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Abstract:The inhalation of many types of chemicals is a leading cause of allergic respiratory diseases, and effective protocols are needed for the detection of environmental chemical-related respiratory allergies. In our previous studies, we developed a method for detecting environmental chemicalrelated respiratory allergens by using a long-term sensitization-challenge protocol involving BALB/c mice. In the current study, we sought to improve our model by characterizing strain-associated differences in respiratory allergic reactions to the well-known chemical respiratory allergen glutaraldehyde (GA). According to our protocol, BALB/c, NC/Nga, C3H/HeN, C57BL/6N, and CBA/J mice were sensitized dermally with GA for 3 weeks and then challenged with intratracheal or inhaled GA at 2 weeks after the last sensitization. The day after the final challenge, all mice were euthanized, and total serum IgE levels were assayed. In addition, immunocyte counts, cytokine production, and chemokine levels in the hilar lymph nodes (LNs) and bronchoalveolar lavage fluids (BALF) were also assessed. In conclusion, BALB/c and NC/Nga mice demonstrated markedly increased IgE reactions. Inflammatory cell counts in BALF were increased in the treated groups of all strains, especially BALB/c, NC/Nga, and CBA/J strains. Cytokine levels in LNs were increased in all treated groups except for C3H/HeN and were particularly high in BALB/c and NC/Nga mice. According to our results, we suggest that BALB/c and NC/Nga are highly susceptible to respiratory allergic responses and therefore are good candidates for use in our model for detecting environmental chemical respiratory allergens.

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People are constantly exposed to environmental chemicals through contact with the atmosphere or by ingestion of food. Therefore, when conducting safety assessments, the immunotoxic effects of combinations of chemicals in addition to toxicities produced by each chemical alone should be considered. The objective of the studies reported here were to demonstrate the combined effects of three well-known environmental immunotoxic chemicals -methoxychlor (MXC), an organochlorine compound; parathion (PARA), an organophosphate compound; and piperonyl butoxide (PBO), an agricultural insecticide synergist -by using a short-term oral exposure method. Seven-week-old Balb/cAnN mice received daily oral exposure to either one or two of the environmental immunotoxic chemicals for 5 consecutive days. On Day 2, all mice in each group were immunized with sheep red blood cells (SRBC), and their SRBC-specific IgM responses were analyzed by using an enzyme-linked immunosorbent assay and plaque-forming cell assay. T-and B-cell counts in the mouse spleens were also assessed via surface antigen expression. Mice that received MXC þ PARA and PBO þ MXC treatment showed marked decreases in SRBC-specific IgM production and T-and B-cell counts compared with those in mice that received vehicle control or the corresponding individual test substance. This suggests that simultaneous exposure to multiple environmental chemicals increases the immunotoxic effects of the chemicals compared to individual exposure.

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