Registration Dossier

Toxicological information

Skin sensitisation

Currently viewing:

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:
other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Acceptable study that followed sound scientific principles.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2,4,4-trimethylpentene (also known as diisobutylene and diisobutene)
- Physical state: clear, colourless liquid
- Analytical purity: 95.19%
- Lot/batch No.: Batch No. 2 (a 50:50 mixture of two original batches of 2,4,4-trimethylpentene - Batch No. R11 supplied by Shell and Batch No. 155833 supplied by Erdolchemie).
- Expiration date of the lot/batch: 29 April 1997
- Storage condition of test material: Under nitrogen, protected from light, in a cool store.

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall, Darley Oaks, Newchurch, Burton on Trent, Staffordshire, England
- Age at study initiation: 6-8 weeks old
- Weight at study initiation: 329-394 g (males); 303-372 g (females)
- Housing: No more than 5/sex/cage in stainless steel cages
- Diet: Guinea pig F D I (Special Diets Services Limited, Witham, Essex, England) ad libitum
- Water: Tap water ad libitum
- Acclimation period: between 6-16 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-24°C
- Humidity: 41-74%
- Air changes: 10/hour
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 3 June 1996 To: 4 July 1996

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
paraffin oil
Concentration / amount:
50% v/v for intradermal injections and 100% (as supplied) for epicutaneous application
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
50% v/v for intradermal injections and 100% (as supplied) for epicutaneous application
No. of animals per dose:
10/sex (test group) 5/sex (negative control group)
Details on study design:
RANGE FINDING TESTS: A primary skin irritation screen was used to determine the concentration of test material used during the main study. The maximum practicable concentration of the test material in the chosen vehicle was taken as 50% v/v for injection administration and as supplied (100%) for topical applications.

MAIN STUDY
A. INDUCTION EXPOSURE
Three pairs of intradermal injections of Freunds Complete Adjuvant, 50% v/v 2,4,4-trimethyl pentene in paraffin oil and 50% v/v 2,4,4,-trimethyl pentene in the adjuvant were made on Day 1.
Seven days later the same area of skin was treated by topical application of 2,4,4-trimethyl pentene as supplied and the test site was covered by an occlusive dressing for 48 hours.
The same induction procedures were carried out on a contemporaneous control group of five male and five female animals, except that the test material was replaced by vehicle in all doses.

B. CHALLENGE EXPOSURE
On Day 22, all animals were challenged by occluded application of paraffin oil to the left flank and 75% and 30% v/v 2,4,4-trimethyl pentene in paraffin oil to two sites on the right flank. The occlusive dressings were removed on the following day and the condition of the test sites was assessed approximately 24 and 48 hours later.
Challenge controls:
The same induction procedures were carried out on a contemporaneous control group of five male and five female animals, except that the test material was replaced by vehicle in all doses.
Challenge was identical as for test animals.

Study design: in vivo (LLNA)

Positive control substance(s):
not specified
Statistics:
Not applicable

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
75%
No. with + reactions:
6
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 75%. No with. + reactions: 6.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
75 %
No. with + reactions:
9
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 75 %. No with. + reactions: 9.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
75%
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 75%. No with. + reactions: 1.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
75%
No. with + reactions:
3
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 75%. No with. + reactions: 3.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
30%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 30%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
30%
No. with + reactions:
3
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 30%. No with. + reactions: 3.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
30%
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: 30%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
30%
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 30%. No with. + reactions: 1.0. Total no. in groups: 10.0.

Any other information on results incl. tables

Intradermal injection of 50% v/v 2,4,4-trimethyl pentene in adjuvant gave rise to moderate erythema, pallor and eschar formation; no dermal reaction resulted from a similar administration of 50% v/v 2,4,4-trimethyl pentene in paraffin oil.

Occluded topical application of 2,4,4-trimethyl pentene as supplied caused slight erythema and exfoliation.

Challenge application of 75% v/v 2,4,4-trimethyl pentene in paraffin oil gave rise to a positive response (slight erythema or a more marked reaction) in nine test and three control animals.

Challenge application of 30% v/v 2,4,4-trimethyl pentene in paraffin oil caused a positive response in three test animals and one control animal. Challenge application of paraffin oil alone caused a positive response in four test animals.

A significant response (a reaction more severe than the most marked amongst the controls) was evident in three test animals following challenge application of 75% v/v 2,4,4-trimethyl pentene in paraffin oil and in no test animals following challenge application of the 30% formulation.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Repeated administration of 2,4,4-trimethyl pentene had, at most, a low potential to cause delayed contact hypersensitivity in guinea-pigs. It does not require classification as a dermal sensitizer according to the EU classification system.
Executive summary:

The delayed contact hypersensitivity potential of 2,4,4 -trimethylpentene was assessed in guinea pigs in a Magnusson-Kligman Maximisation test. Under the conditions of this study, repeated administration of 2,4,4-trimethyl pentene had, at most, a low potential to cause delayed contact hypersensitivity in guinea-pigs. The incidence of significant response was below the EEC limit value (30%) to classify the test material as a dermal sensitizer.