1-(2-hydroxyethyl)pyrrolidin-2-one

Endpoint summary

Description of key information

1-2(hydroxyethyl)-2-pyrrolidone was found to be not irritant to the skin and eye of rabbits. 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

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:

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Principles of method if other than guideline:

Before OECD Guideline 404 was established, skin irritation was tested using an internal method (BASF test). Groups of two animals were treated for 1, 5, or 15 minutes or 20 hours using occlusive conditions. An application site of 2.5x2.5 cm was covered with the liquid test substance. After the application time the skin was washed with Lutrol (50%). The animals were observed for 8 days and skin changes were recorded daily. The report describes findings after 24 hours and at the end of the observation period (8 days).

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Type of coverage:

occlusive

Preparation of test site:

other: intact skin

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin of the same animal

Amount / concentration applied:

about 1 ml

Duration of treatment / exposure:

1, 5 and 15 minutes and 20 hours

Observation period:

8 days

Number of animals:

2 per exposure duration

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm

REMOVAL OF TEST SUBSTANCE
- Washing (if done): skin rinsed with Lutrol 50%
- Time after start of exposure: after treatment (1, 5 and 15 minutes and 20 hours)

Irritation parameter:

erythema score

Remarks:

(1 minute exposure)

Basis:

mean

Time point:

other: 24 hours

Score:

0

Max. score:

4

Remarks on result:

other: 1 minute exposure

Irritation parameter:

erythema score

Remarks:

(5 and 15 minutes exposure)

Basis:

mean

Time point:

other: 24 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: 5 and 15 minutes exposure

Irritation parameter:

erythema score

Remarks:

(20 hours exposure)

Basis:

mean

Time point:

other: 24 hours

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 8 days. Already after 2 days, the erythema were very slight (score 1) in both animals.

Remarks on result:

other: 20 hours exposure

Irritation parameter:

edema score

Remarks:

(1, 5, 15 minutes and 20 hours exposure)

Basis:

mean

Time point:

other: 24 hours

Score:

0

Max. score:

4

Remarks on result:

other: 1, 5, 15 minutes and 20 hours exposure

Irritant / corrosive response data:

After a 20 hours occlusive exposure to the undiluted substance a erythema score 2 was reported for both animals. After 8 days, all findings had disappeared. Already after 2 days, the erythema were very slight (score 1) in both animals. So, the scores triggering classification would not have been reached. Considering the stringent application conditions (20 hours, occlusive, no rinsing), the substance is assessed to be non-irritant to the skin according to regulatory criteria.

Interpretation of results:

GHS criteria not met

Reference 2

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:

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

Fed. Reg., Vol 26, No. 155, p 7336, 12 Aug. 1961

Deviations:

not specified

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 ml, undiluted

Duration of treatment / exposure:

24 hours

Observation period:

24 hours (directly after exposure) and 72 hours (48 hours after first reading)

Number of animals:

6

Details on study design:

A minimum of 6 albino rabbits were used clipped free of hair. Only results for intact skin is reported below. 0.5 ml of the test substance were ntroduced under a square patch 1 inch x 1 inch , two single layers thick. The animals are immobilized with patches secured in place by adhesive tape. The entire trunk is then wrapped with an impervious material such as rubberized cloth for the 24-hour period of exposure. After 24 hours of exposure the patches were removed and the reactions were evaluated . Readings were again made at the end of a 72 hours (48 hours after the first reading).

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 and 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: no signs of erythema at any time point for all animals

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 and 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: no signs of edeme at any time point for all animals

After a 24 and 72 hours of exposure to the undiluted substance no signs of erythema or edeme were reported (score in all animals 0). The substance is assessed to be non-irritant to the skin according to regulatory criteria.

Interpretation of results:

GHS criteria not met

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

Study period:

1971

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not specified

Principles of method if other than guideline:

according to Federal Register, Vol. 29, No. 182, p 13009, 17 Sept 1964

GLP compliance:

no

Species:

rabbit

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

24, 48 and 72 hours

Number of animals or in vitro replicates:

6

Details on study design:

The test material is placed in one eye of each animal by gently pulling the lower lid away from the eyeball to form a cup into which the test substance is dropped. The other eye, remaining untreated, seves as a control. The eyes are not washed following instillation.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animals 1-6

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: no corneal effects observed

Irritation parameter:

iris score

Basis:

mean

Remarks:

animals 1-6

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

2

Remarks on result:

other: iris was not affected in any animal

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animals 1-6

Time point:

other: 24 hours

Score:

1

Max. score:

3

Reversibility:

fully reversible within: one day

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animals 1-6

Time point:

other: 48 and 72 hours

Score:

0

Max. score:

3

Remarks on result:

other: no conjuctival effects observed

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animals 1-6

Time point:

other: 24 hours

Score:

0.16

Max. score:

4

Reversibility:

fully reversible within: one day

Remarks on result:

other: one animal affected grade 1

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animals 1-6

Time point:

other: 48 and 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: no chemosis observed

Irritation parameter:

other: discharge

Basis:

mean

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

3

Remarks on result:

other: no discharge observed at any time point

Interpretation of results:

GHS criteria not met

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Principles of method if other than guideline:

Before OECD Guideline 405 was established, eye irritation was tested using an internal method (BASF test). 50 µL of the test substance was applied to the conjunctival sac of one eye in 2 animals. Findings were recorded daily. The eyes were not washed out after treatment as specified in OECD Guideline 405. Findings were recorded daily, the report describes findings after 1 and 24 hours and at the end of the 8-day observation period.

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of the same animal

Amount / concentration applied:

50 µl

Duration of treatment / exposure:

single application, no washing was performed

Observation period (in vivo):

1 hour, 24 hours and day 8 post-treatment

Number of animals or in vitro replicates:

2

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 1 hour

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 4 days

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24 hours

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 4 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 1 hour

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 24 hours

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 1 hour and 24 hours

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 1 and 24 hours, 8 days

Score:

0

Max. score:

4

Irritant / corrosive response data:

According to the raw data, 24 hours after application of the undiluted substance, conjunctiva and chemosis (both score 2) were reported in one animal. The second animal was without any findings after 24 hours. The findings in animal 1 disappeared completely after 4 days. In addition, fluorescein staining of the cornea was performed after 3 days (slight cloudiness after 3 days in one animal (also seen in the control eye) which disappeared after 4 days). Considering this information and the slight effects observed in the study, the substance is assessed to be non-irritant to the eyes according to regulatory criteria.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

Irritation to the skin was investigated in a study performed according to a BASF internal method which is comparable to OECD guideline 404 (BASF AG, 1970). In this study Vienna White rabbits were exposed to 1-(2-hydroxyethyl)-2-pyrrolidone for 1, 5 or 15 minutes or 20 hours (n=2) under occlusive conditions to about 1 ml of the substance. No edema was observed under any of the test conditions. After 5 minutes exposure, in one animal erythema (score 1) was observed at 24 hours and after 15 minutes exposure, erythema (score 1) was observed in both animals after 24 hours. After 20 hours of exposure, erythema score 2 was reported at 24 hours for both animals. In all cases, the observed effects were fully reversible within 8 days. Already after 2 days, the erythema were very slight (score 1) in both animals. So, the scores triggering classification would not have been reached. Considering the stringent application conditions (20 hours, occlusive, no rinsing), the substance is assessed to be non-irritant to the skin according to regulatory criteria.

In a second study, undiluted 1-2(hydroxyethyl)-2-pyrrolidone was tested for its skin irritation potential according to the method described in the Federal Register, Vol. 26, No. 155, p. 7336 12 Aug. 1961 (Fd. Drug Res. Labs. Inc., 1971). No signs of erythema or edema were observed after 24 and 72 hours (mean score 0).

 

Eye irritation

Eye irritation was investigated in a study performed according to a BASF internal method which is comparable to OECD guideline 405 (BASF AG, 1970). According to this method, 50 µL of the test substance was applied to the conjunctival sac of one eye of groups of 2 test animals. Findings were reported after 1 and 24 hours and an 8 -day observation period followed thereafter. Chemosis (score 2) was observed after 1 and 24 hours in animal 1 (fully reversible within: 4 days). In animal 1 a conjunctivae score of 2 was observed after 1 hour and a score of 1 was observed after 24 hours (fully reversible within: 4 days). In animal 2, a conjunctivae score of 1 was observed after 1 hour (fully reversible within: 24 hours). The findings in animal 1 disappeared completely after 4 days. In addition, fluorescein staining of the cornea was performed after 3 days (slight cloudiness after 3 days in one animal (also seen in the control eye) which disappeared after 4 days). Considering this information and the slight effects observed in the study, the substance is assessed to be non-irritant to the eyes according to regulatory criteria.

After a 20 hours occlusive exposure to the undiluted substance a erythema score 2 was reported for both animals. After 8 days, all findings had disappeared. Already after 2 days, the erythema were very slight (score 1) in both animals. So, the scores triggering classification would not have been reached. Considering the stringent application conditions (20 hours, occlusive, no rinsing), the substance is assessed to be non-irritant to the skin according to regulatory criteria.

In a second study, undiluted 1-2(hydroxyethyl)-2-pyrrolidone was tested for its eye irritation potential according to the method described in the Federal Register, Vol. 29, No. 182, p. 13009, 17 Sept. 1964 (Fd Drug Res. Labs. Inc., 1971). The test material produced only a very slight conjunctival effect in (grade 1) in all of the animals which cleared by the second day of observation and is therefore tassessed to be non-irritant to the eyes of rabbits according to regulatory criteria.

Justification for classification or non-classification

Based on the available data, the substance does need not to be classified for skin and eye irritation according to to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.