Ethyl 4-methyl-2-oxocyclohexanecarboxylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06 April 2017 - 28 April 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

December 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

May 2008

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Appendix to Director General Notification, No. 12-Nousan-8147. Agricultural Production Bureau, Ministry of Agriculture, Forestry and Fisheries of Japan (JMAFF)

Version / remarks:

November 2000, including the most recent revisions.

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl 4-methyl-2-oxocyclohexanecarboxylate

EC Number:

236-910-1

EC Name:

Ethyl 4-methyl-2-oxocyclohexanecarboxylate

Cas Number:

13537-82-1

Molecular formula:

C10H16O3

IUPAC Name:

ethyl 4-methyl-2-oxocyclohexane-1-carboxylate

Test material form:

liquid

Details on test material:

Physical appearance: Clear colourless liquid
Storage conditions: In refrigerator (2-8°C) in clear glass bottle

Specific details on test material used for the study:

pH (1% in water, indicative range): 5.11 – 5.25
Specific gravity / density: 1.04 g/mL

Test animals

Species:

rat

Strain:

other: Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approx. 8 weeks old
- Weight at study initiation: 145 - 156 g
- Fasting period before study: overnight (maximum of 20 hours)
- Housing: group housing up to 5 animals in polycarbonate cages containing sterilized sawdust as bedding material.
- Diet: pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
- Water: municipal tap-water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS (set to maintain)
- Temperature (°C): 21
- Humidity (%): 44-49
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 11 April 2017 - 28 April 2017

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw (since no vehicle was used, the dose volume was based on bodyweight measurement prior to dosing.

DOSAGE PREPARATION: the test Item was stored in the refrigerator and was allowed to warm to room temperature for at least 30 minutes before dosing. Adjustment was made for specific gravity of the test item. No correction was made for the purity/composition of the test item.

CLASS METHOD
- Rationale for the selection of the starting dose: The dose levels were based on the OECD test guidelines and were selected from the series 5 (lowest dose level), 50, 300 and 2000 (highest dose level) mg/kg body weight. The starting dose level should be the one that is likely to produce mortality in at least some of the animals and was selected based on available toxicity data of the test item.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Test groups consisted of 3 female animals. A first group was treated at a dose level of 2000 mg/kg. Based on the results, one additional group was dosed at 2000 mg/kg.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
* mortality: twice daily
* clinical observations: at least three times on the day of dosing (periodic intervals) and once daily thereafter.
* body weights (individually): on day 1, day 8 and day 15.
- Necropsy of survivors performed: yes
- Other observations: descriptions of all internal macroscopic abnormalities were recorded.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Hunched posture, uncoordinated movements and piloerection were noted for all animals on Day 1.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Not classified according to Regulation (EC) No. 1272/2008

Conclusions:

Based on the results of an acute oral toxicity study, performed according to OECD guideline 423, the LD50 of FRET 13-0545 for female Wistar rats exceeded 2000 mg/kg bw. The test item is therefore not classified according to GHS and Regulation (EC) No. 1272/2008.

Executive summary:

In the acute oral toxicity study in rats, performed according to OECD TG 423, the oral LD50 value of FRET 13-0545 in Wistar rats was established to exceed 2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Based on these results, FRET 13-0545 does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).