Impact of dietary exposure to low-dose tris(1,3-dichloro-2-propyl)phosphate in allergic asthmatic mice

Abstract

Objective Tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) is an organophosphorus flame retardant that is an alternative to brominated flame retardants. Although TDCIPP can adversely affect human health, information about its effects on immune and allergic responses is scarce. We aimed to investigate the effects of dietary exposure to TDCIPP using less than the human tolerable daily intake (TDI) in allergic asthmatic mice. Methods Male C3H/HeJSlc mice were fed a chow diet containing TDCIPP equivalent to 0.02 μg/kg/day (low; L), 0.2 μg/kg/day (medium; M), or 2 μg/kg/day (high; H) and were intratracheally administered ovalbumin (OVA, 1 μg/animal) every 2 weeks from 5 to 11 weeks of age. Results In OVA-treated mice, TDCIPP-H exposure tended to enhance pulmonary inflammation compared with vehicle exposure. TDCIPP dose-dependently decreased mRNA level of G protein-coupled estrogen receptor (GPER) in the lungs with or without OVA. OVA + TDCIPP-H treatment tended to increase the total cell number and promoted CD4+ cell activation compared with OVA alone treatment in mediastinal lymph nodes. In splenocytes, an increase in the fraction of Breg cells, but not of total B and T cells, and an increase in IL-5 in cell culture supernatants following OVA re-stimulation in OVA + TDCIPP-H-treated mice was observed compared with OVA-alone-treated mice. Moreover, OVA + TDCIPP-H exposure decreased Gr-1 expression in bone marrow (BM) cells. Discussion These results suggested that dietary exposure to TDCIPP at TDI level slightly enhances allergic diseases, such as allergic asthma, via GPER regulation at inflamed sites and secondary lymphoid tissue and BM cell alternations.