Sandalwood, ext.

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

June 1986 - October 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Results of evaluation of 203 patients for photosensitivity in a 7.3-year period.

Author:

J. Fotiades, MD, N.A. Soter, MD, and H.W. Lim, MD

Year:

1995

Bibliographic source:

Journal of the American Academy of Dermatology 33, 597–602

Materials and methods

Type of sensitisation studied:

skin

Study type:

survey

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The purpose of this study was to evaluate the incidence of photosensitivity disorders, including photocontact dermatitis, in an academic medical center.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

5-(2,3-dimethyltricyclo[2.2.1.02,6]hept-3-yl)-2-methylpent-2-en-1-ol, stereoisomer

EC Number:

204-102-8

EC Name:

5-(2,3-dimethyltricyclo[2.2.1.02,6]hept-3-yl)-2-methylpent-2-en-1-ol, stereoisomer

Cas Number:

115-71-9

Molecular formula:

C15H24O

IUPAC Name:

5-(2,3-dimethyltricyclo[2.2.1.0~2,6~]hept-3-yl)-2-methylpent-2-en-1-ol

Constituent 2

Reference substance name:

[1S-[1α,2α(Z),4α]]-2-methyl-5-(2-methyl-3-methylenebicyclo[2.2.1]hept-2-yl)-2-penten-1-ol

EC Number:

201-027-2

EC Name:

[1S-[1α,2α(Z),4α]]-2-methyl-5-(2-methyl-3-methylenebicyclo[2.2.1]hept-2-yl)-2-penten-1-ol

Cas Number:

77-42-9

Molecular formula:

C15H24O

IUPAC Name:

2-methyl-5-(2-methyl-3-methylenebicyclo[2.2.1]hept-2-yl)pent-2-en-1-ol

Constituent 3

Reference substance name:

(Z)-5-[(6R)-4,6-dimethyl-6-bicyclo[3.1.1]hept-3-enyl]-2-methylpent-2-en-1-ol

Cas Number:

176777-61-0

Molecular formula:

C15H24O

IUPAC Name:

(Z)-5-[(6R)-4,6-dimethyl-6-bicyclo[3.1.1]hept-3-enyl]-2-methylpent-2-en-1-ol

Constituent 4

Reference substance name:

(E)-(R)-(+)-5-(2,3-dimethyltricyclo[2.2.1.0^2,6]hept-3-yl)-2-methyl-2-penten-1-ol

Cas Number:

14490-17-6

Molecular formula:

C15H24O

IUPAC Name:

(E)-(R)-(+)-5-(2,3-dimethyltricyclo[2.2.1.0^2,6]hept-3-yl)-2-methyl-2-penten-1-ol

Constituent 5

Reference substance name:

2-​Hepten-​1-​ol, 2-​methyl-​6-​(4-​methylphenyl)​-​, (2Z)​-

Cas Number:

122442-36-8

Molecular formula:

C15H22O

IUPAC Name:

2-​Hepten-​1-​ol, 2-​methyl-​6-​(4-​methylphenyl)​-​, (2Z)​-

Test material form:

liquid

Specific details on test material used for the study:

The sandalwood oil used as part of fragrances in this study remained unclear.

Method

Type of population:

general

Ethical approval:

not specified

Subjects:

223 consecutive patients were examined for photosensitivity disorders with phototests. Twenty of the 223 patients were referred for evaluation of porphyria and subsequently had an abnormal porphyrin profile; they were excluded from this study. Therefore, the study group consisted of the remaining 203 patients, all of whom were subjected to phototests. Of theses, 128 (63& were women, and 75 (37%) were men. Sixty eight percent of the patients were white, 19% black, and 8% Hispanic; the ethnicity of the other 5% was either Asian/Pacific Islander or not specified. Tbe age range was between 8 and 87 years (mean, 50 years).

Clinical history:

A detailed history was obtained, and a complete skin examination was performed. Particular attention was placed on systemic and topical exposures to photosensitizers. If skin lesions were present, a skin biopsy was performed when possible. In patients with a presumptive diagnosis of polymorphous light eruption, determination of the antinuclear antibodies was performed. Phototests were performed on all patients. In addition, in patients with possible photoallergy, phototoxicity, or chronic actinic dermatitis, photopatch tests were done. Photopatch tests were not usually performed in patients suspected of having polymorphous light eruption or solar urticaria.

Route of administration:

dermal

Details on study design:

These tests have been described in detail previously (Lim HW, Morison WL, Kamide R, et al. Chronic actinic dermatitis: an analysis of 51 patients evaluated in the United States and Japan. Arch Dermatol 1994;30:284-9). Briefly, on day 1 duplicate sets of photoallergens were applied, phototests to UVA, UVB, and visible light were performed, and phototest sites were evaluated 15 to 30 minutes after irradiation was completed. On day 2 the MED-A and MED-B were quantified, the sites exposed to visible light were evaluated, and one set of photoallergens was exposed to UVA (either 10 J/cm2 or 50% of the MED-A, whichever was lower). The MED is defined as the lowest UV dose that produces perceptible erythema uniformly covering the entire irradiated area (typically, a series of 1.5 x 1.5 cm test sites). On days 3 and 7 the irradiated and non-irradiated photopatch test sites were evaluated. The responses were graded with a scoring system recommended by the North American Contact Dermatitis Group (1+: erythema, infiltration, possibly papules; 2+: edema and vesicles; 3+: bullae and ulcers). A positive response at the irradiated site was, in the absence of a response at the nonirradiated site, interpreted as a photoallergic contact dermatitis. A positive response of equal intensity at both irradiated and non-irradiated sites was consistent with an allergic contact dermatitis, whereas a response at both sites, where the reaction was more pronounced at the irradiated site, was defined as a combined response, that is, photoallergic and allergic contact dermatitis. Well-defined erythema that resolved promptly was interpreted as irritant reaction. The photoallergens used were the North American Contact Dermatitis Group photopatch test series (Table I and II) and the New York University Skin and Cancer Unit photopatch and test/sunscreen sensitivity series (Tables III and IV). Tables I and III represent allergens used up to July 1992, and Tables II (including sandalwood oil) and IV reflect series used from July 1992 on.
A previously published normal range for MED-A and MED-B was used as a reference point; any response to visible light radiation was considered abnormal. For the purposes of data analysis, the photoallergens used were grouped into four broad categories: sunscreens and their ingredients, antimicrobial agents, fragrances, and others.

Results and discussion

Results of examinations:

In 3 out of 203 patients, a positive response for photosensitivity was observed. In 4 a postive response was seen in patch tests.

Applicant's summary and conclusion

Conclusions:

Of the 34 positive patch test responses, fragrances most frequently elicited positive reactions (47%), followed by sunscreens (39%) and antimicrobial
agents (7%). Sandalwood oil, musk ambrette, and PAPA esters most commonly elicited positive patch test responses. All of the clinically relevant responses to sandalwood oil 3 males) and musk ambrette occurred in men. Combined positive photopatch and patch test responses were elicited in some patients by musk ambrette, sandalwood oil, Pabanol, and padimate O. Fragrances accounted for most (47%) of the allergic contact reactions, with sandalwood oil and musk ambrette as the most frequent eliciting agents. These agents have been extensively used in men’s perfumes, after-shave lotions, and colognes, which is reflected in our series by the observation that 100% of relevant allergic contact reactions to sandalwood oil and musk ambrette occurred in men.