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Sensitisation data (human)

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Administrative data

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 07 June 1993 and 10 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 were 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

Method

Type of population:
general
Ethical approval:
confirmed and informed consent free of coercion received
Subjects:
One hundred fifty-nine (159) subjects, 37 males and 122 females, ranging in age from 18 to 65 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 dermatological condition 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 7, 1993 (panel No. 93080); February 15, 1995 (panel No. 95022); April 3, 1995 (Panel No. 95045); May 10, 1995 (panel No. 95070) and May 17, 1995 (panel No. 95074).
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 24-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, at the discretion of the Study Director any reactive subjects reaching a 2-level were subsequently Challenge patch tested semi-occlusively.

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 Challenge patch reactivity.
The final Challenge patch reading was made on: July 15, 1993 (panel No. 93080); April 3, 1995 (panel No. 95022); May 11, 1995 (Panel No. 95045); June 16, 1995 (panel No. 95070) and June 23, 1995 (Panel No. 95074).

Results and discussion

Results of examinations:
Test Article C (Same as A) @10% in Mineral Oil
Panel No. 93080: Fifty-three subjects were enrolled; 9 males and 44 females, aged 19 to 65. One (1/53) subject (No. 9) discontinued for reasons unrelated to the study.
Panel No. 95022: Thirty-three (33) subjects were enrolled; 26 females and 7 males aged 20 to 63. One (1/33) subject (no. 25) discontinued for violation of protocol (missed two consecutive visits)
Panel No. 95045: Twenty (20) subjects were enrolled; 12 females and 8 males aged 19-63. One (1/20) subject (no. 41) discontinued for reasons unrelated to the study. Two (2/20) subjects (nos. 42 and 45) were not challenged due to the level of reactivity.
Panel No. 95070: Twenty-three (23) subjects were enrolled; 18 females and 5 males aged 18-65. There were no discontinued subjects.
Panel No. 95074: Thirty (30) subjects were enrolled; 22 females and 8 males aged 18-61. Two (2/30) subjects discontinued for reasons unrelated to the study.

A total of one hundred fifty-four (154/159) subjects satisfactorily completed the study between July 15, 1993 and June 23, 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.
Skin reactivity patterns, which in the opinion of the Principal Investigator are suggestive of allergic contact dermatitis, were observed on 4/154 test panellists (Subject nos. 30, 46 [Panel No. 95022]; 42 and 45 [Panel No. 95045] although not challenge patched, exhibited Induction patched reactions that persisted to Challenge]).

Any other information on results incl. tables

Barely perceptible (+) to moderate (2-level) irritant/cumulative irritant patch test responses were observed on 11/154 test panellists during the Induction and/or Challenge phases of the study. None of these irritant responses was considered to be allergic in nature.

TABLE 1 -Individual Scores
Panel No:93080
Repeated Insult PatchTest-Occlusive
Test Article A (@ 10%in MineralOil)
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 0 0 0 0
3 0 0 0 0 0 0 0 0 0 0 0
4 0 0 0 0 0 0 0 0 0 0 0
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
8 0 0 0 0 0 0 0 0 0 0 0
9 0 0 0 0 0 0 0 0 Discontinued
10 0 0 0 0 0 0 0 0 0 0 0
11 0 0 0 0 0 0 0 0 0 0 0
12 0 0 0 0 0 0 0 0 0 0 0
13 0 0 0 0 0 0 0 0 0 0 0
14 0 0 0 0 0 0 0 0 0 0 0
15 0 0 0 0 0 0 0 0 0 0 0
16 0 0 0 0 0 0 0 0 0 0 0
17 0 0 0 0 0 0 0 0 0 0 0
18 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
22 0 0 0 0 0 0 0 0 0 0 0
23 0 0 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
26 0 0 0 0 1 1ec* 0 + + 0 0
27 0 0 0 0 0 0 0 0 0 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 0 0
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 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 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 0
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 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
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 vesiculation or weeping)
c* = change in patch site at discretion of Study director
e = moderate oedema

TABLE 2 - Individual Scores
Panel No: 95022
Repeated Insult PatchTest -Occlusive
Test Article: C (same as A)
Subj. No. Induction Challenge Virgin Site
Exposure Number
1 2 3 4 5 6 7 8 9 24hr 72hr
21 0 0 0 0 0 0 0 0 0 0 0
22 0 0 0 0 0 0 0 0 0 0 0
23 0 0 0 0 0 0 0 0 0 0 0
24 0 0 0 0 0 0 0 0 0 0 0
25 Discontinued
26 0 0 0 0 0 0 0 0 0 0 0
27 0 0 0 0 0 0 0 0 0 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 2 0 2ps (96 hr = 2)**
31 0 0 0 0 0 0 0 0 0 0 0
32^ 0 0 0 0 0 0 2c 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
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 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 2e 0 0
46^ 0 0 0 2cp 0 2p - - - 1p lps (96hr = lp)*
47 0 0 0 0 0 0 0 0 0 0 0
48^ 0 0 0 0 0 0 + 0 2 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 2c 0 0 0  + (96 hr = +)*
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 vesiculation or weeping)
c = change in patch site
 - =  no patch application
p = mild to severe papular reaction
s = reaction spread beyond contact site
* = (168 hr = +)
 ** = (168 hr = 1)
e = moderate oedema
^ = subject challenge patched semi-occlusively

TABLE 3 - Individual Scores
Panel No: 95045
Repeated Insult Patch Test - Occlusive
Test Article: C (same as A)
Subj. No. Induction Challenge Virgin Site
Exposure Number
1 2 3 4 5 6 7 8 9 24hr 72hr
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 Discontinued
42 0 0 0 1 2c 3e - - - -  -*
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 3eps - -  - **
46 0 0 0 0 0 0 0 0 0 0 0
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^ 0 0 0 0 0 0 2c + + 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 2c 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 vesiculation or weeping)
c = change in patch site
 - =  no patch application
p = moderate papular reaction
e = mild to moderate oedema
^ = subject challenge patched semi-occlusively
* = 21 days after lst patch application, subject had "+" level residual reactivity on the original and changed sites. At the discretion ot the Study Director, the subject was not patched at Challenge.
 ** = 17 days after last patch application, subject hat "+" level residual rectivity on the site. At the discretion of the Study Director the subject was not patched at Challenge.

TABLE 4 - Individual Scores
Panel No:95070
Repeated Insult Patch Test - Occlusive
Test Article: C (same as A)
Subj. No. Induction ChallengeVirgin Site
ExposureNumber
1 2 3 4 5 6 7 8 9 24hr 72hr
28 0 0 0 0 0 0 0 0 0 0 0
29 0 0 0 0 0 0 0 0 0 0 0
39 0 0 0 0 0 0 0 0 0 0 0
31 0 0 0 0 0 0 0 0 1ep 0 0
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 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 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 0
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 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 vesiculation or weeping)
e = mild oedema
p =  mild papular reaction

TABLE 5 - Individual Scores
Panel No: 95074
Repeated Insult Patch Test - Occlusive
Test Article: C (same as A)
Subj, No. Induction Challenge Virgin Site
Exposure Number
1 2 3 4 5 6 7 8 9 24hr 72hr
24 0 0 0 0 0 0 0 0 0 0 0
25^ 0 0 0 0 0 2cep 2 - - 0 0
26 0 0 0 0 0 0 0 0 0 0 0
27 0 Discontinued
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 0 0
32 0 0 0 0 0 0 0 0 0 0 0
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 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 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 0
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 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
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 vesiculation or weeping)
c = change in patch site
 - =  no patch application
e = moderate oedema
p =  moderate papules
^ = subject Challenge patched semi-occlusively

Applicant's summary and conclusion

Conclusions:
Under the conditions of the previously described repeated insult patch test procedure, the test article: A/C (Total Base Number = 13) diluted to 10% in Squibb Mineral Oil induced irritant responses on 11/154 (~7%) 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 4/154 (2.6%) 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 fifty-nine (159) subjects, 37 males and 122 females, ranging in age from 18 to 65 years were empaneled for this test.

The 9 Repeated Insult (occlusive) Patch Test (9 RIPT) was conducted.

Under the conditions of the previously described repeated insult patch test procedure, Test Article: A/C (Total Base Number = 13) diluted to 10% in Squibb Mineral Oil induced irritant responses on 11/154 (~7%) 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 4/154 (2.6%) of the test panellists who completed the study.