1-methyl-2-pyrrolidone

Endpoint summary

Description of key information

Based on key study results and according to the harmonised classification (Annex VI of Regulation (EC) No 1272/2008 (CLP Regulation)), NMP is considered to be irritating to the skin, the eyes and the respiratory system.

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:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not applicable

GLP compliance:

not specified

Specific details on test material used for the study:

- Source: GAF Chemicals Corporation, Wayne, NJ, USA
- Purity: >= 98%, with less than 0.5% of water

Species:

rabbit

Strain:

other: albino

Type of coverage:

occlusive

Preparation of test site:

abraded

Remarks:

back on one side abraded using a sterile 22-gauge needle

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: Skin of the back
- Type of wrap if used: gauze pad secured with an adhesive tape, covered with occlusive wrap

REMOVAL OF TEST SUBSTANCE
- Washing: water moistened towel, skin wiped afterwards
- Time after start of exposure: 24 hours

SCORING SYSTEM: according to Draize (Draize et al. 1944)

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24 and 72 hours

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: abraded or intact skin

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24 and 72 hours

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: abraded or intact skin

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24 and 72 hours

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: abraded or intact skin

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

other: 24 and 72 hours

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: abraded or intact skin

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

other: 24 and 72 hours

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: abraded or intact skin

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

other: 24 and 72 hours

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: abraded or intact skin

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 and 72 hours

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: abraded or intact skin

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24 and 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: abraded or intact skin

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24 and 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: abraded or intact skin

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24 and 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: abraded or intact skin

Irritation parameter:

edema score

Basis:

animal #4

Time point:

other: 24 and 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: abraded or intact skin

Irritation parameter:

edema score

Basis:

animal #5

Time point:

other: 24 and 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: abraded or intact skin

Irritation parameter:

edema score

Basis:

animal #6

Time point:

other: 24 and 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: abraded or intact skin

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 and 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: abraded or intact skin

Irritant / corrosive response data:

Effects ranged fom none to barely perceptible erythema without oedema clearing within 72 hours.

Rabbit	Skin	24 hours		72 hours		7 days
		Erythema	Oedema	Erythema	Oedema	Erythema	Oedema
1	I	1	0	0	0	0	0
	I	1	0	0	0	0	0
	A	1	0	0	0	0	0
	A	1	0	0	0	0	0
2	I	1	0	0	0	0	0
	I	1	0	0	0	0	0
	A	1	0	0	0	0	0
	A	1	0	0	0	0	0
3	I	1	0	0	0	0	0
	I	1	0	0	0	0	0
	A	1	0	0	0	0	0
	A	1	0	0	0	0	0
4	I	1	0	0	0	0	0
	I	1	0	0	0	0	0
	A	1	0	0	0	0	0
	A	1	0	0	0	0	0
5	I	1	0	0	0	0	0
	I	1	0	0	0	0	0
	A	1	0	0	0	0	0
	A	1	0	0	0	0	0
6	I	1	0	0	0	0	0
	I	1	0	0	0	0	0
	A	1	0	0	0	0	0
	A	1	0	0	0	0	0
Mean	I	1.0	0	0	0	0	0
	A	1.0	0	0	0	0	0

 

A: abraded skin, I: intact skin

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal response was rated as minimal.

Executive summary:

In a primary dermal irritation study albino rabbits were dermally exposed to undiluted NMP similar to OECD guideline 404.

Approximately 0.5 mL NMP was applied to the backs of 6 rabbits that had been closely abraded. The undiluted NMP was applied to the intact (concurrent control) and abraded skin. When the examination was repeated 72 hours after the start of exposure, no effects were observed. The tests showed a low potential for skin irritation and resulted (for both intact and abraded skin and averaged reading from 24 and 72 hours) in a primary irritation index (PII) of 0.5.

The dermal response was rated as minimal. Although the results of this study will not lead to classification, the EU has classified NMP as irritating the skin.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

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:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not applicable

GLP compliance:

not specified

Specific details on test material used for the study:

- Source: GAF Chemicals Corporation, Wayne, NJ, USA
- Purity: >= 98%, with less than 0.5% of water

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL

Duration of treatment / exposure:

- treatment during complete period as single intraocular application
- additional animals treated for only 30 seconds (eye washed afterwards)

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

Not specified

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: not specified, in additional animals
- Time after start of exposure: 30 s

SCORING SYSTEM: Draize method (Draize et al., 1944)

Irritation parameter:

overall irritation score

Remarks:

Primary irritation index

Basis:

mean

Time point:

24 h

Score:

41

Max. score:

110

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: unwashed

Irritation parameter:

overall irritation score

Remarks:

Primary irritation index

Basis:

mean

Time point:

48 h

Score:

40

Max. score:

110

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: unwashed

Irritation parameter:

overall irritation score

Remarks:

Primary irritation index

Basis:

mean

Time point:

72 h

Score:

34

Max. score:

110

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: unwashed

Irritation parameter:

overall irritation score

Remarks:

Primary irritation index

Basis:

mean

Time point:

7 d

Score:

8

Max. score:

110

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: unwashed

Irritation parameter:

overall irritation score

Remarks:

Primary irritation index

Basis:

mean

Time point:

14 d

Score:

4

Max. score:

110

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: unwashed

Irritation parameter:

overall irritation score

Remarks:

Primary irritation index

Basis:

mean

Time point:

21 d

Score:

0

Max. score:

110

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: unwashed

Irritation parameter:

overall irritation score

Remarks:

Primary irritation index

Basis:

mean

Time point:

24 h

Score:

35

Max. score:

110

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: washed (30 sec after administration)

Irritation parameter:

overall irritation score

Remarks:

Primary irritation index

Basis:

mean

Time point:

48 h

Score:

26

Max. score:

110

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: washed (30 sec after administration)

Irritation parameter:

overall irritation score

Remarks:

Primary irritation index

Basis:

mean

Time point:

72 h

Score:

18

Max. score:

110

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: washed (30 sec after administration)

Irritation parameter:

overall irritation score

Remarks:

Primary irritation index

Basis:

mean

Time point:

7 d

Score:

1

Max. score:

110

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: washed (30 sec after administration)

Irritation parameter:

overall irritation score

Remarks:

Primary irritation index

Basis:

mean

Time point:

14 d

Score:

0

Max. score:

110

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: washed (30 sec after administration)

Irritation parameter:

overall irritation score

Remarks:

Primary irritation index

Basis:

mean

Time point:

21 d

Score:

0

Max. score:

110

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: washed (30 sec after administration). Value was not measured

Irritant / corrosive response data:

All the animals showed corneal involvement reversing within 14 days for unwashed eyes and within 7 days for washed eyes. Conjunctival effects cleared in unwashed eyes by the end of the 21-day observation period and in washed eyes by day 14.

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Remarks:

Moderate ocular effects observed according to the Draize score system.

Conclusions:

Corneal effects were reversible within 14 days for unwashed eyes and within 7 days for washed eyes. Conjunctival effects cleared in unwashed eyes by the end of the 21 -day observation period and in washed eyes by day 14.

Executive summary:

In an irritation study, New Zealand White rabbits received a single intraocular application of 0.1 mL neat NMP into the conjunctival sac of one eye, the other served as untreated control. Additional animals were dosed but their eyes were washed out 30 seconds after administration. Animals were observed for 21 days. Irritation was scored according to the method of Draize. Corneal effects were reversible within 14 days for unwashed eyes and within 7 days for washed eyes. Conjunctival effects cleared in unwashed eyes by the end of the 21 -day observation period and in washed eyes by day 14. The ocular effects were rated as moderate.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

In a primary dermal irritation study, albino rabbits were dermally exposed to undiluted NMP similar to OECD guideline 404. Approximately 0.5 mL NMP was applied to the backs of 6 rabbits that had been closely abraded. The undiluted NMP was applied to the intact (concurrent control) and abraded skin. When the examination was repeated 72 hours after the start of exposure, no effects were observed. The tests showed a low potential for skin irritation and resulted (for both intact and abraded skin and averaged reading from 24 and 72 hours) in a primary irritation index (PII) of 0.5 (Ansell & Fowler, 1988).

In a primary ocular irritation study equivalent to OECD guideline 405, New Zealand White rabbits received a single intraocular application of 0.1 mL neat NMP into the conjunctival sac of one eye. The other eye served as untreated control. Additional animals were dosed but their eyes were washed out 30 seconds after administration. Animals were observed for 21 days. Irritation was scored according to the method of Draize. Corneal effects were reversible within 14 days for unwashed eyes and within 7 days for washed eyes. Conjunctival effects cleared in unwashed eyes by the end of the 21 -day observation period and in washed eyes by day 14. The ocular effects were rated as moderate (Ansell & Fowler, 1988).

Besides, human data are available resulting from both, epidemiological and controlled human exposure studies. The conflicting results of these studies force regulators to set the risk assessment based on the most clear relevance for workplaces. A controlled human exposure study (van Thriel et al., 2007; Bader et al., 2007) with participating young volunteers, addressing peak exposures and physical and mental work, described no adverse sensory irritation for concentrations up to 160 mg/m3.

Driven by the harmonised classification (Annex VI of Regulation (EC) No 1272/2008 (CLP Regulation)), based mainly on human occupational observations, NMP is considered to elicit irritation to the skin and the eyes.

Justification for classification or non-classification

The available experimental test data are reliable. Based on these results and according to the harmonised classification (Annex VI of Regulation (EC) No 1272/2008 (CLP Regulation)), NMP is considered to be irritating to skin, eyes and the respiratory system as follows:

Category 2, H315, causes skin irritation

Category 2, H319, causes serious eye irritation

STOT SE 3, H335, may cause respiratory irritation.