Reaction mass of propylidynetrimethanol and 2-ethylpropane-1,3-diol and 5-ethyl-1,3-dioxane-5-methanol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1956-09-14

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

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

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

Test material information

Constituent 1

Reference substance name:

Propylidynetrimethanol

EC Number:

201-074-9

EC Name:

Propylidynetrimethanol

Cas Number:

77-99-6

Molecular formula:

C6H14O3

IUPAC Name:

2-ethyl-2-(hydroxymethyl)propane-1,3-diol

Constituent 2

Reference substance name:

Trimethylolpropane

IUPAC Name:

Trimethylolpropane

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source: received from Celanese Corporation of America on 27/07/1956.
- Purity: 100%

OTHER SPECIFICS
- Test material characteristics: a coarse white crystalline solid with a mild aromatic odour

Test animals

Species:

rabbit

Strain:

not specified

Sex:

male

Details on test animals or test system 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:

other: 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.

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:

GHS criteria not met

Conclusions:

The acute dermal LD50 of trimethylolpropane is greater than 10000 mg/kg in male albino rabbits.

Executive summary:

In an acute dermal toxicity study (similar to OECD 402), groups of 4 male albino rabbits were dermally exposed to trimethylolpropane which was moistened with distilled water and applied as a paste to the shaved, intact abdominal skin of the rabbits at doses of 1000, 2150, 4640 and 10000 mg/kg bw for 24 hours. Animals were then observed for 7 days.

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.

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 for male rabbits was therefore greater than 10000 mg/kg under the conditions of this study.