Persistent organic pollutants in smokeless tobacco from Uzbekistan, levels patterns and risk assessment

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This study provides the first comprehensive evaluation of persistent organic pollutants (POPs) in SLT across six key regions of Uzbekistan, focusing on both their presence and associated health risks. Methods Twenty-five SLT samples were systematically collected from Tashkent City, Tashkent Region, Jizzakh, Samarkand, Fergana, and Kashkadarya. Using gas chromatography–mass spectrometry, concentrations of organochlorine pesticides—including hexachlorocyclohexane isomers, endosulfan, DDT, hexachlorobenzene, toxaphene, dieldrin, and mirex—were quantified. Results The study documented marked regional variation in SLT contamination, with Jizzakh and Tashkent displaying notably high levels of endosulfan (endosulfan-1 up to 17.92 ng/g, endosulfan-2 up to 27.34 ng/g), while Fergana showed lower overall contamination. The persistence of legacy pesticides such as DDT and hexachlorobenzene underscores ongoing environmental contamination and inadequate regulatory enforcement. Human exposure estimates indicated that hazard quotients and cumulative hazard indices for individual POPs remained below international safety thresholds under modeled scenarios; nonetheless, the frequent detection of highly toxic and banned substances raises valid public health concerns. Conclusion These results highlight an urgent need for the development and enforcement of systematic safety standards, routine surveillance, and targeted toxicological risk assessments for SLT products. Regulatory intervention is essential to mitigate chronic health risks among SLT users and reduce the long-term burden of pesticide-related diseases in Uzbekistan. Smokeless tobacco Uzbekistan Persistent organic pollutants Hazard index Public Health Figures Figure 1 Background Smokeless tobacco (SLT) products represent a significant global public health concern, with nasvay (also known as naswar or nas) being particularly prevalent in Central Asian countries including Uzbekistan. This traditional oral tobacco product, consumed by placing it between the gum and cheek, consists of finely ground tobacco leaves mixed with slaked lime (calcium hydroxide) to enhance nicotine absorption, along with plant ash, vegetable oils, and various flavorings. Production occurs in largely unregulated cottage industry settings with variable formulations [ 1 , 2 ]. The prevalence of nasvay use in Central Asia is substantial. In Uzbekistan, 22.3% of adult men use nasvay compared to 19.6% who smoke cigarettes, with nearly 50% of smokers consuming nasvay daily. Recent studies confirm significant health risks, including a 2.56-fold increased risk of coronary artery disease and elevated oxidative stress markers in users [ 3 – 5 ]. The widespread consumption of nasvay raises critical concerns regarding exposure to persistent organic pollutants (POPs), particularly organochlorine pesticides (OCPs). These compounds resist degradation, bioaccumulate in fatty tissues, and exhibit environmental persistence with half-lives spanning years to decades. Tobacco cultivation is recognized as pesticide-intensive due to crop susceptibility to pests and diseases. Unlike food crops, tobacco leaves used in nasvay are not washed or processed, potentially resulting in direct human exposure to hazardous chemicals [ 6 – 9 ]. Recent research demonstrates significant pesticide contamination in tobacco products. Studies from 2024–2025 found organochlorine pesticides in fruit-flavored and regular tobacco with detection frequencies of 46–82%, with hexachlorocyclohexane isomers being predominant. Another 2024 study revealed that approximately 37% of pesticide residues are released into smoke during consumption. Evidence shows tobacco fields contribute to diffuse pesticide pollution, with sediment contamination levels ranging from 32.9–98.8 ng/g in tobacco-growing regions [ 6 , 9 , 10 ]. The health implications of POP exposure are well-documented and include increased cancer risk, immune suppression, neurobehavioral effects, endocrine disruption, cardiovascular disease, and diabetes. Recent epidemiological studies using mixture analysis methods confirm associations between POPs and various health outcomes, including metabolic disorders and depression. The International Agency for Research on Cancer classifies several organochlorine pesticides as carcinogenic or possibly carcinogenic to humans [ 7 , 8 , 11 – 14 ]. Despite significant public health implications, research on pesticide contamination in nasvay remains limited. The unregulated nature of production and absence of safety standards in Central Asian countries create substantial knowledge gaps. Current tobacco control policies in Uzbekistan mandate health warnings only on cigarettes, not smokeless tobacco products, highlighting urgent regulatory needs [ 15 ]. Given the substantial health risks associated with POPs and widespread nasvay consumption in Uzbekistan, systematic investigation of pesticide contamination is essential. This study addresses critical knowledge gaps by providing the first comprehensive assessment of organochlorine pesticide contamination in nasvay products across multiple regions of Uzbekistan, contributing essential data for evidence-based public health decision-making and regulatory development. Materials and methods 2.1. Sample collection The SLT products were purchased at retail stores from six different regions of Uzbekistan – the capital – Tashkent city, Tashkent region, Jizzakh region, Samarkand region, Fergana region and Kashkadarya region in November 2023 (Fig. 1 ). For sample collection, we employed a convenience sampling method, and investigators visited markets and picked up 25 SLT samples from major markets. All samples were transported and analyzed in the Laboratory of Health and Environmental Sciences, Graduate School of Medicine, Kyoto University, Japan. Source: WHO GIS Centre for health, DNA/DDI. 2.2. Chemicals The 13 C 12 -2,3,3 '5,5'-Pentachlorobiphenyl (CB-111, CIL) was used as an internal standard. Expanded POPs Pesticides Calibration Solutions CS1-CS6 (ES-5464), Expanded POPs Pesticides Cleanup Spike (ES-5465), syn-DP, anti-DP, POPs Toxaphene Calibration Solutions with PCB Syringe (ES-5351), and octachlorostyrene (ULM-4559) were used as standard solutions for quantification of pesticides. The chemicals were purchased from Cambridge Isotope Laboratories. Hexane, nonane, and dichloromethane used for pesticide residue testing were from Kanto Chemical Co., Ltd. Floridil used in the sample preparation was manufactured by Wako Pure Chemicals. 2.3. Determination of pesticides Our study followed previous analytical methods. A total of 24 pesticides were measured: Aldrin, dieldrin, endrin, dichlorodiphenyltrichloroethanes (p,p'-Dichlorodiphenyltrichloroethanep – p'-DDT; p,p'-Dichlorodiphenyldichloroethylene – p,p'-DDE; p,p'-Dichlorodiphenyldichloroethane – p,p'-DDD), hexachlorocyclohexane (alpha-HCH, beta-HCH, gamma-HCH, delta-HCH), chlordanes (cis-CHL, trans-CHL, oxychlordane, cis-nonachlor, trans-nonachlor), pentachlorobenzene (PeCB), hexachlorobenzene (HCB), heptachlor, cis-heptachlor epoxide (HCE), endosulfans (1, 2), toxaphenes (#26, #50), and mirex [ 16 , 17 ]. One to two grams of SLT sample was placed into a 15 mL polypropylene tube with 5 mL of acetone. The tube was shaken for 1 hour, then centrifuged for 1 minute at 3000 rpm. The supernatant was transferred to a new tube, 5 mL of acetone was added, the tube was shaken for 1 hour and then centrifuged for 1 minute at 3000 rpm. The supernatant was transferred to another polypropylene tube. The extract was then diluted to 12 mL with acetone. Five milliliters of the sample extract was aliquoted into a polypropylene centrifuge tube, and 500 pg of carbon-13 labelled standard of organochlorine pesticides was added and stirred. The organic layer was then concentrated using an air evaporator. The crude extract was diluted to five mL with hexane, mixed with distilled water, and centrifuged after vortex agitation. Next, five mL of the organic layer was passed through a four-gram activated Florisil column and eluted with 20 mL of a 10% dichloromethane/hexane solution. The eluate was concentrated to approximately 1 mL using a rotary evaporator, and 0.1 mL of nonane was added. The final concentrate was labelled with 10 ng of carbon-13 labelled CB-111 and subjected to GC/MS analysis. 2.4. Instruments and quantification Gas chromatography-mass spectrometry (GC/MS) was used to measure organochlorine pesticides in tobacco samples. The analysis was carried out with a 6890GC and 5973MSD instrument (Agilent Technologies, USA). For separation, a capillary HP-5MS column was employed, measuring 30 meters in length, 0.25 mm in diameter, and 0.25 µm in film thickness. Each sample injection was 5 µL, at an inlet temperature of 230°C. The pulsed splitless injection mode was set at 30 psi for 1 minute for optimal compound transfer. The GC oven started at 70°C for 1 minute, raised by 30°C per minute, and held at 280°C for 3 minutes. The lowest signal detectable was set at three times the noise level, defining both the instrument and method detection limits, since no signal was detected in blank samples. Blank samples were also included throughout sample preparation to check for contamination. 2.5. Exposure Assessment To evaluate exposure risks, Hazard Quotient (HQ) and Hazard Index (HI) were calculated for each pesticide with established reference values from WHO or the U.S. EPA. Specific data on oral absorption of these pesticides through smokeless tobacco are lacking. For the exposure assessment, we assumed that the oral mucosal absorption of OCPs from nasvay could plausibly range from 60% to 100%. The lower bound (60%) was informed by studies on khat chewing, which estimated about 60% absorption from the oral mucosa. Equations: $$\:HQ=EDI/RfD$$ $$\:HI=\sum\:HQ$$ Where: HQ: Hazard Quotient EDI: Estimated Daily Intake (ng/kg body weight/day) RfD: Reference Dose (ng/kg bw/day) HI: Hazard Index Estimated Daily Intake (EDI) was calculated as follows: $$\:EDI=Average\:concentration\:(ng/g)\times\:4g\times\:\text{f}\times\:\:\text{a}\text{b}\text{s}\text{o}\text{r}\text{p}\text{t}\text{i}\text{o}\text{n}\:\text{r}\text{a}\text{t}\text{e}÷60\text{k}\text{g}\:\text{b}\text{o}\text{d}\text{y}\:\text{w}\text{e}\text{i}\text{g}\text{h}\text{t}$$ Where: 4 g = Average mass of a single portion of nasvay (based on typical usage range of 3–5 g) f = Frequency of daily use (3 times/day for regular users and 10 times/day for heavy users) Absorption rate = Absorption rate of OCPs via the oral mucosa according to the supposed scenarios (60% and 100%) 60 kg = Assumed average adult body weight Thus, daily intake of pesticides was estimated for different user patterns, providing a range of potential exposures under realistic and extreme conditions. These assumptions reflect typical reports from users in Central Asia and were necessary given the lack of direct data on OCP absorption from smokeless tobacco. 2.6. Statistical analysis The normality of the continuous variables was evaluated using the Shapiro–Wilk test. The variables reported as a mean with 95% confidence intervals (95% CI). Differences in chemical concentrations across geographical regions were assessed using the Kruskal-Wallis test, followed by post-hoc pairwise comparisons with the Steel-Dwass method. All analyses were performed using JMP statistical software (SAS Institute Inc., version 18.0), with statistical significance defined at an α level of 0.05. Results Analysis of 25 nasvay samples collected from Tashkent City, Tashkent Region, Jizzakh, Samarkand, Fergana, and Kashkadarya showed distinct differences in pesticide contamination between regions Table 1 . The investigation identified several persistent organic pollutants in the samples: hexachlorocyclohexane isomers (α-HCH, β-HCH, γ-HCH, δ-HCH), DDT and its breakdown products (pp-DDE, pp-DDD), chlordane isomers (trans-chlordane, cis-chlordane), two types of endosulfan (endosulfan-1 and endosulfan-2), as well as mirex, dieldrin, and hexachlorobenzene (HCB). For HCH isomers, β-HCH was most concentrated in Tashkent City (1.88 ng/g; 95% CI: 0.01 to 6.74) and Tashkent Region (1.76 ng/g; 95% CI: 0.65 to 2.87). γ-HCH was highest in Jizzakh (0.39 ng/g; 95% CI: 0.08 to 0.87), while α-HCH peaked in Kashkadarya (5.89 ng/g), implying location-specific pesticide use. HCB was much higher in Samarkand (1.64 ng/g) than elsewhere (P = 0.003), which is concerning because HCB is a carcinogen and is environmentally persistent. Endosulfan-2 was also at very high levels in Tashkent Region (27.34 ng/g), Tashkent City (24.42 ng/g), and Kashkadarya (23.24 ng/g) (P = 0.002). Endosulfan-1 was high in Jizzakh (17.92 ng/g; 95% CI: 3.44 to 63.08) and Samarkand (6.04 ng/g; P = 0.037). These results matter because endosulfan is banned for its toxic health effects. DDT, though banned globally, was found in all regions, with the highest pp-DDT concentration in Tashkent Region (0.5 ng/g; 95% CI: 0.26 to 0.73). Trans-chlordane was most notable in Jizzakh (0.92 ng/g; P = 0.008). Dieldrin was highest in Tashkent Region (4.66 ng/g; 95% CI: 0.33 to 8.98) and Tashkent City (3.76 ng/g; 95% CI: 2.32 to 5.21) but had no significant regional differences. Other detected pollutants included Toxaphene-P26, highest in Jizzakh (17.62 ng/g), though the difference versus other regions was not significant. Mirex levels were low everywhere, from 0.08 ng/g in Samarkand to 0.18 ng/g in Tashkent City. Health risk assessment showed individual pesticide hazard quotients below 1 in all exposure scenarios (Tables 2 and 3 ). The highest HQs were toxaphene (0.206), aldrin/dieldrin (0.073), and endosulfan (0.054). Total hazard index (HI) didn’t exceed 0.294, so risks appear limited, but may be underestimated because these calculations exclude dietary exposure, cancer risks, and might be affected by nasvay’s alkaline pH. Overall, Tashkent City, Tashkent Region, and Jizzakh had the highest contamination levels, while Fergana had lower pesticide burdens. Discussion This study provides the first comprehensive assessment of organochlorine pesticide contamination in nasvay products across six regions of Uzbekistan. The findings reveal significant public health concerns and highlight critical gaps in regulatory oversight of smokeless tobacco products. The widespread detection of multiple banned persistent organic pollutants indicates systematic contamination that requires immediate intervention [ 18 – 20 ]. The regional variations in pesticide contamination reflect complex interactions between historical agricultural practices, industrial activities, and environmental persistence. The elevated concentrations of β-HCH in Tashkent City and Region, along with high γ-HCH levels in Jizzakh, suggest differential exposure patterns related to past pesticide use and environmental degradation processes. The significant variation in HCB contamination across regions, with Samarkand showing the highest levels, may indicate localized industrial sources or specific agricultural practices. HCB is particularly concerning given its classification as a known human carcinogen and exceptional environmental persistence [ 21 – 24 ]. The detection of endosulfan at exceptionally high concentrations represents the most alarming finding of this study. With levels reaching 27.34 ng/g in Tashkent Region, these concentrations are particularly concerning given endosulfan's well-documented neurotoxic, carcinogenic, and endocrine-disrupting properties. Endosulfan exposure causes central nervous system hyperstimulation through inhibition of calcium and magnesium ATPase and antagonism of chloride transport in GABA receptor complexes. Animal studies demonstrate that endosulfan exposure results in dose-dependent reductions in neurite length, synaptic formation, and neuronal viability, particularly affecting cortical neurons during critical developmental periods. Human exposure has been associated with convulsions, multiorgan damage, and increased cancer risk [ 25 , 26 ]. The continued presence of DDT and its metabolites across all regions, despite decades-long international bans, demonstrates the environmental persistence of organochlorine compounds and ongoing contamination sources. Epidemiological studies have established associations between organochlorine pesticide exposure and increased cancer risk, particularly for hormone-related cancers including breast and prostate cancers. Recent biomonitoring studies in cancer patients showed that exposure to organochlorine pesticides, including DDT and endosulfan, significantly reduced survival time and increased mortality risk [ 27 – 29 ]. Tobacco cultivation is inherently pesticide-intensive due to crop susceptibility to pests and diseases, and unlike food crops, tobacco leaves are not washed or processed before consumption. Studies on tobacco farmers demonstrate high rates of pesticide poisoning, with 55% showing clinically significant depression of plasma cholinesterase levels, indicating acute exposure. The combination of high pesticide use and lack of post-harvest processing makes smokeless tobacco products particularly vulnerable to contamination [ 30 , 31 ]. While our risk assessment showed hazard quotients below threshold levels, several factors suggest potential underestimation of actual health risks. First, the assessment focused solely on non-carcinogenic effects and did not adequately address cancer risks from known carcinogens like HCB, DDT, and dieldrin. Second, the alkaline pH of nasvay may enhance absorption of toxic compounds through damaged oral mucosa. Third, cumulative exposure from dietary and environmental sources was not considered. Recent studies demonstrate that cancer risk from heavy metals in smokeless tobacco products often exceeds acceptable limits by 100 − 10,000 times [ 28 , 32 – 35 ]. The widespread contamination of nasvay with multiple banned pesticides poses significant health risks to users. Approximately 22.3% of adult men in Uzbekistan use nasvay, representing substantial population exposure. Organochlorine pesticides are associated with various cancers, neurological disorders, endocrine disruption, and reproductive toxicity. The International Agency for Research on Cancer has concluded that smokeless tobacco causes cancers of the oral cavity, esophagus, and pancreas, and pesticide contamination may further increase these risks [ 19 , 36 , 37 ]. Current tobacco control policies in Uzbekistan mandate health warnings only on cigarette packaging, leaving smokeless tobacco products largely unregulated. The absence of safety standards, routine monitoring, and enforcement mechanisms allows contaminated products to reach consumers. Comprehensive regulatory intervention is urgently needed, including establishment of maximum allowable pesticide residue limits, mandatory testing protocols, and strict enforcement measures. Several limitations of the study should be acknowledged. The sample size of 25 products may not fully represent contamination levels across all nasvay varieties and regions in Uzbekistan. The study focused on pesticide concentrations without conducting long-term health impact assessments on consumers. Additionally, exposure assessment relied on assumptions about absorption rates due to lack of compound-specific data for oral mucosal absorption of organochlorine pesticides from smokeless tobacco products [ 38 , 39 ]. Future studies should include larger-scale surveillance to confirm contamination trends, longitudinal health impact assessments among nasvay users, and investigation of contamination sources in the tobacco supply chain. Research on biomarkers of organochlorine pesticide exposure in nasvay users would provide valuable data for risk assessment and regulatory decision-making [ 40 – 42 ]. Strength and Limitation Our study has several limitations. The strength of our research is the uniqueness of these results is he study introduces critical evidence for health policymakers in Uzbekistan, offering data-driven recommendations to regulate pesticide use in SLT products and enhance consumer protection. By highlighting contamination risks and exposure levels, this research has the potential to influence tobacco control policies, enforcement measures, and public awareness campaigns. The findings can serve as a foundation for future studies, encouraging further epidemiological research on the health effects of pesticide exposure from SLT consumption. The limitation is the study may not cover all variations of nasvay available in different regions of Uzbekistan. The study included 25 samples, which may not fully represent the contamination levels across the entire country. Larger-scale surveillance is needed to confirm trends. The research focuses on pesticide concentration levels, but it does not provide long-term health impact assessments on consumers of SLT. Conclusion This study demonstrates widespread contamination of nasvay with multiple persistent organic pollutants, including internationally banned pesticides with severe health effects. The findings provide critical evidence for policymakers to implement comprehensive regulatory measures, establish safety standards, and protect public health. Given the documented health risks and substantial user population, immediate action is required to address this significant public health threat. Table 1 Regional mean concentrations and 95% confidence intervals (95%CI) of organochlorine pesticide residues detected in smokeless tobacco (nasvay) samples Tashkent city (n = 5) Tashkent region (n = 5) Jizzakh region (n = 3) Samarkand city (n = 1) Fergana region (n = 5) Kashkadarya region (n = 6) P-value Compound Mean with 95% CI Alpha-HCH 0.74 (0.62–0.87) 0.61 (0.40–0.82) 0.91 (0.3–2.56) 0.33 1.6 (0.27–4.59) 0.53 (0.27–0.80) 0.54 Beta-HCH 1.88 (0.01–6.74) 1.76 (0.65–2.87) 1.05 (0.03–2.06) 0.879 0.86 (0.34–1.39) 0.66 (0.41–0.92) 0.15 Gamma-HCH 0.06 (0.04–0.08) 0.08 (0.04–0.13) 0.39 (0.08–0.87 0.11 0.09 (0.02–0.16) 0.15 (0.05–0.24) 0.09 Delta-HCH 0.1 (0.03–0.53) 0.09 0.27 (0.06–0.61) 0.11 0.07 (0.01–0.13) 0.06 (0.02–0.10) 0.11 Hexachlorobenzene 0.19 (0.15–0.24) 0.21 (0.09–0.33) 0.52 (0.22–0.82) 1.64 0.37 (0.29–0.46) 0.51 (0.16–0.87) < 0.01 Dieldrin 3.76 (2.32–5.21) 4.66 (0.33–8.98) 2.97 (1.61–4.33) 3.53 2.19 (1.65–2.72) 2.78 (1.66–3.94) 0.10 Endrin 1.14 (0.75–1.54) 1.01 (0.63–1.39) 1.25 (0.49–2.99) 0.97 1 (0.23–1.76) 0.84 (0.39–1.29) 0.76 Trans-Chlordane 0.1 (0.05–0.16) 0.08 (0.03–0.13) 0.92 (0.01–3.70) 0.17 0.16 (0.08–0.24) 0.11 (0.08–0.15) < 0.01 pp-DDT 0.32 (0.18–0.46) 0.5 (0.26–0.73) 0.27 (0.14–0.41) 0.35 0.27 (0.07–0.46) 0.36 (0.26–0.47) 0.19 Endosulfan 1 2.17 (1.03–3.21) 4.8 (0.10–9.70) 17.92 (3.44–63.08) 6.04 4.26 (3.02–5.50) 2.24 (1.06–3.43) 0.03 Endosulfan 2 24.42 (11.92–36.93) 27.34 (20.48–34.20) 9.4 (3.72–22.60) 15.6 9.01 (5.52–12.49) 23.24 (14.87–31.60) < 0.01 Toxphene-P26 7.5 (2.97–12.02) 8.05 (6.65–9.46) 17.62 (10.13–39.48) 7.28 12.44 (3.35–21.53) 8.76 (5.09–12.42 0.16 Mirex 0.18 (0.05–0.31) 0.13 (0.05–0.21) 0.14 (0.14–0.30) 0.08 0.1 (0.00-0.19) 0.12 (0.07–0.17) 0.50 HCH = hexachlorocyclohexane isomer, DDT = dichlorodiphenyltrichloroethane, CI = confidence interval. Statistical comparison performed with Kruskal-Wallis test; P-value indicates significance across regions Table 2 Regulatory thresholds and pesticide contamination levels for risk evaluation Chemical compound Reference Dose (RfD)* (mg/kg/day) Mean concentration (ng/g) Peak concentration (ng/g) Gamma-HCH (Lindane) 0.005 0.13 0.61 Hexachlorobenzene (HCB) 0.0006 0.42 1.46 Dichlorodiphenyltrichloroethane (DDT) 0.01 0.62 1.41 Chlordane 0.0005 0.33 2.64 Endosulfan 0.006 24.43 48.58 Mirex 0.0002 0.10 0.35 Toxaphene 0.00009 10.39 27.81 Aldrin and Dieldrin 0.0001 3.41 10.99 Heptachlor and heptachlor epoxide 0.0001 0.15 0.44 *RfD represents the reference dose established by regulatory authorities for daily exposure thresholds. Table 3 Estimated intake (ng/day) of chlorinated POPs from nasvay in Uzbekistan Scenario 1 (absorption ratio 60%) Scenario 2 (absorption ratio 100%) EDI Av. (ng/kg/d) EDI Max (ng/kg/d) HQ Av. HQ Max EDI Av. (ng/kg/d) EDI Max (ng/kg/d) HQ Av. HQ Max Ordinary users (3 times/day) Gamma-HCH (Lindane) 0.015 0.074 0.0000 0.000015 0.025 0.123 0.000005 0.000025 HCB 0.051 0.176 0.0001 0.000293 0.084 0.293 0.00014 0.000488 DDT 0.074 0.169 0.0000 0.000017 0.123 0.281 0.000012 0.000028 Chlordane 0.04 0.317 0.0001 0.000634 0.066 0.528 0.000132 0.001056 Endosulfan 2.932 5.829 0.0005 0.000972 4.886 9.715 0.000814 0.001619 Mirex 0.012 0.042 0.0001 0.000211 0.019 0.07 0.000097 0.000352 Toxaphene 1.246 3.337 0.0138 0.037076 2.077 5.561 0.023082 0.061794 Aldrin and dieldrin 0.409 1.319 0.0041 0.01319 0.682 2.198 0.006816 0.021984 Heptachlor and heptachlor epoxide 0.018 0.053 0.0002 0.00053 0.031 0.088 0.000307 0.000883 HI 0.019 0.053 0.031 0.088 Heavy users (10 times/day) Gamma-HCH (Lindane) 0.0505331 0.245 0.00001 0.000049 0.084 0.409 0.000017 0.000082 HCB 0.1685596 0.585 0.00028 0.000976 0.281 0.976 0.000468 0.001626 DDT 0.2467208 0.563 2.5E-05 0.000056 0.411 0.938 0.000041 0.000094 Chlordane 0.1317658 1.056 0.00026 0.002112 0.22 1.76 0.000439 0.00352 Endosulfan 9.7717116 19.431 0.00163 0.003238 16.286 32.385 0.002714 0.005397 Mirex 0.0386045 0.141 0.00019 0.000704 0.064 0.235 0.000322 0.001174 Toxaphene 4.154751 11.123 0.04616 0.123588 6.925 18.538 0.07694 0.20598 Aldrin and dieldrin 1.363265 4.397 0.01363 0.043967 2.272 7.328 0.022721 0.073279 Heptachlor and heptachlor epoxide 0.061362 0.177 0.00061 0.001765 0.102 0.294 0.001023 0.002942 HI 0.063 0.176 0.105 0.294 *HI - Hazard Index Abbreviations SLT smokeless tobacco POP persistent organic pollutant OCP particularly organochlorine pesticides EDI estimated daily intake HQ hazard quotient HI hazard index RfD reference dose Declarations Acknowledgements We thank the laboratory team at Kyoto University and colleagues at the Institute of Health and Strategic Development, Uzbekistan, for field and logistical support. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Availability of data and materials The datasets are available from the corresponding author on reasonable request. Authors’ contributions JJR and KH conceived the study. MUK, MBB, SSU, YRM and RSM conducted field sampling. JJR, ZL and MF performed GC/MS analyses. JJR, MUK and ZL carried out statistical and risk analyses. JJR drafted the manuscript; KH supervised and critically revised it. All authors read and approved the final manuscript. Ethics approval and consent to participate. Not applicable. This study analyzed retail smokeless tobacco products purchased in public markets and involved no human participants, personal data, or animals. References Stepanov I, Abrams J, Jain V, Walter K, Kittner DL. Variations of toxic and carcinogenic constituents in nasvai: Call for systematic research and regulation. 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00:26:55","extension":"html","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":134594,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8095518/v1/d62346ba3c54b423aa4d89c8.html"},{"id":97485573,"identity":"721fc4c3-03f7-411b-b00c-27ecdea2a095","added_by":"auto","created_at":"2025-12-05 00:26:55","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":385072,"visible":true,"origin":"","legend":"\u003cp\u003eMap of Uzbekistan showing the locations of six regions where SLT products were purchased.\u003c/p\u003e\n\u003cp\u003eSource: WHO GIS Centre for health, DNA/DDI.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8095518/v1/0693d92f30cb3f289d18a8db.png"},{"id":104250642,"identity":"34461a6e-7a81-4595-bbf4-8846a49b7c81","added_by":"auto","created_at":"2026-03-09 16:03:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1286288,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8095518/v1/0e653d20-4e69-4055-9eae-781fda181315.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Persistent organic pollutants in smokeless tobacco from Uzbekistan, levels patterns and risk assessment","fulltext":[{"header":"Background","content":"\u003cp\u003eSmokeless tobacco (SLT) products represent a significant global public health concern, with nasvay (also known as naswar or nas) being particularly prevalent in Central Asian countries including Uzbekistan. This traditional oral tobacco product, consumed by placing it between the gum and cheek, consists of finely ground tobacco leaves mixed with slaked lime (calcium hydroxide) to enhance nicotine absorption, along with plant ash, vegetable oils, and various flavorings. Production occurs in largely unregulated cottage industry settings with variable formulations [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe prevalence of nasvay use in Central Asia is substantial. In Uzbekistan, 22.3% of adult men use nasvay compared to 19.6% who smoke cigarettes, with nearly 50% of smokers consuming nasvay daily. Recent studies confirm significant health risks, including a 2.56-fold increased risk of coronary artery disease and elevated oxidative stress markers in users [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe widespread consumption of nasvay raises critical concerns regarding exposure to persistent organic pollutants (POPs), particularly organochlorine pesticides (OCPs). These compounds resist degradation, bioaccumulate in fatty tissues, and exhibit environmental persistence with half-lives spanning years to decades. Tobacco cultivation is recognized as pesticide-intensive due to crop susceptibility to pests and diseases. Unlike food crops, tobacco leaves used in nasvay are not washed or processed, potentially resulting in direct human exposure to hazardous chemicals [\u003cspan additionalcitationids=\"CR7 CR8\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eRecent research demonstrates significant pesticide contamination in tobacco products. Studies from 2024\u0026ndash;2025 found organochlorine pesticides in fruit-flavored and regular tobacco with detection frequencies of 46\u0026ndash;82%, with hexachlorocyclohexane isomers being predominant. Another 2024 study revealed that approximately 37% of pesticide residues are released into smoke during consumption. Evidence shows tobacco fields contribute to diffuse pesticide pollution, with sediment contamination levels ranging from 32.9\u0026ndash;98.8 ng/g in tobacco-growing regions [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe health implications of POP exposure are well-documented and include increased cancer risk, immune suppression, neurobehavioral effects, endocrine disruption, cardiovascular disease, and diabetes. Recent epidemiological studies using mixture analysis methods confirm associations between POPs and various health outcomes, including metabolic disorders and depression. The International Agency for Research on Cancer classifies several organochlorine pesticides as carcinogenic or possibly carcinogenic to humans [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eDespite significant public health implications, research on pesticide contamination in nasvay remains limited. The unregulated nature of production and absence of safety standards in Central Asian countries create substantial knowledge gaps. Current tobacco control policies in Uzbekistan mandate health warnings only on cigarettes, not smokeless tobacco products, highlighting urgent regulatory needs [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eGiven the substantial health risks associated with POPs and widespread nasvay consumption in Uzbekistan, systematic investigation of pesticide contamination is essential. This study addresses critical knowledge gaps by providing the first comprehensive assessment of organochlorine pesticide contamination in nasvay products across multiple regions of Uzbekistan, contributing essential data for evidence-based public health decision-making and regulatory development.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003e\u003cem\u003e2.1. Sample collection\u003c/em\u003e\u003c/p\u003e\u003cp\u003eThe SLT products were purchased at retail stores from six different regions of Uzbekistan \u0026ndash; the capital \u0026ndash; Tashkent city, Tashkent region, Jizzakh region, Samarkand region, Fergana region and Kashkadarya region in November 2023 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). For sample collection, we employed a convenience sampling method, and investigators visited markets and picked up 25 SLT samples from major markets. All samples were transported and analyzed in the Laboratory of Health and Environmental Sciences, Graduate School of Medicine, Kyoto University, Japan.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eSource: WHO GIS Centre for health, DNA/DDI.\u003c/p\u003e\u003cp\u003e\u003cem\u003e2.2. Chemicals\u003c/em\u003e\u003c/p\u003e\u003cp\u003eThe \u003csup\u003e13\u003c/sup\u003eC\u003csub\u003e12\u003c/sub\u003e -2,3,3 '5,5'-Pentachlorobiphenyl (CB-111, CIL) was used as an internal standard. Expanded POPs Pesticides Calibration Solutions CS1-CS6 (ES-5464), Expanded POPs Pesticides Cleanup Spike (ES-5465), syn-DP, anti-DP, POPs Toxaphene Calibration Solutions with PCB Syringe (ES-5351), and octachlorostyrene (ULM-4559) were used as standard solutions for quantification of pesticides. The chemicals were purchased from Cambridge Isotope Laboratories. Hexane, nonane, and dichloromethane used for pesticide residue testing were from Kanto Chemical Co., Ltd. Floridil used in the sample preparation was manufactured by Wako Pure Chemicals.\u003c/p\u003e\u003cp\u003e\u003cem\u003e2.3. Determination of pesticides\u003c/em\u003e\u003c/p\u003e\u003cp\u003eOur study followed previous analytical methods. A total of 24 pesticides were measured: Aldrin, dieldrin, endrin, dichlorodiphenyltrichloroethanes (p,p'-Dichlorodiphenyltrichloroethanep \u0026ndash; p'-DDT; p,p'-Dichlorodiphenyldichloroethylene \u0026ndash; p,p'-DDE; p,p'-Dichlorodiphenyldichloroethane \u0026ndash; p,p'-DDD), hexachlorocyclohexane (alpha-HCH, beta-HCH, gamma-HCH, delta-HCH), chlordanes (cis-CHL, trans-CHL, oxychlordane, cis-nonachlor, trans-nonachlor), pentachlorobenzene (PeCB), hexachlorobenzene (HCB), heptachlor, cis-heptachlor epoxide (HCE), endosulfans (1, 2), toxaphenes (#26, #50), and mirex [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOne to two grams of SLT sample was placed into a 15 mL polypropylene tube with 5 mL of acetone. The tube was shaken for 1 hour, then centrifuged for 1 minute at 3000 rpm. The supernatant was transferred to a new tube, 5 mL of acetone was added, the tube was shaken for 1 hour and then centrifuged for 1 minute at 3000 rpm. The supernatant was transferred to another polypropylene tube. The extract was then diluted to 12 mL with acetone.\u003c/p\u003e\u003cp\u003eFive milliliters of the sample extract was aliquoted into a polypropylene centrifuge tube, and 500 pg of carbon-13 labelled standard of organochlorine pesticides was added and stirred. The organic layer was then concentrated using an air evaporator. The crude extract was diluted to five mL with hexane, mixed with distilled water, and centrifuged after vortex agitation. Next, five mL of the organic layer was passed through a four-gram activated Florisil column and eluted with 20 mL of a 10% dichloromethane/hexane solution. The eluate was concentrated to approximately 1 mL using a rotary evaporator, and 0.1 mL of nonane was added. The final concentrate was labelled with 10 ng of carbon-13 labelled CB-111 and subjected to GC/MS analysis.\u003c/p\u003e\u003cp\u003e\u003cem\u003e2.4. Instruments and quantification\u003c/em\u003e\u003c/p\u003e\u003cp\u003eGas chromatography-mass spectrometry (GC/MS) was used to measure organochlorine pesticides in tobacco samples. The analysis was carried out with a 6890GC and 5973MSD instrument (Agilent Technologies, USA). For separation, a capillary HP-5MS column was employed, measuring 30 meters in length, 0.25 mm in diameter, and 0.25 \u0026micro;m in film thickness. Each sample injection was 5 \u0026micro;L, at an inlet temperature of 230\u0026deg;C. The pulsed splitless injection mode was set at 30 psi for 1 minute for optimal compound transfer. The GC oven started at 70\u0026deg;C for 1 minute, raised by 30\u0026deg;C per minute, and held at 280\u0026deg;C for 3 minutes. The lowest signal detectable was set at three times the noise level, defining both the instrument and method detection limits, since no signal was detected in blank samples. Blank samples were also included throughout sample preparation to check for contamination.\u003c/p\u003e\u003cp\u003e\u003cem\u003e2.5. Exposure Assessment\u003c/em\u003e\u003c/p\u003e\u003cp\u003eTo evaluate exposure risks, Hazard Quotient (HQ) and Hazard Index (HI) were calculated for each pesticide with established reference values from WHO or the U.S. EPA. Specific data on oral absorption of these pesticides through smokeless tobacco are lacking. For the exposure assessment, we assumed that the oral mucosal absorption of OCPs from nasvay could plausibly range from 60% to 100%. The lower bound (60%) was informed by studies on khat chewing, which estimated about 60% absorption from the oral mucosa.\u003c/p\u003e\u003cp\u003eEquations:\u003cdiv id=\"Equa\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e\n$$\\:HQ=EDI/RfD$$\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Equb\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equb\" name=\"EquationSource\"\u003e\n$$\\:HI=\\sum\\:HQ$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eWhere:\u003c/p\u003e\u003cp\u003eHQ: Hazard Quotient\u003c/p\u003e\u003cp\u003eEDI: Estimated Daily Intake (ng/kg body weight/day)\u003c/p\u003e\u003cp\u003eRfD: Reference Dose (ng/kg bw/day)\u003c/p\u003e\u003cp\u003eHI: Hazard Index\u003c/p\u003e\u003cp\u003eEstimated Daily Intake (EDI) was calculated as follows:\u003cdiv id=\"Equc\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equc\" name=\"EquationSource\"\u003e\n$$\\:EDI=Average\\:concentration\\:(ng/g)\\times\\:4g\\times\\:\\text{f}\\times\\:\\:\\text{a}\\text{b}\\text{s}\\text{o}\\text{r}\\text{p}\\text{t}\\text{i}\\text{o}\\text{n}\\:\\text{r}\\text{a}\\text{t}\\text{e}\u0026divide;60\\text{k}\\text{g}\\:\\text{b}\\text{o}\\text{d}\\text{y}\\:\\text{w}\\text{e}\\text{i}\\text{g}\\text{h}\\text{t}$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eWhere:\u003c/p\u003e\u003cp\u003e4 g\u0026thinsp;=\u0026thinsp;Average mass of a single portion of nasvay (based on typical usage range of 3\u0026ndash;5 g)\u003c/p\u003e\u003cp\u003ef\u0026thinsp;=\u0026thinsp;Frequency of daily use (3 times/day for regular users and 10 times/day for heavy users)\u003c/p\u003e\u003cp\u003eAbsorption rate\u0026thinsp;=\u0026thinsp;Absorption rate of OCPs via the oral mucosa according to the supposed scenarios (60% and 100%)\u003c/p\u003e\u003cp\u003e60 kg\u0026thinsp;=\u0026thinsp;Assumed average adult body weight\u003c/p\u003e\u003cp\u003eThus, daily intake of pesticides was estimated for different user patterns, providing a range of potential exposures under realistic and extreme conditions. These assumptions reflect typical reports from users in Central Asia and were necessary given the lack of direct data on OCP absorption from smokeless tobacco.\u003c/p\u003e\u003cp\u003e\u003cem\u003e2.6. Statistical analysis\u003c/em\u003e\u003c/p\u003e\u003cp\u003eThe normality of the continuous variables was evaluated using the Shapiro\u0026ndash;Wilk test. The variables reported as a mean with 95% confidence intervals (95% CI). Differences in chemical concentrations across geographical regions were assessed using the Kruskal-Wallis test, followed by post-hoc pairwise comparisons with the Steel-Dwass method. All analyses were performed using JMP statistical software (SAS Institute Inc., version 18.0), with statistical significance defined at an α level of 0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eAnalysis of 25 nasvay samples collected from Tashkent City, Tashkent Region, Jizzakh, Samarkand, Fergana, and Kashkadarya showed distinct differences in pesticide contamination between regions Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The investigation identified several persistent organic pollutants in the samples: hexachlorocyclohexane isomers (α-HCH, β-HCH, γ-HCH, δ-HCH), DDT and its breakdown products (pp-DDE, pp-DDD), chlordane isomers (trans-chlordane, cis-chlordane), two types of endosulfan (endosulfan-1 and endosulfan-2), as well as mirex, dieldrin, and hexachlorobenzene (HCB).\u003c/p\u003e\u003cp\u003eFor HCH isomers, β-HCH was most concentrated in Tashkent City (1.88 ng/g; 95% CI: 0.01 to 6.74) and Tashkent Region (1.76 ng/g; 95% CI: 0.65 to 2.87). γ-HCH was highest in Jizzakh (0.39 ng/g; 95% CI: 0.08 to 0.87), while α-HCH peaked in Kashkadarya (5.89 ng/g), implying location-specific pesticide use.\u003c/p\u003e\u003cp\u003eHCB was much higher in Samarkand (1.64 ng/g) than elsewhere (P\u0026thinsp;=\u0026thinsp;0.003), which is concerning because HCB is a carcinogen and is environmentally persistent. Endosulfan-2 was also at very high levels in Tashkent Region (27.34 ng/g), Tashkent City (24.42 ng/g), and Kashkadarya (23.24 ng/g) (P\u0026thinsp;=\u0026thinsp;0.002). Endosulfan-1 was high in Jizzakh (17.92 ng/g; 95% CI: 3.44 to 63.08) and Samarkand (6.04 ng/g; P\u0026thinsp;=\u0026thinsp;0.037). These results matter because endosulfan is banned for its toxic health effects.\u003c/p\u003e\u003cp\u003eDDT, though banned globally, was found in all regions, with the highest pp-DDT concentration in Tashkent Region (0.5 ng/g; 95% CI: 0.26 to 0.73). Trans-chlordane was most notable in Jizzakh (0.92 ng/g; P\u0026thinsp;=\u0026thinsp;0.008). Dieldrin was highest in Tashkent Region (4.66 ng/g; 95% CI: 0.33 to 8.98) and Tashkent City (3.76 ng/g; 95% CI: 2.32 to 5.21) but had no significant regional differences.\u003c/p\u003e\u003cp\u003eOther detected pollutants included Toxaphene-P26, highest in Jizzakh (17.62 ng/g), though the difference versus other regions was not significant. Mirex levels were low everywhere, from 0.08 ng/g in Samarkand to 0.18 ng/g in Tashkent City.\u003c/p\u003e\u003cp\u003eHealth risk assessment showed individual pesticide hazard quotients below 1 in all exposure scenarios (Tables\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The highest HQs were toxaphene (0.206), aldrin/dieldrin (0.073), and endosulfan (0.054). Total hazard index (HI) didn\u0026rsquo;t exceed 0.294, so risks appear limited, but may be underestimated because these calculations exclude dietary exposure, cancer risks, and might be affected by nasvay\u0026rsquo;s alkaline pH.\u003c/p\u003e\u003cp\u003eOverall, Tashkent City, Tashkent Region, and Jizzakh had the highest contamination levels, while Fergana had lower pesticide burdens.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study provides the first comprehensive assessment of organochlorine pesticide contamination in nasvay products across six regions of Uzbekistan. The findings reveal significant public health concerns and highlight critical gaps in regulatory oversight of smokeless tobacco products. The widespread detection of multiple banned persistent organic pollutants indicates systematic contamination that requires immediate intervention [\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe regional variations in pesticide contamination reflect complex interactions between historical agricultural practices, industrial activities, and environmental persistence. The elevated concentrations of β-HCH in Tashkent City and Region, along with high γ-HCH levels in Jizzakh, suggest differential exposure patterns related to past pesticide use and environmental degradation processes. The significant variation in HCB contamination across regions, with Samarkand showing the highest levels, may indicate localized industrial sources or specific agricultural practices. HCB is particularly concerning given its classification as a known human carcinogen and exceptional environmental persistence [\u003cspan additionalcitationids=\"CR22 CR23\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe detection of endosulfan at exceptionally high concentrations represents the most alarming finding of this study. With levels reaching 27.34 ng/g in Tashkent Region, these concentrations are particularly concerning given endosulfan's well-documented neurotoxic, carcinogenic, and endocrine-disrupting properties. Endosulfan exposure causes central nervous system hyperstimulation through inhibition of calcium and magnesium ATPase and antagonism of chloride transport in GABA receptor complexes. Animal studies demonstrate that endosulfan exposure results in dose-dependent reductions in neurite length, synaptic formation, and neuronal viability, particularly affecting cortical neurons during critical developmental periods. Human exposure has been associated with convulsions, multiorgan damage, and increased cancer risk [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe continued presence of DDT and its metabolites across all regions, despite decades-long international bans, demonstrates the environmental persistence of organochlorine compounds and ongoing contamination sources. Epidemiological studies have established associations between organochlorine pesticide exposure and increased cancer risk, particularly for hormone-related cancers including breast and prostate cancers. Recent biomonitoring studies in cancer patients showed that exposure to organochlorine pesticides, including DDT and endosulfan, significantly reduced survival time and increased mortality risk [\u003cspan additionalcitationids=\"CR28\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTobacco cultivation is inherently pesticide-intensive due to crop susceptibility to pests and diseases, and unlike food crops, tobacco leaves are not washed or processed before consumption. Studies on tobacco farmers demonstrate high rates of pesticide poisoning, with 55% showing clinically significant depression of plasma cholinesterase levels, indicating acute exposure. The combination of high pesticide use and lack of post-harvest processing makes smokeless tobacco products particularly vulnerable to contamination [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eWhile our risk assessment showed hazard quotients below threshold levels, several factors suggest potential underestimation of actual health risks. First, the assessment focused solely on non-carcinogenic effects and did not adequately address cancer risks from known carcinogens like HCB, DDT, and dieldrin. Second, the alkaline pH of nasvay may enhance absorption of toxic compounds through damaged oral mucosa. Third, cumulative exposure from dietary and environmental sources was not considered. Recent studies demonstrate that cancer risk from heavy metals in smokeless tobacco products often exceeds acceptable limits by 100\u0026thinsp;\u0026minus;\u0026thinsp;10,000 times [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan additionalcitationids=\"CR33 CR34\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe widespread contamination of nasvay with multiple banned pesticides poses significant health risks to users. Approximately 22.3% of adult men in Uzbekistan use nasvay, representing substantial population exposure. Organochlorine pesticides are associated with various cancers, neurological disorders, endocrine disruption, and reproductive toxicity. The International Agency for Research on Cancer has concluded that smokeless tobacco causes cancers of the oral cavity, esophagus, and pancreas, and pesticide contamination may further increase these risks [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eCurrent tobacco control policies in Uzbekistan mandate health warnings only on cigarette packaging, leaving smokeless tobacco products largely unregulated. The absence of safety standards, routine monitoring, and enforcement mechanisms allows contaminated products to reach consumers. Comprehensive regulatory intervention is urgently needed, including establishment of maximum allowable pesticide residue limits, mandatory testing protocols, and strict enforcement measures.\u003c/p\u003e\u003cp\u003eSeveral limitations of the study should be acknowledged. The sample size of 25 products may not fully represent contamination levels across all nasvay varieties and regions in Uzbekistan. The study focused on pesticide concentrations without conducting long-term health impact assessments on consumers. Additionally, exposure assessment relied on assumptions about absorption rates due to lack of compound-specific data for oral mucosal absorption of organochlorine pesticides from smokeless tobacco products [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eFuture studies should include larger-scale surveillance to confirm contamination trends, longitudinal health impact assessments among nasvay users, and investigation of contamination sources in the tobacco supply chain. Research on biomarkers of organochlorine pesticide exposure in nasvay users would provide valuable data for risk assessment and regulatory decision-making [\u003cspan additionalcitationids=\"CR41\" citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e].\u003c/p\u003e"},{"header":"Strength and Limitation","content":"\u003cp\u003eOur study has several limitations. The strength of our research is the uniqueness of these results is he study introduces critical evidence for health policymakers in Uzbekistan, offering data-driven recommendations to regulate pesticide use in SLT products and enhance consumer protection. By highlighting contamination risks and exposure levels, this research has the potential to influence tobacco control policies, enforcement measures, and public awareness campaigns. The findings can serve as a foundation for future studies, encouraging further epidemiological research on the health effects of pesticide exposure from SLT consumption.\u003c/p\u003e\u003cp\u003eThe limitation is the study may not cover all variations of nasvay available in different regions of Uzbekistan. The study included 25 samples, which may not fully represent the contamination levels across the entire country. Larger-scale surveillance is needed to confirm trends. The research focuses on pesticide concentration levels, but it does not provide long-term health impact assessments on consumers of SLT.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study demonstrates widespread contamination of nasvay with multiple persistent organic pollutants, including internationally banned pesticides with severe health effects. The findings provide critical evidence for policymakers to implement comprehensive regulatory measures, establish safety standards, and protect public health. Given the documented health risks and substantial user population, immediate action is required to address this significant public health threat.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eRegional mean concentrations and 95% confidence intervals (95%CI) of organochlorine pesticide residues detected in smokeless tobacco (nasvay) samples\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"9\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003eTashkent city (n\u0026thinsp;=\u0026thinsp;5)\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003eTashkent region\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eJizzakh region (n\u0026thinsp;=\u0026thinsp;3)\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eSamarkand city (n\u0026thinsp;=\u0026thinsp;1)\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003eFergana region (n\u0026thinsp;=\u0026thinsp;5)\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cem\u003eKashkadarya region\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003e(n\u0026thinsp;=\u0026thinsp;6)\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCompound\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c8\" namest=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMean with 95% CI\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c9\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlpha-HCH\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.74 (0.62\u0026ndash;0.87)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.61 (0.40\u0026ndash;0.82)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.91 (0.3\u0026ndash;2.56)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.6 (0.27\u0026ndash;4.59)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.53 (0.27\u0026ndash;0.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u003cp\u003e0.54\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBeta-HCH\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.88 (0.01\u0026ndash;6.74)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.76 (0.65\u0026ndash;2.87)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.05 (0.03\u0026ndash;2.06)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.879\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.86 (0.34\u0026ndash;1.39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.66 (0.41\u0026ndash;0.92)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u003cp\u003e0.15\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGamma-HCH\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.06 (0.04\u0026ndash;0.08)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.08 (0.04\u0026ndash;0.13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.39 (0.08\u0026ndash;0.87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.09 (0.02\u0026ndash;0.16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.15 (0.05\u0026ndash;0.24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u003cp\u003e0.09\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDelta-HCH\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.1 (0.03\u0026ndash;0.53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.27 (0.06\u0026ndash;0.61)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.07 (0.01\u0026ndash;0.13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.06 (0.02\u0026ndash;0.10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u003cp\u003e0.11\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHexachlorobenzene\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.19 (0.15\u0026ndash;0.24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.21 (0.09\u0026ndash;0.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.52 (0.22\u0026ndash;0.82)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.37 (0.29\u0026ndash;0.46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.51 (0.16\u0026ndash;0.87)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDieldrin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.76 (2.32\u0026ndash;5.21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.66 (0.33\u0026ndash;8.98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.97 (1.61\u0026ndash;4.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.19 (1.65\u0026ndash;2.72)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2.78 (1.66\u0026ndash;3.94)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u003cp\u003e0.10\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEndrin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.14 (0.75\u0026ndash;1.54)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.01 (0.63\u0026ndash;1.39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.25 (0.49\u0026ndash;2.99)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.97\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 (0.23\u0026ndash;1.76)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.84 (0.39\u0026ndash;1.29)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u003cp\u003e0.76\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTrans-Chlordane\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.1 (0.05\u0026ndash;0.16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.08 (0.03\u0026ndash;0.13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.92 (0.01\u0026ndash;3.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.16 (0.08\u0026ndash;0.24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.11 (0.08\u0026ndash;0.15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epp-DDT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.32 (0.18\u0026ndash;0.46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.5 (0.26\u0026ndash;0.73)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.27 (0.14\u0026ndash;0.41)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.27 (0.07\u0026ndash;0.46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.36 (0.26\u0026ndash;0.47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u003cp\u003e0.19\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEndosulfan 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.17 (1.03\u0026ndash;3.21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.8 (0.10\u0026ndash;9.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17.92 (3.44\u0026ndash;63.08)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4.26 (3.02\u0026ndash;5.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2.24 (1.06\u0026ndash;3.43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u003cp\u003e0.03\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEndosulfan 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24.42 (11.92\u0026ndash;36.93)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27.34 (20.48\u0026ndash;34.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9.4 (3.72\u0026ndash;22.60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e15.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e9.01 (5.52\u0026ndash;12.49)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e23.24 (14.87\u0026ndash;31.60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eToxphene-P26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.5 (2.97\u0026ndash;12.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.05 (6.65\u0026ndash;9.46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17.62 (10.13\u0026ndash;39.48)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7.28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e12.44 (3.35\u0026ndash;21.53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e8.76 (5.09\u0026ndash;12.42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u003cp\u003e0.16\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMirex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.18 (0.05\u0026ndash;0.31)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.13 (0.05\u0026ndash;0.21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.14 (0.14\u0026ndash;0.30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.1 (0.00-0.19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.12 (0.07\u0026ndash;0.17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u003cp\u003e0.50\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"9\"\u003eHCH\u0026thinsp;=\u0026thinsp;hexachlorocyclohexane isomer, DDT\u0026thinsp;=\u0026thinsp;dichlorodiphenyltrichloroethane, CI\u0026thinsp;=\u0026thinsp;confidence interval. Statistical comparison performed with Kruskal-Wallis test; P-value indicates significance across regions\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eRegulatory thresholds and pesticide contamination levels for risk evaluation\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChemical compound\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eReference Dose (RfD)* (mg/kg/day)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMean concentration (ng/g)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePeak concentration (ng/g)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGamma-HCH (Lindane)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.61\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHexachlorobenzene (HCB)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0006\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.46\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDichlorodiphenyltrichloroethane (DDT)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.41\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChlordane\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0005\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.64\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEndosulfan\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.006\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24.43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e48.58\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMirex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0002\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.35\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eToxaphene\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.00009\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e27.81\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAldrin and Dieldrin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10.99\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeptachlor and heptachlor epoxide\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.44\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e*RfD represents the reference dose established by regulatory authorities for daily exposure thresholds.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eEstimated intake (ng/day) of chlorinated POPs from nasvay in Uzbekistan\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"9\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eScenario 1 (absorption ratio 60%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e\u003cp\u003eScenario 2 (absorption ratio 100%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEDI Av. (ng/kg/d)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eEDI Max (ng/kg/d)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eHQ Av.\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eHQ Max\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eEDI Av. (ng/kg/d)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eEDI Max (ng/kg/d)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eHQ Av.\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHQ Max\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOrdinary users (3 times/day)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGamma-HCH (Lindane)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.015\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.074\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.000015\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.025\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.123\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.000005\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.000025\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHCB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.051\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.176\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.000293\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.084\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.293\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.00014\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.000488\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDDT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.074\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.169\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.000017\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.123\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.281\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.000012\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.000028\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChlordane\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.317\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.000634\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.066\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.528\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.000132\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.001056\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEndosulfan\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.932\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.829\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0005\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.000972\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4.886\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e9.715\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.000814\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.001619\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMirex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.012\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.042\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.000211\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.019\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.000097\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.000352\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eToxaphene\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.246\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.337\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0138\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.037076\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.077\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5.561\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.023082\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.061794\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAldrin and dieldrin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.409\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.319\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0041\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.01319\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.682\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2.198\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.006816\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.021984\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeptachlor and heptachlor epoxide\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.018\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.053\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0002\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.00053\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.031\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.088\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.000307\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.000883\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.019\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.053\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.031\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.088\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeavy users (10 times/day)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGamma-HCH (Lindane)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0505331\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.245\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.00001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.000049\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.084\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.409\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.000017\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.000082\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHCB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.1685596\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.585\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.00028\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.000976\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.281\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.976\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.000468\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.001626\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDDT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.2467208\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.563\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.5E-05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.000056\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.411\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.938\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.000041\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.000094\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChlordane\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.1317658\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.056\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.00026\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.002112\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.000439\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.00352\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEndosulfan\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.7717116\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19.431\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.00163\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.003238\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e16.286\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e32.385\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.002714\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.005397\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMirex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0386045\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.141\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.00019\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.000704\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.064\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.235\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.000322\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.001174\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eToxaphene\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.154751\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.123\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.04616\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.123588\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6.925\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e18.538\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.07694\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.20598\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAldrin and dieldrin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.363265\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.397\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.01363\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.043967\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.272\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e7.328\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.022721\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.073279\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeptachlor and heptachlor epoxide\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.061362\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.177\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.00061\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.001765\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.102\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.294\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.001023\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.002942\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.063\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.176\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.105\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.294\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"9\"\u003e*HI - Hazard Index\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSLT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003esmokeless tobacco\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePOP\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003epersistent organic pollutant\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eOCP\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eparticularly organochlorine pesticides\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eEDI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eestimated daily intake\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eHQ\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ehazard quotient\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eHI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ehazard index\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eRfD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ereference dose\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the laboratory team at Kyoto University and colleagues at the Institute of Health and Strategic Development, Uzbekistan, for field and logistical support.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJJR and KH conceived the study. MUK, MBB, SSU, YRM and RSM conducted field sampling. JJR, ZL and MF performed GC/MS analyses. JJR, MUK and ZL carried out statistical and risk analyses. JJR drafted the manuscript; KH supervised and critically revised it. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eEthics approval and consent to participate.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. This study analyzed retail smokeless tobacco products purchased in public markets and involved no human participants, personal data, or animals.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eStepanov I, Abrams J, Jain V, Walter K, Kittner DL. Variations of toxic and carcinogenic constituents in nasvai: Call for systematic research and regulation. Tob Control [Internet]. 2016 [cited 2025 Sep 19];26(3):355. 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Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.sciencedirect.com/science/article/abs/pii/S0048969722043650?utm_source=chatgpt.com\u003c/span\u003e\u003cspan address=\"https://www.sciencedirect.com/science/article/abs/pii/S0048969722043650?utm_source=chatgpt.com\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"discover-public-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Public Health](https://link.springer.com/journal/12982)","snPcode":"12982","submissionUrl":"https://submission.springernature.com/new-submission/12982/3","title":"Discover Public Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Smokeless tobacco, Uzbekistan, Persistent organic pollutants, Hazard index, Public Health","lastPublishedDoi":"10.21203/rs.3.rs-8095518/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8095518/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eSmokeless tobacco (SLT) products, notably nasvay, are widely used in Uzbekistan, yet the extent and implications of pesticide contamination in these products are not well understood. This study provides the first comprehensive evaluation of persistent organic pollutants (POPs) in SLT across six key regions of Uzbekistan, focusing on both their presence and associated health risks.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eTwenty-five SLT samples were systematically collected from Tashkent City, Tashkent Region, Jizzakh, Samarkand, Fergana, and Kashkadarya. Using gas chromatography\u0026ndash;mass spectrometry, concentrations of organochlorine pesticides\u0026mdash;including hexachlorocyclohexane isomers, endosulfan, DDT, hexachlorobenzene, toxaphene, dieldrin, and mirex\u0026mdash;were quantified.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe study documented marked regional variation in SLT contamination, with Jizzakh and Tashkent displaying notably high levels of endosulfan (endosulfan-1 up to 17.92 ng/g, endosulfan-2 up to 27.34 ng/g), while Fergana showed lower overall contamination. The persistence of legacy pesticides such as DDT and hexachlorobenzene underscores ongoing environmental contamination and inadequate regulatory enforcement. Human exposure estimates indicated that hazard quotients and cumulative hazard indices for individual POPs remained below international safety thresholds under modeled scenarios; nonetheless, the frequent detection of highly toxic and banned substances raises valid public health concerns.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThese results highlight an urgent need for the development and enforcement of systematic safety standards, routine surveillance, and targeted toxicological risk assessments for SLT products. Regulatory intervention is essential to mitigate chronic health risks among SLT users and reduce the long-term burden of pesticide-related diseases in Uzbekistan.\u003c/p\u003e","manuscriptTitle":"Persistent organic pollutants in smokeless tobacco from Uzbekistan, levels patterns and risk assessment","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-05 00:26:50","doi":"10.21203/rs.3.rs-8095518/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-10T10:20:58+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-06T15:11:45+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-04T05:14:50+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-03T21:38:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"26194601373606541192562618250933766572","date":"2025-12-03T08:56:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"87749531886534789973656430199560056858","date":"2025-12-03T02:11:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"117397058877617433576633676298095813871","date":"2025-12-03T01:56:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"326513796088663483666484376167492146619","date":"2025-12-02T17:14:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"176368858256863280744625883876260256580","date":"2025-12-02T17:02:41+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-02T16:59:54+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-12-02T08:00:44+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-15T07:29:04+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-15T07:27:58+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Public Health","date":"2025-11-12T10:52:15+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-public-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Public Health](https://link.springer.com/journal/12982)","snPcode":"12982","submissionUrl":"https://submission.springernature.com/new-submission/12982/3","title":"Discover Public Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1a1ad4ec-17ad-4d76-9a4a-552349497c31","owner":[],"postedDate":"December 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-09T16:00:57+00:00","versionOfRecord":{"articleIdentity":"rs-8095518","link":"https://doi.org/10.1186/s12982-026-01642-6","journal":{"identity":"discover-public-health","isVorOnly":false,"title":"Discover Public Health"},"publishedOn":"2026-03-02 15:57:43","publishedOnDateReadable":"March 2nd, 2026"},"versionCreatedAt":"2025-12-05 00:26:50","video":"","vorDoi":"10.1186/s12982-026-01642-6","vorDoiUrl":"https://doi.org/10.1186/s12982-026-01642-6","workflowStages":[]},"version":"v1","identity":"rs-8095518","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8095518","identity":"rs-8095518","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}