Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Older, non-GLP proprietary study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1973
Report Date:
1973

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Remarks:
Older study, pre-GLP.
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Trimethylopropane Diallyl Ether (SN-1461-A), was supplied by Celanese Corporation.

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
The animals were male and female young adult albino rabbits of the New Zealand strain. All rabbits were acclimated for at least 7 days prior to testing. During the acclimatisation period, the animals were examined with respect to their general health and suitability at test animals.
The rabbits were housed individually in suspended, wire-bottomed cages and maintained on a standard laboratory diet. Food and water were available ad libitum.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The test substance was applied to the backs of four rabbits at a dose level of 3000 mg/kg. The skin of the test site was abraded in half the rabbits (1 male and 1 female). The test site was covered by wrapping the trunk of the animal with impervious plastic sheeting, held in place with tape. Each rabbit was fitted with a lightweight flexible plastic collar throughout the obesrvation period (to prevent ingestion of the test material).
Duration of exposure:
24 hours
Doses:
3000 mg/kg
No. of animals per sex per dose:
2 rabbits/sex/dose
Control animals:
no
Details on study design:
Twenty four hours prior to the dermal applications, the backs of the rabbits were shaved free of hair with electric clippers. The shaved area on each animal was approximately 30% of the total body surface area.
At the end of the exposure period, the test sites were examined for local skin reactions. Observations for mortality, local skin reactions, and behavioural abnormalities were continued for a total of 14 days post-exposure. Initial and final body weights were recorded. A necropsy was conducted on all animals sacrificed at the end of the observation period.
Statistics:
A formal statistical analysis was not required.

Results and discussion

Preliminary study:
No preliminary results.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no mortalities during the 14 day observation period.
Clinical signs:
No abnormal behavioural reactions were noted among any of the rabbits. 24 hours after application, the test sites showed pale red to red well-defined erythema and slight to mild oedema (area definable but not raised more than 1 mm). 7 days after application, pale red erythema remained with moderate desquamation. Mild desaquamation was still present after 14 days.
Body weight:
All rabbits gained weight during the study.
Gross pathology:
No abnormalities were detected at necropsy.
Other findings:
No other findings reported.

Any other information on results incl. tables

As no mortalities occurred, the LD50 can be considered to be greater than 3000 mg/kg.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 of the test material was found to be greater than 3000 mg/kg bw under the conditions of this study.
Executive summary:

The acute dermal toxicity of trimethylopropane diallyl ether was evaluated in 2 male and 2 female New Zealand White rabbits. The undiluted test substance (3000 mg/kg bw) was applied to the shaved skin of the rabbits, and held in place under an occlusive plastic dressing for 24 hours. Two of the test sites (on 1 male and 1 female rabbit) were abraded, and two remained intact. The rabbits were observed for 14 days after the exposure period

.

There were no mortalities during the study, and all rabbits gained weight. There were no clinical signs of toxicity, although the test substance was noted to be slightly irritating to the skin at the application site. No abnormalities were detected at necropsy.

The acute dermal LD50 of TMPDE is therefore greater than 3000 mg/kg bw in rabbits.