Ethyl enantate

Endpoint summary

Description of key information

The substance is not acute toxic.

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:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

The acute oral effects were investigated in rats by observation of the animals for a period of 2 weeks after administration of a single dose.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Osborne-Mendel

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: young adult
- Fasting period before study: 18 hours
- Diet: food was replaced in cages as soon as animals received their respective doses
- Water: ad libitum

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

Highest administered dose: 34640 mg/kg bw.
Unclear whether also lower doses were examined.

No. of animals per sex per dose:

5 male and 5 female rats

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 7-14 days
- Frequent observations and weighing: yes
- Necropsy of survivors performed: no

Statistics:

LD50 were computed by the method of Litchfield and Wilcoxon (1949).

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 34 640 mg/kg bw

Based on:

test mat.

Remarks on result:

other: This was the highest dose administered.

Mortality:

No animals died.

Clinical signs:

other: Depression, coma, rough and wet fur.

34640 mg/kg bw was the highest dose administered. The confidence limits were not determined.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 was 34640 mg/kg bw.

Executive summary:

The acute oral toxicity effects of the test substances was assessed in rats. No specific guideline was followed. GLP was not indicated. The LD50, the slope function, and their confidence limits, together with toxic signs and times of death were recorded.

The highest dose administered was 34640 mg/kg bw. The confidence limits were not determined.

No animals died, therefore the acute oral LD50 was calculated to be > 34640 mpg/kg bw.

Observed toxic signs were depression, coma and a rough and wet fur.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

34 640 mg/kg bw

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:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

10 rabbits were dermally administered a single dose of the test material and observed during 14 days.

GLP compliance:

not specified

Limit test:

yes

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No details were provided.

Type of coverage:

not specified

Vehicle:

not specified

Details on dermal exposure:

No details were provided.

Duration of exposure:

No details were provided.

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

10 animals in total.

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and mortality

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No animals died during the study.

Clinical signs:

other: Clinical signs included diarrhea in 2/10 animals from days 11 - 14. Skin irritation observed: - mild redness in 6/10, moderate redness in 4/10 - mild edema in 3/10, moderate edema in 7/10

Gross pathology:

Necropsy findings included white nodules in the liver (4/10), bloated and venated large intestines (2/10), blood in the thoracic cavity (1/10), dark spots in parts of the liver (1/10), small white nodules and irregular nodes in the intestines (1/10), and mottled kidneys (2/10).

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal LD50 of the test item was > 5000 mg/kg bw.

Executive summary:

In the current study a group of 2 - 10 rabbits were dermally administered a single dose of the test material. No OECD guideline was followed and the study was not GLP.

After the treatment the animals were observed for mortality and clinical signs during 14 days. Furthermore, necrospy was conducted.

The acute dermal LD50 of the test item in rabbits was reported to be > 5000 mg/kg bw, based on 0/10 deaths at that dose.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Additional information

Acute toxicity: oral

For acute oral toxicity, a weight of evidence approach consisting of studies available on ethyl heptanoate itself and on read-across substances ethyl hexanoate and ethyl nonanoate is applied. Each of the studies is rated with a Klimish 4 score as the studies are not performed in accordance with an OECD guideline, and only limited information on the method and results is available in the study report or publication. Nevertheless, the test setup meets generally accepted scientific principles.

The results of the individual experiments are summarised below:

- Ethyl heptanoate: rat LD50 > 34640 mg/kg bw (Jenner, 1964)

- Ethyl hexanoate: rat LD50 > 5000 mg/kg bw (Moreno, 1975)

- Ethyl nonanoate: rat LD50 > 43000 mg/kg bw (Jenner, 1964)

- Ethyl nonanoate: guinea pig LD50 = 24190 mg/kg bw (Jenner, 1964)

Based on the above described results, it can be concluded that the acute oral toxicity of this set of aliphatic esters is very low. All substances in the set have LD50 values > 5000 mg/kg bw.

Acute toxicity: dermal

Similarly, a weight of evidence approach is also used for the acute dermal toxicity endpoint. The weight of evidence consists of study reports and published experimental data rated with a Klimish 4 score due to limited information on methods and results. However, also in this case the test setup meets generally accepted scientific principles.

The results of the individual experiments is summarised below:

- Ethyl heptanoate: rabbit LD50 > 5000 mg/kg bw (Levenstein, 1975)

- Ethyl heptanoate: rabbit LD50 > 5000 mg/kg bw (Moreno, 1977)

- Ethyl hexanoate: rabbit LD50 > 5000 mg/kg bw (Moreno, 1975)

- Ethyl octanoate: rabbit LD50 > 5000 mg/kg bw (Moreno, 1975)

Based on the above described results, it can be concluded that the acute dermal toxicity is very low with an LD50 value > 5000 mg/kg bw.

In conclusion, the available data is sufficient to not classify the substance as an acute toxic substance. Also, additional acute toxicity animal testing can be avoided as it can be anticipated that no effects will be seen.

Justification for classification or non-classification

According to the CLP legislation a substance is considered acute toxic when the acute toxicity estimates (ATE) for the oral route is =< 2000 mg/kg bodyweight. As the LD50 of the test item > 2000 mg/kg bw, the substance is not to be classified as acute toxic for the oral route.

Moreover, the CLP legislation states that a substance is considered acute toxic via the dermal route when the ATE is =< 2000 mg/kg bodyweight. As the LD50 of the test item > 2000 mg/kg bw, the substance is also not to be classified as acute toxic for the dermal route.

The available data is sufficient to conclude that the substance does not need to be classified as an acute toxic substance.