摘要：Highlights•Perinatal exposure to brominated furans impairs behavior in adult and infant mice.•Adult exploratory behavior and infant calling can be useful behavioral endpoints.•The toxic equivalent factor concept can be applied to brominated dioxins/furans.AbstractPolybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/DFs) have been unintentionally produced and emitted from the lifecycle of products containing brominated flame retardants, such as polybrominated diphenyl ether, which is suspected to cause developmental neurotoxicity (DNT). Although it is plausible that PBDD/DFs can also induce DNT, information regarding their neurotoxic potential is currently limited. Hence, in the present study, we examined the effects ofin uteroand lactational exposure to brominated dibenzofurans on infant and adult offspring behavior to understand the mechanism of PBDD/DFs toxicity and detect effective behavioral endpoints in DNT assessment. We analyzed the behavior of mouse offspring born to dams administered 2,3,7,8-tetrabromodibenzofuran (2,3,7,8-TeBDF; dose of 0, 9, or 45 μg/kg) or 2,3,8-tribromodibenzofuran (2,3,8-TrBDF; dose of 0, 75.6, or 378 μg/kg) on gestational day 12.5. In mouse offspring born to dams exposed to 2,3,7,8-TeBDF, the exploratory behavior in a novel environment in adulthood and ultrasonic vocalization (USV) during infancy were significantly reduced. Additionally, AhR-target genes, such as Cyp1a1, were induced in the liver of 2,3,7,8-TeBDF-exposed offspring in a dose-dependent manner. Conversely, no significant changes in the infant and adult behaviors and expression level of AhR-target genes were observed in the 2,3,8-TrBDF-exposed offspring. These results suggest that 2,3,7,8-TeBDF can induce DNT and that the analysis of exploratory behavior in a novel environment and USV may be useful endpoints to assess DNT of dioxin-related substances.
