Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Older proprietary study, scientifically acceptable and methods comparable to current OECD guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1956
Report Date:
1956

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
The study was conducted prior to development of the guidelines. The methods are however similar to OECD 402. Groups of 4 albino rabbits were evaluated for acute dermal toxicity following single dermal application for 24 hours and a post exposure observation period of 7 days; gross autopsy.
GLP compliance:
no
Remarks:
: older proprietary study, pre-dates GLP
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
The test material was trimethylolpropane, received from Celanese Corporation of America on 27/07/1956. The substance was described as a coarse white crystalline solid with a mild aromatic odour. The purity was considered to be 100%.

Test animals

Species:
rabbit
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
The animals were male albino rabbits, weighing 1.5 to 2.5 kg. They were housed individually in elevated metal cages. Food and water were available ad libitum.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
The test material was moistened with distilled water to form a paste (approximately 0.1 ml water per gram of test material). The paste was spread evenly on a non-absorbant paper backing, which was then applied to the closely clipped intact abdominal skin. The trunks of the rabbits were wrapped securely with a gauze and adhesive tape binder. The dressings were removed after a 24 hour period exposure period, and the test sites were sponged with tap water to remove and residual test material. The animals were observed for 7 days.
Duration of exposure:
24 hours
Doses:
1000, 2150, 4640 and 10000 mg/kg bw.
No. of animals per sex per dose:
Four male rabbits/dose level
Control animals:
no
Details on study design:
The rabbits were observed daily for gross signs of dermal irritation and systemic toxicity, for a period of 7 days. At the end of the observation period the animals were sacrificed and gross autopsies were performed. Body weights were measured at the start of the study and again at the time of sacrifice.
Statistics:
The LD50 value was calculated by the moving average method.

Results and discussion

Preliminary study:
No preliminary study was reported.
Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: There were no mortalities during the 7 day post-exposure observation period
Mortality:
No mortalities occurred during the study.
Clinical signs:
All rabbits exhibited normal appearance and behaviour during the study, a very mild degree of dermal irritation was observed but disappeared the next day. No other signs were observed.
Body weight:
All rabbits gained weight during the study.
Gross pathology:
At autopsy, the kidneys of the majority of the rabbits at the three higher dose levels contained a hyperaemic zone at the cortico-medullary junction. Otherwise there were no abnormal findings.
Other findings:
Following removal of the dressings at the end of the exposure period, the abdomens and dressings of the 1.0 g/kg group showed no gross evidence of test material residue. The abdomens and dressings of the animals at the higher dose levels contained a small quantity of unabsorbed residue; the residue was slightly moist in the 10.0 g/kg group (the residue was dry in the remaining groups).
The single 24 hour application of trimethylolpropane produced a very mild degree of dermal irritation at each dose level tested. The irritation was characterised by a mild erythema at the end of the exposure period. The erythema subsided within 1 day, after which the exposed skin appeared normal.

Any other information on results incl. tables

The acute dermal LD50 of trimethylolpropane is greater than 10000 mg/kg bw in male albino rabbits. The moving average method was used to estimate an LD50 of 14.7 g/kg bw, however the relevance of this method is questionable in the absence of any mortality.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 of trimethylolpropane is greater than 10000 mg/kg in male albino rabbits.
Executive summary:

The acute dermal toxicity of trimethylolpropane was determined in groups of 4 male albino rabbits. The test material was moistened with distilled water and applied as a paste to the shaved, intact abdominal skin of the rabbits. Dose levels were 1000, 2150, 4640 and 10000 mg/kg bw, the exposure period was 24 hours and the rabbits were observed for 7 days following exposure.

Dermal exposure resulted in a very mild degree of dermal irritation, that had subsided within 24 hours. There was no evidence of systemic toxicity, no mortalities occurred during the study, and there were no remarkable findings at gross necropsy. The acute dermal LD50 of trimethylolpropane was therefore greater than 10000 g/kg in male rabbits under the conditions of this study.