Bis(isopropyl)naphthalene

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

: TS concentration for induction was slightly below irritation, composition of application media, application volume, method of topical application

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

A non-LLNA test is available that was performed prior to the current data requirements, stipulated in Regulation (EC) No 1907/2006. In accordance with the same Regulation, the data was included to avoid unnecessary testing.

Test material

Test material information

Constituent 1

Reference substance name:

Bis(isopropyl)naphthalene

EC Number:

254-052-6

EC Name:

Bis(isopropyl)naphthalene

Cas Number:

38640-62-9

Molecular formula:

C16H20

IUPAC Name:

bis(isopropyl)naphthalene

Details on test material:

- Name of test material (as cited in study report): RKKO 131006 (provided by Rütgers Kureha Solvents GmbH, Duisburg, Germany)
- Physical state: colorless, transparent, slightly oily liquid
- Analytical purity: no data
- Isomers composition: no data
- Storage condition of test material: at room temperature in the dark

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: Pirbright, Hoe: DHPK (SPF - LAC.) /Boe.

Sex:

not specified

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Lippische Versuchstierzucht Hagemann GmbH & Co. KG, Extertal, Germany
- Age at study initiation: no data
- Weight at study initiation: mean 275 g (262 - 295 g)
- Fasting period before study: no data
- Housing: 5 per cage in Makrolon cages, type IV with bedding of clean soft wood dedusted and sterilized
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): tap water suited for human use from Makrolon drinking bottles, ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2
- Humidity (%): 50 - 85
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

other: water plus emulsifier Cremophor

Induction 2

Concentration / amount:

Induction: 10% TS in vehicle
Challenge: 15% TS in vehicle

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

other: water plus emulsifier Cremophor

Challenge 2

Concentration / amount:

Induction: 10% TS in vehicle
Challenge: 15% TS in vehicle

No. of animals per dose:

20

Details on study design:

RANGE FINDING TESTS: Yes
2 animals/group were treated (single dermal application) with pure test substance and with solutions of 50%, 25%, 20%, and 15% of test substance in vehicle (5 - 6 drops of Chremophor in 10 mL of distilled water)

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 pairs of 3 intradermal injections (0.05 mL test medium) on the right and left side of the back;
2 topical applications (0.5 mL test medium, right and left side of the back)
- Exposure: day 0 and day 7
- Test groups: TS and FCA
- Control group: vehicle and FCA
- Site: shoulder
- Frequency of applications: 2 (intradermal injection and topical application)
- Duration: topical application 48 h, application sites (right and left) were covered with gauze pads and wrapped with Elastoplast (occlusive dressing)
- Concentrations: intradermal injection, test group: 10% TS in vehicle; 10% TS in FCA; 1:1 vehicle/FCA
controls: pure vehicle, pure FCA, 10% vehicle in FCA
topical application, test group and controls: 10% TS in vehicle (one side), pure vehicle (other side)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: test day 28
- Exposure period: 24 h
- Test groups: TS and vehicle
- Control group: TS and vehicle
- Site: flanks
- Concentrations: 15% TS in vehicle (left flank), pure vehicle (right flank); 0.5 mL of test medium were administered to the application sites.
Then the sites were covered with gauze pad and wrapped with occlusive dressing.
- Evaluation (hr after challenge): 24 h and 48 h

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

15% in vehicle

No. with + reactions:

17

Total no. in group:

20

Clinical observations:

no findings reported grading score (mean): 0.58

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 15% in vehicle. No with. + reactions: 17.0. Total no. in groups: 20.0. Clinical observations: no findings reported grading score (mean): 0.58.

Results 2

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

15% TS in vehicle

No. with + reactions:

7

Total no. in group:

20

Clinical observations:

no findings reported grading score (mean): 0.23

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: concurrent control. Dose level: 15% TS in vehicle. No with. + reactions: 7.0. Total no. in groups: 20.0. Clinical observations: no findings reported grading score (mean): 0.23.

Results 3

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

15% in vehicle

No. with + reactions:

18

Total no. in group:

20

Clinical observations:

no findings reported grading socre (mean): 1.13

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 15% in vehicle. No with. + reactions: 18.0. Total no. in groups: 20.0. Clinical observations: no findings reported grading socre (mean): 1.13.

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

15% TS in vehicle

No. with + reactions:

20

Total no. in group:

20

Clinical observations:

no findings reported grading score (mean): 0.75

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: concurrent control. Dose level: 15% TS in vehicle. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: no findings reported grading score (mean): 0.75.

Results 5

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

see below

No. with + reactions:

0

Total no. in group:

0

Remarks on result:

other:

Remarks:

No postiive control was inlcuded in the study

Any other information on results incl. tables

Range-finding test

The dermal treatment induced slight erythema down to a 20-% dilution. A 15-% dilution exhibited no primary irritation.

 

Main study

The test group as well as the control group showed erythema after 24 and 48 h, with scores ranging predominantly from 0.5 (slight, irregular erythema) to 1 (slight, continuous erythema) and 2 (moderate erythema).

 

There was no significant difference between test and control group.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

In a guinea pig maximization test similar to OECD TG 406, slight erythemas were induced after challenge exposure in control as well as in test group animals. There was no significant difference between control and test group. Thus, the test substance diisopropylnaphthalene is assessed to be not sensitizing.