Propanol, 1(or 2)-[methyl-2-[(1,7,7-trimethylbicyclo[2.2.1]hept-2-yl)oxy]ethoxy]-

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10.03.2006 to 01.06.2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD & EEC guideline study no deviaions GLP

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

470-680-5

EC Name:

-

Cas Number:

958872-63-4

Molecular formula:

C16H30O3

IUPAC Name:

1-[2-({1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl}oxy)propoxy]propan-2-ol; 1-{[1-({1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl}oxy)propan-2-yl]oxy}propan-2-ol; 2-[2-({1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl}oxy)propoxy]propan-1-ol; 2-{[1-({1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl}oxy)propan-2-yl]oxy}propan-1-ol

Details on test material:

- Name of test material (as cited in study report): Dipropylenglykolisobornylether (isomerengemisch)
- Substance type: mixture of isomers
- Physical state: liquid
- Analytical purity: 97.9% (a/a)
- Impurities (identity and concentrations): as submited substance
- Composition of test material, percentage of components: as submited substance
- Isomers composition: as submited substance
- Lot/batch No.: V04/010-13N
- Expiration date of the lot/batch: 01.03.2008
- Storage condition of test material: ambient temperature
- Other: certificate of analysis Nº AZ-212, Clariant GmbH, Analytical services (23.03.2005)

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

Animals were ordered nulliparous and nonpregnant, within the weight range of 250 to 300 grams and 4 to 5 weeks of age. They were
supplied by Harlan Nederland, Kreuzelweg, 53, Horst NL-5960 AD Horst, The Netherlands

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal

Vehicle:

CMC (carboxymethyl cellulose)

Induction 2

Concentration / amount:

Concentration of test material and vehicle used at induction a) intradermal: 0.1 % in 0.5 % carboxy methyl cellulose; b) topical: undiluted test solution
Concentration of test material and vehicle used for each challenge: Undiluted test solution; 5 concentrations (100, 50, 20, 10 and 5% in 0.5% (w/v)
carboxymethylcellulose) of the test item were each dosed in duplicate.

Challenge

Challenge 1

Route:

intradermal

Vehicle:

CMC (carboxymethyl cellulose)

Challenge 2

Concentration / amount:

Concentration of test material and vehicle used at induction a) intradermal: 0.1 % in 0.5 % carboxy methyl cellulose; b) topical: undiluted test solution
Concentration of test material and vehicle used for each challenge: Undiluted test solution; 5 concentrations (100, 50, 20, 10 and 5% in 0.5% (w/v)
carboxymethylcellulose) of the test item were each dosed in duplicate.

No. of animals per dose:

Number of animals in test group: 20
Number of animals in negative control group: 10

Details on study design:

Patches of gauze measuring 20 mm x 20 mm were coated with 0.2 ml aliquots of the undiluted test item. These were placed on the right flank of each animal, of both test and control groups, in the centre of the prepared skin site. The left flank of each animal was similarly treated with patches soaked with 0.2 ml of the vehicle alone (0.5% (w/v) carboxymethylcellulose).

Positive control substance(s):

not required

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:

1

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100 %. No with. + reactions: 1.0. Total no. in groups: 20.0.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

20

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.

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0 %

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0 %. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0 %

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0 %. No with. + reactions: 0.0. Total no. in groups: 10.0.

Any other information on results incl. tables

Maximum concentration not causing irritating effects in preliminary test: 100 %

Signs of irritation during induction: very slight erythema in all of the test animals.

Evidence of sensitisation of each challenge concentration: In connection with the undiluted test solution, one animal from the test group exhibited a very slight erythema after 24 h which had disappeared again after 48 h. The animals from the control group did not exhibit any skin reactions.

The body weights of the animals were considered to be within the normal range of variability.

Other observations: none

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

Under the conditions of the present study, one of the nineteen animals (5.3%) of the treatment group showed a very slight skin response after the challenge procedure. Thus, the percentage of animals reacting positive is below the threshold of 30%. Based of the above mentioned findings Dipropylene glycol isobornyl ether (mixture of isomers) does not cause sensitisation by skin contact according to Commission Directive 67/548/EEC and subsequent revisions.

Executive summary:

The potential of the test item, Dipropylenglykolisobornylether (isomerengemisch), to induce and elicit delayed dermal sensitization was assessed by guinea pig model using the maximization test of Magnusson and Kligman.

The concentration of the test item used in the main study were determined by the resulst of preliminary screening test. The main sensitization test was undertaken using a test group of 20 animals and a control group of 10 animals. In an attempt to induce sensitization, test animals were intradermally injected with an emulsion of Freund's complete adjuvant, the test item at concentration of 0.1 % in the selected vehicle, 0.5% carboxymethylcellulose, and tets item at same concentration in an emulsion of Freund's complete adjuvant.

One week later this was boosted by topical application of the undiluted test item over the injection sites. Control group animals were treated in the same manner but the selected vehicle (0.5% carboxymethylcellulose) wasused in place of the test item. Two weeks after the second induction stage, all animals were challenged by topical application of both the vehicle and the undiluted test item.

At the challenge with the undiluted test item, a very slight response wasapparent in 1 of the 19 animals of the test group (5.3%) at 24 hours examination. No reaction was observed at 48 hours examination. No reaction to th test item was observed in any animal from the control group. No reaction to the vehicle alone was observed in any animal.

Based of the above mentioned findings Dipropylene glycol isobornyl ether (mixture of isomers) does not cause sensitisation by skin contact according to Commission Directive 67/548/EEC and subsequent revisions.