N-(N6-trifluoroacetyl-L-lysyl)-L-proline

Endpoint summary

Description of key information

The test item was tested for skin irritation in a study conducted according to OECD TG 404. Erythema occurred in two rabbits 24 hours after removal of the patch. The treated skin area showed a very slight erythema (grade 1). The finding had completely disappeared at day 3 of observation. Systemic-toxic effects did not occur after dermal application of the test substance. The general condition of the test animals was not affected.

In an eye irritatio/corrosion study conducted according to OECD TG 405 ε-trifluoroacetyl-L-lysyl-L-proline was applied into the conjunctival sac of three rabbits eyes. The animals were examined after 1, 24, 48 and 72 h, and only a slight hyperemia was detected in two animals which was fully reversible within 72 h.

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:

1989-11-14 to 1990-02-15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

1984

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: White russian (Albino)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Males 9 months
- Weight at study initiation: Males 2.42 - 2.83 kg
- Housing: individually, Stainless steel cages with grating floor, type ASTA, size: 48.5x40x36.5 cm (LxBxH), supplied by ASTA Pharma AG, D-4800 Bielefeld 14
- Diet (e.g. ad libitum): Approx. 120 gram/day x animal Standard diet ssniff K, "Special diet for rabbits", supplied by ssniff Spezialfutter GmbH, D-4770 Soest
- Water (e.g. ad libitum): Water was provided ad libitum in drinking water quality from the Stadtwerke Bielefeld (Municipal Works). An automatic watering system with drinking nipples was used.
- Acclimation period: The animals were kept one day under test conditions before application of the product. Veterinary supervision of the animals was done before start of study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.5 - 22.5
- Humidity (%): 40-55
- Photoperiod (hrs dark / hrs light):12/12

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

other: moistened with demineralized water

Controls:

other: contralateral non-treated site at the same animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g moistened with 0.35 mL demineralized water

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.35 mL demineralized water

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72 hours

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: the shorn dorsal skin area between shoulder and sacrum.
- % coverage: (approx. 6.25 cm²)
- Type of wrap if used: (Acrylastic, No. 2408, width 8 cm; supplied by P. Beiersdorf and Co. AG, Hamburg

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the end of the exposition time remaining test material was gently washed off as far as possible.
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
1, 24, 48 and 72 hours after removal of the patches for 3 days p. appl.

SCORING SYSTEM: The evaluation of the cutaneous irritation effect at observation times 1, 24, 48 and 72 hours p. appl. was expressed by an irritation index
- Method of calculation: The arithmetical mean values of the individual grades obtained from the skin areas at observation times 1, 24, 48 and
72 hours were calculated - separately for erythema- /eschar and edema formation. The irritation index is represented by the sum of these two mean values.
A corresponding gradation was allocated to this index by the following scheme in a modified method according to Gilman et al..
Index Ranges Gradation
0.0-0.5 non-irritant
0.6-3.0 slightly irritant
3.1-5.0 moderately irritant
5.1-8.0 severely irritant

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

animal: 1-3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The single application of 0.5 gram ε-trifluoroacetyl-L-lysyl-L-proline to the intact skins of three rabbits caused only very slight changes. Erythema occurred in two animals 24 hours after removal of the patch. The treated skin area showed a very slight erythema (grade 1). The finding had completely disappeared at day 3 of observation.The irritation index is 0.3. ε-trifluoroacetyl-L-lysyl-L-proline therefore is classified as non-irritant in this test system.

Other effects:

None

Reaction of the exposed skin	hours after exposure	DRAIZE grade
		Animal number
Erythema and Eschar formation:
	1	0	0	0
	24	0	1	1
	48	0	1	1
	72	0	0	0
Edema
	1	0	0	0
	24	0	0	0
	48	0	0	0
	72	0	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

The test item was tested for skin irritation in a study conducted according to OECD guideline 404 (1981). Erythema occurred in two animals 24 hours after removal of the patch. The treated skin area showed a very slight erythema (grade 1). The finding had completely disappeared at day 3 of observation. Systemic-toxic effects did not occur after dermal application of the test substance. The general condition of the test animals was not affected. Therefore, ε-trifluoroacetyl-L-lysyl-L-proline is classified as non-irritant in this test system according to Regulation (EC) No1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).

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:

1989-11-16 to 1990-03-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

1984

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: White russian (Albino)

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: Males 7 - 8 months, female 7 months
- Weight at study initiation: Males 2.36; 2.54 kg, female 2.89 kg
- Housing: individually in Stainless steel cages with grating floor, type ASTA, size: 48.5x40x36.5 cm (LxBxH), supplied by ASTA Pharma AG, D-4800 Bielefeld 14
- Diet (e.g. ad libitum): Approx. 120 gram/day x animal Standard Diet ssniff K, "Special diet for rabbits", supplied by ssniff Spezialfutter GmbH, D-4770 Soest
- Water (e.g. ad libitum): Water was provided ad libitum in drinking water quality from the Stadtwerke Bielefeld (Municipal Works), using an automatic drinking water system with drinking nipples.
- Acclimation period: The animals were kept one day under test conditions before application of the product. Veterinary supervision of the animals was done before start of study.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.5 - 23.0
- Humidity (%): 40 - 55
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of the same animal served as control

Amount / concentration applied:

- Amount(s) applied (volume or weight with unit):0.07 or 0.055 g

Duration of treatment / exposure:

single exposure

Observation period (in vivo):

1, 24, 48, 72 hours and 4 days

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eye was not rinsed

SCORING SYSTEM: Signs of irritation on the cornea, iris, and conjunctiva were assessed quantitatively and qualitatively using the DRAIZE scale (1, 2, 4 - 6). In addition, attention was paid to the occurrence of further reactions on the eye (e.g. corrosive effect) and to clinical symptoms (systemic toxic effects).

TOOL USED TO ASSESS SCORE: The treated eye was examined using a Cliptrix pencil light (supplied by Varta, Hannover, No. 645).

Irritation parameter:

cornea opacity score

Basis:

animal: 1-3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal: 1-3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 4 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal: 1-3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The conjunctiva of two animals reacted with hyperemia (grade 1) from day 1 to day 2 or 3 of observation. Immediately after application slight discharge or discharge with moistening of lids and hair just adjacent to lids (grade 1 or 2) were observed and had completely disappeared after 24 or 72 hours. In the cornea and in the iris no alterations were detected. There were no systemic toxic effects after conjunctival application of the test substance.

Interpretation of results:

GHS criteria not met

Conclusions:

In a study conducted according to OECD guideline 405 (1987) ε-trifluoroacetyl-L-lysyl-L-proline was applied into the conjunctival sac of three rabbits eyes. The animals were examined after 1, 24, 48 and 72 h, and only a slight hyperemia was detected in two animals which was fully reversible within 72 h.
ε-trifluoroacetyl-L-lysyl-L-proline therefore is classified as non-irritant in this test system according to Regulation (EC) No1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The test item was tested for skin irritation in a study conducted according to OECD TG 404. Erythema occurred in two animals 24 hours after removal of the patch. The treated skin area showed a very slight erythema (grade 1). The finding had completely disappeared at day 3 of observation. Systemic-toxic effects did not occur after dermal application of the test substance. The general condition of the test animals was not affected. Therefore, ε-trifluoroacetyl-L-lysyl-L-proline is classified as non-irritant in this test system according to Regulation (EC) No1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).

In a study conducted according to OECD TG 405 ε-trifluoroacetyl-L-lysyl-L-proline was applied into the conjunctival sac of three rabbits eyes. The animals were examined after 1, 24, 48 and 72 h, and only a slight hyperemia was detected in two animals which was fully reversible within 72 h. Therefore, ε-trifluoroacetyl-L-lysyl-L-proline is classified as non-irritant in this test system according to Regulation (EC) No1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).