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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1994-11-28 to 1994-12-31
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified reliable without restriction. The study was conducted according to OECD 406 Guidelines and adhered to GLP recommendations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study conducted prior to the implementation of the LLNA method.

Test material

Constituent 1
Reference substance name:
1-dodecene dimer, hydrogenated
IUPAC Name:
1-dodecene dimer, hydrogenated
Details on test material:
- Substance type: 1-dodecene dimer, hydrogenated
- Physical state: liquid, clear colourless
- Lot/batch No.: C1527-04-2
- Storage condition of test material: Room 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: David Hall Limited, Staffordshire, U.K.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 345-450 grams
- Housing: Singly or in pairs in polypropylene cages
- Diet (e.g. ad libitum): Guinea Pig FDI Diet., Special Diets Services Limited, Essex, U.K. ad libitum
- Water (e.g. ad libitum): Mains tap water ad libitum
- Acclimation period: 5 Days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22˚C
- Humidity (%): 50%-67%
- Air changes (per hr): 15 per hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light

IN-LIFE DATES: From: 1994-11-28 To: 1994-12-31

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
arachis oil
Remarks:
Dried Arachis Oil B.P.
Concentration / amount:
Intradermal Induction: 25% w/v in dried arachis oil B.P.
Topical Induction: undiluted as supplied
Topical Challenge: undiluted as supplied and 75% w/v in dried arachis oil B.P.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Remarks:
Dried Arachis Oil B.P.
Concentration / amount:
Intradermal Induction: 25% w/v in dried arachis oil B.P.
Topical Induction: undiluted as supplied
Topical Challenge: undiluted as supplied and 75% w/v in dried arachis oil B.P.
No. of animals per dose:
30 animals (20 test and 10 control)
Details on study design:
RANGE FINDING TESTS:

Selection of Concentration for Intradermal Induction:

Four animals were intradermally injected with preparations of the material (25%, 10%, 5% or 1% w/v in dried arachis oil B.P). The highest concentration that caused only mild to moderate skin irritation and was well tolerated systemically, was selected for the intradermal induction stage of the main study.

Selection of Concentration for Topical Induction:

Two guinea pigs (intradermally injected with Freund's Complete Adjuvant nine days earlier) were treated with the undiluted test material and three preparations of the test material (75%, 50% and 25% w/v in dried arachis oil B.P). The highest concentration producing only mild to moderate dermal irritation after a 48-hour occlusive exposure, was selected for the topical induction stage of the main study.

Selection of Concentration for Topical Challenge:

The undiluted test material and three preparations of the test material (75%, 50% and % 25% w/v in dried arachis oil B.P.) were applied occlusively to the flanks of two guinea pigs for a period of 24 hours. The highest non-irritant concentration of the test material and one lower concentration were selected for the topical challenge stage of the main study.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (1 intradermal followed by topical)
- Exposure period: single injection; topical exposure - 48 hours
- Test groups: Induction:Freund's Complete Adjuvant plus distilled water in the ratio 1:1; 25% w/v formulation of test material in dried arachis oil B.P.; 25% w/v formulation of test material in a 1:1 preparation of Freund's Complete Adjuvant plus distilled water. Topical: Undiluted test material.
- Control group: Freund's Complete Adjuvant plus distilled water in the ratio 1:1; dried arachis oil B.P.; 50% w/v formulation of dried arachis oil B.P. in a 1:1 mixture v/v of Freund's Complete Adjuvant/distilled water. Topical: Nothing applied.
- Site: Intradermal Induction : Shoulder Region; Topical Induction: Shoulder region
- Frequency of applications: Single intradermal injection followed 7 days later by topical induction.
- Duration: Topical: 48 hours
- Concentrations: Intradermal - 25% w/v; Topical - Undiluted

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 21
- Exposure period: 24 hours
- Test groups: 1) Undiluted 2) 75% w/v in Arachis Oil
- Site: shorn right flank of each animal
- Concentrations: 1) Undiluted 2) 75% w/v in Arachis Oil
- Evaluation (hr after challenge): 24
Positive control substance(s):
yes
Remarks:
α-hexylcinnamaldehyde; 2-mercaptobenzothiazole; Ethyl 4-aminobenzoate; 2,4-Dinitrochlorobenzene

Results and discussion

Positive control results:
Results displayed in Table below.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
100% and 75% in Arachis Oil B.P.
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No evidence of erythema or edema observed
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: other: Control. Dose level: 100% and 75% in Arachis Oil B.P.. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No evidence of erythema or edema observed.
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100% and 75% in Arachis Oil B.P.
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No evidence of erythema of edema observed
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100% and 75% in Arachis Oil B.P.. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No evidence of erythema of edema observed.
Reading:
1st reading
Hours after challenge:
48
Group:
positive control
Dose level:
100% and 75% in Arachis Oil B.P.
No. with + reactions:
7
Total no. in group:
10
Clinical observations:
For α-hexylcinnamaldehyde
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 100% and 75% in Arachis Oil B.P.. No with. + reactions: 7.0. Total no. in groups: 10.0. Clinical observations: For α-hexylcinnamaldehyde.

Any other information on results incl. tables

INDIVIDUAL SKIN REACTIONS IN TEST ANIMALS AT CHALLENGE

CHALLENGE CONCENTRATIONS: 100% AND 75% w/v VEHICLE: DRIED ARACHIS OIL B.P.

Animal #

Skin Reactions (Hours after Removal of Dressing)

24 hours

48 hours

100%

75%

100%

75%

Erythema

Edema

Erythema

Edema

Erythema

Edema

Erythema

Edema

1

0

0

0

0

0

0

0

0

2

0

0

0

0

0

0

0

0

3

0

0

0

0

0

0

0

0

4

0

0

0

0

0

0

0

0

5

0

0

0

0

0

0

0

0

6

0

0

0

0

0

0

0

0

7

0

0

0

0

0

0

0

0

8

0

0

0

0

0

0

0

0

9

0

0

0

0

0

0

0

0

10

0

0

0

0

0

0

0

0

11

0

0

0

0

0

0

0

0

12

0

0

0

0

0

0

0

0

13

0

0

0

0

0

0

0

0

14

0

0

0

0

0

0

0

0

15

0

0

0

0

0

0

0

0

16

0

0

0

0

0

0

0

0

17

0

0

0

0

0

0

0

0

18

0

0

0

0

0

0

0

0

19

0

0

0

0

0

0

0

0

20

0

0

0

0

0

0

0

0

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
1-dodecene dimer, hydrogenated produced a sensitization rate of 0% (0/20). Based on the results of this study, 1-dodecene dimer, hydrogenated is not considered to be a skin sensitizer in the guinea pig.
Executive summary:

In a guinea pig maximization test (Driscoll, R., 1995; Klimisch score = 1), 38 albino female Dunkin Hartley guinea pigs were dermally exposed to 1-dodecene dimer, hydrogenated. Following a preliminary screening study, concentrations of 25% w/v in dried Arachis Oil B.P. were selected for the intradermal injection during the induction phase. Topical induction was also conducted in this study and the test material was administered as supplied. For the challenge phase concentrations of 100% (undiluted) and 50% w/v in dried Arachis Oil B.P. were topically administered to the guinea pigs two weeks post topical induction. Animals were observed daily for signs of ill health and toxicity. Body weights were recorded individually and dermal reactions to intradermal injections and topical applications during induction and challenge were also observed for. Challenge sites were evaluated 24 and 48 hours after removal of patches.

 

There was no adverse treatment-related effect seen in the animals through the study period. Bodyweight gains of guinea pigs in the test group, between Day 0 and Day 24, were comparable to those observed in the control group animals over the same period. Well-defined erythema was noted at the intradermal induction sites of all test group animals at the 24 and 48-hour observations. Very slight erythema was noted at the intradermal induction sites of seven control group animals at the 24-hour observation and persisted at the intradermal induction sites of six control group animals at the 48-hour observation. Post topical induction, well-defined erythema was noted at the induction sites of three test group animals with very slight erythema noted at the induction sites of seventeen test group animals at the 1-hour observation. Bleeding at the intradermal injection sites was noted in three test group animals. Very slight erythema was noted at the induction sites of six test group animals at the 24-hour observation. No skin reactions were noted at the treatment sites of the control group animals at the 1 and 24-hour observations. At challenge, for the undiluted test material, no skin reactions were noted at the challenge sites of the test group animals at the 24 and 48-hour observations. Very slight erythema was noted at the challenge site of one control group animal at the 24-hour observation. No skin reactions were noted in the control group animals at the 48-hour observation. At challenge, for the 75% w/v concentration, no skin reactions were noted at the challenge sites of the test and control group animals at the 24 and 48-hour observations.

 

1-dodecene dimer, hydrogenated produced a sensitization rate of 0% (0/20). Based on the results of this study, 1-dodecene dimer, hydrogenated is not considered to be a skin sensitizer in the guinea pig.

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