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Toxicological information

Acute Toxicity: other routes

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Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
other information
Study period:
24. - 31. March 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Principles of method if other than guideline:
An acute intraperitoneal toxicity study in rats with the test substance was conducted. The purpose of the study was to evaluate the acute toxicity of the test material when administered by intraperitoneal injection to rats, to detemine the intraperitoneal LD50 of the material, and to determine whether neurologic effects could be produced with acute administration.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
- Physical state: liquid
- Analytical purity: no data on purity
- Density: 1.03 g/ml

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories Inc., Wilmington, MA, USA
- Age at study initiation: young adults
- Weight at study initiation: males: 209-242 g, females: 193-238 g
- Fasting period before study: no data
- Housing: six/cage in suspended, stainless steel cages with wire mesh bottoms
- Diet: ad libitum, Purina Laboratory Chow
- Water: ad libitum, Municipal water
- Acclimation period: 7 or 15 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C (68-76 °F)
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
corn oil
Details on exposure:
single intraperitoneal injection of the test substance in corn oil
Doses:
0, 275, 325, 375 and 450 mg/kg bw
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: viability checks twice daily, observations for pharmacological and toxicological signs 1, 2 and 4 hours after dosing and daily thereafter for 14 days. weights were examined on the day of dosing and on day 7 and 14 or upon time of death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, neurologic examinations, gross pathology
Statistics:
Estimation of the LD50 and its errors by means of logarithmic-proibt graph paper

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
370 mg/kg bw
95% CL:
> 351 - < 389
Mortality:
No animals died at 275 and 325 mg/kg bw, 4/5 male and 3/5 female animals died at 375 mg/kg bw (days 2-8), 3/5 male and 5/5 female animals died at
450 mg/kg bw (23 hr to day 2)
Clinical signs:
Fetal staining and soft stool were exhibited by single animals in the control group. Most animals treated with the test substance exhibited decreased
activity and respiration rates, nasal discharge, and apparent abdominal discomfort (writhing) on the day of dosing. Unusual signs seen during the
post-dose period included urinary and/or fecal staining, soft stool, and an unthrifty coat. Animals at the 375 mg/kg group also exhibited
piloerection, hynothermia, and decreased food consumption.
Body weight:
Animals which died generally exhibited antemortem weight losses or failure to gain weight. Weight gains in animals which survived were comparable
to those in controls.
Gross pathology:
Animals which died and those which were killed after 14 days exhibited a large number of postmortem abnormalities, most notably in the abdominal
viscera. Most of these appeared to represent irritation and/or infectious sequlae resulting from intraperitoneal injection of the vehicle and/or test
material.
Other findings:
- Other observations: Neurologic signs: Flaccid limb and/or body tone, ataxia and impaired righting responses were seen in some animals in the 275, 325, and 375 mg/kg groups. Although these frequently appeared as antemortem signs in animals which died before 24 hours, these observations were also seen in some animals which subsequently survived. Signs noted only as antemortem findings included tremors, pelvic elevation, and an abnormal startle reflex.

Applicant's summary and conclusion

Conclusions:
Under the conditions of this study the median lethal dose of the test item after oral administration was found to be 370 mg/kg body weight in rats after intraperitoneal injection.
Executive summary:

An acute reliable intraperitoneal toxicity study (Klimisch 2) in rats with the test substance was conducted. The purpose of the study was to evaluate the acute toxicity of the test material when administered by intraperitoneal injection to rats, to detemine the intraperitoneal LD50 of the material, and to determine whether neurologic effects could be produced with acute administration. Experiments were performed with five Sprague-Dawley rats of each sex which were treated with 275, 325, 375 and 450 mg/kg bw of the test item. Appropriate amounts of the test substance were weighed and placed in corn oil to achieve the total desired weighed. The dose selction was based on the observed mortality in a preliminary testing for 7 days with one male and female rat and with doses up to 500 mg/kg bw. This screen revealed no mortality for doses up to 300 mg/kg bw, but 50% or 100% mortality for doses of 400 and 500 mg/kg bw, respectively.

In the LD50-determination study no animals died at 275 and 325 mg/kg bw, 4/5 male and 3/5 female animals died at 375 mg/kg bw (days 2-8), 3/5 male and 5/5 female animals died at

450 mg/kg bw (23 hr to day 2). Fetal staining and soft stool were exhibited by single animals in the control group. Most animals treated with the test substance exhibited decreased activity and respiration rates, nasal discharge, and apparent abdominal discomfort (writhing) on the day of dosing. Unusual signs seen during the post-dose period included urinary and/or fecal staining, soft stool, and an unthrifty coat. Animals at the 375 mg/kg group also exhibited piloerection, hynothermia, and decreased food consumption. Animals which died generally exhibited antemortem weight losses or failure to gain weight. Weight gains in animals which survived were comparable to those in controls. Moreover, a large number of postmortem abnormalities, most notably in the abdominal viscera were observed in animals which died and in those which were killed after 14 days. Most of these appeared to represent irritation and/or infectious sequlae resulting from intraperitoneal injection of the vehicle and/or test material. According to neurological signs a flaccid limb and/or body tone, ataxia and impaired righting responses were seen in some animals in the 275, 325, and 375 mg/kg exposure groups. Although these frequently appeared as antemortem signs in animals which died before 24 hours, these observations were also seen in some animals which subsequently survived. Signs noted only as antemortem findings included tremors, pelvic elevation, and an abnormal startle reflex.

Based on the mortality of this study the median lethal dose of the test item after oral administration was found to be 370 mg/kg body weight in rats after intraperitoneal injection.