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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Directive 84/449/EEC, Method B.6 (skin sensitisation)
GLP compliance:
yes
Type of study:
Freund's complete adjuvant test
Justification for non-LLNA method:
An LLNA study was not performed because there is an existing reliable study for skin sensitisation using the Freund's complete adjuvant test method.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

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: Harlan Porcellus
- Age at study initiation: 7-9 weeks
- Housing: up to five animals per stainless steel wire-mesh cage
- Diet: FD1, S.D.C., Special Diets Services Ltd., ad libitum
- Water: Tap water ad libitum
- Acclimation period: minimum of two weeks

ENVIRONMENTAL CONDITIONS
- Temperature (oC): 19-23oC
- Humidity (%): 30-70%
- Photoperiod (hrs dark/ hrs light): 12 hr day and 12 hr night

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
2% m/v sulfolane in water/FCA for interdermal application; undiluted sulfolane for topical application.
Challenge
No.:
#1
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
2% m/v sulfolane in water/FCA for interdermal application; undiluted sulfolane for topical application.
No. of animals per dose:
10/sex (test groups); 5/sex (control group).
Details on study design:
RANGE FINDING TESTS: Primary skin irritation screens – intradermal and topical application - were 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 2% for intradermal application and undiluted test material for topical applications.

MAIN STUDY
A. INDUCTION EXPOSURE
Two rows of intradermal injections were made, one on either side of the mid-line, of the shaved backs of guinea pigs. In the test animals: 0.1 ml of emulsified Freunds Complete Adjuvant (FCA) to the anterior sites; 0.1 ml 2% sulfolane in water to the middle sites; and 0.1 ml 2% sulfolane in FCA to the posterior sites. For the control animals: 0.1 ml FCA to the anterior sites; 0.1 ml of water (vehicle) to the middle sites; and 0.1 ml of water (vehicle) in FCA to the posterior sites. One week after induction by intradermal injection, the same area of skin was shaven and a patch of filter paper, moistened with 0.2 ml undiluted sulfolane was placed over the intradermal sites, covered with occlusive tape and held in place by elastic adhesive bandage for 48 hours. Similar patches of filter paper moistened with the vehicle alone were applied to the control group of guinea pigs. The dermal test sites were washed with water after removal of the dressings.

B. CHALLENGE EXPOSURE
Three weeks following the intradermal phase of induction, all animals were challenged by occluded application of undiluted sulfolane in acetone for. After 24 hours, the patches were removed and the challenge sites were washed with water. The condition of the test sites was assessed shortly after removal of the challenge patches, and 24 and 48 hours after removal of the challenge patches.
Challenge controls:
The same induction procedures were carried out on a 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 material, with application of a 75% sulfolane solution.
Positive control substance(s):
not specified

Results and discussion

Positive control results:
No information is available.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
2%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
2%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Remarks on result:
other: Positive control not specified

Any other information on results incl. tables

Guinea pigs receiving undiluted sulfolane during the challenge phase only and those animals exposed to the same challenge dose following the induction with a single intradermal injection of 2% sulfolane in water/Freund’s adjuvant plus a topical application of undiluted sulfolane exhibited no dermal irritation at any timepoint.

Applicant's summary and conclusion

Interpretation of results:
other: not senisitising
Remarks:
in accordance with Annex I of 1272/2008/EC (CLP)
Conclusions:
Under the conditions of this study, repeated administration of sulfolane did not result in skin sensitisation to guinea-pigs. Therefore the substance does not need to be classified for skin sensitisation, according to the classification criteria outlined in Annex I of 1272/2008/EC (CLP).


Executive summary:

Primary skin irritation screens – intradermal and topical application - were used to determine the concentration of test material used during the main study.  Induction: Two rows of intradermal injections were made on the shaved backs of guinea pigs (5 animals per sex per dose). Injected were 0.1 ml Freunds Complete Adjuvant (FCA) to the anterior sites; 0.1 ml 2% sulfolane in water to the middle sites; and 0.1 ml 2% sulfolane in FCA to the posterior sites). The control animals were treated with vehicle and/or FCA only. One week after induction the same area of skin was shaven and occlusively exposed to 0.2 ml undiluted sulfolane, or vehicle for 48 hours. The dermal test sites were washed with water after removal of the dressings.  Challenge: Three weeks following the intradermal phase of induction, all animals were challenged by occluded application of undiluted sulfolane in acetone for 24 hours. Afterwards the patches were removed and the challenge sites washed with water. The condition of the test sites was assessed shortly after removal of the challenge patches, and 24 and 48 hours after removal of the challenge patches. In the guinea pig sensitisation test using the method of Magnusson and Kligman, repeated administration of sulfolane did not result in skin sensitisation to guinea pigs.


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