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

Endpoint summary

Description of key information

In an acute oral toxicity study conducted according to OECD TG 401 the LD50 values were above a dose of 5110 mg/kg in male and female rats.

In an acute dermal toxicity study conducted according to OECD TG 402 the LD50 values for male as well as female rabbits were above 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990-01-31 to 1990-04-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

1984

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: Bor: WISW (SPFCpb)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Males 8 weeks Females 8 weeks
- Weight at study initiation: Males 154 - 212 g Females 127 - 131 g
- Fasting period before study: 16 h before treatment
- Housing: individually, Macrolon cages, type II, Bedding: Animal bedding chips, supplied by Jelu-Werk, J. Ehrler, Industriemehle, D-7092 Rosenberg/Württ.
- Diet (e.g. ad libitum): Standard diet ad libitum ssniff R, "Special diet for rats", 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 at least 5 days under test conditions before administration of the test substance. Veterinary supervision of the animals was done before start of study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 -22.5
- Humidity (%): 40 - 65 (for a short period 25 - 30)
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 237 mg/mL
- Amount of vehicle (if gavage): 21.5 mL/kg

MAXIMUM DOSE VOLUME APPLIED: 21.5 mL/kg

Doses:

5110 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 body weights were recorded at the beginning and also 7 and 14 days after administration. The animals were continuously observed for the first 4 to 6 hours after administration and then once daily. The nature of the toxicity as well as the onset, the intensity, and the duration of the signs were recorded. Mortality was checked twice daily (a.m. and p.m.), on Saturdays, Sundays, and on national holidays only once.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, other: Mortality

Statistics:

The LD 50 values were above a dose of 5110 mg/kg in male and female rats, thus no further statistics were performed.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 110 mg/kg bw

Based on:

test mat.

Mortality:

No Mortality occurred

Clinical signs:

other: Signs of toxicity were not observed

Gross pathology:

At necropsy of the animals no abnormalities were detected.

Other findings:

None

Interpretation of results:

GHS criteria not met

Conclusions:

In a study conducted according to OECD guideline 401 (1987) the LD 50 values were above a dose of 5110 mg/kg in male and female rats. 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 acute oral toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 110 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

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

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

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.

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Justification for classification or non-classification

In a study conducted according to OECD TG 401 the LD50 values were above a dose of 5110 mg/kg bw in male and female rats. 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 acute oral toxicity.

In a study conducted according to OECD TG 402 the LD50 values for male as well as female rabbits were above 2000 mg/kg bw. 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.