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LC-MS chromatogram of metabolites and their respective structures.

Autism spectrum disorder (ASD) is characterised by problems with social interaction, verbal and nonverbal communication and repetitive behaviour. In mice, the 14th postnatal day is believed to correspond to the third trimester of human embryonic development and is considered a vital period for central nervous system development. It has been shown that ASD affects 2 to 3 times more male than female individuals. In the present study, ASD was induced in 14 postnatal day (PND) BALB/c mice using valproic acid (VPA). VPA administration brought about substantial differences in the histoarchitecture of the brain in both male and female mice, linked to behavioural deficits. We observed that both male and female mice showed similar morphological changes in the prefrontal cortex, hippocampus and Purkinje cells. We also observed hair loss from PND 17 to 25, which was again similar between male and female mice. However, there were higher rates of change in the cerebral cortex, frontal cortex and temporal lobe and hippocampus in VPA-treated male animals. With respect to the cerebellum, we did not observe any alterations by haematoxylin and eosin (H&E) staining, but detailed morphological observation using scanning electron microscopy (SEM) showed a higher rate of phenotype changes in VPA-treated male animals. Moreover, 5-HT2A receptor protein levels were upregulated in the cerebral cortex, hippocampus and Purkinje cells in VPA-treated male mice compared with control animals and VPA-treated female mice, as shown by immunohistochemical analysis. Based on all these findings, we conclude that male animals are more susceptible to VPA-induced ASD than females.

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The objective of this study is to determine the concentrations of polychlorinated biphenyls (PCBs) in different fish species collected from fish outlets in the south Indian city of Hyderabad. The samples of fish extracted by using Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) and concentrations of polychlorinated biphenyls (PCBs, 45 congeners) were determined by gas chromatography-microelectron capture detection (GC-μECD) method. The intake of individual PCB congeners through fish, toxicity equivalence factors (TEFs), hazardous quotient, quantitative assessment, and risk evaluations was estimated in the Indian population. Daily dietary intakes of PCBs at the 95th-percentile-measured concentrations were twice the values of the 50th-percentile-measured concentrations in all socio-economic groups. The dietary intakes of PCBs through fish consumption in middle-income group, low-income group, and industrial laborers (0.023 μg kg(-1) day(-1)), the high-income group (0.031 μg kg(-1) day(-1)), and slum dwellers (0.039 μg kg(-1) day(-1)) exceeded the reference dose. The observed estimated daily intakes (EDIs) of our study for all socio-economic sections (0.0087 μg/kg/day) crossed the cancer benchmark concentration of 0.0003 μg/kg/day. In slum dwellers, the ingestion of fish from freshwater and marine water results in the highest lifetime cancer risks of 4.7 in 100,000 and 7.8 in 100,000, respectively. Ultimately, the concentrations of PCBs were determined high in all of the fish species collected. Risk assessment showed that the fish were highly contaminated with PCBs and may pose health threats to consumers in the city of Hyderabad as well as a lifetime cancer risk.