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: Meets generally accepted scientific standards, well documented and acceptable for assessment.

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPP 81-1 (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:

- Physical state: greyish-green powder
- Analytical purity: 100%
- Lot/batch No.: 3883559 A
- 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 Inc. Wilmington, Massachusetts.
- Age at study initiation: young adults (9-12 weeks).
- Weight at study initiation: males: 256 - 339 g; females: 224 - 264 g;
- Fasting period before study: overnight (approximately 18 hours).
- Housing: individually.
- Diet: Purina Laboratory Chow , #5001, ad libitum.
- Water: tap water, ad libitum.
- Acclimation period: 10-21 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 24 °C
- Humidity (%): 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12 h/ 12 h

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 ml

Doses:
600, 1200, 2500, 3500, 5000 mg/kg bw.
Initially 5000 mg/kg bw were dosed but due to mortality seen, additional levels were added.
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: twice daily;
- Frequency of weighing: prefast, postfast (just prior to dosing), days 7 and 14;
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,
Statistics:
Lichfield and Wilcoxon method.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
911 mg/kg bw
Based on:
test mat.
95% CL:
728 - 1 140
Mortality:
600 mg/kg bw: 1 female died;
1200 mg/kg bw: 3 males and all females died;
2500, 3500 and 5000 mg/kg bw: all animals died;
Clinical signs:
Signs seen on the day of dosing in most groups included discharge, fecal staining, soft stool, and hypoactivity. On the day after dosing most animals in most groups showed urinary staining; a few animals had ataxia, hypothermia and prostration. Most surviving animals showed decreased food consumption on the day after dosing; this continued in some animals through day 3. Other signs occurred occasionally in a few animals. All surviving animals were free of significant abnormalities from day 6 through termination of the study (day 14).
Body weight:
All surviving animals gained weight.
Gross pathology:
Postmortem examinations of animals which were found dead revealed a variety of changes, primarily in the lungs and gastrointestinal tract. Some animals which were found dead exhibited changes in the stomach and intestine which were suggestive of an irritant effect (discoloration of walls), and most had apparent test material in the gastrointestinal tract. Several animals had accentuated lobular pattern of the liver. Other changes in animals found dead appeared to represent autolytic alterations or were the result of antemortem stress (testes in the body cavity). Changes in animals sacrificed after 14 days were similar to those seen in control animals.

Applicant's summary and conclusion