Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2006-10-23 to 2007-04-10
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study performed according to OECD Guideline 402 (Acute Dermal Toxicity) and EU Method B.3 (Acute Toxicity (Dermal)) without deviations.

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:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Remarks:
The testing facility indicated that the protocol was followed without deviation.
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Remarks:
The testing facility indicated that the protocol was followed without deviation.
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
Department of Health of the Government of the United Kingdom
Test type:
other: Acute Dermal Toxicity
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): VRT-126016
- Molecular formula (if other than submission substance): Not applicable
- Molecular weight (if other than submission substance): Not applicable
- Smiles notation (if other than submission substance): Not applicable
- InChl (if other than submission substance): Not applicable
- Structural formula attached as image file (if other than submission substance): Not applicable
- Substance type: No data
- Physical state: White powder
- Analytical purity: 99.8%
- Impurities (identity and concentrations): No data
- Composition of test material, percentage of components: No data
- Isomers composition: No data
- Purity test date: 2006-02-02
- Lot/batch No.: Lot I-4107-6-02-02/ Batch No. 25719
- Expiration date of the lot/batch: 2008-02-01
- Other: Store at room temperature.

Test animals

Species:
rat
Strain:
other: CD (Crl:CD BR)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, England
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 215 to 315 g
- Fasting period before study: No data
- Housing: The animals were housed individually from Day 1 until Day 7 when they were returned to group housing (in groups of five rats of the same sex).
- Diet (e.g. ad libitum): Standard rodent diet (Rat and Mouse No. 1 Maintenance Diet), ad libitum
- Water (e.g. ad libitum): Potable water taken from the public supply, ad libitum
- Acclimation period: 7 days before treatment

ENVIRONMENTAL CONDITIONS
- Temperature (deg C): 19 to 23 deg C
- Humidity (%): 40 to 70%
- Air changes (per hr): No data
- Photoperiod: 12 hours continuous light and 12 hours continuous dark per 24 hours

IN-LIFE DATES
- From: 2006-11-02 to 2006-11-16

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: 1% aqueous methylcellulose
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorso-lumbar region of each rat
- % coverage: Approximately 10% of the total body surface area
- Type of wrap if used: The treatment area (approximately 50 mm x 50 mm) was covered with porous gauze held in place with a nonirritating dressing, and further covered by a waterproof dressing encircled firmly around the trunk of the animal.

REMOVAL OF TEST SUBSTANCE
- Washing: The treated area of skin was washed with warm water (30 - 40 deg C), to remove any residual test substance. The treated area was blotted dry with absorbent paper.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 3.50 mL/kg bodyweight
- Concentration (if solution): 571 mg/mL
- Constant volume or concentration used: Yes, the amount of test substance necessary to prepare the formulations and the amount actually used were determined on each occasion. The difference between these amounts was checked before the formulations were dispensed.
- For solids, paste formed: Yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 3.50 mL/kg bodyweight
- Concentration (if solution): 1%
- Lot/batch no. (if required): No data
- Purity: No data
Duration of exposure:
24 hours
Doses:
2000 mg/kg bodyweight (single concentration)
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 – morning only). The nature and severity, where appropriate, of the clinical signs and the time were recorded at each observation. The weight of each rat was recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.
- Necropsy of survivors performed: Yes
- Other examinations performed: Cages of rats were checked at least twice daily for any mortalities. Local dermal irritation at the treatment site was assessed daily. All animals were subject to a macroscopic examination which consisted of opening the cranial, thoracic and abdominal cavities. The macroscopic appearance of all examined organs was recorded.
Statistics:
No data

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no deaths during the treatment period.
Clinical signs:
There were no systemic responses to treatment in any animal.
Body weight:
On Day 8, a low bodyweight gain was recorded for two females (An. Nos. K8 and K9) and a bodyweight loss was recorded for one other female (An. No. K7). All other animals were considered to have achieved satisfactory bodyweight gains throughout the study. The low bodyweight gains and loss in some individuals are considered to be within the normal variability limits for female rats and as all animals had good weight gains on Day 15 this was not considered to be of toxicological importance.
Gross pathology:
No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.
Other findings:
- Dermal reactions: Very slight irritation (Grade 1 erythema) was observed in two males following the removal of the dressings on Day 2. These reactions had resolved by Day 6.
- Organ weights: No data
- Histopathology: No data
- Potential target organs: No data
- Other observations: No data

Any other information on results incl. tables

Not applicable

Applicant's summary and conclusion

Conclusions:
The acute median lethal dermal dose (LD50) to rats of the test substance was demonstrated to be greater than 2000 mg/kg bodyweight.
The test substance is in Category 3 according to the EPA Health Effects Test Guidelines OPPTS 870.1000 Acute Toxicity testing EPA 712-C-98-189 August 1998.
Executive summary:

Not applicable