Methoxycarbonyloxycyclooct-4-ene

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April/ May 1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

See below

Principles of method if other than guideline:

Various deviations from the guideline: Limited details on test material; Resting period between induction and challenge is 3 weeks instead of recommended 10-14 days; Contact of test substance with skin 6 hours instead of recommended 48 hours during induction and challenge; Choice of vehicle not justified (same vehicle chosen in induction and in challenge phase); No re-challenge was done. Purity and batch number of test substance not indicated.

GLP compliance:

yes (incl. QA statement)

Type of study:

Buehler test

Justification for non-LLNA method:

An LLNA is not performed because other reliable information is available.

Test material

Test material information

Constituent 1

Reference substance name:

Methoxycarbonyloxycyclooct-4-ene

EC Number:

401-620-8

EC Name:

Methoxycarbonyloxycyclooct-4-ene

Cas Number:

87731-18-8

Molecular formula:

C10H16O3

IUPAC Name:

(1R,3aS,6aS)-octahydropentalen-1-yl methyl carbonate; (1S,3aS,6aS)-octahydropentalen-1-yl methyl carbonate; (3Z)-cyclooct-3-en-1-yl methyl carbonate; (4Z)-cyclooct-4-en-1-yl methyl carbonate; bicyclo[3.2.1]octan-8-yl methyl carbonate

Test material form:

liquid

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Perfection Breeders, Douglasville, Pennsylvania
- Weight at study initiation: 300 - 500 gram
- Housing: two per cage in wire mesh cages
- Diet: Wayne Guinea Pig Diet, ad libitum
- Water: fresh tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: April 23, 1985 To: May 22, 1985

Study design: in vivo (non-LLNA)

Induction

Route:

epicutaneous, occlusive

Vehicle:

other: ethanol/distilled water (4/1)

Concentration / amount:

3%

Challenge

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

other: ethanol/distilled water (4/1)

Concentration / amount:

3%

No. of animals per dose:

Test substance: 20 (10 male and 10 female)

Details on study design:

RANGE FINDING TESTS:
Eight unexposed animals (4 males and 4 females) were exposed to eight concentrations of the test material (0,5%; 1%; 2%; 4%;10%; 25%; 50%; 100%) by the same technique as used for induction exposure. In this test, both sides of the animal were shaved and exposed to eight concentrations of the material. Only 24 hour grades were obtained.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours
- Test groups: Test substance
- Control group: Solvent control and positive control
- Site: Left shoulder; 5x10 cm (appr. 10% of the body surface)
- Frequency of applications: weekly
- Concentrations: Test substance (3%), positive control (0.3%); 0.4 ml/ site
- Site was occluded with Parke-Davis Readi-bandage (R)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: 13 days after last induction
- Exposure period: 6 hours
- Test groups: Test substance,
- Control group: Solvent control, positive control and naive control
- Site: naive site on left side
- Concentrations: 1%
- Evaluation (hr after challenge): 24 and 48
- Site was occluded with Parke-Davis Readi-bandage (R)

Challenge controls:

Solvent control: 10 (5 male and 5 female)
Positive control: 5 (3 males and 2 females)
Naive control (challenge only): 4 (2 males and 2 females)

Positive control substance(s):

yes

Remarks:

1-Chloro-2,4-dinitrobenzene (DNCB) at 0.3%

Results and discussion

Positive control results:

A positive response was elicited in all animals receiving the positive control article.

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

1%

No. with + reactions:

10

Total no. in group:

19

Clinical observations:

slightly patchy erythema (7 animals); slight or confluent or moderate patchy erythema (3 animals)

Results 2

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

1%

No. with + reactions:

8

Total no. in group:

19

Clinical observations:

slightly patchy erythema (7 animals); slight or confluent or moderate patchy erythema (1 animal)

Results 3

Reading:

other: 1st and 2nd reading

Hours after challenge:

24

Group:

negative control

Dose level:

solvent only

No. with + reactions:

2

Total no. in group:

10

Clinical observations:

slightly patchy erythema

Results 4

Reading:

other: 1st and 2nd reading

Hours after challenge:

24

Group:

positive control

Dose level:

0.3%

No. with + reactions:

5

Total no. in group:

5

Clinical observations:

moderate erythema (1 animal); severe erythema with/without edema (4 animals)

Results 5

Reading:

other: 1st and 2nd reading

Hours after challenge:

24

Group:

other: naive

Dose level:

1%

No. with + reactions:

0

Total no. in group:

4

Clinical observations:

none

Any other information on results incl. tables

One animal (f) treated with the test substance died during the course of the study. Necropsy of this animal revealed: hydrothorax, ascites, enlarged spleen and a fluid-filled pericardial sac. The death was determined to be non-compound related.

Number of animals/ dermal Irritation scores at 48 hours after 3rd induction:

Score	Test substance (3%)	Pos. control (0.3%)
no reaction	4	0
slightly patchy erythema	3	0
slight or confluent or moderate patchy erythema	2	0
moderate erythema	5	0
severe erythema with/without edema	6	5

Applicant's summary and conclusion

Interpretation of results:

other: The substance is a skin sensitiser 1B in accordance with EU CLP (1272/2008 and its amendments)

Conclusions:

The substance is a skin sensitiser (1B) in the Buehler test (OECD guideline 406).

Executive summary:

The substance was tested in a Buehler test (OECD TG 406) at a concentration of 3% in the topical induction phase based on the irritancy seen at higher concentrations during a range-finding test. The concentration for the challenge phase was 1%. At the first reading (24 h after the challenge) slightly patchy erythema was observed in 7 animals and slight or confluent or moderate patchy erythema was observed in 3 animals. At the second reading (48 h after the challenge) slightly patchy erythema was observed in 7 animals and slight or confluent or moderate patchy erythema was observed in 1 animal. The clinical observations resulted in a 15.7% sensitised animals which exceeds the threshold of 15%. Based on these results, the substance is a skin sensitiser (1B).