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

Short-term toxicity to fish

Administrative data

Endpoint:

short-term toxicity to fish

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Study of study: November 10, 1997 / End of study: November 14, 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 C.1 (Acute Toxicity for Fish)

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 203 (Fish, Acute Toxicity Test)

GLP compliance:

yes

Remarks:

Principles of Good Laboratory Practice, annex of paragraph 19a, section 1of the chemical law

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: particulate/powder

Remarks:

migrated information: powder

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
- Purity: 98.65%
- Certificate of analysis: Analysenbefund lP 156.1 from August 19, 1997
- Lot/batch No.: TAM 40-96-13 from August 27, 1996
- Appearance: white powder
- Date of production: August 27, 1996
- Date of receiving: August 28, 1997
- Date of expiry: August 1998
- Storage condition of test material: darkness at approximately 5 °C in a refrigerator under dry conditions
- Solubility in water: not soluble

Test solutions

Vehicle:

no

Test organisms

Test organisms (species):

Danio rerio (previous name: Brachydanio rerio)

Details on test organisms:

Origin: Hoechst Marion Roussel Deutschland GmbH Global Preclinical Development - Drug Safety
Date of hatching: August 04, 1997
Delivery date: September 24, 1997

The fish were kept for 14 days before the start of the study in water for dilution under the following conditions:
- Temperature: 22 ± 1 °C
- Oxygen content: >= 80 % of the saturation value
- Duration of light period: 12 hours daily
-Population density: <= 1g fish / L water
- Feeding: twice daily ad libitum
-Food: Tetra Min, Tetra Werke, Melle (Germany)

The body length of 7 representative fish from each batch was measured.
Body lenght (cm): Variation range: 2.5 - 3.2 / mean: 2.7 / s: ± 0.26

Study design

Test type:

static

Water media type:

freshwater

Limit test:

yes

Total exposure duration:

96 h

Test conditions

Hardness:

2.1 -2.3 mmol Ca2+ + Mg2+/L during the study.

Test temperature:

The temperature of the water bath was regulated by a thermostat to 22 ± 1 °C.

pH:

The pH was measured before the use of each study batch. lt was in a range of 8.2- 8.3.

Dissolved oxygen:

The dilution water was prepared as described and was aerated until oxygen saturation.

Nominal and measured concentrations:

0 /100 mg/L (nominal concentration)
0 /11.3 mg/L (mean measured concentration)

Details on test conditions:

The test chambers, which were calibrated to 4 liters, were made of glass (length 20 cm, width 15 cm, height 20 cm) and stood in a water bath made of Hostalit Z® with a Plexiglas viewing panel. The chambers were illuminated from above from 06.00 a.m to 06.00 p.m. The light intensity directly over the chambers was approximately 700 lux.
The test chambers were not aerated during the course of the study.

Results and discussion

Effect concentrations

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

> 100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Details on results:

The 100 mg/L group exhibited symptoms but no lethality.
The fish showed changes in behavior, swimming behavior and respiration rate. Symptoms occurred during the entire exposure time.

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

Under the conditions of this test the LC50 of Fexofenadonethylesterafter 96 hours was > 100 mg/L (based on nominal concentration). No lethality occured up to the solubility limit of the test substance in the test water.