A mixture of isomers of: 1,1'-[(3,5(or 2,4 or 4,6 or 2,6)-dihydroxy-o(or m or p)-phenylene)bis(azo-meta-phenyleneazo{1-[3-(dimethylamino)propyl]-1,2-dihydro-6-hydroxy-4-methyl-2-oxopyridine-5,3-diyl})]dipyridinium-dichloride-dihydrochloride; 1-(1-[3-(dimethylamino)propyl]-5-{3-[x-(4-{1-[3-(dimethylamino)propyl]-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-5-pyridinio-3-pyridylazo}phenylazo)-2,4(or 2,6 or 3,5 or 4,6)-dihydroxyphenylazo]phenylazo}-1,2-dihydro-6-hydroxy-4-methyl-2-oxo-3-pyridyl)pyridinium-dichloride-dihydrochloride (where x is variable)

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1990-01-08 to 1990-02-15

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:

1990

Report date:

1990

Materials and methods

Type of sensitisation studied:

skin

Study type:

study with volunteers

Test material

Test material information

Constituent 1

Reference substance name:

A mixture of isomers of: 1,1'-[(3,5(or 2,4 or 4,6 or 2,6)-dihydroxy-o(or m or p)-phenylene)bis(azo-meta-phenyleneazo{1-[3-(dimethylamino)propyl]-1,2-dihydro-6-hydroxy-4-methyl-2-oxopyridine-5,3-diyl})]dipyridinium-dichloride-dihydrochloride; 1-(1-[3-(dimethylamino)propyl]-5-{3-[x-(4-{1-[3-(dimethylamino)propyl]-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-5-pyridinio-3-pyridylazo}phenylazo)-2,4(or 2,6 or 3,5 or 4,6)-dihydroxyphenylazo]phenylazo}-1,2-dihydro-6-hydroxy-4-methyl-2-oxo-3-pyridyl)pyridinium-dichloride-dihydrochloride (where x is variable)

EC Number:

404-540-1

EC Name:

A mixture of isomers of: 1,1'-[(3,5(or 2,4 or 4,6 or 2,6)-dihydroxy-o(or m or p)-phenylene)bis(azo-meta-phenyleneazo{1-[3-(dimethylamino)propyl]-1,2-dihydro-6-hydroxy-4-methyl-2-oxopyridine-5,3-diyl})]dipyridinium-dichloride-dihydrochloride; 1-(1-[3-(dimethylamino)propyl]-5-{3-[x-(4-{1-[3-(dimethylamino)propyl]-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-5-pyridinio-3-pyridylazo}phenylazo)-2,4(or 2,6 or 3,5 or 4,6)-dihydroxyphenylazo]phenylazo}-1,2-dihydro-6-hydroxy-4-methyl-2-oxo-3-pyridyl)pyridinium-dichloride-dihydrochloride (where x is variable)

Cas Number:

159405-95-5

Molecular formula:

C50H56Cl4N14O6

IUPAC Name:

1'-[3-(dimethylamino)propyl]-5'-(2-{3-[2-(4-{2-[3-(2-{1'-[3-(dimethylamino)propyl]-6'-hydroxy-4'-methyl-2'-oxo-1',2'-dihydro-1λ⁵-[1,3'-bipyridin]-1-ylium-5'-yl}diazen-1-yl)phenyl]diazen-1-yl}-2,6-dihydroxyphenyl)diazen-1-yl]phenyl}diazen-1-yl)-6'-hydroxy-4'-methyl-2'-oxo-1',2'-dihydro-1λ⁵-[1,3'-bipyridin]-1-ylium 1'-[3-(dimethylamino)propyl]-5'-(2-{4-[2-(4-{2-[4-(2-{1'-[3-(dimethylamino)propyl]-6'-hydroxy-4'-methyl-2'-oxo-1',2'-dihydro-1λ⁵-[1,3'-bipyridin]-1-ylium-5'-yl}diazen-1-yl)phenyl]diazen-1-yl}-2,6-dihydroxyphenyl)diazen-1-yl]phenyl}diazen-1-yl)-6'-hydroxy-4'-methyl-2'-oxo-1',2'-dihydro-1λ⁵-[1,3'-bipyridin]-1-ylium tetrahydrochloride tetrachloride

Method

Type of population:

general

Ethical approval:

confirmed and informed consent free of coercion received

Subjects:

- Number of subjects exposed: 114 (enrolled), 104 (completed the study). 6 subjects discontinued for personal reasons; 2 subjects were discontinued due to non-compliance; 1 subject discontinued when a rash developed after taking erythromycin; 1 subject discontinued after developing flu.
- Sex: M and F
- Age: 21- 81 y
- Race: caucasoid, hispanic

Clinical history:

INCLUSION CRITERIA
1. Individuals eighteen (18) years of age or older.
2. Individuals free of any systemic or dermatologic disorder which, in the opinion of the investigator, would interfere with the test results.
3. Individuals with fair, uniformly-colored skin on the lower thoracic area of the back.
4. Individuals who had completed a patch testing Medical Screening form as well as a Medical/Personal History form (prerequisite for all studies conducted at TKL Research).
5. Individuals who had read, understood and signed an informed consent agreement.

EXCLUSION CRITERIA
1. Individuals with any visible skin disease at the test site which, in the opinion of the investigative personnel, might have interfered with the evaluation.
2. Individuals taking medication which, in the opinion of the investigative personnel, would have interfered with the test results.
3. Individuals who are currently under treatment for asthma.
4. Individuals with psoriasis and/or active atopic dermatitis/eczema.
5. Females who were pregnant, planning a pregnancy or nursing a child.
6. Individuals with a known sensitivity to cosmetics, skin care products or topical drugs.

Route of administration:

dermal

Details on study design:

Product identification: paper undyed and paper dyed by Brown HM 2763
Amount applied: approx. 4 cm2

SITE DEFINITION
The patches were applied to the infrascapular area of the back, either to the right or left of the midline.

PATCH DEFINITION
Occlusive: non-porous, plastic film adhesive bandage with a 2 cm × 2 cm Webril pad affixed with hypo-allergenic tape such as Scanpor or Micropore as needed.

The entire study extended over a 6 week period. It involved 3 phases: (1) Induction, (2) Rest, and (3) Challenge. Prior to study entry, the subjects were screened to assure that they met the inclusion/exclusion criteria. Informed consent was obtained. Each subject was provided with a schedule of the study activities. They were told to avoid wetting the test sites and were asked not to engage in activities that caused excessive perspiration. They were instructed to notify the staff if they experienced any discomfort beyond mild itching and/or observed any adverse changes at the test sites, while on the study or within 2 weeks of completing the study.

The Induction Phase consisted of 9 consecutive applications of the test material and subsequent evaluations of the test sites. Prior to application of the patches, the sites were outlined with a skin marker, e.g., gentian violet. The subjects were required to remove the patches approximately 24 hours after application. They returned to the facility at 48 hour intervals to have the sites evaluated and identical patches reapplied. Patches applied on Friday were removed by subjects after 24 hours and sites were evaluated on the following Monday, i.e., 72 hours after patch application. Following the ninth evaluation, the subjects were dismissed for a 14 day rest period.
The Challenge Phase was initiated during the sixth week of the study, with identical patches applied to sites previously unexposed to the test material. These patches were removed by subjects after 24 hours and the sites graded after additional 24 hour and 48 hour periods, i.e., 48 and 72 hours after application.
To be considered a completed case, a subject must have 6 or more applications and subsequent readings during induction and at least one reading during challenge. Only completed cases are used to assess sensitization.
Rechallenge, if required, was performed whenever there was evidence of possible sensitization. The rechallenge test was conducted on naive sites on the back under both occlusive and semi-occlusive conditions approximately 1 or 2 weeks after challenge testing had been completed. Patches were applied for 24 hours, the patches removed and the sites evaluated 48, 72 and 96 hours after patch application.

Results and discussion

Any other information on results incl. tables

Summary reaction data

grade	induction									challenge
	1	2	3	4	5	6	7	8	9	1	2
-	102	104	104	101	101	101	103	102	100	103	104
?	1	0	0	0	0	0	0	0	0	1	0
	0	0	0	0	0	0	0	0	0	0	0
*	0	0	0	0	0	0	0	0	0	0	0
++	0	0	0	0	0	0	0	0	0	0	0
++	0	0	0	0	0	0	0	0	0	0	0
+D	0	0	0	0	0	0	0	0	0	0	0
NP	0	0	0	0	0	0	0	0	0	0	0
tot readings	103	104	104	101	101	101	103	102	100	104	104
absent	11	10	10	13	13	13	11	12	14	10	10
not applied	0	0	0	0	0	0	0	0	0	0	0
patch disl	0	0	0	0	0	0	0	0	0	0	0

- No reaction

? Doubtful response, barely perceptible erythema, only slightly different from surrounding skin

+ Definite erythema No edema T

+* Definite erythema Minimal or doubtful edema

++ Definite erythema Definite edema

+++ Definite erythema Definite edema & vesiculation

D or d Damage to epidermis: d = drying/scaling; D = oozing, crusting and/or superficial erosions

X Subject absent

NA Not Applied

PD Patch Dislodged

Applicant's summary and conclusion

Conclusions:

Under the conditions employed in this study, there was no evidence of sensitization to either of the products tested.

Executive summary:

2 products, paper undyed and paper Brown HM 2763, were tested to determine their ability to sensitize the skin of normal volunteer subjects using an occlusive repeated insult patch test. The entire study extended over a 6 week period. It involved three phases: (1) induction, (2) rest, and (3) challenge. Induction consisted of 9 consecutive applications at 48 h intervals, except for the weekend (72 h interval); a patch was hold in place for 24 h, then removed by subjects. Rest period was 14 days, after the ninth induction. At challenge, patch was applied for 24 h and skin reactions were evaluated 24 and 48 h after removal of patch.

104 subjects completed the study. To be considered a completed case, a subject must have 6 or more applications and subsequent readings during induction and at least one reading during challenge. Only completed cases were used to assess sensitization.

Under the conditions employed in this study, there was no evidence of sensitization to either of the products tested.