[No public or meaningful name is available]

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Experiment start date - 19 January 2010; Experiment completion date - 09 February 2010; Study completion date - 16 March 2010.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Specific details on test material used for the study:

Identification: FAT 40851/A TE
Batch Number: TZ 5891 / BOP 02-09
Purity: 69.9 % all coloured components
Appearance: Orange powder
Expiry Date: July 31, 2014
Storage Conditions: At room temperature at about 20 °C

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS RccHan: WIST(SPF)
- Source: Harlan Laboratories B.V. Kreuzelweg 53 5961 NM Horst / The Netherlands Postbus 6174 5960 AD Horst / The Netherlands
- Age at study initiation: Males: 9 weeks, Females: 11 weeks
- Weight at study initiation: Males 233.6 - 246.6 g ; Females: 187.9 - 209.2g
- Housing: During acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding
- Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 30/09 (Provimi Kliba AG, 4303 Kaiseraugst / Switzerland) ad libitum.
- Water (e.g. ad libitum): Community tap water from Füllinsdorf ad libitum.
Acclimatization: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: Relative humidity between 30-70 % (values above 70 % during cleaning process possible)
- Air changes: Air-conditioned with 10-15 air changes per hour
- Photoperiod: Automatically controlled light cycle of 12 hours light and 12 hours dark, music during the daytime light period.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

Deionised water which was processed and treated by the PURELAB Option-R unit, which links four purification technologies: reverse osmosis, adsorption, ion-exchange and photo oxidation.

Details on dermal exposure:

TEST SITE
- Area of exposure: back of the animals
- % coverage: approx. 10 % of the body surface
- Type of wrap if used: skin with a syringe and covered with a surgical gauze pad (ca. 5 x 5 cm) held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and an elastic adhesive restrainer bandage wrapped around the abdomen.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, flushed with lukewarm water and dropped off with disposable paper towels.
- Time after start of exposure: 24h

TEST MATERIAL AND VEHICLE
- Amount(s) applied (volume or weight with unit): 6mL/kg
- Concentration (if solution): dose: 2000 mg/kg BW
- Constant volume or concentration used: yes
- Test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle was added (weight: volume).

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Viability / Mortality: Daily during the acclimatization period, within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15.

Clinical Signs: Daily during the acclimatization period, within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15.

Local Dermal Signs: Once daily during days 2 (following dressing removal) through day 15 using the numerical scoring system described in Appendix I.

Body Weights: On test days 1 (prior to administration), 8 and 15.

- Necropsy of survivors performed: yes
- Other examinations performed: macroscopic examinations were performed. An external examination and opening of the abdominal and thoracic cavities for examinations of major organs were performed. The appearance of any macroscopic abnormalities was recorded. No organs or tissues were retained.

Statistics:

No statistical analysis was used.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

No intercurrent deaths occurred during the course of the study.

Clinical signs:

other: No clinical signs were recorded throughout the complete observation period.

Gross pathology:

No macroscopic findings were recorded at necropsy.

Other findings:

Local Dermal Signs
Orange staining of the treated skin caused by the test item was observed in all animals from test day 2 up to test days 7 or 9. Otherwise, no local dermal signs were recorded in any of the animals until the end of the observation period.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose of FAT 40851/A after single dermal administration to rats of both sexes, observed over a period of 14 days, is: LD50 (rat): greater than 2000 mg/kg bw.

Executive summary:

Five male and five female RccHan:WIST (SPF) rats were treated with FAT 40851/A at 2000 mg/kg by dermal application in accordance with EU Method B.3 and under GLP conditions. The test item was formulated in purified water at a concentration of 0.33 g/mL and administered at a volume dosage of 6 mL/kg. The application period was 24 hours. The animals were examined daily during the acclimatisation period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after treatment start on test day 1 and once daily during test days 2-15. Local signs were noted once daily from test day 2 to 15. Mortality/viability was recorded within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically. No intercurrent deaths occurred during the course of the study. No clinical signs were recorded throughout the complete observation period. Orange staining of the treated skin caused by the test item was observed in all animals from test day 2 up to test days 7 or 9. Otherwise, no local dermal signs were recorded in any of the animals until the end of the observation period. The body weight of all animals was considered to be within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy. The median lethal dose of FAT 40851/A after single dermal administration to rats of both sexes, observed over a period of 14 days, is: LD50 (rat): greater than 2000 mg/kg bw. Based upon the classification criteria according to the Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008, FAT 40851/A does not have to be classified with respect to acute dermal toxicity in rats.