Registration Dossier

Diss Factsheets

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

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

Data source

Reference Type:
Report date:

Materials and methods

Test guideline
equivalent or similar to guideline
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
Test type:
standard acute method
Limit test:

Test material

Constituent 1
Chemical structure
Reference substance name:
Pivaloyl chloride
EC Number:
EC Name:
Pivaloyl chloride
Cas Number:
Molecular formula:
2,2-dimethylpropanoyl chloride
Details on test material:
Purity of test material was not analytically confirmed. It was used as received from PPG Industries. Purity of that material is listed as > 99% on the MSDS.

Test animals

Details on test animals or test system and environmental conditions:
- Weight at study initiation: The males and females weighed 235-338 g and 178-247 g when tested, respectively
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: for at least one week before use

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
other: unchanged (no vehicle)
Details on inhalation exposure:
Animals were individually housed in stainless steel cages in the chambers (200 liter stainless steel) during exposure.

The aerosol was generated by pumping the test material through a pressure operated spray nozzle. The aerosol was the diluted with dried, filtered air and drawn into the exposure chamber. Air flow into the chamber was maintained through the use of a calibrated critical orifice. Air flow was recorded at 30 min intervals during the exposure period. Air flow was sufficient to ensure adequate oxygenation of the exposure atmosphere. Temperature and humidity were recorded at 30 min intervals from a wet bulb/dry bulb hygrometer located in the exposure chamber.
The concentration of test material in atmosphere samples collected twice for each exposure (at 30 and 60 minutes) was determined analytically using a gas chromatograph. The nominal concentration was determined by dividing the loss in weight of the test material after exposure by the total volume of air that passed through the chamber. Due to the volatility of the test material, gravimetric and particle size determinations could not be performed.
Analytical verification of test atmosphere concentrations:
Duration of exposure:
1 h
nominal 1.90, 2.46, 4.49, 4.11, 4.06 and 7.63 mg/l (analytical concentrations were 1.14, 1.47, 2.28, 2.57, 2.75 and 5.15 mg/l)
No. of animals per sex per dose:
5 (exept the 2.28 mg/l treatment; here, only males were tested)
Control animals:
Details on study design:
Animals were observed frequently on the day of exposure (4 animals per group) and at least once daily thereafter (all animals) for 14 days for signs of toxicity. Individual body weights were recorded just prior to exposure and on days 7 and 14 (or as soon as possible after death). Gross necropsies were performed on all animals upon euthanization on day 14 or as soon as possible after death.
The LD50 values were calculated by the method of Litchfield and Wilcoxon (J Pharm Ther 96:99-115, 1949).

Results and discussion

Effect levels
Dose descriptor:
Effect level:
2.69 mg/L air (analytical)
95% CL:
2.57 - 2.82
Exp. duration:
1 h
Remarks on result:
other: The LC50 values in males and females are 2.57 (2.38-2.78) mg/l and 2.77 (2.67 - 2.87) mg/l, respectively. The value in females was estimated. The slopes of the curves for males, females and all animals were 1.06, 1.03 and 1.08, respectively.
The number of deaths (and time of death) in the 1.14, 1.47, 2.28 (males only), 2.57, 2.75 and 5.15 mg/l (analytical) groups were as follows : 0; 0; 0; 3 males (all within Day 1); 4 males (all within Day 10 and 2 females (Days 4 and 5); and all animals (9/10 within Day 1, one female by Day 2).
Clinical signs:
other: Signs observed during exposure were activity decrease, constricted pupils, dilated pupils, emaciation, epistaxis, gasping, lacrimation, nasal discharge, piloerection, ptosis, respiratory gurgle, and/or salivation.
Body weight:
Thirty-one of the 36 animals that survived for 14 days gained body weight.
Gross pathology:
There were no unusual findings at necropsy in animals exposed to 1.14 or 2.28 mg/l or survivors exposed to 2.57 mg/l. Four animals (3 males, 1 female) exposed to 1.47 mg/l had pale and edematous lungs, and 2 survivors of exposure to 2.75 mg/l had mottled, red lungs. Gross necropsy findings in animals that died before study termination included signs of lacrimation, nasal discharge, polyuria, salivation, discoloration of lungs and small intestine, serosal blood vessels pronounced on small intestine and testes drawn into the abdominal cavity.

Applicant's summary and conclusion