2-ethoxy-2,6,6-trimethyl-9-methylenebicyclo[3.3.1]nonane

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Buehler, E.V., Arch. Dermatol. 91, 171, 1965 (updated by Buehler, E.V. and Ritz, H.L., Current Concepts in Cutaneous Toxicity, pp 215-40, 1980.

GLP compliance:

yes (incl. QA statement)

Type of study:

Buehler test

Justification for non-LLNA method:

LLNA not available at the time of testing.

Test material

Test material information

Constituent 1

Reference substance name:

rel-(1R,2R,5S)-2-ethoxy-2,6,6-trimethyl-9-methylenebicyclo[3.3.1]nonane

Cas Number:

125673-86-1

Molecular formula:

C15H26O

IUPAC Name:

rel-(1R,2R,5S)-2-ethoxy-2,6,6-trimethyl-9-methylenebicyclo[3.3.1]nonane

Constituent 2

Reference substance name:

rel-(1R,2S,5S)-2-ethoxy-2,6,6-trimethyl-9-methylenebicyclo[3.3.1]nonane

Molecular formula:

C15H26O

IUPAC Name:

rel-(1R,2S,5S)-2-ethoxy-2,6,6-trimethyl-9-methylenebicyclo[3.3.1]nonane

impurity 1

Reference substance name:

4-(2,6,6-trimethyl-2-cyclohexen-1-yl)butan-2-one

EC Number:

250-657-4

EC Name:

4-(2,6,6-trimethyl-2-cyclohexen-1-yl)butan-2-one

Cas Number:

31499-72-6

Molecular formula:

C13H22O

IUPAC Name:

4-(2,6,6-trimethylcyclohex-2-en-1-yl)butan-2-one

Test material form:

liquid

Specific details on test material used for the study:

Test item: ST 50 C 85 (ST 50 C 85 corresponds to the substance with CAS Nr 68845-00-1 and EC Nr 272-447-1 Boisiris)
Aspect: clear colourless liquid

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

Female guinea pigs of the Dunkin-Hartley strain were supplied by D.Hall, Darley Oakes, Burton-on-Trent, Staffordshire, England. After arrival at the testing facilities the animals were allowed an acclimatisation period of 17 days.

The animals were housed in groups of five in grid bottomed polypropylene cages and identified, within the cage, by ear marking. A commercially available pelleted diet with additional vitamin C and tap water containing 0.01 % vitamin C were provided ad libitum.

The animal room was air conditioned, set to maintain a temperature within the range 17 - 25 °C. Artificial lighting by fluorescent tubes was set to an artificial cycle of twelve hours light/twelve hours dark.

Study design: in vivo (non-LLNA)

Details on study design:

Dose range finding
The primary irritancy of the test material was determined by an initial study in four guinea pigs. The day before dosing the backs and flanks, the animals were clipped free of fur. Four concentrations of the test material (100%, 50%, 25% and 12.5%) were used. The dilutions were prepared using ethanol. Each concentration rotated on each animal (two either side of the mid line) and the relative position of each concentration roated on each animal to minimise any variation in response arising from different skin locations.
The material was applied by soaking a 20 mm square of surgical lint with 0.5 ml of the material and placing this onto the selcted site. The lint was held in position by a length of 'Blenderm' surgical tape which acted as an impermeable barrier. This assembly was secured to the animal using a length of 'Elastoplast' elastic adhesive bandage. The patch assemblies were removed after six hours. 24 and 48 hours after dosing commenced, the treatment sites were examined for erythema and oedema.

Main study
The left shoulder of the ten test animals was clipped free of fur. The following day (Day 1 of the study) a 20 mm square of surgical lint was soaked with 0.5 ml of the undiluted test material and placed onto the prepared skin. The site was covered by a length of 'Blenderm' surgical tape and this was secured by wrapping the animal with a length of 'Elastoplast' elastic adhesive bandage. The dressings remained in place for six hours. This dosing procedure was repeated at weekly intervals on days eight and fifteen.

Main study - Challenge Procedure
On day 28 of the study the right flank of the animals in both test and control groups was clipped free of fur. The following day (Day 29) all animals of both groups were dosed with 0.5 ml of the undiluted test material and 0.5 ml a 50 % concentration of test material. Each concentration was applied to a 20 mm square surgical lint patch. The patches were secured to the right flank in the same manner as described for the induction procedure and remained in position for six hours. 24 and 48 hours after dosing commenced each treatment site was examined and scored.

The following scoring scale was used to describe any observed response:

0 = No reaction
0.5 = Very faint erythema, non confluent
1 = Faint erythemam usually confluent
2 = Moderate erythema
3 = Strong erythema, with or without oedema

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

4

Clinical observations:

None

Remarks on result:

no indication of skin sensitisation

Results 2

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

4

Clinical observations:

None

Remarks on result:

no indication of skin sensitisation

Any other information on results incl. tables

No visible response was exhibited by any animal of the test or control group when chalenged with the undiluted material and a 50 % concentration of the material in ethanol.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

From the results of this study there was no evidence to suggest that the test material acts as a sensitiser in the guinea pig.

Executive summary:

Boisiris is not a skin sensitiser.