Developmental neurotoxic effects of two pesticides: Behavior and biomolecular studies on chlorpyrifos and carbaryl.

In recent times, an increased occurrence of neurodevelopmental disorders, such as neurodevelopmental delays and cognitive abnormalities has been recognized. Exposure to pesticides has been suspected to be a possible cause of these disorders, as these compounds target the nervous system of pests. Due to the similarities of brain development and composition, these pesticides may also be neurotoxic to humans. We studied two different pesticides, chlorpyrifos and carbaryl, which specifically inhibit acetylcholinesterase (AChE) in the nervous system. The aim of the study was to investigate if the pesticides can induce neurotoxic effects, when exposure occurs during a period of rapid brain growth and maturation. The results from the present study show that both compounds can affect protein levels in the developing brain and induce persistent adult behavior and cognitive impairments, in mice neonatally exposed to a single oral dose of chlorpyrifos (0.1, 1.0 or 5mg/kg body weight) or carbaryl (0.5, 5.0 or 20.0mg/kg body weight) on postnatal day 10. The results also indicate that the developmental neurotoxic effects induced are not related to the classical mechanism of acute cholinergic hyperstimulation, as the AChE inhibition level (8-12%) remained below the threshold for causing systemic toxicity. The neurotoxic effects are more likely caused by a disturbed neurodevelopment, as similar behavioral neurotoxic effects have been reported in studies with pesticides such as organochlorines, organophosphates, pyrethroids and POPs, when exposed during a critical window of neonatal brain development.

Developmental neurotoxic effects of two pesticides: Behavior and neuroprotein studies on endosulfan and cypermethrin.

Developmental neurotoxicity of industrial chemicals and pharmaceuticals have been of growing interest in recent years due to the increasing reports of neuropsychiatric disorders, such as attention deficit hyperactivity disorder (ADHD) and autism. Exposure to these substances during early development may lead to adverse behavior effects manifested at a later phase of life. Pesticides are a wide group of chemicals which are still actively used and residues are found in the environment and in food products. The present study investigated the potential developmental neurotoxic effects of two different types of pesticides, endosulfan and cypermethrin, after a single neonatal exposure during a critical period of brain development. Ten-day-old male NMRI mice were administrated an oral dose of endosulfan or cypermethrin (0.1 or 0.5 mg/kg body weight, respectively). Levels of proteins were measured in the neonatal and adult brain, and adult behavioral testing was performed. The results indicate that both pesticides may induce altered levels of neuroproteins, important for normal brain development, and neurobehavioral abnormalities manifested as altered adult spontaneous behavior and ability to habituate to a novel home environment. The neurotoxic behavioral effects were also presentseveral months after the initial testing, indicating long-lasting or even persistent irreversible effects. Also, the present study suggests a possible link between the altered levels of neuroprotein and changes in behavior when exposed during a critical period of brain development.

Effects of neonatal exposure to the flame retardant tetrabromobisphenol-A, aluminum diethylphosphinate or zinc stannate on long-term potentiation and synaptic protein levels in mice.

Brominated flame retardants such as tetrabromobisphenol-A (TBBPA) may exert (developmental) neurotoxic effects. However, data on (neuro)toxicity of halogen-free flame retardants (HFFRs) are scarce. Recent in vitro studies indicated a high neurotoxic potential for some HFFRs, e.g., zinc stannate (ZS), whereas the neurotoxic potential of other HFFRs, such as aluminum diethylphosphinate (Alpi), appears low. However, the in vivo (neuro)toxicity of these compounds is largely unknown. We therefore investigated effects of neonatal exposure to TBBPA, Alpi or ZS on synaptic plasticity in mouse hippocampus. Male C57bl/6 mice received a single oral dose of 211 µmol/kg bw TBBPA, Alpi or ZS on postnatal day (PND) 10. On PND 17-19, effects on hippocampal synaptic plasticity were investigated using ex vivo extracellular field recordings. Additionally, we measured levels of postsynaptic proteins involved in long-term potentiation (LTP) as well as flame retardant concentrations in brain, muscle and liver tissues. All three flame retardants induced minor, but insignificant, effects on LTP. Additionally, TBBPA induced a minor decrease in post-tetanic potentiation. Despite these minor effects, expression of selected synaptic proteins involved in LTP was not affected. The flame retardants could not be measured in significant amounts in the brains, suggesting low bioavailability and/or rapid elimination/metabolism. We therefore conclude that a single neonatal exposure on PND 10 to TBBPA, Alpi or ZS does affect neurodevelopment and synaptic plasticity only to a small extent in mice. Additional data, in particular on persistence, bioaccumulation and (in vivo) toxicity, following prolonged (developmental) exposure are required for further (human) risk assessment.

A single neonatal exposure to perfluorohexane sulfonate (PFHxS) affects the levels of important neuroproteins in the developing mouse brain.

Perfluorohexane sulfonate (PFHxS) is an industrial chemical and belongs to the group of perfluorinated compounds (PFCs). It has recently been shown to cause developmental neurobehavioral defects in mammals. These compounds are commonly used in products such as surfactant and protective coating due to their ability to repel water- and oil stains. PFCs are globally found in the environment as well as in human umbilical cord blood, serum and breast milk. In a previous study on other well-known PFCs, i.e. PFOS and PFOA, it was shown that neonatal exposure caused altered neuroprotein levels in the hippocampus and cerebral cortex in neonatal male mice. The present study show that neonatal exposure to PFHxS, during the peak of the brain growth spurt, can alter neuroprotein levels, e.g. CaMKII, GAP-43, synaptophysin and tau, which are essential for normal brain development in mice. This was measured for both males and females, in hippocampus and cerebral cortex. The results suggest that PFHxS may act as a developmental neurotoxicant and the effects are similar to that of PFOS and PFOA, but also to other substances such as PCBs, PBDEs and bisphenol A.

Adult dose-dependent behavioral and cognitive disturbances after a single neonatal PFHxS dose.

Perfluoroalkyl acids, including perfluorohexane sulfonate (PFHxS), are fluorinated organic compounds used as surfactants and water and stain repellents in carpets, paper, and textiles, with characteristics to bioaccumulate and biomagnify in the food chain. PFHxS is found in umbilical cord blood, human milk and child serum from all over the world. We have recently reported that neonatal exposure to certain perfluoroalkyl acids, PFOS and PFOA, can induce persistent aberrations in spontaneous behavior and also affect learning and memory functions in the adult animal. The present study indicates that a single exposure to PFHxS on postnatal day 10, during a vulnerable period of brain development can alter adult spontaneous behavior and cognitive function in both male and female mice, effects that are both dose-response related and long-lasting/irreversible. PFHxS affected the cholinergic system, manifested as altered nicotine-induced behavior in adult animals. This is also in agreement with earlier studies on neonatal exposure to PFOS and PFOA. The present findings show that PFHxS, a member of the perfluoroalkyl acid group, can act as a developmental neurotoxicant and affect the cholinergic system and cognitive function and the effects show similarities with effects earlier reported after neonatal exposure to other POPs, such as bisphenol A, PBDEs and PCBs.

A single exposure to bisphenol A alters the levels of important neuroproteins in adult male and female mice.

Bisphenol A (BPA) is widely used in polymer products in food and beverage containers, baby bottles, dental sealants and fillings, adhesives, protective coatings, flame retardants, water supply pipes, and compact discs, and is found in the environment and in placental tissue, fetuses and breast milk. We have recently reported that a single neonatal exposure to bisphenol A can induce persistent aberrations in spontaneous behavior, in a dose-dependent manner, and affect the adult response to the cholinergic agent nicotine. Furthermore, other recent reports indicate that pre- and perinatal exposure to bisphenol A can induce neurotoxic effects. The present study indicates that a single neonatal exposure to bisphenol A, on postnatal day 10, during the peak of the brain growth spurt, can alter the adult levels of proteins important for normal brain development (CaMKII and synaptophysin). These alterations are induced in both male and female mice and effects are seen in both hippocampus and cerebral cortex. These results further support our recent study showing that neonatal exposure to bisphenol A can act as a developmental neurotoxicant and the effects are similar to effects seen after a single postnatal exposure to other POPs, such as PBDEs, PCBs and PFCs.

Influence of earthworm activity on microbial communities related with the degradation of persistent pollutants.

Earthworms may promote the biodegradation of polycyclic aromatic hydrocarbons (PAHs) in soil, but the mechanism through which they exert such influence is still unknown. To determine if the stimulation of PAH degradation by earthworms is related to changes in microbial communities, a microcosm experiment was conducted consisting of columns with natural uncontaminated soil covered with PAH-contaminated dredge sediment. Columns without and with low and high Eisenia andrei densities were prepared. Organic matter and PAH content, microbial biomass, and dehydrogenase activity (DHA) were measured in soil and sediment over time. Biolog Ecoplate™ and polymerase chain reaction using denaturing gradient gel electrophoresis were used to evaluate changes in metabolic and structural diversity of the microbial community, respectively. Earthworm activity promoted PAH degradation in soil, which was significant for biphenyl, benzo[a]pyrene, and benzo[e]pyrene. Microbial biomass and DHA activity generally did not change over the experiment. Earthworm activity did change microbial community structure, but this did not affect its functioning in terms of carbon substrate consumption. Results suggest no relationship between changes in the microbial community by earthworm activity and increased PAH disappearance. The role of shifts in soil microbial community structure induced by earthworms in PAH removal needs further investigation.