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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:
15 August and 5 September 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was conducted according to OECD and in accordance with GLP. The study material is well characterize

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
Intended use: Pharmaceutical intermediate
Expiry date: No data available
Purity: 99.6% excluding organic solvents
Appearance: White to off-white crystalline solid
Storage conditions: Room temperature
Date received: 19 May 1995

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: 4-7 weeks
- Weight at study initiation: 112 to 146 g
- Fasting period before study: Were fasted but no data on durations
- Housing: housed in groups of up to five rats of the same sex in metal cages with wire mesh floors in Building Rl4 Room 6
- Diet (e.g. ad libitum): A standard laboratory rodent diet (SOS LAD 1) and drinking water were provided ad libitum. Access to food only was prevented overnight prior to and approximately 4 hours after dosing.
- Acclimation period: 12 days before

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): not controlled but was anticipated to be in the range 30 - 70 %
- Air changes (per hr): maintained at 10 to 15 air changes per hour
- Photoperiod (hrs dark / hrs light):time switch to provide 12 hours of artificial light (0700 - 1900 hours) in each 24-hour period.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
Single dose by oral gavage
Doses:
A preliminary study was carried out by dosing one female rat at 500 or 2000 mg/kg bodyweight.
Rats were given a single dose by oral gavage of the test substance, formulated in distilled water, at a dose level of 2000 mg/kg bodyweight in main test
No. of animals per sex per dose:
10 males/females
Control animals:
no
Details on study design:
Preliminary study

A preliminary study was carried out by dosing one female rat at 500 or 2000 mg/kg bodyweight. Main study
A group of ten rats (five males and five females) was treated at 2000 mg/kg bodyweight. The dose level was selected on the basis of the preliminary study.

Control animals

No control animals were included in this study.




ADMINISTRATION OF TEST SUBSTANCE

The appropriate dose volume of the test substance was administered to each rat by oral gavage using a syringe and plastic catheter (8 choke).

The day of dosing was designated Day 1.

Results and discussion

Preliminary study:
The results of the preliminary study indicated that the acute lethal oral dose to female rats of UK- 143, I 08 was greater than 2000 mg/kg bodyweight
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
discriminating dose
Effect level:
ca. 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No Deaths
Sex:
female
Dose descriptor:
discriminating dose
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No Deaths
Mortality:
The results of the preliminary study indicated that the acute lethal oral dose to female rats of UK- 143, I 08 was greater than 2000 mg/kg bodyweight.

Clinical signs:
Piloerection was observed in all rats within five minutes of dosing and was accompanied at this time in one male and one female rat only by increased salivation. There were no other clinical signs and recovery, as judged by external appearance and behaviour, was complete in all instances by Day
Body weight:
A slightly low bodyweight gain was recorded for one male on Day 15. All other rats achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
Macroscopic examination of animals killed on Day 15 revealed no abnormalities

Applicant's summary and conclusion

Interpretation of results:
other: discriminating oral dose 2000 mg/kg bodyweight
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The discriminating oral dose to rats of UK-143, 108 was established to be 2000 mg/kg bodyweight