γ-valerolactone

Endpoint summary

Description of key information

Acute oral toxicity

Treatment of rats and rabbits with different doses of the test item resulted in a LD50(rat) of 8.8 mL/kg bw (9249 mg/kg bw) and a LD50(rabbit) of 2.48 mL/kg bw (2606 mg/kg bw).

 

Acute inhalation toxicity

In studies with rats, mice and rabbits the LC50 was highter than 10000 mg/m³ after exposure with different concentrations of test item vapors and aerosols.

 

Acute dermal toxicity

In a study with rabbits, 2 mL/kg bw (2102 mg/kg bw) of the test item did not induce irritation or damage to the skin of 6 rabbits. The LD50 was thus found to be >2102 mg/kg bw.

 

 

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:

Not available, publication received 1945-05-31

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: The purpose of this investigation was to determine the immediate toxicity of the test item by oral administration to rats and its effects upon respiration and blood pressure.

- Short description of test conditions: Rats were treated with different volumes of the test item by gavage. No details about sex, environmental conditions or time schedule of the experiment are given.

- Parameters analysed / observed: Clinical signs, blood pressure and mortality

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

No details given.

Species:

rat

Strain:

Wistar

Sex:

not specified

Details on test animals or test system and environmental conditions:

IN-LIFE DATES: At least 36 hours

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED:
16 mL/kg bw

Doses:

4.7, 7.0, 10.0, 16.0 mL/kg bw

No. of animals per sex per dose:

10 animals per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 36 hours
- Necropsy of survivors performed: No
- Clinical signs: Locomotor system, state of consciousness, respiration
- Other examinations: Blood pressure was recorded by means of a kymograph

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

9 249 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Effect level was converted from 8.8 mL/kg bw to 9249 mg/kg bw

Mortality:

10% mortality at 4.7 mL/kg bw (survival time 36 hours), 20% mortality at 7.0 mL/kg bw (survival time 10-14 hours), 70% mortality at 10 mL/kg bw (survival time 1-6 hours), 90% mortality at 16 mL/kg bw (survival time 35 min to 12 hours)

Clinical signs:

other: Clinical signs were marked muscular weakness, mild anesthesia, increase in the rate of respiration, followed by dyspnea and occasionally by mild asphyxial convulsions. Death resulted from combined effects of circulatory and respiratory failure.

Gross pathology:

No information given

Other findings:

No information given

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

9 249 mg/kg bw

Quality of whole database:

Study well documented, meets generally accepted scientific principles, acceptable for assessment

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

Study period:

Not available, publication received 1945-05-31

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: The purpose of this investigation was to determine the effects resulting from the inhalation of an atmosphere saturated with the vapor and containing in addition droplets of the compound in the form of a mist.

- Short description of test conditions: Rats were exposed to a mixture of vapor and mist of the test item in air for 7 hours daily for several days. No details about sex, environmental conditions or MMAD/GSD are given.

- Parameters analysed / observed: Clinical signs and body weights

GLP compliance:

not specified

Test type:

traditional method

Limit test:

no

Specific details on test material used for the study:

No details given

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

IN-LIFE DATES: From day 0 to day 4 (1st experiment), from day 0 up to day 92 (2nd experiment)

Route of administration:

inhalation: mixture of vapour and aerosol / mist

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Air was passed through a tower containing calcium chloride, the air flow is then measured by a rotameter, the air was further passed over the test item heated in a volatilizer and finally into the exposure chamber.
- Exposure chamber volume: 388 Liter
- Method of holding animals in test chamber: In cages
- Source and rate of air: 15 Liters per minute
- Method of conditioning air: Heating and volatilizing of the test item
- Treatment of exhaust air: The air was expelled from the cage through stack opening under a hood.
- Temperature in air chamber: 24-28°C

TEST ATMOSPHERE
- Brief description of analytical method and equipment used: Air samples were mixed with ethyl alcohol. A saturated solution of hydroxylamine hydrochloride (~7%) in 95% ethyl alcohol was added, followed by a 20% KOH solution. The mixture was heated and cooled down. afterwards HCl was added. The transmission of light at 490 µm of the solution was compared with those of water in a photoelectric colorimeter.

- Samples taken from breathing zone: No

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

7 h

Remarks on duration:

1st experiment: 7 hours exposure/day for 4 successive days
2nd experiment: 7 hours exposure/day on successive days (Saturdays and Sundays excepted). Those that survived were so exposed on 60 days over a total period of 92 days.

Concentrations:

Between 3 and 10 mg/L (1st experiment) and approx. 1.5 mg/L (2nd experiment)

No. of animals per sex per dose:

1st experiment: 4 rats
2nd experiment: 4 rats

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 4 days (1st experiment), upt to 92 days (2nd experiment)
- Necropsy of survivors performed: No
- Examinations performed: Clinical signs, body weight

Statistics:

No statistics available

Key result

Sex:

not specified

Dose descriptor:

LC50

Effect level:

> 10 000 mg/m³ air

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

1st experiment: No mortality

2nd experiment: No mortality

Body weight:

No information given

Gross pathology:

No information given

Other findings:

1st experiment: No signs of illness

2nd experiment: No signs of illness

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating conc.

Value:

> 10 000 ca. mg/m³ air

Physical form:

inhalation: mixture of vapour and aerosol / mist

Quality of whole database:

Study well documented, meets generally accepted scientific principles, acceptable for assessment

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:

Not available, publication received 1945-05-31

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: The purpose of this investigation was to determine the effects resulting from its application upon the skin.

- Short description of test conditions: The test substance was applied to the shaved belly of rabbits for 2 hours, the procedure was repeated on several days. No details about sex, environmental and treatment are given.

- Parameters analysed / observed: Local and systemic illness, body weights

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

No information available.

Species:

rabbit

Strain:

other: Albino rabbits

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Albino rabbits were purchased from a local breeder
- Acclimation period: About 2 weeks

IN-LIFE DATES: From day 0 to day 45

Type of coverage:

not specified

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

REMOVAL OF TEST SUBSTANCE
- Washing: The test item was washed off the skin with soap and water
- Time after start of exposure: 2 hours

TEST MATERIAL
- Amount applied: 2 mL/kg bw
- Constant volume or concentration used: No
- For solids, paste formed: No

Duration of exposure:

2 hours per exposure, exposure for 33 days over a period of 45 days

Doses:

2 mL/kg bw

No. of animals per sex per dose:

6 animals per dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: Animals were exposed and observed over a period of 45 days.
- Frequency of weighing: At the beginning and end of the exposure period
- Necropsy of survivors performed: No
- Examinations performed: Clinical signs, body weight

Statistics:

No statistics performed

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 2 102 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Remarks:

Effect level was converted from 2 mL/kg bw to 2102 mg/kg bw

Mortality:

No mortality occured

Clinical signs:

other: None of the animals displayed signs of local or systemic illness. The compound did not produce irritation or damage to the skin of these animals.

Gross pathology:

No gross pathology was performed.

Other findings:

No other findings were observed.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

> 2 102 mg/kg bw

Additional information

Acute oral toxicity, rat, RL2

In an acute oral toxicity study in rats, 10 animals per dose were treated with the test item by gavage. Doses of 4.7, 7.0, 10.0 and 16.0 mL/kg bw were used. Oral doses of the test item were given to the rats by means of a blunt hypodermic needle. The test item induced dose-dependent effects comprising muscular weakness, mild anesthesia and an increase in the rate of respiration. These signs were followed by dyspnea and by mild asphyxial convulsions. Death resulted from the combined effects of circulatory and respiratory failure. The lethal quantity given orally in one dose at which 50% of the animals died was 8.8 mL/kg bw, corresponding to 9249 mg/kg bw (Deichmann, 1945).

 

Acute oral toxicity, rabbit, RL2

In an acute oral toxicity study in rabbits, 10 animals per dose were treated with the test item by gavage. Doses of 0.94, 1.4, 2.1, 3.2, 4.7 and 7.0 mL/kg bw were used. Oral doses of the test item were given to rabbits by means of a rubber catheter. The test item induced dose-dependent effects comprising muscular weakness, mild anesthesia and an increase in the rate of respiration. These signs were followed by dyspnea and by mild asphyxial convulsions. Death resulted from the combined effects of circulatory and respiratory failure. The lethal quantity given orally in one dose at which 50% of the animals died was 2.48 mL/kg bw, corresponding to 2606 mg/kg bw (Deichmann, 1945).

 

Acute oral toxicity, rabbit, RL4

In an acute oral toxicity study in rabbits, the LD50 was reported to exceed 5000 mg/kg bw. No further details were given (Opdyke, 1962-1980; based on the original study of Moreno, 1978).

 

Acute oral toxicity, rat, RL4

In an acute oral toxicity study in rats, the LD50 was reported to be 9200 mg/kg bw. No further details were given (Baer&Griepentrog, 1966).

 

Acute inhalation toxicity, mouse, RL2

In an acute inhalation toxicity study, 4 mice (1st experiment) and another 6 mice (2nd experiment) were treated with 3-10 mg/L air of the test item (1st experiment) or with approx. 1.5 mg/L air of the test item (2nd experiment). Mice developed systemic illness after acute treatment with 1.5 - 10 mg/L air, comprising signs of respiratory disturbance. After longer treatment with 3-10 mg/L of the test item, one mice showed a complete paralysis of the hind quarters. One mouse died after the first exposure to 3-10 mg/L air. As only 1/4 mice died after acute exposure, no LC50 could be determined (Deichmann, 1945).

 

Acute inhalation toxicity, rat, RL2

In an acute inhalation toxicity study, 4 rats (1st experiment) and another 4 rats (2nd experiment) were treated with 3-10 mg/L air of the test item (1st experiment) or with approx. 1.5 mg/L air of the test item (2nd experiment). Rats showed no signs of illness after exposure to 1.5-10 mg/L of the test item for up to 60 seven-hour periods. No LC50 could be determined (Deichmann, 1945).

 

Acute inhalation toxicity, rabbit, RL2

In an acute inhalation toxicity study, 2 rabbits (1st experiment) and another 2 rabbits (2nd experiment) were treated with 3-10 mg/L air of the test item (1st experiment) or with approx. 1.5 mg/L air of the test item (2nd experiment). Rabbits showed no signs of illness after exposure to 1.5-10 mg/L of the test item for up to 60 seven-hour periods. No LC50 could be determined (Deichmann, 1945).

 

Acute dermal toxicity, rabbit, RL2

In an acute dermal toxicity study in rabbits, 6 animals were treated with 2 mL/kg bw. Therefore, the hair on the belly was clipped short over an area of about 20 square inches. After application, animals were kept under mild restraint for 2 hours. The compound was then washed off with soap and water and the animal returned to their cages. Applications were given daily, except sundays for 45 days. None of the animals displayed signs of local or systemic illness. The compound does not produce irritation or damage to the skin of the animals. The LD50 was thus found to be >2102 mg/kg bw (Deichmann, 1945).

 

Acute dermal toxicity, rabbit, RL4

In an acute dermal toxicity study in rabbits, the LD50 was reported to exceed 5000 mg/kg bw. No further details were given (Opdyke 1962-1980, based on the original study of Moreno, 1978).

 

Acute i.m. toxicity, guinea pig, RL4

Different organic esters were examined for systemic toxicity, local irritation and action upon the neuro-muscular functions after intramuscular injection in the guinea pig's leg. A single dose of 2.5 cc./kg bw (2.5 mL/kg bw) of the test item was injected i.m. and animals were observed for one week. 75% of the animals died within 2 days (Lipschitz, 1942).

 

Acute i.p. toxicity, mouse, RL2

In an acute oral toxicity study, small groups of mice were injected intraperitoneally with increasing dosage levels of the test item and the resulting mortality was recorded for one week. The approximate LD50 (7-day) was used as the basis for selecting the dosage levels for a radioprotectivity study. The LD50 of the test item was found to be higher than 500 mg/kg bw (Doull, 1962).

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. The LD50 was greater than 2000 mg/kg bw for both acute oral and dermal toxicity and the LC50 was greater than 3000-10000 mg/m³ air. As a result, the substance is not considered to be classified for acute oral, inhalation and dermal toxicity under Regulation (EC) No 1272/2008, as amended for fifteenth time in Regulation (EU) No 2020/217.