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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
Study period:
1995-05-10 until 1995-06-26
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Scientifically valid study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
Version / remarks:
November 1984
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Olac Ltd, Bicester, Oxon, England
- Age at study initiation: 7 - 10 weeks
- Weight at study initiation: 192 - 260 g
- Housing: metal cages with wire mesh floors
- Diet: a standard laboratory rodent diet (SDS LAD 1), ad libitum
- Water: ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3°C
- Humidity: 30 - 70 %
- Air changes: 10 - 15 air changes per hour
- Photoperiod: 12 hours of artificial light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 1 % w/v aqueous methylcellulose
Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/ kg

Doses:
5000, 3200, 1600 mg/kg bw
No. of animals per sex per dose:
10 rats per dose: 5 males, 5 females
Control animals:
other: not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily - clinical signs - daily and weighing 3 times during the observation period (once a week)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights
Statistics:
The acute median lethal oral dose (LD50) to male and female rats was calculated using the method of Finney [FINNEY, D.J. (1971) Probit Analysis, 3rd Cambridge University Press, Cambridge].

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 000 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD50
Effect level:
4 800 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
3 300 mg/kg bw
Based on:
test mat.
Mortality:
Two females at 3200 mg/kg bw and 3 males and all females at 5000 mg/kg died during the study. Deaths occurred between 24 to 48 hours of dosing.
Clinical signs:
Clinical signs of reaction to treatment included piloerection and soft to liquid faeces, seen among rats at all three dosages. In addition, abnormal body carriage, abnormal gait, lethargy, decreased respiratory rate, partially closed eyelids, pallor of the extremities, increased urine production, increased salivation, gasping, walking on toes, unsteadiness, increased lacrimation, bluish colour to skin/extremities, cold body surfaces, prostration, brown staining around nose and mouth and red stained urine were seen among rats at one or more dose levels. Recovery of surviving rats was complete in all instances by day 7.
Body weight:
Slight bodyweight losses were recorded for all decedents. A slightly low bodyweight gain was recorded on day 8 for one male at 5000 mg/kg and two females at both 1600 and 3200 mg/kg. A similar trend was noted on day 15 for two males and one female at 1600 m g/kg, with one further female at 1600 mg/kg showing a slight bodyweight loss at this time. All other surviving animals achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
Macroscopic examination revealed changes to all major organs and tissues of animals who died during the observation period. No abnormalities were recorded at the macroscopic examination on day 15.

Applicant's summary and conclusion