Inhalation study of very low dose of formaldehyde in mice relate to a model for multiple chemical sensitivity

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Multiple chemical sensitivity (MCS) is characterized by various somatic symptoms which cannot be explained organically and by sensitivity to extremely low concentrations of chemicals including formaldehyde. Formaldehyde is a flammable, colorless and readily polymerized gas at ambient temperature. Formaldehyde exposure is considered to be one of initiating event for induction of MCS. In this study, we developed an animal model to investigate the effect of chronic exposure to low levels of formaldehyde in mice. Female mice (BALB/c and C3H/He) with or without ovalbumin (OVA)-immunization were exposed to either ambient air or formaldehyde gas obtained by depolymerization of paraformaldehyde at a dose of 80, 400 and 2000 ppb for four or twelve weeks (16 hours/day x 5 days/week). The formaldehyde gas concentration in the chamber was measured by a 2,4-dinitrophenylhydrazine (DNPH) - high performance liquid chromatography (HPLC). The body weights of animals exposed to formaldehyde were similar to those of their controls. Formaldehyde exposure did not show any adverse effects including epithelial cell proliferation, epithelial dysplasia and squamous metaplasia on morphology of the lung and trachea. We also investigated chronic effects of formaldehyde on the neuronal function, especially on hippocampus. We observed the decrease in recurrent inhibition in the dentate gyrus, that may contribute to alter the excitability of the hippocampus. As for changes in behavior, exposure to formaldehyde induced dose dependent increases in sneezing reflexes. Sneezing reflexes in the mice sensitized with OVA was significantly high compared with non-sensitized mice even in exposure to 80ppb formaldehyde. Further study is necessary to determine how theses changes could relate to a model for MCS.