Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 March 2007 to 28 March 2007 (in-life phase)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted under GLP conditions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report date:
2007

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:
other: EC, Council Directive 67/548/EEC, Annex V, B.3 (1992) "Acute Toxicity (Dermal)"
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: EPA, OPPTS 870. 1200 (1998), "Acute Dermal Toxicity"
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF Guidelines (2000), including the most recent revisions.
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): MTDID 6675
- Substance type: Clear colourless liquid
- Physical state: liquid
- Analytical purity: Formulation tested is 30 % active ingredient in water
- Purity test date: 12/20/2005
- Lot/batch no.: 140499-19/10
- Expiration date of the lot/batch: 01 December 2008
- Storage condition of test material: At room temperature in the dark

Test animals

Species:
rat
Strain:
other: Wistar Crl:WI (outbred, SPF-Quality)
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: Approximately 8 weeks old.
- Weight at study initiation: Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: No data
- Housing: Individually housed 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.
- Diet (e.g. ad libitum): Pelleted rodent diet (SM R/M-Z from SSNIFF Spezialdiaten GmbH, Soest, Germany ad libitum.
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: At least 5 days before treatement. During acclimation period animals were group housed in Macrolon cages (MIV type).
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.3-23.6 degrees Celsius
- Humidity (%): 41-55%
- Air changes (per hr): 15 per hour.
- Photoperiod (12 hrs dark / 12 hrs light):
IN-LIFE DATES: From: 14 March 2007To: 28 March 2007

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Shaved area on the back of the animal approximately 25 square cm for males and 18 square cm for females
- % coverage: 10% of the total body surface
- Type of wrap if used: Test substance was held in contact with the skin with a dresssing, consisting of a surgical gauze patch (Surgy 1D), sucessively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was used for fixation of the bandages in females only
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test substance was removed using tap water after 24 hours
- Time after start of exposure: 24 hours
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 6689 mg/kg (5.766 mL/kg) body weight (2000 mg/kg of the active ingredient)
- Concentration (if solution): Formulation tested is 30% of the active ingredient in water
Duration of exposure:
24 hours
Doses:
One dose: 6689 mg/kg (5.766 mL/kg) body weight (2000 mg/kg of the active ingredient)
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: At hours 0, 2, and 4 after treatment, and daily thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occured during the study.
Clinical signs:
Hunched posture and chromodacryorrhoea were noted among the animals. Piloerection was noted in one female. The animals had recovered from the symptoms between days 2 and 5. General erythema and/or scales were seen in the treated skin-area of the animals during the observation period.
Body weight:
The changes noted in body weight gains 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:
Category 5 based on GHS criteria
Remarks:
Migrated information
Conclusions:
Under the conditions of the study, the acute dermal LD50 of the test article in rats was greater than 2000 mg/kg as the active ingredient.
Executive summary:

The objective of this study was to evaluate the acute dermal toxicity of the test article in rats according to current OECD, EC, EPA and JMAFF guidelines. The test article was administered to Wistar rats by single dermal application (10% of total body surface, covered with an occlusive dressing) at a dose of 2000 mg/kg as the active ingredient for 24 hours. Clinical observations were performed daily and body weights recorded weekly. Necropsies were performed after terminal sacrifice on Day 15. No deaths occurred. Clinical signs included hunched posture, chromodacryorrhoea, piloerection and erythema and scales at the test site. Body weight gains were normal. No macroscopic abnormalities were observed at necropsy. Under the conditions of the study, the acute dermal LD50 of the test article in rats was greater than 2000 mg/kg as the active ingredient.