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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:
other: GLP-compliant, according to OECD TG 401.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982

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
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): 81-218-01
- Physical state: clear liquid
- Stability under test conditions: stable

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Blue Spruce Farms, Altamont, New York
- Weight at study initiation: 180-280 gm (after fasting)
- Fasting period before study: 18 hours
- Housing: individually in stainless steel 1/2'' wire mesh cages
- Diet: Wayne Lab Blox, ad libitum
- Water: fresh tap water, fit for human consumption, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
- Rationale for the selection of the starting dose: based on the results of a dose-range finding study
Doses:
In the range-finding study: 0.5, 1.6 and 5 mL/kg bw.
In the main study: 4.0, 4.5, 5.0, 5.5 and 6.0 mL/kg bw
No. of animals per sex per dose:
In the dose-range finding study: 2/sex/dose
In the main study: 5/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days in the main study and 72 hours in the dose-range finding study.
- Frequency of observations and weighing: before the study (after fasting) and at day 14 in the main study and day 3 in the dose-range finding study
- Necropsy of survivors performed: yes (in the main study)
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
> 3 976 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Calculated based on the relative density of 0.9941 and LD50 of > 4 mL/kg bw
Sex:
male
Dose descriptor:
LD50
Effect level:
> 4 971 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Calculated based on the relative density of 0.9941 and LD50 of > 5 mL/kg bw.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 4 971 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Calculated based on the relative density of 0.9941 and LD50 > 5 mL/kg bw.
Mortality:
In the dose-range finding study, one of the rats died at 5 mL/kg bw. In the main study, 3 of 10 rats died at 4.0 (2 m, 1 f) and 4.5 mL/kg bw (3 f), 4 of 10 rats died at 5.0 (1 m, 3 f) and 5.5 mL/kg bw (1 m, 3 f), and 5 of 10 rats died at 6 mL/kg bw (2 m, 3 f).
Clinical signs:
In the dose-range finding study, signs observed included decreased activity, flaccid body tone, ptosis, abnormal stance, hunched body position, red exudate around nasal area, chromodacryorrhea, pilorection and vasodilation.
In the main study, signs observed included ptosis, prostration, decreased activity, flaccid body tone and abnormal stance.
Body weight:
All animals in the 4 mL/kg bw, 4.5 mL/kg bw and 5 mL/kg bw gained weight during the study. Two animals in 5.5 mL/kg bw and 2 animals in 6 mL/kg bw groups lost weight during the studies.
Gross pathology:
Necropsy of the animals dying on study revealed distended, fluid-filled intestines and bladder, bright red lungs and blanched adrenals. Terminal necropsy of the remaining animals revealed no visible lesions at any dose level.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In the acute oral toxicity study with rats, the LD50 was > 3976 mg/kg bw for female rats, > 4971 mg/kg bw/day for male rats and > 4971 mg/kg bw for both sexes combined.
Executive summary:

In the oral study, performed according to a protocol similar to OECD guideline 401 and without GLP, LD50 values of >3976 mg/kg bw and >4971 mg/kg bw were obtained for female and male Sprague-Dawley rats, respectively. The combined LD50 value for both sexes was >4971 mg/kg bw. The observed clinical signs included ptosis, prostration, decreased activity, flaccid body tone and abnormal stance. Necropsy of the animals dying during the study revealed distended, fluid-filled intestines and bladder, bright red lungs and blanched adrenals. Terminal necropsy of the remaining animals revealed no visible lesions at any dose level.