Lanolin, acetate

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 October 1976 to 26 November 1976

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1976

Report date:

1976

Materials and methods

Study type:

study with volunteers

Endpoint addressed:

skin irritation / corrosion

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

To determine the irritation and sensitisation potential of the test material, a human repeat insult patch test was performed in 53 human volunteers. The test material was applied via occlusive patch at a dosing rate of 0.1 mL/cm². To determine a suitable dosing regimen, the volunteers were dosed in groups of 10 (minimum) with the following concentrations in petrolatum, 100 %, 80%, 60 %, 40 % and 20 % (titration skin tolerance). The test material was found to be well tolerated, therefore after the first week of induction exposures a single exposure concentration of 100 % was selected for the remained of the study.
Patches were applied Monday through Thursday for 3 weeks, with observations performed after each patch removal. The patch site was rested over the weekend and dosing recommenced the following Monday. A total of 12 inductions applications were administered. On day 36 (just over 2 weeks after the induction exposures), the test material was challenge application was administered as a single exposure at 100 % for 24 hours. The test site was then read at patch removal for immediate response, then again at 24, 48 and 72 hours to determine skin reactions.

GLP compliance:

no

Remarks:

Not applicable

Test material

Test material information

Constituent 1

Reference substance name:

Lanolin, acetate

EC Number:

262-979-2

EC Name:

Lanolin, acetate

Cas Number:

61788-48-5

Molecular formula:

Variable

IUPAC Name:

Lanolin, Acetates

Test material form:

solid

Method

Type of population:

general

Subjects:

- Number of subjects exposed: 53 (56 volunteers were selected and individuals 5, 8 and 43 dropped out prior to study initiation).
- Age: Over the age of 18
- History of allergy or casuistics for study subject or populations: Volunteers were selected based on general well-being and absence of skin disease.

Ethical approval:

confirmed and informed consent free of coercion received

Route of exposure:

dermal

Reason of exposure:

intentional

Exposure assessment:

measured

Details on exposure:

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

ADMINISTRATION
- Type of application: occlusive
- Vehicle / solvent: Petrolatum (skin irritation titration during the first week of inductions)
- Concentrations: 20, 40, 60, 80 and 100 % during the first week of induction exposures (skin titration for irritation tolerance). All other applications were performed at 100 %.
- Volume applied: 0.1 mL/cm²

- Testing/scoring schedule:
Induction: A total of 12 induction applications were performed. The test site was examined after each patch removal. If the reaction was not substantial (a score not in excess of 1), then the test material was re-applied to the same site).
Week 1, skin titration was performed, volunteers were split into 5 groups. Patches were applied Monday through Thursday. The test material patches remained in situ for 24 hours, and renewed after scoring at the end of each 24 hour period. On Friday, the patch was removed and the site scored. The skin was then allowed to rest over the weekend.
Volunteers 1-10 were dosed with neat material
Volunteers 11-19 were dosed with 40 % test material in petrolatum
Volunteers 20-31 were dosed with 80 % test material in petrolatum
Volunteers 32-43 were dosed with 20 % test material in petrolatum
Volunteers 44-56 were dosed with 60 % test material in petrolatum
Weeks 2 and 3, after the test material was found to be well tolerated, all subjects were dosed with the neat test material (100 %). Patches were applied Monday through Thursday. The test material patches remained in situ for 24 hours, and renewed after scoring at the end of each 24 hour period. On Friday, the patch was removed and the site scored. At the end of the second week the test site was allowed to rest over the weekend before commencing again on week 3.
In the event of a significant response at the test site (Score greater than 2), the study director could, at his discretion, elect to apply the patch at a fresh test site.
Challenge exposure: On day 36 (slightly more than 2 weeks after the last induction exposure), the test material (100 %) was applied to a new test site and left in situ for 24 hours.

Examinations:

- Schedule for Examinations: Test sites were examined after each patch removal during the induction phase. During the challenge phase, the test site was evaluated immediately after patch removal, then once every 24 hours for 3 days.

EXAMINATIONS
- Grading/Scoring system:
0 = No visible erythema
1 = Erythema
2 = Erythema plus swelling
3 = Erythema, swelling, plus papules
4 = Sever irritation consisting of erythema, swelling papules, and necrosis and extenion beyond the boundries of contact
- Statistical analysis: Statistical consideration were performed using Tables for use with binomial samples (1956) Mainland D et al, Sutcliffe Department of Medical Statistics, New York University of College Medicine.

Results and discussion

Results of examinations:

SYMPTOMS
- Frequency, level, duration of symptoms observed: No visible irritation was observed in any individual after the first application. The test material didn't elicit any visible evidence of irritation in 51 of the individuals under the test. Individual 29 and 37 demonstrated minimal erythema on the 12 and 11th and 12th applications, respectively. This recovered within 24 hours of patch removal.
At challenge, no visible reactions were noted. These were interpreted as skin fatigue and not evidence of irritation. The test material was incapable of acting as a primary irritant.

Any other information on results incl. tables

Table 1: Dermal observations

Subject	Concentration (%) Skin Titration	Application (Monday - Thursday)												Challenge (Day 36) (100 %)
		Induction Week 1 (Skin Irritation Titration)				Induction Week 2 (100 %)				Induction Week 3 (100%)
		1	2	3	4	5	6	7	8	9	10	11	12	Immediate Response	24 Hours	48 Hours	72 Hours
1	100%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
2	100%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
3	100%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
4	100%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
5	100%	Dropped out
6	100%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
7	100%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
8	40%	Dropped out
9	40%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
10	40%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
11	40%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
12	40%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
13	40%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
14	40%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
15	40%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
16	40%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
17	40%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
18	40%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
19	40%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
20	40%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
21	80%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
22	80%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
23	80%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
24	80%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
25	80%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
26	80%	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
27	80%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
28	80%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
29	80%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
30	80%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
31	80%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
32	20%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
33	20%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
34	20%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
35	20%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
36	20%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
37	20%	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0
38	20%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
39	20%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
40	20%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
41	20%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
42	20%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
43	20%	Dropped out
44	60%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
45	60%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
46	60%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
47	60%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
48	60%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
49	60%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
50	60%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
51	60%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
52	60%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
53	60%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
54	60%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
55	60%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
56	60%	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Applicant's summary and conclusion

Conclusions:

Under the conditions of the test, the test material was found to be non-irritating to skin when dosed as the neat material in human volunteers.

Executive summary:

To determine the irritation and sensitisation potential of the test material, a human repeat insult patch test was performed in 53 human volunteers. The test material was applied via occlusive patch at a dosing rate of 0.1 mL/cm². To determine a suitable dosing regimen, the volunteers were dosed in groups of 10 (minimum) with the following concentrations in petrolatum, 100 %, 80%, 60 %, 40 % and 20 % (titration skin tolerance). The test material was found to be well tolerated, therefore after the first week of induction exposures a single exposure concentration of 100 % was selected for the remained of the study.

Patches were applied Monday through Thursday for 3 weeks, with observations performed after each patch removal. The patch site was rested over the weekend and dosing recommenced the following Monday. A total of 12 inductions applications were administered. On day 36 (just over 2 weeks after the induction exposures), the test material was challenge application was administered as a single exposure at 100 % for 24 hours. The test site was then read at patch removal for immediate response, then again at 24, 48 and 72 hours to determine skin reactions.

No visible irritation was observed in any individual after the first application. The test material didn't elicit any visible evidence of irritation in 51 of the individuals under the test. Individual 29 and 37 demonstrated minimal erythema on the 12 and 11th and 12th applications, respectively. This recovered within 24 hours of patch removal.

At challenge, no visible reactions were noted. These were interpreted as skin fatigue and not evidence of irritation. The test material was incapable of acting as a primary irritant.

Under the conditions of the test, the test material was found to be non-irritating to skin in human volunteers when dosed as the neat material.