|Year : 2019 | Volume
| Issue : 6 | Page : 2073-2078
Evaluation of cholinesterase and lipid profile levels in chronic pesticide exposed persons
Usha Kiran Pothu, Anil Kumar Thammisetty, Lakshmana Kumar Nelakuditi
Department of Biochemistry, GSL Medical College and General Hospital, Rajahmundry, Andhra Pradesh, India
|Date of Submission||21-Mar-2019|
|Date of Decision||21-Mar-2019|
|Date of Acceptance||02-Apr-2019|
|Date of Web Publication||26-Jun-2019|
Dr. Anil Kumar Thammisetty
Flat No-F4, Door No- 8-22-5/1, Neeladri Towers, Gandhinagar, Kakinada, Andhra Pradesh - 533 004
Source of Support: None, Conflict of Interest: None
Background: Agriculture being the predominant occupation in India with rampant usage of pesticides to meet its enormous population needs. This pesticide abuse is taking a toll on the health of the persons involved in this work. Objectives: To evaluate pesticide exposure by assessing serum cholinesterase levels, and comparing them with the serum lipid profile levels which assumes the cardiovascular risk status. Study Design: It is a cross-sectional comparative study involving around 283 agricultural farm workers in Rajamahendravaram, Andhra Pradesh. The study period was for about 3 months during pesticide spraying season. Materials and Methods: All the blood samples were collected and analysed for biochemical parameters like plasma glucose, blood urea, serum creatinine, and lipid profile and serum cholinesterase levels using XL 640 fully automated random access analyser. Statistical Analysis Used: Results were analysed using SPSS software version 20. Results: The study group was classified into two groups based on serum cholinesterase levels. It was observed that there were significant alterations in lipid profile levels in the study group with decreased cholinesterase levels when compared to those of normal cholinesterase levels. There was significant negative correlation between cholinesterase levels and non-HDL cholesterol and total cholesterol/HDL ratio. Conclusion: This study implicates that the pesticides have an adverse health effect with regard to cardiovascular risk status.
Keywords: Cardiovascular risk, cholinesterase levels, lipid profile, pesticide exposure
|How to cite this article:|
Pothu UK, Thammisetty AK, Nelakuditi LK. Evaluation of cholinesterase and lipid profile levels in chronic pesticide exposed persons. J Family Med Prim Care 2019;8:2073-8
|How to cite this URL:|
Pothu UK, Thammisetty AK, Nelakuditi LK. Evaluation of cholinesterase and lipid profile levels in chronic pesticide exposed persons. J Family Med Prim Care [serial online] 2019 [cited 2019 Jul 23];8:2073-8. Available from: http://www.jfmpc.com/text.asp?2019/8/6/2073/261388
| Introduction|| |
Pesticides are extensively used in the agriculture which is the predominant occupation in developing countries. Farmers often use pesticides usually at higher concentrations than recommended.,,
Despite the usage of such a large amount of pesticides, there is an estimated 10-30% loss due to pests alone. Organophosphates are irreversible inhibitors of cholinesterase resulting in impairment of metabolism of carbohydrates, fats and protein.,,,,,,,
The elevated levels of pesticide pollutants are associated with raised serum lipids which are a major risk factor for cardiovascular disease. If this association appears to be causal, it may have significant effects on human health.
| Materials and Methods|| |
The study was conducted in the Department of Biochemistry, Andhra Pradesh, India, from the period April 2018 to July 2018. The study protocol was approved by the Institutional Research and Ethics Committee.
The study population comprised of farm workers using pesticides, and non-exposed controls from villages in Rajamahendravaram. The Sample size included 283 farm workers aged between 20-60 years. They were divided into two groups based on cholinesterase levels. Venous blood samples (about 5 ml) were taken by veni-puncture and the samples were left without anticoagulant to allow blood to clot. The serum samples were obtained by centrifugation at room temperature by Remi centrifuge at 4000 rpm/10 minutes. Serum samples were then used for bio-chemical analysis.
All the parameters were analysed using ERBA system pack reagents on Erba XL-640 fully automated analyser. Glucose was determined by using GOD-POD method, Urea by Urease-GLDH method, Creatinine by Enzymatic method, Cholinesterase by Spectrophotometric method, Cholesterol by CHOD-POD method, Triglycerides by GPO method and HDL by PVS/PEGME precipitation method.
Data were computer analysed using SPSS software version 20.0 and MS Excel-2007. The independent sample t-test procedure was used to compare different continuous variables between the two groups separated based on serum cholinesterase levels. Descriptive data was presented as mean ± standard deviation. The correlation was used to assess the relation between continuous variables. For all statistical analysis, P < 0.05 was considered as statistically significant.
| Results|| |
The mean values of the various biochemical parameters are shown in [Table 1]. Correlation between cholinesterase and other biochemical parameters are shown in [Table 2]. From Table1 it is seen that all lipid profile parameters showed significant increase in cases when compared to controls including the calculated parameters like non-HDL Cholesterol and cholesterol/HDL ratio except HDL cholesterol which showed significant decrease. [Table 2] shows that there is a significant correlation between cholinesterase and other biochemical parameters like fasting plasma glucose, total cholesterol, non-HDL cholesterol and total cholesterol/HDL ratio.
|Table 1: Mean values of biochemical parameters in pesticide exposed worker as compared to control|
Click here to view
|Table 2: Correlation of serum cholinesterase levels with other parameters in cases|
Click here to view
| Discussion|| |
The role of pesticides in the development of diseases in humans is still controversial, despite their widespread use. Organophosphate (OP) and Carbamate insecticides form are the groups of chemicals that are mainly used in agriculture  which are replaced by organic pesticides like pyrethroids which can be exposed to in several ways such as breath, oral cavity, and skin. Occupational exposure to pesticides is a possible risk factor for the development of chronic diseases in humans including diabetes and obesity., The early life exposure to endocrine disrupting chemicals (EDC) such as insecticides has been associated with later life adversities such as obesity, diabetes and cancer. The mechanisms underlying such associations are unknown but are likely to be mediated by epigenetic changes such as DNA methylation and histone modifications.
In our study we divided the total study group into two based on cholinesterase levels. The group with decreased cholinesterase levels was considered as cases and normal cholinesterase levels as controls. The determination of cholinesterase activity has been used as a measure of exposure to organophosphates and carbamates and in the diagnosis of poisoning with anticholinesterase compounds. The strong lipophilic insecticides get incorporated in to bio membrane. Due to the crucial functional role of membranes in health, the insecticide effects are certainly membrane related. There are many studies in this aspect indicating the role of insecticide compounds in inducing perturbations of membrane permeability and enzyme dynamics (Antunes-Madeira and Madeira, 1979 and 1982; Antunes-Madeira et al., 1981). Mainly membrane mechanisms are based on the membrane physical state and organization (Sikkema et al., 1995). Hence the effects of insecticides are due to physical changes at the level of lipid-lipid and lipid-protein interaction. Partition studies by Antunes-Madeira and Madeira, 1989 state that membrane undergoes modulation for the incorporation of insecticide. Lipids undergo rapid breakdown, re-synthesis and inter conversion. It is essential to study various lipid fractions in different tissues to provide a clear picture of lipid metabolism in response to pesticides which we have not done in our study (Srinivasulu Reddy and Ramana Rao, 1989). In a study done by Ghosh and Chatterjee, 1989, where B.dissimilis was exposed to pesticides, they found that there is decrease in tissue lipid and proteins under pesticide stress. It could be due to several mechanisms viz., formation of lipoproteins which are utilized for repair of damaged cell and tissue organelles, direct utilization by cells for energy requirements, increased lipolysis, and damage to cellular organization.
Blood is an easily available fluid. So, we used it as an important diagnostic tool to assess toxicity of pesticides instead of tissue studies. Almost every living tissue is exposed to this fluid for exchange of material. Therefore, alteration of any component of blood can be assessed by evaluating serum biochemistry (Stonard, Evans 1999; Fetoui et al. 2008).
Regarding the blood glucose levels in our study, we measured only fasting and post prandial blood glucose levels which showed nothing significant change as shown in [Table 1]. But fasting blood glucose levels are more than normal reference level in cases when compared to controls which is not significant. An investigation of glucometabolic state in larger number of human subjects is necessary. There is growing evidence that prevalence of diabetes in newly diagnosed may be underestimated if FPG tests only had been performed. In the Austrian study, 59% of patients with newly diagnosed AGR had fasting blood glucose levels below 5.5 mmol/L and so would have remained undiagnosed without the performance of OGTTs. Even we did not perform OGTT in our study. So prevalence of diabetes could not be traced.
For the biochemical analysis of the sera, the BUN and creatinine which are primarily indicators of kidney function did not differ between the two groups though creatinine is shown as significantly elevated in cases the rise is within normal reference limit.
Fasting blood glucose levels showed significant negative correlation with cholinesterase levels which indicates some alteration in glucose metabolism. A study by Daniels SI et al. showed that South Asian immigrants have a higher body burden of organo chlorine pesticides than European whites. Diabetes mellitus is associated with higher pesticide concentrations in this population. The toxicity of pesticides possibly is due to its stress-causing effect (Singh et al. 2009; Sadeghi-Hashjin et al. 2011). Stress conditions cause release of adrenocorticotropic hormone, triggering consequent secretion of cortisol by the adrenal cortex (Hayes, Laws 1991). The altered carbohydrate levels might be due to conversion to fats including triglycerides via intermediatory metabolism (Bhushan 2011; Guyton, Hall 2001). Phospholipids have both metabolic and structural function in mammals and are the main precursors of lipoproteins, the carriers for triglyceride transport (Zubay et al. 1995). Decreased serum cholinesterase activity (Kale et al. 1999), may also be responsible for enhanced serum phospholipid concentration. Increased serum cholesterol levels observed in the present study might be an outcome of cholestasis, along with endogenous synthesis of cholesterol (Saxena, Sharma 1999). Lack of study on parameters indicative of cholestasis might be a drawback for this study.
Xenobiotic substances activate the sympathetic nervous system, resulting in release of epinephrine and norepinephrine by adrenal medulla (Harrison 1994; Sadeghi-Hashjin et al. 2011). They activate hormone-sensitive triglyceride lipase in tissue, resulting in hydrolysis of stored triglycerides from fat stores and mobilization of free fatty acids in the blood stream causing raised serum total lipid concentration (Rani, Dua 1995; Guyton, Hall 2001). Free fatty acid estimation which is indicative of lipolysis was not done in this study.
From [Table 1], it is seen that in our study serum cholesterol, triglycerides and LDL levels had increased significantly in patients with decreased cholinesterase levels compared to the ones with normal cholinesterase levels. This indicates pesticides have effect on serum lipids. One of the causes of increased total lipid concentration appears to be disturbance of carbohydrate metabolism, due to probable cytotoxic effect on cells of the pancreas leading to relative deficiency of insulin (Kalender et al. 2005). In insulin deficiency, carbohydrates are not used as energy source and most of the energy is derived from fats. To meet the energy demands lipolysis occurs and the amount of free fatty acids in blood is increased, which we have not estimated in our study, resulting in increased serum total lipid concentration (Guyton, Hall 2001; Rezg et al. 2004).
For other markers of lipid metabolism, there were no effects of pesticides on high-density lipoprotein cholesterol (HDL-cholesterol), except one study reported negative correlation between organo chlorines and HDL  which corresponds to our study as HDL cholesterol levels were decreased in cases when compared to controls. Others reported that pyrethroid were linked with disturbed lipid metabolism by increasing triglycerides, phospholipids, very low-density lipoprotein cholesterol (VLDLC), but no effects on HDL. Hyperstimulation of the nervous system triggers energy demands resulting in the disorder of energy homeostasis that can lead to altered glucose and lipid metabolisms.,,,
There are many studies which state that elevated levels of persistent organic pollutants such as pesticides are associated with increased levels of serum lipids which are a major risk factor for cardiovascular disease. If this association appears to be causal, it may have significant effects on human health. In our study, we have used non-HDL cholesterol and HDL/Total cholesterol ratio as the measurements tools for risk factor assessment for cardiovascular status. There are studies which show that chronic pesticide exposure leads to metabolic syndrome as shown by the one done by Mustieles V et al. This study shows that human adipose tissue levels of persistent organic pollutants results in metabolic syndrome as evidenced by having prevalence of more than one diagnosis of type 2 diabetes, hypertension, hypertriglyceridemia, and/or low HDL cholesterol in their study group.
There are certain clinical trials on animal and humans in which they exposed the subjects to pesticides. In 1978 two laboratories reported that feeding rats with organo chlorines resulted in elevation of serum cholesterol., Oda et al. reported that feeding rats with organic pollutants resulted in hypercholesterolemia which might be due to stimulation of de novo synthesis of liver lipids. Azaïs-Braesco et al. studied the effects of two different PCB congeners and found that the changes in lipid profiles varied with congener structure. Monkeys fed Aroclor 1254 developed elevated triglycerides, but decreased total cholesterol, HDL and LDL cholesterol. Sanyal et al. reported elevations in lipid synthesis by the liver in DDT-treated monkeys.
Another animal study on mice by Sun Q et al., indicated that imidacloprid, a neonicotinoid insecticide, may potentiate high fat diet-induced adiposity in female C57BL/6J mice and enhance adipogenesis in 3T3-L1 adipocytes via the AMPKα-mediated pathway. Imidacloprid might also influence glucose homeostasis partially by inducing cellular oxidative stress in C2C12 myotubes.
In experimental studies on humans, several authors have reported elevations in triglycerides , and total cholesterol.,, Studies on occupationally exposed persons noted elevations in rates of cardiovascular deaths. In a study on Native American population, they have noted that higher pesticide levels were associated with elevations of both triglycerides and total cholesterol which resulted in increased self-reported cardiovascular disease. But the study was limited by the self-reported nature of the diagnosis. However in a study by General Electric scientists, they have argued that the elevated level of organophosphates is a consequence, not a cause, of the hyperlipidemia., This is in contrast with our study which shows that the risk assessment by using HDL/total cholesterol ratio or non-HDL cholesterol levels negatively correlated with cholinesterase levels which is shown in [Table 2].
Exposure to pesticides influences the genetic patterns of lipid metabolism., This conclusion was made by an experimental animal study where they fed either an olive oil or a corn-oil rich diet, and then exposed to pesticides. They found that the pesticide exposure caused induction of genes involved in fatty acid degradation. Petriello et al. also showed that diets high in omega-6 fatty acids can worsen organophosphate-induced vascular toxicity while diets enriched with bioactive food components such as omega-3 polyunsaturated fatty acids can improve the toxicant-induced inflammation.
The precise mechanisms underlying the associations between serum persistent organic pollutants and the various serum lipid components are uncertain. Organo chlorines exposure induces various degradative enzymes such as cytochrome P450s., In addition; several persistent organic pollutants like chlorinated pesticides can alter DNA methylation levels which induce epigenetic changes. Enzyme induction in highly exposed conditions can be identified by doubling of liver size in animals. Other studies have shown that pesticide exposure can cause specific alternations of enzymes involved in lipid synthesis. Enzyme alterations are dependent on variety of genes that are either up-or down-regulated.,,, Thus, there are multiple possible pathways that might lead to selective alterations in metabolism of body fat store that can be reflected in change of serum lipids.
Our results are consistent with the hypothesis that higher levels of persistent organic pollutants, especially higher organo chlorines, organophosphates or pyrethroids, result in elevations of serum lipids. The risk of cardiovascular disease is, at least in part, as a consequence of the elevations in serum lipids that result from exposure. There might be a component of abnormal blood glucose regulation which is inconclusive from this study. The results from cross-sectional study in Spain showed that persistent levels of pesticides were significantly higher among subjects having diabetes. These findings should be considered by public health authorities to implement measures devoted to minimize human exposure to pollutants that could be harmful to the population. This study will help us to create awareness and implementation of the concept of safe occupational practice in agriculture farm workers in our country. The estimation of blood glucose and lipid profile play important role in the diagnosis of risk of coronary heart diseases in organophosphorus poisoning. Regular monitoring of Acetylcholinesterase (AChE) and Pseudocholinesterase in addition to effective interventions in regards to reducing pesticide exposure to prevent health effects should be provided to farmers. Routine monitoring of AChE may allow for early recognition of chronic low-level exposure to organophosphates when they are in use by farmers. It is suggested that non farmers may also be exposed but are less likely to regularly monitor their chemical exposure and use personal protective equipment when using chemicals.
| Conclusion|| |
Our results are consistent with the hypothesis that higher levels of pesticides exposure for chronic period result in elevations of serum lipids and that risk of cardiovascular disease. Unsafe practices among agriculture workers cause significant decrease in cholinesterase levels and altered glucose metabolism. Hence farm workers need to practice basic personal protective equipment and regular health checkups to minimize adverse health effects.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA 2001;285:2486-97.
Ishikawa TT, McNeely S, Steiner PM, Glueck CJ, Mellies M, Gartside PC, et al.
Effects of chlorinated hydrocarbons on plasma-lipoprotein cholesterol in rats. Metabolism 1978;27:89-96.
Kato N, Kato M, Kimura T, Yoshida A. Effect of dietary addition of PCB, DDT, or BHT and dietary protein on vitamin A and cholesterol metabolism. Nutr Rep Int 1978;18:437-45.
Oda H, Matsushita N, Hirabayashi A, Yoshida A. Cholesterol-rich very low density lipoproteins and fatty liver in rats fed Polychlorinated Biphenyls. Biosci Biotech Biochem 1994;58:2152-8.
Abou-Donia MB. Organophosphorus ester-induced chronic neurotoxicity. Arch Environ Health2003;58:484-97.
Nauen R, Bretschneider T. New modes of action of insecticides. Pestic Outlook 2002;13:241.
Casida JE, Quistad GB. Organophosphate toxicology: Safety aspects of nonacetylcholinesterase secondary targets. Chem Res Toxicol 2004;17:983-98.
Sparks TC. Insecticide discovery: An evaluation and analysis. Pestic Biochem Physiol2013;107:8-17.
Chambers JE. Toxicity of pesticides. In: Cockerham LG, Shane BS, editors. Basic Environmental Toxicology. Boca Raton: CRC Press; 1994. p. 185-98.
Azaïs-Braesco V, Macaire JP, Bellenand P, Robertson LW, Pascal G. Effects of two prototypic polychlorinated biphenyls (PCBs) on lipid composition of rat liver and serum. J Nutr Biochem 1990;1:350-4.
Bell FP, Iverson F, Arnold D, Vidmar TJ. Long-term effects of Aroclor 1254 (PCBs) on plasma lipid and carnitine concentrations in rhesus monkey. Toxicology 1994;89:139-53.
Sanyal S, Agarwal N, Dudeja PK, Mahmood A, Subrahmanyam D. Effect of a single oral dose of DDT on lipid metabolism in protein-calorie malnourished monkeys. Indian J Biochem Biophys 1982;19:111-4.
Jaga K, Dharmani C. Sources of exposure to and public health implications of organophosphate pesticides. RevPanam Salud Publica 2003;14:171-85.
Xiao X, Clark JM, Park Y. Potential contribution of insecticide exposure and development of obesity and type 2 diabetes. Food Chem Toxicol 2017;105:456-74.
Gangemi S, Miozzi E, Teodoro M, Briguglio G, De Luca A, Alibrando C, et al.
Occupational exposure to pesticides as a possible risk factor for the development of chronic diseases in humans. Mol Med Rep 2016;14:4475-88.
Alavian-Ghavanini A, Rüegg J. Understanding epigenetic effects of endocrine disrupting chemicals: From mechanisms to novel test methods. Basic Clin Pharmacol Toxicol 2018;122:38-45.
Bartnik M, Rydén L, Ferrari R, Malmberg K, Pyörälä K, Simoons M, et al.
The prevalence of abnormal glucose regulation in patients with coronary artery disease across Europe. The Euro Heart Survey on diabetes and the heart[J]. Eur Heart J 2004;25:1880-90.
Wascher TC, Sourij H, Roth M, Dittrich P. Prevalence of pathological glucose metabolism in patients undergoing elective coronary angiography[J]. Atherosclerosis 2004;176:419-21.
Daniels SI, Chambers JC, Sanchez SS, La Merrill MA, Hubbard AE, Macherone A, et al.
Elevated levels of organochlorine pesticides in South Asian immigrants are associated with an increased risk of diabetes. J Endocr Soc 2018;2:832-41.
Lee DH, Lee IK, Porta M, Steffes M, Jacobs DR. Relationship between serum concentrations of persistent organic pollutants and the prevalence of metabolic syndrome among non-diabetic adults: Results from the National Health and Nutrition Examination Survey 1999-2002. Diabetologia2007;50:1841-51.
Casida JE, Durkin KA. Neuroactive insecticides: Targets, selectivity, resistance, and secondary effects. Annu Rev Entomol2013;58:99-117.
Matin MA, Sattar S, Husain K. Modification of malathion induced neurochemical changes by adrenalectomy in rats. Mol Chem Neuropathol1990;13:119-28.
Matin MA, Husain K, Khan SN. Modification of diazinon-induced changes in carbohydrate-metabolism by adrenalectomy in rats. Biochem Pharmacol1990;39:1781-6.
Rezg R, Mornagui B, El-Fazaa S, Gharbi N. Caffeic acid attenuates malathion induced metabolic disruption in rat liver, involvement of acetylcholinesterase activity. Toxicology 2008;250:27-31.
Pournourmohammadi S, Ostad SN, Azizi E, Ghahremani MH, Farzami B. Minaie B, et al.
Induction of insulin resistance by malathion: Evidence for disrupted islets cells metabolism and mitochondrial dysfunction. Pestic Biochem Physiol2007;88:346-52.
Mustieles V, Fernández MF, Martin-Olmedo P, González-Alzaga B, Fontalba-Navas A, Hauser R, et al.
Human adipose tissue levels of persistent organic pollutants and metabolic syndrome components: Combining a cross-sectional with a 10-year longitudinal study using a multi-pollutant approach. Environ Int 2017;104:48-57.
Sun Q, Qi W, Xiao X, Yang SH, Kim D, Yoon KS, et al.
Imidacloprid promotes high fat diet-induced adiposity in female C57BL/6J mice and enhances adipogenesis in 3T3-L1 adipocytes via the AMPKα-mediated pathway. J Agric Food Chem 2017;65:6572-81.
Baker EL Jr, Landrigan PJ, Glueck CJ, Zack MM Jr, Liddle JA, Burse VW, et al.
Metabolic consequences of exposure to polychlorinated biphenyls (PCB) in sewage sludge. Am J Epidemiol 1980;112:553-63.
Chase KH, Wong O, Thomas D, Berney BW, Simon RK. Clinical and metabolic abnormalities associated with occupational exposure to polychlorinated biphenyls (PCBs). J Occup Med 1982;24:109-14.
Takamatsu M, Oki M, Maeda K, Inoue Y, Hirayama H, Yoshizuka K. PCBs in blood of workers exposed to PCBs and their health status. Prog Clin Biol Res 1984;137:59-68.
Stehr-Green PA, Welty E, Steele G, Steinberg K. Evaluation of potential health effects associated with serum polychlorinated biphenyl levels. Environ Health Perspect 1986;70:255-9.
Tokunaga S, Kataoka K. A longitudinal analysis on the association of serum lipids and lipoproteins concetnrations with blood polychlorinated biphenyls level in chronic “Yusho” patients. Fukuoka Acta Med 2003;94:110-7.
Gustavsson P, Hogstedt C. A cohort study of Swedish capacitor manufacturing workers exposed to polychlorinated biphenyls (PCBs). Am J Ind Med 1997;32:234-9.
Goncharov A, et al
. High serum PCBs are associated with elevation of serum lipids and cardiovascular disease in a Native American population. Environ Res 2008;106:226-39.
Lawton RW, Ross MR, Feingold J, Brown JF Jr. Effects of PCB exposure on biochemical and hematological findings in capacitor workers. Environ Health Perspect 1985;60:165-84.
Brown JF Jr, Lawton RW. Factors controlling the distribution and levels of PCBs after occupational exposure. In: Robertson LW, Hansen LG. Lexington, KY, editors. PCBs: Recent Advances in Environmental Toxicology and Health Effects. The University Press of Kentucky; 2001.
Boll M, Weber LW, Messner B, Stampfl A. Polychlorinated biphenyls affect the activities of gluconeogenic and lipogenic enzymes in rat liver: Is there an interference with regulatory hormone actions? Xenobiotica 1998;28:479-92.
Hennig B, Reiterer G, Toborek M, Matveev SV, Daugherty A, Smart E. Dietary fat interacts with PCBs to induce changes in lipid metabolism in mice deficient in low-density lipoprotein receptor. Environ Health Perspect 2005;113:83-7.
Petriello MC, Newsome B, Hennig B. Influence of nutrition in PCB-induced vascular inflammation. Environ Sci Pollut Res Int 2014;21:6410-8.
Ngui JS, Bandiera SM. Induction of hepatic CYP2B is a more sensitive indicator of exposure to aroclor 1260 than CYP1A in male rats. Toxicol Appl Pharmacol 1999;161:160-70.
Pang S, Cao JQ, Katz BH, Hayes CL, Sutter TR, Spink DC. Inductive and inhibitory effects of non-ortho-substituted polychlorinated biphenyls on estrogen metabolism and human cytochromes P450 1A1 and 1B1. Biochem Pharmacol 1999;58:29-38.
Rusiecki JA, Baccarelli A, Bollati V, Tarantini L, Moore LE, Bonefeld-Jorgensen EC. Global DNA hypomethylation is associated with high serum-persistent organic pollutants in Greenlandic Inuit. Environ Health Perspect 2008;116:1547-52.
Imsilp K, Hansen L. PCB profiles in mouse skin biopsies and fat from an environmental mixture. Environ Toxicol Pharmacol 2005;19:71-84.
Matsusue K, Ishii Y, Ariyoshi N, Oguri K. A highly toxic coplanar polychlorinated biphenyl compound suppresses Delta5 and Delta6 desaturase activities which play key roles in arachidonic acid synthesis in rat liver. Chem Res Toxicol 1999;12:1158-65.
Borlak J, Dangers M, Thum T. Aroclor 1254 modulates gene expression of nuclear transcription factors: Implications for albumin gene transcription and protein synthesis in rat hepatocyte cultures. Toxicol Appl Pharmacol 2002;181:79-88.
Vezina CM, Walker NJ, Olson JR. Subchronic exposure to TCDD, PeCDF, PCB126, and PCB153: Effect on hepatic gene expression. Environ Health Perspect 2004;112:1636-44.
Kelce WR, Lambright CR, Gray LE Jr, Roberts KP. Vinclozolin and p, p'-DDE alter androgen-dependent gene expression: In vivo
confirmation of an androgen receptor-mediated mechanism. Toxicol Appl Pharmacol 1997;142:192-200.
Adeeko A, Li D, Doucet J, Cooke GM, Trasler JM, Robaire B, et al.
Gestational exposure to persistent organic pollutants: Maternal liver residues, pregnancy outcome, and effects on hepatic gene expression profiles in the dam and fetus. Toxicol Sci 2003;72:242-52.
Henríquez-Hernández LA, Luzardo OP, Valerón PF, Zumbado M, Serra-Majem L, et al.
Persistent organic pollutants and risk of diabetes and obesity on healthy adults: Results from a cross-sectional study in Spain. Sci Total Environ 2017;607-608:1096-102.
Nganchamung T, Robson MG, Siriwong W. Association between blood cholinesterase activity, organophosphate pesticide residues on hands, and health effects among chili farmers in Ubon Ratchathani Province, northeastern ThailandRocz Panstw Zakl Hig 2017;68:175-83.
Cotton J, Edwards J, Rahman MA, Brumby S. Cholinesterase research outreach project (CROP): Point of care cholinesterase measurement in an Australian agricultural community. Environ Health 2018;17:31.
[Table 1], [Table 2]