2-(4-fluorophenyl)-5-(5-iodo-2-methylbenzyl)thiophene

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 03/09/2008 to 26/09/2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented GLP study performed according to OECD guideline 423 and EEC method B.1 Tris.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-(4-fluorophenyl)-5-(5-iodo-2-methylbenzyl)thiophene

EC Number:

618-312-6

Cas Number:

898566-17-1

Molecular formula:

C18H14FIS

IUPAC Name:

2-(4-fluorophenyl)-5-(5-iodo-2-methylbenzyl)thiophene

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study reports): JNJ-39453193-AAA (T003063)
- Physical state: solid (powder)
- Appearance: white to almost white powder

Test animals

Species:

rat

Strain:

other: HanRcc: WIST(SPF)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services, Wölferstrasse 4, 4414 Füllinsdorf / Switzerland
- Age at study initiation: 11 weeks
- Weight at study initiation: 182.3 - 199.5 g
- Fasting period before study: approximately 17 to 17,5 hours (access to water was permitted)
- Housing: In groups of 3 in Makrolon type-4 cages with wire mesh tops and standard softwood bedding
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): between 30-70%
- Air changes (per hr): 10 - 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark, music during the daytime light period

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Polyethylene glycol 300 (PEG 300)

Details on oral exposure:

VEHICLE
- Lot/batch no. : 1349048

The dose formulations were made shortly before each dosing occasion using a magnetic stirrer and a spatula as homogenizers. The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight:volume).

Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

Doses:

2000 mg/kg

No. of animals per sex per dose:

2 groups of 3 females, one dose tested

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality / Viability: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15.
Body weights: On test days 1 (prior to administration), 8 and 15.
Clinical signs: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on day 1. Once daily during days 2 - 15.
- Necropsy of survivors performed: yes: all animals were killed at the end of the observation period by carbon dioxide asphyxiation and discraded after macroscopic examinations were performed. No organs or tissues were retained.

Statistics:

No statistical analysis was used.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the study.

Clinical signs:

No clinical signs were observed during the course of the study.

Body weight:

The body weight of the animals was within the range commonly recorded for this strain and age.

Gross pathology:

No macroscopic findings were recorded at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose of T003063 after single oral administration to female rats, observed over a period of 14 days is: LD50 (female rat): greater than 2000 mg/kg body weight.