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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1994-01-11 to 1994-03-16

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

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

Species:

rabbit

Strain:

other: White russian (Albino)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Males 11 - 17 months Females 9 - 11 months
- Weight at study initiation: Males 2.33 - 2.79 kg Females 2.75 - 3.39 kg
- Fasting period before study:
- Housing: individually, Stainless steel cages with grating floor, type ASTA, size: 48.5x40x36.5 cm (LxBxH)
- Diet (e.g. ad libitum): Approx. 120 g/day and animal Standard diet, ssniff K, Special diet for rabbits (composition of the diet see attachment 2)
supplied by ssniff Spezialdiaten GmbH, D-59494 Soest
- Water (e.g. ad libitum): Water was provided ad libitum in drinking water quality from the Stadtwerke Halle, using an automatic drinking water system with drinking nipples.
- Acclimation period: The animals were kept at least 5 days under test conditions before substance application after hair clipping. Veterinary supervision of the animals was done before start of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.0 - 20.0
- Humidity (%): 52 - 67%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: shorn skin between shoulder and sacral region
- % coverage: not reported

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period bandage and patch were removed and the skin was cleaned from the residual test substance by washing with tapwater as far as possible.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg moistened with water

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

Duration of exposure:

24 hours

Doses:

2000 mg/kg b.w.

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were continuously observed for the first 4 to 6 hours after application and then once daily. The nature of the toxicity as well as the onset, the intensity, and the duration of the signs were recorded (1, 2, 4).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, other: Mortality

Statistics:

The LD 50 values for male as well as female rabbits were above 2000 mg/kg b.w. (limit test), thus no further statistics were performed.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Not observed

Clinical signs:

other: Not observed

Gross pathology:

No effects observed

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In a study conducted according to OECD guideline 402 (1987) the LD 50 values for male as well as female rabbits were above 2000 mg/kg b.w., thus, the test item does not need to be classified according Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS) with respect to dermal acute toxicity.