The Profiles Of Neonicotinoids Insecticides And Their Specific Metabolites In Indoor Dust And Human Urine

Neonicotinoids（NNIs）,an acetylcholine-interfering neurotoxic class of insecticides,are mainly used for pest control and play an indispensable role in agriculture,urban landscaping,and daily life.With the widespread use of NNIs in various countries in the world,it also brings great potential safety hazard to the ecosystems and human health.In recent years,NNIs has been widely detected in various environmental and biological media.Humans can be exposed to NNIs through ingestion（diet,water,hand-to-mouth exposure pathway）and inhalation,of which hand-to-mouth is the main exposure pathway in the indoor environment for the sensitive population（especially infants and toddlers）.However,limited data are available to assess population exposure to NNIs and their metabolites in indoor environments,and the data on NNIs in indoor dust in China is still lacking.Meanwhile,although some studies have reported the levels of NNIs in human urine,they only focused on the parent compounds and non-specific metabolites of NNIs.Relevant data on specific metabolites of NNIs in human urine and the characteristics of human exposure to NNIs are scarce.The inter-day and seasonal variations of NNIs and their metabolites in human urine remain unclear.In this study,the residual levels of NNIs and some of their metabolites in 336 indoor dust samples from three cities in South,Central,and North China（Shenzhen,Wuhan,and Taiyuan）were detected to analyze the spatial and temporal distribution of NNIs in indoor dust.Meanwhile,the relative potency factor（RPF）method was used to assess the combined exposure risk of NNIs for the general population in China through the indoor dust ingestion.Furthermore,this study was conducted to demonstrate the exposure levels and characteristics of NNIs using 408 urine samples collected from adults among the general population in Central China to determine the inter-day reliability and seasonal variations of NNIs and their specific metabolites and to assess related human exposure.Part Ⅰ:Neonicotinoids in Indoor Dust from Three Cities in China:Spatial and Temporal VariationsObjective:This study intends to measure the levels of NNIs in indoor dust samples from Shenzhen,Wuhan,and Taiyuan in China,evaluate the exposure of NNIs in the indoor environment in these three areas,and reveal the spatial and temporal distribution of NNIs.Meanwhile,the daily exposure of the general population was evaluated based on the exposure levels of indoor dust NNIs detected.Methods:In this study,336 indoor dust samples were collected from 3 cities,including Taiyuan（October 2016）,Wuhan（October 2016 and 2018）,and Shenzhen（February 2019）,locatedin North,Central,and South China,for determination of the residues of ten NNIs（ACE、CLO、DNT、IMI、THCP、THM、NTP、FLO、IMIT、SUL）and two of their metabolites（DM-ACE and 5-OH-IMI）by using ultra-performance liquid chromatography-tandem mass spectrometry（UPLC-MS/MS）.The relative potency factor（RPF）method was used to assess the combined exposure risk of NNIs through indoor dust ingestion for the general population in China.Results:ACE and IMI were found to be the major target analytes in dust samples from all selected cities with detection frequencies of 98.8%and 99.7%,respectively,while the other NNIs detection rates were relatively low.At least one target NNI was detected for all of the dust samples,with the median concentration of 25.8 ng/g for the imidacloprid-equivalent total neonicotinoids(IMI_eq:generated by the relative potency factor method).The highest median concentration of IMI_eq was found in Wuhan 2018（70.1 ng/g）,followed by Shenzhen（35.6 ng/g）,Wuhan in 2016（20.0 ng/g）,and Taiyuan（11.1 ng/g）.Higher levels of several NNIs were found in urban areas of Taiyuan and Wuhan than those in rural areas（P<0.05）.A significant increase of the NNI residues was observed in dust of Wuhan from 2016 to 2018（P<0.05）.Finally,the estimated daily intake（EDI）of IMI_eq for infants and toddlers were higher than that found in other age groups through dust ingestion.Conclusions:Among all of the indoor dust samples,ACE and IMI were the most frequently detected target NNIs,suggesting that the study population was mainly exposed to ACE and IMI through the dust ingestion.An increasing trend of NNIs was observed in Wuhan from 2016 to 2018,which indicated that the pollution of NNIs in indoor dust in Wuhan was aggravated and some measures needs to be implemented.Infants and toddlers may be susceptible to current residue of NNIs in indoor dust,and dust ingestion of NNIs might be<1%of that reported for dietary intakes in China.Part Ⅱ: Neonicotinoids and their Specific Metabolites in Human Urine from Wuhan,China-Implications for Human ExposureObjective: This study aimed to reveal the exposure levels and characteristics of NNIs in human urine from Wuhan,China,to explore the specific metabolites of major NNIs,to determine the inter-day reliability and seasonal variations of NNIs and their specific metabolites,and to assess human exposure.Methods: In this study,the ultra high liquid chromatography tandem mass spectrometry（UPLC-MS/MS）was used to detect the levels of ten parent compounds（IMI,ACE,THM,CLO,DNT,THCP,FLO,IMIT,NTP and SUL）,and six of their metabolites（DN-IMI,IMI-olefin,5-OH-IMI,IMI-urea,DM-ACE and DM-THM）in 408 urine samples（containing repeated samples in 3 days from 75 volunteers）collected from 129 healthy adults in Wuhan,Central China,during autumn and winter,2018,and the urinary NNIs were adjusted by urine specific gravity.Spearman rank correlation test was used to evaluate the correlation between urinary NNIs.Independent sample t test and one-way analysis of variance（one-way ANOVA）or non-parametric tests were used to analyze the exposure characteristics of the target analytes.Results: DM-ACE,DN-IMI,IMI-olefin,CLO,and THM were detected in more than 90% of urine samples.Urinary levels of DN-IMI,IMI-olefin,and DM-ACE were higher（4 – 40 times）than their parent compound: IMI and ACE.DN-IMI and IMI-olefin accounted for 92% of urinary ∑3IMI（the sum of IMI and its specific metabolites measured）.Positive correlations were observed between DN-IMI and IMI（r = 0.50,P < 0.0001）,IMI-olefin and IMI（r = 0.75,P < 0.0001）,and DM-ACE and ACE（r = 0.53,P < 0.0001）.Good inter-day reliabilities（unadjusted intraclass correlation coefficients）were observed for DM-ACE（ICC: 0.81;95%CI: 0.74-0.87）and IMI-olefin（0.61;0.49-0.72）,while moderate for DN-IMI（0.43;0.30-0.57）.Urinary NNIs levels were significantly higher in autumn than in winter（P < 0.05）,and higher urinary NNIs in urban than in rural（P < 0.05）;while no significant gender-or age-related differences were observed（P > 0.05）.Conclusions: This study confirmed that DN-IMI,IMI-olefin,and DM-ACE could be used as biomarkers for human biomonitoring in IMI and ACE related exposure,respectively,due to their specificities and relatively good inter-day reliabilities.DM-ACE,DN-IMI,IMI-olefin,CLO and THM were the major target NNIs in human urine of the general population in Wuhan,China.Significant correlations were observed among target NNIs,indicating that they have a common exposure source.Urban-rural and seasonal variation of urinary NNIs were observed in the population studied.But the concentration distribution of urinary NNIs were not significantly affected by gender and age.