@article{starnes_jackson_rock_belcher_2024, title={Quantitative cross-species comparison of serum albumin binding of per- and polyfluoroalkyl substances from five structural classes}, ISSN={["1096-0929"]}, url={https://doi.org/10.1093/toxsci/kfae028}, DOI={10.1093/toxsci/kfae028}, abstractNote={Abstract}, journal={TOXICOLOGICAL SCIENCES}, author={Starnes, Hannah M. and Jackson, Thomas W. and Rock, Kylie D. and Belcher, Scott M.}, year={2024}, month={Mar} }
 @article{rock_polera_guillette_starnes_dean_watters_stevens-stewart_belcher_2023, title={Domestic Dogs and Horses as Sentinels of Per- and Polyfluoroalkyl Substance Exposure and Associated Health Biomarkers in Gray's Creek North Carolina}, volume={57}, ISSN={["1520-5851"]}, url={https://doi.org/10.1021/acs.est.3c01146}, DOI={10.1021/acs.est.3c01146}, abstractNote={Central North Carolina (NC) is highly contaminated with per- and polyfluoroalkyl substances (PFAS), in part due to local fluorochemical production. Little is known about the exposure profiles and long-term health impacts for humans and animals that live in nearby communities. In this study, serum PFAS concentrations were determined using liquid chromatography high-resolution mass spectrometry and diagnostic clinical chemistry endpoints were assessed for 31 dogs and 32 horses that reside in Gray's Creek NC at households with documented PFAS contamination in their drinking water. PFAS were detected in every sample, with 12 of the 20 PFAS detected in ≥50% of samples from each species. The average total PFAS concentrations in horses were lower compared to dogs who had higher concentrations of PFOS (dogs 2.9 ng/mL; horses 1.8 ng/mL), PFHxS (dogs 1.43 ng/mL, horses < LOD), and PFOA (dogs 0.37 ng/mL; horses 0.10 ng/mL). Regression analysis highlighted alkaline phosphatase, glucose, and globulin proteins in dogs and gamma glutamyl transferase in horses as potential biomarkers associated with PFAS exposure. Overall, the results of this study support the utility of companion animal and livestock species as sentinels of PFAS exposure differences inside and outside of the home. As in humans, renal and hepatic health in domestic animals may be sensitive to long-term PFAS exposures.}, number={26}, journal={ENVIRONMENTAL SCIENCE & TECHNOLOGY}, author={Rock, Kylie D. and Polera, Madison E. and Guillette, Theresa C. and Starnes, Hannah M. and Dean, Kentley and Watters, Mike and Stevens-Stewart, Debra and Belcher, Scott M.}, year={2023}, month={Jun}, pages={9567–9579} }
 @article{zierden_marx-rattner_rock_montgomery_anastasiadis_folts_bale_2023, title={Extracellular vesicles are dynamic regulators of maternal glucose homeostasis during pregnancy}, volume={13}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-023-31425-x}, abstractNote={Abstract}, number={1}, journal={SCIENTIFIC REPORTS}, author={Zierden, Hannah C. C. and Marx-Rattner, Ruth and Rock, Kylie D. D. and Montgomery, Kristen R. R. and Anastasiadis, Pavlos and Folts, Lillian and Bale, Tracy L. L.}, year={2023}, month={Mar} }
 @article{newell_kapps_cai_rai_st armour_horman_rock_witchey_greenbaum_patisaul_2023, title={Maternal organophosphate flame retardant exposure alters the developing mesencephalic dopamine system in fetal rat}, volume={191}, ISSN={["1096-0929"]}, DOI={10.1093/toxsci/kfac137}, abstractNote={Abstract}, number={2}, journal={TOXICOLOGICAL SCIENCES}, author={Newell, Andrew J. and Kapps, Victoria A. and Cai, Yuheng and Rai, Mani Ratnam and St Armour, Genevieve and Horman, Brian M. and Rock, Kylie D. and Witchey, Shannah K. and Greenbaum, Alon and Patisaul, Heather B.}, year={2023}, month={Feb}, pages={357–373} }
 @article{belcher_guillette_robb_rock_2022, title={Comparative assessment of blood mercury in American alligators (Alligator mississippiensis) from Coastal North Carolina and Florida}, volume={8}, ISSN={["1573-3017"]}, url={https://doi.org/10.1007/s10646-022-02573-z}, DOI={10.1007/s10646-022-02573-z}, abstractNote={Mercury (Hg) is a widespread and harmful persistent pollutant of aquatic ecosystems. Except for the northern most populations of American alligators (Alligator Mississippiensis) found in North Carolina, the potential adverse health impacts of Hg on ecosystems and humans consuming alligator meat have been studied for over three decades. Now that alligators are being recreationally hunted and consumed across their range, it is especially important to monitor toxic contaminant levels to best understand possible adverse impacts of exposures on alligator populations and human health. In this study, we determined blood Hg concentrations in American alligators from an urbanized site in Wilmington, NC, a nearby site at Lake Waccamaw, NC, and a site on the St Johns River in Florida. Median blood total Hg (tHg) concentrations were particularly high at Lake Waccamaw (526 ng/g, range 152–946 ng/g), resulting in median muscle concentrations (0.48 mg/kg, range 0.13–0.88 mg/kg) well above US EPA screening values for fish consumption. Median concentrations at the Wilmington site (69 ng/g, range 22–336 ng/g) were generally low, and Hg concentrations from the St Johns River site (143 ng/g, range 54–244 ng/g) were comparable to those reported in previous studies. Analysis of relationships between tHg concentrations and a panel of blood chemistry biomarkers found only modest concentration-dependent impact on biomarkers of renal function. The results of this study reveal that local environmental factors greatly impact Hg bioaccumulation in alligators, findings that reaffirm local contaminant biomonitoring in alligator populations will be critical for affective management and determination of guidelines for safe consumption of harvested alligators.}, journal={ECOTOXICOLOGY}, publisher={Springer Science and Business Media LLC}, author={Belcher, Scott M. and Guillette, Matthew P. and Robb, Frank and Rock, Kylie D.}, year={2022}, month={Aug} }
 @article{macari_rock_santos_lima_szawka_moss_horman_patisaul_2020, title={Developmental Exposure to the Flame Retardant Mixture Firemaster 550 Compromises Adult Bone Integrity in Male but not Female Rats}, volume={21}, ISSN={["1422-0067"]}, DOI={10.3390/ijms21072553}, abstractNote={Flame retardants (FRs) are used in a variety of common items from furniture to carpet to electronics to reduce flammability and combustion, but the potential toxicity of these compounds is raising health concerns globally. Organophosphate FRs (OPFRs) are becoming more prevalent as older, brominated FRs are phased out, but the toxicity of these compounds, and the FR mixtures that contain them, is poorly understood. Work in a variety of in vitro model systems has suggested that FRs may induce metabolic reprogramming such that bone density is compromised at the expense of increasing adiposity. To address this hypothesis, the present studies maternally exposed Wistar rat dams orally across gestation and lactation to 1000 µg daily of the FR mixture Firemaster 550 (FM 550) which contains a mixture of brominated FRs and OPFRs. At six months of age, the offspring of both sexes were examined for evidence of compromised bone composition. Bone density, composition, and marrow were all significantly affected, but only in males. The fact that the phenotype was observed months after exposure suggests that FM 550 altered some fundamental aspect of mesenchymal stem cell reprogramming. The severity of the phenotype and the human-relevance of the dose employed, affirm this is an adverse outcome meriting further exploration.}, number={7}, journal={INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, author={Macari, Soraia and Rock, Kylie D. and Santos, Mariana S. and Lima, Virginia T. M. and Szawka, Raphael E. and Moss, Jamal and Horman, Brian and Patisaul, Heather B.}, year={2020}, month={Apr} }
 @article{rock_st armour_horman_phillips_ruis_stewart_jima_muddiman_stapleton_patisaul_2020, title={Effects of Prenatal Exposure to a Mixture of Organophosphhate Flame Ritardants on Placental Gene Expression and Serotonergic Innervaion in the Fetal Rat Brain}, volume={176}, ISSN={["1096-0929"]}, DOI={10.1093/toxsci/kfaa046}, abstractNote={Abstract}, number={1}, journal={TOXICOLOGICAL SCIENCES}, author={Rock, Kylie D. and St Armour, Genevieve and Horman, Brian and Phillips, Allison and Ruis, Matthew and Stewart, Allison K. and Jima, Dereje and Muddiman, David C. and Stapleton, Heather M. and Patisaul, Heather B.}, year={2020}, month={Jul}, pages={203–223} }
 @article{jackson_bendfeldt_beam_rock_belcher_2020, title={Heterozygous mutation of sonic hedgehog receptor (Ptch1) drives cerebellar overgrowth and sex-specifically alters hippocampal and cortical layer structure, activity, and social behavior in female mice}, volume={78}, ISSN={["1872-9738"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85080064843&partnerID=MN8TOARS}, DOI={10.1016/j.ntt.2020.106866}, abstractNote={Sonic hedgehog (SHH) signaling is essential for the differentiation and migration of early stem cell populations during cerebellar development. Dysregulation of SHH-signaling can result in cerebellar overgrowth and the formation of the brain tumor medulloblastoma. Treatment for medulloblastoma is extremely aggressive and patients suffer life-long side effects including behavioral deficits. Considering that other behavioral disorders including autism spectrum disorders, holoprosencephaly, and basal cell nevus syndrome are known to present with cerebellar abnormalities, it is proposed that some behavioral abnormalities could be inherent to the medulloblastoma sequalae rather than treatment. Using a haploinsufficient SHH receptor knockout mouse model (Ptch1+/−), a partner preference task was used to explore activity, social behavior and neuroanatomical changes resulting from dysregulated SHH signaling. Compared to wild-type, Ptch1+/− females displayed increased activity by traveling a greater distance in both open-field and partner preference tasks. Social behavior was also sex-specifically modified in Ptch1+/− females that interacted more with both novel and familiar animals in the partner preference task compared to same-sex wild-type controls. Haploinsufficiency of PTCH1 resulted in cerebellar overgrowth in lobules IV/V and IX of both sexes, and female-specific decreases in hippocampal size and isocortical layer thickness. Taken together, neuroanatomical changes related to deficient SHH signaling may alter social behavior.}, journal={NEUROTOXICOLOGY AND TERATOLOGY}, author={Jackson, Thomas W. and Bendfeldt, Gabriel A. and Beam, Kelby A. and Rock, Kylie D. and Belcher, Scott M.}, year={2020} }
 @article{ruis_rock_hall_horman_patisaul_stapleton_2019, title={PBDEs Concentrate in the Fetal Portion of the Placenta: Implications for Thyroid Hormone Dysregulation}, volume={160}, ISSN={["1945-7170"]}, DOI={10.1210/en.2019-00463}, abstractNote={Abstract}, number={11}, journal={ENDOCRINOLOGY}, author={Ruis, Matthew T. and Rock, Kylie D. and Hall, Samantha M. and Horman, Brian and Patisaul, Heather B. and Stapleton, Heather M.}, year={2019}, month={Nov}, pages={2748–2758} }
 @article{rock_gillera_devarasetty_horman_knudsen_birnbaum_fenton_heather_2019, title={Sex-specific behavioral effects following developmental exposure to tetrabromobisphenol A (TBBPA) in Wistar rats}, volume={75}, ISSN={["1872-9711"]}, url={https://doi.org/10.1016/j.neuro.2019.09.003}, DOI={10.1016/j.neuro.2019.09.003}, abstractNote={Tetrabromobisphenol A (TBBPA) has become a ubiquitous indoor contaminant due to its widespread use as an additive flame retardant in consumer products. Reported evidence of endocrine disruption and accumulation of TBBPA in brain tissue has raised concerns regarding its potential effects on neurodevelopment and behavior. The goal of the present study was to examine the impact of developmental TBBPA exposure, across a wide range of doses, on sexually dimorphic non-reproductive behaviors in male and female Wistar rats. We first ran a pilot study using a single TBBPA dose hypothesized to produce behavioral effects. Wistar rat dams were orally exposed using cookie treats to 0 or 0.1 mg TBBPA/kg bw daily from gestational day (GD) 9 to postnatal day (PND) 21 to assess offspring (both sexes) activity and anxiety-related behaviors. Significant effects were evident in females, with exposure increasing activity levels. Thus, this dose was used as the lowest TBBPA dose in a subsequent, larger study conducted as part of a comprehensive assessment of TBBPA toxicity. Animals were exposed to 0, 0.1, 25, or 250 mg TBBPA/kg bw daily by oral gavage starting on GD 6 through PND 90 (dosed dams GD 6 - PND 21, dosed offspring PND 22 - PND 90). Significant behavioral findings were observed for male offspring, with increased anxiety-like behavior as the primary phenotype. These findings demonstrate that exposure to environmental contaminants, like TBBPA, can have sex-specific effects on behavior highlighting the vulnerability of the developing brain.}, journal={NEUROTOXICOLOGY}, publisher={Elsevier BV}, author={Rock, Kylie D. and Gillera, Sagi Enicole A. and Devarasetty, Pratyush and Horman, Brian and Knudsen, Gabriel and Birnbaum, Linda S. and Fenton, Suzanne E. and Heather, Patisaul B.}, year={2019}, month={Dec}, pages={136–147} }
 @article{rock_horman_phillips_mcritchie_watson_deese-spruill_jima_sumner_stapleton_patisaul_et al._2018, title={EDC IMPACT: Molecular effects of developmental FM 550 exposure in Wistar rat placenta and fetal forebrain}, volume={7}, ISSN={["2049-3614"]}, DOI={10.1530/ec-17-0373}, abstractNote={Firemaster 550 (FM 550) is a flame retardant (FR) mixture that has become one of the most commonly used FRs in foam-based furniture and baby products. Human exposure to this commercial mixture, composed of brominated and organophosphate components, is widespread. We have repeatedly shown that developmental exposure can lead to sex-specific behavioral effects in rats. Accruing evidence of endocrine disruption and potential neurotoxicity has raised concerns regarding the neurodevelopmental effects of FM 550 exposure, but the specific mechanisms of action remains unclear. Additionally, we observed significant, and in some cases sex-specific, accumulation of FM 550 in placental tissue following gestational exposure. Because the placenta is an important source of hormones and neurotransmitters for the developing brain, it may be a critical target of toxicity to consider in the context of developmental neurotoxicity. Using a mixture of targeted and exploratory approaches, the goal of the present study was to identify possible mechanisms of action in the developing forebrain and placenta. Wistar rat dams were orally exposed to FM 550 (0, 300 or 1000 µg/day) for 10 days during gestation and placenta and fetal forebrain tissue collected for analysis. In placenta, evidence of endocrine, inflammatory and neurotransmitter signaling pathway disruption was identified. Notably, 5-HT turnover was reduced in placental tissue and fetal forebrains indicating that 5-HT signaling between the placenta and the embryonic brain may be disrupted. These findings demonstrate that environmental contaminants, like FM 550, have the potential to impact the developing brain by disrupting normal placental functions.}, number={2}, journal={ENDOCRINE CONNECTIONS}, author={Rock, K. D. and Horman, B. and Phillips, A. L. and McRitchie, S. L. and Watson, S. and Deese-Spruill, J. and Jima, D. and Sumner, S. and Stapleton, H. M. and Patisaul, Heather and et al.}, year={2018}, month={Feb}, pages={305–324} }
 @article{bagley_ekelof_rock_patisaul_muddiman_2018, title={IR-MALDESI mass spectrometry imaging of underivatized neurotransmitters in brain tissue of rats exposed to tetrabromobisphenol A}, volume={410}, ISSN={["1618-2650"]}, DOI={10.1007/s00216-018-1420-0}, abstractNote={There is a pressing need to develop tools for assessing possible neurotoxicity, particularly for chemicals where the mode of action is poorly understood. Tetrabromobisphenol A (TBBPA), a highly abundant brominated flame retardant, has lately been targeted for neurotoxicity analysis by concerned public health entities in the EU and USA because it is a suspected thyroid disruptor and neurotoxicant. In this study, infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) coupled to a Q Exactive Plus mass spectrometer was used for the analysis of neurotransmitters in the brains of rats exposed to TBBPA in gestation and lactation through their mothers. Three neurotransmitters of interest were studied in three selected regions of the brain: caudate putamen, substantia nigra (SN), and dorsal raphe. Stable isotope labeled (SIL) standards were used as internal standards and a means to achieve relative quantification. This study serves as a demonstration of a new application of IR-MALDESI, namely that neurotransmitter distributions can be confidently and rapidly imaged without derivatization.}, number={30}, journal={ANALYTICAL AND BIOANALYTICAL CHEMISTRY}, author={Bagley, M. Caleb and Ekelof, Mans and Rock, Kylie and Patisaul, Heather and Muddiman, David C.}, year={2018}, month={Dec}, pages={7979–7986} }
 @article{phillips_chen_rock_horman_patisaul_stapleton_2016, title={Transplacental and Lactational Transfer of Firemaster (R) 550 Components in Dosed Wistar Rats}, volume={153}, ISSN={["1096-0929"]}, DOI={10.1093/toxsci/kfw122}, abstractNote={UNLABELLED
Firemaster® 550 (FM 550) is a commercial mixture of organophosphate and brominated flame retardants currently in use as a replacement for pentaBDE. Its organophosphate components include triphenyl phosphate (TPHP) and a suite of isopropylated triarylphosphate isomers (ITPs); its brominated components include 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) and bis (2-ethylhexyl)-2,3,4,5-tetrabromophthalate (BEH-TEBP). Taken together, these chemicals have been shown to be endocrine disrupting and potentially toxic, and human exposure to them is widespread. In this study, maternal transfer of FM 550 components, and in some cases their metabolites, was investigated in dosed Wistar rats. Gestational and lactational transfer were examined separately, with dams orally exposed to 300 or 1000 µg of FM 550 for 10 consecutive days during gestation (gestational day [GD] 9-18) or lactation (postnatal day [PND] 3-12). Levels of parent compounds were measured in fetus and whole pup tissue homogenates, and in dam and pup serum, and several metabolites were measured in dam and pup urine. EH-TBB body burdens resulting from lactational transfer were approximately 200- to 300-fold higher than those resulting from placental transfer, whereas low levels of BEH-TEBP were transferred during both lactation and gestation. TPHP and ITPs were rapidly metabolized by the dams and were not detected in whole tissue homogenates. However, diphenyl phosphate (DPHP) and mono-isopropylphenyl phenyl phosphate (ip-PPP) were detected in urine from the dosed animals. This study is the first to confirm ip-PPP as a urinary metabolite of ITPs and establish a pharmacokinetic profile of FM 550 in a mammalian model.


KEY WORDS
Firemaster 550 ;: lactational transfer ;: gestational transfer; metabolites; rodent.}, number={2}, journal={TOXICOLOGICAL SCIENCES}, author={Phillips, Allison L. and Chen, Albert and Rock, Kylie D. and Horman, Brian and Patisaul, Heather B. and Stapleton, Heather M.}, year={2016}, month={Oct}, pages={246–257} }