3-ethoxy-1,1,5-trimethylcyclohexane

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05 - 19 November 1992

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

GLP study conducted in compliance with OECD Guideline 402 with minor deviations: purity of test item and animal room conditions not reported; 4 females tested instead of 5

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

purity of test item and animal room conditions not reported; 4 females tested instead of 5

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-ethoxy-1,1,5-trimethylcyclohexane

EC Number:

266-722-5

EC Name:

3-ethoxy-1,1,5-trimethylcyclohexane

Cas Number:

67583-77-1

Molecular formula:

C11H22O

IUPAC Name:

3-ethoxy-1,1,5-trimethylcyclohexane

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): Trimethyl cyclohexyl ethyl ether
- Physical state: Clear liquid
- Storage condition of test material: Protected from light and stored in the refrigerator

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace animals
- Weight at study initiation: 2.2-2.4 kg for males and 2.2-2.5 kg for females
- Housing: Animals were housed individually in suspended wire mesh cages.
- Diet: Fresh Purina rabbit chow (Diet #5321), ad libitum
- Water: Water, ad libitum
- Acclimation period: At least 1 week

ENVIRONMENTAL CONDITIONS
- Photoperiod: 12 h dark / 12 h light

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsal area of the trunk
- % coverage: Approximately 10 % of the body surface
- Type of wrap if used: Test item was applied to the prepared dermal site and test site was covered with a gauze patch, secured with non-irritating tape and gentle pressure was applied to the gauze to aid the distribution of the test item over the area. The torso was wrapped with plastic which was secured with non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At 24 h after application, the residual test item was gently washed-off with distilled water prior to dermal observations.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): Undiluted
- Constant volume or concentration used: Yes

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males and 4 females

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Test sites were scored for dermal irritation at 24 h post dose and on Days 7 and 14 using the numerical Draize scale. Animals were observed 1, 2 and 4 h post dose and once daily for 14 days for toxicity and pharmacological effects. Animals were observed twice daily for 14 days for mortality.
Body weights were recorded pretest, weekly and at death or termination.
- Necropsy of survivors performed: Yes; all animals were examined for gross pathology.
- Other examinations performed: Abnormal tissues were preserved in 10 % buffered formalin for microscopic examination.

Statistics:

The LD50, 95 % confidence limits, dose response curve and slope were calculated, if possible, by the method of Litchfield and Wilcoxon, 1949.

Results and discussion

Preliminary study:

Not applicable

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality was observed

Mortality:

No mortality was observed.

Clinical signs:

other: - Diarrhea was the only abnormal physical sign noted during the observation period in one male at Day 6 and one female at Days 2, 3 and 5 after administration - Dermal reactions, well defined on day 1, were absent to slight on Day 7 and absent on Day 14.

Gross pathology:

Necropsy results were normal in 7/9 animals. One animal showed slight or scattered white nodules on liver and one animal showed slightly pitted and moderately mottled kidneys.

Other findings:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 for Trimethyl cyclohexyl ethyl ether is higher than 2000 mg/kg bw in rabbits therefore it is not classified according to the Annex VI of the Regulation (EC) N°1272-2008 (CLP) and to the GHS.

Executive summary:

In an acute dermal toxicity study performed according to OECD Guideline 402 and in compliance with GLP, New Zealand White rabbits (5 males/4 females) were exposed to a single dermal application of Trimethyl cyclohexyl ethyl ether at 2000 mg/kg bw. The test item was applied on dorsal area of the trunk representing approximately 10 % of the total body surface of the animals. The test site was then covered by a semi-occlusive dressing for 24 h. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

No mortality was observed. Diarrhea was the only abnormal physical sign noted during the observation period in one male at Day 6 and one female at Days 2, 3 and 5 after administration. Dermal reactions, well defined on day 1, were absent to slight on Day 7 and absent on Day 14. Body weight changes were normal in 8/9 animals. One male lost weight during the first week of the study. Necropsy results were normal in 7/9 animals. One animal showed slight or scattered white nodules on liver and one animal showed slightly pitted and moderately mottled kidneys. In this study, the dermal LD50 of test item was considered to be higher than 2000 mg/kg bw in rabbits.

 

The dermal LD50 for Trimethyl cyclohexyl ethyl ether is higher than 2000 mg/kg bw in rabbits therefore it is not classified according to the Annex VI of the Regulation (EC) N°1272 -2008 (CLP) and to the GHS.