4-(1-ethoxyvinyl)-3,3,5,5-tetramethylcyclohexanone

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

4-(1-ethoxyvinyl)-3,3,5,5-tetramethylcyclohexanone

EC Number:

252-961-2

EC Name:

4-(1-ethoxyvinyl)-3,3,5,5-tetramethylcyclohexanone

Cas Number:

36306-87-3

Molecular formula:

C14H24O2

IUPAC Name:

4-(1-ethoxyethenyl)-3,3,5,5-tetramethylcyclohexan-1-one

impurity 1

Reference substance name:

(3E,6E)-8-ethoxy-4,6,8-trimethylnona-3,6-dien-2-one

Molecular formula:

C14H24O2

IUPAC Name:

(3E,6E)-8-ethoxy-4,6,8-trimethylnona-3,6-dien-2-one

impurity 2

Reference substance name:

(E)-6-ethoxy-4,6,8-trimethylnona-3,7-dien-2-one

IUPAC Name:

(E)-6-ethoxy-4,6,8-trimethylnona-3,7-dien-2-one

impurity 3

Reference substance name:

(3E,6Z)-8-ethoxy-4,6,8-trimethylnona-3,6-dien-2-one

IUPAC Name:

(3E,6Z)-8-ethoxy-4,6,8-trimethylnona-3,6-dien-2-one

impurity 4

Reference substance name:

1,3-diethoxy-5,7,7-trimethylbicyclo[3.3.1]non-2-ene

IUPAC Name:

1,3-diethoxy-5,7,7-trimethylbicyclo[3.3.1]non-2-ene

impurity 5

Reference substance name:

3,5-diethoxy-1,7,7-trimethylbicyclo[3.3.1]non-2-ene

IUPAC Name:

3,5-diethoxy-1,7,7-trimethylbicyclo[3.3.1]non-2-ene

Test material form:

liquid

Specific details on test material used for the study:

Identification: Kephalis
Batch: VE00274898
Purity: 86.2%
Expiry date: 02 March 2014
Storage Conditions: ambient 10 to 30° C in the dark

Test animals

Species:

rat

Strain:

Wistar

Remarks:

RccHan™:WIST

Sex:

female

Details on test animals or test system and environmental conditions:

Female Wistar (RccHan™:WIST) strain rats were supplied by Harlan Laboratories UK Ltd., Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant. After an acclimatization period of at least five days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card. At the start of the study the animals were eight to twelve weeks of age. The body weight variation did not exceed ±20% of the body weight of the initially dosed animal.
The animals were housed in groups of up to three in suspended solid-floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and
Harlan Study Number: 41302013 Report Page 9
food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analyzed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Justification
Rats are the preferred species of choice as historically used for safety evaluation studies and are specified in the appropriate test guidelines.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each group to confirm the survival of the previously dosed animals.
The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
Individual body weights were recorded prior to dosing and seven and fourteen days after treatment.
At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Doses:

300 mg/kg

No. of animals per sex per dose:

3 animals per dose

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: Hunched posture was noted two and four hours after dosing in three animals treated at a dose level of 2000 mg/kg. There were no signs of systemic toxicity noted in the remaining animals.

Gross pathology:

No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight (Globally Harmonized Classification System - Unclassified).
The test item does not meet the criteria for classification according to Regulation (EC) No 1272/2008, relating to the Classification, Labeling and Packaging of Substances and Mixtures.