N-2-hydroxyethylacetamide

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 July 1977 to 2 September 1977

Reliability:

2 (reliable with restrictions)

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:

1977

Report date:

1977

Materials and methods

Type of sensitisation studied:

skin

Study type:

study with volunteers

Principles of method if other than guideline:

The ability of the skin to tolerate a 7.5 % w/v preparation (in distilled water) of the test material was determined in the absence of visible skin changes resulting from the first 24 hour application.
Each individual’s tolerance was established and the test was continued with the 7.5 % preparation.
The material was scheduled to be applied daily, Monday through Thursday for three consecutive weeks. If substantial irritation occurred attributed to the application of the test material, the study director at his discretion, could either change the site of the application or modify the method of applying the test material. Throughout the test, the investigator chose a change of test site in the event of any substantial irritation.
A total of 12 induction applications were applied to the 50 volunteers. The occlusive patches were held in place for 24 hours. At the end of each 24 hours, the patches were removed and the test site were scored for effects. In the event of no significant irritation, the test material was re-applied to the same test site. This was repeated Monday through Thursday for 3 weeks. After the Patch was removed on the Friday for scoring, the test site was then rested over the weekend, with patching recommencing on the following week. Following the last induction exposure, the challenge application was commenced on day 36 of the study at a fresh test site. The test material was applied as an occlusive patch and held in place for 24 hours. The test site was then scored after 24, 48 and 72 hours for reactions.

GLP compliance:

no

Remarks:

Not applicable.

Test material

Test material information

1

Reference substance name:

Reaction mass of N-2-hydroxyethylacetamide and N,O-diacetyl-2-aminoethanol

Molecular formula:

C4H9NO2 (amide) & C6H11NO3 (amido ester)

IUPAC Name:

Reaction mass of N-2-hydroxyethylacetamide and N,O-diacetyl-2-aminoethanol

Method

Type of population:

general

Ethical approval:

confirmed and informed consent free of coercion received

Subjects:

- Number of subjects exposed: 50

Clinical history:

- History of allergy or casuistics for study subject or populations: The criteria for participants were to have general good health and well-being. Participants were also selected on the basis that they were free of any illnesses which may give rise to lesions which may erroneously be attributed to the test material. All participants were determined to have no skin lesions at admission to the study.- History of allergy or casuistics for study subject or populations:
- Symptoms, onset and progress of the disease:
- Exposure history:
- Aggravating factors both in home and workplace:
- Family history:
- Medical history (for respiratory hypersensitivity):
- Any other allergic or airway disorders:
- Smoking history:
- Other:

Controls:

Not included.

Route of administration:

dermal

Details on study design:

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

ADMINISTRATION
- Type of application: occlusive
- Vehicle / solvent: Distilled water
- Concentrations: 7.5 % w/v
- Testing/scoring schedule: The test material was applied via occlusive patch commencing on Monday and remained in place for 24 hours. After twenty-four hours, the patch was removed and the contact site examined and scored for reactions. If the reaction was non-significant (a score of no greater than 1), then the test material was re-applied to the same site for a further twenty-four hours. This procedure was then repeated on the Wednesday and Thursday. The patch was removed on Friday and scored for reactions. The test site was rested over Saturday and Sunday. This procedure was repeated for three weeks during the induction phase. In all, a total of twelve applications and readings were scheduled. For the Challenge phase, the test material was applied to a new test site as a challenge on day 36. At the end of the 24-hour period, the occluded patch was removed and the site was read for the immediate response. Follow-up readings were performed at 24, 48 and 72 hours.


EXAMINATIONS
- Grading/Scoring system:
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 and extension beyond the boundaries of contact.

- Statistical analysis:
The binomial confidence limits were evaluated in accordance with “Table No. 9 Binomial Confidence Limits,” Tables for use with Binomial Samples (Mainland D et al, (1956) Sutcliffe, Department of Medical Statistics, New York University College of Medicine.

Results and discussion

Results of examinations:

SYMPTOMS
- Frequency, level, duration of symptoms observed:

NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION
- Number of subjects with positive reactions: 0
- Number of subjects with negative reactions: 50
- Number of subjects with equivocal reactions: 0


OTHER RESULTS:
- Applications
Week 1: No visible irritation was observed in any of the 50 indviduals in the test
Week 2: 1 individual demonstrated a reaction recorded as 1+.
Week 3: Visible irritation was observed in two individuals. One subject manifested a reaction graded as 2+ on the 11th application. A new application site was used. A further subject manifested a reaction of 1+ on the 10th application.

- Observations:
The absence of any visible irritation following the first application of this material indicated that the test material was not acting as a primary irritant under the conditions of the test.
The appearance of visible irritation in one individual starting with the 11tha application, indicates that he material was acting as a fatiguing agent to the skin resulting from the cumulative effect of two or more application periods.
The absence of any visible irritation resulting from the challenge application confirms that the material was not acting as a primary irritant under the condition of the test and was not a sensitiser to any of the individuals participating in the study.
In two individuals, a 1+ response was noted without any confirmation of repetition on subsequent applications. Therefore, these solitary observations were not considered significant.

- Limiting Factors:
The variance of the conditions of general use from those of the test. The conditions of the test are designed to intentionally elicit irritation to give the investigator a level for comparison. The conditions of the test which are exaggerated when comparted to the normal use of the test products are the duration of contact and the cover which tends to maintain a steady state of a micro-climate under the patch.
Based on the number of the individuals participating (50) and the numbers showing sensitisation (0), it is possible to predict with 95 % certainty that the test material will be tolerated by 92.89-100 % of a general population.

Any other information on results incl. tables

Table 1: Number of subjects showing reactions:

Number of Application	Number of Reactions In Grades Indicated
	0	1+	2+	3+	4+	NP
1	50	0	0	0	0	0
2	50	0	0	0	0	0
3	50	0	0	0	0	0
4	50	0	0	0	0	0
5	50	0	0	0	0	0
6	50	0	0	0	0	0
7	49	1	0	0	0	0
8	50	0	0	0	0	0
9	50	0	0	0	0	0
10	49	1	0	0	0	0
11	49	0	1	0	0	0
12	50	0	0	0	0	0
Challenge	50	0	0	0	0	0
Scoring criteria: 0 = No reaction 1+ = Slight erythema 2+ = Marked erythema 3+ = Marked erythema, oedema, with or without a few vesicles 4+ = Marked erythema, oedema, with vesicles and oozing NP = No patch

 

Table 2: Individual Reactions

	Exposure number
Subject Number	1	2	3	4	5	6	7	8	9	10	11	12	Challenge
1	0	0	0	0	0	0	0	0	0	0	0	0	0
2	0	0	0	0	0	0	0	0	0	0	0	0	0
3	0	0	0	0	0	0	0	0	0	0	0	0	0
4	0	0	0	0	0	0	0	0	0	0	0	0	0
5	0	0	0	0	0	0	0	0	0	0	0	0	0
6	0	0	0	0	0	0	0	0	0	0	0	0	0
7	0	0	0	0	0	0	0	0	0	0	0	0	0
8	0	0	0	0	0	0	0	0	0	0	0	0	0
9	0	0	0	0	0	0	0	0	0	0	0	0	0
10	0	0	0	0	0	0	0	0	0	0	0	0	0
11	0	0	0	0	0	0	0	0	0	0	0	0	0
12	0	0	0	0	0	0	0	0	0	0	0	0	0
13	0	0	0	0	0	0	0	0	0	0	0	0	0
14	0	0	0	0	0	0	0	0	0	0	0	0	0
15	0	0	0	0	0	0	0	0	0	0	0	0	0
16	0	0	0	0	0	0	1+	0	0	0	0	0	0
17	0	0	0	0	0	0	0	0	0	0	0	0	0
18	0	0	0	0	0	0	0	0	0	0	0	0	0
19	0	0	0	0	0	0	0	0	0	0	0	0	0
20	0	0	0	0	0	0	0	0	0	0	0	0	0
21	0	0	0	0	0	0	0	0	0	0	0	0	0
22	0	0	0	0	0	0	0	0	0	0	0	0	0
23	0	0	0	0	0	0	0	0	0	0	2+	0	0
24	0	0	0	0	0	0	0	0	0	0	0	0	0
25	0	0	0	0	0	0	0	0	0	0	0	0	0
26	0	0	0	0	0	0	0	0	0	0	0	0	0
27	0	0	0	0	0	0	0	0	0	0	0	0	0
28	0	0	0	0	0	0	0	0	0	0	0	0	0
29	0	0	0	0	0	0	0	0	0	0	0	0	0
30	0	0	0	0	0	0	0	0	0	0	0	0	0
31	0	0	0	0	0	0	0	0	0	0	0	0	0
32	0	0	0	0	0	0	0	0	0	1+	0	0	0
33	0	0	0	0	0	0	0	0	0	0	0	0	0
34	0	0	0	0	0	0	0	0	0	0	0	0	0
35	0	0	0	0	0	0	0	0	0	0	0	0	0
36	0	0	0	0	0	0	0	0	0	0	0	0	0
37	0	0	0	0	0	0	0	0	0	0	0	0	0
38	Dropped
39	0	0	0	0	0	0	0	0	0	0	0	0	0
40	0	0	0	0	0	0	0	0	0	0	0	0	0
41	0	0	0	0	0	0	0	0	0	0	0	0	0
42	0	0	0	0	0	0	0	0	0	0	0	0	0
43	0	0	0	0	0	0	0	0	0	0	0	0	0
44	0	0	0	0	0	0	0	0	0	0	0	0	0
45	0	0	0	0	0	0	0	0	0	0	0	0	0
46	0	0	0	0	0	0	0	0	0	0	0	0	0
47	0	0	0	0	0	0	0	0	0	0	0	0	0
48	0	0	0	0	0	0	0	0	0	0	0	0	0
49	0	0	0	0	0	0	0	0	0	0	0	0	0
50	0	0	0	0	0	0	0	0	0	0	0	0	0
51	0	0	0	0	0	0	0	0	0	0	0	0	0
52	Dropped

 

Applicant's summary and conclusion

Conclusions:

The test material, when tested as a 7.5 % w/v solution in distilled water was capable of eliciting irritation in 1 out of 50 volunteers. In the opinion of the investigator, this was a manifestation of skin fatigue resulting from the cumulative effect of eleven or more applications of the test material under occlusive conditions. The test material did not manifest any evidence of primary irritation or sensitisation.
Under the conditions of the test, it was concluded that the test material was not a sensitiser or a primary irritant.

Executive summary:

The ability of the skin to tolerate a 7.5 % w/v preparation (in distilled water) of the test material was determined in the absence of visible skin changes resulting from the first 24 hour application.

Each individual’s tolerance was established and the test was continued with the 7.5 % preparation.

The material was scheduled to be applied daily, Monday through Thursday for three consecutive weeks. If substantial irritation occurred attributed to the application of the test material, the study director at his discretion, could either change the site of the application or modify the method of applying the test material. Throughout the test, the investigator chose a change of test site in the event of any substantial irritation.

A total of 12 induction applications were applied to the 50 volunteers. The occlusive patches were held in place for 24 hours. At the end of each 24 hours, the patches were removed and the test sites were scored for effects. In the event of no significant irritation, the test material was re-applied to the same test site. This was repeated Monday through Thursday for 3 weeks. After the Patch was removed on the Friday for scoring, the test site was then rested over the weekend, with patching recommencing on the following week. Following the last induction exposure, the challenge application was commenced on day 36 of the study at a fresh test site. The test material was applied as an occlusive patch and held in place for 24 hours. The test site was then scored after 24, 48 and 72 hours for reactions.

The test material, when tested as a 7.5 % w/v solution in distilled water was capable of eliciting irritation in 1 out of 50 volunteers. In the opinion of the investigator, this was a manifestation of skin fatigue resulting from the cumulative effect of eleven or more applications of the test material under occlusive conditions. The test material did not manifest any evidence of primary irritation or sensitisation.

Under the conditions of the test, it was concluded that the test material was not a sensitiser or a primary irritant.