Linking pesticide exposure to neurodegenerative diseases: An in vitro investigation with human neuroblastoma cells.

Although many organochlorine pesticides (OCPs) have been banned or restricted because of their persistence and linkage to neurodegenerative diseases, there is evidence of continued human exposure. In contrast, registered herbicides are reported to have a moderate to low level of toxicity; however, there is little information regarding their toxicity to humans or their combined effects with OCPs. This study aimed to characterize the mechanism of toxicity of banned OCP insecticides (aldrin, dieldrin, heptachlor, and lindane) and registered herbicides (trifluralin, triallate, and clopyralid) detected at a legacy contaminated pesticide manufacturing and packing site using SH-SY5Y cells. Cell viability, LDH release, production of reactive oxygen species (ROS), and caspase 3/7 activity were evaluated following 24 h of exposure to the biocides. In addition, RNASeq was conducted at sublethal concentrations to investigate potential mechanisms involved in cellular toxicity. Our findings suggested that aldrin and heptachlor were the most toxic, while dieldrin, lindane, trifluralin, and triallate exhibited moderate toxicity, and clopyralid was not toxic to SH-SY5Y cells. While aldrin and heptachlor induced their toxicity through damage to the cell membrane, the toxicity of dieldrin was partially attributed to necrosis and apoptosis. Moreover, toxic effects of lindane, trifluralin, and triallate, at least partially, were associated with ROS generation. Gene expression profiles suggested that decreased cell viability induced by most of the tested biocides was related to inhibited cell proliferation. The dysregulation of genes encoding for proteins with anti-apoptotic properties also supported the absence of caspase activation. Identified enriched terms showed that OCP toxicity in SH-SY5Y cells was mediated through pathways associated with the pathogenesis of neurodegenerative diseases. In conclusion, this study provides a basis for elucidating the molecular mechanisms of pesticide-induced neurotoxicity. Moreover, it introduced SH-SY5Y cells as a relevant in vitro model for investigating the neurotoxicity of pesticides in humans.

Herbicides and pesticides synergistically interact at low concentrations in complex mixtures.

Assessing a complex mixture of pesticides at the impacted sites has been challenging for risk assessors for 50 years. The default assumption is that at low concentrations, pesticides interact additively with one another; thus, the risk posed by each component of a complex mixture could be simply added up. The EPA interaction-based hazard index (HIInteraction) modifies this assumption using a binary weight-of-evidence (BINWOE). However, data gaps often preclude HIInteraction use at most sites. This study evaluated these assumptions using the BINWOE to estimate the hazard index (HI) of select pesticide mixtures. The lack of in vivo binary interaction data led us to use a cell line, SH-SY5Y, to obtain the data necessary for the BINWOE approach. In the risk assessment, we considered the most active exposure scenario inhaling a mixture of volatile pesticides from contaminated soil and groundwater. The potential interactions between pesticides in 15 binary mixtures were investigated using the MTT assay in SH-SY5Y cells. Our findings showed that 60% of the binary mixtures elicited synergism (in at least one concentration), 27% displayed antagonism, and 13% showed additive effects in SH-SY5Y cells. Combining human safety data with in vitro interaction data indicated that adults and toddlers were at the highest risk when considering industrial and commercial land use, respectively, compared to other subpopulations. Incorporating interaction data into the risk assessment either increased the risk by up to 20% or decreased the risk by 2%, depending on the mixture. Our results demonstrate the predominant synergistic interactions, even at low concentrations, altered risk characterization at the complex operating site. Most concerning, organochlorine pesticides with the same mechanism of action did not follow dose additivity when evaluated by SH-SY5Y cell lines. Based on our observations, we caution that current HI methods based on additivity assumptions may underestimate the risk of organochlorine mixtures.

Heavy metal contamination of vegetables in Isfahan, Iran.

Vegetables are an inevitable and important part of a healthy and balanced diet. They could be contaminated by heavy metals in many ways including irrigation by sewage water and industrial effluents sewage sludge, vehicular emissions, industrial waste and atmospheric deposition. In this study, we sought to determine if some vegetables (cucumbers, tomatoes, cabbage, lettuce, potatoes, onions, carrots, persian leeks, dill, spinach, coriander, parsley) grown locally in the suburban of Isfahan city and sold in the urban markets are contaminated with cadmium (Cd), chromium (Cr) and lead (Pb). Vegetables were sampled from August to October 2010. After washing, they were oven-dried and digested using three-acid mixture (70% HNO3, 65% HClO4 and 70% H2SO4). Analyzes of the heavy metals was performed using atomic absorption spectrophotometry. To validate the assay method, intra-day and inter-day variation studies were performed. The concentrations (µg/g) of heavy metals in the samples ranged from 0.00 to 3.66 for Cd, 0.00 to 6.00 for Cr and 0.00 to 7.14 for Pb. The highest concentration of heavy metals was for Pb. The results showed that the amount of Cd, Cr and Pb of some samples exceeded the recommended levels. The amount of Cd in cucumber, tomatoes, potatoes with skin, carrots, and spinach was significantly higher in the samples collected from Isfahanak, Dashti and Ilchi farms than those of Dorche farms. Also, the amount of Cr in onion, carrots, and spinach was significantly higher in samples collected from Isfahanak, Dashti and Ilchi farms than those of Dorche farms. However, the amount of Pb in the carrots and leek was significantly higher in the samples collected from Dorche farms than those of Isfahanak, Dashti and Ilchi farms. It can be concluded from the findings of this study that the amounts of Cd, Cr, and Pb were higher than the acceptable levels recommended by WHO/FAO. Also, higher amount of Cd and Cr in some samples collected from Isfahanak, Dashti and Ilchi farms compared to that of the samples collected from Dorche farms may indicate the influence of contaminants that enter ZayadeRood River as it passes Isfahan.