1H-Tetrazole, 5-(4-chlorobutyl)-1-cyclohexyl-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study has been performed in accordance with OECD guideline No.:423.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

5-(4-chlorobutyl)-1-cyclohexyl-1H-1,2,3,4-tetrazole

EC Number:

616-036-0

Cas Number:

73963-42-5

Molecular formula:

C11H19ClN4

IUPAC Name:

5-(4-chlorobutyl)-1-cyclohexyl-1H-1,2,3,4-tetrazole

Test material form:

solid: crystalline

Details on test material:

- Name of test material (as cited in study report): Cilostazol Starting Material 2
- Physical state: white crystalline powder
- Lot/batch No.: PL2488
- Date of analysis: 2009.03.
- Storage condition of test material: In well-closed closed brown vial-up to 25 °C.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: TOXI COOP ZRT. Cserkesz u. 90. 1103
- Age of animals: Young adult rat, 8 weeks old
-Number of animals: 3 animals/group
- Body weight range at starting (first step): 219-232 g
- Body weight range at starting (second step): 212-225 g
- Acclimation time: 5 days in first step, 6 days in second step

HUSBANDRY
- Temperature (°C): 22 ± 3 ºC
- Humidity (%): 30-70 %
- Air changes (per hr): 8-12
- Light: Artificial light from 6 a.m. to 6 p.m.

Administration / exposure

Route of administration:

oral: gavage

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/l
- Amount of vehicle (if gavage): 10 ml/kg bw)

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw

Doses:

2000 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2000 mg/kg bw dose level, so treatment with 2000 mg/kg bw was repeated on further three female rats.

No. of animals per sex per dose:

2 groups of female rats, 3 rats/group , 1 dose / group.

Control animals:

no

Details on study design:

- Dosages: Starting dose was selected on the basis of the available information about the test item.
- Procedure: A single oral administration - followed by a 14 days observation period - was performed by gavage. Animals were weighed before the application and the food was given back 3 hours after the treatment.
- Duration of the experimental period: 5 days in first step and 6 days in second step of acclimatization, treatment's day, 14 days post-treatment observation period including the treatment day, necropsy on day 15.
- Body weights were recorded on day 0 (just before the treatment) and at day 7 and at day 15 with precision of 1 g.
- Necropsy: At the and of the observation period all rats were sacrificed under isofluran anaesthesia.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

approximate LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

no mortality

Clinical signs:

other: In group 1 treated with 2000 mg/kg dose clinical sign of reaction comprised of decreased activity (15 cases out of 57 observations), incoordination (10/57), dyspnoea (4/57) and decreased righting reflex (4/57). Decreased activity (score -1, -2, -3) and in

Gross pathology:

Severe hydrometria in one animal, and moderate hydrometria in one animal. No pathological changes were found.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute toxic class method (OECD Guideline No. 423) was carried out involving a stepwise procedure with the use of 2000 mg/kg bw dose. The test item is ranked into classes of Globally Harmonized Classification System as GHS category 5 since the LD50 (mg/kg bw) value is above 2000.