Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 29 Nov. 1994 to 21 Dec. 1994
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 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
Adopted 17th July 1992
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
Test material identification: ST 02 C 94
Description: colourless liquid
Date received; 25th November 1994
Specific details on test material used for the study:
Storage conditions: refrigerator in the dark

Test animals

Species:
rat
Strain:
other: Crl: CD (SD) BR strain (VAF plus)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK)Limited, Margate, Kent- U.K.
- Age at study initiation: 4-6 weeks
- Weight at study initiation: See Tables of results
- Fasting period before study: yes overnight
- Housing: in groups ofup to 5, by sex, in grid-bottomed cages suspended over cardboard lined excreta trays. Cardboard tray liners were changed as often as necessary to maintain hygiene.
- Diet (e.g. ad libitum): ad libitum apart from an overnight fast before dosing (a pelleted diet (SQC Rat and Mouse Maintenance Diet No.1 Expanded, produced by Special Diets Services, Witham, Essex). Certificates of analysis for both diet and drinking water are held on file at Toxicol Laboratories.
- Water (e.g. ad libitum): ad libitum apart from an overnight fast before dosing
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24 °C
- Humidity (%): 40-66%
- Air changes (per hr): air conditionned room
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 25 & 100 mg/mL
- Amount of vehicle (if gavage): 20 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw

DOSAGE PREPARATION (if unusual): N.A.
Doses:
Preliminary range finding study: 1 female with 500 mg/kg bw, then another female with 2000 mg/kg bw.
Main Study: 2000 mg/kg/bw (5 males + 5 females)
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: Observations: after 0.5, 1, 2, 4 hours and daily during 14 days. Weighing: Before dosing and weekly therafter (days 1, 8 and 15).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight.
Statistics:
Not applicable/relevant

Results and discussion

Preliminary study:
1 female with 500 mg/kg bw: no clinical signs
1 female with 2000 mg/kg bw: no clinical signs
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
none (see "Illustration" for detailed results)
Clinical signs:
none (see "Illustration" for detailed results)
Body weight:
no significant changes (see "Illustration" for detailed results)
Gross pathology:
no significant effects (see "Illustration" for detailed results)
Other findings:
None

Any other information on results incl. tables

none

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Oral LD50 combined > 2000 mg/kg bw
Executive summary:

Introduction. The purpose of this study was to assess the acute oral toxicity of Fructalate, in the rat using the Fixed Dose Method. The study complies with the requirements of OECD Guideline for the Testing of Chemicals No 420, adopted 17th July 1992 and method B.1bis described in 0.J. L 383 A, an Annex to EEC Commission Directive 92/69/EEC of 31st July 1992.

These guidelines require that the main study be conducted at one (or more if necessary) of the following fixed dose levels: 5, 50, 500 or 2000 mg/kg bw.

Method. In a preliminary range finding study, the test article was administered orally at a dose level of 500 mg/kg bw to a single female rat. As this first animal was still alive 24 hours after dosing, a second female wasdosed with 2000 mg/kg bw test article. Both animals were examined frequently on the day of dosing and daily thereafter for a further 7 days. As neither animal exhibited clinical signs of toxicity and both were alive at the end of the observation period, no further range finding animals were dosed.

Since the results of the range finding study indicated that a test article dose of 2000 mg/kg bw produced no significant toxicity, in the main study, the test article was administered as a single oral dose of 2000mg/kg bw to a group of 5 male and 5 female rats which had been fasted overnight. The animals were examined frequently on the day of dosing and daily thereafter for a further 14 days at the end of which, they were killed and subjected to necropsy.

None of the animals died and all maintained a healthy appearance throughout the 15 days observation period.

There was no adverse effect on bodyweight gain in animals of either sex.

At necropsy, the submandibularlymph nodes were swollen in one male. No abnormalities were detected in the remaining animals.

Conclusions. Both the discriminating dose and the minimum lethal dose of the test material are estimated to be in excess of 2000 mg/kg bodyweight. According to the criteria in the guidelines quoted above, the test material is considered not to have significant acute toxicity under the conditions of this study.

The test material does not meet the criteria for classification according to the Regulation( EC) No. 1278/2008 (CLP)