2-{2-chloro-4-mesyl-3-[(tetrahydrofuran-2-ylmethoxy)methyl]benzoyl}cyclohexane-1,3-dione

Acute Toxicity: oral

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 guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adopted 17 Dec 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

THE DEPARTMENT OF HEALTH, UK

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-(2-chloro-4-methanesulfonyl-3-{[(oxolan-2-yl)methoxy]methyl}benzoyl)cyclohexane-1,3-dione

EC Number:

695-022-6

Cas Number:

473278-76-1

Molecular formula:

C20 H23 Cl O7 S

IUPAC Name:

2-(2-chloro-4-methanesulfonyl-3-{[(oxolan-2-yl)methoxy]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:

other: 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.

Gross pathology:

No abnormalities were noted at necropsy.

Any other information on results incl. tables

Table 1. Results for the acute oral toxicity study (mortality and clinical signs)

Dose [mg/kg bw]	Toxicological results*	Duration of clinical signs	Time of death	Mortality (%)
Females
2000	0/1/5	24h	-	0
LD50 ≥5000 mg/kg bw

* number of dead animals / number of animals with clinical signs / number of animals used

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.

Conclusions:

The study was performed in accordance to OECD TG 423 under GLP conditions and is considered reliable. The acute oral LD50 cut-off of the test material (as defined in the OECD TG 423) was ≥5000 mg/kg bw.