Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Remarks:
Read-across from a structural analogue
Adequacy of study:
key study
Study period:
27 September 2006 to 11 October 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
Sample ID: AD-1500
Physicalstate:white powder
-Expiration date of the lot/batch: 01 August 2008
-Stability under storage conditions: stable
- Storage condition of test material: At room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
-Source: Charles River Deutschland, Sulzfeld, Germany
-Age at study initiation: approx. 9 weeks old
-Weight at study in iation: Variation in body weight did not exceed=/- 20% of the sex mean.
- Fasting period before study: not applicable
-Housing: Individually housed in labeled Macrolon cages (Mill type, height 18 em.) containing sterilized sawdust as bedding material and
paper as cage-enrichment.
-Diet (e.g. ad lib um): Free access to standard pelleted rodent diet
-Water (e.g. ad libitum): Free access to tap water.
-Acclimation period: Acclimatization period was at least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
-Temperature ("C): 21.0 +/- 3.0
-Humidity(%): 30- 70
-Air changes (per hr): 15
-Photoperiod (hrs dark I hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
propylene glycol
Details on dermal exposure:
TEST SITE
-Area of exposure: approx. 25 cm2 for males and 18 cm2 for females (10% of total body surface)
- % coverage: all
-Type of wrap if used: The formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch, successively
covered with aluminum foil and Caban elastic bandage. A piece of Micropore tape was additionally used for fccation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
-Washing (if done): skin cleaned of residual test substance using tap water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with un ): 2000 mglkg (10 mUkg) body weight
-Constant volume or concentration used: yes

VEHICLE: Propylene glycol (specific gravity 1.036).
Rationale: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor. Preparation: The formulation (wlw) was prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle.
Duration of exposure:
24h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Details on study design:
-Duration of observation period following administration: 14 days
MortalityNiability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
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:
Necropsy: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy.
Descriptions of all internal macroscopic abnormalities were recorded.

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 mortalities
Clinical signs:
Signs of toxicity: Flat posture, ptosis and/or chromodacryorrhoea were noted among the animals on day 1
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.
Gross pathology:
Effects on organs:
No abnormalities were found at macroscopic post mortem examination of the animals
Other findings:
Signs of toxicity (local}:
Scales, scabs and/or erythema were seen in the treated skin- area of the animals during the observation period.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Dermal LD50 for the test substance for rats was established at >2000 mg/kg bw.