Dimethylbis[2-[(1-oxooctadecyl)oxy]ethyl]ammonium chloride

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:

weight of evidence

Study period:

1993-01-18 to 1993-02-26

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 good clinical practices guideline 21CFR parts 50 and 56 and proposed ICH guidelines).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

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 Stotts 1980 and P&G Protocol issued 18th September 1989.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

MDEA-Esterquat C16-18 and C18 unsatd.

IUPAC Name:

MDEA-Esterquat C16-18 and C18 unsatd.

Details on test material:

- Name of test material (as cited in study report): FV-base E 4676.01
- Diethyl ester dimethyl ammonium chloride
- Molecular formula (if other than submission substance): C42H84NO4.Cl
- Molecular weight (if other than submission substance): 702.582
- Substance type: Active
- Physical state: Liquid
- Analytical purity: confidential detail
- Impurities (identity and concentrations): confidential detail
- Composition of test material, percentage of components: confidential detail
- Isomers composition: Not available
- Purity test date: confidential detail
- Lot/batch No.: confidential detail
- Expiration date of the lot/batch: confidential detail
- Stability under test conditions: Not available
- Storage condition of test material: Ambient temperature
- Other: None

Method

Type of population:

general

Ethical approval:

confirmed and informed consent free of coercion received

Subjects:

- Number of subjects exposed: 103 subjects were enrolled and 95 completed the study. A total of eight subjects failed to complete the test. None of these subjects dropped out of the study as a result of skin problems due to application of the test material or as a result of test procedures.
- Sex: 102 Females and 1 Males
- Age: Females - (18 to 65+), Male- (35 to 44)
- Race: Predominantly caucasian
- Demographic information: Corn exchange, Dunbar, East Lothian, Scotland
- Other: None

Clinical history:

- History of allergy or casuistics for study subject or populations: Not available
- Symptoms, onset and progress of the disease: Not available
- Exposure history: Not available
- Aggravating factors both in home and workplace: Not available
- Family history: Not available
- Medical history (for respiratory hypersensitivity): Not available
- Any other allergic or airway disorders: Not available
- Smoking history: Not available
- Other: None

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)
Test substance concentration: 2 % a.i of test substance. ( 20 % w/v dilution of a provided substance, with concentration of 10 % a.i)

ADMINISTRATION
- Type of application: patch application
- Description of patch: Not given
- Concentrations: 20% w/v in distilled water
- Volume applied: not given
- Testing/scoring schedule: 48 hours after each of the 9 induction patches and at 48 and 96 hours after the challenge patch application
- Removal of test substance: 24 hour 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: 0/95
- Number of subjects with negative reactions: 95/95
- Number of subjects with equivocal reactions: 0/95
- Number of subjects with irritating reactions: 14/95 exhibited mild erythema (grade 1) and 1/95 exhibited moderate erythema (grade 2)

Any other information on results incl. tables

103 volunteers took part in this study. 8 dropped out before challenge, therefore a total of 95 subjects were challenged in this study.

Results are summarized in the table below.

Induktion	No. Of Occasions Scores were given									Not Patched	Dropped out
	0	1	1E	2	2E	3	3E	4	N9G
1	98	1	0	0	0	0	0	0	0	4	0
2	75	24	0	3	0	0	0	0	0	1	0
3	32	59	0	3	0	0	0	0	0	9	0
4	32	67	0	3	0	0	0	0	0	1	0
5	19	81	0	1	0	0	0	0	0	1	1
6	16	79	0	1	0	0	0	0	0	3	4
7	13	78	0	2	0	0	0	0	0	5	5
8	10	83	0	4	0	0	0	0	0	0	6
9	8	83	0	3	0	0	0	0	3	0	6
MU	1	13	0	0	0	0	0	0	6	77	6
Challenge										Not scored	Dropped out
48 h O	84	10	0	1	0	0	0	0	0	0	8
48 h A	86	9	0	0	0	0	0	0	0	0	8
96 h O	86	8	0	1	0	0	0	0	0	0	8
96 h A	89	6	0	0	0	0	0	0	0	0	8

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 2.0 % 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 95 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 nine induction exposures. A total of 88/95 subjects completing the study had mild erythema (grade 1) and 3/95 subjects had moderate erythema (grade 2). After 2 weeks, treatment sites were challenged and observed at 48 and 96 hours after patch. A total of 14/95 subjects completing the study had mild erythema (grade 1) and 1/95 subjects had moderate erythema (grade 2). No responses indicative of skin sensitization was observed.

Applicant's summary and conclusion

Conclusions:

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

Executive summary:

In a dermal sensitization study according to the publication of Stotts, J., (1980), Planning, Conduct and Interpretation Human Predictive Sensitisation Patch Test, Current Concepts in Cutaneous Toxicity, pp 41-53 with MDEA-Esterquat C16-18 and C18 unsatd.  2,0 % aqueous dilution a total of 95 volunteers were tested using a Human Repeat Insult Patch method. 

103 volunteers took part in the study and were exposed to 9 induction patches under occlusive dressing during a three week period. 8 volunteers dropped out, due to personal reason. 95 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 erthema 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.