3,4,5,6,7,8,9,10,11,12,13,14-dodecahydro-2H-cyclododeca[b]pyran

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 1984-09-18 and 1984-10-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP test

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: "Approved Code of Practice: Methods for determination of toxicity" to comply with the Notification of New Substances Regulations 1982

Test guideline 2

Qualifier:

no guideline available

Principles of method if other than guideline:

The test method is based on that originally described by Magnusson B. and Kligman A.M., J. Invest. Derm. 1969, 52, 268-276 with modifications as indicated in the U.K. Health and Safety Commission publication "Approved Code of Practice: Methods for determination of toxicity" to comply with the Notification of New Substances Regulations 1982.

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Test material

Test material information

Constituent 1

Reference substance name:

3,4,5,6,7,8,9,10,11,12,13,14-dodecahydro-2H-cyclododeca[b]pyran

EC Number:

251-090-5

EC Name:

3,4,5,6,7,8,9,10,11,12,13,14-dodecahydro-2H-cyclododeca[b]pyran

Cas Number:

32539-83-6

Molecular formula:

C15H26O1

IUPAC Name:

2H,3H,4H,5H,6H,7H,8H,9H,10H,11H,12H,13H,14H-cyclododeca[b]pyran

Details on test material:

- Name of test material (as cited in study report): DDP
- Substance type: active
- Physical state: clear liquid
- Isomers composition: no isomers
- Stability under test conditions: no data
- Storage condition of test material: ambient temperature

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 & Sons Ltd., Battlesbridge, Essex
- Age at study initiation: five to eight weeks
- Weight at study initiation: 297-375g
- Housing:in groups of up to four in solid-floor polypropylene cages and furnished with softwood shavings
- Diet (e.g. ad libitum): Guinea Pig FD1 Diet saupplied ad libitum
- Water (e.g. ad libitum): mains tap water, supplied ad libitum.
- Acclimation period: minimum period of five days prior to the start of the study


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.5±2.5°C
- Humidity (%): 60-70 %RH recorded daily, but not controlled
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 hrs/12hrs


IN-LIFE DATES: no data

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

arachis oil

Induction 2

Concentration / amount:

Intradermal induction: 5% in arachis oil B.P.
Topical Induction: 100% undiluted
Topical Challenge: 100% undiluted

Challenge

Challenge 1

Route:

intradermal and epicutaneous

Vehicle:

arachis oil

Challenge 2

Concentration / amount:

Intradermal induction: 5% in arachis oil B.P.
Topical Induction: 100% undiluted
Topical Challenge: 100% undiluted

No. of animals per dose:

Preliminary test: 2 animals for the intradermal injection; 2 animals for the topical application
Main Test: 20 animals + 10 animals for the control

Details on study design:

RANGE FINDING TEST: (to determine its primary cutaneous irritation and systemic toxicity properties)
- No. of exposures: 2
- Test groups: 2, one for intradermal injection, one for topical application
- Control group: no
- Site: Intradermal injection: shoulder region, topical application: both flanks of 2 guinea pigs (which have been intradermally injected with Freunds complete adjuvant between one and three weeks previously)
- Frequency of applications: once
Duration: topical application: patches left in position for 24hours
- Observation: intradermal injection: animals observed 24, 48, 72 hours and 7 days following treatment; topical application: animals observed 1hour following removal of the patches, and 24h and 48hours later
- Concentrations: intradermal injection: 1% and 5% (both in Arachis oil B.P.), topical application: 50% (in Petroleum Jelly B.P.) and 100%


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3*2 injections (for maximisation) in day0
- Exposure period: -
- Test groups:
- Control group: yes, 10 animals
- Site: area measuring 4cm * 6cm in the shoulder region
- Frequency of applications: Intradermal injection: only one in day0; Topical applications: only one in day21
- Duration: Topical applications: 24 hours
- Concentrations: (day0) 0.1 ml of Freunds complete adjuvant, 0.1 ml of 5% of test material, 0.1 ml of 50:50 of a 5% concentration of the test material emulsified in the adjuvant


B. CHALLENGE EXPOSURE
- No. of exposures: only one
- Day(s) of challenge: one day
- Exposure period: Topical applications: (day 7) patches for 48h
- Test groups: one group of 20 animals
- Control group: one group of 10 animals
- Site: an area meauring 5cm * 5cm on both flanks
- Concentrations: 100%
- Evaluation (hr after challenge): (21hours following removal of the patches the area was clipped) at 48 hours and 72 hours the reactions were observed at the test material and vehicle control sites


OTHER:

Challenge controls:

One group of 10 female guinea pigs, received in the shoulder the induction: 0.1 ml of Freunds complete adjuvant alone, 0.1 ml of vehicle alone, 0.1 ml of 50:50 of a vehicle emulsified in the adjuvant. As induction, a patch was applied with the vehicle alone to the shoulder of the 10 guinea pigs. As challenge, at the right flank each animal received an occlusive patch with the test material at the highest not-irritant concetrantion (100%) ; an occlusive patch with the vehicle alone was applied to the clipped left flank.

Positive control substance(s):

no

Study design: in vivo (LLNA)

Vehicle:

other: arachis oil B.P.

Concentration:

Intradermal Induction: 5% in arachis oil B.P.
Topical induction: 100% undiluted
Topical challenge: 100% undiluted

No. of animals per dose:

20 animals received the substance + adjuvant
10 animals received adjuvant, vehicle alone, vehicle + adjuvant

Details on study design:

20 animals received simultaneously in different area 0.1ml of Freunds complete adjuvant, 0.1 ml of 5% test material, 0.1 ml of a 50:50 mixture of a 5% concentration of the test material emulsified in the adjuvant
10 animals received simultaneously 0.1ml of Freunds complete adjuvant, 0.1 ml of vehicle alone, 0.1 ml of a 50:50 mixture of vehicle emulsified in Freunds complete adjuvant

Positive control substance(s):

not specified

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

The test material DDP was found to be a non-sensitizer in the guinea pig.

Executive summary:

Introduction

This study was performed according toSafepharmStandard Protocol Number GM 09/83/856B and was designed to assess the contact sensitization potential of the test material.

Methods

Before commencing the Main Study a preliminary screen was carried out on the test material in order to determine its primarycutaneousirritation and systemic toxicity properties following both topical application andintradermalinjection.

The test method is based on that originally described by Magnusson B. andKligmanA.M., J. Invest.Derm.1969, 52, 268-276 with modifications as indicated in the U.K. Health and Safety Commission publication "Approved Code of Practice: Methods for determination of toxicity" to comply with the Notification of New Substances Regulations 1982.

Thirty-six female, albino Dunkin-Hartley guinea pigs were treated byintradermalinjection in the shoulder region with Freund's Complete Adjuvant, the test material and vehicle and a mixture of Freund's Complete Adjuvant and the test material. Seven days later this induction procedure was boosted by topical application of the test material over the injection site. A second group of ten guinea pigs was similarly treated but test material was substituted with vehicle alone at the injection stage and for the topical application. Two weeks after this induction phase all animals of both test and control groups were challenged with two concentrations of the test material which were applied topically to the flanks.

Results

With the result of the preliminary screen Table 1 and 2 of the attached "Background material", a concentration of 100% undiluted test material for Topical Induction and Topical Challenge was chosen.

As it is indicated in table 3 of the attached "Background material", no reactions were observed at the test material or vehicle control sites of any of the Experimental Control Group guinea pigs at either the 24 or 48 hour readings.

The test material therefore produced a 0% (0/20) sensitization rate and is classified as  NON-SENSITIZER according to DSD (67/548/EEC) and CLP (1272/08/EEC).