Ethyl 4-methyl-2-oxocyclohexanecarboxylate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05 July 2017 - 20 July 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 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

August 1998

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

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:

fixed dose procedure

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 (in this study, adjustment was made for the density of the test item)

Test animals

Species:

rat

Strain:

other: Crl: WI(Han)

Sex:

male/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. 10 weeks old
- Weight at study initiation: males: 273-299 g; females: 195-202 g.
- Fasting period before study: no
- Housing: Group housing (up to 5 animals of the same sex together) on arrival and individual housing during the study. Polycarbonate cages (Makrolon MIV type; height 18 cm.) containing sterilized sawdust were used.
- Diet: Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany), ad libitum throughout the study, except during designated procedures.
- Water: Municipal tap-water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Humidity (%): 45-72 (Temporary deviations from the maximum level of target humidity occurred. This study plan deviation did not affect the integrity of the study because laboratory historical data do not indicate an effect of these deviations.)
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 6 July 2017 To: 20 July 2017

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 25 cm^2 for males, 18 cm^2 for females
- % coverage: 10% of the total body surface
- Type of wrap if used: The test item was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): using water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: The dose volume for each animal was based on the body weight measurement prior to dosing. Dose volume (mL/kg body weight) was calculated as follows: Dose level (g/kg) / spec.gravity or density (g/mL).
- Constant volume or concentration used: no

Duration of exposure:

24 hours

Doses:

2000 mg/kg bodyweight

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Mortality: twice daily; Clinical observations: at periodic intervals on the day of dosing (at least three times) and once daily thereafter; Body weights: on day 1 (pre-administration), day 8 and day 15.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Chromodacryorrhoea (snout) was noted for one male between Days 2 and 4 and three females on Day 1. No further clinical signs were noted.

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 dermal toxicity study in rats, performed according to OECD guideline 402 and GLP principles, FRET 13-0545 is not classified according to GHS and Regulation (EC) No. 1272/2008.

Executive summary:

In an acute dermal toxicity study in rats, performed according to OECD guideline 402 and GLP principles, FRET 13-0545 was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours.

The dermal LD50 value of FRET 13-0545 in Wistar rats was established to exceed 2000 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 dermal 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).