Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: study performed under GLP and in accordance with the corresponding OECD-/EU-testing guidelines
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): P5175
- Appearance and physical state: dark brown liquid
- Stability under test conditions: stable
- Storage condition of test material: at room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd., Manston Road, Margate, Kent
- Age at study initiation: between 6 and 10 weeks
- Weight at study initiation: males 129 to 151 g, females 125 to 148 g
- Housing: gang-housing in groups of 5 by sex
- Diet (e.g. ad libitum): SQC Rat and Mouse Maintenance Diet No.1, Expanded, Special Diets Services Ltd., Stepfield, Witham, Essex
- Water (e.g. ad libitum): Tap water, free of contaminants
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21°C, single air-conditioned room
- Humidity (%): 52-70%
- Photoperiod: Fluorescent lighting, automatically controlled to give a cycle of 12 hours light (06.00 to 18.00 hr) and 12 hours darkness

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
see table under subsection "any other information on materials and methods incl. tables"
Doses:
1770, 2500, 3530 and 5000 mg/kg
No. of animals per sex per dose:
5 males and 5 females
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: at 15 minutes, 1, 2 and 4 hours after treatment and subsequently once daily for 14 days
- Frequency of weighing: on the day before treatment (day -1), on the day of treatment, 7 and 14 days after treatment and at death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: yes
Statistics:
The acute oral median lethal dose (LDso) for combined male and female groups were calculated using a probit analysis (Finney, D.J. (1964), Statistical Method for Biological Assay, 2nd Edition, London, Charles Griffin). Separate LDso values were calculated for male and female animals. The mortalities did not allow the calculation of 95% fiducial limits for male animals.

Results and discussion

Preliminary study:
Four groups, each of 2 fasted rats (1 male, 1 female), were treated with dose levels of 50, 250, 1250 and 5000 mg/kg.
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 077 mg/kg bw
Based on:
test mat.
95% CL:
3 331 - 6 052
Sex:
male
Dose descriptor:
LD50
Effect level:
5 107 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no CL determined
Sex:
female
Dose descriptor:
LD50
Effect level:
3 710 mg/kg bw
Based on:
test mat.
95% CL:
2 816 - 5 272
Mortality:
A total of 12 (5 male, 7 female) of the 40 animals died during the study period. All deaths were noted 24 or 48 hours after treatment.
Clinical signs:
1770 mg/kg:
All animals treated with 1770 mg/kg appeared normal 2 hours after dosing. The antmals appeared prostrate and/or lethargic 4 hours after dosing but recovered and all animals appeared normal on day one and throughout the study period.

2500 mg/kg:
The major sign of toxicity noted 2 to 4 hours in animals treated with 2500 mg/kg after dosing were prostration and/or lethargy. One animal also showed tremors 4 hours after treatment. Surviving animals appeared normal 2 days after treatment.

3530 mg/kg:
Major signs of toxicity noted during the day of dosing in animals treated with 3530 mg/kg were prostration and/or lethargy. Occasional signs of ataxia and tremors were also noted. All surviving animals appeared normal on day 1 and throughout the study period.

5000 mg/kg:
Animals treated with 5000 mg/kg also showed prostration and/or lethargy during the day of dosing and in surviving animals the day after dosing. Occasional signs of ataxia, tremors and piloerection were noted during the day of dosing. All surviving animals appeared normal 2 days after treatment.
Body weight:
All surviving animals showed body weight gains at the end of the study period.
Gross pathology:
Major pathological findings in animals dying during the study were associated with the stomach and gastrointestinal tract. These organs appeared distended or filled with gas.The lungs occasionally showed red patches on all lobes.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral toxicity LD50 on Wistar rats was determined to be 4077 mg/kg combined for both sexes, 5107 mg/kg for male and 3710 mg/kg for female rats.
Executive summary:

The study was performed 1983, in accordance with OECD 401 and under GLP. Following a screening study, 4 groups, each of 10 fasted rats (5 male, 5 female) were treated with a single oral dose of P5175 at dose levels of 1770, 2500, 3530 and 5000 mg/kg. The vehicle used was corn oil.

1. Clinical observations:

Clinical signs were observed throughout all dose groups and included prostration, lethargy, tremor, ataxia and piloerection. Surviving animals appeared normal within 1-2 days after treatment.

2. Mortality:

5 males and 7 females died during the study period. All deaths occured 24 or 48 hours after treatment.

Based on the test results, the test item has no classification/labelling requirements.