2-(2-oxo-5-(1,1,3,3-tetramethylbutyl)-2,3-dihydro-1-benzofuran-3-yl)-4-(1,1,3,3-tetramethylbutyl)phenyl acetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10.06. - 05.09.1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline study, GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted on 1996

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Remarks:

NOTOX B.V., Hambakenwetering 7, 5231 DD ‘s-Hertogenbosch, The Netherlands

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

431-770-1

EC Name:

-

Cas Number:

216698-07-6

Molecular formula:

C32 H44 O4

IUPAC Name:

2-[2-oxo-5-(2,4,4-trimethylpentan-2-yl)-2,3-dihydro-1-benzofuran-3-yl]-4-(2,4,4-trimethylpentan-2-yl)phenyl acetate

Details on test material:

- Physical state: White solid
- Analytical purity: 98.7%
- Stability under test conditions: stable
- Storage condition of test material: At room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL Ltd., Basel, Switzerland.
- Age at study initiation: approx. 7 weeks old
- Fasting period before study: Food was withheld overnight (for a maximum of 20 hours) prior to dosing until approximately 3-4 hours after administration of the test substance.
- Housing: Group housing of 3 animals per sex per cage in labeled polycarbonate cages containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany).
- Diet: standard pelleted laboratory animal diet, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days before start of treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12

Administration / exposure

Route of administration:

oral: gavage

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle: The vehicle was selected based on a pretest performed at NOTOX.

DOSAGE PREPARATION:
The formulations (w/w) were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of vehicle.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 (two groups of 3, stepwise treatment)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Body weights: days 1 (pre-administration), 8 and 15
- Mortality: checked twice daily
- Clinical signs:
At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded.
At the end of the observation period, all animals were sacrificed by asphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.

Statistics:

No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Lethargy was observed in all animals on the day of treatment. Uncoordinated movements were seen in all females and in one male also on day 1. All animals had recovered from the symptoms on day 2.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Conclusions:

The oral LD50 value of the test article in Wistar rats was established to exceed 2000 mg/kg body weight.

Executive summary:

In an oral toxicity study according to OECD guideline 423 (Acute Toxic Class Method), three male and three female Wistar rats were dosed once with the test article in propylene glycol by gastric intubation at a dose level of 2000 mg/kg body weight and observed for 14 days. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15). No mortalities were recorded. Lethargy was observed in all animals on the day of treatment. Uncoordinated movements was seen in all females and one male also on day 1. All animals had recovered from the symptoms on day 2. The body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals. The oral LD50 value of the test article in Wistar rats was established to exceed 2000 mg/kg body weight.