Concern has been raised over the potential association of diacetyl, a chemical used in the production of butter flavorings, with lung disease clinically resembling broncholitis obliterans in food manufacturing workers. This has resulted in the need for identification of alternative chemicals to be used in the manufacturing process. We have previously shown diacetyl to be a dermal irritant and sensitizer (EC3 1.9) when tested in a combined murine local lymph node assay (LLNA). Structurally similar chemicals, 2,3-pentanedione 2,3-hexanedione 3,4-hexanedione and 2,3- heptanedione, used as constituents of synthetic flavoring agents have been suggested as potential alternatives for diacetyl. Immunotoxicity data on these chemicals are limited. The present study evaluated the dermal irritation and sensitization potential of diacetyl alternatives using a murine model. None of the chemicals were identified as dermal irritants when tested at concentrations up to 50%. Similar to diacetyl, concentration-dependent increases in lymphocyte proliferation were observed following exposure to all four chemicals, with calculated EC3 values of 15.4% (2,3-pentanedione), 18.2% (2,3-hexanedione), 15.5% (3,4-hexanedione) and 14.1% (2,3-heptanedione). No biologically significant elevations in total serum IgE were identified, however significant elevations in local IgE (IgE+B220+ lymphocytes), IL-4, and INF-gamma production by stimulated draining lymphocytes were observed after exposure to 25-50% concentrations of these chemicals. These results demonstrate the potential for development of hypersensitivity responses to these proposed alternatives and raise concern about their use as a replacement for diacetyl as flavoring agents.
Biological-effects; Cell-biology; Cell-function; Cellular-reactions; Chemical-analysis; Chemical-composition; Chemical-hypersensitivity; Chemical-properties; Chemical-reactions; Cytotoxic-effects; Immune-reaction; Immunochemistry; Immunotoxins; Lung-cells; Lung-disease; Lung-disorders; Lung-irritants; Lymphatic-system; Microscopic-analysis; Molecular-biology; Physiological-effects; Pulmonary-disorders; Pulmonary-system; Pulmonary-system-disorders; Quantitative-analysis; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Skin-exposure; Skin-irritants; Statistical-analysis; Toxic-effects; Toxic-materials; Toxicology; Work-environment; Workplace-studies
The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC