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Inhalation of ortho-phthalaldehyde vapor causes systemic sensitization and allergic inflammation in the lymph nodes, nasal mucosa, and lung of mice.
Johnson VJ; Wang W; Fluharty K; Yucesoy B; Reynolds JS
Toxicologist 2011 Mar; 120(Suppl 2):20
Ortho-Phthalaldehyde (OPA) is increasingly being substituted for glutaraldehyde as a high-level disinfectant for sensitive medical devices. However, toxicological data on OPA safety is lacking. Safety concerns for glutaraldehyde include acute nasal toxicity and sensory irritation as well as sensitization leading to occupational rhinitis and asthma. Since OPA is a dialdehyde like glutaraldehyde and functions as a disinfectant due to its high reactivity for biological macromolecules, it is reasonable to expect similar respiratory hazards. Several case reports have been published supporting this hypothesis showing development of respiratory hypersensitivity reactions in healthcare workers and patients exposed to OPA. The purpose of this study was to determine if OPA is a respiratory sensitizer using a murine model. Mice were exposed via inhalation to OPA vapor 4 hrs/day for 3 days; rested for 11 days; challenged with OPA vapor 4 hrs/day for 3 days and then sacrificed 24 hrs after the final exposure. Lungs, nasal mucosa, head-draining lymph nodes (LN) and serum were collected and processed for cytokine gene expression and flow cytometry. OPA-specific antibodies were detected in the serum of exposed mice. OPA inhalation induced a dose dependent increase in LN IL-4 expression and B-cell proliferation. Importantly, there was a concomitant increase in IgE+ B-cells. Strong Th2 cytokine expression in the nasal mucosa increased with OPA dose whereas the inverse was observed for IFN(y) expression, a cytokine expression pattern commonly observed in response to respiratory allergens. Th2 cytokine expression was also increased in the lung although to a lesser extent. These data demonstrate that OPA inhalation induces a predominant Th2 cytokine response in the respiratory tract and draining LN. Importantly, OPA inhalation induced isotype switching to IgE in the draining LN supporting the development of an allergic immune response. Overall, this study suggests that inhalation of OPA vapor in mice can induce respiratory allergy.
Allergic-reactions; Biological-effects; Cell-biology; Cellular-reactions; Chemical-cleaning; Chemical-hypersensitivity; Chemical-reactions; Cytotoxic-effects; Dose-response; Exposure-levels; Health-care-personnel; Inhalation-studies; Laboratory-animals; Laboratory-testing; Lung-cells; Lung-disorders; Lung-irritants; Medical-facilities; Microscopic-analysis; Physiological-effects; Quantitative-analysis; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Statistical-analysis; Toxic-dose; Toxic-effects; Toxicology; Toxic-vapors
The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC
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