Evaluation of the immunomodulatory potential of diethyl phthalate following dermal exposure in a murine model.
Franko JL; Lukomska E; Meade BJ; Anderson SE
Toxicologist 2011 Mar; 120(Suppl 2):144
Over the past 50 years the prevalence of asthma and allergy has increased throughout the US and other industrialized nations. During the same period there has been an increase in the production and use of phthalate compounds. Previous studies have suggested that certain phthalate compounds, including diethy-hexyl phthalate and butyl benzyl phthalate, have contributed to allergic disease by functioning as adjuvants, augmenting immunologic responses to other chemical and protein antigens without being allergenic themselves. Diethyl phthalate (DEP), another phthalate ester, used as a plasticizer in a variety of consumer products, has the potential for widespread exposure, both occupationally and in the general population. Although DEP is not an immune sensitizer, little is known about other immunological effects that may be associated with DEP exposure. The current study evaluated the immunotoxic potential of DEP. Dermal exposure to DEP concentrations as low as 50% were shown to be immunosuppressive, resulting in a modest reduction in thymus weights (%) and numbers of CD4+ and CD8+ thymocytes (30.7 and 37.6% respectively) in BALB/c mice. A dose responsive decrease in the primary IgM response to sheep red blood cells was observed following dermal exposure to DEP reaching 54% reduction at the highest concentration. Conversely, prior dermal exposure to 75% DEP enhanced airway hyperreactivity responses to aerosolized methacholine in mice sensitized to increasing concentrations of OVA, suggesting that despite its immunosuppressive properties, DEP may enhance airway responsiveness to environmental and occupationally relevant antigens and thereby contributing to the increased prevalence of allergic disease. These results warrant the need for additional investigation into the mechanisms underlying the immunotoxic effects associated with DEP exposure.
Aerosol-particles; Aerosols; Allergic-reactions; Allergies; Biological-effects; Cell-biology; Chemical-hypersensitivity; Chemical-properties; Dose-response; Exposure-levels; Immune-reaction; Immune-system; Immunochemistry; Immunotoxins; Laboratory-animals; Laboratory-testing; Physiological-effects; Quantitative-analysis; Skin-absorption; Skin-exposure; Skin-irritants; Skin-sensitivity; Statistical-analysis; Statistical-analysis; Toxic-effects
The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC