Acetic acid, esters with lanolin alcs.

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

18 October 1976 to 26 November 1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, well documented and acceptable for assessment.

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1976

Report date:

1976

Materials and methods

Endpoint addressed:

skin irritation / corrosion

skin sensitisation

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Irritation and sensitisation potentials of test material ascertained under conditions of a stringently supervised and monitored patch test.

GLP compliance:

no

Remarks:

investigation took place prior to introduction of GLP

Test material

Test material information

Constituent 1

Reference substance name:

Hexadecyl acetate

EC Number:

211-103-7

EC Name:

Hexadecyl acetate

Cas Number:

629-70-9

Molecular formula:

C18H36O2

IUPAC Name:

hexadecyl acetate

Constituent 2

Reference substance name:

Acetic acid, esters with lanolin alcs.

EC Number:

262-980-8

EC Name:

Acetic acid, esters with lanolin alcs.

Cas Number:

61788-49-6

Molecular formula:

C29H48O2

IUPAC Name:

Acetic acid, esters with lanolin alcs.

Test material form:

liquid

Method

Ethical approval:

not specified

Details on study design:

PARTICIPANTS
- A group of 56 individuals were 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 statement of consent, age 18 or over.

PROCEDURE
- In order to evaluate the test material, the investigator was authorised to use that concentration which he felt was best suited to achieve the objective of the study.
- It was considered logical that the validity of the result would be improved by using a higher concentration of test material. It was therefore necessary from the outset to determine the maximum concentration which human skin could tolerate under the patch conditions and which would pertain throughout the procedure.
- Patch conditions were (i) complete occlusion (ii) 24 hour duration of contact (iii) density of application of approximately 0.1 mL of the test material per square centimetre.
- To determine the concentration, the group of participants were divided into five subgroups each receiving a different concentration of test material.
- 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 to determine whether successive 24 hour applications showed that the test material was cumulatively irritating.
- This “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 a lower concentration would be used for subsequent applications.
- If the first 24 hour application was tolerated, but intolerance developed after the second or third exposure, the provision was made for change of site only. In the event that the new site responded, the concentration would then be lowered.
- In this manner, each individual’s tolerance was established.
- After the fourth application, the results were analysed and one concentration was selected for all future applications on all individuals. The concentration selected for the test material was 50 %.
- After establishing the maximum concentration of test material which could be tolerated by the 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.
- The investigator reserved the option changing the concentration if, in his opinion, the irritation obtained on subsequent readings justified such a change. If such a change was made, the change was described as a deviation from scheduled procedure.
- The second phase of the study consisted of the challenge, which was scheduled to be applied on the 36th day of the procedure on a virgin site. This application took place after a hiatus of seventeen days from the last reading in the induction series.

Exposure assessment:

not specified

Details on exposure:

TEST MATERIAL CONCENTRATION
- Individuals 1 to 10: Test material 10 % in petrolatum
- Individuals 11 to 19: Test material 30 % in petrolatum
- Individuals 20 to 31: Test material 20 % in petrolatum
- Individuals 32 to 43: Test material 40 % in petrolatum
- Individuals 44 to 56: Test material 50 % in petrolatum

INDUCTION PHASE
- Each subject was patched with test material on Monday, 18 October.
- The patch was occlusive and remained in situ for 24 hours.
- The patch was removed on Tuesday and the contact site was examined and reactions, if any, were scored as 0 = no visible erythema; 1 = erythema; 2 = erythema plus swelling; 3 = erythema, swelling, plus papules; 4 = severe irritation consisting of erythema, swelling, papules, and necrosis with extension beyond the boundaries of contact.
- If the reaction was not substantial (ie not in excess of grade 1), the test material was reapplied 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 site developed a reaction of ≥ 2, the investigator had the discretion to continue subsequent applications on the same site, and continue the same type of patch (occlusive), or to change to semi-occluded or open applications.
- A total of twelve applications and readings were scheduled for the induction period.

CHALLENGE PHASE
- On the 36th day 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 the 24 hours, the occlusive patch was removed and the site was read for the immediate response.
- Follow-up readings were made 24, 48 and 72 hours later.
- In the event that the challenge application produced significant reactions, additional challenge applications were performed in an attempt to ascertain whether or not the reaction was a bona fide case of sensitisation and, if so, what effect the changes in concentration and cover have on the recall mechanism.

Results and discussion

Results:

APPLICATION 1
- The test material did not elicit any visible evidence of irritation in any of the individuals under test.

APPLICATIONS 2-12
- The test material did not elicit any visible responses in 50 out of 53 individuals who completed the test.
- In subject 29, the test material produced a reaction of grade 2 as a result of the tenth application. This necessitated a change of site on the eleventh and twelfth applications.
- In subject 37, the test material elicited reactions of grade 1 after the third, sixth, seventh, eighth and eleventh applications. The reaction disappeared within 48 hours after discontinuation of applications.
- In subject 51, the test material produced a reaction of grade 2 after the eleventh application. This necessitated a change of site on the twelfth application.

APPLICATION 13
- The test material did not elicit any visible response in any of the individuals under test.

Any other information on results incl. tables

DEVIATIONS FROM PROTOCOL

- Two individuals (29 and 51) required change of sites because of substantial irritation.

- For subject 29, the site was changed for the eleventh application.

- For subject 51, the site was changed on the twelfth application.

- Details of deviations are shown in Chart 3 (attached).

 

CORRECTIONS

- Three individuals (5, 8 and 43) were scheduled to participate but dropped out of the study prior to its initiation.

Applicant's summary and conclusion

Conclusions:

Results of the first application indicate that the test material was incapable of acting as a primary irritant in any of the individuals in the test panel. The presence of irritation as a result of exposure during applications 2 to 12 indicate that the test material was capable of eliciting irritation in 3 out of 53 individuals as a consequence of cumulative effect. The evidence that the 50 % solution is capable of fatiguing the skin should not be construed as an indication that the test material is unsafe but, in the opinion of the investigator, such a high concentration should be avoided if possible in favour of a lower one in general use. With respect to skin sensitisation, it was predicted with 95 % certainty that at least 92.89 % of a general population will not be sensitised by the test material.

Executive summary:

METHOD

Test material in concentrations of 10, 20, 30, 40 and 50 % in petrolatum, was applied to the skin of human volunteers on four consecutive days for three weeks.

RESULTS

No visible damage to the skin of 53 individuals was observed with respect to primary irritation. However, there were responses in two individuals which were compatible with a classification of cumulative irritation or fatigue of the skin. Evidence for skin sensitisation was absent.

CONCLUSION

Results of the first application indicate that the test material was incapable of acting as a primary irritant in any of the individuals in the test panel. The presence of irritation as a result of exposure during applications 2 to 12 indicate that the test material was capable of eliciting irritation in 3 out of 53 individuals as a consequence of cumulative effect. The evidence that the 50 % solution is capable of fatiguing the skin should not be construed as an indication that the test material is unsafe but, in the opinion of the investigator, such a high concentration should be avoided if possible in favour of a lower one in general use. With respect to skin sensitisation, it was predicted with 95 % certainty that at least 92.89 % of a general population will not be sensitised by the test material.