Infant and early childhood physical health assessments in the HEALthy Brain and Child Development (HBCD) Study.

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social and emotional development beginning prenatally and planned through early childhood. Many prenatal and early childhood exposures impact both later physical health and development. Moreover, early deficits in physical health, such as growth and vision, are associated with differences in brain development, language and cognitive functioning. For these reasons, the HBCD Study includes measures of early childhood physical health, many of which have clinical relevance, and are applicable for use as both predictors and outcomes. Study measures assess a broad range of physical health domains and include both objective measurement of child growth and health and subjective caregiver report of behaviors and attitudes about constructs known to influence growth and physical development. Lastly, we obtain caregiver report of the child's routine medical care as well as acute and chronic medical issues. We anticipate that these data will contextualize the impact of child physical growth and health on child brain development and function. In this report we present the rationale for each domain and an overview of the physical health measures included in the current HBCD Study protocol.

Integrated Short-TE and Hadamard-edited Multi-Sequence (ISTHMUS) for advanced MRS.

BACKGROUND: To examine data quality and reproducibility using ISTHMUS, which has been implemented as the standardized MR spectroscopy sequence for the multi-site Healthy Brain and Child Development (HBCD) study. METHODS: ISTHMUS is the consecutive acquisition of short-TE PRESS (32 transients) and long-TE HERCULES (224 transients) data with dual-TE water reference scans. Voxels were positioned in the centrum semiovale, dorsal anterior cingulate cortex, posterior cingulate cortex and bilateral thalamus regions. After acquisition, ISTHMUS data were separated into the PRESS and HERCULES portions for analysis and modeled separately using Osprey. In vivo experiments were performed in 10 healthy volunteers (6 female; 29.5±6.6 years). Each volunteer underwent two scans on the same day. Differences in metabolite measurements were examined. T2 correction based on the dual-TE water integrals were compared with: 1) T2 correction based on the default white matter and gray matter T2 reference values in Osprey and 2) shorter WM and GM T2 values from recent literature. RESULTS: No significant difference in linewidth was observed between PRESS and HERCULES. Bilateral thalamus spectra had produced significantly higher (p<0.001) linewidth compared to the other three regions. Linewidth measurements were similar between scans, with scan-to-scan differences under 1 Hz for most subjects. Paired t-tests indicated a significant difference only in PRESS NAAG between the two thalamus scans (p=0.002). T2 correction based on shorter T2 values showed better agreement to the dual-TE water integral ratio. CONCLUSIONS: ISTHMUS facilitated data acquisition and post-processing and reduced operator workload to eliminate potential human error.

Integrated Short-TE and Hadamard-edited Multi-Sequence (ISTHMUS) for Advanced MRS.

Background: To examine data quality and reproducibility using ISTHMUS, which has been implemented as the standardized MR spectroscopy sequence for the multi-site Healthy Brain and Child Development (HBCD) study. Methods: ISTHMUS is the consecutive acquisition of short-TE PRESS (32 transients) and long-TE HERCULES (224 transients) data with dual-TE water reference scans. Voxels were positioned in the centrum semiovale, dorsal anterior cingulate cortex, posterior cingulate cortex and bilateral thalamus regions. After acquisition, ISTHMUS data were separated into the PRESS and HERCULES portions for analysis and modeled separately using Osprey. In vivo experiments were performed in 10 healthy volunteers (6 female; 29.5±6.6 years). Each volunteer underwent two scans on the same day. Differences in metabolite measurements were examined. T2 correction based on the dual-TE water integrals were compared with: 1) T2 correction based the default white matter and gray matter T2 reference values in Osprey; 2) shorter WM and GM T2 values from recent literature; and 3) reduced CSF fractions. Results: No significant difference in linewidth was observed between PRESS and HERCULES. Bilateral thalamus spectra had produced significantly higher (p<0.001) linewidth compared to the other three regions. Linewidth measurements were similar between scans, with scan-to-scan differences under 1 Hz for most subjects. Paired t-tests indicated a significant difference only in PRESS NAAG between the two thalamus scans (p=0.002). T2 correction based on shorter T2 values showed better agreement to the dual-TE water integral ratio. Conclusions: ISTHMUS facilitated and standardized acquisition and post-processing and reduced operator workload to eliminate potential human error.

Evaluation of hexabromocyclododecane (HBCD), polybrominated dibenzo-p-dioxins/furans (PBDD/Fs) and polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) outflows during the destruction of HBCD wastes in a hazardous waste incinerator.

This paper presents an evaluation of hexabromocyclododecane (HBCD), polybrominated dibenzo-p-dioxins/furans (PBDD/Fs) and polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) outflows during the destruction of HBCD waste stockpiles in IZAYDAS Hazardous Waste Incinerator (HWI) in Kocaeli, Türkiye. HBCD wastes containing 100 % pure HBCD were in 25 kg packages with 63 % Br content were co-incinerated in a 3-day test burn with average feed rate of 26 kg/h. HBCD, PBDD/Fs and PCDD/Fs were measured in the outlet streams to quantify the amount of unintended POPs releases associated with the processing of HBCD waste and to observe the POP removal performance of air pollution control equipment (APCE) of the incinerator. Total mass outflow rate of HBCDs is calculated as 2.6 g/day, corresponding to destruction efficiency of 99.9996 %. Total toxicity of the brominated dioxins was measured as 0.00044 ng TEQ/Nm3 on average, while highly brominated congeners are dominant. PCDD/F concentrations in the outflow streams during HBCD test burns are produced similar congener distributions with those given in the previous studies, with the dominance of 7,8-chlorinated congeners. Mass flows in the outlet streams indicated that the efficiency of ESP and wet scrubbers for the removal of PCDD/Fs and HBCDs. Flue gas concentrations of PCDD/Fs, HBCDs and PBDD/Fs obtained in HBCD burn test indicated that burning HBCD wastes cause no significant emissions as operational parameters and total halogen content in the menu are kept within the incinerator limits.

Bioaccumulation and Male Reproductive Toxicity of the New Brominated Flame Retardant Tetrabromobisphenol A-Bis(2,3-dibromo-2-methylpropyl ether) in Comparison with Hexabromocyclododecane.

Tetrabromobisphenol A-bis(2,3-dibromo-2-methylpropyl ether) (TBBPA-DBMPE) has come into use as an alternative to hexabromocyclododecane (HBCD), but it is unclear whether TBBPA-DBMPE has less hazard than HBCD. Here, we compared the bioaccumulation and male reproductive toxicity between TBBPA-DBMPE and HBCD in mice following long-term oral exposure after birth. We found that the concentrations of TBBPA-DBMPE in livers significantly increased with time, exhibiting a bioaccumulation potency not substantially different from HBCD. Lactational exposure to 1000 µg/kg/d TBBPA-DBMPE as well as 50 µg/kg/d HBCD inhibited testis development in suckling pups, and extended exposure up to adulthood resulted in significant molecular and cellular alterations in testes, with slighter effects of 50 µg/kg/d TBBPA-DBMPE. When exposure was extended to 8 month age, severe reproductive impairments including reduced sperm count, increased abnormal sperm, and subfertility occurred in all treated animals, although 50 µg/kg/d TBBPA-DBMPE exerted lower effects than 50 µg/kg/d HBCD. Altogether, all data led us to conclude that TBBPA-DBMPE exerted weaker male reproductive toxicity than HBCD at the same doses but exhibited bioaccumulation potential roughly equivalent to HBCD. Our study fills the data gap regarding the bioaccumulation and toxicity of TBBPA-DBMPE and raises concerns about its use as an alternative to HBCD.

Hexabromocyclododecane-induced reproductive toxicity in Brachionus plicatilis: Impacts and assessment.

Hexabromocyclododecane (HBCD), third-generation brominated flame retardants (BRFs), has aroused worldwide concern because of its wide application and potentially negative impacts on marine ecosystems, but an information gap still exists regarding marine low-trophic organisms. Brachionus plicatilis, the model marine zooplankton, was used in the present study, and its reproductive responses were used as the endpoint to indicate HBCD-induced toxicity. HBCD was suggested to be extremely highly toxic compounds regarding the 96 h-LC50 of 0.58 mg L-1. The sublethal exposure of HBCD injured the reproduction of B. plicatilis: The total number of offspring per female and the key population index calculated from the life table, including the intrinsic rate of population increase (rm) and net reproductive rate (R0), were significantly influenced in a concentration-dependent manner. The reproductive process was also altered, as indicated by the first spawning time, first hatching time and oocyst development time. At the same time, individual survival and growth (body length) were also negatively affected by HBCD. Reactive oxygen species (ROS) were suggested to be responsible for reproductive toxicity mainly because the total ROS contents as well as the main components of •OH and H2O2 greatly increased and resulted in the oxidative imbalance that presented as malondialdehyde (MDA) elevation. Simultaneous activation of the glutathione antioxidant system was accompanied by the apoptosis marker enzymes Caspase-3 and 9, as well as the correlation between ROS content, physiological alteration and cell apoptosis, providing further evidence for this. The integrated biomarker response (IBR) and adverse outcome pathway (AOP) showed that HBCD had a significant toxic effect on B. plicatilis near the concentration range of 96 h-LC50. The establishment of this concentration range will provide a reliable reference for future environmental concentration warning of HBCD in marine.

Addition of low concentration of cholesterol-loaded cyclodextrin (CLC) has a positive effect on cryopreserved canine spermatozoa evaluated by andrological and biophysical methods.

BACKGROUND: This study was conducted to find the best concentration of cholesterol-loaded cyclodextrin (CLC) which has a positive impact on canine post thaw semen quality. Three different concentrations of CLC (0.83 mg/ml; 1.66 mg/ml; 3.32 mg/ml) and 2-hydroxylpropyl-beta-cyclodextrin (HBCD) (1.66 mg/ml) were used in addition to cryopreservation extender and compared with the control after thawing. Samples were assessed using computer-assisted semen analyzer (CASA), flow cytometry, fluorimeter by measuring the fluorescence anisotropy (ANISO) and determining the generalized membrane polarization (GP). RESULTS: An addition of 0.83 mg/ml CLC significantly increased the percentage of progressive motile (PROG) and rapid spermatozoa (RAP) (P < 0.05). 1.66 mg/ml HBCD decreased progressive motility of spermatozoa and population with rapid movement relative to the control (P < 0.05). Furthermore, the groups with an addition of 1.66 mg/ml and 3.32 mg/ml of CLC, as well as the group with only cyclodextrin, increased percentage of dead spermatozoa without lipid peroxidation and decreased percentage of viable spermatozoa without LPO which was lower in these groups than in the control (P < 0.05). Other sperm parameters assessed on flow cytometer were not significantly different. The addition of CLC at 0.83 mg/ml and 3.32 mg/ml concentrations and 1.66 mg/ml of HBCD caused an increase in ANISO measured at 23 ºC (P < 0.05). CONCLUSIONS: In conclusion, the results suggest that increasing cholesterol in the plasma membrane of canine spermatozoa can improve their freezability. However, only low concentrations of CLC may improve semen quality after thawing without adversely affecting other parameters.

Hexabromocyclododecane (HBCD) induced PANoptosis of chondrocytes via activation of the NLRP3 inflammasome and decreased the exercise ability of mice in vivo.

Hexabromocyclododecane (HBCD) is a persistent organic pollutant (POP). HBCD is found in the blood and tissues of most populations and causes a range of toxicological damage to tissues and cells. However, the toxicological effects of HBCD on chondrocytes are not fully understood. Here, we evaluated the toxicological effects of HBCD on chondrocytes and cartilaginous tissue. For this, a model of primary cartilage cells was established. Chondrocytes were exposed to different concentrations of HBCD. Western blot, indirect immunofluorescence, ELISA and other biochemical experiments were performed to analyze the toxicological effects of HBCD on chondrocytes/articular cartilage tissue. Cell proliferation assays showed that HBCD caused a reduction in the proliferative capacity of chondrocytes, and further work indicated that HBCD induces chondrocyte death. Further experiments demonstrated that HBCD caused an inflammatory response in chondrocytes by evaluating the levels of inflammatory factors. We found that HBCD led to PANoptosis in chondrocytes by detecting panapoptosis-related marker molecules, and experimental data indicated that apoptosis markers (cleaved caspase-3/7), pyroptosis markers (caspase-1/GSDMD-N) and necroptosis markers (pMLKL/RIPK3) were upregulated after HBCD treatment. Subsequent experiments illustrated that HBCD activated the DAMP sensor NLRP3, which then mediated ZBP1-induced PANoptosis. In the in vivo model, the experimental animals were administered HBCD at 25, 50 and 100 µg/kg/week for 15 weeks. We found that HBCD led to an inflammatory response in articular cartilage tissue. The safranin O-fast green assay showed a certain degree of damage to cartilage tissue under HBCD treatment. Furthermore, HBCD resulted in an increase in MMP13 expression and a downregulation of COL2 expression in chondrocytes/cartilaginous tissues. HBCD decreased the exercise ability of mice in vivo. These data indicate that HBCD leads to chondrocyte damage. In summary, this study lays the foundation for further exploration of the toxicological effects of HBCD on bone and joints.

Occurrence and Health Effects of Hexabromocyclododecane: An Updated Review.

Hexabromocyclododecane (HBCD) is a non-aromatic compound belonging to the bromine flame retardant family and is a known persistent organic pollutant (POP). This compound accumulates easily in the environment and has a high half-life in water. With a variety of uses, the HBCD is found in house dust, electronics, insulation, and construction. There are several isomers and the most studied are α-, ß-, and γ-HBCD. Initially used as a substitute for other flame retardants, the polybrominated diphenyl ethers (PBDEs), the discovery of its role as a POP made HBCD use and manufacturing restricted in Europe and other countries. The adverse effects on the environment and human health have been piling, either as a result from its accumulation or considering its power as an endocrine disruptor (ED). Furthermore, it has also been proven that it has detrimental effects on the neuronal system, endocrine system, cardiovascular system, liver, and the reproductive system. HBCD has also been linked to cytokine production, DNA damage, increased cell apoptosis, increased oxidative stress, and reactive oxygen species (ROS) production. Therefore, this review aims to compile the most recent studies regarding the negative effects of this compound on the environment and human health, describing the possible mechanisms by which this compound acts and its possible toxic effects.

Investigating the debrominations of a subset of brominated flame retardants by biogenic reactive sulfur species.

Brominated flame retardants (BFRs) are persistent organic pollutants. Many bacteria are able to debrominate BFRs, but the underlying mechanism is unclear. Herein, we discovered that reactive sulfur species (RSS), which have strong reductive activity and are commonly present in bacteria, might be one of the reasons leading to such ability. Experiments performed with RSS (H2S and HSSH) and BFRs indicated that RSS can debrominate BFRs via two different mechanisms simultaneously: the substitutive debromination that generates thiol-BFRs and the reductive debromination that generates hydrogenated BFRs. Debromination reactions rapidly happened under neutral pH and ambient temperature, and the debromination degree was around 30% - 55% in one hour. Two Pseudomonas strains, Pseudomonas sp. C27 and Pseudomonas putida B6-2 both produced extracellular RSS and showed debromination activity. C27 debrominated HBCD, TBECH, and TBP by 5.4%, 17.7%, and 15.9% in two days. Whereas, B6-2 debrominated the three BFRs by 0.4%, 0.6%, and 0.3% in two days. The two bacteria produced different amounts and species of RSS, which were likely responsible for the contrasted degrees of the debromination. Our finding unveiled a novel, non-enzymatic debromination mechanism that many bacteria may possess. RSS producing bacteria have potentials to contribute to bioremediation of BFRs-polluted environments.

The effects of hexabromocyclododecane on the transcriptome and hepatic enzyme activity in three human HepaRG-based models.

The disruption of thyroid hormone homeostasis by hexabromocyclododecane (HBCD) in rodents is hypothesized to be due to HBCD increasing the hepatic clearance of thyroxine (T4). The extent to which these effects are relevant to humans is unclear. To evaluate HBCD effects on humans, the activation of key hepatic nuclear receptors and the consequent disruption of thyroid hormone homeostasis were studied in different human hepatic cell models. The hepatoma cell line, HepaRG, cultured as two-dimensional (2D), sandwich (SW) and spheroid (3D) cultures, and primary human hepatocytes (PHH) cultured as sandwich were exposed to 1 and 10 µM HBCD and characterized for their transcriptome changes. Pathway enrichment analysis showed that 3D models, followed by SW, had a stronger transcriptome response to HBCD, which is explained by the higher expression of hepatic nuclear receptors but also greater accumulation of HBCD measured inside cells in these models. The Pregnane X receptor pathway is one of the pathways most upregulated across the three hepatic models, followed by the constitutive androstane receptor and general hepatic nuclear receptors pathways. Lipid metabolism pathways had a downregulation tendency in all exposures and in both PHH and the three cultivation modes of HepaRG. The activity of enzymes related to PXR/CAR induction and T4 metabolism were evaluated in the three different types of HepaRG cultures exposed to HBCD for 48 h. Reference inducers, rifampicin and PCB-153 did affect 2D and SW HepaRG cultures' enzymatic activity but not 3D. HBCD did not induce the activity of any of the studied enzymes in any of the cell models and culture methods. This study illustrates that for nuclear receptor-mediated T4 disruption, transcriptome changes might not be indicative of an actual adverse effect. Clarification of the reasons for the lack of translation is essential to evaluate new chemicals' potential to be thyroid hormone disruptors by altering thyroid hormone metabolism.

Bioavailability of non-aromatic brominated flame retardants in rats from dust and oil vehicles.

Hexabromocyclododecane (HBCD) is a brominated flame retardant (BFR) labeled by the Stockholm Convention as a persistent organic pollutant (POP) and exists primarily as three stereoisomers, i.e. α-, ß-, and γ. One of the major routes of human exposure to HBCD is dust found in homes, offices, and cars and dust may be the most important route of HBCD exposure in young children. A study was conducted to determine the oral bioavailability of HBCD from household dust in rats over a 21-d feeding period relative to HBCD bioavailability from a corn oil matrix. Twenty-four hours after the last exposure, rats were sacrificed, and various tissues were collected. HBCD diastereomers were detected in adipose, blood, and liver of both dose groups, suggesting HBCD is bioavailable from both oil and dust. ß-HBCD concentrations were below the limit of detection in all tissues, but α-HBCD was detected in the brain of oil-dose rats and in adipose and liver of both dose groups. γ-HBCD was the dominant diastereomer in adipose, blood, and liver samples regardless of dosing matrix. Except for γ-HBCD in muscle of the oil-dosed group, muscle did not contain measurable HBCDs. Adipose tissue accumulated HBCD to a greater extent than muscle or liver, having bioaccumulation factors greater than 1.

A Review of Distribution and Profiles of HBCD in Different Environmental Media of China.

Hexabromocyclododecane (HBCD) is the most important flame retardant that has been used in Expanded Polystyrene foam and Extruded Polystyrene foam in the past forty years across the world. China was the major producer and user of HBCD, and the total HBCD production was about 0.3 million tons. Although HBCD was completely banned in China in 2021 because of its long-range transport, bioaccumulation and toxicity, there is still a lot of residue in the environment. Therefore, we reviewed multiple studies concerning the distribution of HBCD in diverse environmental matrices, such as in the air, dust, soil, water, sediment, and biota. Results revealed that HBCD levels in different environments in China present geographical variation and were at a high level compared with other countries. In all environmental media, relatively high HBCD concentrations have been found in industrial and urban areas. Industrialization and urbanization are two important factors that influence the concentration and distribution of HBCD in the environment. In terms of isomer, γ-HBCD was the dominant isomer in soil, water, and sediment, while in the biota α-HBCD was the predominant isomer.

Bioaccumulation and Biomagnification of Hexabromocyclododecane in Marine Biota from China: A Review.

Hexabromocyclododecane (HBCD) was listed in Annex A of the Stockholm Convention on Persistent Organic Pollutants for its persistence, bioaccumulation and toxicity, and pose significant adverse effects on natural environments and human health. HBCDs are ubiquitously found in marine environments worldwide and can be biomagnified in marine organisms with a high trophic level. In the present study, we reviewed the available data on contamination of HBCDs in the marine biota from China, including mollusks, crustaceans, fish and mammals. Bioaccumulation and biomagnification of HBCDs in the marine food web were summarized as well. This study also prospected the future research of HBCDs, including the transport and fluxes of HBCDs to and within the marine environment, the biomagnification of HBCDs in different ecosystems, and the metabolism of HBCDs in different marine species.

Levels, distribution and risk assessment of hexabromocyclododecane (HBCD) in fish in Xiamen, China.

In this study, hexabromocyclododecane (HBCD) was detected in 114 fish samples collected from 6 administrative regions of Xiamen city, China. HBCD amounts ranged between ND (not detected) and 2.216 ng g-1 ww (mean, 0.127 ± 0.318 ng g-1 ww). Besides, α-HBCD was the main diastereoisomer in these fish specimens, followed by ß-HBCD. Meanwhile, γ-HBCD was not detected in any of the samples. Significant differences were recorded among fish species. The results indicated that the levels and detection rates of HBCD were higher in Trachinotus ovatus compared with other aquatic organisms. Therefore, Trachinotus ovatus could be used as a marine biological indicator of HBCD. Within the regions investigated, Siming was significantly different from Jimei, Haicang, and Xiang'an. The spatial distribution of HBCD concentrations indicated higher mean levels in samples collected from Haicang, Jimei, and Xiang'an, respectively, with the highest detection rates in Jimei and Xiang'an, which might be related to geographical location and intense industrial and urban activities. Estimation of daily HBCD intake was performed according to fish consumption in Xiamen residents. The medium bound HBCD amounts in fish were approximately 0.073 and 0.088 ng kg bw-1d-1 for male and female residents of Xiamen, respectively. Exposure doses of HBCD indicated no health concern for Xiamen residents.

Global interlaboratory assessments on PCBs, organochlorine pesticides and brominated flame retardants in various environmental matrices 2017/2019.

In support of the United Nations Environment Programme (UNEP) global monitoring plan under the Stockholm Convention contributing laboratories were offered to take part in a series of interlaboratory assessments on persistent organic pollutants (POPs). The results of two rounds of these assessments are reported. The target compounds were polychlorinated biphenyls, organochlorine pesticides, polybrominated diphenylethers, one polybrominated biphenyl and hexabromocyclododecane diastereomers. The matrices distributed were a test solution, fish, sediment, human milk, and air extracts. The number of participants in each round was well over 100, showing the interest of laboratories worldwide. The results showed that many laboratories still struggle to obtain acceptable standard deviations of around 25% for their determinations. In particular for organochlorine pesticides serious improvement in quality is required. Acceptable results were obtained for the air extracts and for the determination of polybrominated diphenylethers in various matrices.

Determination of Hexabromocyclododecane in Expanded Polystyrene and Extruded Polystyrene Foam by Gas Chromatography-Mass Spectrometry.

A gas chromatography-mass spectrometry (GC/MS) method for the determination of hexabromocyclododecane (HBCD) in expanded polystyrene and extruded polystyrene foam (EPS/XPS) was developed. The EPS/XPS samples were ultrasonically extracted with acetone and the extracts were purified by filtration through a microporous membrane (0.22 µm) and solid-phase extraction. The samples were analyzed using a GC/MS using the selected ion monitoring mode. The ions 157, 319 and 401 were selected as the qualitative ions, while ion 239 was chosen as the quantitative ion. An HBCD standard working solution with a concentration range of 1.0-50.0 mg/L showed good linearity. The detection limit of HBCD was 0.5 mg/kg, meeting the LPC limit (<100 or 1000 mg/kg). Six laboratories were selected to verify the accuracy of the method, and 10 samples were tested. The interlaboratory relative standard deviation range was 3.68-9.80%. This method could play an important role in controlling HBCD contamination in EPS/XPS.

Innovative methods for remote assessment of neurobehavioral development.

In response to the COVID-19 pandemic, research institutions across the globe have modified their operations in ways that have limited or eliminated the amount of permissible in-person research interaction. In order to prevent the loss of important developmentally-timed data during the pandemic, researchers have quickly pivoted and developed innovative methods for remote assessment of research participants. In this manuscript, we describe methods developed for remote assessment of a parent child cohort with a focus on examining the perinatal environment, behavioral and biological indicators of child neurobehavioral development, parent-child interaction, as well as parent and child mental and physical health. We include recommendations relevant to adapting in-laboratory assessments for remote data collection and conclude with a description of the successful dissemination of the methods to eight research sites across the United States, each of whom are involved in Phase 1 of the HEALthy Brain and Child Development (HBCD) Study. These remote methods were born out of pandemic-related necessity; however, they have much wider applicability and may offer advantages over in-laboratory neurodevelopmental assessments.

Towards a more inclusive and equitable developmental cognitive neuroscience.

Brain and cognitive development is a burgeoning area of scientific inquiry, with tremendous potential to better the lives of children. Large scale longitudinal neuroimaging studies offer opportunities for significant scientific advances in our understanding of developing brain structure and function. The proposed manuscript will focus on the scientific potential of the HEALthy Brain and Cognitive Development (HBCD) Study, highlighting what questions these data can and what they cannot answer about child development. Specifically, we caution against the misuse of these data for advancing de-contextualized and scientifically questionable narratives about the development of children from marginalized communities. We will focus on building and organizing a framework for interpreting HBCD data through the lens of sampling, cultural context, measurement, and developmental science theory. Our goal is to thoughtfully offer the scientific community opportunities to use the large scale and collaborative nature of HBCD to collectively revise practices in developmental science that to-date have not carefully considered their own role in perpetuating narratives that support systemic injustice.

A PBPK model describing the pharmacokinetics of γ-HBCD exposure in mice.

The brominated flame retardant, hexabromocyclododecane (HBCD), is added-but not bound-to consumer products and is eventually found in the environment and human tissues. Commercial-grade HBCD mixtures contain three major stereoisomers, alpha (α), beta (ß), and gamma (γ), that are typically at a ratio of 12%:6%:82%, respectively. Although HBCD is widely used, the toxicological effects from its exposure in humans are not clearly understood. Using a physiologically based pharmacokinetic (PBPK) model could help improve our understanding of the toxicity of HBCD. The aim of this work was to develop a PBPK model, consisting of five permeability limited compartments (i.e., brain, liver, adipose tissue, blood, and rest of the body), to evaluate the pharmacokinetics of γ-HBCD in C57BL/6 mice. Physiological parameters related to body size, organ weights, and blood flow were taken from the literature. All partition coefficients were calculated based on the log Kow. The elimination in urine and feces was optimized to reflect the percent dose eliminated, as published in the literature. Compared with data from the literature for brain, liver, blood, and adipose tissue, the model simulations accurately described the mouse data set within 1.5-fold of the data points. Also, two examples showing the utility of the PBPK model supplement the information regarding the internal dose that caused the health effects observed during these studies. Although this version of the PBPK model expressly describes γ-HBCD, more efforts are needed to clarify and improve the model to discriminate between the α, ß, and γ stereoisomers.