2-(3,5-dimethylhex-3-en-2-yloxy)-2-methylpropyl cyclopropanecarboxylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 22 May To 11 August, 2008.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted in compliance with OECD Guideline No. 423 without any deviation.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 17 December 2001

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

29 April 2004

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Remarks:

Swiss legislation on Good Laboratory Practice (signed in September 04, 2008)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-{[(2R)-3,5-dimethylhex-3-en-2-yl]oxy}-2-methylpropyl cyclopropanecarboxylate; 2-{[(2S)-3,5-dimethylhex-3-en-2-yl]oxy}-2-methylpropyl cyclopropanecarboxylate

EC Number:

700-118-9

Cas Number:

676532-44-8

Molecular formula:

C16H28O3

IUPAC Name:

2-{[(2R)-3,5-dimethylhex-3-en-2-yl]oxy}-2-methylpropyl cyclopropanecarboxylate; 2-{[(2S)-3,5-dimethylhex-3-en-2-yl]oxy}-2-methylpropyl cyclopropanecarboxylate

Test material form:

liquid

Details on test material:

- Description: Colourless liquid
- Formula: C16H28O3
- Molecular weight: 268,4 g/mol

Specific details on test material used for the study:

- Storage conditions: In the refrigerator at +2 to +8°C, protected from light

Test animals

Species:

rat

Strain:

other: HanRCC: WIST (SPF)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Biotechnology & Animal Breeding Division, CH-4414 Füllinsdorf, Switzerland
- Age at study initiation: 11 weeks
- Weight at study initiation: 184-202 g
- Fasting period before study: Animals were fasted approximately 18 to 19 hours (access to water was permitted) prior to incubation of the test substance by gavage, and 3 hours after the dosing.
- Housing: Animals were housed in groups of 3 in Makrolon type-4 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz)
- Diet: Pelleted standard Provimi Kliba 3433 rat maintenance diet, batch number 21/08 (Provimi Kliba AG, CH-4303, Kaiseraugst, Switzerland), ad libitum.
- Water: Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: 7 days under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/-3 °C
- Humidity: 30-70 %
- Air changes: 10-15 changes/h
- Photoperiod: 12 h dark / 12 h light
- Music was played during the light period.

IN-LIFE DATES: From 27 May To 19 June, 2008.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 300

Details on oral exposure:

VEHICLE
PEH 30 was chosen after a non-GLP solubility trial.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: Test material was prepared shortly before each dosing occasion using a magnetic stirrer as homogenizer. The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight/volume). Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Using available information on the toxicity of the test material, 2000 mg/kg bw was chosen as the starting dose.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighting: On test days 1 (prior to administration), 8 and 15.
- Frequency of observations:
Mortality / viability: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15.
Clinical observations: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: Yes; All animals were killed at the end of the observation period by Carbon dioxide asphyxiation and discarded after macroscopic examinations were performed. No organs or tissues were retained.

Statistics:

None

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths occurred during the study.

Mortality:

No deaths occurred during the study.

Clinical signs:

other: One female showed slightly ruffled fur 2 to 5 hours after treatment and on test days 3 to 6. In the other five females the slightly ruffled fur was observed from test day 2 or 3 up to test days 5, 6, 7 or 8. Additionally, hunched posture was recorded in f

Gross pathology:

No macroscopic findings were recorded at necropsy

Other findings:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the oral LD50 of the test substance is >2000 mg/kg bw in rats. In accordance with OECD Guideline 423, the LD50 cut-off of the test substance may be considered to be > 5000 mg/kg bw by oral route in the rat. Therefore it is not classified according to the Regulation (EC) N° 1272-2008 and according to the GHS. No signal word or hazard statement is required.

Executive summary:

In an acute oral toxicity study (limit test) performed according to OECD Guideline No. 423 and in compliance with GLP, female HanRCC: WIST (SPF) rats were administered a single oral dose of test material diluted in PEG-300 by gavage.

The animals (6 females) received a single dose of the test item on a 2000 mg/kg bw and were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination.

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximately 30 minutes, 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded at approximately 30 minutes, 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

 

All animals survived until the end of the study period. One female showed slightly ruffled fur 2 to 5 hours after treatment and on test days 3 to 6. In the other five females the slightly ruffled fur was observed from test day 2 or 3 up to test days 5, 6, 7 or 8. Additionally, hunched posture was recorded in five females 2, 3 or 5 days post-treatment and persisted up to test days 3, 4, 5 or 6. Otherwise, no clinical signs were recorded in any animal at any observation.

The body weight of the animals was within the range commonly recorded for this strain and age.

No macroscopic findings were recorded at necropsy.

Under the test conditions, the oral LD50 of the test substance is > 2000 mg/kg bw in rats. In accordance with OECD Guideline 423, the LD50 cut-off of the test substance may be considered to be > 5000 mg/kg bw by oral route in the rat. Therefore it is not classified according to the Regulation (EC) N° 1272-2008 and according to the GHS. No signal word or hazard statement is required.

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.