Registration Dossier

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: Guideline study (OECD 402)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report date:
2005

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
- Temporary deviations from the minimum level of relative humidity occurred. However, laboratory historical data do not indicate an effect of the deviations
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Details on test material:

- Physical apprearance: Light yellow viscous liquid
- Batch: 99/484
- Storage: RT in the dark
- Specific gravity: 1.23
- Purity: 99% (HPLC)
- Stability under storage conditions: not indicated
- Expiry date: 10 june 2005 (allocated by NOTOX, 1 year after receipt of the test substance)

Test animals

Species:
rat
Strain:
other: Wistar strain, Crl:WI (outbred, SPF-quality)
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: Charles River Deutschland, Germany
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: Body weight variation did not exceed +/- 20% of the sex mean
- Housing: no data
- Diet: ad libitum; standard pelleted laboratory animal diet (from Altromin (code VRF 1), Lage, Germany
- Water: ad libitum; tap water
- Acclimation period: 5 days, A health inspection was performed prior to cornmencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from any abnormality.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.3-21.3
- Humidity (%): 25-68
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: undiluted
Details on dermal exposure:
TEST SITE
- Clipping: One day before exposure (day -1) an area of approximately 5x7 cm on the back of the animal
- Area of exposure: 10% of total body surface; approx 25 cm2 in males and 18 cm2 in females
- % coverage: no data
- Type of wrap if used: The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze (Surgy 1 D); successively covered with aluminium foil and Coban elastic bandage. A piece of Micropore tape' was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.63 ml/kg bw
- Concentration (if solution): undiluted
- Constant volume or concentration used: yes

Duration of exposure:
24 h
Doses:
2000 mg/kg (1.63 ml/kg)
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Frequency of application: single dosage, on day 1
- Duration of observation period following administration: 14 days
- Mortality: Checked twice daily.
- Frequency of observations: clinical signs; at periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The time of onset, degree and duration were recorded and the symptoms graded according to fixed scales: Maximum grade 4: grading slight (I) to very severe (4) Maximum grade 3: grading slight (I) to severe (3) Maximum grade 1: presence is scored (1).
- Frequency of weighing: Days 1 (pre-administration), 8 and 15 days
- Necropsy of survivors performed: at the end of the observation period, all animals were sacrificed by asphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: No mortality occured
Mortality:
No mortality occured
Clinical signs:
Flat and/or hunched posture, chromodacryorrhoea, lethargy and/or ptosis were shown by most animals on days 1 and/or 2. Scales were seen in the treated skin-area of one male and two females between days 3 and 9.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.

Mean weights: Male ( Day 1 352 +/- 19g: Day 8 368 +/- 22g and Day 15 403 +/- 25g), Females (day 1 227 +/- 9g, Days 8 240 +/- 15g and 255 +/- 26 g)
Gross pathology:
No test substance related abnormalities were found at macroscopic post mortem examination of the animals. A reduced size of the testes and epididymis was noted in one animal, which is occasionally noted among rats of this age and strain and was therefore considered not toxicologically significant.

Applicant's summary and conclusion