Environmental monitoring and potential health risk assessment from Pymetrozine exposure among communities in typical rice-growing areas of China

Pymetrozine is one of the most commonly used insecticides in China. This study was conducted to analyse Pymetrozine’s potential exposures through various environmental routes beyond the treatment areas. The aim was to estimate the potential health risk for communities due to non-dietary exposures to Pymetrozine in soil and paddy water. Data on registration of pesticides in China, government reports, questionnaires, interviews and literature reviews as well as toxicological health investigations were evaluated to determine the hazard and dose–response characteristics of Pymetrozine. These were based on the US EPA exposure and human health risk assessment methods and exposure data from soil and paddy water samples collected between 10 and 20 m around the resident’s location. The exposure doses from dermal contact through soil and paddy water were estimated. The potential cancer risk from the following exposure routes was evaluated: ingestion through soil; dermal contact exposure through soil; dermal contact exposure through paddy water. The potential total cancer risk for residents was estimated to be less than 1 × 10−6. These were relatively low and within the acceptable risk levels. The potential hazard quotient (HQ) from acute and lifetime exposure by dermal contact through paddy water and soil and acute and lifetime exposure by soil ingestion for residents was less than 1, indicating an acceptable risk level. This study suggested that there were negligible cancer risk and non-cancer risks based on ingestion and dermal contact routes of exposure to residents.


Introduction
Pesticides play a significant role in reducing losses of agricultural production and improve yield and quality of foods (Aktar et al. 2009;Schreinemachers et al. 2017 can contaminate air, water, soil and crops, and thus bring toxicity risks to other biological organisms, including birds, fish, beneficial insects and non-target plants (Tudi et al. 2021), and the toxicity risks can still exist even being away from the application areas, through environmental pathways or food contamination (Yadav et al. 2015). Although some measures have been proposed to reduce the negative effects of pesticides on the environment and human health (Phung et al. 2012c), both acute and chronic human toxicities resulting from these substances remain a serious problem (Tudi et al. 2021). It is estimated that pesticide exposure will increase over the next decade globally, developing countries in particular (Delcour et al. 2015). China has the largest pesticide production and consumption . There was an increase in the use of pesticides from 1.28 million tons in 2000 to 1.8 million tons in 2013, with an average annual increase of 2.7% reported for 2018 (Shuqin and Fang 2018).
However, 70% of the pesticides used in China were not absorbed by plants and other organisms, and then entered into the environment (Wang et al. 2018). Thus, many nonfarm worker residents living close to agricultural lands where pesticides are often used intensively are exposed to pesticides. Owing to the intrinsic toxicity of pesticides, it is important to evaluate the potential health consequences for this specific population, but such evaluations are largely absent in studies to date. P y m e t r o z i n e { 4 , 5 -d i hy d r o -6 -m e t hyl -4 -[ ( 3pyridylmethylene)-amino]-1,2,4-triazine-3(2H)-one} has the basic structure of a pyridine azomethine . Currently, it is widely used in China (Jia et al. 2019;Gong et al. 2019;Kovacova et al. 2013). In addition, Pymetrozine has recently replaced organic phosphate pesticides although organophosphate pesticides continue to be used in some other countries in the world (Hamsan et al. 2017;Atabila et al. 2018a, b, Phung et al. 2012a). Pymetrozine has a negative impact on reproduction and can cause irritation to the respiratory system (European Food Safety 2017). The United States Environmental Protection Agency (USEPA) classifies Pymetrozine as a possible human carcinogen and it has a cancer slope factor of 0.0019 mg/kg (USEPA 2010).
At present, studies on the Pymetrozine mainly focus on its residues (Gong et al. 2019;Jia et al. 2019;Xu et al. 2021;Yu et al. 2020), the metabolites (Gong et al. 2019). Although some safety risk assessment were conducted based on the concentration in food (Xu et al. 2021;Yu et al. 2020), very few studies have concerned the potential carcinogenic and non-carcinogenic risk of Pymetrozine posed to the residents living in the neighbouring application land (Hamsan et al. 2017). A first step in the development of a potential health risk assessment in respect to this chemical must be to gain an understanding of its environmental distribution, attenuation and fate under field conditions. However, most previous studies of these parameters were not carried out under field conditions (Europe Food safety Authority 2014).
The objectives of this study were thus to analyse potential exposure of Pymetrozine through the environmental exposure for the residents living adjacent to Pymetrozine application areas, and to assess the potential health risk due to non-dietary exposure to Pymetrozine in soil and paddy water under the field conditions. The study provided scientific information for policy makers to set the proper pesticide application techniques and methods to minimize the pesticide exposure relating to health effects for communities.

Study area
The study area was identified with the assistance of the Institute of Plant Protection Chinese Academy of Agricultural Science and Beijing ECO-SAF Technology Co., Ltd. Based on the location of the Institute of Plant Protection Chinese Academy of Agricultural Science and Beijing ECO-SAF Technology Co., Ltd. and local government, two typical rice-growing areas, Yun-Wen Village, Shang Lin Country, Nan Ning City of Guangxi Province, and Hua Tang Village, Chang Sha Country, Chang Sha City of Hunan Province, were selected as the study areas (Fig. 1).
Samples of paddy soil and paddy water were collected in association with a spraying event. Farmers sprayed pesticides once a month. Residents lived within 10-20 m of their agriculture areas.

Sample collection
The quartering sampling method (Li 2008) was used to collect soil and paddy water samples. Four samples were collected from the surface (0-to 15-cm layer) in every plot (size about 2000 m 2 ), composited and stored in a polyethylene bag as one sample. Fifteen soil and fifteen paddy water samples were collected in each region. Samples were collected on the day prior to spraying insecticides; the day of spraying; and 1, 3, 5, 7, 9, 14, 21 and 28 days after spraying. All the samples were stored at − 20 °C immediately prior to analysis and the samples were analysed within 1 month.

Sample analysis
Based on the previous study (Li et al. 2011), the modified QuEChERS method was adapted to analyse both of the soil and paddy water samples. The parameters including linearity, linear range, LOQs, accuracy, precision and stability were considered to evaluate the method validation. The result indicated that the analytical method of Pymetrozine was accurate and precise.

Exposure assessment through environmental media
Pymetrozine has only recently replaced organophosphate insecticides in China and previous studies have mainly discussed the dynamic and environmental residuals of the Pymetrozine (Li et al. 2011, Shen et al. 2009Jia et al. 2019, Gong et al. 2019, Kovacova et al. 2013, Yu et al. 2020. However, there are very few studies regarding the exposure of operators and the community. Ingestion of vegetables and fruits is considered the main exposure route of Pymetrozine in previous studies conducted in China (Jia et al. 2019;Gong et al. 2019;Kovacova et al. 2013;Yu et al. 2020). However, there is little study focus on the Pymetrozine exposure from soil and paddy water and its environmental health risk assessment for the agriculture communities in China.
In this study, the soil and paddy water samples collected within 10-20 m of the residents' apartments and two main potential pathways of the exposure, dermal contact and ingestion, were considered.
Developing a conceptual site model (CSM) can assist the process of understanding how human 'receptors' may be exposed to chemicals from relevant environmental sources. The CSM describes the sources of contamination, the pathways by which contaminants may migrate through the various environmental media and the populations that may potentially be exposed. CSMs are particularly important in environmental health risk assessment of contaminated sites and based on these aspects, the conceptual framework was established in Fig. 2.

Calculation of absorbed daily dose (ADD) of Pymetrozine from dermal exposure
The absorbed daily dose (ADD) of Pymetrozine from dermal exposure in one spraying event was estimated by using the following equation: where ADD is the average daily dose via dermal contact; C is the concentration of Pymetrozine in soil or water sample (µg/kg); BW is body weight (kg); SA is the exposed skin area (m 2 ), reported by the Environmental Ministry of (1) ADDdermal = C * SA * SL * ABS BW * 10 −6  (Table S1).

Calculation of absorbed daily dose (ADD ingestion) Pymetrozine from ingestion exposure
ADD of Pymetrozine from ingestion exposure in one spraying event was estimated using the following equation: where ADD ingestion is the average daily dose via ingestion; C is the concentration of Pymetrozine in soil sample (µg/kg); IngR is the ingestion rate for Pymetrozine (US EPA 2000); and BW is body weight (Environmental Ministry of China 2010) (Table S1).

Total acute dermal and ingestion exposure dose of Pymetrozine with communities
In this section, based on the results of the acute ingestion exposure level of Pymetrozine from soil (on the day insecticide spraying, 1, 3, 5, 7, 9, 14 and 21 days after insecticide spraying in one spraying event separately), the acute dermal exposure level of Pymetrozine from soil (on the day of insecticide spraying, 1, 3, 5, 7, 9, 14 and 21 days after insecticide spraying in one spraying event separately) and the acute dermal exposure level of Pymetrozine from paddy water (on the day insecticide spraying, 1, 3, 5, 7, 9 and 14 days after insecticide spraying in one spraying event separately) were calculated, and then sum of the post-application exposure dose to calculate the total acute dermal exposure level of Pymetrozine from soil, the total acute dermal exposure level of Pymetrozine from paddy water and the total acute ingestion exposure level of Pymetrozine from soil separately.

Calculation of lifetime average daily dose (LADD) of Pymetrozine from dermal and ingestion exposure
The lifetime average daily doses (LADD) of Pymetrozine from dermal exposure and ingestion by the communities were estimated using the following equations: where ADD (mg/kg/day) is the sum of dermal absorbed daily dose and the ingestion absorbed daily dose of Pymetrozine of the communities; LADD is the lifetime average daily dose of Pymetrozine; EF is the exposure frequency (number of days per year); there are four spraying times in this study (3) LADDdermal = (ADD(dermal) × EF × ED)∕AT (4) LADDingestion = (ADD(ingestion) × EF × ED)∕AT area and the concentration level of the Pymetrozine in soil was detected from the day insecticide spraying until after 21-day insecticide spraying; and the concentration level of Pymetrozine in paddy water was detected from the day insecticide spraying until after 14-day insecticide spraying; thus, the frequencies of exposure for soil and paddy water were 84 days and 56 days separately. ED is the exposure duration (lifetime years) and the exposure duration for adults is 70 years. AT is the life expectancy in years and the life expectancy for adults is (365*70 day) (Table S1).

Potential environmental health risk characterization
The potential health risks caused by main routes of exposure to chemical contaminants in environment were assessed based on the health risks models of the U.S. EPA (2004).

Non-carcinogenic hazard quotient (HQ)
The non-cancer risks of exposure to Pymetrozine in soil and paddy water are usually characterized by the hazard quotient (HQ), which is the ratio of LADD of the Pymetrozine for each ingestion and dermal exposure pathway to the corresponding reference dose (RFD) expressed in mg/kg/day. Acute and lifetime average daily doses (LADD) of Pymetrozine in soils and paddy water through multiple pathways were calculated using Eqs. (1)-(4), respectively. The reference doses (RFD) were taken from the U.S. Department of Energy's RAIS compilation (U.S. Department of Energy 2000 and 2010). The HQ are calculated as follows (Eq. (5)).
The hazard index (HI) represents the total non-carcinogenic risk for Pymetrozine through different exposure pathways (Table 1).

Carcinogenic risk
The carcinogenic risk (CR) is the incremental probability of an individual developing cancer over a lifetime due to carcinogenic exposure. The carcinogenic risk is evaluated by Eq. (7): The estimated CR is the probability of an individual developing in any type of cancer from lifetime exposure to carcinogenic factors. LADD is the average daily dose of Pymetrozine, and CSF is the cancer slope factor (µg/kg/ day) −1 .
To evaluate the total potential cancer risks (TCR) from different pathways for soil and paddy water, these parameters were calculated using Eq. (8).
CR is the individual carcinogenic risk of every pathway; n is the different pathways that cause cancer risk.

Hazard identification of Pymetrozine
The identification of Pymetrozine as the major hazard to community's health was carried out by using data on registration of pesticide in China, government report, questionnaire and interview and literature reviews, as well as toxicological health investigation.

Pymetrozine formulations used in China
In China, since 2008, because Pymetrozine is being employed as a main substitute for pesticides of high toxicity, there exists a need to properly quantitate the human health risks that result from the use of Pymetrozine in rice paddies (Wu et al. 2017; Jiang Su government report 2017).

Human health effects of Pymetrozine usage in China
Residents are exposed to the residue of pesticides through environmental media such as soil, water and food by different routes of exposure including inhalation, ingestion and dermal contact; and that lead to acute and chronic diseases (Damalas and Eleftherohorinos 2011). From the survey and interview in our study (Table S2), it could be found that most of the farmers use the locally made spraying equipment which does not have appropriate safeguards. As a result of substandard construction of the equipment, cracks and leaks can happen easily during the application. In addition, applicators have either inadequate or no protective clothing, masks and gloves. Furthermore, owing to the lack of proper instruction and training, farmers do not distinguish the harmful pests from the other nonharmful pests and use the incorrect nozzles. The spraying equipment which farmers use is not properly cleaned and handled when they finish the spraying. Therefore, owing to the spills and splashes, direct spray contact or even drift during the pesticide application under the improper way, agriculture workers and residents living around the agriculture land are potentially exposed to pesticides via dermal contact, ingestion and respiratory inhalation (Sugeng et al. 2013).
It was observed that there are many discarded pesticide packaging bags in the study areas. After pesticides are used to target plants, they will go through transfer/migration and degradation in the environment (Tudi et al. 2021). Improper use of pesticide, its management and behaviour also lead to environmental pollution (Connell 2018) including soil, water, air and food contamination. The residues of pesticides from these different environmental media may enter the human body and result in negative impact on human health (Tudi et al. 2021).
Currently, there are very few studies related to the health effects of Pymetrozine in China and other countries. Previous studies indicate that acute toxic effects always occur from within a few minutes to several hours after poisoning by pesticides (Yang and Deng 2007, DEBLEECKER 1995, Pereira et al. 2015, Atabila et al. 2018b. Also, the documented issues indicate that various chronic diseases and disorders sometimes occur after people being exposed to pesticides (Wesseling et al. 1997, URAM 1989, Phung et al. 2012b). Therefore, there may be exposure and potential health effects from Pymetrozine application by the occupational, environmental and dietary routes to both agriculture workers and residents who are living around the agriculture areas.
Potential exposure assessment of Pymetrozine through environmental media

Baseline exposure levels of Pymetrozine through environment with agriculture communities
Soil and paddy water were collected 1 day prior to application, and the concentration levels of Pymetrozine in soil and paddy water were analysed. The Pymetrozine concentration level in soil and paddy water which were collected 1 day prior to application is under the detection line; thus, the exposure baseline of Pymetrozine in the environment was set to be zero.

Potential acute dermal and ingestion exposure levels of Pymetrozine in communities
Based on the concentration level of Pymetrozine in soil and paddy water and the US EPA (2004) exposure assessment method, the potential acute dermal exposure level of Pymetrozine in soil and paddy water and the potential acute ingestion exposure level of Pymetrozine in soil were calculated for each day of each sampling site during one spraying event (day of insecticide spraying, 1, 3, 5, 7, 9, 14 and 21 days after insecticide spraying).
The concentration level of Pymetrozine on the day of insecticide spraying varies in different agriculture lands. The application amount by different farmers, the target areas of the sprayed insecticide and the kind of equipment used by different farmers are different, and these are the main reasons that caused the differences in the initial concentration level of Pymetrozine in the soil and the exposure level of Pymetrozine through the soil (Li 2010). In addition, the previous study also shows that the initial concentration level of Pymetrozine is related to the difference in sampling strategy, the difference in climate and soil characteristic, the density of rice planting and the difference in growth trends (Yang 2011). These are further main reasons for the difference in Pymetrozine acute dermal exposure level and acute ingestion exposure level through soil in different agriculture lands in both Hunan and Guangxi areas.
The potential minimum, mean, 95th percentile and maximum values of the potential acute dermal exposure through soil and paddy water and potential acute ingestion exposure levels through soil for adults in Guangxi and Hunan after Pymetrozine application are plotted in Tables S3, S4 and S5, separately. The result indicates that adults were exposed to Pymetrozine from the day of insecticide spraying until 21 days after insecticide spraying. The potential acute dermal exposure through soil was higher than acute dermal exposure through paddy water in both Guangxi and Hunan areas. The potential acute dermal exposure level through soil and the potential acute dermal exposure level through paddy water were lower than the potential acute ingestion exposure level through soil for adults in both areas separately. Table S3 indicates that the potential acute dermal exposure level for adults through soil in Hunan on the day of Pymetrozine application was increased to 1.2E*10 −6 µg/ kg/day, which was 1.2 E*10 −sixfold higher than the baseline exposure level. The potential exposure level decreased to 0.02 E*10 −6 µg/kg/day after 21 days of insecticide spraying. The potential acute dermal exposure level for adults through soil in Guangxi on the day of Pymetrozine application increased to 1.1 E*10 −6 µg/kg/day, which was 1.1 E*10 −sixfold higher than the baseline exposure level. The potential exposure level decreased to 0.02 E*10 −6 µg/kg/ day after 21 days of insecticide spraying. Table S4 indicates that the potential acute dermal exposure level for adults through paddy water in Hunan on the day of Pymetrozine application increased to 0.5 E*10 −6 µg/ kg/day, which was 0.5 E*10 −sixfold higher than the baseline exposure level. The potential exposure level decreased to 0.04 E*10 −6 µg/kg/day after 14 days of insecticide spraying. The potential acute dermal exposure level for adults through paddy water in Guangxi on the day of Pymetrozine application increased to 0.6 E*10 −6 µg/kg/day, which was 0.6 E*10 −sixfold higher than the baseline exposure level. The potential exposure level decreased to 0.04 E*10 −6 µg/kg/day after 14 days of insecticide spraying. Table S5 indicates that the acute ingestion exposure level for adults through soil in Hunan on the day of Pymetrozine application increased to 1.02 E*10 −4 µg/kg/day, which was 1.02 E*10 −fourfold higher than the baseline exposure level.
The potential exposure level decreased to 1.73 E*10 −6 µg/ kg/day after 21 days of insecticide spraying. The potential exposure level decreased to 4.18 E*10 −6 µg/kg/day after 21 days of insecticide spraying. The potential acute ingestion exposure level for adults through soil in Guangxi on the day of Pymetrozine application increased to 7.64 E*10 −5 µg/ kg/day, which was 7.64 E*10 −fivefold higher than the baseline exposure level. The potential exposure level decreased to 5.439E*10 −5 µg/kg/day after 14 days of insecticide spraying.

Potential total acute exposure of Pymetrozine in communities
There is no significant difference between the total dermal exposure from soil (on the day insecticide spraying, 1, 3, 5, 7, 9, 14 and 21 days after insecticide spraying) and the acute soil dermal exposure on the day insecticide spraying; there is no significant difference between the total dermal exposure from paddy water and the acute dermal exposure from paddy water on the day insecticide spraying; and there is no significant difference between the total ingestion exposure level from soil and the acute ingestion exposure level from soil on the day insecticide spraying for adults in Guangxi and Hunan (Table S6).

Potential lifetime average daily dose (LADD)
Based on the potential total acute dermal exposure levels of Pymetrozine through soil; potential total acute ingestion exposure levels of Pymetrozine through soil; and the potential total acute dermal exposure levels of Pymetrozine through paddy water during the one spraying event, the potential lifetime exposure levels of Pymetrozine in soil and paddy water were calculated for each sampling point. The results of the descriptive analysis are indicated in Table S7. The LADD for Pymetrozine exposure with agriculture communities assumed that the farmers sprayed the same amount of Pymetrozine for every spray event and communities are exposed to Pymetrozine in short-time period in every year.

Dose-response relationship of Pymetrozine based on human and animal data
In the previous section, hazard identification of Pymetrozine among farmers and communities and exposure level of the Pymetrozine were determined. The objectives of this section are to evaluate the dose-response relationships for Pymetrozine with humans and animals. This can be achieved by reviewing the scientific literature for adverse effects of Pymetrozine reported from human epidemiological and animal studies.

Acute toxicity
Previous studies (US EPA 2000) indicate that Pymetrozine has low acute toxicity. It is classified as Toxicity Category III for acute dermal and primary eye irritation studies and Toxicity Category IV for acute oral, acute inhalation and primary dermal studies. It is a slight sensitizer. Table 2 provides a summary of acute tests.  Table 3 summarizes the results of sub-chronic and chronic toxicity, metabolism and dermal penetration studies in animals. These studies indicate that Pymetrozine impacts three major areas in the body, including the liver, the haematopoietic system and the lymphatic system. In addition, from both the sub-chronic and chronic dog studies, it is found that the chemical affects muscle tissue, perhaps secondarily. Pymetrozine has significant effects on tumours in the livers of mice and rats, necrosis of the livers of mice and dogs, hyperplasia in the bile ducts of dogs, anaemia in dogs, atrophy in the thymus of young rats and dogs and myopathy in the muscles of dogs. Hepatocellular hypertrophy is often related to the induction of drug-metabolizing enzymes. The red blood cell effects in rats and mice were not significant (Table 3).

Carcinogenic effects
Based on the study about the male mouse liver benign hepatoma and/or carcinoma, the US EPA (2001) has classified Pymetrozine as a 'likely' human carcinogen.
In the rat reproduction study, systemic/developmental toxicity for the pups was observed at parentally toxic dose levels (parental systemic NOAEL: 1.4 mg/kg/day for males, 1.6 mg/kg/day for females, LOAEL: 13.9 mg/kg/day for males, 16.0 mg/kg/day for females (liver effects in the F0 and F1 males); offspring systemic/developmental NOAEL: 13.9 mg/kg/day for males, 16.0 mg/kg/day for females, LOAEL: 136.9 mg/kg/day for males, 151.6 mg/kg/day for females (decreased pup weight and delay in eye opening in both F1 and F2 litters)). There was no reproductive toxicity at dose levels up to 136.9 mg/kg/day for males and 151.6 mg/kg/day for females.

Neurotoxic effects
In the acute mammalian neurotoxicity study, there was a transient decrease in the body temperature and indications of decreased activity in the FOB and motor activity assessments at a dose level of 125 mg/kg, the lowest dose tested. In the sub-chronic mammalian neurotoxicity study, stereotypy in males and tiptoe gate or walking on toes in females was observed when administered dose levels of 201 mg/kg/ day (males) or 224 mg/kg/day (females). The frequency and magnitude of these effects were low.

Toxicological endpoints for use in human risk assessment
Based on its review of the toxicological data, the Agency selected specific studies (US EPA 2000), endpoints (adverse biological effects), a lowest observed adverse effect level (LOAEL) and several no observed adverse effect levels (NOAELs), modified by several safety (SF) or uncertainty factors (UF), to derive acceptable exposure doses in mg/kg/ day for use in acute and chronic risk assessments. Table 3 lists the studies, endpoints, exposure doses, uncertainty safety factors and exposure profiles that the Agency used in these risk assessments (

Potential environmental risk characterization of Pymetrozine exposure for agriculture communities
The potential cancer risk assessment of Pymetrozine through dermal contact and ingestion exposure routes for adults, as well as the exposure doses of Pymetrozine in relation to adults' potential non-carcinogenic risk through dermal contact and ingestion exposure routes in Hunan and Guangxi, was calculated using the parameters of the US EPA health risk assessment method in this study.
Since there are no human studies about the Pymetrozine, to make summaries derived from the results of sub-chronic and chronic toxicity, metabolism and dermal penetration studies in animals, these studies indicate that Pymetrozine impacts on three major organs in the body including liver, haematopoietic system and lymphatic system. In addition, from both sub-chronic and chronic studies from dogs, it is found that this chemical affects muscle tissue. Pymetrozine has been reported that it has significant adverse health effects on mice, rats and dogs (US EPA 2000). For example, hepatocellular hypertrophy is related to induction of drug-metabolizing enzymes (USEPA 2010). The EPA also classifies Pymetrozine as a possible human carcinogen (USEPA 2010).
According to the available slope factors discussed by the US EPA (2010), dermal contact and ingestion were involved in the risk estimation of Pymetrozine. The cancer slop factor is 0.0019 mg/kg. The value of the chronic populationadjusted dose of 0.0038 mg/kg/day from Pymetrozine for general population was used to calculate the non-cancer risk for lifetime exposure dose. The value of the acute population-adjusted dose of 0.42 mg/kg from Pymetrozine for general population was used to calculate the non-cancer risk for acute exposure dose.

Potential cancer risk
The distribution of potential cancer risk is presented in Fig. 3 and Table S8. The potential cancer risk of dermal contact through soil for adults in both areas was slightly higher than the cancer risk of dermal contact through paddy water. The potential cancer risk of dermal contact through soil for adults in both areas was significantly lower than the potential cancer risk of ingestion through soil in both areas.
In general, the minimum, average, 95th percentile and maximum of the potential cancer risk of dermal contact through soil and water for adults; the minimum, average, 95th percentile and maximum of the potential cancer risk of ingestion through soil for adults; and the potential total cancer risk through soil and paddy water in both areas were less than 1*10 −6 , within the acceptable level.

Potential non-cancer risk from lifetime exposure dose and acute exposure dose
The distribution of the potential non-cancer risk from both lifetime and acute exposure dose is presented in Fig. 4 and Table S9, and Fig. 5 and Table S10, respectively.
The results indicate that the minimum, average, 95th percentile and maximum of the potential non-cancer risk from both of lifetime and acute dermal contact exposure dose through soils and paddy water and the minimum, average, 95th percentile and maximum of the potential non-cancer Long-term (dermal and inhalation) The current use pattern does not indicate a concern for long-term dermal or inhalation exposure Potential, therefore, these risk assessments are NOT required Cancer Cancer Classification: 'Likely to be carcinogen to humans' (Q* of 0.0119 mg/kg/day) risk from the both lifetime and acute ingestion exposure dose through soil for adult in two study areas were all below 1. The minimum, average, 95th percentile and maximum of the potential non-cancer risk from both lifetime and acute dermal contact exposure dose through soils and paddy water and the minimum, average, 95th percentile and maximum of the potential non-cancer risk from both lifetime and acute ingestion exposure dose through soil for adults of these two areas were all below 1. The potential total non-cancer risks from both lifetime exposure dose and acute exposure dose through paddy water and soil in these two areas were less than 1. Based on the US EPA (2010) report, if HI < 1, the exposed individual was unlikely to obviously experience adverse health effects, and vice versa. Thus, the potential non-cancer risks from Pymetrozine through both soil and paddy water were relatively low, indicating an acceptable risk level.
The results also indicated that the potential non-cancer risks from both lifetime and acute dermal contact dose through soil for adults in both areas were higher than potential non-cancer risk from both lifetime and acute dermal contact dose through paddy water. The potential non-cancer risks from both lifetime and acute dermal contact exposure dose through soil for adults in both areas were lower than the potential non-cancer risk from both lifetime and acute ingestion exposure dose through soil in both areas and these results are consistent with the previous results (Bhandari et al. 2020;Landrigan and Goldman 2011;Pan et al. 2018;Yadav et al. 2016).

Sensitivity analysis
The percentage contribution of exposure pathways is used to determine which variables and pathways most strongly influence the potential risk estimate (Tudi et al. 2019). Percentage contribution of exposure pathways to potential total risk is calculated by the following equation: The result indicated that in both areas, the Hazard index from ingestion exposure dose from Pymetrozine through soil took up the highest percentage in the potential total cancer risk (98.46%) and the potential total non-cancer risk (98.28%), followed by the potential risk index of dermal contact exposure dose from Pymetrozine through soil and then the potential risk index of dermal contact exposure dose from Pymetrozine through paddy water (Table 1).

Uncertainty analysis
Some limitations need to refer. Firstly, the concentrations of pesticides across the different rice-growing seasons are different (Zhu et al. 2017), but seasonal variation of pesticides was not investigated. Thus, the exposure and potential risk level of Pymetrozine may not present the real situation. Secondly, CSF and RFD were treated as constants for the population investigated, but they can differ from one person to another (Phung et al. 2012a(Phung et al. , 2013. In this study, each input parameter and exposure factors were treated as a point estimate with no classification. The traditional way of managing uncertainty and variability in risk assessment has been through application of safety factors or use of conservative assumptions, which can lead to inaccurate estimations (ATABILA 2017), as a result of individual variabilities inherent in these exposure factors, which must be considered in risk assessments (Sadler et al. 2016;Tudi et al. 2019). Thirdly, the concentrations of the parent material of Pymetrozine found in the water and soil samples were considered the main hazardous substance that residents exposed to, while the metabolism products of Pymetrozine in both soil and paddy water were not considered in this study, which could also pose risk to humans (US EPA 2010). In addition, we only considered dermal contact and ingestion, and did not consider respiratory intake, while during our field investigation, most farmers did not wear normal masks during the Pymetrozine application. Thus, there might be underestimation on the levels of both cancer and non-cancer risk assessment, in particular for the farmers who do the spraying.

Conclusions
The potential acute dermal exposure levels and the acute ingestion exposure of Pymetrozine through soil and paddy water peaked at the day of insecticide application and returned to the normal range approximately 21 days after insecticide application. The potential total dermal exposure and ingestions exposure levels of Pymetrozine through soil and paddy water were slightly different from the potential acute dermal exposure levels on the day of insecticide spraying due to the small contribution after 1-, 3-, 5-, 7-, 9-, 14and 21-day exposure levels to the ADDT. For both areas, the main exposure routes for potential carcinogenic and potential non-carcinogenic risks of Pymetrozine were the soil ingestion, followed by the soil dermal contact and then the paddy water dermal contact. In summary, the results of potential risk characterization indicate that agriculture communities have a relatively low potential risk of adverse health effects from the Pymetrozine application in rice-growing areas.