration time is 1 h instead of 4 h
Principles of method if other than guideline:
exposure duration time: 1 h
GLP compliance:
not specified
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
The test material's purity is >= 99%. The supplier was Olin Corporation.
The imurities are not identified.
Specific details on test material used for the study:
Purity: >99.0%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Sprague Dawley Crl:CD BR VAF/Plus from charles River Laboratories, Inc. in Protage, Mich.
weight range males on the day of exposure: 223-275 g
weight range females on the day of exposure: 159-199 g
The animals wer acclimated for a period of at least seven days prior to exposure.

Administration / exposure

Route of administration:
other: combination vapor/aerosol with 95% vapor
Type of inhalation exposure:
whole body
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
>= 2.6 - <= 8 µm
Geometric standard deviation (GSD):
>= 3.03 - <= 4.25
Details on inhalation exposure:
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 air flow of 0.85 L/min. The material was delivered in 160 L stainless steal and glass exposure chamber through the center of the top turret. Dilution air was introduced though a side-arm on the top turret at 90° to the test material, imput with a Fischer Porter flowmeter. It was demonstrated that this design generates test atospheres of uniform distribution.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
The concentration of oxalyl chloride was indirectly determined by electrochemical determination of Chloride and calculation of of oxalyl chloride concentration .
Duration of exposure:
1 h
Concentrations:
Group 1 462 ppm,
Group 2 866 ppm,
Group 3 1694 ppm,
Group 4 2233 ppm
Group 5 1232 ppm
Group 6 control
No. of animals per sex per dose:
Group 1-4:
10 animals per dose group
5 animals per sex per dose group
Group 5:
six males
Group 6:
four males
Control animals:
yes
Details on study design:
wholde body exposure

Results and discussion

Preliminary study:
No preliminary study was documented in the publication.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
1 840 ppm
Based on:
act. ingr.
95% CL:
> 1 531 - < 2 210
Exp. duration:
1 h
Mortality:
Group 1 462 ppm M 0/5 F 0/5
Group 2 866 ppm M 2/5 F 0/5
Group 3 1694 ppm M 3/5 F 2/5
Group 4 2233 ppm M 5/5 F 2/5
Group 5 1232 ppm M 0/4
Group 6 control M 0/4
Clinical signs:
The significant pharmaco-toxic signs noted immediately post-exposure and during the 14-day observation periiod was dyspnea with gasping, increased salivation and necrotic areas on forefeet and nose. The singsn were qualitativly similar in all groups, although severity increased in direct proportion to concentration.
Body weight:
Group 1: Body weight gain was normal for all animals in this group diring the entire post exposure period
Group 2-4: Body weight gain was decreased during the first week for both malees and females but returned to normal for both sexes diring the second week.
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 Grpup 3,4 and 5.
Other findings:
Goup 5:
Increased lung trachea weight; microscopic examination: pulmonary edema
Acute bronchiolitis, involved terminal and respiratory brochioles
Exudate witin the alveoli (contained fibrin, neutrophils, macrophages and red blood cells) and congestion
This observation is indicative of an acute inflammatory reaction ocurring in the alveolar walls. the affected alveoli were frequently located around the terminal bronchioles. This histopathological changes were multifocal and involved all lobes of the lungs.

Any other information on results incl. tables

See attached background material "Results LC50"

Applicant's summary and conclusion

Interpretation of results:
toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LC50 is 1840 ppm (vapor). Pulmonary edema appears to contribute significantly to mortality produced by oxalyl chloride.
Executive summary:

The acute inhalation LC50 of oxalyl chloride was determined following a 1 h expsoure. Four groups of 10 animals per group (5 males and 5 females) were exposed to a concentration range of 462 -2233 ppm of an aerosol/vapor mixture with a vapor portion of 95%. One set of six animals was exposed to a concentration of 1232 ppm for 1 h to evaluate hisstopathological change to the lungs. The LC50 is 1840 ppm with a 95% confidence intervalbetween 1531 ppm and 2210 ppm. Microscopically, the lungs from the treated animals exhibited acute brochiolitis, exudate within the alveoli, and congestion. Pulmonary edema appears to contribute significantly to mortality produced by oxalyl chloride.