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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1991-07-23 to 1991-09-04
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restrictions because it is in compliance with the OECD principles of GLPs.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report date:
1991

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
Information regarding the nature of the test material was not provided, but was noted to be the responsibility of the Sponsor. This deviation was not expected to affect the study results.
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
yes
Remarks:
Information regarding the nature of the test material was not provided, but was noted to be the responsibility of the Sponsor. This deviation was not expected to affect the study results.
GLP compliance:
yes
Type of study:
other: Not specified, but similar to the Guinea-pig Maximization test method, using Draize dermal scores and Freunds Complete Adjuvant (FCA)
Justification for non-LLNA method:
The sensitisation test used is a scientifically valid method that is equivalent or similar to the Guinea-pig Maximization test method and follows OECD Guideline 406 for assessing skin sensitisation potential. As the data exists and is adequate for hazard assessment, performing a new LLNA test is not scientifically justified.

Test material

Constituent 1
Chemical structure
Reference substance name:
2-methylbutane
EC Number:
201-142-8
EC Name:
2-methylbutane
Cas Number:
78-78-4
Molecular formula:
C5H12
IUPAC Name:
2-methylbutane
Details on test material:
- Name of test material (as cited in study report): MRD-91-964
- Substance type: C5 aliphatic
- Physical state: liquid, colorless
- Analytical purity: information provided by the Sponsor, Exxon Chemical International - Performance Intermediates, Kraainem, Belgium
- Composition of test material, percentage of components: information provided by the Sponsor, Exxon Chemical International - Performance Intermediates, Kraainem, Belgium
- Lot/batch No.: II
- Stability under test conditions: test material is stable up to 6 hours under test conditions
- Storage condition of test material: room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Products, Inc., Denver, Pennsylvania
- Age at study initiation: approximately 6 weeks
- Weight at study initiation: 313 to 416 g
- Housing: individual, suspended stainless steel caging, indirect bedding
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): not reported
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): maintained 18 to 22°C
- Humidity (%): maintained 40 to 70%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hours dark and 12 hours light

IN-LIFE DATES: From: 1991-07-23 to 1991-09-04

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
other: intradermal at day 0 and epicutaneous, occlusive at day 7
Vehicle:
other: ethanol and reverse osmosis water
Concentration / amount:
Nominal: 5.0% at first induction, 100% at second induction, and 1.0% at challenge
Actual: 4.14% at first induction and 0.717% at challenge
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: ethanol and reverse osmosis water
Concentration / amount:
Nominal: 5.0% at first induction, 100% at second induction, and 1.0% at challenge
Actual: 4.14% at first induction and 0.717% at challenge
No. of animals per dose:
20; only 10 control animals used for challenge exposure
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
Day 0
- Exposure: intradermal
- Application: three pairs of injections
- Dose: 0.1 mL
- Test groups: exposed to FCA and test material
- Site 1: along spinal cord, near first thoracic vertebra; FCA/water
- Site 2: along spinal cord, near first thoracic vertebra; 5.0% test material in carrier
- Site 3: along spinal cord, caudal from first thoracic vertebra; 5.0% test material in FCA/water
- Control group: exposed to FCA and carrier
- Site 1: along spinal cord, near first thoracic vertebra; FCA/water
- Site 2: along spinal cord, near first thoracic vertebra; 100% carrier
- Site 3: along spinal cord, caudal from first thoracic vertebra; 5.0% carrier in FCA/water

Day 7
- Exposure: occlusive topical application
- Duration: 48 hours
- Dose: 0.5 mL
- Test groups: exposed to 100% test material
- Control group: exposed to 100% carrier
- Site: injected area on the dorsal surface

B. CHALLENGE EXPOSURE
Day 21
- Exposure: occlusive topical application
- Duration: 24 hours
- Dose: 0.4 mL
- Test groups: exposed to 1.0% test material in carrier on right flank, 100% carrier on left flank
- Control group: exposed to 1.0% test material in carrier on right flank, 100% carrier on left flank (10 animals only)
- Site: right and left flanks in the abdominal region
- Evaluation (hr after challenge): 24 and 48 hours after removal of challenge patches
Challenge controls:
Control group responses were used to distinguish true sensitization from local irritation produced by a single exposure to the same concentration of test material. Test material was applied to the left flank of all treated and ten of the control group animals, while carrier alone was applied to the right flank of all treated and the same ten control group animals.
Positive control substance(s):
yes
Remarks:
1 chloro-2,4-dinitrobenzene (DNCB)

Results and discussion

Positive control results:
The positive control material (DNCB) elicited reactions from all 20 animals both at 24 and 48 hours after removal of the challenge patch. Based on these results, the animals and methods used are capable of detecting the sensitisation potential of the test material.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
1.0% test material (0.4 mL)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No abnormal clinical observations were noted
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 1.0% test material (0.4 mL). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No abnormal clinical observations were noted.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
1.0% test material (0.4 mL)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No abnormal clinical observations were noted
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1.0% test material (0.4 mL). No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No abnormal clinical observations were noted.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.1% DNCB (0.4 mL)
No. with + reactions:
15
Total no. in group:
15
Clinical observations:
-
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.1% DNCB (0.4 mL). No with. + reactions: 15.0. Total no. in groups: 15.0. Clinical observations: -.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
1.0% test material (0.4 mL)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No abnormal clinical observations were noted
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 1.0% test material (0.4 mL). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No abnormal clinical observations were noted.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
1.0% test material (0.4 mL)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No abnormal clinical observations were noted
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1.0% test material (0.4 mL). No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No abnormal clinical observations were noted.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.1% DNCB (0.4 mL)
No. with + reactions:
10
Total no. in group:
15
Clinical observations:
-
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.1% DNCB (0.4 mL). No with. + reactions: 10.0. Total no. in groups: 15.0. Clinical observations: -.

Any other information on results incl. tables

All animals survived to study termination and displayed a weight gain from their day 0 values. No abnormal clinical inlife observations were noted for any animals during the study. One control group animal displayed very slight erythema 24 hours following patch removal for the ethanol dose site. No other signs of dermal irritation were noted for either dose group on days 23 and 24. Based on the lack of signs of dermal irritation during the challenge phase of this study, isopentane shows no sensitization potential.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
2-methylbutane was considered non-irritating.
Executive summary:

In this skin sensitisation study with isopentane young adult Hartley albino guinea pigs (20 females per dose) were tested using the Guinea Pig Maximization Test method. Guinea pigs were exposed to the test material via induction twice to allow for development of sensitisation, then challenged and compared to the control group and examined for signs of dermal irritation.

There was no evidence of dermal irritation or sensitisation in this study. 2 -methylbutane is not a dermal sensitizer. This study is classified with a Klimisch score of 1, reliable without restrictions, because it is in compliance with the OECD principles of GLP and because it is similar to OECD Guideline 406 and EU Method B.6.