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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From the 22nd of November to the 1st of December, 2002
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Justification for Read Across is detailed in the section summary and it is further detailed in the report attached to the IUCLID section 13.
Cross-reference
Reason / purpose:
read-across source

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Principles of method if other than guideline:
Article 14-functionary and the Ethical Committee of NOTOX (DEC NOTOX 97-03-13) as required by the Dutch Act on Animal Experimentation (February 1997).
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
Description Brown powder
Test substance storage At room temperature in the dark
Stability under storage conditions Not indicated
Expiry date 29 August 2002 (allocated by NOTOX, 1 year after)

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
ANIMALS
Species: Rat, Wistar strain Crl:(WI) BR (outbred, SPF-QuaIity).
Source: Charles River Deutschland, Sulzfeld, Germany.
Number of animals: 5 males and 5 females (females were nulliparous and non- pregnant).
Age and body weight: Young adult animals (approx. 11 weeks old) were selected. Body weight variation did not exceed +/- 20% of the sex mean.
Identification: Earmark
ANIMAL HUSBANDRY
Conditions: a controlled environment was maintained in the room with optimal conditions considered as being approximately 15 air changes per hour, a temperature of 21 ± 3°C, a relative humidity of 30-70% and 12 hours artificial fluorescent light and 12 hours dark per day.
Deviations from the maximum level for relative humidity (with a maximum of 20%) occurred which might have been caused by cleaning procedures in the room.
Based on laboratory
historical data these deviations were considered not to have affected the study integrity.

ACCOMODATION
Individually housed in labelled polycarbonate cages (type Ill, height 15 cm.) containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany). Certificates of analysis were examined and then retained in the NOTOX archives.
Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet: Free access to standard pelleted laboratory animal diet (from Altromin (code VRF 1), Lage, Germany). Certificates of analysis were examined and then retained in the NOTOX archives.
Water: Free access to tap—water, Certificates of quarterly analysis were examined and then retained in the NOTOX archives.
Analysis of bedding, diet and water did not reveal any findings that were considered to have affected study integrity.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
Vehicle: Based on trail formulations performed at NOTOX, propylene glycol was selected. inadvertently, polyethylene glycol 400 (specific
gravity 1.127) was used as the vehicle. As this vehicle also formed a visually homogenous suspension, the study integrity was considered not to have been adversely affected. Since the density of propylene glycol (1.036) was used, the animals received approximately 2176 mg/kg instead of 2000 mg/kg. This slightly higher dose was considered not to have been of significant influence on the study outcome.
Preparation: The formulation (w/w) was prepared within 4 hours prior to dosing.
Homogeneity: was accomplished to a visually acceptable level.
Adjustment was made for specific gravity of vehicle.


Duration of exposure:
Application period 24 hours, after which dressings were removed and the skin cleaned of residual test substance using water.

Doses:
Dose level (volume) 2000 mg/kg (10 ml/kg) body weight (actual dose 2176 mg/kg body weight).
No. of animals per sex per dose:
5 males and 5 females (females were nulliparous and non- pregnant)
Control animals:
no
Details on study design:
TREATMENT
A health inspection was performed prior to commencement 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.
Method Dermal application.
Clipping One day before exposure (day -1) an area of approximately 5x7 cm on the back of the animal was clipped.
Application The formulation was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm2 for males and 18 cm' for females.
The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D) , successively covered with aluminium foil and Coban flexible bandage . A piece of Micropore tape was additionally used for fixation of the bandages in females only.

Statistics:
No statistical analysis was performed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
not specified
Mortality:
No mortality occurred.




Clinical signs:
Brown staining of various body parts (considered to be related to staining properties of the test substance) and/or chromodacryorrhoea was noted among all animals between days 1 and 8.
Body weight:
No variations from the normal bodyweight increase have been observed
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
other:
Remarks:
Not classified according to the CLP Regulation
Conclusions:
LD50 > 2000 mg/kg bw
Executive summary:

Method

The study was carried out based on the guidelines described int EC Commission Directive 92/69/EEC, Part B.3, "Acute Toxicity Dermal" and OECD No.402, "Acute Dermal Toxicity". The substance was administered to five Wistar rats of each sex by dermal application at 2000 mg/kg

body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15).

Observations

No mortality occurred. Brown staining of various body parts (considered to be related to staining properties of the test

substance) and/or chromodacryorrhoea was noted among all animals between days 1 and 8. The body weight gain during the observation period was within the range expected for rats used in this type of study.

No abnormalities were found at macroscopic post mortem examination of the animals.

Result

The dermal LD50 value in Wistar rats was established to exceed 2000 mg/kg body weight (actual dose 2176 mg/kg body weight).