Amides, C8-18 (even numbered) and C18-unsatd., N-(hydroxyethyl)

Endpoint summary

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From February 16,1988 to March 02, 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Not GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

no

Species:

rabbit

Strain:

other: Small White Russian

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Biberach, Germany
- Weight at study initiation: 2.2 - 2.7 kg
- Housing: steel cages
- Diet (e.g. ad libitum): K4 diet for rabbit, Ssniff Special Diets, Soet, Germany
- Water (e.g. ad libitum): tap water

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/-1°C
- Humidity (%): 60 +/- 5%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light):12/12

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of product with 0.5 cm3 water

Duration of treatment / exposure:

4 h

Observation period:

14 d

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 6 cm2
- Type of wrap if used: exposure site covered with 2.5 x 2.5 cm patch. 6 x 6 cm Polyethylene wrapping placed on top and fixed with an elastic band.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsing with warm water directly after patch removal.
- Time after start of exposure: 4 h


SCORING SYSTEM: OECD 404 method

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 d

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

fully reversible within: 14 d

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 14 d

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 14 d

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 14 days

Table 1: Skin irritation responses in rabbit exposed to test substance

Animal N°	1 h		24 h		48 h		72 h		6 d		8 d		10 d		14 d
	R	S	R	S	R	S	R	S	R	S	R	S	R	S	R	S
1	2	1	2	1	2	1	x2	1	Sc		SciA		0	0	0	0
2	2	2	3	1	2	1	x2	1	Sc		SciA		SciA		0	0
3	2	3	3	2	3	1	x3	1	Sc		SciA		SciA		0	0

R: redness (erythema); S: swelling (oedema); x: spotty skin reaction; Sc: eschar; iA: detaching

Absolute average

4,00 4,00 3,33 3,33 => 14.66/4 = 3.67

Assessment according to Appendix VI of Directive 79/831/EC:

Redness (erythema): average = 2.44

Swelling (oedema): average = 1.11

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Under the study conditions, the test substance was considered to be moderately irritating to rabbit skin.

Executive summary:

A study was conducted to assess the skin irritation potential of the test substance, C8-18 and C18-unsatd. MEA, in rabbits according to OECD Guideline 404. The substance was applied in water to the shaved skin of three Small White Russian rabbits using an occlusive bandage. After 4 h, the exposed skin was rinsed, then observed for 14 d. Redness (erythema), swelling (oedema) and eschar formation was apparent in all animals. The effects were reversible within 14 d. The overall irritation index was 3.67 (on a total possible of 8). Under the study conditions, the test substance was considered to be moderately irritating to rabbit skin (Mürmann, 1988).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From February 16, 1988 to March 09, 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

no

Species:

rabbit

Strain:

other: Small White Russian

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Biberach, Germany
- Weight at study initiation: 2.4 - 32.5 kg
- Housing: wire mesh cages, one animal/cage
- Diet (e.g. ad libitum): K4 diet for rabbits, Ssniff Special diet GmbH, Soest, Germany
- Water (e.g. ad libitum): tap water

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1°C
- Humidity (%): 60 +/- 5%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: Right eye treated, left eye served as a control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g of ground material

Duration of treatment / exposure:

72 h after application, the treated eyes were analysed for cornea damage using a Na-fluorescein solution, then rinsed with warm physiological solution.

Observation period (in vivo):

21 d

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): after 72 h


SCORING SYSTEM: Draize (Appraisal of the safety of chemicals in foods, drugs and cosmetics, FDA, Austin 1, Texas 1959)


TOOL USED TO ASSESS SCORE: fluorescein and a slit lamp

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: up to 21 d

Score:

26.8

Max. score:

110

Reversibility:

other: Irreversible effects (cornea, iris) in 1/3 animals

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible

Remarks:

in 2/3 animals

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0.55

Max. score:

2

Reversibility:

fully reversible

Remarks:

in 2/3 animals

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 2.67

Max. score:

3

Reversibility:

fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0.89

Max. score:

4

Reversibility:

fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Table 1: Scores for corneal effects (opacity) according to Draize, 1959

Animal N°	1 h	24 h	48 h	72 h	6, 8, 10, 13, 17 and 21 d
39653	0	20	20	10	0
39657	0	30	20	10	0
39689	0	30	30	20	10
Absolute average	0	26.67	23.33	13.33	3.33

Table 2: Scores for iris effects according to Draize, 1959

Animal N°	1 h	24 h	48 h	72 h	8, 10, 13, 17 and 21 d
39653	0	5x	5*	0	0
39657	0	5x	0	0	0
39689	0	5x	5*	0	5c
Absolute average	0	5.00	3.33	0	1.67

x: clear redness of the iris; * partial redness of the iris; c: circumcorneal injection

Table 3a: Scores for conjunctival effects (redness, swelling exsudation) according to Draize, 1959

Animal N°	1 h	24 h	48 h	72 h	6 d
39653	10	12	8	4	2
39657	10	12	8	2	0
39689	10	12	10	8	8
Absolute average	10.00	12.00	8.67	4.67	3.33

Table 3b: Scores for conjunctival effects (redness, swelling, exsudation) according to Draize, 1959 (cont'd)

Animal N°	8 d	10 + 13 d	17 d	21 d
39653	0	0	0	0
39657	0	0	0	0
39689	6	2	2	0
Absolute average	2.00	0.67	0.67	0

Interpretation of results:

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

Conclusions:

Under the study conditions, the test substance was considered to be highly irritating to rabbit eyes.

Executive summary:

A study was conducted to assess the eye irritation potential of the test substance, C8-18 and C18-unsatd. MEA, in rabbits according to OECD Guideline 405. Ground neat test substance (0.1 g) was placed in the lid of the right eye of each Small White Russian rabbit. Seventy-two h after application, the treated eyes were analysed for corneal damage using a Na-fluorescein solution, then rinsed with warm physiological solution. Effects were evaluated at 1, 24, 48 and 72 h, as well as at 6, 8, 10, 13, 17 and 21 d after application, according to Draize (1959). Damage to the cornea and iris of one animal was still present after 21 d. This was considered irreversible. The mean overall score was 26.8 (maximum possible: 110). Under the study conditions, the test substance was considered to be highly irritating to rabbit eyes (Mürmann, 1988).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

A study was conducted to assess the skin irritation potential of the test substance, C8-18 and C18-unsatd. MEA, in rabbits according to OECD Guideline 404. The substance was applied in water to the shaved skin of three Small White Russian rabbits using an occlusive bandage. After 4 h, the exposed skin was rinsed, then observed for 14 d. Redness (erythema), swelling (oedema) and eschar formation was apparent in all animals. The effects were reversible within 14 d. The overall irritation index was 3.67 (on a total possible of 8). Under the study conditions, the test substance was considered to be moderately irritating to rabbit skin (Mürmann, 1988).

Eye irritation

A study was conducted to assess the eye irritation potential of the test substance, C8-18 and C18-unsatd. MEA, in rabbits according to OECD Guideline 405. Ground neat test substance (0.1 g) was placed in the lid of the right eye of each Small White Russian rabbit. Seventy-two h after application, the treated eyes were analysed for corneal damage using a Na-fluorescein solution, then rinsed with warm physiological solution. Effects were evaluated at 1, 24, 48 and 72 h, as well as at 6, 8, 10, 13, 17 and 21 d after application, according to Draize (1959). Damage to the cornea and iris of one animal was still present after 21 d. This was considered irreversible. The mean overall score was 26.8 (maximum possible: 110). Under the study conditions, the test substance was considered to be highly irritating to rabbit eyes (Mürmann, 1988).

Justification for classification or non-classification

Skin 

The key in vivo skin irritation study conducted with the test substance, C8-18 and C18-unsatd. MEA, demonstrated that a 4 h occlusive exposure was irritating to skin. On the basis of this study, the substance was classified as Skin Irrit. 2 - H315 (causes skin irritation) according to CLP (EC 1272/2008) criteria. 

Eye 

The key in vivo eye irritation study suggests that the test substance, C8-18 and C18-unsatd. MEA, is highly irritating to eyes, with irreversible eye effects in one animal. Since the effects seen in this study were severe and irreversible, the substance was classified as Eye Damage 1 - H318 (causes serious eye damage) according to CLP (EC 1272/2008) criteria.