Selenium disulphide

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

From Feb. 26, 1990 to Jan. 30, 1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Please refer to Section 13.2 - Weight of Evidence Approach for the Assessment of Skin Sensitisation Potential of Selenium Disulphide, CAS 7488-56-4, EC 231-303-8

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to other study

Reference

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

From Feb. 28, 1990 to Jan. 30, 1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Please refer to Section 13.2 - Weight of Evidence Approach for the Assessment of Skin Sensitisation Potential of Selenium Disulphide, CAS 7488-56-4, EC 231-303-8

Reason / purpose for cross-reference:

reference to other study

Reason / purpose for cross-reference:

reference to other study

Type of sensitisation studied:

skin

Study type:

study with volunteers

Principles of method if other than guideline:

The objective of this study was to determine the absence of the test substance to cause sensitization by repeated occlusive topical applications to human skin. The test substance (0.15%) was applied to human subjects on upper part of arm for 24 hours at each of 9 consecutive applications. The subjects were challenged 12 days after the last induction patch application with same concentration of test substance for 24 hours. Individuals were observed for signs of irritation/sensitization 48 hours after patch application during induction phase and 48 and 96 hours after challenge applications. Subjects were also rechallenged with test substance, if a positive outcome was obtained in induction phase.

GLP compliance:

not specified

Type of population:

general

Ethical approval:

not specified

Subjects:

- Number of subjects exposed: 126 subjects and 110 completed the study
- Sex: Females and males
- Age: Female: 15 - 65+ and Male: 18 - 65+
- Demographic information: God's Bible School, Cincinnati, Ohio

Clinical history:

- History of allergy or casuistics for study subject or populations: Detailed information is provided in the table 1 under "any other information on material and methods incl. tables section". In original study report, this data is represented on Appendix IV, page 14.

Controls:

None

Route of administration:

dermal

Details on study design:

ADMINISTRATION
- Description of patch: Webril pad (Diameter: 7/8 inch), reinforced with extra tape and coban elastic wrap was used to assure patch adherence
- Concentrations: 0.15% w/v G3099.01 w/v aqueous solutions for both induction and challenge
- Volume applied: 0.5 mL/patch
- Testing/scoring schedule: 48 hours after each of 9 induction patches and at 48 and 96 hours after the challenge patch application
- Removal of test substance: 24 hours after each of 9 induction patch and a challenge patch

EXAMINATIONS
- Grading/Scoring system:
0: No visible reaction (including superficial skin response such as glazing, peeling, cracking)
1: Mild erythematous reaction (faint pink to definite pink)
1E*: Mild erythematous reaction with papules and/or edema
2: Moderate erythematous reaction (definite pink to red erythema, similar to sunburn)
2E*: Moderate erythematous reaction with edema and/or papules
3: Strong erythematous reaction (beef red)
3E*: Strong erythematous reaction with marked edema, papules and/or few vesicles
4: Severe reaction with erythema, edema, papules and vesicles (may be evidence of weeping)
5: Bullous reaction
(S): Reaction spread beyond webril pad area
*Erythema, papules, edema and vesicles are judged to be present if they involve 25% or more of patch site. If papules are present append P to the grade i.e. EP. If vesicles are present, append a V to grade i.e EV.

- Statistical analysis: Not reported

Results of examinations:

SYMPTOMS
- Frequency, level, duration of symptoms observed:

INDUCTION PHASE
After 9 induction patches,
-1/110 subjects showed positive response

CHALLENGE PHASE
No effect was observed.

NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION
- Number of subjects with positive reactions: 1/110
- Number of subjects with negative reactions: 109/110 subjects
- Number of subjects with equivocal reactions: 0/110 subjects
- Number of subjects with irritating reactions: 0/110 subjects

There was no evidence of skin sensitization production in the 109 volunteer panelists who completed the test. One subject exhibited responses during induction that leads to further investigation. The panelist was rechallenged five months later using 0.15 and 0.015% formulation (G3099.01) and a distilled water control, there were no signs of sensitization. Detailed information is provided in the table 3 under "any other information on results incl. tables". In original study report, this data is represented on table III, page 26.

Table 2: Reasons for failure to complete test (WTDS# 36097)

Subject No.	Date	Reason
6	03-Mar-90	Didn't want to wear patch
18	14-Mar-90	Out of town
22	14-Mar-90	Out of town
27	19-Mar-90	Out of town
31	07-Mar-90	Work schedule
39	02-Apr-90	Forgot
48	02-Apr-90	Forgot
52	05-Mar-90	Out of town
70	07-Mar-90	Rash: Not test related
74	02-Mar-90	Needed to use med. For eczema
77	12-Mar-90	Hives: Not test related
93	07-Mar-90	Schedule conflict
101	05-Mar-90	Schedule conflict
110	03-Mar-90	Schedule conflict
124	07-Mar-90	Schedule conflict
126	02-Apr-90	Forgot

Table 3: Results of rechallenge of panelist #86 (WTDS#36097)

Rechallenge code	Test material	Scores (Hours after application)
		48 hours	72 hours
O-1	Conditioning version H&S E (0.60%) (0.15% C3099.01; 0.60% C0711.02)	0	0
A-1		0	0
O-2	Distilled water control	0	0
A-2		0	0
O-3	Conditioning version H&S E (0.60%) (0.15% C3099.01; 0.60% C0711.02)	0	0
A-3		0	0

Patch date: 4-Sept-90

Scoring date: 6-Sept-90 and 7-Sept-90

O: Original induction arm (left)

A: Alternate arm (right)

Patching material: H&S E Conditioning Version BY0908. (G3099.01)

Patch Size: 7/8 inch and diameter: 0.5 mL/patch

Patches were reinforced with extra tape; Coban elastic wrap was used to assure patch adherence

Patches were worn for 24 hours and scored at 48 and 72 hours

Conclusions:

No sign of skin sensitization was observed in 110 subjects when exposed to H&S E conditioning version with 0.60% DMDM hydantoin (0.996% selenium disulfide) formulation.

Executive summary:

The absence of the skin sensitization potential of H&S E conditioning version with 0.60% DMDM hydantoin (0.996% selenium disulfide) formulation was assessed in a human repeat insult patch study. A total of 126 subjects participated in the study. Subjects were exposed to 9 induction patches containing H&S E conditioning version with 0.60% DMDM hydantoin (0.996% selenium disulfide) on the upper part of arm. Patches were removed 24 hours each application and patch sites were graded at 48 hours after patch application prior to the next patch application. After 12 days rest period, subjects were challenged with the same concentration (24 hour patch exposure). Challenge patch sites were graded at 48 and 96 hours after patch application.

In this study, 110/126 subjects completed the study. A total 16 subjects dropped from the study. None of them showed sensitization reactions. These were dropped due to schedule conflicts (4 subjects), were out of town (4 subjects), forgot (3 subjects), non-test related hives (1 subject), non-test related rash (1 subject), needed to use medicine for eczema (1 subject), work schedule (1 subject) and didn't want to wear patch (1 subject).

There was no evidence of skin sensitization on 109 subjects who completed the test, although 1 subject exhibited responses during induction that warranted further investigation. On subsequent rechallenge after four months with 0.15 and 0.015% of formulation and a distilled water control, there were no signs of sensitization.

Under the study conditions, no sign of skin sensitization was observed in 110 subjects when exposed to H&S E conditioning version with 0.60% DMDM hydantoin (0.996% selenium disulfide) formulation.

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Reference

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

From May 11, 1987 to July 8, 1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Justification for type of information:

Please refer to Section 13.2 - Weight of Evidence Approach for the Assessment of Skin Sensitisation Potential of Selenium Disulphide, CAS 7488-56-4, EC 231-303-8

Reason / purpose for cross-reference:

reference to other study

Reason / purpose for cross-reference:

reference to other study

Type of sensitisation studied:

skin

Study type:

study with volunteers

Principles of method if other than guideline:

The objective of this study was to confirm the absence of test substance to cause sensitization by repeated occlusive topical applications to human skin. The test substance was applied to human subject’s lengthwise midway between the shoulder and elbow, on the lateral surface of the arm for 24 hours at each of 9 consecutive applications. The subjects were challenged 10 days after the last induction patch application (14 days for make-up subjects) with same concentration of test substance for 24 hours. Individuals were observed for signs of irritation/sensitization 48 hours after patch application during induction phase (72 hours after a weekend) and 48 and 96 hours after challenge applications

GLP compliance:

not specified

Type of population:

general

Ethical approval:

confirmed and informed consent free of coercion received

Subjects:

- Number of subjects exposed: 135 subjects and 120 completed the study
- Sex: Males (41) and Females (94)
- Age: 19 - 79
- Demographic information: Calvary Lutheran and Southwood Lutheran Church, Lincoln, NE

Clinical history:

- History of allergy or casuistics for study subject or populations: Detailed information is provided in the table 1 under "any other information on material and methods incl. tables section". In original study report, this data is represented on page 31.

Controls:

None

Route of administration:

dermal

Details on study design:

TYPE OF TEST(S) USED: patch test (epicutaneous test)

ADMINISTRATION
- Type of application: Occlusive
- Description of patch: Webril non woven cotton pad (Diameter: 7/8 inch) were centrally fixed on 2 to 2 1/2 wide and 7 inches long strip of Blenderm surgical tape
- Vehicle / solvent: Distilled water
- Concentrations: 0.15% w/v aqueous solution for induction and challenge
- Volume applied: 0.5 mL
- Testing/scoring schedule: 48 hours (72 hours after a weekend) after each of 9 induction patches and 48 and 96 hours after challenge patch application
- Removal of test substance: 24 hours after each of 9 induction patch and a challenge patch

EXAMINATIONS
- Grading/Scoring system:
0: No visible reaction (including superficial skin response such as glazing, peeling, cracking)
1: Mild erythematous reaction (faint pink to definite pink)
1E: Mild erythematous reaction with papules and/or edema
2: Moderate erythematous reaction (definite pink to red erythema, similar to sunburn)
2E: Moderate erythematous reaction with edema and/or papules
3: Strong erythematous reaction (beef red)
3E: Strong erythematous reaction with marked edema, papules and/or few vesicles
4: Severe reaction with erythema, edema, papules and vesicles (may be evidence of weeping)
5: Bullous reaction
(S): Reaction spread beyond webril pad area
Erythema, papules, edema and vesicles are judged to be present if they involve 25% or more of patch site.

- Statistical analysis: Not reported

Results of examinations:

SYMPTOMS
- Frequency, level, duration of symptoms observed:

INDUCTION PHASE
Detailed information is provided in table 2 under “any other information on results incl. tables section”. In original study report, this data is represented on page 27.

CHALLENGE PHASE:
At 48 hours: Out of 120 subjects who completed this study, 5 subjects at original site and one subject at alternate site showed mild erythema (score 1).

NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION
- Number of subjects with positive reactions: 106/120
- Number of subjects with negative reactions: 14/120
- Number of subjects with equivocal reactions: 0/120
- Number of subjects with irritating reactions: 5/120 subjects showed mild erythema (grade 1)

Table 2: Summary of grading score by visit

Grading Score	Induction grading visits										Challenge visit
											1		2
	1	2	3	4	5	6	7	8	9	MU	Original	Alternate	Original	Alternate
0	102	62	77	62	42	82	61	52	49	18	115	119	120	120
1	16	56	47	58	75	40	54	67	67	31	5	1	0	0
1E	0	3	1	0	0	0	0	0	0	0	0	0	0	0
2E	0	0	0	0	0	0	0	0	0	0	0	0	0	0
3	0	0	0	0	0	0	0	0	0	0	0	0	0	0
3E	0	0	0	0	0	0	0	0	0	0	0	0	0	0
4	0	0	0	0	0	0	0	0	0	0	0	0	0	0
5	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Table 3: List of dropouts from study

Total dropouts: 15

Subjects Number	Number of exposures	Reason	Reaction at time of dropout
16	9	Forgot	1
23	2	Hospitalized : unrelated to study	0
32	6	Work schedule conflict	1
35	9	Out of town	1
61	9	Out of town	0
67	1	Out of town	Unknown: no grading
74	1	Wants to swim daily	Unknown: no grading
75	1	Illness: unrelated to study	Unknown: no grading
95	3	Conflict with number of visits required	0
100	1	Unable to locate	Unknown: no grading
106	1	Does not wish to contine	Unknown: no grading
111	3	Forgot	0
113	1	Illness: unrelated to study	Unknown: no grading
122	4	Death in family	1
126	10	Work schedule conflict: no challenge grades	1

Conclusions:

No skin sensitization was observed in 120 subjects when exposed to H&S E N/Dry with 0.5% menthol (1.004% selenium disulfide) formulation.

Executive summary:

The absence of a skin sensitization potential of H&S E N/Dry with 0.5% menthol (1.004% selenium disulfide) formulation was assessed in a human repeat insult patch study. A total of 135 subjects participated in the study. Subjects were exposed to 9 induction patches containing 0.15% w/v H&S E N/Dry with 0.5% menthol (1.004% selenium disulfide) formulation on the lateral surface of arm. Patches were removed 24 hours each application and patch sites were graded at 48 hours after patch application prior to the next patch application. After 10 days rest period, subjects were challenged with the same concentration (24 hour patch exposure). Challenge patch sites were graded at 48 and 96 hours after patch application.

 

In this study, 120/135 subjects completed the study. A total 15 subjects dropped from the study and 5 subjects out of these showed mild erythema (score 1) at the time of dropout. These were dropped due to work schedule conflicts (2 subjects), were out of town (3 subjects), forgot (2 subjects), non-test related hospitalization/illness (3 subjects), death in family (1 subject), wanted to swim daily (1 subject), conflict with number of required visits (1 subject), unable to locate (1 subject) and didn't wished to continue (1 subject).

 

There was no evidence of skin sensitization in 120 subjects who completed the test, although 106/120 subjects showed at least one positive reaction.

 

Under the study conditions, no sign of skin sensitization was observed in 120 subjects when exposed to H&S E N/Dry with 0.5% menthol (1.004% selenium disulfide) formulation.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Type of sensitisation studied:

skin

Study type:

study with volunteers

Principles of method if other than guideline:

The objective of this study was to confirm the absence of test substance to cause sensitization by repeated occlusive topical applications to human skin. The test substance (0.15%) was applied to human subjects on upper part of arm for 24 hours at each of 9 consecutive applications. The subjects were challenged 12 days after the last induction patch application with same concentration of test substance for 24 hours. Individuals were observed for signs of irritation/sensitization 48 hours after patch application during induction phase and 48 and 96 hours after challenge applications. Subjects were also rechallenged with test substance, if a positive outcome was obtained in induction phase.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Selenium disulphide

EC Number:

231-303-8

EC Name:

Selenium disulphide

Cas Number:

7488-56-4

Molecular formula:

S2Se

IUPAC Name:

selenium disulphide

Test material form:

liquid

Details on test material:

- Name of test material: H&S E Conditioning version with 0.75% DMDM Hydantoin
- TSIN: G3098.01
- Physical form: Liquid
- Color: Peach
- pH: 5.40
- Storage conditions: Room temperature
- Expiry date: Feb. 01, 1991

Method

Type of population:

general

Ethical approval:

not specified

Subjects:

- Number of subjects exposed: 125 subjects and 115 completed the study
- Sex: Females and males
- Age: Female: 18 - 65+ and Male: 18 - 54
- Demographic information: Northwest High School PTS, Cincinnati, Ohio

Clinical history:

- History of allergy or casuistics for study subject or populations: Detailed information is provided in the table 1 under "any other information on material and methods incl. tables section". In original study report, this data is represented on Appendix IV, page 44.

Controls:

None

Route of administration:

dermal

Details on study design:

TYPE OF TEST(S) USED: patch test (epicutaneous test)

ADMINISTRATION
- Description of patch: Webril pad (Diameter: 7/8 inch), reinforced with extra tape and coban elastic wrap was used to assure patch adherence
- Concentrations: 0.15% w/v G3098.01 w/v aqueous solutions for both induction and challenge
- Volume applied: 0.5 mL/patch
- Testing/scoring schedule: 48 hours after each of 9 induction patches and at 48 and 96 hours after the challenge patch application
- Removal of test substance: 24 hours after each of 9 induction patch and a challenge patch

EXAMINATIONS
- Grading/Scoring system:
0: No visible reaction (including superficial skin response such as glazing, peeling, cracking)
1: Mild erythematous reaction (faint pink to definite pink)
1E*: Mild erythematous reaction with papules and/or edema
2: Moderate erythematous reaction (definite pink to red erythema, similar to sunburn)
2E*: Moderate erythematous reaction with edema and/or papules
3: Strong erythematous reaction (beef red)
3E*: Strong erythematous reaction with marked edema, papules and/or few vesicles
4: Severe reaction with erythema, edema, papules and vesicles (may be evidence of weeping)
5: Bullous reaction
(S): Reaction spread beyond webril pad area
*Erythema, papules, edema and vesicles are judged to be present if they involve 25% or more of patch site. If papules are present append P to the grade i.e. EP. If vesicles are present, append a V to grade i.e EV.

- Statistical analysis: Not reported

Results and discussion

Results of examinations:

SYMPTOMS
- Frequency, level, duration of symptoms observed:

INDUCTION AND CHALLENGE PHASE
After 9 induction patches,
-1/115 subjects showed positive response

CHALLENGE PHASE
At 96 hours: Only 1/115 showed positive response

NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION
- Number of subjects with positive reactions: 1/115 subjects
- Number of subjects with negative reactions: 114/115 subjects
- Number of subjects with equivocal reactions: 0/115 subjects
- Number of subjects with irritating reactions: 0/115 subjects

There was no evidence of skin sensitization production in the 114 volunteer panelists who completed the test. Two subjects and exhibited responses during induction that warranted further investigation. The panelists were rechallenged four months later with using 0.15 and 0.015% formulation (G3098.01) and a distilled water control, there were no signs of sensitization. Detailed information is provided in the table 3 under "any other information on results incl. tables". In original study report, this data is represented on table III, page 55.

Any other information on results incl. tables

Table 2: Reasons for failure to complete test (WTDS# 36096)

Subject No.	Date	Reason
5	07-Mar-90	Jury duty
16	19-Mar-90	Forgot
33	04-Apr-90	In hospital (Not test related)
44	02-Mar-90	Schedule conflict
47	19-Mar-90	Sick (Not test related)
53	02-Mar-90	Sick (Not test related)
67	02-Mar-90	Got a job
117	09-Mar-90	Sick (Not test related)
123	09-Apr-90	Out of town
125	19-Mar-90	Forgot

Table 3: Results of rechallange of Panelist #16 and #74 (WTDS# 36096)

Rechallenge code	Test material	Scores (Hours after application)
		Panelist #16		Panelist #74
		48 hours	72 hours	48 hours	72 hours
O-1	Conditioning H&S E version (0.15% C3098.01; 0.75% C0711.02)	0	0	0	0
A-1		0	0	0	0
O-2	Distilled water control	0	0	0	0
A-2		0	0	0	0
O-3	Conditioning version H&S E (0.015% C3098.01; 0.075% C0711.02)	0	0	0	0
A-3		0	0	0	0

Patch date: 6-Aug-90

Scoring date: 8-Aug-90 and 10-Aug-90

O: Original induction arm (left)

A: Alternate arm (right)

Patching material: H&S E Conditioning Version BY0908. G3098.01

Patch Size: 7/8 inch and diameter: 0.5 mL/patch

Patches were reinforced with extra tape; Coban elastic wrap was used to assure patch adherence

Patches were worn for 24 hours and scored at 48 and 72 hours

Applicant's summary and conclusion

Conclusions:

No sign of skin sensitization was observed in 115 subjects when exposed to a H&S E conditioning version with 0.75% DMDM Hydantoin (0.998% selenium disulfide) formulation.

Executive summary:

The absence of a skin sensitization potential of H&S E conditioning version with 0.75% DMDM Hydantoin (0.998% selenium disulfide) formulation was assessed in a human repeat insult patch study. A total of 125 subjects participated in the study. Subjects were exposed to 9 induction patches containing 0.15% w/v H&S E conditioning version with 0.75% DMDM Hydantoin (0.998% selenium disulfide) formulation on the upper part of arm. Patches were removed 24 hours each application and patch sites were graded at 48 hours after patch application prior to the next patch application. After a 12 days rest period, subjects were challenged with the same concentration (24 hour patch exposure). Challenge patch sites were graded at 48 and 96 hours after patch application.

In this study, 115/125 subjects completed the study. A total 10 subjects were dropped from the study. One of them showed positive reactions. These were dropped due to jury duty (1 subject), forgot (2 subjects), in hospital (not test related; 1 subject), schedule conflict (1 subject), sick (3 subjects; not test related), got a job (1 subject) and out of town (1 subject).

There was no evidence of skin sensitization on 114 subjects who completed the test, although 2 subjects, #16 (a drop from the study) and #74 exhibited responses during induction that warranted further investigation. On subsequent rechallenge after four months with 0.15 and 0.015% formulation and a distilled water control, there were no signs of sensitization. 

Under the study conditions, no sign of skin sensitization was observed in 115 subjects when exposed to H&S E conditioning version with 0.75% DMDM Hydantoin (0.998% selenium disulfide) formulation.