Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline study in accordance with GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: Powder (grey)
- Storage condition of test material: Room temperature and humidity

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Boyertown, PA, USA.
- Age at study initiation: Not specified.
- Weight at study initiation: Males, 301 - 307 g; females, 193 - 248 g.
- Fasting period before study: 16 - 20 hours.
- Housing: 3/sex/cage.
- Diet (e.g. ad libitum): PMI Rat Chow, ad libitum.
- Water (e.g. ad libitum): Ad libitum.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not specified.
- Humidity (%): Not specified.
- Air changes (per hr): Not specified.
- Photoperiod (hrs dark / hrs light): 12-hours light/dark.

IN-LIFE DATES: From: March 25, 2009 To: April 21, 2009

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Doses:
2000 mg/kg bw (20% dilution in vehicle)
300 mg/kg bw (20% dilution in vehicle)
No. of animals per sex per dose:
2000 mg/kg bw: 3 females
300 mg/kg bw: 3 males/3 females
Control animals:
no
Details on study design:
Three female Wistar rats were dosed orally with the test item at 2000 mg/kg bw. As all animals died at this dose, a further three male and three female Wistar rats were dosed orally with the test item at 300 mg/kg bw.
The animals were observed for 0.5, 1, 2, 3 and 4 hours post-dose and then once daily for 14 days for mortality, toxicity and pharmacological effects. Body weights were recorded at intervals to termination. All animals were examined for gross pathology on termination.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 300 - <= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All three females given 2000 mg/kg bw died within 2 hours of dosing.
There were no mortalities at 300 mg/kg bw.
Clinical signs:
At 2000 mg/kg bw, ante-mortem clinical signs included convulsions, negative righting reflex, brown staining of the mouth/nose area and rigid muscle tone.
At 300 mg/kg bw, the only clinical signs were brown staining of the nose/mouth area in one animal.
Body weight:
Body weight during the 14 day observation period was essentially unaffected at 300 mg/kg bw..
Gross pathology:
Necropsy results at 2000 mg/kg bw, included brown staining of the nose and wetness of the mouth area.

All necropsy results were normal at 300 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 was greater than 300 mg/kg bw, but less than 2000 mg/kg bw in rats. Accordingly, the test item was considered to be in Acute Toxic
Category 4.
Executive summary:

Three female Wistar rats were dosed orally with the test item at 2000 mg/kg bw. As all animals died at this dose, a further three male and three female Wistar rats were dosed orally with the test item at 300 mg/kg bw.

The animals were observed for 0.5, 1, 2, 3 and 4 hours post-dose and then once daily for 14 days for mortality, toxicity and pharmacological effects. Body weights were recorded at intervals to termination. All animals were examined for gross pathology on termination.

The LD50was greater than 300 mg/kg bw, but less than 2000 mg/kg bw in rats. Accordingly, the test item was considered to be in Acute Toxic Category 4.