1,3,5-Triazine-2,4-diamine, N2-[(1R,2S)-2,3-dihydro-2,6-dimethyl-1H-inden-1-yl]-6-(1-fluoroethyl)-

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-[(1R,2S)-2,6-dimethyl-2,3-dihydro-1H-inden-1-yl]-6-[(1R)-1-fluoroethyl]-1,3,5-triazine-2,4-diamine

EC Number:

619-749-5

Cas Number:

730979-19-8

Molecular formula:

C16H20FN5

IUPAC Name:

N-[(1R,2S)-2,6-dimethyl-2,3-dihydro-1H-inden-1-yl]-6-[(1R)-1-fluoroethyl]-1,3,5-triazine-2,4-diamine

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan/Winkelmann GmbH, 33178 Borchen, Germany
- Age at study initiation: 9-13 weeks
- Weight at study initiation: males 236-247 g; females 210-229 g
- Fasting period before study: 16-24 hours before administration until 2-4 hours after administration
- Housing: individually in polycarbonate cages on low dust wood granulate bedding
- Diet (e.g. ad libitum): standard diet Provimi Kliba 3883.0.15 Maus/Ratte Haltung, Kaiseraugst Switzerland, ad libitum
- Water (e.g. ad libitum): tap water ad libitum from polycarbonate bottles
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2
- Humidity (%): 55±5
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back and flanks, shorn one day before the start of the treatment.
- % coverage: approximately 10% of the body surface area (30 cm²)
- Type of wrap if used: For each dose and animal the required amount of pure solid test substance was weighed and transferred to a wet gauze-layer (6.0 cm x 5.0 cm = 30.0 cm²) of a "Cutiplast® steril" coated with air-tight "Leukoflex®". The gauze strip was placed on the rat's back and secured in place using "Peha®-Haft" cohesive stretch tape (8 cm x 23 cm) and additionally covered with a "Lomir biomedical Inc rat jacket", which was connected with a safety pin to the stretch tape to ensure that the animals could not ingest the test substance.

REMOVAL OF TEST SUBSTANCE
- Washing: yes, with tepid water using soap, and gently patting the area dry.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw: males 16.7-17.5 mg/cm², females 14.8-16.2 mg/cm²
- Constant volume or concentration used: yes, pure solid test substance
- For solids, paste formed: no, solid test substance was applied via a wet gauze layer.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations several times on the day of administration and subsequently at least once daily, weight gain weekly until the end of the study
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (nature, duration, intensity), body weight

Statistics:

The LD50 value was calculated with the aid of a software program according to Spearman, Kaerber (D.J. Finney; Statistical method in biological assay, 2nd Edition, Griffin, London, 524-530; 1971). The algorithm was taken from L. Sachs (Angewandte Statistik, 6th Edition 1984, pp. 178 ff.).
Where calculation of the LD50 using the software program was not possible or meaningful, an assessment was made based on the applied dose and dose-response curve, respectively.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: No clinical signs were observed.

Gross pathology:

Necropsy at the end of the study revealed no particular findings.

Any other information on results incl. tables

Conclusion:

The dermal LD50 of the test material was determined to be >2000 mg/kg bw. According to the criteria of Directive 57/548/EEC and the Regulation (EC) No 1272/2008 the test material does not have to be classified for acute dermal toxicity.

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008