Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

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: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no deviations from standard test guidelines and no methodological deficiences, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Description: clear colourless liquid
Storage conditions: room temperature in the dark
Purity: 99.4 %
Water content: 0.02 %

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant. After an acclimatization period of et least five dayx the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card. At the start of the study the animals were eight to twelve weeks of age. The bodyweight variation did not exceed ± 20% of the initial/mean bodyweight of any previous dosed animals.
The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately three to for hours after dosing, free access to mains drinking water and food was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.
The temperature and relative humidity were set to acheive limits of 19 to 25°C and 30 to 70 % respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchenge was at least fifteen changes per hour and the ligjting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain anay contaminant of a level that might have affected the purpose or integrity of the study.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
All animals were dosed once only by gavage using a metin cannula attached to a graduated syringe. The volume administered to each animal was calculated according to ist fasted bodyweight at the time of dosing.
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 females
Control animals:
no
Details on study design:
Clinical observations were made 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for up to fourteen days. Morbidity and mortality checks were made twice daily.
Individual bodyweights were recorder on day 0 and on days 7 and 14 or at death.
At the end of the observation period the surviving animals were killed. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Preliminary study:
Using available information on the toxicity of the test material, 2000 mg/kg was chosen as the strating dose.
In the absence of mortality at a dose level of 2000 mg/kg, an additional group of animals was treated.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One animals was killed in extremis one day after dosing
Clinical signs:
Signs of systemic toxicity noted were hunched posture, pilo-erection, ataxia, tiptoe gait, lethargy, decreased respiratory rate, laboured respiration, dehydration and hypothermia.
Surviving animals appeared normal one, two, eight or thirteen days after dosing.
Body weight:
Surviving animals showed expected gains in bodyweight during the study, except for one animal which showed bodyweight loss during the first week but expected gain in bodyweight during the second week.
Gross pathology:
Patchy pallor of the liver animal was noted at necropsy of the animal that was killed in extremis. No abnormalities were noted at necropsy of animals that were killed at the end of the test.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight.
Executive summary:

In a GLP-compliant acute toxicity study conducted in accordance with standardised guideline OECD 420, the LD50 of the test material was calculated by exposing 4 females Wistar rats to a dose of 2000 mg/kg of body weight by oral gavage. Under the conditions of the test no systemic signs of toxicity were reported over a period of 14 days and the LD50 was determined to be > 2000 mg/kg.