Dietary Exposure to Flame Retardant Tris (2-Butoxyethyl) Phosphate Altered Neurobehavior and Neuroinflammatory Responses in a Mouse Model of Allergic Asthma

Abstract

Tris (2-butoxyethyl) phosphate (TBEP) is an organophosphate flame retardant and used as a plasticizer in various household products such as plastics, floor polish, varnish, textiles, furniture, and electronic equipment. However, little is known about the effects of TBEP on the brain and behavior. We aimed to examine the effects of dietary exposure of TBEP on memory functions, their-related genes, and inflammatory molecular markers in the brain of allergic asthmatic mouse models. C3H/HeJSlc male mice were given diet containing TBEP (0.02 (TBEP-L), 0.2 (TBEP-M), or 2 (TBEP-H) μg/kg/day) and ovalbumin (OVA) intratracheally every other week from 5 to 11 weeks old. A novel object recognition test was conducted in each mouse at 11 weeks old. The hippocampi were collected to detect neurological, glia, and immunological molecular markers using the real-time RT-PCR method and immunohistochemical analyses. Mast cells and microglia were examined by toluidine blue staining and ionized calcium-binding adapter molecule (Iba)-1 immunoreactivity, respectively. Impaired discrimination ability was observed in TBEP-H-exposed mice with or without allergen. The mRNA expression levels of N-methyl-D aspartate receptor subunits Nr1 and Nr2b, inflammatory molecular markers tumor necrosis factor-α oxidative stress marker heme oxygenase 1, microglia marker Iba1, and astrocyte marker glial fibrillary acidic protein were significantly increased in TBEP-H-exposed mice with or without allergen. Microglia and mast cells activation were remarkable in TBEP-H-exposed allergic asthmatic mice. Our results indicate that chronic exposure to TBEP with or without allergen impaired object recognition ability accompanied with alteration of molecular expression of neuronal and glial markers and inflammatory markers in the hippocampus of mice. Neuron-glia-mast cells interaction may play a role in TBEP-induced neurobehavioral toxicity.

Exposures to Organophosphate Esters and Respiratory Morbidity among School-Aged Children with Asthma

“…While there is a lack of epidemiologic studies evaluating OPE exposures and child asthma-related symptoms, several in vivo studies using an asthma mouse model have found evidence that exposures to TPHP and TDCIPP (parent compounds for DPHP and BDCIPP, respectively) may alter immunomodulatory processes and induce oxidative stress, effects possibly leading to increased allergic responses involved in the development and exacerbation of asthma. − Respiratory health effects of the parent compounds of DBuP, BCEtP, and DPCP remain widely understudied, warranting further analysis.…”

“…While several biological mechanisms may underlie these associations, the exact mechanism has not been clearly elucidated. Laboratory studies report that OPEs are involved in the development and exacerbation of asthma by eliciting increased allergic responses through immunomodulatory effects and oxidative stress, both of which are recognized risk factors in the pathophysiology of asthma. − A recent nested case-cohort study among children (ages 9–15 years) also reported significant positive associations between the OPE urinary biomarkers 2-ethylhexyl phenyl phosphate (EHPHP), bis­(2-butoxyethyl) phosphate (BBOEP), and diphenyl phosphate (DPHP) with increased levels of oxidative stress biomarkers (i.e., 8-hydroxy-2′-deoxyguanosine, hexanoyl-lysine, and 4-hydroxynonenal) …”

The key constituents underlying the combined toxicity of eight cosmetic contaminants towards Vibrio qinghaiensis

“…32 Tris(2-butoxyethyl) phosphate (TBEP) is also extensively used as a plastic plasticizer. 33 Studies conducted in Spain have revealed a range of TBEP concentrations in the Iberian River, ranging from 5.3 to 659 ng L −1 , 34 while the maximum concentration observed in effluent from a sewage treatment plant in Sweden was as high as 35 000 ng L −1 . 35 Moreover, TBEP has been ubiquitously detected in the environment, with even low doses of this compound exerting adverse effects on ecosystems.…”