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

Eye irritation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1984

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

402-920-1

EC Name:

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

Cas Number:

103300-89-6

Molecular formula:

C13H20F3N3O4

IUPAC Name:

(2S)-1-[(2R)-2-amino-6-(2,2,2-trifluoroacetamido)hexanoyl]pyrrolidine-2-carboxylic acid

Test material form:

solid: particulate/powder

Test animals / tissue source

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

Test system

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).

Results and discussion

In vivo

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

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

Results 5

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

Results 6

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.

Applicant's summary and conclusion

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).