Leucophor 1111X

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

From July 27th to August 18th, 2005

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted according to internationally accepted testing guidelines and performed in compliance with Good Laboratory Practice. Justification for read across approach is given in the endpoint summary and in the read across justification report attached to the Section 13 of this dossier.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted February 24, 1987

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

July 31, 1992

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Test material

Test material information

Constituent 1

Test animals

Species:

rat

Strain:

other: HanRcc:WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services CH-4414 Fiillinsdorfl Switzerland.
- Age at study initiation: males 7- 8 weeks; females 12-13 weeks.
- Weight at study initiation: males 219.7 - 233.0 g; females 189.4 - 217.5 g.
- Housing: during acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makroloh type-3 cages with standard softwood bedding ("LighoceI“, Schill AG, CH-4132 l\/Iuttenz) during treatment and observation.
- Diet: pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 25/05 (Provimi Kliba AG, CH-4303 Kaiseraugst/ Switzerland), ad Iibitum.
- Water: community tap water from Fullinsdorf, ad libitum.
- Acclimation period: under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

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

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

deionised

Details on dermal exposure:

DOSE FORMULATION
The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight:voIume). The formulation was prepared shortly before the application using a magnetic stirrer, a spatula and an Ultra-Turrax (Janke & Kunkel, D-79219 Staufen) as homogenizers.
Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

TEST SITE
- Area of exposure: one day before treatment, the backs of the animals were clipped with an electric clipper. Only those animals without injury or irritation on the skin were used in the test.
- % coverage: exposing an area of approximately 10 % of the total body surface.
- Type of wrap if used: covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: the skin was flushed with lukewarm tap water and dried with disposable paper towels.
- Time after start of exposure: twenty-four hours after the application.

TEST MATERIAL
- Amount applied: on test day 1, the test item was applied at a dose of 2000 mg/kg body weight evenly on the intact skin with a syringe (application volume/kg body weight: 4 ml).

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Details on study design:

- Duration of observation period following administration: 14 days
- Mortality / Viability: daily during the acclimatization period, during 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.
- Frequency of observations and weighing: on test days 1 (prior to administration), 8 and 15.
- Necropsy of survivors performed: yes. All animals were killed at the end of the observation period by an intraperitoneal injection of Vetanarcol at a dose of at least 2.0 ml/kg body weight (equivalent to at least 324 mg sodium pentobarbitone/kg body weight) and discarded after macroscopic examinations were performed. No organs or tissues were retained.
- Other examinations performed: clinical signs were recorded daily during the acclimatization period, during 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 signs Once daily during days 2-15.

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.

Mortality:

No deaths occurred during the study.

Clinical signs:

No systemic or local signs of toxicity were observed during the study period.

Body weight:

The body weight ofthe animals was within the range commonly recorded for this strain and age.

Gross pathology:

No macroscopic findings were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information according to the CLP Regulation (EC 1272/2008) Criteria used for interpretation of results: EU

Conclusions:

LD50 (rat) greater than 2000 mglkg body weight

Executive summary:

Five male and five female HanRcc:WIST (SPF) rats were treated with the test item at 2000 mg/kg by dermal application. The test item was diluted in vehicle (purified water) at a concentration of 0.5 g/ml and administered at a volume dosage of 4 ml/kg. The application

period was 24 hours.

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximately 30 minutes, 1, 2, 3 and 5 hours after treatment on 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 at approximately 30 minutes, 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 day1 (prior to administration) and on days8 and 15. All animals were necropsied and examined macroscopically.

No deaths occurred during the study.

No clinical signs were observed during the course of the study.

The body weight of the animals was within the range commonly recorded for this strain and age.

No macroscopic findings were observed at necropsy.

Conclusion

The median lethal dose of the test item after single dermal administration to rats of both sexes, observed over a period of 14 days is:

LD50 (rat): greater than 2000 mglkg body weight