3-ethoxy-1,1,5-trimethylcyclohexane

Endpoint summary

Description of key information

- Acute toxicity: oral: LD50 > 2000 mg/kg bw
- Acute toxicity: dermal: LD50 > 2000 mg/kg bw
- Acute toxicity: inhalation: waiving

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Study performed similarly to the OECD guideline 401 with minor deviation: material tested as a suspension in CMC; it could have been tested undiluted. Certificate of analysis of the test substance is not included, some details on test material and tested animals are missing.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

material tested as a suspension in CMC; it could have been tested undiluted. Certificate of analysis of the test substance is not included, some details on test material and tested animals are missing.

Principles of method if other than guideline:

not applicable

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

mouse

Strain:

CF-1

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Average weight : 26 g
- Diet (e.g. ad libitum): Altromin No. 1324 ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): about 50
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

The application volume was a constant volume of 20 cm3/kg bw
The test material was suspended in 2% CMC
The concentration of the solution was 99.5 g/L

Doses:

1.99 g/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: before administration, 2, 7 and 14 days after administration
- Necropsy of survivors performed: 2 animals

Statistics:

none

Preliminary study:

not applicable

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: The following symptoms could be observed: decreased activity, prone position, decreased respiratory rate

Gross pathology:

No effect

Other findings:

None

Table 7.2.1/1 : Mean body weights (g)

Before application	48 h	1 week	2 weeks
25.8	27.02	31.35	34.69

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, 3,3,5-Trimethylcyclohexyl-ethyl-ether is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS. Oral LD50 males > 2000 mg/kg bw

Executive summary:

In an acute oral toxicity study performed similarly to OECD guideline 401, 10 adult male CF-1 mice were administered a single oral dose of test compound suspended in CMC at 2000 mg/kg bw by gavage. The animals were observed for mortality, clinical signs and body weight for 14 days and some of them were necropsied for macroscopic observations.

No mortality was observed. The following symptoms could be observed: decreased activity, prone position, decreased respiratory rate. However, bodyweight increased normally. In these test conditions, oral LD50 in males was considered higher than 2000 mg/kg bw.

Under the test conditions, 3,3,5-Trimethylcyclohexyl-ethyl-ether is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

 

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Study performed similarly to OECD guideline 401 with only minor deviations therefore considered as appropriate and reliable to complete this endpoint.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

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

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

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

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.

Preliminary study:

Not applicable

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

None

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Study performed similarly to OECD guideline 402 with only minor deviations therefore considered as appropriate and reliable to complete this endpoint.

Additional information

Acute toxicity: oral

In an acute oral toxicity study performed similarly to OECD guideline 401, 10 adult male CF-1 mice were administered a single oral dose of test compound suspended in CMC at 2000 mg/kg bw by gavage. No mortality was observed. The following symptoms could be observed: decreased activity, prone position, decreased respiratory rate. However, bodyweight increased normally. In these test conditions, oral LD50 in male mice was considered higher than 2000 mg/kg bw.

Acute toxicity: dermal

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. 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 the test item was considered to be higher than 2000 mg/kg bw in rabbits.

Acute toxicity: inhalation

No relevant study was available for this endpoint. However, an acute study by inhalation is available (2h at 1%), showing effects that were not of toxicological concern. Moreover, considering that the substance does not induce mortality or systemic effects and is not skin and eye irritant, no respiratory irritation is anticipated that could increase inhalation absorption.

However, in accordance with column 2 of REACH Annex VIII (§8.5), the acute toxicity by inhalation does not need to be conducted since the acute toxicity is already provided for the oral and the dermal routes.

Justification for classification or non-classification

Harmonized classification:

The test material has no harmonized classification according to the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

Self classification:

Based on the available data no additionnal self-classification is proposed regarding:

- both acute oral and dermal toxicity and,

- specific target organ toxicity -single exposure according to the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

- aspiration hazard (based on the acute oral toxicity study)

No reliable data available for acute inhalation toxicity.