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Administrative data

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

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1987
Report date:
1987

Materials and methods

Principles of method if other than guideline:
other
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Pivaloyl chloride
EC Number:
221-921-6
EC Name:
Pivaloyl chloride
Cas Number:
3282-30-2
Molecular formula:
C5H9ClO
IUPAC Name:
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

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.4 to 3.05 kg
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: for at least one week before use

Administration / exposure

Type of coverage:
semiocclusive
Details on dermal exposure:
The animals did not have any evidence of pre-existing skin irritation or defects. The hair on the dorsal surface of the trunk of each animal was clipped on the day prior to treatment. On the day of treatment, surgical gauze (2 layers thick) was applied to the site and taped with non-irritating adhesive tape. The entire trunk of each animal was wrapped with a semi-permeable material and secured with the tape. The test material (2010 mg/kg; 2.05
ml/kg) was introduced under the gauze. The exposure area was not washed.

Duration of exposure:
24 h
Doses:
2010 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Animals were observed for toxicity at 1/2, 3, and 6 hour after treatment and at least once daily thereafter for 14 days. They were observed for erythema (and eschar formation) and edema 24 hours after treatment and on Days 2, 3, 4, 7, 10 and 14. The maximum possible scores on each day were 4 for both endpoints. At each time, all erythema and edema scores were added and the sum was divided by the number of animals to determine an irritation score.
Body weights were recorded just prior to treatment and on
Days 7 and 14. A gross necropsy was performed on each animal
upon euthanization on day 14.
Statistics:
The LD50 values were calculated by the method of Litchfield and Wilcoxon (J Pham Ther 96: 99-115, 1949).

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 010 mg/kg bw
Mortality:
One female died on Day 11. There were no other deaths.
Clinical signs:
other: Toxicological effects observed in 1-4 animals during the study included activity decrease, ataxia, constricted pupils, decreased defecation and urination, diarrhea, emaciation, hemorrhaging (at exposure area), nasal discharge, polyuria and small feces.
Gross pathology:
Gross necropsy findings in the animal that died included extensive ulceration throughout the exposure area, signs of emaciation, liver mottled pale red and red-brown, stomach distended with gas and almost empty, brown slurry in small intestine and green-brown paste in cecum. One other animal had significant necropsy findings (GI tract distended with gas, stomach filled with green liquid, and green slurry throughout the intestinal tract).
Other findings:
The maximum irritation score was 6.9. Since necrosis and ulceration were present on all animals, the test material was given a descriptive rating of corrosive.

Applicant's summary and conclusion

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