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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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted on 1996
Deviations:
no
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

Constituent 1
Chemical structure
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:
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.
Body weight:
The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.
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.