Chronic Toxicity Of Organophosphate Flame Retardants To Caenorhabditis Elegans

Organophosphorus flame retardants(OPFRs)are a new class of commonly used fire-resistantmaterial additives.OPFRs are frequently added to consumer products including furniture,textiles,building materials and electronics.Companying with increasing applications,OPFRs have been frequently detected in various environmental matrices and organisms,and the ecological risks and health effects have been concerned in recent years.There are nearly twenty kinds of organophosphorus flame retardants,among which tris(2-chloroethyl)phosphate(TCEP)and tris(chloropropyl)phosphate(TCPP)are the most widely used OPFRs.Recent studies have shown that organic phosphorus flame retardants present endocrine disrupting effects and neurotoxicity;yet the environmental and health risks and their mechanisms have not been fully elucidated.In the present study,chronic toxicityof two typical OPFRs,TCEP and TCPP,to C.elegans were fully investigated including developmental and neural toxicity.The main results are as followings:1.The median lethal concentrations(LC50)of TCEP are 1,825mgL-1 for 1d exposure,1578 mgL-1 for 3d and 1381mgL-1 for 6d.LC50 of TCEP is 857mgL-1 for 1d exposure,852mgL-1 for 3d and 897 mgL-1 for 6d.Sublethal concentrations of TCEP or TCPP could result in significant inhibition of body length and body width of nematodes.50mg/L or above TCEP,and 250mg/L or above TCPP induced a significant decrease in the number of eggs;and the date of egg maturation was delayed more than 0.5d after exposure.In addition,750mg/L or above TCEP/TCPP resulted in a significant shortening of the average longevity of nematodes.2.More than 500mgL-1 TCEP/TCPP led to a significant decline in locomotor frequency of body bending and head thrashing,but not obvious changes in pharyngeal pump frequency.Results of crawling videos showed that crawling tracks were irregularly curved,crawling distances were shortened,amplitude of bending wave became smaller and the crawling angles changed slower after exposure.3.Using fluorescent-labeled transgenic nematodes,we found chronic exposure to TCEP or TCPP caused down-expression of dat-1 and damage of the dopaminergic neurons including deformation of the cell body and dendritic fracture.The most severe damages occurred in PDE neurons in the tail of nematodes.However,the same exposure showed no observable effects on GABA ergicand glutamatergic neurons in C.elegans.It suggests that OPFRs maybe were susceptible to some specific types of neurons in vivo.4.Exposure to TCEP or TCPP resulted inup-expression of unc-54 and abnormal aggregation of a-synucleinin C.elegans.The abnormal expression of this protein may be related to the damage of dopaminergic neurons and locomotor deficits.These results indicate that:1.As representatives of organic phosphorus flame retardants,TCEP and TCPP possess chronic lethality on C.elegans.Sublethal levels of organic phosphorus flame retardantscan induce inhibitory effects on developmentand reproduction,and shorten the longevity of C.elegans.These results indicate that organic phosphorus flame retardants have the risk of inducing reproductive and developmental toxicity.2.Chronic exposure to TCEP/TCPP can induceand Parkinsonian-like movement impairment including bradykinesia,hypokinesia and unbalance.It indicates that OPFRs possess behavior toxicity under chronic exposure condition.3.TCEP/TCPP exposurecaused down-expression of dat-1,and resulted in specific degeneration of dopamine neurons.The exposure also enhanced expression of unc-5,which encodes a subunit of ?-synuclein.It indicates that OPFRs may possess the neurotoxicity risk of Parkinson's disease.In this study,toxicity and risks of organophosphorus flame retardants were,for the first time,investigated on the C.elegans system.We found that TCEP and TCPP can lead to reproduction toxicity,locomotor deficits and degeneration of dopaminergic neurons.For the first time,the neurotoxicity of OPFRs involved in Parkinson's disease was revealed.The mechanisms are linked to the enhanced expression of unc-54 and aggregation of a-synuclein.These findings provide some crucialin formation for understanding of environmental and health risks of organophosphorus flame retardants.It also provides important data for pathopoiesis of Parkinson's disease.