1-Propanaminium, N-(3-aminopropyl)-2-hydroxy-N,N-dimethyl-3-sulfo-, N-(C8-18(even numbered) acyl) derivs., hydroxides, inner salts

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:

May - June 1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Controlled clinical study - the detailed composition of the test solution, which remained private company property, is not reported

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Materials and methods

Study type:

study with volunteers

Endpoint addressed:

skin irritation / corrosion

skin sensitisation

Principles of method if other than guideline:

Modification of the Repeated Insult Patch Test of Draize

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxooctyl)amino]propyl]ammonium hydroxide

Molecular formula:

C16H34N2O5S

IUPAC Name:

(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxooctyl)amino]propyl]ammonium hydroxide

Constituent 2

Reference substance name:

(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxodecyl)amino]propyl]ammonium hydroxide

Molecular formula:

C18H38N2O5S

IUPAC Name:

(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxodecyl)amino]propyl]ammonium hydroxide

Constituent 3

Reference substance name:

(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxododecyl)amino]propyl]ammonium hydroxide

EC Number:

242-893-1

EC Name:

(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxododecyl)amino]propyl]ammonium hydroxide

Cas Number:

19223-55-3

Molecular formula:

C20H42N2O5S

IUPAC Name:

N-[3-(dodecanoylamino)propyl]-2-hydroxy-N,N-dimethyl-3-sulfopropan-1-aminium hydroxide

Constituent 4

Reference substance name:

(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxotetradecyl)amino]propyl]ammonium hydroxide

Molecular formula:

C22H46N2O5S

IUPAC Name:

(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxotetradecyl)amino]propyl]ammonium hydroxide

Constituent 5

Reference substance name:

(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxohexadecyl)amino]propyl]ammonium hydroxide

Molecular formula:

C24H50N2O5S

IUPAC Name:

(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxohexadecyl)amino]propyl]ammonium hydroxide

Constituent 6

Reference substance name:

[2-hydroxy-3-sulphopropyl]dimethyl[3-[(1-oxooctadecyl)amino]propyl]ammonium hydroxide

EC Number:

264-390-6

EC Name:

[2-hydroxy-3-sulphopropyl]dimethyl[3-[(1-oxooctadecyl)amino]propyl]ammonium hydroxide

Cas Number:

63663-12-7

Molecular formula:

C26H54N2O5S

IUPAC Name:

2-hydroxy-N,N-dimethyl-N-[3-(stearoylamino)propyl]-3-sulfopropan-1-aminium hydroxide

Constituent 7

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

Water

impurity 1

Reference substance name:

Sodium chloride

EC Number:

231-598-3

EC Name:

Sodium chloride

Cas Number:

7647-14-5

Molecular formula:

ClNa

IUPAC Name:

sodium chloride

impurity 2

Reference substance name:

Glycerol

EC Number:

200-289-5

EC Name:

Glycerol

Cas Number:

56-81-5

Molecular formula:

C3H8O3

IUPAC Name:

glycerol

impurity 3

Reference substance name:

Disodium 2-hydroxypropane-1,3-disulfonate

Molecular formula:

C3H8O7S2.Na2

IUPAC Name:

Disodium 2-hydroxypropane-1,3-disulfonate

impurity 4

Reference substance name:

Sodium (±)-2,3-dihydroxypropanesulphonate

EC Number:

252-542-4

EC Name:

Sodium (±)-2,3-dihydroxypropanesulphonate

Cas Number:

35396-47-5

Molecular formula:

C3H8O5S.Na

IUPAC Name:

sodium (±)-2,3-dihydroxypropanesulphonate

impurity 5

Reference substance name:

Amides, C8-18 even numbered, N-[3-(dimethylamino)propyl]

EC Number:

930-947-3

IUPAC Name:

Amides, C8-18 even numbered, N-[3-(dimethylamino)propyl]

Test material form:

liquid

Method

Type of population:

general

Subjects:

- Number of subjects exposed: 44
- Sex: male and female
- Age: 16 to over 60 years old
- Race: Not specified
- Demographic information: Panelists from the Phoenix, Arizona area
- Known diseases: Anyone in poor health, under corticosteroid medication, with diabetes, psoriasis or any other hematological condition contraindicating participation was excluded

Ethical approval:

confirmed and informed consent free of coercion received

Route of exposure:

dermal

Reason of exposure:

intentional

Exposure assessment:

not specified

Details on exposure:

All 8 test materials (including our substance of interest) were applied to each panelist as occlusive patches. These consisted of 20x20 mm saure of a thick non-woven absorbent cotton fabric affixed to the center of 40x40 mm adhesive squares. The swatches were moistened with 0.3 mL of respective test solutions shortly before application. Four patches were applied to each upper arm. Assignment of test samples positions was varied so that each test solution was applied to each of the 8 test sites on approximately an equal number of panelists. All patches were removed 24 hours after application. The panelists were instructed to keep the patches dry during the contact period.
The test was divided into 3 phases:
- Phase 1 = one week for selecting test dose and challenge dose based on preliminary tests
- Phase 2 = induction period (3 weeks of 3 weekly applications, on Mondays, Wednesdays and Fridays)
- Phase 3 = challenge period (one-week period, application on original and fresh adjacent skin sites)

For the test solution of interest, the concentration used in all 3 phases was 2.5% (v/v) in distilled water.

Examinations:

Skin reactions were scored by an experienced evaluator, according to a predefined scale.
Reactions were scored 48 and 96 hours following preliminary and challenge applications. Reactions to serial induction patches were scored just before application Nos. 2 through 9, and 48 hours following application No. 9.

Medical treatment:

Not applicable

Results and discussion

Clinical signs:

The sample of interest was essentially non-irritating following a single application as a 2.5% solution for 24 hours. Following repeated applications of 2.5% solutions, about 45% of the panelists developed slight to moderate irritation. Two panelists (Nos. 11 and 27) developed strong irritation once during the serial applications.

There was no indication that contact sensitization was induced by repeated applications of any of the test material, including our substance of interest.

Results of examinations:

See above

Effectivity of medical treatment:

Not applicable

Applicant's summary and conclusion

Conclusions:

Repeated dermal application of a 2.5% aqueous solution of Varion CAS to 44 healthy human volunteers under occlusive conditions did not result in any skin reaction indicative of irritation or sensitization.

Executive summary:

A Repeated Insult Patch Test using occluded patches was carried out on 44 male and female healthy volunteers with eight test materials, including an aqueous solution of Varion CAS.

The sample of interest was essentially non-irritating following a single application as a 2.5% solution for 24 hours. Following repeated applications of 2.5% solutions, about 45% of the panelists developed slight to moderate irritation. Two panelists (Nos. 11 and 27) developed strong irritation once during the serial applications.

There was no indication that contact sensitization was induced by repeated applications of any of the test material, including our substance of interest.

Repeated dermal application of a 2.5% aqueous solution of Varion CAS to 44 healthy human volunteers under occlusive conditions did not result in any skin reaction indicative of irritation or sensitization.