1-Propanaminium, 2-hydroxy-N-(2-hydroxypropyl)-N,N-dimethyl-, esters with fatty acids, C16-18 (even numbered) and C18 unsatd., Me sulfates (salts)

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

1986-05-12 to 1986-07-04

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards and is described in sufficient detail, (study conducted according to the good clinical practices regulation 21CFR part 50, 56).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Type of sensitisation studied:

skin

Study type:

study with volunteers

Test guideline

Qualifier:

no guideline available

Deviations:

no

Principles of method if other than guideline:

According to the publication of Griffith 1969 and Stotts 1980

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-Propanaminium, 2-hydroxy-N-(2-hydroxypropyl)-N,N-dimethyl-, esters with fatty acids, C16-18 (even numbered) and C18 unsatd., Me sulfates (salts)

Cas Number:

1079184-43-2

Molecular formula:

n.a. (UVCB)

IUPAC Name:

1-Propanaminium, 2-hydroxy-N-(2-hydroxypropyl)-N,N-dimethyl-, esters with fatty acids, C16-18 (even numbered) and C18 unsatd., Me sulfates (salts)

Details on test material:

- Name of test material (as cited in study report): FV-base, E 2819.01
- (Diethyl ester dimethyl ammonium chloride) (FV-Base)
- Molecular formula (if other than submission substance): C42H84NO4.Cl
- Molecular weight (if other than submission substance): 702.582
- Substance type: Active
- Physical state: Solid paste
- Analytical purity: confidential detail
- Impurities (identity and concentrations): confidential detail
- Composition of test material, percentage of components: confidential detail
- Isomers composition: confidential detail
- Purity test date: confidential detail
- Lot/batch No.: confidential detail
- Expiration date of the lot/batch: confidential detail
- Stability under test conditions: Not given
- Storage condition of test material: 5-30 degree C
- Other: None

Method

Type of population:

general

Ethical approval:

confirmed and informed consent free of coercion received

Subjects:

- Number of subjects exposed: 90 volunteers commenced the study and 84 completed the study
- Sex: males and females
- Age: Females (16-64),males (25-65+)
- Race: Predominately Caucasian
- Demographic information: Haddington and surrounding area
- Other: Not applicable

Subjects with skin conditions such as cancer, active eczema, psoriasis or diseases of the skin that might interfere with the evaluation of study were excluded from the study. Systemic intake of anti-inflammatory steroid or application of any drugs to the area of the body being used in the test lead to exclusion from study. Volunteers with severe diabetes (require insulin), severe asthma and bilateral mastectomy or a mastectomy within the last year were excluded from the study.

Clinical history:

Questionnaire was completed before study start, to record personal data, participation in further HRIP-test, skin problems, current use of medication, diabetes, severe asthma and Mastectomy.

Controls:

None; however the use of positive control substances in human sensitization tests is not indicated due to ethical considerations.

Route of administration:

dermal

Details on study design:

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

ADMINISTRATION
- Type of application: occlusive
- Description of patch: 2 cm square Webril pad located down the centre line of a piece of Blenderm tape
- Concentrations: 1.50 % w/v aqueous solution of test substance
- Volume applied: 0.5 mL
- Testing/scoring schedule: 48 hours after each of the 9 induction patches and at 48 & 96 hours after the challenge patch application.
2 subjects were graded after 96 hours and 1 subject after 48 hours only
- Removal of test substance: 24 hours after each of the 9 induction patch and 24 hours after the challenge patch.

Results and discussion

Results of examinations:

NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION
- Number of subjects with positive reactions: 0/84
- Number of subjects with negative reactions: 84/84
- Number of subjects with equivocal reactions: 0/84
- Number of subjects with irritating reactions: 16/84 exhibited mild skin irritation (grade 1) during challenge

Any other information on results incl. tables

26 volunteers took part in and completed the preliminary panel, 64 volunteers formed the main group and 6 dropped out before challenge. A total of 58 subjects were challenged in the main panel. Thus a total of 84 subjects were challenged and graded in both panels.

Results are summarized in the table below.

Two subjects were graded after ninety-six hours only and one subject was finally graded after forty-eight hours.

Induktion	No. Of Occasions Scores were given									Not Patched	Dropped out
	0	1	1E	2	2E	3	3E	4	N9G
1	60	14	0	0	0	0	0	0	0	16	0
2	52	30	0	0	0	0	0	0	0	4	4
3	36	46	0	0	0	0	0	0	0	4	4
4	23	59	0	1	0	0	0	0	0	2	5
5	14	64	0	2	0	0	0	0	0	5	5
6	10	70	0	2	0	0	0	0	0	3	5
7	8	73	0	2	0	0	0	0	0	1	6
8	7	73	0	1	0	0	0	0	0	3	6
9	6	73	0	4	0	0	0	0	1	0	6
MU	4	25	0	0	0	0	0	0	3	52	6
Challenge										Not scored	Dropped out
48 h O	67	15	0	0	0	0	0	0	0	2	6
48 h A	74	8	0	0	0	0	0	0	0	2	6
96 h O	77	6	0	0	0	0	0	0	0	1	6
96 h A	82	1	0	0	0	0	0	0	0	1	6

MU     Subject who were absent once during the insult period received a make up patch on the fourth Monday.

N9G    No ninth grade. Subject has worn nine induction patches, but was not present for scoring following ninth induction application.

O         Original site

A        Alternate site

The test material was applied at 1.5 % w/v dilution throughout the study and caused an acceptable level of irritation (mild to particular moderate erythema) during the induction stage. There was no evidence of sensitization observed in any of the 84 subjects who were challenged at the end of the study.

SYMPTOMS

- Frequency, level, duration of symptoms observed: Treatment sites were observed 48 hours after patching on a Monday, Wednesday, Friday regimen for 3 weeks for 9 induction exposures. A total of 74/84 subjects completing the study had mild erythema (grade 1) and 4/84 subjects had moderate erythema (grade 2) during induction. After two weeks, treatment sites were challenged and observed at 48 & 96 hours after patch. A total of 16/84 subjects completing the study had mild erythema (grade 1)

Applicant's summary and conclusion

Conclusions:

MDEA-Esterquat C16-18 and C18 unsatd. did not produce skin sensitization in this human Repeat Insult Patch Test.

Executive summary:

In a dermal sensitization study, according to the publications of Griffith, J.F., (1969), Predictive and Diagnostic Testing for Contact Sensitisation, Toxicol. Appl. Pharmacol., Suppl.3:90 and Stotts, J., (1980), Planning, Conduct and Interpretation Human Predictive Sensitisation Patch Test, Current Concepts in Cutaneous Toxicity, pp 41-53 with MDEA-Esterquat 1,5 % aqueous dilution a total of 84 volunteers were tested using a Human Repeat Insult Patch method.

90 volunteers took part in the study and were exposed to 9 induction patches containing 0.5 ml w/v aqueous solution of test substance under occlusive dressing during a three week period. 6 volunteers dropped out, due to personal reason. 84 volunteers were challenged using the same concentration and procedure 14 days after the final induction patch.

Results were graded using a scoring system 1 -6 for erythema and edema after 48 and 96 hours. Acceptable irritation with mild (score 1) to particular moderate (score 2) erythema was observed throughout the study. No edema, which would be indicative for sensitisation was observed.

In this study, MDEA-Esterquat C16-18 and C18 unsatd.  is not a dermal sensitizer.