Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012
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:
2012
Report Date:
2012

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Principles of method if other than guideline:
Commission Regulation (EC) No 440/2008, B3: "Acute Toxicity (Dermal)"
EPA, OPPTS 870.1200 (1998), "Acute Dermal Toxicity"
JMAFF Guidelines (2000), including the most recent revisions
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: waxy solid
Details on test material:
- Name of test material (as cited in study report: MTDID 7831
- Substance type: Off-white to white waxy solid
- Physical state:Solid
- Analytical purity: 93.96 w%
- Purity test date:11-10-2011
- Lot/batch no.: Batch 40177
- Expiration date of the lot/batch: 31 October 2016
- Stability under test 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 and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Approx. 11 weeks old
- Weight at study initiation: Males 282-317 g, Females 199-218 g
- Fasting period before study: No data
- Housing: Individually housed in labeled Makrolon cages (MIII type, height 18 cm) with sterilized sawdust as bedding and paper as cage-enrichment
- Diet (e.g. ad libitum): Pelleted rodent diet (SM R/M-Z from SSNIFF Sezialdaten GmbH, Soest, Germany) ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: At least 5 days before start of treatment
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 +/- 3.0 degrees Celsius
- Humidity (%): 40-70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 light/12 dark
IN-LIFE DATES: From:09 February 2012 To:23 February 2012

Administration / exposure

Type of coverage:
occlusive
Vehicle:
polyethylene glycol
Remarks:
Polyethylene glycol 400 (Merck, Darmstadt, Germany)(specific gravity 1.125)
Details on dermal exposure:
TEST SITE
- Area of exposure: 5x7 cm clipped area on the back of the animal
- % coverage:10% of total body surface
- Type of wrap if used: Surgical gauze patch (Surgy 1D), covered with aluminum foil and Coban elastic bandage.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Washed with tap water
- Time after start of exposure: 24 hours after exposure
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): "Homogeneity was accomplished to a visually acceptable level"
- Constant volume or concentration used: no data
- For solids, paste formed: No data
VEHICLE
- Amount(s) applied (volume or weight with unit): No data
- Concentration (if solution): "Homogeneity was accomplished to a visually acceptable level"
- Lot/batch no. (if required):
- Purity:
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
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: Mortality/Viability: Twice daily; Body weights: Day 1, 8, 15; Clinical signs: Periodic intervals on day of dosing and once daily thereafter until day 15.
- Necropsy of survivors performed: yes
- Other examinations performed:

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: Only one dose level used (2000 mg/kg bw).
Mortality:
No mortality occured
Clinical signs:
Hunched posture, chromodarcryorrhoea and/or piloerection were noted among the animals on day 1 only.
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 the macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 value of the test article was established to exceed 2000 mg/kg body weight.
Executive summary:

The acute dermal toxicity of MTDID 7831 (off-white to white waxy solid, composition 93.96 w%, Batch 40177) was evaluated in Wistar rats. The study was performed in compliance with OECD GLP (1997). The study design was based on OECD No 402 (1987), EC 440/2008 B3 L142 (2008), EPA OPPTS 870.1200 (1998), and JMAFF No. 8147 (2011). The test article was prepared in polyethylene glycol (w/w) and dermally applied to a 5 x 7 cm area of clipped fur on male and female rats (5/sex) for a single application at a 2000 mg/kg body weight (10 mL/kg) dose. The application represented 10% total body surface of the rats and was applied with a gauze patch backing and covered in aluminum foil, an elastic bandage, and tape (females only). After 24 hours, the dressing was removed and the skin cleaned of any residual test substance with tap water. Observations were made for mortality (twice daily), body weights (Day 1, 8, and 15), and clinical signs of toxicity (Days 1-15). All animals were euthanized at the end of Day 15 and a necropsy was performed. All animals survived for the length of the study and no abnormalities were found at time of necropsy. Hunched posture (1 male), chromodarcryorrhoea (2 males and 3 females), and pilioerection (1 female) were noted only on Day 1. Body weights were within a historical expected range for the duration of the study. Based on the results of the study, the dermal LD50 of the test article is greater than 2000 mg/kg body weight.