Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2009-03-11, 209-03-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Performed according to OECD guideline and under GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: JMAFF Guidelines (2000), including the most recent revisions
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Substance type: organic
- Physical state: solid, yellow powder
- Expiration date of the lot/batch: 2009-12-31
- Stability under test conditions: at least 6 hours at room temperature (concentration range 6 to 200 mg/mL) in vehicle
- Storage condition of test material: at room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: did not exceed +/- 20% of the sex mean
- Housing: Individually in labeled Macrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
- Diet: ad libitum, pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: ad libitum, tap water
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 – 20.7
- Humidity (%): 41 - 65
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
CMC (carboxymethyl cellulose)
Details on dermal exposure:
TEST SITE
- Area of exposure: back
- % coverage: approx. 10 %
- Type of wrap if used: the test substance formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum 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): with tap water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg (10 mL/kg) body weight
- Constant volume or concentration used: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 1 % aqueous carboxymethyl cellulose
Duration of exposure:
24 hours
Doses:
1
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: twice daily (mortality/viability); days 1 (pre-administration), 8 and 15 (body weights)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Statistics:
Observations/measurements in the study were recorded electronically using the following programme(s):
REES Centron Environmental Monitoring system version SQL 2.0 (REES scientific, Trenton, NJ, USA);
TOXDATA version 8.0 (NOTOX B.V., ‘s-Hertogenbosch, The Netherlands): Clinical signs, Body weights

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occurred
Clinical signs:
Hunched posture, piloerection, chromodacryorrhoea and/or hypothermia were noted among animals on Days 1 and/or 2.
Scales were observed in the treated skin-area of one animal during the observation period.
Yellow staining of the treated skin-area was noted for all animals during the observation period. This was considered related to the staining properties of the test substance and therefore of no toxicological relevance.
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:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 value in Wistar rats was established to exceed 2000 mg/kg body weight.