title: Sensitizing capacity of azole derivatives: Part III. Investigations with anthelmintics, antimycotics, fungicides, antithyroid compounds, and proton pump inhibitors.
abstract: BACKGROUND
  More than hundred azole derivatives are used today for different purposes. The majority possess antimycotic, antibacterial, anthelmintic, and antiprotozoal properties. They are used as agricultural fungicides; topical antimycotics, and, for example, in antidandruff cosmetics. More recently the antithyroid and antiulcerative activity of certain imimidazoles and benzimidazoles also has been proven, which led to the introduction of proton pump inhibitors and antithyroid drugs to the market.
  
  
  OBJECTIVE
  Case reports from the literature and experimental studies suggest that some of the azole derivatives possess a distinct sensitizing potency. Occupational exposure either in the pharmaceutical manufacture or in the pesticide's application by farmers caused allergic contact dermatitis (ACD). However, experimental studies in guinea pigs to determine their sensitizing capacity have been performed only sporadically.
  
  
  METHODS
  Guinea pigs were sensitized by a modified Freund's complete adjuvant (FCA) method, with 35 azoles used as agricultural fungicides, proton pump inhibitors, antimycotics, antithyroid agents, antiprotozoals, antimicrobials, anthelmintics, and wood preservatives.
  
  
  RESULTS
  Four azoles exhibited a strong sensitizing capacity, 3 a moderate, and 11 a weak sensitizing capacity. Seventeen derivatives remained negative. Among the strong sensitizers were the 3 proton pump inhibitors omeprazole, pantoprazole, and rabeprazole, as well as the antithyroid drug carbimazole. The latter displayed the highest sensitizing power (mean response = 2.50) of all 62 azole derivatives investigated in the present and the 2 previous experimental studies.
  
  
  CONCLUSIONS
  As long as the strong sensitizing azoles are used only systemically the risk of acquiring contact hypersensitivity is low. However, if the idea should arise to use them topically, for example in ointments, tinctures, or lotions against fungal infections, skin problems will probably be observed abundantly.
authors.affiliation: Dermatologisches Zentrum Buxtehude, Germany.
authors.forename: B M
authors.initials: BM
authors.lastname: Hausen
authors.forename: R
authors.initials: R
authors.lastname: Lücke
authors.forename: E
authors.initials: E
authors.lastname: Rothe
authors.forename: A
authors.initials: A
authors.lastname: Erdogan
authors.forename: H
authors.initials: H
authors.lastname: Rinder
mesh_terms: D000818:Animals; D001393:Azoles / Q000009:adverse effects* / Q000737:chemistry; D017449:Dermatitis, Allergic Contact / Q000209:etiology*; D004353:Drug Evaluation, Preclinical; D006168:Guinea Pigs; D007428:Intradermal Tests; D007509:Irritants / Q000009:adverse effects*
chemical_list: D001393:Azoles; D007509:Irritants