P-1401

Acute Toxicity: dermal

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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:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

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

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

solid

Details on test material:

- Physical state: Yellow solid
- Analytical purity: 96%
- Lot/batch No.: PQR0501558 (dried)
- Storage condition of test material: At room temperature (range of 20 ± 5 ºC), light protected.

Test animals

Species:

rat

Strain:

other: Rat, 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 Füllinsdorf / Switzerland
- Age at study initiation: Males: 8 weeks; Females: 11 weeks
- 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 ("Lignocel", Schill AG, CH-4132 Muttenz) during treatment and observation.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse mainte-nance diet, batch no. 67/06 (Provimi Kliba AG, CH-4303 Kaiseraugst/ Switzerland) ad libitum.
- Water (e.g. ad libitum): Community tap water from Füllinsdorf 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 (°C): 22 ± 3 ºC
- Humidity (%): 30-70 %
- Air changes (per hr): Air-conditioned with 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): automatically controlled light cycle of 12 hours light and 12 hours dark

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: One day before treatment, the backs of the animals were clipped with an electric clipper.
- % coverage: 10 % of the total body surface.
- Type of wrap if used: The test item was applied with a syringe and 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 (if done): the dressing was removed and the skin was flushed with lukewarm tap water and dried with disposable paper towels.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 mL
- Preparation: The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight:volume). The formulation was prepared shortly before the application using a magnetic stirrer, a spatula and an Ultra-Turrax.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
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.
Body weights: On test days 1 (prior to administration), 8 and 15.
Clinical signs: 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. All abnormalities were recorded.
Local signs: Once daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: All animals were killed at the end of the observation period by Carbon dioxide asphyxiation and discarded after macroscopic examinations were performed. No organs or tissues were retained.

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:

No deaths occurred during the study.

Clinical signs:

No clinical signs of toxicity were noted during the course of the study.

Body weight:

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

Gross pathology:

At the scheduled necropsy one male was observed with enlarged kidneys. Otherwise, there were no macroscopic findings in the animals.

Other findings:

Local effects: At removal of the application patch, two animals expressed a slight erythema which was present at that obsevation, only.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

CLP Implementation.

Conclusions:

The dermal LD50 of the test substance in rats was determined to be greater than 2000 mg/kg bw.

Executive summary:

An acute dermal toxicity test was performed with the test substance P0310 according to OECD guideline 402 and EU Method B.3, and following GLP. 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 day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically. No deaths occurred during the study. No clinical signs of toxicity were noted during the course of the study. At removal of the application patch, two animals expressed a slight erythema which was present at that observation, only. The body weight of the animals was within the range commonly recorded for this strain and age. At the scheduled necropsy one male was observed with enlarged kidneys. Otherwise, there were no macroscopic findings in the animals. Based on these results, the dermal LD50 for the test substance in rats was determined to be greater than 2000 mg/kg bw.