title: Irritancy and allergic responses induced by topical application of ortho-phthalaldehyde.
abstract: Although ortho-phthalaldehyde (OPA) has been suggested as an alternative to glutaraldehyde for the sterilization and disinfection of hospital equipment, the toxicity has not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of OPA. The EpiDerm Skin Irritation Test was used to evaluate in vitro irritancy potential of OPA and glutaraldehyde. Treatment with 0.4125 and 0.55% OPA induced irritation, while glutaraldehyde exposure at these concentrations did not. Consistent with the in vitro results, OPA induced irritancy, evaluated by ear swelling, when mice were treated with 0.75%. Initial evaluation of the sensitization potential was conducted using the local lymph node assay at concentrations ranging from 0.005 to 0.75%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.051% compared to that of 0.089%, previously determined for glutaraldehyde. Immunoglobulin (Ig) E-inducing potential was evaluated by phenotypic analysis of draining lymph node (DLN) cells and measurement of total and specific serum IgE levels. The 0.1 and 0.75% exposed groups yielded significant increases in the IgE+B220+ cell population in the lymph nodes while the 0.75% treated group demonstrated significant increases in total IgE, OPA-specific IgE, and OPA-specific IgG(1). In addition, significant increases in interleukin-4 messenger RNA and protein expression in the DLNs were observed in OPA-treated groups. The results demonstrate the dermal irritancy and allergic potential of OPA and raise concern about the proposed/intended use of OPA as a safe alternative to glutaraldehyde.
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA.
authors.forename: Stacey E
authors.initials: SE
authors.lastname: Anderson
authors.forename: Christina
authors.initials: C
authors.lastname: Umbright
authors.forename: Rajendran
authors.initials: R
authors.lastname: Sellamuthu
authors.forename: Kara
authors.initials: K
authors.lastname: Fluharty
authors.forename: Michael
authors.initials: M
authors.lastname: Kashon
authors.forename: Jennifer
authors.initials: J
authors.lastname: Franko
authors.forename: Laurel G
authors.initials: LG
authors.lastname: Jackson
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Johnson
authors.forename: Pius
authors.initials: P
authors.lastname: Joseph
mesh_terms: D000287:Administration, Topical; D000485:Allergens / Q000145:classification / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017449:Dermatitis, Allergic Contact / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D004202:Disinfectants / Q000145:classification / Q000633:toxicity*; D004359:Drug Therapy, Combination; D004431:Ear, External / Q000187:drug effects / Q000473:pathology; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood; D007509:Irritants / Q000145:classification / Q000633:toxicity*; D023441:Local Lymph Node Assay; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009764:o-Phthalaldehyde / Q000145:classification / Q000633:toxicity*
chemical_list: D000485:Allergens; D004202:Disinfectants; D007509:Irritants; D007073:Immunoglobulin E; D009764:o-Phthalaldehyde