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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19th July - 2nd August 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Reference substance name:
New Eporva 800
IUPAC Name:
New Eporva 800
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): New Eporva 800
- Physical state: Orange coloured liquid
- Analytical purity: 40%
- Batch No.: 504008
- Expiration date of the lot/batch: 31 October 1995
- Storage condition of test material: Room temperature in dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Olac Ltd, Bicester, Oxon, England
- Age at study initiation: approximately 4 to 7 weeks
- Weight at study initiation: 97 to 114 g
- Fasting period before study: overnight prior to and approximately 4 hours after dosing
- Housing: Housed in groups of up to 5 rats of the same sex in metal cages with win mesh floors
- Diet (e.g. ad libitum): standard laboratory rodent diet (SDS LAD 1) ad libitum
- Water (e.g. ad libitum): drinking water ad libitum
- Acclimation period: 6 days

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

IN-LIFE DATES: From: To: 19 July and 2 August 1995

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The dose level was chosen in compliance with the guideline.
Doses:
2.0 g/kg bodyweight
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- Mortality: Checked at least twice daily for any mortalities
- Clinical signs: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1 (a period of six hours). Thereafter animals were observed twice daily (with the exception of Day 15- morning only).
- Bodyweight: The bodyweight of each rat was recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.
- Necropsy of survivors performed: yes
- Other examinations performed: macroscopic examination

Results and discussion

Preliminary study:
No prelimunary study undertaken.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
Piloerection was observed in all rats within five minutes of dosing, accompanied at this time by increased salivation in two males only. In addition, hunched posture, waddling gait and pallor of the extremities were seen in all rats at later intervals on Day 1. There were no other clinical signs and recovery, as judged by external appearance and behaviour, was complete by either Day 3 (males) or by Day 4 (females).
Body weight:
All rats achieved satisfactory bodyweight gains throughout the study (see table 2 of the attached report).
Gross pathology:
Macroscopic examination on Day 15 revealed no abnormalities.

Any other information on results incl. tables

A study was performed to assess the acute oral toxicity of New Eporva 800 to the rat.

A group of ten fasted rats (five males and five females) was given a single dose by oral gavage of the test substance, as supplied, at a dose level of 2.0 g/kg bodyweight. All animals were killed and examined macroscopically on Day 15, the end of the observation period.

There were no deaths. Clinical signs of reaction to pregnant were confined to piloerection, hunched posture, waddling gait, and pallor of the extremities, seen in all rats with increased salivation seen in two males only. Recovery was complete in all instances by Day 4.

All rats achieved satisfactory bodyweight gains throughout the study.

Macroscopic examination on Day 15 revealed no abnormalities.

The acute lethal oral dose to rats of New Eporva 800 was found to be greater than 2.0 g/kg bodyweight.


According to GHS criteria, New Eporva 800 should be classified as “category 5” or “not classified” with regard to acute oral toxicity.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Conclusions:
The acute lethal oral dose to rats of New Eporva 800 was found to be greater than 2.0 g/kg bodyweight.

According to GHS criteria, New Eporva 800 should be classified as “category 5” or “not classified” with regard to acute oral toxicity.