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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:
April 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Name as cited in the report: AMIDET A-111
- Lot number: 2020430
- Date received: 22 January 1996
- Description: cream coloured flakes
- Storage conditions: room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Male and female Sprague-Dawley CD strain rats supplied by Charles River (UK) were used. At the start of the main study the males weighed 152 to 182g, and the females 140 to 156g, and were five to eight weeks of age. After an acclimatisation period of at least five days 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.
The animals were housed in groups of up to live by sex in solid-floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately two hours after dosing, free access to mains drinking water and lood (Rat and Mouse Expanded Diet No. 1, Special Diets Services Limited, Witham, Essex, UK) was allowed throughout the study.
The animal room was maintained at a temperature of 19 to 21°C and relative humidity of 44 to 65%. The rate of air exchange was approximately fifteen changes per hour and the Iighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
For the purpose of the study the test material was freshly prepared, as required, as a solution at the appropriate concentration in arachis oil BP. The test
material formulation was warmed in a warming bath to aid preparation and allowed to cool before dosing.
All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
- Range Finding Study: 1
- Main Study: 5
Control animals:
no
Details on study design:
Range-finding Study
A range-finding study was performed to establish a dosing regime starting with a dose level of 2000 mg/kg bw. The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for five days.
Individual bodyweights were recorded on the day of dosing to allow calculation of individual treatment volumes. No necropsies were performed.

Main Study
Based on the results of the range-finding study a further group of animals was treated with a dose level of 2000 mg/kg bw. The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. Individual bodyweights were recorded prior to dosing on Day 0 and on Days 7 and 14.
At the end of the study the animals were killed by cervical dislocation and subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Data evaluations Included the relationship, if any, between the animals' exposure to the test material and the incidence and severity of all abnormalities
including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.
Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made.

Results and discussion

Preliminary study:
There were no deaths or clinical signs of toxicity.
Based on this information, a dose level of 2000 mg/kg bodyweight was selected for the main study.
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:
No signs of systemic toxicity were noted during the study.
Body weight:
All animals showed an expected gain in bodyweight during the study except for one female which showed reduced bodyweight gain during the second week.
Gross pathology:
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater Ihan 2000 mg/kg bodyweight.
Executive summary:

A study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley CD strain rat. The method followed that in the OECD Guidelines for Testing of Chemicals No. 401 "Acute Oral Toxicity" (adopted 24 February 1987) and Method B1 of Commission Directive 92169/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

The results may be used as a basis for classification and labelling under Annex VI of Council Directive 671548JEEC (as adapted to technical progress by Commission Directive 93/21/EEC) relating to the classification, packaging and labelling of dangerous substances.

Following a range-finding study, a group of ten fasted animals (five males and five females) was given a single oral dose of test material as a solution in arachis oll SP at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after lhe day of dosing and were then killed and subjected to gross pathological examination.

There were no deaths. No signs of systemic toxicity were noted during the study.

All anlmals showed an expected gain in bodyweight during the study except for one female which showed reduced bodyweight gain during the second week.

No abnormalities were noted at necropsy.

The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater Ihan 2000 mg/kg bodyweight. No symbol and rlsk phrase are required according to EU labelling regulations.