Dechlorane Plus Exposure Research Articles

Characterizing the effects of Dechlorane Plus on β-cells: a comparative study across models and species

ABSTRACT Epidemiological studies consistently link environmental toxicant exposure with increased Type 2 diabetes risk. Our study investigated the diabetogenic effects of a widely used flame retardant, Dechlorane Plus (DP), on pancreatic β-cells using rodent and human model systems. We first examined pancreas tissues from male mice exposed daily to oral gavage of either vehicle (corn oil) or DP (10, 100, or 1000 μg/kg per day) and fed chow or high fat diet for 28-days in vivo. DP exposure did not affect islet size or endocrine cell composition in either diet group. Next, we assessed the effect of 48-hour exposure to vehicle (DMSO) or DP (1, 10, or 100 nM) in vitro using immortalized rat β-cells (INS-1 832/3), primary mouse and human islets, and human stem-cell derived islet-like cells (SC-islets). In INS-1 832/3 cells, DP did not impact glucose-stimulated insulin secretion (GSIS) but significantly decreased intracellular insulin content. DP had no effect on GSIS in mouse islets or SC-islets but had variable effects on GSIS in human islets depending on the donor. DP alone did not affect insulin content in mouse islets, human islets, or SC-islets, but mouse islets co-exposed to DP and glucolipotoxic (GLT) stress conditions (28.7 mM glucose + 0.5 mM palmitate) had reduced insulin content compared to control conditions. Co-exposure of mouse islets to DP + GLT amplified the upregulation of Slc30a8 compared to GLT alone. Our study highlights the importance and challenges of using different in vitro models for studying chemical toxicity.

Dechlorane Plus in environmental samples and human serum samples from new and old electronic waste dismantling areas in East China: Levels, composition profiles, and human exposure

The global presence of Dechlorane Plus (DP) in environmental and human samples highlights the need for further research into its ecological risks and health effects. This study determined DP concentrations in soil and air samples from an old electronic waste dismantling area (Fengjiang) and a new electronic waste dismantling area (Binhai) in Taizhou City, China. Both syn-DP and anti-DP isomers were found in all soil and air samples. The median concentrations of DP in soil and air were 90.5 ng/g and 48.4 pg/m3 in Fengjiang, and 6.69 ng/g and 28.8 pg/m3 in Binhai. DP were widespread in the local environment, and in general at moderate levels compared with reports from other electronic waste dismantling areas. The analysis of DP isomer profiles in different seasons and the calculation of related fugacity fraction showed that anti-DP perhaps easier than syn-DP to migrate from soil to air in summer. DP concentrations in serum of residents from Fengjiang (median 9.74 ng/g) were significantly higher than those from Huangyan (common control area, median 2.77 ng/g; p < 0.01), while the fanti value showed that Fengjiang was significantly lower than Huangyan (p < 0.05). This revealed that DP exposure levels in serum perhaps one of the crucial factors influencing fanti value. Moreover, DP concentrations in serum showed an increasing trend with increasing body mass index (BMI) or age. However, the relationship between DP and sex was not observed. The fanti values of serum samples were higher than those in soil and air samples, suggested that DP perhaps stereo-selectively absorbed into the body or stereo-selectively metabolised.

Dechlorane Plus exposure on gut microbiome evaluated by using both in vivo and in vitro assays

The gut microbiome is crucial for the health of animals including human and is sensitive to environmental factors. Dechlorane Plus (DP) is a widely used polychlorinated flame retardant in commercial products for which general human population has been exposed to, but its effects on the gut microbiota are largely unknown. In this work, experiments were conducted to examine the effect of DP exposure on the intestinal microbiota by using Sprague-Dawley rats and a simulator of the human intestinal microbial ecosystem (SHIME). 16S rRNA gene high-throughput sequencing revealed that DP exposure in vivo reduced the relative abundance of the genera Prevotella, Quinella, and Ruminococcus, exposure in vitro decreased the relative abundance of Coriobacteriaceae, Parabacteroides, Bilophila, Sporolactobacillus, and Klebsiella. The phyla Synergistetes and Lentisphaerae were only detected in the descending colon. DP exposure also increased the concentrations of short-chain fatty acids (SCFAs) produced by the gut microbe both in vivo and in vitro, but SCFA metabolism was gradually inhibited as the increase of DP concentrations. These results indicated that DP exposure changed both the structure and metabolic function of the gut microbiota, suggesting more attention should be concentrated on the health effects of DP exposure, especially at higher doses.

Effects of dechlorane plus on intestinal barrier function and intestinal microbiota of Cyprinus carpio L

Dechlorane Plus (DP) is a typical polychlorinated flame retardant that has been emerged in chemical products. Due to its accumulation and amplification effect, the toxicity of DP has become a widespread environmental safety issue. However, whether DP can affect the intestinal tract of teleost fish remains largely unclear. To understand its effects on the intestinal barrier, morphological characteristics and intestinal microbiome of common carp, different concentrations (30, 60 and 120 μg/L) of DP were exposed to common carps for 4 weeks. The results indicated that DP evidently shortened the intestinal folds and damaged the intestinal epithelium layer. In addition, the mRNA expression levels of occludin, claudin-2 and zonula occludens-1 (ZO-1) were significantly decreased with increasing DP concentrations. Furthermore, the relative abundance of some microbiota species were also changed significantly. Our study first demonstrated that DP could cause damage to the intestinal epithelium and destroy the intestinal barrier and increase the relative abundance of pathogenic bacteria, thereby increasing the probability of contact between intestinal epithelium and pathogenic bacteria, which in turn lead to an increased susceptibility to various diseases and poor health. In summary, our findings reveal that chronic DP exposure can have a harmful effect on the intestinal flora balance and is potentially linked to human disease.

Exposure to Low Doses of Dechlorane Plus Promotes Adipose Tissue Dysfunction and Glucose Intolerance in Male Mice.

The prevalence of type 2 diabetes (T2D) continues to increase worldwide. It is well established that genetic susceptibility, obesity, overnutrition and a sedentary life style are risk factors for the development of T2D. However, more recently, studies have also proposed links between exposure to endocrine-disrupting chemicals (EDCs) and altered glucose metabolism. Human exposure to environmental pollutants that are suspected to have endocrine disruptor activity is ubiquitous. One such chemical is Dechlorane Plus (DP), a flame retardant, that is now detected in humans and the environment. Here we show that exposure of mice to low, environmentally relevant doses of DP promoted glucose intolerance in mice fed a high-fat diet independent of weight gain. Furthermore, DP had pronounced effects on the adipose tissue, where it induced the development of hypertrophied white adipose tissue (WAT), and increased serum levels of resistin, leptin, and plasminogen activator inhibitor-1. In addition, DP exposure induced "whitening" of brown adipose tissue (BAT), and reduced BAT uncoupling protein 1 expression. Importantly, some of these effects occurred even when the mice were fed a regular, low-fat, diet. Finally, WAT adipogenic markers were reduced with DP treatment in the WAT. We also show that DP directly inhibited insulin signaling in murine adipocytes and human primary subcutaneous adipocytes in vitro. Taken together, our results show that the exposure to low and environmentally relevant levels of DP may contribute to the development of T2D.

Intergenerational transfer of Dechlorane Plus and the associated long-term effects on the structure and function of gut microbiota in offspring

The gut microbiota has been shown to be highly involved in many vital physiological processes that play key roles in human health. The intergenerational transfer of Dechlorane Plus (DP) and the complex interaction between DP and microbiota has been poorly studied. Additionally, the structural and functional effects of DP on the gut microbiota have not been studied. This study aimed to investigate the DP transfer in Sprague-Dawley rats during pregnancy and the effects of DP exposure on gut microbiota, as detected by 16S rRNA gene sequencing. The results showed that excretion in feces is a very important elimination pathway of orally dosed DP. The main intergenerational transfer pathway of DP might be via lactation rather than transplacental transport. The 16S rRNA sequencing revealed that DP exposure could decrease the richness and diversity of gut microbiota, especially at the genus level. Furthermore, in DP exposure groups, the gut microbiota production of metabolites of short-chain fatty acids was dramatically increased. The results demonstrated that DP exposure not only altered the gut microbiota structures, but also immensely influenced metabolic functions, causing long-term impact to offspring. This data indicates that more attention should be paid to the long-term health effects related to DP exposure.

Toxic effects of dechlorane plus on the common carp (Cyprinus carpio) embryonic development

Dechlorane Plus (DP) is a widely used chlorinated flame retardant, which has been extensively detected in the environment. Although DP content in the surface water is low, it can pose a continuous exposure risk to aquatic organisms due to its strong bioaccumulation. Considering that the related studies on the toxicity mechanism of DP exposure are limited, the effect of DP on carp embryo development was evaluated. In the present work, carp embryos were exposed to different concentrations (0, 30, 60, and 120 μg/L) of DP at 3 h post-fertilization (hpf). The expression levels of neural and skeletal development-associated genes, such as sox2, sox19a, Mef2c and BMP4, were detected with quantitative PCR, and the changes in different developmental toxicity endpoints were observed. Our results demonstrated that the expression levels of sox2, sox19a, Mef2c and BMP4 were significantly altered and several developmental abnormalities were found in DP-exposed carp embryos, such as DNA damage, increased mortality rate, delayed hatching time, reduced hatching rate, decreased body length, and increased morphological deformities. In addition, the activities of reactive oxygen species and malondialdehyde were remarkably higher in 60 and 120 μg/L DP exposure groups than in control group. These results suggest that DP can exhibit a unique modes of action, which lead to aberration occurrence in the early development stage of common carps, which may be related to some gene damage and oxidative stress. Besides, the parameters evaluated here can be used as tools to access the environmental risk for biota and humans exposed to DP.

Effects of dechlorane plus on oxidative stress, inflammatory response, and cell apoptosis in Cyprinus carpio

The levels of the chlorinated organic compound Dechlorane Plus (DP) are increasing in aquatic ecosystems. To investigate the adverse effects of DP on aquatic animals, common carp (Cyprinus carpio) were subjected to three different DP concentrations (30 μg L−1, 60 μg L−1, and 120 μg L−1) for 1 d, 15 d, and 30 d. Histology and the hepatic and cerebral expression levels of several key antioxidant, detoxification, and apoptotic factors were then examined. Histopathological inspections showed that the liver and brain were severely damaged in carp exposed to 60 μg L−1 and 120 μg L−1 DP. Relative to the controls, the superoxide dismutase and glutathione activity levels and the malondialdehyde content were also changed in livers and brains exposed to DP. Besides, significant alterations in the expression levels of the inflammatory cytokines IL-1β, IL-6, and IL-10 were observed in the livers of carp subjected to DP. Relative to the control, the brains of DP-exposed carp presented with significantly upregulated IL-1β and IL-6 in carp treated with 120 μg L−1 DP for 30 d. The transcription levels of hepatic cyp2b4, cyp1b1, and cyp3a138 were all increased compared with the untreated at all DP exposure concentrations. The aforementioned results suggest that DP exposure perturbs fish metabolism and causes liver injury by inhibiting antioxidant enzyme activity, increasing lipid peroxidation, promoting inflammation, and inducing cell apoptosis. This information and the analytical methodology used to acquire it may form the basis for future ecological risk assessments on DP and related xenobiotics in aquatic animals.

Enrichment and physiological responses of dechlorane plus on juvenile marine macroalgae (Ulva pertusa)

Dechlorane Plus (DP), a chlorinated flame retardant, is increasingly reported in aquatic ecosystems worldwide. But little information is available regarding the toxicity of DP in marine organisms, especially in macroalgae. The objective of this study was to investigate effects of DP exposure on photosynthesis, oxidative stress and its enrichment in juvenile marine macroalgae (Ulva pertusa). Following 21- day uptake and 21- day depuration (10−8 mol/L), algae accumulated 1.18 times of DP compared to the initial concentration. Anti-DP was prone to accumulate in juvenile macroalgae. The enrichment of DP affected the physiological responses in algae. After 1, 7 and 14 days DP exposure (10−8, 10−7 and 10−6 mol/L), antioxidant enzymes (SOD and CAT) activities and MDA content changed in a dose and time depended manner. Chlorophyll fluorescence parameters, including Fv/Fm, ΦPSII and ETR decreased with the increasing DP concentration. It indicated that DP leads to a low rate of light energy utilization in algae which may ascribe to the oxidative damage induced by DP enrichment. Present study provides insight into the toxicological effects of DP on marine macroalgae, which is useful for risk assessment of DP in intertidal zone ecosystems.

Dechlorane Plus induces oxidative stress and decreases cyclooxygenase activity in the blue mussel

Dechlorane Plus (DP) is a chlorinated flame retardant used mainly in electrical wire and cable coating, computer connectors, and plastic roofing materials. Concentrations of DP (syn and anti isomers) are increasingly being reported in aquatic ecosystems worldwide. However, there is exceedingly little information on the exposure-related toxicity of DP in aquatic organisms, especially in bivalves. The objective of this study was to investigate the in vivo and in vitro effects of DP exposure on histopathology, lipid peroxidation (LPO) levels, cyclooxygenase (COX) activity, phagocytosis capacity and efficiency, and DNA strand breakage in the blue mussel (Mytilus edulis) following a 29days exposure (0.001, 0.01, 0.1 and 1.0μg DP/L). Blue mussels accumulated DP in muscle and digestive gland in a dose-dependent manner. LPO levels in gills were found to increase by 82% and 67% at the 0.01 and 1.0μg DP/L doses, respectively, while COX activity in gills decreased by 44% at the 1μg/L dose. No histopathological lesion was found in gonads following DP exposure. Moreover, no change in hemocyte DNA strand breakage, phagocytosis rate, and viability was observed following DP exposure. Present study showed that toxicity of DP may occur primarily via oxidative stress in the blue mussel and potentially other bivalves, and that gills represent the most responsive tissue to this exposure.

Effects of Dechlorane Plus exposure on axonal growth, musculature and motor behavior in embryo-larval zebrafish

Developmental neurobehavioral toxicity of Dechlorane Plus (DP) was investigated using the embryo-larval stages of zebrafish (Danio rerio). Normal fertilized embryos were waterborne exposed to DP at 15, 30, 60 μg/L beginning from 6 h post-fertilization (hpf). Larval teratology, motor activity, motoneuron axonal growth and muscle morphology were assessed at different developmental stages. Results showed that DP exposure significantly altered embryonic spontaneous movement, reduced touch-induced movement and free-swimming speed and decreased swimming speed of larvae in response to dark stimulation. These changes occurred at DP doses that resulted no significant teratogenesis in zebrafish. Interestingly, in accord with these behavioral anomalies, DP exposure significantly inhibited axonal growth of primary motoneuron and induced apoptotic cell death and lesions in the muscle fibers of zebrafish. Furthermore, DP exposure at 30 μg/L and 60 μg/L significantly increased reactive oxygen species (ROS) and malondialdehyde (MDA) formation, as well as the mRNA transcript levels of apoptosis-related genes bax and caspase-3. Together, our data indicate that DP induced neurobehavioral deficits may result from combined effects of altered neuronal connectivity and muscle injuries.

Toxicological responses following short-term exposure through gavage feeding or water-borne exposure to Dechlorane Plus in zebrafish (Danio rerio).

Dechlorane Plus (DP) is a chlorinated flame retardant widely used worldwide, and has been reported in environment and humans. However, only limited information is currently available on its toxicity on aquatic organisms. In this study, we employed zebrafish to evaluate possible toxicological responses including oxidative stress and endocrine disruption following exposure to DP. DP was dissolved in corn oil and was delivered to adult male zebrafish via gavage feeding. Delivery of DP was carried out twice on days 0 and 2, at up to 3 μg/g fish wet weight. Body residue level of DP in the fish at day 6 was within a range that has been reported in hot spot areas of China. On day 6, blood, liver, testis, and brain were collected and were evaluated for oxidative damage and endocrine disruption. Following DP exposure, hepatic catalase activity significantly increased, implying its oxidative damage potential. In addition, plasma thyroxine (T4) concentrations increased along with up-regulation of corticotropin releasing hormone and thyroid stimulating hormone β genes in brain. Following DP exposure, transcriptional responses of sex hormone related genes in brain were observed, suggesting possible sex hormone disrupting potentials of DP. However, water-borne exposure to DP up to 267 μg/L among the embryo and larval fish did not show any adverse effects on hatching time and transcription of thyroid hormone related genes. Our observations indicate for the first time that DP disrupts thyroid hormone balance of zebrafish by altering regulatory pathways in the brain. Handling editor: David Volz.

Ecotoxicological effects of earthworm following long-term Dechlorane Plus exposure.

Dechlorane Plus (DP), similar to persistent organic pollutants, has been widely detected in environmental matrices, especially in sediment and soil. In this study, earthworms Eisenia fetida were exposed to 0.1, 0.5, 6.25 and 12.5 mg kg(-1) DP for 28 d. Lethality, oxidative stress, neurotoxicity and cellulase of E. fetida were assessed to investigate ecotoxicological effects of DP after long-term exposure. Results showed that the direct toxicity of DP was very low. However, death rate, as well as SOD activity, together with changes in activities of CAT, GSH-Px, and GSH levels, indicating that oxidative stress may play a significant role in DP exposure. In addition, DP also changes the AChE and cellulase activity of earthworms even under low DP concentration after long-term exposure. Moreover, comet assay results showed that DP exposure increased the levels of tDNA significantly (p < 0.05) even in the lowest treatment (0.1 mg kg(-1) DP). Combined with the results of enzyme activity, oxidative damage and comet assay, it can be suggested that earthworms experience more stress of DP during long-time exposure. This study provides insight into the toxicological effects of DP on earthworm model, and may be useful for risk assessment of DP on soil ecosystems.

Occurrence, behavior and human health risk assessment of dechlorane plus and related compounds in indoor dust of China

Levels of dechlorane plus (DP) and “DP-like” compounds were measured in indoor dust samples collected across China. The concentrations of ΣDP and “DP-like” compounds ranged from 0.35 to 1000ngg−1 and<0.21 to 2.4ngg−1, respectively. The total DP concentration in urban sites were significantly higher than those of rural sites, while no significant difference was found for “DP-like” compounds, suggesting different sources of these compounds. Significant positive correlations were found between fsyn and latitude, and between fsyn and longitude. The deleterious risk associated with DP exposure via indoor dust for the general population in China was low and safer than expectation. For estimating human exposure via indoor dust, sensitivity analysis showed that more attention should be given to the influential variables such as the level of pollutants, body weight, and the amount of ingestion and adsorption.

Dechlorane Plus in paired hair and serum samples from e-waste workers: Correlation and differences

Dechlorane Plus (DP) and a dechlorinated product of DP were measured in 34 matched human hair and serum samples (19 males and 15 females) collected from e-waste recycling workers in South China. The DP (sum of syn- and anti-DP) concentrations in hair and serum samples ranged from 6.3 to 1100ngg−1 dry weight and from 22 to 1400ngg−1 lipid weight (lw). The levels of anti-Cl11-DP ranged from 0.02 to 1.8ngg−1 in hair and from not detected to 7.9ngg−1 lw in serum. Significant positive correlations for both DP and anti-Cl11-DP concentrations between hair and serum samples were found (p<0.05), indicating hair to be a suitable matrix for human DP exposure. However, a significant difference was found in the DP isomer composition between hair and serum, suggesting stereoselective bioaccumulation during the absorption of DP into hair. A sharp gender difference was found in the levels of DP in hair. Moreover, syn-DP, anti-DP and anti-Cl11-DP in hair significantly correlated with those in serum for male samples, but not for female samples. The observed gender differences in the present study may be, in part, ascribed to the much longer hair exposure time for females than males due to the difference in sampling distance from the scalp.

Placental Transfer of Dechlorane Plus in Mother–Infant Pairs in an E-Waste Recycling Area (Wenling, China)

It has been reported that breastfeeding can expose newborns to dechlorane plus (DP), but transplacental transfer of DP has not been documented. We measured DP and its dechlorinated analogs in matched maternal blood-placenta-cord blood samples from 72 residents of the e-waste recycling area of Wenling, China. DP was detected in cord sera, indicating the occurrence of prenatal DP exposure and the transfer of DP across the placenta. The concentration ratio in the cord serum and maternal serum was estimated to be 0.45 for syn-DP and 0.35 for anti-DP, indicating the placenta partially limited DP transfer with a greater extent for anti-DP. The DP concentrations in the maternal serum, placenta, and cord serum strongly correlated, indicating that DP could transfer between the tissues. The DP concentrations in the matched samples could be predicted from each other. The anti-DP/total DP concentration ratios in the placentas and cord sera were significantly different from those in the maternal sera, suggesting that DP stereoselectively bioaccumulates in human tissues. When the congener concentrations of polybrominated diphenyl ethers (PBDEs) were used as control variables, DP and total triiodothyronine concentrations were associated in the sera from mothers who had lived in Wenling for over 20 years.

Short-term effects of Dechlorane Plus on the earthworm Eisenia fetida determined by a systems biology approach

Dechlorane Plus (DP), a chlorinated flame retardant, has been widely detected in environmental matrices, especially in sediment and soil. DP has characteristics similar to persistent organic pollutants. However, no toxicity data of DP on terrestrial invertebrate are available. In this study, earthworms Eisenia fetida were exposed to 0.1, 1, 10, and 50mg/kg DP for 14 days. Lethality, oxidative stress and damage, neurotoxicity, and transcriptomic profiles of E. fetida were assessed on day 7 and day 14 of exposure. Results showed that the acute toxicity of DP was very low. However, DP exposure induced an increase in the oxidative stress markers malonaldehyde (MDA) and 8-Hydroxy-2′-deoxyguanosine (8-OHdG), and altered acetylcholinesterase (AChE) activities. High throughput sequencing-based transcriptomic analysis showed that DP exposure significantly altered gene expression and pathways related to antioxidant enzymes, stress responses, neurological dysfunctions, calcium binding, and signal transduction. The results from different toxicological endpoints indicate that DP toxicity on the earthworm is primarily through oxidative damage and neurotoxicity. Based on these results, we deduce that changes in oxidative stress and neurotoxicity might be the primary mechanisms of DP toxicity. This study provides insight into the toxicological effects of DP on earthworm model, and may be useful for risk assessment of DP on soil ecosystems.

Accumulation and effects of 90‐day oral exposure to Dechlorane Plus in quail (Coturnix coturnix)

While a number of studies have addressed bioaccumulation of the flame retardant Dechlorane Plus (DP), little information is available regarding the adverse effects of DP on animals, especially on bird species. In the present study, male common quails (Coturnix coturnix) were consecutively exposed to commercial DP-25 by gavage for 90 d at 1-mg/kg/d, 10-mg/kg/d, and 100-mg/kg/d dosages. Concentrations of DP isomers in liver, muscle, and serum were determined after exposure. Liver enzyme activity involved in xenobiotic biotransformation processes and oxidative stress was measured, as well as glutathione and maleic dialdehyde content. The results showed that DP was more prone to accumulate in the liver than in muscle and serum in all exposed groups. In tested tissues, syn-DP dominated in the high-exposure groups (10 and 100 mg/kg/d), whereas anti-DP tended to accumulate in the low-exposure group (1 mg/kg/d). The concentration ratios of anti-DP to total DP (fanti values) in the tissues examined were close to commercial DP in the low-exposure group; however, the fanti values were significantly decreased in the high-exposure groups. Enzyme activity of 7-pentoxyresorufin-O-demethylase (PROD) decreased significantly in all exposed groups compared with the control group, whereas activity of erythromycin N-demethylase (ERND) and the antioxidant enzyme catalase significantly increased in high-exposure groups. The results implied that DP exposure levels influenced isomeric compositions in organs and that DP exposure altered hepatic alkoxyresorufin O-dealkylase (AROD) activity and contributed to the biological effects of DP.

Accumulation pattern of Dechlorane Plus and associated biological effects on rats after 90 d of exposure

Recent studies have indicated that Dechlorane Plus (DP) is widespread in the environments. However, different isomer-specific enrichment pattern of syn-DP and anti-DP was reported in biological samples from the field. In this study, Sprague–Dawley rats were consecutively exposed to commercial DP 25 by gavage for 90d at different doses (0, 1, 10, and 100mgkg−1d−1) to investigate the accumulation pattern of syn-DP and anti-DP in liver, muscle, and serum of rats. The possible biological effects of DP on rats were also examined. Results showed that DP preferentially accumulated in the liver rather than in muscle at all exposure levels. No significant stereoselectivity of anti-DP or syn-DP in tissues was observed in the low DP exposure groups (0 and 1mgkg−1d−1) with fanti values (defined as the concentration of the anti-DP divided by the sum of concentrations of anti- and syn-DP) ranging from 0.74 to 0.78. However, fanti values reduced (fanti ranged from 0.26 to 0.30) significantly in the high DP exposure groups (10 and 100mgkg−1d−1) and syn-DP was predominant in all tissues. Biochemical parameters in serum, the mRNA expression levels of certain enzymes and their activities in liver were detected. There was no observable-effect in histopathology and death during the experiment, although the mRNA expression levels of some genes in the low dosage group decreased significantly and enzyme activity of CYP 2B2 increased.

Responses of Mouse Liver to Dechlorane Plus Exposure by Integrative Transcriptomic and Metabonomic Studies

Dechlorane plus (DP), a chlorinated flame retardant, has been widely detected in different environmental matrices and biota. However, toxicity data for DP have seldom been reported. In the present study, we investigated hepatic oxidative stress, DNA damage, and transcriptomic and metabonomic responses of male mice administered 500 mg/kg, 2000 mg/kg, and 5000 mg/kg of DP by gavage for 10 days. The results showed that DP exposure increased the level of superoxide dismutase (SOD) and 8-hydroxy-2-deoxyguanosine (8-OHdG). The microarray-based transcriptomic results demonstrated that DP exposure led to significant alteration of gene expression involved in carbohydrate, lipid, nucleotide, and energy metabolism, as well as signal transduction processes. The NMR-based metabonomic analyses corroborated these results showing changes of metabolites associated with the above altered mechanisms. Our results demonstrate that an oral exposure to DP can induce hepatic oxidative damage and perturbations of metabolism and signal transduction. These observations provide novel insight into toxicological effects and mechanisms of action of DP at the transcriptomic and metabonomic levels.