2-ethylhexyl 7-oxabicyclo[4.1.0]heptane-3-carboxylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2017

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-ethylhexyl 7-oxabicyclo[4.1.0]heptane-3-carboxylate

EC Number:

263-471-3

EC Name:

2-ethylhexyl 7-oxabicyclo[4.1.0]heptane-3-carboxylate

Cas Number:

62256-00-2

Molecular formula:

C15H26O3

IUPAC Name:

2-ethylhexyl 7-oxabicyclo[4.1.0]heptane-3-carboxylate

Test material form:

liquid

Details on test material:

The test substance is identified as 2-ethylhexyl 7-oxabicyclo[4.1.0]heptane-3-carboxylate. The purity is 100%. The physical state/appearance of material is clear colorless liquid. The expiry date of material is 01 February 2019. The substance can be stored at 4 oC in dark conditions.

Specific details on test material used for the study:

Identification: 2-ethylhexyl 7-oxabicyclo[ 4.1.0]heptane-3-carboxylate
Batch: AH03201
Purity: 100%
Physical state/ Appearance: clear colorless liquid
Expiry Date: 01 February 2019
Storage Conditions: approximately 4 C in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Animal Information

Female Wistar (RccHan™:WIST) strain rats were supplied by Envigo RMS (UK) Limited, 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 5 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 ofthe study the animals were 8 to 12 weeks of age. The body weight variation did not exceed ±20% ofthe mean body weight at the start of treatment.

Animal Care and Husbandry
The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing, free access to mains drinking water. and food (2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, 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. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

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 dose group to confirm the survival of the previously dosed animals.

One rat was initially treated with 2000 mg/kg of the test article. When no toxicity was observed, four additional rats were treated with the same concentration.

Doses:

2000 mg/kg

No. of animals per sex per dose:

Initially one, followed by four more.

Control animals:

no

Details on study design:

One female rat was initially treated with 2000 mg/kg of the test article. There was no toxicity observed, so four additional rats were given the same treatment.

Statistics:

None

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

1 of the second group of 4 was sacrificed for humane reasons 1 day after dosing.

Clinical signs:

other: There were no signs of systemic toxicity noted in the initial treated animal. Hunched posture was noted in the four additional treated animals with ataxia also noted in three animals and pilo-erection noted in two animals. Signs of systemic toxicity confi

Gross pathology:

Patchy pallor of the liver was noted at necropsy of the animal that was humanely killed during the study. No abnormalities were noted at necropsy of animals that were killed at the end ofthe study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 was > 2000 mg/kg bw

Executive summary:

The study was performed to assess the acute oral toxicity of the test item in the Wistar strain rat.

Following a sighting test at a dose level of2000 mg/kg, an additional four fasted female animals were given a single oral dose of test item at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. One animal was killed for humane reasons, 1 day after dosing, due to the occurrence of clinical signs of toxicity that exceeded the severity limit set forth in the UK Home Office Project License.

Clinical Observations. There were no signs of systemic toxicity noted in the initial treated animal. Hunched posture and ataxia or pilo-erection were noted in the four additional treated animals with lethargy, decreased respiratory rate, labored respiration, loss of righting reflex and dehydration also noted the animal that was humanely killed 1 day after dosing.

Body Weight. Surviving animals showed expected gains in body weight.

Necropsy. Patchy pallor of the liver was noted at necropsy of the animal that was humanely killed during the study. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

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