N,N-bis(2-methylpropyl)formamide

Endpoint summary

Description of key information

The test substance is not considered irritating to the skin (BASF 1988, 18H0172/882097).
The test substance is considered to cause irreversible damage to the eye (BASF 1988, 11H0172/882139).

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

Study period:

1988-04-11 to 1988-04-26

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981

Deviations:

no

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Gaukler, 6050 Offenbach/Main, Germany
- Weight at study initiation: 2.77
- Housing: Single housing in stainless steel cages with wire mesh walk floors (floor area: 40 cm x 51 cm).
- Diet: Standardized animal laboratory diet (about 130 g/animal/day Kliba 341, Firma Klingentalmuehle AG, 4303 Kaiseraugst, Switzerland)
- Water: About 250 mL tap water/animal/day
- Acclimation period: At least 15 hours before study start
- Animal identification: Ear tattoo

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 24 °C
- Humidity: 30 - 70 %
- Photoperiod: 12 hours darkness/12 12 hours light

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin of the same animal

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

8 d

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: Upper third of the back flanks (2.5 cm x 2.5 cm)
- Type of wrap if used: Test patches were secured in position with a porous dressing (four layers of absorbent gauze and porous bandage)

REMOVAL OF TEST SUBSTANCE
- Washing: At the end ot the exposure period with lutrol and lutrol/water (1:1)
- Readings: 30 - 60 min after removal of the test patches and 24, 48, 72 h and 8 d after beginning of the study

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

0

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

1.2

Max. score:

4

Reversibility:

fully reversible within: 8 d

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24, 48, 72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24, 48, 72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24, 48, 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Reading	Animal	Erythema	Edema	Symptoms
1h	1	1	0
	2	1	0
	3	1	0
24 h	1	2	0
	2	1	0
	3	2	0
48 h	1	2	0
	2	1	0
	3	1	0
72 h	1	2	0	S
	2	0	0
	3	0	0	S
8 d	1	0	0	S
	2	0	0
	3	0	0	S
Mean	1	2.0	0.0
	2	0.7	0.0
	3	1.0	0.0
Mean		1.2	0.0

S: scaling

 

Interpretation of results:

GHS criteria not met

Conclusions:

Based on this results, the test substance is not considered to be irritating to the skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988-05-16 to 1988-06-27

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Gaukler, 6050 Offenbach/Main, Germany
- Age at study initiation:
- Weight at study initiation (mean): 2.92 kg
- Housing: Singly housing in stainless steel cages with wire mesh walk floors.
- Diet: Standardized animal laboratory diet (ca. 130 g/animal/day Kliba 341, Firma Klingentalmuehle AG, 4303 Kaiseraugstr, Switzerland)
- Water: About 250 mL tap water/animal/day
- Acclimation period: At least 8 days before the beginning of the study
- Animal identification. Ear tattoo

ENVIRONMENTAL CONDITIONS
- Temperature: 20 -24 °C
- Humidity: 30 - 70 %
- Photoperiod: 12 hours dark/ 12 hours light

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of the same animal

Amount / concentration applied:

0.1 mL to the conjunctival sac of the right eye

Duration of treatment / exposure:

24 h

Observation period (in vivo):

21 d

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- The substance was not washed out

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

1

Max. score:

1

Reversibility:

not fully reversible within: 21 d

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 8 d

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

1.6

Max. score:

2

Reversibility:

fully reversible within: 21 d

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.9

Max. score:

2

Reversibility:

fully reversible within: 8 d

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24, 48, 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 21 d

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 24, 48, 72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 21 d

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: 24, 48, 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 d

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24, 48, 72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 48 h

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 24, 48, 72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible within: 8 d

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24, 48, 72 h

Score:

1.7

Max. score:

3

Reversibility:

fully reversible within: 8 d

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24, 48, 72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 21 d

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 24, 48, 72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 8 d

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24, 48, 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24, 48, 72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 8 d

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Readings	Animal	Cornea		Iris	Conjunctiva			Symptoms
		op	ar		red	sw	di
1 h	1	1	2	0	2	2	3
	2	0	0	0	2	2	2
	3	0	0	0	2	2	2
24 h	1	1	4	1	2	2	2
	2	1	4	0	2	1	1
	3	1	4	0	1	0	1
48 h	1	1	4	0	2	1	0	PC/RE/S/LC
	2	1	4	1	2	2	2
	3	1	3	0	1	0	1
72 h	1	1	4	0	1	0	0	PC/RE/S/LC
	2	1	4	1	2	2	2
	3	1	2	0	1	0	0
8 days	1	1	2	0	0	0	0	PC/RE/LC/MV
	2	1	2	0	2	0	2
	3	0	0	0	0	0	0
15 days	1	1	1	0	0	0	0	RE/LC/MV
	2	1	1	0	1	0	0
	3	0	0	0	0	0	0
21 days	1	0	0	0	0	0	0	RE/LC/MV
	2	1	1	0	0	0	0
	3	0	0	0	0	0	0
Mean	1	1.0		0.3	1.7	1.0
	2	1.0		0.7	2.0	1.7
	3	1.0		0.0	1.0	0.0
Mean		1.0		0.3	1.6	0.9

LC - Loss of corneal tissue

MV - Marginal vascularization of the cornea

PC - Pupil contracted

RE - Small retractions in the eyelids

S - Suppuration

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

Based in the effects of the test substance to the cornea, the test substance is regarded as causing irreversible damage to the eye.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

In a primary dermal irritation study (BASF 1988, 18H0172/882097) according to OECD 404, three female Vienna White rabbits were dermally exposed to 0.5 mL of the unchanged test item. The test substance was applied in a single dose to the clipped upper third of the back or flanks of an experimental animal for 4 hours (2.5 cm x 2.5 cm). At the end of the exposure period the test substance was washed off. Untreated skin areas served as the control. The degree of irritation was observed after 4 h, 24 h, 48 h, 72 h and 8 d. For the evaluation of the results, the scheme was converted to the OECD Draize scheme. The test item did not cause edema in the test animals (mean edema score (24, 48, 72 h) = 0). A mean erythema score (24, 48, 72h) of 1.2 was observed, but all effects were fully reversible within 8 days. The highest mean erythema score (24, 48, 72 h) observed in one test animal was 2 (slight redness), the other two test animals showed mean erythema scores of 0.7 and 1. Based on this results, the test substance is not considered to be irritating to the skin.

Eye irritation:

In a primary irritation study (BASF 1988, 11H0172/882139) according to OECD 405, 0.1 mL of the unchanged test item were instilled to the conjunctival sac of the right eye of three male Vienna White rabbits. The left eye served as the untreated control for each rabbit. The test substance was not washed out. The animals were then observed after 1 h, 24 h, 48 h, 72 h, 8 d, 15 d and 21 d. For the evaluation of the results, the BASF scheme was converted into the OECD Draize scheme. The highest mean (24. 48, 72 h) iris score observed in one animal was 0.7. 1/3 animals showed a mean (24, 48, 72 h) conjunctivae score of 2 and the maximum mean (24, 48, 72 h) chemosis score determined was 1.7. All these effects were fully reversible within the observation period. 3/3 animals showed a mean (24, 48, 72 h) cornea score of 1 and in one animal this effect was not reversible within 21 days. Based in the effects of the test substance to the cornea, the test substance is regarded as causing irreversible damage to the eye.

Justification for selection of skin irritation / corrosion endpoint:
Only available study for this endpoint performed according to guideline criteria.

Justification for selection of eye irritation endpoint:
Only available study for this endpoint performed according to guideline criteria.

Effects on eye irritation: corrosive

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance needs to be classified and labelled as eye irritating cat. 1, H318 "Causes serious eye damage" under Regulation (EC) No 1272/2008, as amended for the sixth time in Regulation (EC) No 605/2014.