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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
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
Report Date:
1989

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EPA OPP 81-2 (Acute Dermal 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-siobutylphosphate
- Physical state: clear liquid
- Analytical purity: 99.7%
- Lot/batch No.: NBP 3983659
- Storage condition of test material: room temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Animals, Inc. Denver, Pennsylvania
- Age at study initiation: at least 8 weeks old
- Weight at study initiation: Males: 2.4 - 2.9 kg. Females: 2.6 - 3.0 kg
- Fasting period before study: not specified
- Housing: individually housed. Suspended, stainless steel
- Diet (ad libitum): Lab Rabbit Chow HF (Purina #5326), (125 g/day while on test) .
- Water (ad libitum): Automatic watering system, Municipal water supply (Elizabethtown Water Co.).
- Acclimation period: 57 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15.6- 21.1°C
- Humidity (%):30-70%
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

IN-LIFE DATES:
Not specified

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: the dorsal area of the trunk
- % coverage: not specified
- Type of wrap if used: impervious plastic sleeve. The sleeve was secured with tape.

REMOVAL OF TEST SUBSTANCE
- Washing: with gauze and water
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount(s) applied: 5.2 mL/kg

VEHICLE
Not applicable
Duration of exposure:
24 hours
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 Dail y
Observations of Phamacologic and Toxicologic Signs: Approximately 1, 2 and 4 hours after dosing and daily thereafter for fourteen days.
Body Weights: Pre-test (at the time of clipping). Pre-dose (weights used for calculation of doses). Day 7 and 14
- Necropsy of survivors performed: yes (day 14)
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
Statistics:
No data

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality occurred
Mortality:
All animals survived throughout the study.
Clinical signs:
Most animals exhibited severe dermal effects (necrosis, followed by eschar formation, and exfoliation of the eschar tissue) at a small portion or
less than half the dose site which persisted throughout the study. Single occurrences of nasal discharge, and evidence of urinary and fecal staining were also seen. All animals were free of signs of abnormalities from Day 8 through termination of the study (Day 14).
Body weight:
Most animals exhibited slight body weight losses at Day 7, but gained weight between Days 7 and 14.
Gross pathology:
Except for one animal which exhibited clear fluid in the abdominal cavity, other gross postmortem observations were similar to those seen in control animals in this laboratory or were considered to represent normal physiological variation.
Other findings:
Most animals had decreased food consumption on Days 2 and 3; this continued in a few animals through Day 7 .

Applicant's summary and conclusion