Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
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 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral 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:
acute toxic class 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:
female
Details on test animals and environmental conditions:
Species: Rat Wistar strain Crl:(WI)BR (outbred, SPF-Quality).
Source: Charles River Deutschland, Sulzfeld, Germany.
Age and body weight: Young adult animals (approx. 9-10 weeks old) were selected. Body weight variation did not exceed +/- 20% of the 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

Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
Vehicle: Propylene glycol (specific gravity 1.036)
Rationale: The vehicle was selected based on trial formulations performed at NOTOX.
Preparation: The formulations (w/w) were prepared within 4 hours prior to dosing. Homogenicity was accomplished to a visually acceptable level.
Adjustment was made for specific gravity of the vehicle.
Doses:
2000 mg/kg (10 ml/kg) body weight
No. of animals per sex per dose:
6 females (nulliparous and non-pregnant). Each dose group consisted of 3 animals
Control animals:
no
Details on study design:
The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 2000 mg/kg. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups.
Statistics:
No statistical analysis was performed

Results and discussion

Preliminary study:
not done
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Dose level: 2000 mg/kg Mortality 1/3, Date 07/09/04
Dose level: 2000 mg/kg Mortality 1/3, Date 14/09/04
The decendents were found within 2 hr post treatment
Clinical signs:
Lethargy, restless behaviour, hunched posture, ventro-lateral recumbency, flat gait, uncoordinated movements, laboured respiration, piloerection, salivation, ptosis, squeaking, and/or hypothermia were noted among animals between days 1 and 3.
One animal showed alopecia and scabs on the cheeks between day 7 and 15. Alopecia is commonly seen in group housed rats and therefore no toxicological significance was attached to this finding.
Body weight:
The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected of normal untreated animals of the same age or strain.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals

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 oral LD50 value of FR-513 in Wistar rats was established to exceed 2000 mg/kg body weight
According to the OECD 423 test guideline the LD50 cut-off value was considered to be 2500 mg/kg body weight.
Executive summary:

Acute oral toxicity with FR-513 in the rat was carried out using appropriate guidelines of OECD 423, OPPTS 870.1100.

FR-513 was administered by oral gavage to two subsequent groups of three female Wistar rats at 2000 mg/kg body weight.

Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15). The incidance of mortality was 1/3 based on two observations. Lethargy, restless behaviour, hunched posture, ventro-lateral recumbency, flat gait, uncoordinated movements, laboured respiration, piloerection, salivation, ptosis, squeaking, and/or hypothermia were noted among animals between days 1 and 3. The body weight was considered normal and no abnormalities were found at macroscopic post mortem examination of the animals. The oral LD50 value of FR-513 in Wistar rats was established to exceed 2000 mg/kg body weight

According to the OECD 423 test guideline the LD50 cut-off value was considered to be 2500 mg/kg body weight.

Based on the results FR-513 is considered not classified.