Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and appropriate guidelines
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
other: JMAFF Japanese test guidelines (2000)
Principles of method if other than guideline:
not relevant
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Identification: FR-513
Mol. formula: C5H9Br3O
Mol. Weight: 324.92
CAS #: 36483-57-5
Description: White flakes
Batch: 039084 (taken from label)
Composition: Tribromoneopentyl alchohol 97%, Dibromoneopentyl glycol < 0.1%
Storage: At room temperature in the dark
Stability under storage conditions: Stable

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Species: Rat, Wistar strain Crl:(WI)BR (outbred, SPF-Quality). source: Charles River Deuchland, Sulzfeld, Germany.
Numbers of animals: 5 male and 5 females (females were nulliparous and non-pregnant).
Age and body weight: Young adult animals (approx. 8 weeks old) were selected. Body weight variation did not exceed +/_ 20% of sex mean.
Identification: Earmark
Animals were housed in a controlled environment with optimal conditions with 15 air changes/hr, temp of 21 ± 3 °C (actual range: 20.0 - 22.5 °C), a relative humidity of 30-70% (actual range: 35-75%) and 12 hr artificial fluorescent light and 12 hr darkness per day.
Diet: free accsess to standard pelleted laboratory animal diet.
Water: Free access to tap water.



Administration / exposure

Type of coverage:
other: dermal application
Vehicle:
propylene glycol
Details on dermal exposure:
Clipping: One day before exposure (day-1) an area of approx. 5X7 cm on the back of the animal was clipped.
Application: The formulation was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm2 for males and 18 cm2 for females.
The formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminium foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.
Frequency: Single dosage, on day 1
Application period: 24 hr, after which dressings were removed and the skin cleaned of residual test substance using water.

Duration of exposure:
FR-513 was administered for 24 hr.
Doses:
2000 mg/kg (10 ml/kg) body weight
No. of animals per sex per dose:
5 male and 5 females
Control animals:
no
Details on study design:
Mortality/viability: twice daily
Body weights: Days 1 (pre-administration), 8 and 15
Clinical signs: At periodic intervals on 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:
Maximum grade 4: grading slight (1) to vey severe (4)
Maximum grade 3: grade slight (1) to severe (3)
Maximum grade 1: presence is scored (1)
Necroscopy: At the end of the observation period, all animals were sacrificed by asphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
not done

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
no
Clinical signs:
Lethargy, flat posture, hunched posture, piloerection, ptosis, red urine, chromodacryorrhoea and/or shallow respiration were noted among the animals. The animals had recovered from the symptoms by day 5.
In animal 6 chromodacryorrhoea was noted in the eye before and during the study period. This finding is occasionally noted among rats and was considered not indicative of toxicity, based on the absence of any corroborative findings in the animal.
General or maculate erythema, necrosis, scales, scars and/or scabs were seen in the treated skin-area of the animals during observation period.
Body weight:
The changes noted in body weight gain in females and males were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
Macroscopic post mortem did not reveal any abnormalities that were not commonly noted among rats of this age and strain
Watery-clear cyst(s) found in ovaries in one female, is related to a stage in the oesterous cycle and is a normal finding.

Any other information on results incl. tables

see attached document on tables

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 FR-513 in Wistar rats was established to exceed 2000 mg/kg body weight
Executive summary:

Acute dermal toxicity was conducted with FR-513 in the rat according to various OECD guidelines such as OECD 402 and OPPTS 870.1200. FR-513 was administered to five Wistar rats of each sex by dermal application at 2000 mg/kg body weight for 24 hr. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15). No mortality occured. Lethargy, flat posture, hunched posture, piloerection, ptosis, red urine, chromodacryorrhoea and/or shallow respiration were noted among the animals. The animals had recovered from the symptoms by day 5.

General or maculate erythema, necrosis, scales, scars and/or scabs were seen in the treated skin-area of the animals during the observation period.

The mean body weight gain during the observation period was within the range expected for rats used in this type of study.

Macroscopic post mortem did not reveal any abnormalities that were not commonly noted among rats of this age and strain.

The dermal LD50 value FR-513 in Wistar rats was established to exceed 2000 mg/kg body weight, hence considered non classified in the EU.