Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From January 03, 1996 to February 21, 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
- Product code: 06 FHFR555
- pH: Approximately 5 (10 g/L)
- Appearence: Light yellowish scales
- Melting point: 60-70⁰C
- Solubility: >10 g/L in water, ethanol, isopropanol
- Batch number: 1061969521
- Storage conditions: Darkness at room temperature in a fume cupboard
-Active ingredient 79.8%

Test animals

Species:
rat
Strain:
other: Hoe: WISKf (SPF71)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hoechst aktiengesellschaft, Kastengrund, SPF breeding colony
- Age at study initiation: Approximately 7 wk (m) and 8 wk (f)
- Weight at study initiation: Mean: 185g (m) and 171g (f)
- Fasting period before study: Yes
- Housing: In fully air-conditioned rooms in macrolon cages on soft wood granulate in group of 5 animals
- Diet: Ssniff R/M-H (V 1534), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: Atleast one day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 50 ± 20%

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Deionized
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 6.3, 8, 12.5 and 20% in deionised water
- Justification for choice of vehicle: Test substance is soluble in water

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Dose range finding study
Doses:
800 and 2,000 mg/kg bw for males and 630, 800, 1,250 and 2,000 mg/kg bw
No. of animals per sex per dose:
5 per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14d
- Frequency of observations and weighing: Symptoms and lethality were recorded twice every day, on weekends and public holiday only once. weighing was done weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
Statistics:
The LD50 and the equation of the probit line were established in female animals on the basis of the lethality rates by probit analysis.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
702.5 mg/kg bw
Based on:
test mat.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 800 - < 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD100
Effect level:
1 250 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD100
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Mortality:
Yes, although in males there was no mortality at 800 mg/kg bw, all animals died at 2,000 mg/kg bw. In females, only 2 and 3 animals survived at 630 and 800 mg/kg bw, respectively. At 1,250 and 2,000 mg/kg bw, all females died.
Clinical signs:
Decreased spontaneous activity, squatting posture, narrowed palpebrae fissures and irregular respiration. Also, stupor was observed only in the animals of the 2,000 mg/kg bw group. One female animal of the 800 mg/kg bw group showed blood encrusted lid margin on Day 6 of the study. All clinical signs were reversible at Day 8 of the study.
Body weight:
No effects
Gross pathology:
Macroscopic examination of the dead animals:
Stomach: Full of clear fluid, full of gas, detachment of the mucosa, petechial bleeding
Intestinal tract: Full of yellowish mucous, full of clear fluid, detachment of the mucosa, full of reddish mucosa

The animals killed at the end of the observation period showed macroscopically visible changes.

Applicant's summary and conclusion

Conclusions:
Under the study conditions, the LD50 for the female Wistar rats was found to be 702.5 mg test substance/kg bw (i.e., 560.5 mg a.i./kg bw). Male animals did not show a higher sensitivity to the test substance.
Executive summary:

A study was conducted to determine the oral acute toxicity of the test substance (purity 79.8%) according to OECD Guideline 401 and EU Method B.1, in compliance with GLP. The experiment was performed in Wistar rats. The test substance was administered as a single dose to 5 female rats per group at 630, 800, 1250 and 2000 mg/kg bw (equivalent to 503, 638, 998 and 1596 mg a.i./kg bw) and to 5 males rats per group at doses of 800 and 2000 mg/kg bw (equivalent to 638 and 1596 mg a.i./kg bw, after which animals were examined for 14 days. Examinations performed were mortality, body weights, clinical signs and gross necropsy for any macroscopic abnormalities. In males, there was no mortality at 800 mg/kg bw, however all animals died at 2000 mg/kg bw. In females, only 2 and 3 animals survived at 630 and 800 mg/kg bw respectively. At 1250 and 2000 mg/kg bw, all females died. Females, therefore, appeared to be more susceptible to the effects of treatment than males. Decreased spontaneous activity, squatting posture, narrowed palpebrae fissures and irregular respiration were recorded. Also, stupor was observed only in the animals of the 2000 mg/kg bw group. One female animal of the 800 mg/kg bw group showed blood encrusted lid margin on Day 6 of the study. All clinical signs were reversible at Day 8 of the study. No effects were seen on the body weight. The animals killed at the end of the observation period showed macroscopically visible changes. Under the study conditions, the LD50 for the female Wistar rats was found to be 702.5 mg test substance/kg bw (i.e. 560.5 mg a.i./kg bw) (Jensch, 1996).