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Sensitisation data (human)

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Endpoint:
sensitisation data (humans)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
Between 09 June 1993 and 31 May 1995
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Good clinical practices (GCP) statement; uses one of a number of acceptable methods but criteria for subject selection was not described.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Type of sensitisation studied:
skin
Study type:
study with volunteers
Test guideline
Guideline:
other: no guideline stated
Principles of method if other than guideline:
To determine the irritation and/or sensitization potential of the test article after repeated application under occlusive patch test conditions to the skin of human subjects (non-exclusive panel).
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
Description: Brown viscous liquid
Date received: February 18, 1993

Method

Type of population:
general
Ethical approval:
confirmed and informed consent free of coercion received
Subjects:
One hundred sixty-six (166) subjects, 26 males and 140 females, ranging in age from 19 to 68 years were empaneled for this test.
The subjects were informed of the nature of the test, including possible adverse reactions. Written informed consent was obtained.
Additionally, the subjects were considered dependable and able to read and understand instructions. The subjects did not exhibit any physical or dermatologicaI condtion that would have precluded application of the test article.
Clinical history:
The subjects did not exhibit any physical or dermatological condition that would have precluded application of the test article.
Route of administration:
dermal
Details on study design:
Induction Phase
The Induction Phase was initiated on: June 9, 1993 (Panel No. 93081); January 30, 1995 (Panel No. 95000.); February 6, 1995 (Panel No.: 95016); March 13; 1995 (Panel No. 95032); March 22, 1995 (Panel No. 95037) and April 19, 1995 (Panel No. 95052).
A sufficient amount of the test article (approximately 0.2 mL) was placed onto a Parke-Davis ReadiBandage occlusive patch, which was applied to the back of each subject between the scapulae and waist. adjacent to the spinal mid-line.
The subjects were instructed to remove the patch 2 hours after application. Twenty-four hour rest periods followed the Tuesday and Thursday removals and 48-hour rest periods followed each Saturday removal. The site was scored by a trained examiner just prior to the next patch application. This procedure was repeated every Monday, Wednesday and Friday until nine (9) applications of the test article had been made.
Procedurally, if a subject developed a positive reaction of a 2-level erythema or greater during the Induction phase or, at the discretion of the Study Director, if the skin response warranted a change in site, the patch would be applied to a previously unpatched adjacent site for the next application.
If a 2-level reaction (or greater) occurred at the new site no further applications would be made. However, any reactive subjects would be subsequently Challenge patch tested.
Challenge Phase.
After a rest period of approximately two weeks (no applications of the test article), the Challenge patch was applied to a previously unpatched (virgin) test site. The site was scored 24 and 72-hours after application. All subjects were instructed to report any delayed skin reactivity which might have occurred after the final Challenge patch reading. When warranted, selected test subjects were; called back to the Clinic for additional examinations and scoring to determine possible increases or decreases in ChaIlenge patch reactivity.
The final Challenge patch reading was made on July 16, 1993 (Panel No. 93081); March 13, 1995 (Panel No. 95009); March 20, 1995 (Panel No. 95016); April 24, 1995 (Panel No. 95032); April 28, 1995 (Panel No. 95037) and May 31, 1995 (Panel No. 95052).

Results and discussion

Results of examinations:
Panel No. 93081:
Forty-six (46/53) subjects satisfactorily completed the test procedure. Seven (7/53) subjects discontinued for personal reasons unrelated to the conduct of the study.

Panel No. 95009:
Twenty four (24/34) subjects satisfactorily completed the study. Ten (10) subjects discontinued [6 subjects (nos.23, 2,6,33, 36,37,42) discontinued for reasons unrelated to the study, 1 subject (no. 30) did not wish to patch, 3 subjects were discontinued due to violation of protocol (no. 32 had been patched with a sulfonate on a previous RIPT Panel; no. 50 had a history of sensitivity to soaps; no. 53 was unsuitable for patching)].

Panel No. 95016:
Twenty-two (22/26) subjects satisfactorily completed the study. Four (4) subjects discontinued [1 subject (no. 14 discontinued for reasons unrelated to the study, 1 subject (no. 12) was discontinued due to reaction to the patch adhesive, 2 subjects (nos. 8, 39) were discontinued due to violation of protocol-they had been patched with a sulfonate on a previous panel].

Panel No. 95032:
Sixteen (16/17) subjects satisfactorily completed the study. One (1/17) subject (no. 38) discontinued for reasons unrelated to the study.

Panel No. .9 50.37. .:
Twenty-two (22/22) subjects satisfactorily completed the study.

Panel No. 95052:
Twelve (12/14) subjects satisfactorily completed the study. Two (2/14) subjects (nos. 41 and;46) discontinued for reasons unrelated to the study.

A total of one hundred and forty-two (142/166) subjects satisfactorily completed the study between June 9, 1993 and May 31, 1995. Discontinued panellist data are shown up to the point of discontinuation, but are not used in the Results, Discussion or Conclusions sections of this final report.

Scattered, barely perceptible (+) to mild (1-level) non-specific patch test responses were observed on 10/142 test panellists (Subject nos. 24, 39, 48, 50 [Panel No. 93081 to mild (1-Ievel)]; 47 [panel No. 95009]; 15;23 [Panel No. 95016]; 44 [Panel no. 95037]; 44 and48 [Panel 95052]) during the Induction and/or Challenge phases of the study. None of these non-specific reactions was considered to be irritant or allergic in nature.

Barely-perceptible (+) to moderate (2-level) irritant/cumulative irritant patch test responses were observed on 26/142 test panellists (Subject nos. 14, 16, 19, 22, 27, 31, 35, 40 [Panel no. 93081]; 27, 39, 41, 43, 45, 48, 50, 55 [Panel no. 95009]; 2, 32, 38, 43, 44 [Panel no. 95016]; 50 [Panel
no. 95032]; 45, 48, 49 [Panel no. 95037]) and 50 [Panel no. 95052]) during the Induction and/or Challenge Phases of the study. None of these skin reactivity patterns was considered to be allergic in nature.
Skin reactivity patterns, which in the opinion of the Principal Investigator, are suggestive of allergic contact dermatitis, were observed on 8/142 test panellists (Subject nos. 11 and 47 [Panel no. 95016]; 39, 40, 46 [Panel no. 95032]; 46, 47 [Panel no. 95037]; and 40 [panel no. 95052].
Subject no. 11 (Panel No. 95016) experienced 4-level erythema at the 72-hour Challenge patch reading which was reported as an adverse event.

Any other information on results incl. tables

SUMMARY OF REACTION:

At the 72 hour challenge patch reading, the subject exhibited 4-level erythema with severe dryness, severe oedema, and mild papules in contact site. Also there was a 2 level erythema with moderate, papular reaction, spreading about 1" beyond contact site.

At the 96 hour reading, the subject exhibited 3-level erythema with moderate vesiculation on the patch site, and a severe papular reaction covering approximately 1/2 of the upper back area.

At the 168 hour reading the subject exhibited 2-level erythema with moderate dryness and a moderate papular reaction, extending beyond the contact site covering approximately, 1/4 of the upper back.

At this point (168 hours) the reaction was subsiding and no further action was taken.

For the test subject's protection, a decision was made to patch anyone who reacted with a "2-level" or greater during induction semi-occlusively rather than occlusively during challenge.

TABLE 1 - Individual Scores
Panel No: 93081
Repeated Insult Patch Test - Occlusive
Test Article: Calcium sulfonate (@ 10% in Mineral Oil)
Subj. No. Induction Challenge Virgin Site
Exposure Number
1 2 3 4 5 6 7 8 9 24hr 72hr
1 0 0 0 0 0 0 0 0 0 0 0
2 0 0 0 0 0 0 0 Discontinued
3 0 0 0 0 0 0 0 0 0 0 0
4 0 0 0 + 0 0 Discontinued
5 0 0 0 0 0 0 0 0 0 0 0
6 0 0 0 0 0 0 0 0 0 0 0
7 0 0 0 0 0 0 0 0 0 0 0
X 0 0 0 Discontinued
9 0 0 0 0 0 0 0 0 0 0 0
10 0 0 0 0 0 0 0 0 0 0 0
11 0 0 0 0 0 0 0 0 0 OH 0
12 Discontinued
13 0 0 0 0 0 0 0 0 0 0 0
14 0 0 0 0 0 0 + 0 1 0 0
15 0 0 0 0 0 0 0 0 0 0 0
16 0 0 0 0 0 0 0 0 1 0 0
17 0 0 0 0 0 0 0 0 0 0 0
18 0 0 0 0 Discontinued
19 0 0 0 0 2dc 0 + 0 2e 0 0
20 0 0 0 0 0 0 0 0 0 0 0
21 0 0 0 0 0 0 0 0 0 0 * (96h = 0)
22 0 0 0 + 2dc 0 1 2e - 0 1 (96h = +)
23 0 0 0 0 0 0 0 0 0 0 0
24 0 0 0 0 0 0 + 0 0 0 0
25 0 0 0 0 0 Discontinued
26 0 0 0 0 0 0 0 0 0 0 0
27 0 0 0 0 0 0 0 1 1e 0 0
28 0 0 0 0 0 0 0 0 0 0 0
29 0 0 0 0 0 0 0 0 0 0 0
30 0 0 0 0 0 0 0 0 0 0 0
31 0 0 0 0 0 0 0 0 0 1 +
32 0 0 0 0 0 0 0 0 0 0 0
33 0 0 0 0 0 0 0 0 0 0 0
34 0 0 0 0 0 0 0 0 0 0 0
35 0 0 0 0 1 1 1 2c + 0 0
36 0 0 0 0 0 0 0 0 0 0 0
37 0 0 0 0 Discontinued
38 0 0 0 0 0 0 0 0 0 0 0
39 0 0 0 0 0 0 0 0 + 0 0
40 0 0 0 1 + + + 0 0 0 0
41 0 0 0 0 0 0 0 0 0 0 0
42 0 0 0 0 0 0 0 0 0 0 0
43 0 0 0 0 0 0 0 0 0 0 0
44 0 0 0 0 0 0 0 0 0 0 0
45 0 0 0 0 0 0 0 0 0 0 0
46 0 0 0 0 0 0 0 0 0 0 * (96hr = 0)
47 0 0 0 0 0 0 0 0 0 0 0
48 0 0 0 0 + 0 0 0 0 0 0
49 0 0 0 0 0 0 0 0 0 0 0
50 0 0 0 0 0 + 0 0 0 0 0
51 0 0 0 0 0 0 0 0 0 0 0
52 0 0 0 0 0 0 0 0 0 0 0
53 0 0 0 0 0 0 0 0 0 0 0
Scale: 0 = No evidence of any effect
+ = barely Perceptible {Minimal faint, uniform or spotty erythema)
1 = Mild (Pink, uniform erythema covering most of the contact site)
2 = Moderate (Pink-red erythema uniform in the entire contact site)
3 = Marked (Bright-red erythema with/without petechiae or papules)
4 = Severe (Deep-red erythema with/without vesiculadon or weeping) 
e = mild oedema
d = moderate dryness
H = mild Hyperigmentation 
c = change in patch site
 - = no patch application
 * = missed visit, no reading taken

TABLE 2 - Individual Scores
Panel No: 95009
Repeated Insult Patch Test - Occlusive
Test Article: Calcium sulfonate (@10% in Mineral Oil)
Subj. No. Induction Challenge
Virgin Site
Exposure Number
1 2 3 4 5 6 7 8 9 24hr 72hr
23 0 0 0 0 0 0 Discontinued
25 0 0 0 0 0 0 0 0 0 0 0
26 Discontinued
27 0 + 0 + + + 1d 2cc 0 0 0
29 0 0 0 0 0 0 0 0 0 0 0
30 Discontinued
31 0 0 0 0 0 0 0 0 0 0 0
32 Discontinued
33 0 Discontinued
34 0 0 0 0 0 0 0 0 0 0 0
35 0 0 0 0 0 0 0 0 0 0 0
36 Discontinued
37 Discontinued
38 0 0 0 0 0 0 0 0 0 0 0
39 0 0 0 0 0 0 0 0 0 0 1 (96 hr = 0)
40 0 0 0 0 0 0 0 0 0 0 0
4L 2c 2 - - - - - - - 1 1 (168 hr = +d)
42 Discontinued
43 0 0 0 0 0 0 0 0 0 1 0
44 0 0 0 0 0 0 0 0 0 0 0
45 0 0 0 2c 0 0 0 0 0 0 0
46 0 0 0 0 0 0 0 0 0 0 0
47 0 +d  +d 0 + + + + 0 0 0
48 1 0 0 0 0 0 0 1d 0d 0 0
49 0 0 0 0 0 0 0 0 0 0 0
50 0 0 0 0 2c 1 2edp - - 1 * 0
51 0 0 0 0 0 0 0 0 0 0 0
52 0 0 0 0 0 0 0 0 0 0 0
53 Discontinued
54 0 0 0 0 0 0 0 0 0 0 0
55 0 0 2dc 0 1 1 1 2 - +  +(96 hr = 0)
56 0 0 0 0 0 0 0 0 0 0 0
58 0 0 0 0 0 0 0 0 0 0 0
1 0 0 0 0 0 0 0 0 0 0 0
Scale: 0 = No evidence of any effect
+ = barely Perceptible {Minimal faint, uniform or spotty erythema)
1 = Mild (Pink, uniform erythema covering most of the contact site)
2 = Moderate (Pink-red erythema uniform in the entire contact site)
3 = Marked (Bright-red erythema with/without petechiae or papules)
4 = Severe (Deep-red erythema with/without vesiculadon or weeping) 
d = mild to severe dryness
 - = no patch application
c = change in patch site
e =  mild oedema
 * = Subject was inadvertently Challenge patched, it was found that she had a sensitivity to soap and was discontinued previous to Challenge
p =  mild papular reaction

TABLE 3 - Individual Scores
Panel No: 95016
Repeated Insult Patch Test - Occlusive
Test Article: Calcium sulfonate (@10% in Mineral Oil)
Subj. No. Induction Challenge
Virgin Site
Exposure Number
1 2 3 4 5 6 7 8 9 24hr 72hr
1 0 0 0 0 0 0 0 0 0 0 0
2 0 0 0 0 0 0 0 + 1 0 0
3 0 0 0 0 0 0 0 0 0 0 0
8 0 Discontinued
11 1 + + + + 2cedv 2ed - - 2 4dpe ( 96 hr = 3vp) *
12 0 0 0 + Discontinued
14 0 Discontinued
15  +~ + 0 0 0 0 0 0 0 0 0
16 0 0 0 0 0 0 0 0 0 0 0
19 0 0 0 0 0 0 0 0 0 0 0
20 0 0 0 0 0 0 0 0 0 0 0
21 0 0 0 0 0 0 0 0 0 0 0
23 0 1 0 0 0 0 0 0 0 0 0
24 0 0 0 0 0 0 0 0 0 0 0
25 0 0 0 0 0 0 0 0 0 0 0
28 0 0 0 0 0 0 0 0 0 0 0
31 0 0 0 0 0 0 0 0 0 0 ** (96 hr = 0)
32 0 2c 0 0 0 0 0 0 0 0 0
38 0 0 2ce~ 0 0 0 + 0 1 0 0
39 Discontinued
42 0 0 0 0 0 0 0 0 0 0 0
43 2cep 2ep - - - - - - - 0 0
44 0 0 0 0 0 0 + + 2p 0 0
47 0 1 + 1 2cp 2ep - - 0 0 ( 96 hr = 2p) ^
54 0 0 0 0 0 0 0 0 0 0 ** (96 hr = 0)
55 0 0 0 0 0 0 0 0 0 0 0
Scale: 0 = No evidence of any effect
+ = barely Perceptible {Minimal faint, uniform or spotty erythema)
1 = Mild (Pink, uniform erythema covering most of the contact site)
2 = Moderate (Pink-red erythema uniform in the entire contact site)
3 = Marked (Bright-red erythema with/without petechiae or papules)
4 = Severe (Deep-red erythema with/without vesiculadon or weeping) 
* = (168 hr = 2dp) Reactions at 72 r, 96 hr and 168 hr were spread beyond contact site
 ~ = Patch inadvertently left on for 48 hrs, Removed at clinic
p =  mild to moderate papular reaction
d =  mild to severe dryness
 ** = missed visit, no reading taken
 - =  no patch application
^ = ( 168 hr = +p)
v = mild to moderate vesiculation
e = mild to severe oedema

TABLE 4 - Individual Scores
Panel No: 95032
Repeated Insult Patch Test - Occlusive
Test Article: Calcium sulfonate (@10% in Mineral Oil)
Subj. No. Induction Challenge
Virgin Site
Exposure Number
1 2 3 4 5 6 7 8 9 24 hr 72 hr
38 Discontinued
39^ 0 0 0 0 0 + 2cep 2ep - 1e 1 *(~)
40^ 0 + 0 0 0 1 2ced 2 - 1ep  +p (96 hr = +)
42 0 0 0 0 0 0 0 0 0 0 0
43 0 0 0 0 0 0 0 0 0 0 0
44 0 0 0 0 0 0 0 0 0 0 0
45 0 + 0 0 0 0 0 0 0 0 0
46 0 0 0 1c*dh 0 0 0 1e - 0 1e
47 0 0 0 0 0 0 0 0 0 0 0
48 0 0 0 0 0 0 0 0 0 0 0
49 0 0 0 0 0 0 0 0 0 0 0
50 + 1 0 + + 0 0 0 0 0 0
51 0 0 0 0 0 0 0 0 0 0 0
52 0 0 0 0 0 0 0 0 0 0 0
53 0 0 0 0 0 0 0 0 0 0 0
54 0 0 0 0 0 0 0 0 0 0 0
55 0 0 0 0 0 0 0 0 0 0 0
Scale: 0 = No evidence of any effect
+ = barely Perceptible {Minimal faint, uniform or spotty erythema)
1 = Mild (Pink, uniform erythema covering most of the contact site)
2 = Moderate (Pink-red erythema uniform in the entire contact site)
3 = Marked (Bright-red erythema with/without petechiae or papules)
4 = Severe (Deep-red erythema with/without vesiculadon or weeping) 
c = change in patch site
c* = change in patch site at the discretion of the Study Director
 - = no patch application
e = mild oedema
p = mild to moderate papular reaction
* =  ( 96 hr = 2peis)
h = hyperpigmentation
d = mild to moderate dryness
i = moderate itching
^ = subject challenge patched serni-occlusively
s = reaction spread beyond contact site
(~) =  (168 hr = 1p)

TABLE 5 - Individual Scores
Panel No: 95037
Repeated Insult Patch Test - Occlusive
Test Article: Calcium sulfonate (@ 10 % in Mineral Oil)
Subj, No. Induction Challenge
Virgin Site
Exposure Number
1 2 3 4 5 6 7 8 9 24hr 72hr
34 0 0 0 0 0 0 0 0 0 0 0
35 0 0 0 0 0 0 0 0 0 0 0
36 0 0 0 0 0 0 0 0 0 0 0
37 0 0 0 0 0 0 0 0 0 0 0
38 0 0 0 0 0 0 0 0 0 0 0
39 0 0 0 0 0 0 0 0 0 0 0
40 0 0 0 0 0 0 0 0 0 0 0
41 0 0 0 0 0 0 0 0 * 0 0
42 0 0 0 0 0 0 0 0 0 0 0
43 0 0 0 0 0 0 0 0 0 0 0
44 0 0 1 0 0 0 0 0 0 + 0
45 0 0 0 2cp + + + 0 + 0 0
46 0 0 0 0 0 0 0 0 0 0 2pe (96 h r= +)
47^ 0 0 0 0 0 2c 0 2 -  +p 1g ( 96 hr = +p)
48 0 0 0 0 1 + 0 1d + 0 0
49 1 0 0 2c 0 0 0 0 0 0 0
50 0 0 0 0 0 0 0 0 0 0 0
51 0 0 0 0 0 0 0 0 0 0 0
52 0 0 0 0 0 0 0 0 0 0 0
53 0 0 0 0 0 0 0 0 0 0 0
54 0 0 0 0 0 0 0 0 0 0 0
55 0 0 0 0 0 0 0 0 0 0 0
Scale: 0 = No evidence of any effect
+ = barely Perceptible {Minimal faint, uniform or spotty erythema)
1 = Mild (Pink, uniform erythema covering most of the contact site)
2 = Moderate (Pink-red erythema uniform in the entire contact site)
3 = Marked (Bright-red erythema with/without petechiae or papules)
4 = Severe (Deep-red erythema with/without vesiculadon or weeping) 
c = change in patch site
 * = missed visit, no reading taken
 - = no patch application
p = mild to moderate papular reaction
d = moderate peripheral dryness
e = mild oedema
^ = subject was challenged patched semi-occlusively. At 72hr and 96hr, reaction was spread beyond contact site.

TABLE 6 - Individual Scores
Panel No: 95052
Repeated Insult Patch Test - Occlusive
Test Article: Calcium sulfonate (@10% in Mineral Oil)
Subj. No, Induction Challenge
Virgin Site
Exposure Number
1 2 3 4 5 6 7 8 9 24hr 72hr
40 + 0 0 0 0 0 0 0 0 0 2 (216 hr = 0)
41 0 0 0 0 0 Discontinued
42 0 0 0 0 0 0 0 0 0 0 0
43 0 0 0 0 0 0 0 0 0 0 0
44 0 0 1 0 0 0 0 0 0 0 0
45 0 0 0 0 0 0 0 0 0 0 * (96 hr = 0)
46 0 0 Discontinued
47 0 0 0 0 0 0 0 0 0 0 0
48 0 0 0 + 0 0 0 0 0 0 0
49 0 0 0 0 0 0 0 0 0 0 0
50 + 0 0 0 0 0 0 0 1p 0 0
51 0 0 0 0 0 0 0 0 0 0 0
52 0 0 0 0 0 0 0 0 0 0 0
53 0 0 0 0 0 0 0 0 0 0 0
Scale: 0 = No evidence of any effect
+ = barely Perceptible {Minimal faint, uniform or spotty erythema)
1 = Mild (Pink, uniform erythema covering most of the contact site)
2 = Moderate (Pink-red erythema uniform in the entire contact site)
3 = Marked (Bright-red erythema with/without petechiae or papules)
4 = Severe (Deep-red erythema with/without vesiculadon or weeping) 
 * = missed visit, no reading taken
p = mild papular reaction

Applicant's summary and conclusion

Conclusions:
Under the conditions, of the previouly described repeated insult patch test procedure, Test Article: Calcium sulfonate (Total Base Number = 30) at 10% in Squibb Mineral Oil induced irritant responses on 26/142 (18.3%) of the test panellists who completed the study, and induced reactivity patterns that, in the opinion of the Principal Investigator, are suggestive of allergic contact dermatitis on 8/142 (5.6%) of the test panellists who completed the study.
Executive summary:

To determine the irritation and/or sensitization potential of the test article after repeated application under occlusive patch test conditions to the skin of human subjects (non-exclusive panel). One hundred sixty-six (166) subjects, 26 males and 140 females, ranging in age from 19 to 68 years were empaneled for this test. The 9 Repeated Insult (occlusive) Patch Test (9 RIPT) was conducted.

Under the conditions, of the previouly described repeated insult patch test procedure, the test article: Calcium sulfonate (Total Base Number = 30) at 10% in Squibb Mineral Oil induced irritant responses on 26/142 (18.3%) of the test panellists who completed the study, and induced reactivity patterns that, in the opinion of the Principal Investigator, are suggestive of allergic contact dermatitis on 8/142 (5.6%) of the test panelists who completed the study.