1-ethylpyrrolidin-2-one

Endpoint summary

Description of key information

1-Ethyl-pyrrolidin-2 -one (NEP) is practically non-toxic after acute inhalative or dermal exposure. After ingestion NEP is of low acute toxicity.

LD50 (rat; oral) : 3200 mg/kg
LC50 (rat; inhal.): > 5.1 mg/l/4h
LD50 (rat; dermal): > 2000 mg/kg

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: non-GLP study and non-guideline study, but basic information given

Principles of method if other than guideline:

similar to OECD 401

GLP compliance:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

The mean body weights for males was 208 g and for females 165 g.
The animals were offered Herilan MRH concentrated feed and water ad libitum. Feed was withdrawn 16 hours before the beginning of the study.

Route of administration:

oral: gavage

Vehicle:

water

Doses:

10.0; 21.5; 31.6 and 50% solution in distilled water in doses of 1,000; 2,150; 3,160 and 5,000 mglkg

No. of animals per sex per dose:

5

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 3 200 mg/kg bw

Mortality:

see below

Clinical signs:

other: see below

Gross pathology:

Animals that died: Heart: acute dilatation; kidneys: some of them pale; lungs: infarctoid congestion with edematization; intestines: atonic
Sacrificed animals: Organs: no abnormalities detected

Mortality:

Dose (mg/kg)	Conc. (%)	No. of animals	Died within
			1 hour	24 hours	48 hours	7 days	14 days
5,000	50	5 males	0/5	5/5	5/5	5/5	5/5
		5 females	0/5	3/5	4/5	4/5	4/5
3,160	31.6	5 males	0/5	0/5	1/5	1/5	1/5
		5 females	0/5	2/5	4/5	4/5	4/5
2,150	21.5	5 males	0/5	0/5	0/5	0/5	0/5
		5 females	0/5	0/5	0/5	0/5	0/5
1,000	10.0	5 males	0/5	0/5	0/5	0/5	0/5
		5 females	0/5	0/5	0/5	0/5	0/5

Symptoms:

	5,000 mg/kg	3,160 mg/kg	2,150 mg/kg	1,000 mg/kg
Dyspnea	15 min - 6 d	< 15 min - 4 h	1 h - 5 h
Apathy	15 min - 5 d	< 15 min - 4 h	1 h - 5 h
Lateral position	1 h - 2 d	30 min - 4 h
Abdominal position	30 min - 4 h	2 h - 4 h
Dorsal position	4 h
Staggering	15 min - 1 d	< 15 min - 4 h
Atony	1 h - 4 h
Paresis	15 min - 2 d
Pain reflex absesnt	1 h
Narcotic-like state	1 h
Urine orange				1 d - 5 d
Erythema	1 h - 2 d
Exsiccosis	1 h - 2 d
Ames blood test	15 min - 6 d	< 15 min - 4 h	1 h - 5 h

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Only animals free from clinical signs of disease were used for the study. The females were nulliparous and non-pregnant. The animals were subjected to an acclimatization period of at least 1 week in which they were adapted to the surroundings. Age of the animals at the beginning of the study was approx . 8 - 10 weeks for males and approx. 11 - 13 weeks for females. The animals were identified individually numbered consecutively on the tail. The feed used in the study was assayed for chemical as well as for microbiological contaminants. The drinking water is regularly assayed for chemical contaminants by the municipal authorities as well as for the presence of microbes. The animals were kept in fully air-conditioned rooms in which temperatures in the range of 20 - 24°C and relative humidities in the range of 30 - 70% were regulated by means of a central air-conditioning system. The animals were housed singly in cages type DK III without bedding, with a light/dark cycle of 12 hours.

Route of administration:

inhalation

Type of inhalation exposure:

nose/head only

Vehicle:

other: The test substance was doses unchanged. A liquid aerosol was generated.

Details on inhalation exposure:

Considering the vapor pressure of the test substance, the test atmosphere was supposed to be a mixture of vapor and liquid aerosols.
After the exposure, the animals were observed for 14 days.
The body weight of the animals was determined just prior to exposure (day 0), weekly thereafter and at the end of the observation period. A check for overt clinical signs of toxicity or mortality as well as a check for the presence of feed and drinking water was made twice a day on workdays and once daily on weekends and public holidays. Detailed clinical observations were recorded for each animal separately several times during exposure and at least once on each workday of the observation period. At the end of the observation period the animals were sacrificed with CO2 and were subjected to gross-pathological examination.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5.1 mg/l

No. of animals per sex per dose:

5

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.1 mg/L air

Exp. duration:

4 h

Remarks on result:

other: aerosol

Mortality:

No mortality occurred at the tested concentration.

Clinical signs:

other: Clinical signs of toxicity comprised visually accelerated respiration, squatting posture, piloerection, smeared and contaminated fur. Findings were observed from hour 0 of exposure until including study day 1.

Body weight:

The mean body weights of the male and female animals did not increase adequately during the first post exposure observation week, but increased during the second week.

Gross pathology:

No gross pathological abnormalities were noted in the animals necropsied at termination of the post exposure observation period.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Female animals were nulliparous and non-pregnant. Individual identification by cage cards and tail marking. The animals were housed in fully air-conditioned rooms. Central air-conditioning guaranteed a range of 20 - 24°C for temperature and of 30 - 70% for relative humidity. There were no deviations from these ranges, which influenced the results of the study. Day/night rhythm: 12h/12h. Stainless steel wire mesh cages were used and the animals were housed singly. Diet was Kliba-Labordiät, water was available ad libitum. Acclimatization for at least 5 days. Clipping of the fur about 24 hours before the beginning of the study.

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The test material was applied to the clipped skin (dorsal and dorsolateral parts of the trunk). Application area about 40 cm2 (corresponds to at least 10% of the body surface).
Observation period at least 14 days. Body weight determination: Individual body weights shortly before application (day 0), weekly thereafter and at the end of the study.
Recording of signs and symptoms several times on the day of administration, at least once each workday for the individual animals. Scoring of skin findings: Individual readings 30 - 60 minutes after removal of the semiocclusive dressing (day 1), as a rule weekly thereafter and at the end of the study (last day of the observation period). A check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays. Gross-pathology examination on the last day of the observation period after killing with CO2.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occurred

Clinical signs:

other: No systemic clinical observations were observed during clinical examination. No local effects were observed.

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined at termination of the study.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

In an oral toxicity study, comparable to OECD 401, rats (5/sex/dose) were given 1000, 2150, 3160 and 5000 mg/kg 1-Ethyl-pyrrolidin-2 -one (NEP) in water by gavage. No mortality was observed at 1000 and 2150 mg/kg. No clinical signs were noted at 1000 mg/kg but in the 2150 mg/kg dose group dyspnea and apathy were observed: Clinical signs were reversible within 24 h. At higher concentration mortality and severe clinical signs like dyspnea, apathy, abdominal position and CNS effects (staggering, paresis, narcotic-like state). In animals that died pale kidneys were noted. There were no findings in animals that were sacrificed at termination of the study. The LD50 was determined to be about 3200 mg/kg (BASF 1978; reliability 2).

Wistar rats (5/sex) were exposed to 5.1 mg/l NEP (aerosol) for 4 h. The limit test was conducted according to OECD 403 and GLP. No mortality occurred. Clinical signs like accelerated respiration, Squatting posture and a poor general condition on the first day was noted. Body weight gain was reduced. Necropsy revealed no abnormalities (LC50 is > 5.1 mg/l/4h) (BASF 2005, reliability 1).

NEP was administered to Wistar rats (5/sex) in a dermal toxicity study at a dose of 2000 mg/kg according to OECD 402 and GLP. No substance related effect was observed in this limit test. The LD50 is therefore > 2000 mg/kg (BASF 2005, reliability 1).

Justification for classification or non-classification

Classification is not warranted according to the criteria of EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.