Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 9 May 1995 and 1 June 1995.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted 24 February 1987
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
of Commission Directive 92169/EEC (which constitutes Annex V of Council Directive 67/548/EEC)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
Clear colourless liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 99/26.12.94

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature under nitrogen

FORM AS APPLIED IN THE TEST (if different from that of starting material): clear colourless liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate, Kent, UK.
- Age at study initiation: At the start of the main study the males and the females were five to eight weeks of age.
- Weight at study initiation: At the start of the main study the males weighed 150 to 170g, and the females 145 to 155g.
- Fasting period before study: an overnight fast immediately before dosing and for approximately two hours after dosing,
- Housing: The animals were housed in groups of up to five by sex in solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): With the exception of an overnight fast immediately before dosing and for approximately two hours after dosing, free access to food (Rat and Mouse Expanded Diet No. 1, Special Diets Services Limited, Witham, Essex, UK) was allowed throughout the study.
- Water (e.g. ad libitum):With the exception of an overnight fast immediately before dosing and for approximately two hours after dosing, free access to mains drinking water was allowed throughout the study.
- Acclimation period: acclimatisation period of at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23 °C
- Humidity (%): 45 to 58%
- Air changes (per hr): approximately 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.24 mL/kg 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:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 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 14 days.
Individual bodyweights were recorded prior to dosing on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes. 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.
Statistics:
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 mL/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:
Animals showed expected gain in bodyweight during the study.
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, ISONOX 232, in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. No symbol and risk phrase are required according to EU labelling regulations.
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 Guideline for Testing Chemicals No. 401 "Acute Oral Toxicity" (adopted 24 February 1987) and Method B1 of Commission Directive 92169/EEC (which vonstitutes 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 67/548/EEC (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 undiluted test material at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the 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.

Animals showed expected bodyweight gain during the study. 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 than 2000 mg/kg bodyweight. No symbol and risk phrase are required according to EU labelling regulations.