7,8,9,10-Tetrahydro-8-(trifluoroacetyl)-6,10-methano-6H-pyrazino[2,3-h][3]benzazepine

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

8 November - 22 November 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,2,2-trifluoro-1-{5,8,14-triazatetracyclo[10.3.1.0²,¹¹.0⁴,⁹]hexadeca-2,4,6,8,10-pentaen-14-yl}ethan-1-one

EC Number:

810-682-9

Cas Number:

230615-70-0

Molecular formula:

C15H12F3N3O

IUPAC Name:

2,2,2-trifluoro-1-{5,8,14-triazatetracyclo[10.3.1.0²,¹¹.0⁴,⁹]hexadeca-2,4,6,8,10-pentaen-14-yl}ethan-1-one

Test material form:

solid: particulate/powder

Details on test material:

Buff coloured solid or pale brown powder depending on which batch
Storage conditions: room temperature. in the dark

Specific details on test material used for the study:

Buff coloured solid
Storage conditions: room temperature in the dark
Batch number: 53650-10-11

Test animals

Species:

rat

Strain:

other: Sprague-Dawley CD (Cri: CD (SD) IGS BR)

Sex:

male/female

Details on test animals or test system and environmental conditions:

After an acclimatisation period of at least five days the animals were selected at random and given a unique number. At the start of the study the animals weighed 230 to 298g. and were approximately eight weeks of age. The animals were housed in suspended polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study. Free access to drinking water and food was allowed throughout the study. The temperature and relative humidity were set to achieve limits of 19 to 25°C and 30 to 70% respectively.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

The appropriate amount of test material, moistened with distilled water, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area). A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive
bandage. The animals were caged individually for the 24-hour exposure period. Shortly after dosing the dressings were examined to ensure that they were securely in place. After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material. The animals were returned to group housing for the remainder of the study period.

The animals were observed for deaths or overt signs of toxicity 1/2. 1. 2 and 4 hours after dosing and subsequently once daily for fourteen days. Morbidity/mortality checks were made twice daily during normal working days and once daily at weekends and public holidays. After removal of the dressings and subsequently once dail3, for fourteen days. the test sites were examined for evidence of primary irritation and scored according to the following scale from Draize J H.

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

A group of ten rats (five males and five females)

Control animals:

no

Details on study design:

EVALUATION OF SKIN REACTIONS
Erythema and Eschar Formation Value
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to
slight eschar formation (injuries in depth) 4

Oedema Formation
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area
well-defined by definite raising) 2
Moderate oedema (raised
approximately 1 millimetre) 3
Severe oedema (raised more than
1 millimetre and extending beyond
the area of exposure) 4

Any other skin reactions, if present were also recorded.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

There were no deaths.

Clinical signs:

other: There were no signs of systemic toxicity.

Other findings:

Dermal Reactions
There were no signs of dermal irritation.

Necropsy
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

There were no deaths in any animal throughout the study following a single dermal application of CP-548,507 to a groupd of ten rats (five males and five females) at a dose level of 2000 mg/kg bodyweight.

Executive summary:

The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD (Crl: CD (SD) IGS BR) strain rat was found to be greater than 2000 mg/kg bodyweight. The test material does not meet the criteria for classification and will not require labelling for dermal toxicity in accordance with EU labelling regulations Commission Directive 93/21/EEC and does not meet GHS criteria.