Registration Dossier

Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
other: not possible to assign reliability score to a case report (non-methodology-based study)
Rationale for reliability incl. deficiencies:
other: Reliability cannot be scored as the study cannot be compared with a guideline as these do not exist for human case reports.

Data source

Reference
Reference Type:
publication
Title:
Granulomas from topical zirconium in poison ivy dermatitis.
Author:
Baler GR
Year:
1956
Bibliographic source:
Arch. Dermat. Vol. 91

Materials and methods

Type of sensitisation studied:
skin
Study type:
case report
Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
Case reports do not fulfill guideline requirements.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Ointment containing 4% zirconium oxide

Method

Type of population:
general
Ethical approval:
not applicable
Subjects:
- Number of subjects exposed: 1
- Sex: female
- Age: 15
- Race: white
- Demographic information: no data
Clinical history:
During previous summers (before 1962), patient suffered from contact dermatitis due to poison ivy. In the summer of 1962, she suffered from 3 episodes of poison ivy dermatitis and during each attack an ointment containing zirconium oxide was applied. The poison ivy dermatitis was very severe: blisters developed in the neck, face, upper extremities and right knee. The skin healed without any apparent after-effects.
No history of contact with zirconium-containing preparations. No other remarkable (family) history.
In October 1962 asymptomatic papules appeared in the skin of all areas previously involved with poison ivy dermatitis and treated with the zirconium ointment. The number of lesions increased in the involved areas during the next two months. In December, numerous reddish-brown papules and nodules varying in size (few to several millimeters) were apparent. No lymphadenopathy was observed.
Lungs, liver, spleen, blood, chest x-ray and other physical examinations were normal.
Controls:
No controls.
Route of administration:
dermal
Details on study design:
Several investigations were performed:
1) A biopsy specimen was taken of one of the papules on the forearm.
2) The zirconium-containing ointment was tested semi-occlusively on the abraded skin of the back for 2 days. Another test was done after preparing a 4% ointment of pure zirconium oxide powder in hydrophilic ointment USP.
3) Patch tests were done with the two ointments on nonabraded skin for 4 weeks.
4) After the tests, therapy with prednisone was started. Also therapy with fluocinolone was applied.
5) Emission spectrography was performed on a granulomatous nodule that was excised 17-18 months after the lesions had first developed.

Results and discussion

Results of examinations:
1) Biopsy specimen: dermis was heavily infiltrated with nodules composed of epithelioid cells and associated with a few lymphocytes and multinucleated giant cells of the Langerhans type. Histopathology was similar to that of sarcoidosis. No acid-fast bacilli nor refractile bodies were observed.
2) The previously used ointment developed a reddish-brown papule after 4 weeks on the back of the patient. Upon biopsy, it revealed a sarcoid-like granulomatous infiltrate. The newly prepared ointment developed identical results.
3) Patch tests were negative after 48 and 72 h and after 4 weeks.
4) On administration of systemic prednisone, lesions completely disappeared (except for pigmentation). Discontinuation of the therapy caused a complete recurrence of the eruption. Identical observations were seen when a therapy with occlusive fluocinolone cream was started/discontinued. Untreated lesions showed no evidence of improvement over 20 months.
5) A nodule was excised 17-18 months after the lesions had first developed. Emission spectrography showed zirconium oxide to be present in the nodule in the order of 0.01% after drying.

Applicant's summary and conclusion

Conclusions:
In general, zirconium granulomas are either rare or not being recognized. However, many cases have been reported with regard to axillary zirconium granulomas. In the axillae, penetration of the soluble zirconium species incorporated in deodorants is larger compared to that on other parts of the body where insoluble zirconium forms are mostly used in ointments (e.g. to treat poison ivy dermatitis). The observed effects in the tests done with the 4% ointments containing ZrO2 evidenced the granulomas to represent a delayed allergic hypersensitivity reaction. The insoluble zirconium species seem not to be removed easily by the body, as the lesions did not disappear if untreated for 20 months and zirconium can still be observed in the lesion.