1-ethylpyrrolidin-2-one

Endpoint summary

Description of key information

NEP caused irreversible damage to the eye in a OECD 405 conform study, but produced only minimal effects in a skin irritation study according to OECD 404.

In a guideline study (OECD TG 404), 0.5 mL of undiluted 1 -Ethyl-pyrrolidin-2 -one (NEP) was applied onto the shaved intact skin of 3 Vienna White rabbits under semi-occlusive conditions for 4 hours (BASF AG, 1986; reliability 2). The animals were scored for dermal effects or irritation 4, 24, 48, and 72 hours and 8 days after removal of the patch. Erythema but no edema was observed. The maximum mean irritation score of 1.3 was obtained at 24 – 72 h. These effects were fully reversible within 8 days (BASF 1986).

 

NEP (0.1 ml) was instilled into the conjunctival sac of the right eye of 3 New Zeeland White rabbits in a OECD 405 guideline study (BASF AG, 2005; reliability 2). Eyes were not washed after instillation. Eyes were observed for corneal effect, iritis and conjunctival effects 1, 24, 48 and 72 hours and 7, 14 and 28 days after instillation of material. Mean values 24- 72 h are: 1.2 (Cornea) 0.6 (iris); 3 (erythema) and 1.9 (edema). Corneal opacity was observed in all animals from 24 to 72 in all animals. Opacity was not reversible within 21 in 2/3 animals. At day 28 a slight corneal opacity was still visible in one animal. Therefore, NEP causes irreversible damage to the eye in this study. This study confirms a result of a former study with a 15 days post application observation period (BASF, 1986).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: non-GLP study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

Stainless steel cages with an floor area of 40 x 51 cm were used. One animal per cage. 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. The day/night rhythm was 12 h dark and 12 h light. No bedding were used in the cages, saw-dust in the waste trays. Kliba 341 was used as diet and about 250 ml tap water per animal per day was available. Acclimatization period: at least 8 days before the beginning of the study; same housing conditions as during the study. The mean body weights were 2.77 kg for males and 3.11 kg for females.

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin sites of the same animal

Amount / concentration applied:

Wetting of the test patch with the undiluted substance, and thus about 0.5 ml of the test liquid is absorbed.

Duration of treatment / exposure:

4 h

Observation period:

30 - 60 min after removal of the test patches and 24 h, 48 h, 72 h, 8 d after the beginning of application

Number of animals:

3

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 -72 h

Score:

1.3

Max. score:

2

Reversibility:

fully reversible within: 8 days

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 - 72 h

Score:

0

Max. score:

0

Readings	Animal No.	Intact Skin		Symptoms
		Erythema	Edema
4 hours	1	1	0
	2	1	0
	3	0	0
24 hours	1	2	0
	2	1	0
	3	1	0
48 hours	1	2	0
	2	1	0
	3	1	0
72 hours	1	2	0
	2	1	0
	3	1	0
8 days	1	0	0	scaling
	2	0	0
	3	0	0

Interpretation of results:

not irritating

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

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

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

The animals were housed in fully air-conditioned rooms, in which a central air-conditioning system ensured a temperature in the range of 20 - 24°C and a relative humidity in the range of 30 - 70%. Deviations from these specifications that would have had an adverse effect on the test results did not occur. Illumination period was 12 h light (6.00 a.m. - 6 .00 p.m.) and 12 h darkness (6.00 p.m. - 6.00 a.m. Stainless steel wire mesh cages with grating were used; the animals were housed singly. The diet was Kliba Labordiät and water was available ad libitum. Acclimatization period was at least 5 days before the beginning of the study.
Before the beginning of application both eyes were investigated for signs of pre-existing irritation. Only animals with intact cornea and conjunctiva were used.

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated left eye

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

single ocular application

Observation period (in vivo):

The ocular reactions were assessed approximately 1, 24, 48 and 72 hours after application and then in weekly intervals until day 28.

Number of animals or in vitro replicates:

3

Details on study design:

About 24 hours after application the eye was rinsed with tap water.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24 - 72 h

Score:

1.2

Max. score:

2

Reversibility:

not fully reversible within: within 28 d

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24 - 72 h

Score:

0.6

Max. score:

1

Reversibility:

fully reversible

Remarks:

within 7 d

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24 - 72 h

Score:

2.7

Max. score:

3

Reversibility:

fully reversible

Remarks:

14 d

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24 - 72 h

Score:

1.9

Max. score:

2

Reversibility:

fully reversible

Remarks:

14 d

 

 

 

Readings	Animal	Cornea		Iris	Conjunctiva			Additional findings
		Opacity	Area of cornea involved		Redness	Chemosis	Discharge
1 h	01	0	0	0	3	3	3	49
	02	0	0	0	2	3	3	49
	03	0	0	0	2	3	3	49
24 h	01	1	2	0	2	1	1	PC, 48
	02	1	4	1	3	2	2	PC, DB, 49
	03	1	4	1	3	3	2	PC, DB, 49
48 h	01	1	1	0	2	1	1	PC, 48
	02	1	4	1	3	2	2	PC, DB, 48
	03	1	4	1	3	3	1	PC, DB, 49
72 h	01	1	1	0	2	1	0	PC, 48
	02	2	4	0	3	2	1	PC, DB, 48
	03	2	4	1	3	2	1	PC, DB, 49
7 d	01	0	0	0	0	0	0	SD
	02	1	3	0	1	0	0	PC, 48
	03	2	1	0	2	2	1	S, PC, 44, 49
14 d	02	1	1	0	0	0	0	44, 48
	03	1	1	0	0	0	0	44, 48
21 d	02	0	0	0	0	0	0	SD
	03	1	1	0	0	0	0	45, 48
28 d	03	1	1	0	0	0	0	45, 48
Mean 24 - 72 h	01	1.0		0.0	2.0	1.0
	02	1.3		0.7	3.0	2.0
	03	1.3		1.0	3.0	2.7
Mean		1.2		0.6	2.7	1.9

 

Explanation of findings:

S  = Suppuration

PC    = Pupil contracted

DB    = Discharge of blood

SD    = Study discontinued because the animal was free of findings

 

44 = Vascularization of the cornea, circumscribed area, marginal

45 = Vascularization of the cornea, circumscribed area, into the central part

48 = Scleral vessels injected, circumscribed area

49 = Scleral vessels injected, circular

Conclusions:

Considering the described ocular reactions as well as the average score for irritation, N-Ethyl-2-pyrrolidon shows a severe eye irritation potential under the test conditions chosen.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: non-GLP study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye

Amount / concentration applied:

0.1 ml

Observation period (in vivo):

15 days

Number of animals or in vitro replicates:

3

Details on study design:

The test substance was not washed out.

Irritation parameter:

cornea opacity score

Basis:

mean

Score:

1

Max. score:

1

Reversibility:

not fully reversible within: 15 d

Irritation parameter:

iris score

Basis:

mean

Score:

0.2

Max. score:

1

Reversibility:

fully reversible

Remarks:

48 h

Irritation parameter:

conjunctivae score

Basis:

mean

Score:

1.3

Max. score:

2

Reversibility:

fully reversible

Remarks:

8 d

Irritation parameter:

chemosis score

Basis:

mean

Score:

0.7

Max. score:

2

Reversibility:

fully reversible

Remarks:

72 h

Readings	Animal No.	Cornea Opacity	IRIS	Conjunctiva		Symptoms
				Redness	Chemosis
1 hour	1	0	0	2	2
	2	0	0	2	2
	3	0	0	2	2
24 hours	1	1	0	1	1
	2	1	1	2	2
	3	1	1	1	1
48 hours	1	1	0	1	0	S3
	2	1	0	2	1
	3	1	0	2	1
72 hours	1	1	0	1	0	S3
	2	1	0	1	0
	3	1	0	1	0
8 days	1	1	0	0	0	S3/MV
	2	0	0	0	0
	3	2	0	0	0	S3/MV/RE
15 days	1	1	0	0	0	S3/MV/RE
	2	0	0	0	0
	3	1	0	0	0	S3/MV/RE/PC

 

EXPLANATION OF SYPMPTOMS:

 S3      - Loss of corneal tissue

MV     - Marginal vascularization of the cornea

PC      - Pupil contracted

RE      - Small retractions in the eyelids

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Classification criteria (eye cat. 1) according to EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 are fulfilled.

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