Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
27 July - 17 Aug 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report date:
2004

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted 17 Dec 2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147
Version / remarks:
amended 10 Dec 2002
GLP compliance:
yes (incl. QA statement)
Remarks:
THE DEPARTMENT OF HEALTH, UK
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2-{2-chloro-4-(methylsulfonyl)-3-[(tetrahydrofuran-2-ylmethoxy)methyl]benzoyl}cyclohexane-1,3-dione
Cas Number:
473278-76-1
Molecular formula:
C20 H23 Cl O7 S
IUPAC Name:
2-{2-chloro-4-(methylsulfonyl)-3-[(tetrahydrofuran-2-ylmethoxy)methyl]benzoyl}cyclohexane-1,3-dione
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
other: CD (Crl: CD (SD) IGS BR)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, UK
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 184 - 232 g
- Fasting period before study: overnight fast immediately before dosing and for approximately 3 to 4 h after dosing
- Housing: in groups of three in suspended solid-floor polypropylene cages on woodflakes, environmental enrichment items were provided
- Diet: certified Rat and Mouse Diet, Code 5LF2 (BCM IPS Limited, London, UK), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Justification for choice of vehicle: the test material did not dissolve/suspend in distilled water

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: all available information on the toxicity of the test substance was used
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 females in total
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 0.5, 1, 2 and 4 h after dosing and subsequently once daily for 14 days. Individual body weights were recorded prior to dosing and 7 and 14 days after treatment.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 cut-off according to OECD 423
Mortality:
No mortality occurred during the study period.
Clinical signs:
Hunched posture was noted in one animal 2 and 4 h after dosing. Five animals appeared normal throughout the study and the remaining animal appeared normal one day after dosing.
Body weight:
All animals showed expected gains in body weight over the study period.
Gross pathology:
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In this acute oral toxicity study a LD50 cut-off value of 5000 mg/kg bw in female rats was found.