Registration Dossier

Administrative data

Description of key information

Sulfolane did not induce skin sensitization in a guinea pig study.

No animal or human data have been found with regard to respiratory sensitisation potential of sulfolane.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Not GLP compliant, available as unpublished report.
Justification for type of information:
.
Qualifier:
according to
Guideline:
other: not specified
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An LLNA study was not performed because there is an existing reliable study for skin sensitisation using the Guinea Pig Maximisation test method.
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dutchland Laboratory Animals, Inc., USA
- Weight at study initiation: 300-500 g
- Housing: Individual animal per cage
- Diet: Purina Guinea Pig Chow ad libitum
- Water: Tap water ad libitum
- Acclimation period: minimum of one week
Route:
other: epicutaneous
Vehicle:
other: acetone
Concentration / amount:
75% v/v for epicutaneous application
Route:
epicutaneous, occlusive
Vehicle:
other: acetone
Concentration / amount:
75% v/v for epicutaneous application
No. of animals per dose:
5/sex (test and negative control groups)
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 75% v/v for topical applications.

MAIN STUDY
A. INDUCTION EXPOSURE
A topical application of 75% sulfolane solution was applied to the shaved backs of 5 male and 5 female guinea pigs and covered by an occlusive dressing for six hours. 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 the vehicle acetone. The test material and control vehicle were reapplied once per week for three weeks.

B. CHALLENGE EXPOSURE
Fifteen days following the last induction application, all animals were challenged by occluded application of 75% sulfolane in acetone for 4 to 6 hours. The condition of the test sites was assessed approximately 24, 48 and 72 hours later.
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):
yes
Remarks:
Dinitrochlorobenzene (DNCB) at 0.15% and 0.1% was used for the induction and challenge phases, respectively.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
75%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
75 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test group
Dose level:
75 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
75%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
75%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test group
Dose level:
75%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
Dinitrochlorobenzene (DNCB) at 0.1% and 0.15%
Remarks on result:
other: See "Remarks"
Remarks:
Guinea pigs treated with 0.1% DNCB in acetone during the challenge phase only exhibited very slight erythema in 3/10 animals at 24 hours, which persisted in one animal at the 48-hr timepoint. Animals exposed to the same challenge concentration of DNCB, following the induction with 0.15% DNCB in acetone and a rest period, exhibited very slight to moderate to severe erythema at 24 hours, with persisted to some degree to the 48- and 72-hr timepoints in several animals. There was also slight edema in one animal at the 24-hr timepoint, and blanching in 4/10 animals at the 24-hr timepoint. It is concluded that the guinea pigs responded to hypersensitisation when a known sensitiser was used.

Guinea pigs receiving 75% sulfolane in acetone during the challenge phase only and those animals exposed to the same challenge dose following the induction with 75% sulfolane in acetone exhibited no dermal irritation at any timepoint.

Positive control: Guinea pigs treated with 0.1% DNCB in acetone during the challenge phase only exhibited very slight erythema in 3/10 animals at 24 hours, which persisted in one animal at the 48-hr timepoint. Animals exposed to the same challenge concentration of DNCB, following the induction with 0.15% DNCB in acetone and a rest period, exhibited very slight to moderate to severe erythema at 24 hours, with persisted to some degree to the 48- and 72-hr timepoints in several animals. There was also slight edema in one animal at the 24-hr timepoint, and blanching in 4/10 animals at the 24-hr timepoint. It is concluded that the guinea pigs responded to hypersensitisation when a known sensitiser was used.

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, repeated administration of sulfolane did not result in skin sensitisation to guinea-pigs.
Executive summary:

Under the conditions of this study, repeated administration of sulfolane did not result in skin sensitisation to guinea-pigs.

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
Qualifier:
according to
Guideline:
other: Directive 84/449/EEC, Method B.6 (skin sensitisation)
Principles of method if other than guideline:
No information is available.
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.
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
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
2% m/v sulfolane in water/FCA for interdermal application; undiluted sulfolane for topical application.

No.:
#1
Route:
epicutaneous, occlusive
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
Positive control results:
No information is available.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
2%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
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
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Undiluted
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Undiluted
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
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

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.

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, repeated administration of sulfolane did not result in skin sensitisation to guinea-pigs.


Executive summary:

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Dermal Sensitisation

In a Freund's complete adjuvant test (SRC, 1993), a test group of 20 guinea pigs received 2% sulfolane in vehicle(water) or Freund's adjuvant for intradermal induction, followed by percutaneous induction with undiluted sulfolane under occlusive dressing for 48 hours. For challenge, undiluted sulfolane (in acetone) in vehicle was applied to the intact skin for 24 hours (occlusive). The challenge in no response in all test animals.

Hazleton (1982a) reported in a guinea pig maximisation test that sulfolane was not a dermal sensitiser to guinea pigs. A test group of 10 animals received a topical application of 75% sulfolane in vehicle (acetone) under occlusive dressing for six hours, once per week for three weeks. All animals were challenged by occluded application of 75% sulfolane in acetone for 4 to 6 hours. There was no irritation response in any of the test animals.


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

Respiratory Sensitisation

No animal or human data have been found with regard to respiratory sensitisation.



Justification for classification or non-classification

Dermal Sensitisation

Classification proposal regarding dermal sensitisation: GHS/CLP: None. 

Respiratory Sensitisation

Although there are no specific data on respiratory respiration, there is no evidence that classification is warranted under GHS/CLP.