Ethyl formate

Endpoint summary

Description of key information

Acute oral toxicity: 

Acute oral toxicity dose (LD50) was considered based on different studies conducted on rats, rabbits and guinea pigs for the test chemical. The LD50 value was considered to be 5600 mg/kg in rats. The study concluded that the LD50 value is >2000 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute oral toxicity.

Acute Inhalation toxicity: 

Acute Inhalation toxicity dose (LC50) was considered based on different studies conducted on rats for the test chemical. The LC50 value was considered to be 28950 mg/m3. The study concluded that the LC50 value is >5 mg/L, for acute inhalation toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute inhalation toxicity.

Acute Dermal toxicity: 

Acute Dermal toxicity dose (LD50) was considered based on different studies conducted on rabbits for the test chemical. The LD50 value was considered to be >20000 mg/kg bw. The study concluded that the LD50 value is >2000 mg/kg bw, for acute dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute dermal toxicity.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Justification for type of information:

Data is from study report.

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Acute oral toxicity test of the given test chemical in rat.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

15-35 % emulsion in 0.5% aqueous carboxymethylcellulose preparation

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 5600 mg/kg
- Amount of vehicle (if gavage): The product was administered as 15-35% emulsion in 0.5% aqueous carboxymethylcellulose preparation

Doses:

5600 mg/kg

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: Animals were observed for mortality and clinical signs.
- Other examinations performed: Animals were observed for symptoms of intoxication, macroscopical examination.

Statistics:

not specified

Preliminary study:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

5 600 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Mortality:

50% mortality was observed

Clinical signs:

other: Symptoms of poisoning such as tumbling, apathy, dyspnoea, abdominal lateral position, spasmodic twitching, partly spastic gait, and cyanosis was observed in animals.

Gross pathology:

Acute cardiac dilation on both sides, acute congestive hyperemia, loam color liver with peripheral lappchenzeichnung(drawing) was observed.

Other findings:

not specified

Interpretation of results:

other: Not classified

Conclusions:

The LD50 value was considered to be 5600 mg/kg bw, when rats were treated with the given test chemical via oral gavage route.

Executive summary:

The acute oral toxicity of the given test chemical was tested in rat at the dose concentration of 5600 mg/kg bw.

The given test chemical was administered as 15-35% emulsion in 0.5% aqueous carboxymethylcellulose preparation. Animals were observed for mortality and clinical signs for 7days. Also the symptoms of intoxication, macroscopic examination were performed.

50% mortality observed was observed. Symptoms of poisoning such as tumbling, apathy, dyspnoea, abdominal lateral position, spasmodic twitching, partly spastic gait, and cyanosis was observed in animals. Acute cardiac dilation on both sides, acute congestive hyperemia, loam color liver with peripheral lappchenzeichnung(drawing) was observed.

Therefore, thar LD₅₀value was considered to be 5600 mg/kg bw, when rats were treated with test chemical via oral gavage route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 600 mg/kg bw

Quality of whole database:

Data is Klimisch 1 and from study report.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data is from secondary source.

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Acute inhalation toxicity of the given test chemical in rat.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

inhalation

Type of inhalation exposure:

not specified

Vehicle:

not specified

Remark on MMAD/GSD:

not specified

Details on inhalation exposure:

not specified

Analytical verification of test atmosphere concentrations:

not specified

Remarks on duration:

not specified

Concentrations:

28950 mg/m3

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

not specified

Dose descriptor:

LC50

Effect level:

28 950 mg/m³ air

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Mortality:

50% mortality was observed

Clinical signs:

other: not specified

Body weight:

not specified

Gross pathology:

not specified

Other findings:

not specified

Interpretation of results:

other: Not classified

Conclusions:

The acute inhalation LC50 value was considered to be 28950 mg/m3, when rats were treated with the given test chemical by inhalation route.

Executive summary:

Acute inhalation toxicity study of the given test chemical was conducted in rats at the dose concentration of 28950 mg/m3.

Animals were observed for mortality. No mortality was observed at 28950 mg/m3.

Therefore, the LC50 value was considered to be 28950 mg/m3, when rats were treated with the given test chemical by inhalation route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

28 950 mg/m³ air

Quality of whole database:

Data is Klimisch 4 and from secondary source.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from publication.

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Acute dermal toxicity of the given test chemical in rabbit.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Species:

rabbit

Strain:

other: New Zealand giant albino rabbits

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.5 – 3.5 gm

Type of coverage:

occlusive

Vehicle:

not specified

Details on dermal exposure:

TEST SITE
- Area of exposure: clipped skin
- % coverage: 1/10 of the body surface
- Type of wrap if used: an impervious plastic film
REMOVAL OF TEST SUBSTANCE
- Washing (if done): the film was removed
- Time after start of exposure:24 hours

Duration of exposure:

24 hours

Doses:

20000 mg/kg bw

No. of animals per sex per dose:

4 rabbits/dose

Control animals:

not specified

Details on study design:

- Other examinations performed: Animals were observed for a period of 14 days for signs of systemic toxic effects.

Statistics:

not specified

Preliminary study:

not specified

Sex:

male

Dose descriptor:

LD50

Effect level:

> 20 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality was observed

Mortality:

All rabbits survived the maximum dosage that could be retained in contact with the skin by the method employed.

Clinical signs:

other: No adverse effects were reported.

Gross pathology:

not specified

Other findings:

not specified

Interpretation of results:

other: Not classified

Conclusions:

The acute dermal LD50 value was considered to be >20000 mg/kg bw, when group of 4 male New Zealand giant albino rabbits were treated with the given test chemical by dermal application occlusively.

Executive summary:

Acute dermal toxicity study of the given test chemical was conducted in group of 4 male New Zealand giant albino rabbits at the dose concentration of 20000 mg/kg bw.

Test chemical applied to the skin (hair removed by clipping) over about 1/10 of the body surface and retained in contact with the skin by means of an impervious plastic film. After an exposure period of 24 hours, the film was removed.

Animals were observed fora period of 14 days for signs of systemic toxic effects. All rabbits survived the maximum dosage that could be retained in contact with the skin by the method employed. No adverse effects were reported.

Therefore, LD50 value was considered to be >20000 mg/kg bw, when group of 4 male New Zealand giant albino rabbits were treated with test chemical by dermal application occlusively.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

20 000 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from publication.

Additional information

Acute oral toxicity:

In different studies, the given test chemical has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats, rabbits and guinea pigs for test chemical. The studies are summarized as below –

 

The experimental study conducted on rats and mentioned in study report for the test chemical was designed to determine acute oral toxicity dose. The study was conducted in rat at the dose concentration of 5600 mg/kg bw.

The given test chemical was administered as 15-35% emulsion in 0.5% aqueous carboxymethylcellulose preparation. Animals were observed for mortality and clinical signs for 7days. Also the symptoms of intoxication, macroscopic examination were performed.

50% mortality observed was observed. Symptoms of poisoning such as tumbling, apathy, dyspnoea, abdominal lateral position, spasmodic twitching, partly spastic gait, and cyanosis was observed in animals. Acute cardiac dilation on both sides, acute congestive hyperaemia, loam colour liver with peripheral lappchenzeichnung(drawing) was observed.

Therefore, the LD50 value was considered to be 5600 mg/kg bw, when rats were treated with test chemical via oral gavage route.

 

The above experimental study is supported with the study mentioned in publication, handbooks, authoritative databases and secondary sources, for the test chemical and conducted in groups of 5 male Carworth–Wistar rats at the dose concentration of 4290 (3070–5980) mg/kg bw.

The test chemical was dissolved in water, corn oil or 1% aqueous solution of 25% Na-3,9-diethyl-6- tridecanol sulfate and administered as volumes to 1 ml to 10 ml via oral gavage route. After administration of the substance, the animals became 14 days long observed. 50% mortality was observed at 4290 mg/kg bw.

Therefore, the LD50 value was considered to be 4290 mg/kg bw, with 95% confidence limit of 3070–5980 mg/kg bw, when groups of 5 male Carworth–Wistar rats were treated with test chemical via oral gavage route.

 

This study is supported by the study conducted on rats and data mentioned in secondary sources, for the test chemical at the dose concentration of 2699 mg/kg bw.

Animals were observed for mortality and clinical signs. 50% mortality was observed at 2699 mg/kg bw. Clinical signs were observed in animals as – Behavioural changes: general anaesthetic; alteration of classical conditioning; dyspnea.

Hence, the LD50 value was considered to be 2699 mg/kg bw, when rats were treated with test chemical via oral route.

 

The above studies are supported by the study conducted on rabbits and mentioned in publications, handbooks, authoritative databases and secondary sources, for the chemical. The acute oral toxicity study of the given test chemical was conducted in male and female rabbits at the dose concentration of 28 mmol/kg (2075 mg/kg bw).

Animals were observed for mortality and clinical signs. Death in one–half of the rabbits within 24 hours after administration was observed. At this dose level, narcotic effects (stupor, loss of voluntary movements) were observed in onehalf of the animals. Larger doses caused disappearance of corneal reflexes, nystagmus, dyspnea and bradycardia.

Hence, the LD50 value was considered to be 2075 mg/kg bw, when male and female rabbits were treated with test chemical via oral gavage route.

 

All the above experimental studies are contradicted with the study conducted on rats and mentioned in publications, handbooks, authoritative databases and secondary sources, for the test chemical. The acute oral toxicity study of the given test chemical was conducted in groups of 10 male and female Osborne-Mendel rats at the dose concentration of 1850 (1520-2240) mg/kg bw).

Rats evenly divided by sex were fasted for approximately 18 hr prior to treatment. Animals had access to water at all times, and the food was replaced in cages as soon as animals received their respective doses.

All animals were maintained under close observation for recording toxic signs and time of death. Such observation was continued until animals appeared normal and showed weight gain. LD50's were computed by the method of Litchfield & Wilcoxon (1949).

Mortality was observed between 15 min-2 hr. Depression within 5-10 min, labored respiration was observed in animals.

Therefore, the LD50 value was considered to be1850 mg/kg, with 95% confidence limit of 1520-2240 mg/kg bw, when male and female Osborne-Mendel rats were treated with test chemical via oral gavage route.

 

Another study mentioned in publications, handbooks, authoritative databases and secondary sources, for the test chemical and conducted in groups of 10 male and female guinea pigs at the dose concentration of 1110 (887-1390 mg/kg bw).

Guinea pigs evenly divided by sex were fasted for approximately 18 hr prior to treatment. Animals had access to water at all times, and the food was replaced in cages as soon as animals received their respective doses.

All animals were maintained under close observation for recording toxic signs and time of death. Such observation was continued until animals appeared normal and showed weight gain. LD50's were computed by the method of Litchfield & Wilcoxon (1949).

Mortality was observed between 10 min-2 hr. Depression and Irritated gastro-intestinal tract was observed in animals.

Therefore, the LD50 value was considered to be 1110 mg/kg, with 95% confidence limit of 887-1390 mg/kg bw, when male and female guinea pigs were treated with test chemical via oral gavage route.

 

From all the above experimental studies on test chemical conducted on rats, rabbits and guinea pigs, the maximum number of studies concluded that the LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute oral toxicity.

Acute Inhalation Toxicity:

In different studies, the given test chemical has been investigated for acute inhalation toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rats for the test chemical. The studies are summarized as below –

 

The experimental study mentioned in secondary source, for the test chemical was designed to determine acute inhalation toxicity on rats at the dose concentration of 28950 mg/m3. Animals were observed for mortality. No mortality was observed at 28950 mg/m3. Therefore, the LC50 value was considered to be 28950 mg/m3, when rats were treated with the given test chemical by inhalation route.

 

The above experimental study is supported with the study mentioned in publication and secondary sources for the test chemical. The acute Inhalation toxicity study was conducted in rats at the dose concentration of 24000 mg/m3. Animals were observed for mortality and clinical signs. 5 out of 6 rats at 24000 mg/m3 were died. No LC50 values were mentioned. Signs of toxicity included depression of the central nervous system (CNS) and respiratory and circulatory effects were observed. Hence, the LC90 value was considered to be 24000 mg/m3 in rats.

 

These studies are further supported with the study mentioned in authoritative database and secondary source and was conducted according to OECD Guideline 403 in rats at the dose concentration of 21200 mg/m3. Animals were observed for mortality and clinical signs. No mortality was observed at 21200 mg/m³. Narcotic effect was observed.Hence, LC50 value was considered to be >21200 mg/m3, when rats were treated with test chemical by inhalation route for 4 hour exposure.

 

All these studies are further supported with the study mentioned in report for the test chemical and conducted in group of 3 male and female CD® (Sprague-Dawley) rats at the dose concentration of 21 mg/L. 

The test substance was administered into the breathing zone of the animals as a vapour on at a target concentration of 21 mg/L. One group (Group I) consisting of three male and three female rats was exposed to an atmosphere containing vapour for four hours at an analytical concentration of 21 milligrams per liter of air (mg/l).

All survivors were held for a 7-day post exposure observation period. At the end of the observation period, all animals were euthanized and discarded without a post-mortem examination.

No mortality was observed. Observations noted during exposure included lacrimation, reduced activities, and eyes closed. Signs exhibited by animals upon removal from the chamber and during the two-hour post-exposure observation period on Day included a few secretary signs and ano-genital staining. During the 7-day observation period test animals exhibited virtually no continuing signs of treatment. Body weights were considered unremarkable.

Hence, LC50 value was considered to be >21 mg/L(>21000 mg/m3), when group of 3 male and female CD® (Sprague-Dawley) rats were treated with test chemical by inhalation route for 4 hour exposure.

 

Thus, based on the above studies on test chemical, it can be concluded that LC50 value is >5 mg/L. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute inhalation toxicity.

Acute Dermal toxicity:

In different studies, the given test chemical has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rabbits for the test chemical. The studies are summarized as below:

 

The experimental study conducted on rabbits and mentioned in publication, authoritative databases, and secondary sources, for the test chemical was designed to determine acute dermal toxicity dose. The study was conducted in group of 4 male New Zealand giant albino rabbits at the dose concentration of 20000 mg/kg bw.

Test chemical applied to the skin (hair removed by clipping) over about 1/10 of the body surface and retained in contact with the skin by means of an impervious plastic film. After an exposure period of 24 hours, the film was removed.

Animals were observed for a period of 14 days for signs of systemic toxic effects. All rabbits survived the maximum dosage that could be retained in contact with the skin by the method employed. No adverse effects were reported.

Therefore, LD50 value was considered to be >20000 mg/kg bw, when group of 4 male New Zealand giant albino rabbits were treated with test chemical by dermal application occlusively.

 

The above experimental study is supported with the study conducted on rabbits and mentioned in publication, handbooks and secondary source, for the test chemical at the dose concentration of 20000 mg/kg bw. Animals were observed for mortality. 50% mortality was observed at 20000 mg/kg bw. Therefore, the LD50 value was considered to be 20000 mg/kg bw, when rabbits were treated with test chemical by dermal application.

 

Another study available for the test chemical was conducted on rabbits and mentioned in authoritative database and secondary source to determine acute dermal toxicity dose at the dose concentration of 18000 mg/kg bw. Animals were observed for mortality. No mortality was observed at 18000 mg/kg bw. Therefore, LD50 value was considered to be >18000 mg/kg bw, when rabbits were treated with test chemical by dermal application.

 

The study mentioned in publication and secondary source was supported with the above studies for the test chemical was conducted in rabbits at the dose concentration of 5000 mg/kg bw. Animals were observed for mortality. No mortality was observed at 5000 mg/kg bw. Therefore, LD50 value was considered to be >5000 mg/kg bw, when rabbits were treated with test chemical by dermal application.

 

These studies are also supported by the study mentioned in authoritative database, for the given test chemical. The acute dermal toxicity study of the given test chemical was conducted in rabbits at the dose concentration of 18300 mg/kg bw. Animals were observed for mortality. No mortality was observed at 18300 mg/kg bw. Therefore, LD50 value was considered to be >18300 mg/kg bw, when rabbits were treated with test chemical by dermal application.

All the above studies are further supported by the study mentioned in secondary source for the test chemical. The acute dermal toxicity study of the test chemical was conducted in group of 4 New Zealand albino rabbits at the dose concentration of 18400 mg/kg bw. Rabbits weighing 2.5 to 3.5 kg exposed for 24 hour to occlusive application (1/10 of the body surface) to the skin and observed for 14 days for mortality. No mortality was observed at 18400 mg/kg bw. Therefore, LD50 value was considered to be >18400 mg/kg bw, when group of 4 New Zealand albino rabbits were treated with test chemical by dermal application occlusively for 24–hour of exposure.

 

Thus, based on the above studies on test chemical, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above summarised studies on test chemical, it can be concluded that LD50 value is >2000 mg/kg bw for acute oral and acute dermal toxicity; and LC50 value is >5 mg/L for acute inhalation toxicity. Thus, comparing these values with the criteria of CLP regulation, the given test chemical cannot be classified for acute oral, acute dermal and acute inhalation toxicity.