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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:
other company data
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
other: TSCA
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
- Name of test material: Tri-isobutylphosphate
- Physical state: clear liquid
- Analytical purity: 99.7%
- Lot/batch No.: NBP 3983659
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
other: CD (Sprague-Dawley derived)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc. Wilmington, Massachusetts, 01887
- Age at study initiation: 9-12 weeeks
- Weight at study initiation: males: 274-339 grams. Females: 224-242 grams
- Fasting period before study: approximately 18 hours
- Housing: Group-housed (six/cage) during equilibration. Individually housed during study. Cages: Suspended, stainless steel with wire mesh bottoms.
- Diet (ad libitum): Purina Laboratory Chow, #5001
- Water (ad libitum): Automatic watering system. Municipal water supply (Elizabethtown Water Co.)
- Acclimation period: 22 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.4-24.4°C
- Humidity (%): 30-70%
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12 hrs light, 12 hrs dark

IN-LIFE DATES: not specified

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
Not applicable

MAXIMUM DOSE VOLUME APPLIED:
5.2 mL/kg

DOSAGE PREPARATION:
No preparation was necessary

CLASS METHOD
not applicable
Doses:
5000 mg/kg
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Viability check: twice daily
Observations of Pharmacologic and Toxicologic Signs: App. 1, 2, and 4 hours after dosing and daily thereafter for 14 days.
Body weights: Pre-fast, Post-fast (just prior to dosing; weights used for calcuulation of doses). Day 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
Statistics:
Not specified

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
One female was found dead on day 1; all five males and four of the five females survived throughout the study.
Clinical signs:
Signs seen on the day of dosing in several animals included oral discharge, wet rales, urinary staining, fecal staining, unthrifty coat, abdominal griping and hypoactivity. Signs seen on the day after dosing included dry rales, hypoactivity and evidence of red nasal discharge. All surving animals had decreased food consumption on the day after dosing; this continued in some animals through Day 3. All surviving animals were free of significant abnormalities from Day 4 through termination of the study (Day 14).
Body weight:
The majority of surviving animals gained weight both 7 and 14 days after dosing. One of the five males exhibited a slight weight loss (4 grams) at Day 7 but gained weight between Days 7 and 14.
Gross pathology:
Examinations of the animal which was found dead revealed a variety of changes, primarily in the lungs and gastrointestinal tract. Changes seen in the intestine were suggestive of an irritant effect (the presence of red fluid), and apparent test material was found in the stomach. Except for two animals which exhibited dilated renal pelves and/or a renal pelvis containing white fluid, changes in animals killed after 14 days were similar to those seen in control animals in the laboratory killed by carbon dioxide inhalation.

Applicant's summary and conclusion