6-glycidyloxynapht-1-yl oxymethyloxirane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05.06.1986 to 19.06.1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study performed under GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1175 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

429-960-2

EC Name:

-

Cas Number:

27610-48-6

Molecular formula:

C16H16O4

IUPAC Name:

2-[({6-[(oxiran-2-yl)methoxy]naphthalen-1-yl}oxy)methyl]oxirane

Details on test material:

Purity: >99%
Lot N°. B-001
Appearance: Viscous liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Equal numbers of male and female CFY (Sprague-Dawley origin) rats were obtained from Interfauna UK Ltd., (fromely Hacking and Churchill Ltd.), Cambridgeshire, England.

They were in a weight range of 109 to 150 g prior to dosing (Day 1) in the main study and approximately four to six weeks of age. All rats were acclimated to the experimental environment for a period of 7 days prior to the start of the main study.

The rats were allocated to cages within the treatment group. They were housed in groups by sex in metal cages with wire mesh floors. A standard laboratory rodent diet (labsure LAD 1) and water were provided ad Libitum. The batch of diet used for the study was analysed for certain chemical and microbiological contaminants. Access to food only was prevented overnight prior to and approximately 4 hours after dosing.

The mean daily minimum and maximum temperatures of the animal room were 22°C and 25°C respectively and the mean daily relative humidity value was 54%. The rate of air exchange was maintained at approximately 15 air changes/hour. lighting was controlled by means of a time switch to 12 hours artificial in each 24 hour period.

Each animal was identified by cage number and ear punching.
Each cage was identified by a coloured label displaying the dose level, study schedule number and the initials of the study Director.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

Preliminary study:
-A trial test was carried out to establish a dosing regimen using groups of two male and two female rats at two dose levels of 1.0 and 5.0 g/kg bodyweight.

Main study:
-A group of ten rats (five males and five females) was treated at 2.0 g/kg bodyweight.

Doses:

-Preliminary study: 1.0 and 5.0 g/kg bodyweight
-Main study: 2.0 g/kg bodyweight.

No. of animals per sex per dose:

-Preliminary study: 2 males and 2 females rats.
-Main study: ten rats (5 males and 5 females)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed soon after dosing; then at frequent intervals fot the remainder of Day1. On subsequent days the animals were observed once in the morning and again at the end of the experimental day. This latter observations was at approximately 16.30 hours on weekdays or 11.30 hours on Saturday and Sunday. Clinical signs were recorded at each observation.
The animals on the preliminary study were observed for 5 days (dose 1.0 g/kg) or 7 days (dose 5.0 g/kg). Those on the main study were observed for 14 days after dosing.
Individual bodyweights of rats on Day 1 (day of dosing), 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights.

Results and discussion

Preliminary study:

A trial test was carried out to establish a dosing regimen using groups of two male and two female rats at two dose levels of 1.0 and 5.0 g/kg bodyweight. Losses of bodyweight were recorded on Day 8 for each of the three rats surviving administration of Epiclon EXA-4032 at 5.0 g/kg. Autopsyof these animals on Day 8 revealed gross thickening of the gatsric epithelium and adhesions of the stomach to the abdominal wall and adjacent viscera. Thus, although the preliminary study indicated the acute median lethal oral dose of Epiclon EXA-4032 was in the region of 5.0 g/kg, it was inappropriate to establish the LD50with greater precision on humane grounds. The study was completed by demonstrating that the lethal threshold dose (acute lethal dose) of Epiclon EXA-4032 was greater than 2.0 g/kg bodyweight.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths following a single oral dose of EPICLON EXA-4032 at 2.0 g/kg bodyweight.

Clinical signs:

other: Signs of reaction to treatment seen in all rats during the first three days of the observation period were pilo-erection and abnormal body carriage (hunched posture). All rats showed pallor of the extremities between days 8 and 11. Recovery, as judged by

Gross pathology:

Terminal autopsy revealed thickening or ulceration of the epithelium of the non-glandular zone of the stomach and adhesions of the stomach to the diaphragm, adjacent viscera and or the abdominal wall.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

In conclusion, the acute lethal oral dose to rats of EPICLON EXA-4032 was found to be greater than 2.0g/kg bodyweight.
LD50>2.0 g/kg bodyweight.

Executive summary:

This study was designed to assess the toxicity following a single oral dose and to determined the LD50.

The LD50 of EPICLON EXA-4032 was determined and the experimental procedure was based on the Testing Guidelines as given in Federal Register Vol.50 N°. 188, PartII dated 27 September 1985.Section 798.1175 -Acute Oral Toxicity.

For this experiment, a preliminary study was done to establish a dosing regimen using groups of 2 male and 2 female rats at 2 doses levels of 1.0 and 5.0 g/kg.

For the main study, a group of ten rats (five males and five females) was treated at 2.0 g/kg bodyweight..

The dose volume of the etst substance was administred to each rat using a syringue and plastic catheter and te viscosity of the test substance prevented it's administartion in the undiluted state.

In conclusion, the acute lethal oral dose to rats of EPICLON EXA-4032 was found to be greater than 2.0g/kg bodyweight.

LD50>2.0 g/kg bodyweight.