Cyclopropanecarboxylic acid, 2-[1-(3,3-dimethylcyclohexyl)ethoxy]-2-methylpropyl ester

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

07-05-2004 to 01-06-2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study performed under GLP. All relevant validity criteria were met.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

inspected: November 2002 ; signature: March 2003

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

460-490-0

EC Name:

-

Cas Number:

477218-42-1

Molecular formula:

C18H32O3

IUPAC Name:

2-[(1S)-1-[(1R)-3,3-dimethylcyclohexyl]ethoxy]-2-methylpropyl cyclopropanecarboxylate; 2-[(1S)-1-[(1S)-3,3-dimethylcyclohexyl]ethoxy]-2-methylpropyl cyclopropanecarboxylate

Test material form:

liquid

Details on test material:

Physical state: Liquid
- Storage condition of test material: at room temperature (range of 20 ± 3 °C), light protected.
- Other: colourless liquid

Test animals

Species:

rat

Strain:

Wistar

Remarks:

HanBrl: WIST (SPF)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Recognised supplier
- Age at study initiation: 12 weeks
- Weight at study initiation: 157.1 - 171.5 g
- Fasting period before study: 18-19h (overnight)
- Housing: The animals were housed in 3 per cage suspended solid-floor cages furnished with woodflakes (cage enrichment)
- Water: ad libitum
- Acclimation period: 7 days, under laboratory conditions, after health examination.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 (controlled)
- Humidity (%): 30-70 (controlled) (values above 70% possible during cleaning process)
- Air changes (per hr): 10-15/hour
- Photoperiod (hrs dark / hrs light): 12 hours light/dark, controlled cycle, music during daylight period.

IN-LIFE DATES: From: 07-05-2004 To: 01-06-2004

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 300

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2000 mg test item in 10 mL vehicle (200 mg/mL)
- Amount of vehicle (if gavage): 10 mL
- Justification for choice of vehicle: Choice based on the results of a non-GLP solubility trial (documented in the full study report).
- Lot/batch no. (if required): 448174/1 21203148.
- Purity: Not specified; source documented in the full study report

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION (if unusual): Not applicable.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: In the absence of data suggesting the test item was toxic, 2000 mg/kg was chosen as the starting dose.

Doses:

2000 mg/kg

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: prior to and then 1, 2, 3 and 5 hours after dosing; twice daily. Individual bodyweights prior to and at 7 and 14 days after treatment.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities.

Clinical signs:

other: Hunched posture observed from the 1 hour to 5 hours reading in three of six females. Slightly ruffled fur observed in the same three females from 1-hour to test day 6. Slightly-ruffled fur was also noted in two females at the 2 and 3 hours examinations.

Gross pathology:

No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the test item oral median LD50 was determined to be greater than 2000 mg/kg bw in female HanBrl: WIST (SPF) strain rat.

Executive summary:

The study was performed according to OECD 423 and EU Method B1 tris Acute Toxicity under GLP to assess the acute oral toxicity of the test item following a single oral administration in the HanBrl: WIST (SPF) strain rat. A group of three fasted females was treated with the test item at a dose level of 2000 mg/kg bodyweight. This was followed by a further group of three fasted females at the same dose level. The test item was administered orally in a vehicle of 10 mL PEG-300. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy. There were no mortalities. Hunched posture was noted in three of six females during the day of dosing and up to 4 hours after dosing. Additionally, these three females were observed to have slightly ruffled fur from the day of dosing to test day 6. Slightly ruffled fur was noted in two of the other females, but only during two examinations on the day of dosing. All females showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy. The acute oral median lethal dose (LD50) of the test item in the female HanBrl: WIST (SPF) strain rat was estimated to be greater than 2000 mg/kg bw. Applicant assessment indicates: under the conditions of this study the acute toxicity estimate would be considered to be > 5000 mg/kg bw.