title: Experimental study on phototoxicity and the photosensitization potential of ketoprofen, suprofen, tiaprofenic acid and benzophenone and the photocross-reactivity in guinea pigs.
abstract: BACKGROUND
  Ketoprofen, suprofen and tiaprofenic acid are arylpropionic anti-inflammatories. Their chemical structures share the same elements as the benzoyl radical and the tiophene ring. We experienced nine cases of ketoprofen photoallergy, seven cases of suprofen photoallergy and three cases of tiaprofenic photoallergy.
  
  
  OBJECTIVE
  To find the key structure of photosensitivity and photocross-reactivity to ketoprofen, suprofen and tiaprofenic acid.
  
  
  METHODS
  : Three animals were tested for phototoxicity and six animals for the photosensitization potentials of ketoprofen, suprofen, tiaprofenic acid and benzophenone, and the photocross-reactivity of the above chemicals. Test substances were applied symmetrically on both sides of the animals' backs. The animals were irradiated with 180 mJ/cm2 UVB ((1/2) MED) and 10 J/cm2 UVA on the left side. The reactions were read on days 2, 3 and 4. The photosensitization potentials of ketoprofen, suprofen, tiaprofenic acid and benzophenone were determined using the Adjuvant-Strip method. Six animals were assigned to each test group and to a control group.
  
  
  RESULTS
  Ketoprofen, suprofen, tiaprofenic acid and propionic acid showed negative reactions with the phototoxic test. Benzophenone showed phototoxic reactions to 40% acetone (ac.), 20% ac. and 10% ac. Therefore, we used 5% aq. benzophenone with the photosensitization test. Ketoprofen was the strongest photosensitizer (6/6) and showed photocross-reactivities to suprofen (2/6), tiaprofenic acid (3/6) and benzophenone (6/6). Suprofen was a strong photosensitizer (4/6) and showed photocross-reactivities to ketoprofen (1/4) and tiaprofenic acid (2/4), but not to benzophenone. Tiaprofenic acid was also a photosensitizer (2/6) but showed a photocross-reactivity only to benzophenone (2/2). Benzophenone was also the strongest photosensitizer (6/6), but did not photocross-react to the above three chemicals.
  
  
  CONCLUSIONS
  From the test results, it appears that benzoyl radical is the key structure for photosensitivity and the photocross-reactivity of ketoprofen, suprofen and tiaprofenic acid. The whole structure of benzophenone was needed to induce photosensitization of benzophenone. The animals that were photosensitized from the entire structure of benzophenone did not photocross-react to ketoprofen, suprofen or tiaprofenic acid.
authors.affiliation: Department of Environmental Dermatology, Nagoya University School of Medicine, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Sugiura
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Hayakawa
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Xie
authors.forename: Keiji
authors.initials: K
authors.lastname: Sugiura
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hiramoto
authors.forename: Mikihiro
authors.initials: M
authors.lastname: Shamoto
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001577:Benzophenones / Q000009:adverse effects*; D017454:Dermatitis, Photoallergic / Q000209:etiology*; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007660:Ketoprofen / Q000009:adverse effects*; D017319:Photosensitizing Agents / Q000009:adverse effects*; D011422:Propionates / Q000009:adverse effects*; D013496:Suprofen / Q000009:adverse effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001577:Benzophenones; D017319:Photosensitizing Agents; D011422:Propionates; C021270:tiaprofenic acid; C047723:benzophenone; D007660:Ketoprofen; D013496:Suprofen