8-azaspiro[4,5]decane-8-{4-[4''-(2'''-pyrimidinyl)-1''-piperazinyl]-butyne/2/-yl}-7,9-dione /E/-2-butenedionate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP, available as unpublished report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

Adopted 24 February 1987

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

8-azaspiro[4,5]decane-8-{4-[4''-(2'''-pyrimidinyl)-1''-piperazinyl]-butyne/2/-yl}-7,9-dione /E/-2-butenedionate

EC Number:

947-290-3

Cas Number:

118286-97-8

Molecular formula:

C21H27N5O2 × C4H4O4

IUPAC Name:

8-azaspiro[4,5]decane-8-{4-[4''-(2'''-pyrimidinyl)-1''-piperazinyl]-butyne/2/-yl}-7,9-dione /E/-2-butenedionate

Test material form:

solid: crystalline

Details on test material:

- Name of test material (as cited in study report): Buspiron XI. fázistermék
- Physical state: white odourless powder
- Lot/batch No.: 1/1992
- Storage condition of test material: room temperature, protected from light

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Species: Rat
- Strain: Wistar
- Sex of animals: female and male rats
- Number of animals: 6 males and 6 females for the treatment group plus 6 males and 6 females in the control group - a total of 24 animals (including control animals)
- Source of test animals: Laboratóriumi Állatokat Tenyésztő és Takarmányellátó Kft. (LATI Kft., 2100 Gödöllő Táncsics Mihály utca 17.)
- Weights of study animals determined at the beginning of the study : 222-264 g (males), 163-185 g (females)

ENVIRONMENTAL CONDITIONS
- Housing conditions: Animals were kept in cages - group-caged by dose
- 6 animals per cage
- Size of boxes: 19.5 x. 43.5 x 29.0 cm
- Bedding: wood shavings
- Temperature in the experimental animal room: 22ºC +/- 3ºC
- Relative humidity: 50-70%
- Lighting: artificial - sequence: 12 hours light, 12 hours dark

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The animals were acclimatised to the laboratory conditions for a week prior to the start of the study.
Before administration of the test chemical, all fur was removed from the dorsal area of the test animals (on approximately 30cm2 of the surface area) by closely clipping.
The animals were treated with the unchanged test material (the test material has not been diluted).
The test chemical was held in contact with the skin with a porous gauze dressing and non-irritating tape (Leukoplast) throughout the 24-hour exposure period - in order to retain the gauze dressing and test chemical and ensure that the animals don't ingest the test chemical.
At the end of the exposure period, residual test chemical was removed, using saline solution (temperature: 37 degrees Celsius).

Duration of exposure:

Single exposure.
Duration: 24 hours.

Doses:

Only one dose was tested in the study (limit dose): 10000 mg/kg body weight).

No. of animals per sex per dose:

Control groups: 6 males, 6 females.
Treatment groups: 6 males, 6 females.

Control animals:

yes

Statistics:

Body weight - mean and standard deviation values.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

approximate LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Remarks:

undiluted substance, limit dose test

Effect levels 2

Key result

Sex:

female

Dose descriptor:

approximate LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Remarks:

undiluted substance, limit dose

Mortality:

No deaths have been observed in the course of the 14-day study.

Clinical signs:

Following the treatment, animals showed no signs of toxicity.
This was true for both the 6-hour period after the treatment, and the whole 14-day observational period of the study.

Body weight:

The body weight value of animals measured on Days 7 and Day 14 did not differ from that of the control groups.
This was true for both male and female test animals.

Gross pathology:

No signs of macroscopic changes were found in post-mortem examinations.

Any other information on results incl. tables

Mortality

Dose (mg/kg body weight)	Mortality - male rats (number of dead animals/number of animals in the group)	Moratlity - female rats (number of dead animals/number of animals in the group)
control	0/6	0/6
10000	0/6	0/6

Clinical signs in the 6 hours following the treatment

Dose (mg/kg body weight)	Clinical signs observed - male rats  (number of animals in which the clinical sign have been observed/number of animals in the group)	Clinical signs observed - female rats  (number of animals in which the clinical sign have been observed/number of animals in the group)
	showed no clinical signs of toxicity	showed no clinical signs of toxicity
control	6/6	6/6
10000	6/6	6/6

Body weight measurements - male rats

Dose group		Body weight prior to treatment (g)	Body weight on Day 7 (g)	Body weight on Day 14 (g)
control	number of data points	6	6	6
	mean	239.8	277.7	298.3
	standard deviation	17.3	20.5	23.1
10000 mg/kg bw	number of data points	6	6	6
	mean	240.8	269.5	297.5
	standard deviation	12.3	10.6	15.7

Body weight measurements - female rats

Dose group		Body weight prior to treatment (g)	Body weight on Day 7 (g)	Body weight on Day 14 (g)
control	number of data points	6	6	6
	mean	179.0	191.2	200.5
	standard deviation	6.1	5.7	6.4
10000 mg/kg bw	number of data points	6	6	6
	mean	174.7	187.7	205.8
	standard deviation	8.4	12.5	14.5

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The substance is not classified for Acute Toxicity (dermal exposure route) according to classification criteria laid down in Regulation EC No 1272/2008.