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

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 November - 26 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

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

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

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

Sixteen female CBA (CBA/CaCruBR) strain mice were supplied by Charles River UK Limited, Margate, Kent, UK. At the start of the study the animals were in the weight range of 17 to 20 g, and were approximately seven to twelve weeks old. After an acclimatisation period of at least five days, each animal was selected at random and given a unique number The animals were housed in groups of four in suspended polypropylene cages fitted with stainless steel mesh lids and furnished with softwood woodflakes. Free access to mains tap water and food was allowed throughout the study. The temperature and relative humidity were controlled to remain within target ranges of 19 to 25°C and 30 to 70% respectively. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06.00 to 18.00) and twelve hours darkness.

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

In a preliminary investigation the test material was found to be soluble at a concentration of 10% w/v in acetone/olive oil 4:1. With consideration of the toxicity of the test material concentrations of 10%. 1% and 0.1% were chosen for the main study.

No. of animals per dose:

Groups of four mice were treated with the test material at concentrations of 0.1, 1 or 10% w/v in acetone/olive oil 4:1. A further group of four mice received the vehicle alone in the same manner.

Details on study design:

Sixteen mice were used, twelve test and four control. The bodyw-eight of each animal was recorded at the start and end of the study.
The mice were treated by daily application of 25 ul of the appropriate concentration of the test material to the dorsal surface of each ear for three consecutive days (Days 0. 1, 2). The test material formulation was administered using an automatic micropipette and spread over the dorsal surface of the ear using the tip of the pipette.
Five days following the first topical application of the test material (Day 5) all mice were injected via the tail vein with 250 p.1 of phosphate buffered saline containing 3H-methyl thymidine (3HTdR: 80 uCi/ml. specific activity 2.0 Ci/mmol. Amersham Pharmacia Biotech UK Ltd) giving a total of 20 uCi to each mouse.

Positive control substance(s):

other: 1-chloro-2,4-dinitrobenzene, 2-Mercaptobenzothiazole, a-hexylcinnamaldehyde, 4-Ethoxymethylene-2-phenyl-2-oxazolin-5-one

Results and discussion

Positive control results:

All seven positive controls had positive reults.

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

other: Test/Control Ratio

Value:

1.24

Test group / Remarks:

Concentration of 0.1

Results 2

Key result

Parameter:

other: Test/Control Ratio

Value:

1.3

Test group / Remarks:

Concentration of 1

Results 3

Key result

Parameter:

other: Test/Control Ratio

Value:

1.16

Test group / Remarks:

Concentration of 10

Any other information on results incl. tables

There were no deaths. No signs of systemic toxicity were noted in the test or control animals throughout the study period. Bodyweiaht changes of the test animals between Day 0 and Day 5 were comparable to those observed in the corresponding control group animals over the same period.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

CP-548,507 test material was considered not to be a moderate to strong sensitiser under the conditions of the test.

Executive summary:

As a result of CP-548,507 not being a moderate to strong sensitiser, it does not meet the GHS criteria.