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Diss Factsheets

Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1994
Report date:
1994
Reference Type:
secondary source
Title:
Unnamed
Year:
1994
Report date:
1994

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Neodecanoyl chloride
EC Number:
254-875-0
EC Name:
Neodecanoyl chloride
Cas Number:
40292-82-8
Molecular formula:
C10H19ClO
IUPAC Name:
2,2-dimethyloctanoyl chloride
Details on test material:
The purity of the test material was approximately 99%.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
ANIMALS
Forty, eight to nine week old male (300 +/- 17 g) and female (205 +/- 11 g) rats were used in the study. They were randomly allocated into 4 test groups of 5 rats/sex/group.

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
Animals were exposed in an whole-body inhalation system with a volume of 200 liter. The animals were housed singly in compartmentalized wire cages within the exposure chambers. The vapor/air mixture was generated by a continuous infusion pump and a glass vaporizer with a thermostat. The vapor was mixed with supply air (3000 l/hr) and passed into the ventilation system. The temperatures and relative humidities in the exposure systems ranged from 20-24 degrees C and 30-70%, respectively. The pressure ratios in the inhalation system were adjusted so that the amount of exhaust air was about 3% higher (negative pressure).
Exposure concentrations: The nominal concentration of test material was calculated from the amount of substance consumed and the air flow. The atmosphere in each exposure chamber immediately adjacent to the animals' noses was sampled hourly for test material concentration using 2 absorption vessels and a fritted glass flask, connected in series and filled with sorption solvent (DMF). Solvent in the absorption vessels (DMF) was analyzed by gas chromatography for each sample.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
0.12, 0.27, 0.41, and 0.62 mg/l (analytical)/ 0.143, 0.32, 0.46 or 0.73 mg/l (nominal)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Observation
The observation period was 14 days and 25 days; animals from the 0.41 mg/l group were observed for 15 days. They were weighed before exposure, and 7 and 14 days after exposure (15 days for the 0.41 mg/l group). Clinical findings were recorded several times during exposure and at least once each workday during the observation period.

Pathology
Animals that died during the study were necropsied as soon as possible after death. Surviving animals were euthanized on Day 14 (0.41 mg/l on day 15) and subjected to gross pathological examination.
Statistics:
The LC50 value was analyzed using a FORTRAN program.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
ca. 0.4 mg/L air (analytical)
Exp. duration:
4 h
Mortality:
None of the animals exposed to 0.12 or 0.27 mg/l died. All 5 males and 2 females exposed to 0.41 mg/l died within 1 day. All animals exposed to 0.62 mg/l died during exposure.

Dose level males females
-----------------------------------------
0.12 mg/l 0/5 0/5
0.27 mg/l 0/5 0/5
0.41 mg/l 5/5 2/5
0.62 mg/l 5/5 5/5
-----------------------------------------
Clinical signs:
other: Accelerated respiration, snout wiping, apathy, squatting posture and piloerection were noted in animals exposed to 0.12 and 0.27 mg/l on the day of exposure and up to day 3, respectively. Animals exposed to 0.41 mg/l exhibited these symptoms plus irregula
Body weight:
Animals in the lower two dose groups and survivors of the higher dose gained weight normally over the course of the study. Survivors exposed to 0.41 mg/l lost weight over the first week, but recovered over the second week.
Gross pathology:
Gross pathology revealed general congestion in all animals that died. Hyperemia, edema, and focal emphysema of the lungs were noted. A histopathological examination of one of the high dose animals showed degeneration of bronchiolar and alveolar epithelium, slight intraalveolar lipoproteinosis, and marked congestion of the lungs. In liver and kidney hepatocellular degeneration and tubular nephrosis also were observed, respectively.
No macroscopic findings were noted in animals that survived to study termination.
Other findings:
Average (+/- SD) analytical concentrations were 0.12 +/- 0.029, 0.27 +/- 0.013, 0.41 +/- 0.017 and 0.62 +/- 0.046 mg/l.

Applicant's summary and conclusion