Sex-specific behavioral effects following developmental exposure to tetrabromobisphenol A (TBBPA) in Wistar rats

Rock, Kylie D.; Gillera, Sagi Enicole A.; Devarasetty, Pratyush Pavan; Horman, Brian; Knudsen, Gabriel A.; Birnbaum, Linda S.; Fenton, Suzanne E.; Patisaul, Heather B.

doi:10.1016/j.neuro.2019.09.003

Cited by 26 publications

(26 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Wistar rats were obtained from Charles River (Raleigh, NC) and/or bred in house as indicated in humidity-and temperature-controlled rooms, each with 12-h:12-h light:dark cycles at 25°C and 45-60% average humidity in the AAALAC approved Biological Resource Facility at NCSU. As in our prior studies (Patisaul and Adewale, 2009;Rock et al, 2019), and in accordance with recommended practices for endocrine disrupting chemical (EDC) research, all rats were housed in conditions specifically designed to minimize unintended EDC exposure including use of glass water bottles with metal sippers, soy free diet (Teklad 2020, Envigo), woodchip bedding, and thoroughly washed polysulfone caging (Howdeshell et al, 2003;Li et al, 2008;Thigpen et al, 1999).…”

Section: Animalsmentioning

confidence: 99%

Perinatal exposure to FireMaster® 550 (FM550), brominated or organophosphate flame retardants produces sex and compound specific effects on adult Wistar rat socioemotional behavior

Witchey

Samara

Horman

et al. 2020

Hormones and Behavior

Self Cite

View full text Add to dashboard Cite

Section: Animalsmentioning

confidence: 99%

Perinatal exposure to FireMaster® 550 (FM550), brominated or organophosphate flame retardants produces sex and compound specific effects on adult Wistar rat socioemotional behavior

Witchey

Samara

Horman

et al. 2020

Hormones and Behavior

Self Cite

View full text Add to dashboard Cite

“…In addition, DM induces oxidative stress and lipid peroxidation, which most likely also contribute to its neurotoxicity (reviewed in Pitzer et al (2021) ). The flame retardant (FR) TBBPA interferes with brain development in rodents ( Hendriks et al, 2015 ; Rock et al, 2019 ) and its DNT-relevance for humans is supported by studies reporting bioaccumulation in maternal serum, cord blood and breast milk ( Cariou et al, 2008 ; Kim and Oh, 2014 ). The adverse effects of TBBPA on OL differentiation in the NPC5 assay were accompanied by deregulation of a gene cluster involved in cholesterol metabolism suggesting lipotoxicity as TBBPA’s MoA ( Klose et al, 2021b ).…”

Section: Resultsmentioning

confidence: 99%

Scientific Validation of Human Neurosphere Assays for Developmental Neurotoxicity Evaluation

et al. 2022

View full text Add to dashboard Cite

There is a call for a paradigm shift in developmental neurotoxicity (DNT) evaluation, which demands the implementation of faster, more cost-efficient, and human-relevant test systems than current in vivo guideline studies. Under the umbrella of the Organisation for Economic Co-operation and Development (OECD), a guidance document is currently being prepared that instructs on the regulatory use of a DNT in vitro battery (DNT IVB) for fit-for-purpose applications. One crucial issue for OECD application of methods is validation, which for new approach methods (NAMs) requires novel approaches. Here, mechanistic information previously identified in vivo, as well as reported neurodevelopmental adversities in response to disturbances on the cellular and tissue level, are of central importance. In this study, we scientifically validate the Neurosphere Assay, which is based on human primary neural progenitor cells (hNPCs) and an integral part of the DNT IVB. It assesses neurodevelopmental key events (KEs) like NPC proliferation (NPC1ab), radial glia cell migration (NPC2a), neuronal differentiation (NPC3), neurite outgrowth (NPC4), oligodendrocyte differentiation (NPC5), and thyroid hormone-dependent oligodendrocyte maturation (NPC6). In addition, we extend our work from the hNPCs to human induced pluripotent stem cell-derived NPCs (hiNPCs) for the NPC proliferation (iNPC1ab) and radial glia assays (iNPC2a). The validation process we report for the endpoints studied with the Neurosphere Assays is based on 1) describing the relevance of the respective endpoints for brain development, 2) the confirmation of the cell type-specific morphologies observed in vitro, 3) expressions of cell type-specific markers consistent with those morphologies, 4) appropriate anticipated responses to physiological pertinent signaling stimuli and 5) alterations in specific in vitro endpoints upon challenges with confirmed DNT compounds. With these strong mechanistic underpinnings, we posit that the Neurosphere Assay as an integral part of the DNT in vitro screening battery is well poised for DNT evaluation for regulatory purposes.

show abstract

“…TBBPA causes endocrine disrupting effects, 29,30 neurotoxicity, 31,32 and reproductive and developmental toxicity. 33,34 However, the toxicity of glycosylated metabolites themselves has been scarcely investigated.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…TBBPA causes endocrine disrupting effects, , neurotoxicity, , and reproductive and developmental toxicity. , However, the toxicity of glycosylated metabolites themselves has been scarcely investigated. Indeed, according to our results, the toxicities of glycosyl TBBPAs are very difficult to accurately ascertain because the observed rapid deglycosylation makes glycosyl TBBPAs and TBBPA (transformed from glycosyl TBBPAs) always simultaneously present.…”

Section: Resultsmentioning

confidence: 99%

Two Typical Glycosylated Metabolites of Tetrabromobisphenol A Formed in Plants: Excretion and Deglycosylation in Plant Root Zones

Hou

Wei

Tang

et al. 2021

Environ. Sci. Technol. Lett.

View full text Add to dashboard Cite

The glycosylation process was investigated for the common brominated flame retardant tetrabromobisphenol A (TBBPA) in hydroponic exposure systems with pumpkin seedlings. Two typical glycosylation metabolites of TBBPA formed in pumpkin seedlings, TBBPA mono-β-d-glucopyranoside (TBBPA MG) and TBBPA di-β-d-glucopyranoside (TBBPA DG), increasing their mass early in the exposure (reaching maximum masses of 608 ± 53 and 3806 ± 1570 pmol at 12 h, respectively) and then falling throughout exposure. These two metabolites were released from roots to rhizosphere solutions, where they also exhibited initial increases followed by decreasing trends (reaching maximum masses of 595 ± 272 pmol at 3 h and 77.1 ± 36.0 pmol at 6 h, respectively). However, a (pseudo)zero-order deglycosylation of TBBPA MG and TBBPA DG (during the first 1.5 h) back to TBBPA was unexpectedly detected in the hydroponic solutions containing pumpkin exudates and microorganisms. The function of microorganisms in the solutions was further investigated, revealing that the microorganisms were main contributors to deglycosylation. Plant detoxification through glycosylation and excretion, followed by deglycosylation of metabolites back to the toxic parent compound (TBBPA) in hydroponic solutions, provides new insight into the uptake, transformation, and environmental fate of TBBPA and its glycosylated metabolites in plant/microbial systems.

show abstract

Sex-specific behavioral effects following developmental exposure to tetrabromobisphenol A (TBBPA) in Wistar rats

Cited by 26 publications

References 78 publications

Perinatal exposure to FireMaster® 550 (FM550), brominated or organophosphate flame retardants produces sex and compound specific effects on adult Wistar rat socioemotional behavior

Perinatal exposure to FireMaster® 550 (FM550), brominated or organophosphate flame retardants produces sex and compound specific effects on adult Wistar rat socioemotional behavior

Scientific Validation of Human Neurosphere Assays for Developmental Neurotoxicity Evaluation

Two Typical Glycosylated Metabolites of Tetrabromobisphenol A Formed in Plants: Excretion and Deglycosylation in Plant Root Zones

Contact Info

Product

Resources

About