DDT and titanium dioxide nanoparticle coexposure induced neurobehavioral deficits in zebrafish.

Both dichlorodiphenyltrichloroethane (DDT) and titanium dioxide nanoparticle (TiO2 NP) have worldwide-scale commercial applications, resulting in their co-pollution in the ecosystems and posing combined health risks. However, there is a lack of toxicity studies for the interactions of DDT and TiO2 NP in the environmental relevant concentrations. In this study, we characterized the coexposures using a zebrafish waterborne exposure approach and evaluated the neurotoxicity response of the treated embryos or adults. Our results showed that DDT/TiO2 NP coexposure enhanced the DDT accumulation in vivo and increased the larval locomotor. The chronic DDT/TiO2 NP coexposure did not affect the overall survival rate, sex ratio and growth. However, DDT/TiO2 NP coexposure severely affected the adult locomotor activity, social contact, shoaling and aggressive behaviors compared to single treatment groups or controls. These adult behavioral deficits were accompanied by changes in neurotransmitter acetylcholine (ACH) level in the brain and muscle tissues, as well as neural development genes expression activation of growth-associated protein 43 (gap43) and synaptic vesicle glycoprotein 2 (sv2) in the brain. The significantly increased ACH level and the activated neural genes expression in the DDT/TiO2 NP co-exposed fish may account for the observed hyperactivity and social deficits.

DDT exposure induces tremor-like behavior and neurotoxicity in developmental stages of embryonic zebrafish.

Dichlorodiphenyltrichloroethane (DDT) is a broad-spectrum insecticide, widely detected in environments due to its high stability characteristic and long natural half-life period. The adverse impact of DDT exposure on organisms and humans has attracted great concern worldwide. The current study explored the developmental and neurobehavioral toxicity response of DDT in embryonic zebrafish. The embryos were treated with DDT (0, 0.1, 1, 2.5 and 5 µM) during 6 h post fertilization (hpf) to 144 hpf. Our result indicated that DDT exposures increased the embryo hatching rate at 48 and 60 hpf, the larval malformation rate at 120 hpf and mortality rate at 144 hpf. The manifested malformations included uninflated swim bladder, bent spine and tail, deformed liver, and pericardial edema. The 120 hpf larval organs size of the gut and swim bladder was decreased in higher exposed concentration groups. Besides, DDT exposure resulted in hyperactivity for the embryo spontaneous movement at 24 hpf and tremor like movement measured by the free larval activity at 72 hpf, as well as the larval activity at 96 hpf under light-dark transition stimulus. Mechanistic examinations at 120 hpf revealed DDT exposure elevated oxidative stress through MDA formation increase, ATP level decrease as well as antioxidant enzyme genes (sod1 and gpx1a) expression decrease. DDT exposure induced abnormal neurotransmitters expression with DA level increase, 5-HT and NOS level decrease. DDT exposure suppressed the gene expressions involved in axon development (rab33a and nrxn2a) and potassium channel (kcnq2 and kcnq3). Our results suggest that the hyperactivity and tremor like movement in DDT-exposed embryos/larvae may result from oxidative stress involved with neuronal damage.

Tissue distribution of tetrabromobisphenol A and cadmium in mixture inhalation exposure.

Tetrabromobisphenol A (TBBPA) and cadmium chloride (CdCl2) are the typical representative pollutants of brominated flame retardants and heavy metals found in the air of e-waste recycling workshops. However, their metabolic kinetics through mixture inhalation is unknown. In the present study, 8-week old Institute of Cancer Research (ICR) male mice were whole-body exposed to TBBPA and CdCl2 mixtures by inhalation. Tissue samples were collected for TBBPA and cadmium (Cd) analysis at 2, 4, 6, and 8 weeks during exposure and at 4 and 8 weeks after the completion of the 8-week exposure period. TBBPA was mainly distributed to the lungs, liver, kidney, testis, and spleen, with a high amount accumulated in the brain, liver, and spleen. Cd was mainly distributed to the lungs, liver, and kidney, with a high amount accumulated in the liver, kidney, and testis and a low amount accumulated in brain and serum. Tissue burden of TBBPA and Cd in all organs increased in a dose- and time-dependent manner during the exposure period. However, 4 weeks after the completion of an 8-week exposure, TBBPA concentrations in the liver, testis, brain, and serum and Cd concentrations in the liver, testis, and kidney were higher than the corresponding tissue concentrations during the exposure period. The rapid accumulation of both TBBPA and Cd in the lungs after inhalation exposure indicated a high risk of the respiratory system diseases for workers in e-waste recycling workshops. In addition, the migration of both TBBPA and Cd from lungs to liver and testis may result in more complex toxic effects in vivo.