Registration Dossier

Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1999
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented publication which meets basic scientific principles.

Data source

Reference
Reference Type:
publication
Title:
Contact cheilitis due to glyceryl isostearate: a case study
Author:
Tanabe, N. et al.
Year:
1999
Bibliographic source:
Environ Dermatol 6:171-179

Materials and methods

Type of sensitisation studied:
skin
Study type:
case report
Principles of method if other than guideline:
A subject presented with persistent erythema on the lips and a rash extending to the neck that had persisted for 2 months. Patch testing was performed initially with cosmetic products suspected to have caused the skin reaction. Subsequently, patch testing was performed using the individual ingredients of a lipstick that caused a positive skin reaction. The substance(s) provoking renewed positive skin reaction could then be identified as the cause of the allergic contact dermatitis.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): glyceryl triisostearate
- Analytical purity: no data

Method

Type of population:
general
Ethical approval:
not specified
Subjects:
- Number of subjects exposed: 1
- Sex: female
- Age: 23
- Other: office worker
Clinical history:
- History of allergy or casuistics for study subject or populations: subject had not experienced erythema or symptoms indicative of allergic contact dermatitis in the past
- Symptoms, onset and progress of the disease: symptoms (erythema of the lips, including itching, scaling, and rash extending to the neck) started two months prior to presentation
- Family history: subject did not have a family history of skin sensitisation
Controls:
not required, untreated sites of the subject served as control
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: occlusive patch, Finn-chamber (EPITEST Ltd, Tuusula, Finland) on Scanpor tape (Alpharma AS, Norway)
- Vehicle / solvent: none
- Concentrations: lipsticks were tested undiluted; glyceryl triisostearate tested at 0.1, 1, 5, 10 and 30% dilution in petrolatum (pet)
- Volume applied: no data
- Testing/scoring schedule: results were scored 48 and 72 hours after application
- Removal of test substance: no data
- Other:
1) patch testing was first performed with: white petrolatum, fragrance mix from the Japanese Society of Contact Dermatitis (JSCD), JSCD standard test series, lipsticks A-G (patient’s own), medical lip salve (patient’s own), lip salve (patient’s own)
2) patch testing was performed with the ingredients of lipstick G: white petrolatum, glyceryl diisostearate in various concentrations, undefined colour additives, diluted R202, jojoba oil, candelila wax, 1,1,1-trimethylopropanetriisostearate, D-delta-tocopherol
3) patch testing was performed with 0.0001, 0.0005, 0.001, 0.005, 0.01, 0.05, 0.1 and 0.2% pet glyceryl monoisostearate, 0.1, 1, 5, 10 and 30% pet glyceryl diisostearate, 0.1, 1, 5, 10 and 30% pet glyceryl triisostearate, and white petrolatum

The test samples of glyceryl monoisostearate, glyceryl diisostearate and glyceryl triisostearate were prepared by purifying samples of 'crude diglycerides' by silica gel chromatography and gas liquid chromatography. The 'crude diglycerides' are used in cosmetics and consist of unspecified amounts of various mono-, di- and triglycerides.

EXAMINATIONS
- Grading/Scoring system: scoring of contact dermatitis was performed according to the criteria of the International Contact Dermatitis Research Group

Results and discussion

Results of examinations:
RESULT OF CASE REPORT:
A subject presented with persistent erythema on the lips and a rash extending to the neck that had persisted for 2 months. Patch testing was performed on the subject; initially with cosmetic products suspected to have caused the skin reaction. Subsequently, patch testing was performed using the individual ingredients of a lipstick that caused a positive skin reaction. Glyceryl triisostearate was tested as one of the potential ingredients to cause the allergic contact dermatitis, because a positive reaction was noted when testing a mix of glycerol mono-, di- and triisostearate.

Patch test results:
1) Results were positive for all lipsticks, both lip salves and the fragrance mix, at the 48 and 72-hour reading time point (see table 1 “any other information on results including tables”)
2) Results were positive for glyceryl diisostearate and diluted R202 (crude) at the 48 and 72-hour reading time point (see table 2 “any other information on results including tables”). Results were inconclusive for purified and 38% commercial diluted R202 at the 48-hour reading time point.
3) Results for glycerol triisostearate and glyceryl diisostearate were negative. Results were positive for 0.005 - 0.2% dilution in petrolatum (pet) glyceryl monoisostearate at the 48 and 72-hour reading time point (see table 3 “any other information on results including tables”).

Any other information on results incl. tables

Table 1

Allergens

Concentration

48 hours

72 hours

White petrolatum

As is

-

-

Fragrance mix (JSCD)

 

+

+

JSCD standard series

 

-

-

Lipstick A*

As is

+

+

Lipstick B*

As is

+

+

Lipstick C*

As is

+

+

Lipstick D*

As is

+

+

Lipstick E*

As is

+

+

Lipstick F*

As is

+

+

Lipstick G*

As is

+

+

Medical lip salve A*

As is

+

+

Lip salve B*

As is

+

+

*Patient’s own

Table 2

Allergens

Concentration**

48 hours

72 hours

White petrolatum

As is

-

-

glyceryl diisostearate

50% pet

++

++

glyceryl diisostearate

20%pet

++

++

glyceryl diisostearate

10% pet

++

++

glyceryl diisostearate

1% pet

++

++

Colour additives (legal)

As is

-

-

diluted R202 (crude)

0.1% pet

+

+

diluted R202 (purified)

1% pet

+?

-

diluted R202 commercial 38%

1% pet

+?

-

jojoba oil

As is

-

-

candelila wax

1% pet

-

-

1,1,1-trimethylopropanetriisostearate

35% pet

-

-

D-delta-tocopherol

0.05% pet

-

-

 ** all dilutions in petrolatum (pet)

Table 3

Allergens

Concentration**

48 hours

72 hours

White petrolatum

As is

-

-

glyceryl monoisostearate

0.2% pet

+ +

+ +

glyceryl monoisostearate

0.1% pet

+ +

+ +

glyceryl monoisostearate

0.05% pet

+ +

+ +

glyceryl monoisostearate

0.01% pet

+ +

+ +

glyceryl monoisostearate

0.005% pet

-

-

glyceryl monoisostearate

0.001% pet

-

-

glyceryl monoisostearate

0.0005% pet

-

-

glyceryl monoisostearate

0.0001% pet

-

-

glyceryl diisostearate

30% pet

-

-

glyceryl diisostearate

10%pet

-

-

glyceryl diisostearate

5% pet

-

-

glyceryl diisostearate

1% pet

-

-

glyceryl diisostearate

0.1% pet

-

-

glyceryl triisostearate

30% pet

-

-

glyceryl triisostearate

10% pet

-

-

glyceryl triisostearate

5% pet

-

-

glyceryl triisostearate

1% pet

-

-

glyceryl triisostearate

0.1% pet

-

-

 ** all dilutions in petrolatum (pet)

Applicant's summary and conclusion

Conclusions:
A subject presented with allergic contact dermatitis as a persistent erythema on the lips and a rash extending to the neck that had persisted for 2 months. Patch testing was performed with cosmetic products and cosmetic ingredients suspected to have caused the skin reaction. Glyceryl triisostearate did not cause any skin reaction at concentrations up to and including 30% pet (petrolatum).