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Toxicological information

Acute Toxicity: oral

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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:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River laboratories, Inc., Wilmington Massachusetts
- Age at study initiation: 6-10 weeks
- Weight at study initiation: 180-334 g
- Fasting period before study: yes
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): no data
- Acclimation period: min 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12h light, 12h dark


IN-LIFE DATES: From: july 14, 1992 To: july 17, 1992 (dose-finding study);
IN-LIFE DATES: From: sept 10, 1992 To: sept 24, 1992 (difinitive LD50 study)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
no vehicle
Doses:
dose range finding study: 500, 2500, 5000 mg/kg
definitive LD50 study: 320, 630, 1000 mg/kg
No. of animals per sex per dose:
5 rats per sex per dose
Control animals:
other: not required according to OECD guideline 401
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 1h, 4h and 24h after dosing + daily until day 14
- Necropsy of survivors performed: yes
- Other examinations performed: incidence of clinical signs, toxic signs, mortality; body weight, gross necropsy findings
Statistics:
using the method of Litchfield and Wilcoxon via the Innovative Programming Associates, LABCAT Module Version 4.24

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
377.1 mg/kg bw
95% CL:
203.3 - 699.3
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
442.7 mg/kg bw
95% CL:
322.8 - 607.1
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
410 mg/kg bw
95% CL:
288.1 - 584
Mortality:
320 mg/kg: male 1/5 dead (day6); female 2/5 dead (day1 and day3)
630 mg/kg: male 4/5 dead (2x day1, day3; day6); female 4/5 dead (2x 3h after dosing, 2x day6)
1000 mg/kg: male 5/5 dead (3x 3h after dosing, 2x on day 1); female 5/5 dead (3 x 3h, 2x day 1)
5/5 died between 6h and 24h after exposure (dosage: 2.5 ml/kg)
1/5 died between 6h and 24h after exposure (dosage: 1.25 ml/kg)
2/5 died on the 4th day after exposure (dosage: 1.25 ml/kg)
Clinical signs:
following clinical signs are observed: decreased activity, abnormal gait, abnormal stance, dyspnea, chromodacryorrhea, diarrhea, decreased
body tone, piloerection, prostration, tremors, flaccid body tone, salivation, discolored urine, body drop and poor grooming.
Body weight:
with the exception of a slight decrease in body weight of one male in the 320·mg/kg dose level, there was an apparent increase in body weight of all surviving animals.
Gross pathology:
Necropsy of the animals dying on study revealed fluid-filled, discolored and/or distended intestines, spleen, bladder and stomach. No visible lesions
were observed in any animal at terminal necropsy.

Applicant's summary and conclusion