Ortho-phthalaldehyde inhalation induces immune activation in the nasal mucosa and draining lymph nodes in mice.
Johnson-VJ; Reynolds-JS; Wang-W; Fluharty-K; Yucesoy-B
Toxicologist 2009 Mar; 108(1):313
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. Concerns regarding the safety of 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 hypothesize that OPA may pose 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 the respiratory toxicity of OPA using a murine model. A nose-only vapor inhalation system was used to expose mice to OPA vapor for 4 hours/day for 3 consecutive days followed by sacrifice on day 5. The lungs, nasal mucosa and head-draining lymph nodes were collected and processed for cytokine gene expression analysis. Expressions of TNFalpha and IL-1beta, cytokines important for activation and migration of dendritic cells, were increased in the draining lymph nodes as well as the nasal mucosa. Increased IL-4 and IL-10 expression was observed in the draining lymph nodes as well as increased IL-4 expression in the nasal mucosa. In contrast, the expression of IFN„ was not changed in either tissue following OPA inhalation. Lung cytokine expression was also examined; however, no changes were evident. These data demonstrate that OPA inhalation induces an immune response locally in the nasal mucosa. Importantly, OPA inhalation induced activation of lymphocytes in the mandibular lymph nodes that drain the nasal mucosa, thus supporting the potential for sensitization to this chemical. The Th2-dominant expression pattern in the draining lymph nodes suggests that OPA may have the potential to cause respiratory sensitization.
Biological-factors; Breathing; Chemical-cleaning; Chemical-hypersensitivity; Employee-exposure; Exposure-assessment; Exposure-levels; Exposure-methods; Laboratory-animals; Laboratory-testing; Lymph-nodes; Lymphatic-system; Occupational-exposure; Occupational-hazards; Occupational-health; Inhalation-studies; Respiratory-hypersensitivity; Respiratory-system-disorders; Risk-factors; Risk-analysis; Safety-measures; Safety-practices; Toxic-effects; Nasal-disorders; Mucous-membranes
Healthcare and Social Assistance
The Toxicologist. Society of Toxicology 48th Annual Meeting and ToxExpo, March 15-19, 2009, Baltimore, Maryland