1,2-Cyclohexanedicarboxylic acid, 1-[2-[(1-oxo-2-propen-1-yl)oxy]ethyl] ester

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was performed between 16 May 2006 and 15 June 2006.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

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:

Date of Inspection: 30th August 2005 Date of signature: 21 November 2005

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

57043-35-3

Cas Number:

57043-35-3

IUPAC Name:

57043-35-3

Details on test material:

Sponsor's identification : MAHP
Description : Clear, colourless slightly viscous liquid
Batch number : L508708-A
Date received : 29 March 2006
Storage conditions : room temperature in the dark

Specific details on test material used for the study:

Sponsor's identification: MAHP
Description: clear colourless slightly viscous liquid
Batch number: L508708-A
Date received: 29 March 2006
Storage conditions: room temperature in the dark

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Female Sprague-Dawley CD (Crl: CD® (SD) IGS BR) strain rats were supplied by Charles River (UK) Ltd, Margate, Kent, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant.
After an acclimatisation 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 bodyweight variation did not exceed ± 20% of the initial/mean bodyweight of any previously dosed animal(s).

The animals were housed in groups of 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 food (Certified Rat and Mouse Diet (Code 5LF2) supplied by BCM IPS Limited, London, UK) was allowed throughout the study.
The diet, drinking water and bedding were routinely analysed 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.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

Preparation of Test Material:
For the purpose of the 2000 mg/kg dose level the test material was used as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level. For the purpose ofthe 300 mg/kg dose level the test material was freshly prepared, as required, as a solution at the appropriate concentration in arachis oil BP. Arachis oil BP was used because the test material did not dissolve/suspend in distilled water.
Determination by analysis of the concentration, homogeneity and stability of the test material preparations was not appropriate because it was not specified in the Study Plan and is not a requirement of the Test Guideline.
Procedure:
Using available information on the toxicity of the test material, 300 mg/kg was chosen as the starting dose. 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 bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each group and each dose level to confirm the survival of the previously dosed animals. At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. 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 (with vehicle) and 2000 (undiluted) mg/kg.

No. of animals per sex per dose:

300 mg/kg bw: 3
2000 mg/kg bw: 2 x 3

Control animals:

no

Details on study design:

- Duration of observation period following administration: The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2, and 4 hours after dosing and subsequently once daily for up to fourteen days.
- Frequency of observations and weighing: Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment or at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, necropsy.

Statistics:

Not applicable.

Results and discussion

Preliminary study:

Not applicable.

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Remarks:

See attached figure.

Effect level:

> 2 500 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Effect levels 2

Sex:

female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: There were no signs of systemic toxicity.

Gross pathology:

Not reported

Other findings:

Necropsy:
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

Category 5 or unclassified (see attached flow-chart)

Conclusions:

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 2500 mg/kg bodyweight (Globally Harmonised Classification System - Unclassified).

Executive summary:

Introduction. The study was performed to assess the acute oral toxicity of the test material following a single oral administration in the Sprague-Dawley CD strain rat. The method was designed to meet the requirements of the following:

- OECD Guidelines for the Testing of Chemicals No. 423 "Acute Oral Toxicity - Acute Toxic Class Method" (adopted 17 December 2001).

- Method B1 tris Acute Toxicity (Oral) of Commission Directive 2004/73/EC

Method. A group of three fasted females was treated with the test material at a dose level of 300 mg/kg bodyweight. Based on the results from this dose level further groups of fasted females were treated at a dose level of 2000 mg/kg bodyweight. Dosing was performed sequentially.

The test material was administered orally as a solution in arachis oil BP for the 300 mg/kg dose level and orally undiluted for the 2000 mg/kg dose level. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. There were no deaths.

Clinical Observations. There were no signs of systemic toxicity.

Bodyweight. The surviving animals showed expected gains in bodyweight over the study period.

Necropsy. No abnormalities were noted at necropsy.

Conclusion. The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 2500 mg/kg bodyweight (Globally Harmonised Classification System - Unclassified).