title: Adjuvant effect of di-n-butyl-, di-n-octyl-, di-iso-nonyl- and di-iso-decyl phthalate in a subcutaneous injection model using BALB/c mice.
abstract: During the last decades, the prevalence of the allergic airway diseases, asthma and rhinitis, has increased world-wide. Introduction of environmental chemicals with adjuvant effect may play a role in this increase. In the present study, the adjuvant effects of di-n-butyl-, di-n-octyl-, di-iso-nonyl- and di-iso-decyl phthalate are studied in a screening model. Ovalbumin, used as the model antigen, was injected subcutaneously in the neck region of BALB/cJ mice with the selected phthalate in concentrations from 2-2000 microg/ml. Additionally, the mice were boosted once or twice with ovalbumin alone. Immunization with ovalbumin alone, the ovalbumin control group, served as the baseline for antibody production, whereas aluminium hydroxide served as the positive control. The levels of ovalbumin-specific IgE, IgG1 and IgG2a antibodies in sera were determined. Adjuvant effect was accepted to be present if a statistical increase in antibody production occurred in a test group as compared to an ovalbumin control group together with the fulfillment of dose-response relationships. Adjuvant effect varied strongly between the phthalates investigated. Phthalates with 8 or 9 carbon atoms in the alkyl side chains were the stronger adjuvants whereas phthalates with shorter or longer alkyl side chains possessed less adjuvant activity. Adjuvant effects were apparent either from the IgE or the IgG1 response or both, whereas no effect was seen on the IgG2a response. Additional studies with airborne exposure are required to establish whether the hazards also result in a significant risk for the development of allergy in man.
authors.affiliation: Department of Chemical Working Environment, National Institute of Occupational Health, Copenhagen, Denmark. stl@ami.dk
authors.forename: Søren T
authors.initials: ST
authors.lastname: Larsen
authors.forename: Rikke M
authors.initials: RM
authors.lastname: Lund
authors.forename: Gunnar D
authors.initials: GD
authors.lastname: Nielsen
authors.forename: Peter
authors.initials: P
authors.lastname: Thygesen
authors.forename: Otto M
authors.initials: OM
authors.lastname: Poulsen
mesh_terms: D000276:Adjuvants, Immunologic / Q000633:toxicity*; D000818:Animals; D000917:Antibody Formation; D003993:Dibutyl Phthalate / Q000008:administration & dosage / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006967:Hypersensitivity / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010795:Phthalic Acids / Q000008:administration & dosage / Q000633:toxicity*; D010968:Plasticizers / Q000008:administration & dosage / Q000633:toxicity*; D013329:Structure-Activity Relationship
chemical_list: D000276:Adjuvants, Immunologic; D004785:Environmental Pollutants; D007074:Immunoglobulin G; D010795:Phthalic Acids; D010968:Plasticizers; D003993:Dibutyl Phthalate; D007073:Immunoglobulin E; C012125:diisononyl phthalate; C010715:di-n-octyl phthalate; D010047:Ovalbumin; C042080:diisodecyl phthalate