Benzeneacetic acid, 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-oxobutyl]-.alpha.,.alpha.-dimethyl-, ethyl ester

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Start of study: October, 08, 1997 / End of study: October 22, 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study according to international guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-[4-[4-(Hydroxydiphenylmethyl)-1-piperidinyl]-1-oxobutyl]-α,α-dimethyl-ethyl ester benzeneacetic acid

EC Number:

616-391-1

Cas Number:

76812-02-7

Molecular formula:

C34 H41 N O4

IUPAC Name:

4-[4-[4-(Hydroxydiphenylmethyl)-1-piperidinyl]-1-oxobutyl]-α,α-dimethyl-ethyl ester benzeneacetic acid

Constituent 2

Reference substance name:

4-(4-(4-Hydroxydiphenylmethyl)-1-piperidinyl)-1-oxobutyl- alpha,alphadimethylbenzeneacetic acid ethyl ester

IUPAC Name:

4-(4-(4-Hydroxydiphenylmethyl)-1-piperidinyl)-1-oxobutyl- alpha,alphadimethylbenzeneacetic acid ethyl ester

Test material form:

solid - liquid: suspension

Details on test material:

- Name of test material (as cited in study report): Fexofenadonethylester
- Synonyms: Terfenadonethylester
- Chemical name: 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-oxobutyl]- a,a-dimethylbenzeneacetic acid ethyl ester
- Certificate of analysis: lP 156.1 of August 19, 1997
- Physical state: white powder
- Lot/batch No.: TAM 40-96-13
- Date of production: August, 27, 1996
- Date of receiveding: August, 28, 1997
- Date of expiry: August 1998
- Storage conditions: darkness at approximately 5°C in a refrigerator
- Stability and homogeneity in the vehicle is guaranteed for 4 hours

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Body weight at start of study
male animals mean = 175 g (= 100 %)
s = ± 5 g
min = 167 g (- 4.6 %)
max = 180 g (+ 2.9 %)
n = 5

female animals mean = 170 g (= 100 %)
s = ± 6g
min = 163 g (- 4.1 %)
max = 177 g (+ 4.1 %)
n = 5

Age at the start of the study: male animals approximately 7 weeks
female animals approximately 8 weeks

Randomization : Randomization schemes 96.0520 and 97.0538
Animal maintenance: in fully air-conditioned rooms in macrolon cages (type 4) on soft wood granulate in groups of 5 animals
Room temperature: 22 ± 3°C
Relative humidity: 50 ± 20%
Lighting time: 12 hours daily
Acclimatization: at least one day (breeding at identical conditions)
Food: ssniff R/M-H (V 1534), ad libitum
Withdrawal of food: from about 16 hours before to 3 - 4 hours after treatment
Water: tap water in plastic bottles, ad libitum
Animal identification: fur marking with KMn04 and cage numbering

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: sesame oil (Oleum sesami DAB 10)

Doses:

The acute oral toxicity of Fexofenadonethylester was tested only at a dose level of 2000 mg/kg body weight.
The administration volume being 10 ml/kg body weight.

No. of animals per sex per dose:

5 per sex

Control animals:

not specified

Details on study design:

The prepared test substance was administered by gavage to fasted animals at the stated dosage. The observation period following treatment lasted for 14 days. Symptoms were recorded twice every day (in the morning and in the afternoon), on week­ ends and public holidays only once. During this time the animals were weighed weekly. At the end of the observation period the animals were killed by carbon dioxide asphyxiation, dissected and examined for macroscopically visible changes.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the whole study.

Clinical signs:

other: No symptoms were observed after administration of 2000 mg/kg body weight.

Gross pathology:

No visible changes.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the results obtained in this study the median lethal dose value (LD50) of Fexofenadonethylester for the male and female rat is greater than 2000 mg/kg body weight.