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Description of key information

The test item was not found to be a primary irritant or a skin sensitiser. The evidence of apparent innocuousness of the test item gathered in the study enabled the investigator to express the opinion that there was nothing in the results which could be construed as being a contraindication to the use of the material in a general human population.

Additional information

The objective of the study was to ascertain the irritation and sensitisation potentials of the test item under conditions of a stringently supervised patch test.

 

The evidence of apparent innocuousness of the test item gathered in the study enabled the investigator to express the opinion that there was nothing in the results which could be construed as being a contraindication to the use of the material in a general human population.

 

A group of 55 individuals was selected from a local population. Criteria for selection were general well-being, absence of skin disease, willingness to cooperate and expression of dependability, able to understand and follow directions, able to understand and sign an informed consent form, age 18 or over. The test item was one of six materials being evaluated simultaneously on the same volunteer panel.

In order to evaluate the t e s t material, the investigator was given full rein to use that concentration which he felt was best suited to achieve the objective of this study. Logically, the higher the concentration which could be used in the study, the more valid would seem the results. Therefore, it was necessary from the outset to determine what was the maximum concentration which human skin could tolerate under the patch conditions, which would pertain throughout the procedure (complete occlusion, 24-hour duration of contact and density of application approximately 0.1 mL test material per cm2).

To determine the concentration, the group of participants were divided into five sub-groups: Group I (consisting of 11 subjects) received 100% test item; Group II (consisting of 10 subjects) received 80% test item in petroleum; Group III (consisting of 11 subjects) received 60% test item in petroleum; Group IV (consisting of 11 subjects) received 40% test item in petroleum; Group V (consisting of 12 subjects) received 20% test item in petroleum.

 

Not only was it necessary to determine whether or not each individual could tolerate his or her respective concentration for the first 24 hours, but also repetitively to successive 24-hour applications to ascertain if the material was cumulatively irritating. Titration of skin tolerance proceeded with the provision that if, after the first 24 hours, any individual responded with a significant irritation, the site would be changed, and lower concentration would be used for subsequent applications. If the first 24-hour contact was tolerated, but intolerance developed after the second or third exposure, the provision was made for change of site only. If the new site responded, then in that event the concentration would be lowered. In this manner, each individual’s tolerance wasestablished. After the fourth application, the results were analysed, and one concentration was selected for all future applications on all individuals. The concentration of test item selected was 100 % (material as supplied).

After establishing the maximum concentration of test material that could be tolerated by individuals in the panel, that concentration was scheduled to be used throughout the remaining applications during the second and third weeks and during the challenge. However, the investigator reserved the option of changing the concentration if, in his opinion, the irritation obtained on subsequent readings justified such a change. Any such changes were described as deviations from scheduled procedure.

 

The second phase of the study consisted of the challenge, which was scheduled to be applied to a virgin site on Day 36 of the procedure. This application occurred after a hiatus of 17 days from the last reading in the induction series.

Each subject was patched with the test material on Monday, 12 September 1977. The patch was occlusive and remained in situ for 24 hours. The patch was removed on Tuesday and the contact site was examined. Any reactions were scored according to the following scale: no visible erythema (0); very slight, questionable, erythema (+/-); erythema (1); erythema plus swelling (2); erythema, swelling plus papules (3); severe irritation consisting of erythema, swelling, papules and necrosis with extension beyond the boundaries of contact (4).

 

If the reaction was not substantial (not in excess of grade 1), the test material was re-applied to the same site for 24 hours. This procedure was repeated on Wednesday and Thursday for a total of four consecutive exposures each week for three weeks. After the fourth patch was removed and read each Friday, the patch sites were rested on Saturday and Sunday. If any patch developed a reaction of 2 or greater, the investigator could, at his discretion, continue subsequent applications on the same site or on a new site. The investigator could also continue the same type of patch (occlusive) or change to semi-occlusive or open applications. A total of 12 applications and readings were scheduled for the induction period.

Two individuals scheduled to participate in the study were absent during the induction period. Subject number 35 was absent during the third week of the study and subject number 54 was absent from application 4 through application 8. Both subjects were available for the challenge application.

 

On Day 36 of the study, after a rest period of slightly more than two weeks, the test material was applied on a new site as a challenge. At the end of 24 hours, the occluded patch was removed, and the site was read for the immediate response. Follow-up readings were made 24, 48 and 72 hours later.

Following application 1, the test material did not elicit any visible evidence of irritation in any of the individuals under test at concentrations ranging from 20 % to 100 %. Following application 2, the test material did not elicit any visible evidence of irritation in any of the individuals under test at concentrations ranging from 20 % to 100 %. On the basis of these results, it was decided that all subsequent applications would be at 100 % concentration. Following applications 5 to 12, the test material (100 %) elicited visible irritation in one individual of 1+ intensity on the eleventh application. Following application 13 (challenge), the test material did not elicit any visible evidence of irritation in any of the individuals under test at a concentration of 100 %.

The absence of any visible irritation resulting from application 1 indicates that the test item, at concentrations of 20 % to 100 %, did not act as a primary irritant. The absence of any irritation resulting from applications 2 to 4, in concentrations of 20 %, 40 %, 60 %, 80 % and 100 %, indicates that the test material did not act as a fatiguing agent. The absence of any irritation resulting from applications 5 to 12, at 100 % concentration, indicates that the test material did not act as a fatiguing agent. The presence of a minimal irritation (1+) in one individual (number 6) was not considered significant by the investigator. The absence of any irritation resulting from application 13 (challenge) indicates that the test material, at 100 % concentration, did not act as a sensitiser and confirms the previous interpretation that the test material does not act as a primary irritant.