Climbazole

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No study period specified, but the study report was finalized on 1975-01-08.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to a method that is largely comparable to the current OECD guideline 401. However, it was not conducted according to the principles of GLP, as GLP had not yet been implemented at the time the study was performed.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1975

Report date:

1975

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

The test item was administered orally to groups of 10 male and female Wistar rats at dose levels of 160, 200, 250, 320, 400, 500, 630, 800, and 1000 mg/kg. Toxicity symptoms and mortality rates were recorded for a 14-d observation period. Animals that died were, whenever possible, autopsied and examined for pathological changes. The surviving rats were killed at the end of the trial and also autopsied. Computation of the LD50 values, with a confidence range of p = 0.05 was carried out by means of programmed probit analysis.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Climbazole

EC Number:

253-775-4

EC Name:

Climbazole

Cas Number:

38083-17-9

Molecular formula:

C15H17ClN2O2

IUPAC Name:

1-(4-chlorophenoxy)-1-(1H-imidazol-1-yl)-3,3-dimethylbutan-2-one

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: breeder Winkelmann (Kirchborchen, Germany)
- Weight at study initiation: 170-253 g
- Housing: Animals were kept in Makrolon cages type I or type III in groups of 5 animals per cage.
- Diet: standard diet (Altromin GmbH, Lage/Lippe, Germany), ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: about 24°C

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: aqueous solution with 5% cremophor

Details on oral exposure:

The test item was suspended in tap water with the addition of 5% cremophor and was administered to the animals in a volume of 10 mL/kg via a stomach tube.

Doses:

The test item was administered at dose levels of 160, 200, 250, 320, 400, 500, 630, 800, and 1000 mg/kg.

No. of animals per sex per dose:

10 animals were used per dose (no data on animals per sex given).

Control animals:

not specified

Details on study design:

Toxicity symptoms and mortality rates were recorded for a 14-d observation period. Animals that died were, whenever possible, autopsied and examined for pathological changes. The surviving rats were killed at the end of the trial and also autopsied.

Statistics:

Computation of the LD50 values, with a confidence range of p=0.05 was carried out by means of the programmed probit analysis according to Fink and Hund [Fink H, Hund G (1965) Probitanalyse mittels programmgesteuerter Rechenanlagen. Arzneim-Forsch / Drug Res 15:624-630].

Results and discussion

Preliminary study:

not applicable

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

400 mg/kg bw

Based on:

test mat.

95% CL:

334 - 481

Mortality:

See table 1 in section "Any other information on results incl. tables".

Clinical signs:

other: Except for the dose of 160 mg/kg, which was symptom-free tolerated, all animals showed coordination disturbances and tonic-clonic convulsions about 1 h after administration. After 2 h, motility was reduced and the animals were temporarily laying on their

Gross pathology:

The autopsies did not provide any pathological findings.

Other findings:

no data

Any other information on results incl. tables

Table 1: Acute oral toxicty of crinipan in rats

Dose (mg/kg)	Number of animals used	Toxicological result
		Number of animals that died	Number of animals showing toxic symptoms
160	10	0	0
200	10	1	10
250	10	2	10
320	10	5	10
400	10	5	10
500	10	7	10
630	10	6	10
800	10	9	10
1000	10	10	10

Applicant's summary and conclusion

Interpretation of results:

moderately toxic

Remarks:

Migrated information Criteria used for interpretation of results: not specified

Conclusions:

Crinipan was found to be moderately toxic upon a single oral administration to male and female rats.

Executive summary:

The acute toxicity of crinipan upon oral administration was studied in male and female Wistar rats (n=10 per dose). Crinipan was found to be moderately toxic, with a LD₅₀ of 400 mg/kg.