Tricyclodecanedimethanol

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 9 DEC 1980 to 2 JAN 1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with marginal deviations; number of test animals restricted to 10; no data on purity of test substance.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Principles of method if other than guideline:

The study is a pre-guideline study following the experimental procedure of Magnusson and Kligman (J. Invest. Derm. 1969, 52, 268-276).
.

GLP compliance:

no

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The method used is equivalent to the Guinea Pig Maximisation Test (GPMT) of OECD Guideline 406 (Skin Sensitisation)

Test material

Test material information

Constituent 1

Reference substance name:

Tricyclodecanedimethanol

EC Number:

248-096-5

EC Name:

Tricyclodecanedimethanol

Cas Number:

26896-48-0

Molecular formula:

C12H20O2

IUPAC Name:

[3-(hydroxymethyl)tricyclo[5.2.1.0²,⁶]decan-8-yl]methanol

Details on test material:

- Name of test material (as cited in study report): TCD - Alkohol DM
- Physical state: viscous liquid
- Analytical purity: no data
- Stability under test conditions: no data
- Storage condition of test material: no data

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Tuck and Sons Limited, Battlesbridge, Essex, England
- Age at study initiation: no data
- Weight at study initiation: 300 - 450 g
- Fasting period before study: no data
- Housing: in groups of 5 animals in solid floor polypropylene cages furnished with softwood sawdust
- Diet (e.g. ad libitum): guinea pig diet, J. Waring (Feeds) Limited, Shardlow, Derbyshire, England, supplemented with a daily ration of hay together with vitamin C tablets (Redoxon 200, Roche Products Limited) dissolved in the drinking water.
- Water (e.g. ad libitum): yes
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 ± 3°C
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 10 /14

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

other: isopropyl alcohol

Induction 2

Concentration / amount:

Intradermal induction:
- 0.1 mL FCA
- 0.1 mL of 5% test substance in isopropyl alcohol
- 0.1 mL of 5% test substance in isopropyl alcohol emulsified in FCA

Epicutaneous induction:
- pure test substance

Challenge exposure:
- pure test substance

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

other: isopropyl alcohol

Challenge 2

Concentration / amount:

Intradermal induction:
- 0.1 mL FCA
- 0.1 mL of 5% test substance in isopropyl alcohol
- 0.1 mL of 5% test substance in isopropyl alcohol emulsified in FCA

Epicutaneous induction:
- pure test substance

Challenge exposure:
- pure test substance

No. of animals per dose:

10

Details on study design:

RANGE FINDING TESTS
Intradermal injection
Four simultanous intrademal injections with 0.1 mL of a solution of 1% and 5% test substance in isopropyl alcohol were examined (one test animal for each concentration). Observations were made 24, 48, and 72 hours and 7 days following treatment.

Topical application
Test material at two concentration (100% and 50% test substance in petrolatum) was topically applied under an occlusive patch to four sites on the shaved backs of four test animals. Each animal was treated with both concentrations and had previously been intradermally injected with Freud Complete Adjuvant.The degree of irritancy at the test sites were evaluated for erythema immediately after removal of the patches and then at 24 and 48 hours.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous)
- Exposure period: epicutaneous induction: 48 hrs, occlusive application
- Test groups: TS in vehicle and TS with vehicle in FCA
- Control group: only vehicle and vehicle in FCA (no TS)
- Site: area measuring 4 x 6 cm in the shoulder region
- Frequency of applications: epicutaneous induction 7 days after intradermal induction
- Duration: 0-9 days
- Concentrations: same throughout see above under Concentration

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 21 (14 days after topical induction)
- Exposure period: 24 hrs
- Test groups: TS
- Control group: TS
- Site: flank of animals
- Concentrations: 100% test substance, occlusive application
- Evaluation (hr after challenge): 48 and 72 hours after start of challence (24 and 48 hours after removal of the patches)

OTHER
24 hours before epicutaneous induction, the exposure area was pretreated with 10% sodium lauryl sulfate in petrolatum.
Effects of the challenge exposure were graded according to Magnusson and Kligman 1969.

Challenge controls:

A group of 5 animals received similar treatment to the test group except that the test material vehicle alone was used, instead of the test material, at the Intradermal and Topical Induction stages.

Positive control substance(s):

no

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

pure test substance

No. with + reactions:

1

Total no. in group:

10

Clinical observations:

scattered mild redness

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: pure test substance. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: scattered mild redness.

Results 2

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

pure test substance

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: pure test substance. No with. + reactions: 0.0. Total no. in groups: 10.0.

Any other information on results incl. tables

One animal of the test group showed scattered mild redness (score 1) at the challenge site at the 24 hour reading. No reaction was observed in the controls.

As no reaction was observed in the control animals, the authors attributed this effect to contact sensitization.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The authors regarded the test material to be a mild (Grade II) contact sensitizer in the guinea pig. However, only a small number of test animals (10) was used and only 1/10 animals showed a marginal reaction.

Executive summary:

In a dermal sensitization study with octahydro-4,7-methano-1H-indenedimethanol (TCD Alkohol DM), ten female Dunkin-Hartley guinea pigs were tested using the method of Magnusson and Kligman (equivalent to OECD Test Guideline 406 - Skin Sensitization).

 

One of ten tested animals showed scattered mild redness (score 1) at the challenge site at 48 hours but not any longer at 72 hours after start of challenge exposure (Collier/Safepharm, 1981b).

 

In this study, octahydro-4,7-methano-1H-indenedimethanol (TCD Alkohol DM) is not a dermal sensitizer according to EU Legislation.

 

This dermal sensitization study is acceptable and satisfies the guideline requirement for a skin sensitization study (OECD 406).