Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP compliant, comparable to guideline study with acceptable restrictions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material; MRD-89-374
- Description: the test material was a colourless liquid which was assumed to be sufficiently pure for purposes of dosing
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles river
- Age at study initiation: 8-11 weeks
- Weight at study initiation: 200-350 gram
- Fasting period before study: overnight prior to dosing
- Housing: 5 per cage/per sex/per dose
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature: 68-76 degrees Fahrenheit
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1989-03-28 To: 1989-04-11

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
vehicle: none
exposure: by oral intubation via syringe and a No. 13 stainless steel straight, ball-tipped feeding needle

Doses:
2000, 2500 and 3000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
The dose range was based on a range-finding study. Clinical observations were recorded at 1, 2, 4 and 6 hours after dosing and once daily for 14 days after dosing. Body weights were recorded on the day before dosing, the day of the dosing (day 0), day 7 and day 14 and at termination followed by a gross necropsy.
Statistics:
The body weights were analysed using standard deviations.
The LD50-value was calculated using the Litchfield-Wilcoxon method with equal weighing of the data points.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
2 417 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
1 602 mg/kg bw
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 152 mg/kg bw
Mortality:
Four animals died in the 2000 mg/kg bw group, seven animals in the 2500 mg/kg bw group and eight animals in the 3000 mg/kg bw group. One animal was found dead on day 0 but this was thought to have resulted from a dosing error. The animal was replaced by another.
Clinical signs:
Clinical observations showed typical signs of sedation and included, for example, ataxia, emaciation, prostration, hypothermia, hypoactivity, dyspnoea,
hypopnea, wet and dry rales, both clear and red nasal and oral discharge, staining of the fur and piloerection and unthrifty coat. These observations were most prevalent during day 0 and day 1 in all groups. None of the surviving animals showed any observable abnormalities from day 2.
Body weight:
There was an increase in body weight over the initial values at the end of the study.
Gross pathology:
The animals that died showed in gross necropsy abnormalities of the gastro-intestinal tract and the urinary bladder, discolouration of the thymus, lungs and liver and staining of the fur. There was a single incident of enlarged heart atrium and one of dilated pelvis in both kidneys. Surviving animals had no observable abnormalities apart from a single incidence of dilated kidneys and one liver abnormality in the 2500 mg/kg bw group.

Applicant's summary and conclusion