L-Arginine, N2-(2,3-dihydroxypropyl)-, monohydrochloride

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Only 50 panelists, not 200 as referenced in Appraisal of the safety of chemicals in Food, Drugs and Cosmetics by the US FDA

Justification for type of information:

The study was conducted to provide information on contact irritation/sensitisation potential of consumer product or raw material designed for consistent reapplication to area of the skin under proper condition of use.

In accordance with REACH Regulation (EC) 1907/2006 as amended: Annex VII, section 8.3: the in chemico or in vitro, or in vivo skin sensitisation study does not need to be conducted based on existing data sufficient for classification and labelling being already available. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7a: Endpoint Specific Guidance, R.7.3, July 2017) the study does not need to be conducted. Available data to fulfil this endpoint were obtained from a Repeat Insult Patch Test Skin Irritation/Sensitisation study (RIPT) conducted on N-Glyceryl Arginine HCI, as described in this study summary.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Type of sensitisation studied:

skin

Study type:

study with volunteers

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics, Published by the Association of Food and Drug Official of The United States.

Version / remarks:

Not specified

Deviations:

yes

Remarks:

50 panelists instead of 200 and 9 inductive patched instead of 10.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

L-Arginine, N2-(2,3-dihydroxypropyl)-, monohydrochloride

EC Number:

843-143-1

Cas Number:

709647-81-4

Molecular formula:

C9H21ClN4O4

IUPAC Name:

L-Arginine, N2-(2,3-dihydroxypropyl)-, monohydrochloride

Test material form:

liquid

Remarks:

Clear, colourless

Details on test material:

Sponsor's substance name ID: N-glyceryl arginine HCl
Storage conditions ~4 ºC, in the dark

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL:

- Source and lot/batch No.of test material: Seiwa case Company Ltd. Lot.050323

- Expiration date of the lot/batch:Not specified

- Purity test date: Not specified

RADIOLABELLING INFORMATION (if applicable): N/A

- Radiochemical purity:

- Specific activity:

- Locations of the label:

- Expiration date of radiochemical substance:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL: Not specified
- Storage condition of test material:
- Stability under test conditions:
- Solubility and stability of the test substance in the solvent/vehicle: assumed stable
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Diluted to 16.66% in distilled water. The test material is prepared freshly on each day of applications.
- Preliminary purification step (if any): Not specified
- Final dilution of a dissolved solid, stock liquid or gel: 0.2ml or 0.2g dispensed onto occlusive patches.
- Final preparation of a solid: Not specified

FORM AS APPLIED IN THE TEST (if different from that of starting material): Not specified

OTHER SPECIFICS: N/A

Method

Type of population:

general

Ethical approval:

confirmed and informed consent free of coercion received

Subjects:

A total of 54 study subjects were recruited for this study. Out of those, 2 subjects (019 and 053) did not meet the inclusion criteria or presented any of the exclusion criteria.
The study was initiated with 54 subjects, 39 of which were female and the rest male, aged above 18 years. This was to ensure objectives of obtaining at least a minimum of 50 responses.

Clinical history:

Inclusion Criteria
-Healthy study subjects;
-Intact skin on test site;
-Agreement to adhere to the procedures and requirements of the study and to report to the institute on the day(s) and at the time(s) scheduled for the assessments;
-Ability of giving a written consent for participating in the study;
-Aged from years old;

Non Inclusion Criteria
- Under 18 years old;
-Individual current under doctor’s care or taking any medication (topical or systemic) that may mask or interfere with the test result;
-Previous history of any acute or chronic disease that might interfere with or increase the risk associated with study participation;
-Subjects with history of chronic skin allergies;
-Pregnancy or lactating;

Controls:

Not specified

Route of administration:

dermal

Details on study design:

Subjects are requested to bathe or wash as usual before arrival at the facility.
As per client requests, the test material K-7470 was diluted to 16.66% in distilled water. Dilutions were freshly prepared on each application day. 0.2 ml or 0.2 g of the test material is dispensed onto the occlusive, hypoallergenic patch. The patch is then applied directly to the skin of the intrascapular regions of the back, to the right or left of the midline and the subject is dismissed with instructions not to wet or exposed the test area to direct sunlight.
After 24 hours the patch is removed by the panellist at home. This procedure is repeated until a series of consecutive 24 hour exposures have been made for every Monday, Wednesday, and Friday for three consecutive weeks. In the event of an adverse reaction, the area of erythema and edema is measured. The edema is estimated by the evaluation of the skin with respect to the contour of the unaffected normal skin. Reactions are scored just before applications two through nine and the next test date following application nine. In most instances this is approximately 24 hours after patch removal. Clients are notified immediately in the case of adverse reaction and determination is made as to treatment program if necessary. Subjects are given a 10 -14 day rest period after which a challenge or retest dose is applied once to the previously unexposed test site. The retest dose is equivalent to any one of the original nine exposures. Reactions were scored 24 and 48 hours after application. Comparison is made between the nine inductive responses and the test dose.

Results and discussion

Results of examinations:

No adverse reactions of any kind were noted during the course of the study.

Applicant's summary and conclusion

Conclusions:

Under the condition of the study, the test material did not induce skin sensitisation reaction.

Executive summary:

STUDY OBJECTIVE

To prove the absence of the skin sensitisation potential of a product applied to the skin, under maximized conditions, with controlled product amount and application site, supervised by a dermatologist.

 

METHODOLOGY

As per client requests, the test material K-7470 was diluted to 16.66% in distilled water. Dilutions were freshly prepared on each application day. 0.2 ml or 0.2g of the test material is dispensed onto the occlusive, hypoallergenic patch.  The patch is then applied directly to the skin of the intrascapular regions of the back, to the right or left of the midline and the subject is dismissed with instructions not to wet or exposed the test area to direct sunlight.  After 24 hours the patch is removed by the panellist at home.  This procedure is repeated until a series of 9 consecutive 24 hour exposure have been made for every Monday, Wednesday, and Friday for three consecutive weeks. In the event of an adverse reaction, the area of erythema and edema is measured. The edema is estimated by the evaluation of the skin with respect to the contour of the unaffected normal skin. Reactions are scored just before applications two through nine and the next test date following application nine. In most instances this is approximately 24 hours after patch removal. Clients are notified immediately in the case of adverse reaction and determination is made as to treatment program if necessary. Subjects are given a 10 -14 day rest period after which a challenge or retest dose is applied once to the previously unexposed test site. The retest dose is equivalent to any one of the original nine exposures. Reactions were scored 24 and 48 hours after application. Comparison is made between the nine inductive responses and the test dose.  

 

STUDY LENGTH

6 weeks.

 

FREQUENCY OF APPLICATION

9 applications on the 3 first weeks (induction period).

1 application on the last week (challenge period).

 

APPLICATION SITE

Back (Scapular area).

 

NUMBER OF SUBJECTS

52 subjects completed the study.

 

POPULATION DESCRIPTION

Female and male, age range from 18 to 69 years old.

 

ETHICS

This study was conducted in conformance with the Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics, Published by the Association of Food and Drug Official of The United States.

 

RESULTS

During the study, no subjects presented skin clinical signs related to the product.

 

CONCLUSION

The test material  did not induce a skin sensitisation process in the study group when tested under occlusion at a 16.66% diluted in distilled water.

Therefore, the test material  was considered as a non-irritant and non-primary sensitiser to the skin according to the reference (Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics, Published by the Association of Food and Drug Official of The United States).