Risk Assessment Of Inhalation Exposure To Pesticide Multiresidue Based On Bioaccessibility

The environmental air pollution caused by the drift of chemical pesticide spraying has raised significant concerns.The widespread use of pesticide formulations and the simultaneous use of different pesticides have led to a serious problem of pesticide residues in ambient air.Human inhalation of multiple pesticide residues can produce combined toxic effects and increase the potential risk to human health.Inhalational bioaccessibility is an important indicator for the scientific evaluation of pesticide residue exposure assessment,which can accurately reflect the actual exposure level of pesticide residues in the human body.In this study,the risk level of inhalation exposure of single residues of difenoconazole and lambda-cyhalothrin to the spray personnel was studied,and the toxic effects of the combined exposure of eight different pesticides,including lambda-cyhalothrin and emamectin benzoate,on the proliferation of A549 cells under single and combined exposure were clarified.One representative pesticide combination was selected from each of the three types of combined action:antagonistic,additive and synergistic.Conduct an assessment on the inhalation bioaccessibility and combined toxic effects of the tested pesticide,while quantitatively evaluating the health risk level.The results provide a fundamental basis for accurate evaluating the inhalation exposure risks of pesticide multiple residues to spray personnel and populations around the spray environment in farmland spray scenarios.The main findings are as follows:1.Risk assessment of pesticide single residue inhalation exposure in electric spray application scenarioAn in vitro method for the determination of bioaccessibility of difenoconazole and lambda-cyhalothrin was established.The bioaccessibility of difenoconazole and lambda-cyhalothrin were 43.33%and 45.85%,respectively.Using non-small cell lung cancer cell A549 as the end point,the toxicity thresholds of single exposure were 0.471 mmol/L and5.60 mmol/L,respectively,by benchmark dose method.Based on the unit exposure of difenoconazole and lambda-cyhalothrin in the farmland spray scenarios,combined with the obtained inhalation bioaccessibility of the tested pesticide,an inhalation exposure assessment was conducted for the spray personnel.The margin of exposure（MOE）of difenoconazole and lambda-cyhalothrin based on inhalation bioaccessibility were 8.97×10⁵-5.47×10⁶ and 4.87×10³-5.24×10⁴,respectively,which were all within the acceptable range（>100）.2.Multiresidue combined toxicity threshold of pesticides based on A549 cell proliferation activityUsing lambda-cyhalothrin as the study subject,the toxic effects of lambda-cyhalothrin combined with emamectin benzoate,phoxim,malathion,thiamethoxam,imidacloprid,clothianidin,dinotefuran,acetamiprid on the proliferation of A549 cells under single and combined exposure were studied.The types of combined effects of lambda-cyhalothrin with emamectin benzoate,phoxim and acetamiprid were synergistic,antagonistic or additive,respectively,which could be used as representative pesticide combinations.The toxicity thresholds of single exposure and combined exposure were derived by the benchmark dose method.The results showed that the toxicity thresholds（BMDL）of emamectin benzoate,phoxim and acetamiprid on the proliferation activity of A549 cells were 0.009 mmol/L,0.151 mmol/L and 0.031 mmol/L,respectively.The toxicity thresholds（BMDL）for combined exposure of lambda-cyhalothrin with emamectin benzoate,phoxim and acetamiprid were 0.006 mmol/L,0.273 mmol/L and 0.098 mmol/L,respectively,to provide data support for risk assessment of pesticide multiresidue inhalation exposure.3.Development and optimization of a method for in vitro simulation of bioaccessibility of multiresidue of tested pesticidesAn in vitro method for the determination of inhaled bioaccessibility of the tested pesticide was established.The response surface method was used to optimize the design and determine the inhaled bioaccessibility of the tested pesticide residues.The results showed that the maximum bioaccessibility of acetamiprid was 64.07%（GS）,58.36%（ALF）and 67.14%（SLF）,respectively.The maximum bioaccessibility of phoxim was 65.11%（GS）,51.01%（ALF）and 57.99%（SLF）,respectively.In vitro and in vivo correlation analysis（IVIVC）was conducted between the bioaccessibility data of the tested pesticides and their inhaled bioavailability data in model animals（mice）.It was clear that when S/L was 1/1000,the IVIVC model had a good correlation（R²=0.7715-0.8595）.Therefore,the parameters of the in vitro lung simulation method to determine the tested pesticide residues were as follows:the retention time was 21-24 h,the solid-liquid ratio was 1/1000,and the oscillation rate was 50-250 r/min.Under this method,the inhaled bioaccessibility of acetamiprid,phoxim and lambda-cyhalothrin were40.31%,67.12%and 46.09%,respectively,to provide a method basis for risk assessment of multiresidue inhalation exposure of test pesticides by inhalation bioaccessibility.4.Risk assessment of inhalation exposure to pesticide multiresidue based on bioaccessibilityBased on the unit exposure amount of the tested pesticide under the farmland spray scenarios and combined with the obtained inhalation bioaccessibility of the tested pesticide,the inhalation exposure assessment for the spray personnel and the population around the spraying environment（50 m down the air outlet）showed that when the combined exposure of lambda-cyhalothrin and acetamiprid,phoxim and emamectin benzoate was carried out,the average daily exposure（ADD）of the spray personnel was 1.52×10^-5-1.72×10^-5mg/kg·day,1.49×10^-5-1.83×10^-5 mg/kg·day and 7.82×10^-6-8.79×10^-6 mg/kg·day,respectively.The average daily exposure（ADD）of the population around the spraying environment was 1.16×10^-9-3.18×10^-8 mg/kg·day,2.24×10^-7-2.25×10^-9 mg/kg·day and1.04×10^-8-7.65×10^-10 mg/kg·day,respectively.The margin of exposure（MOE）for combined exposure of lambda-cyhalothrin and acetamiprid,phoxim and emamectin benzoate based on inhalation bioaccessibility were 1.84×10⁴-2.72×10⁹,1.11×10⁴-9.01×10⁸,9.95×10²-1.14×10⁸,respectively,which were all within the acceptable range（>100）.If the important factor of inhaled bioaccessibility is not taken into account,the MOE of the tested pesticides will be overestimated by 32-60%.