Relationship between butyrylcholinesterase activity and hepatic transaminases: a cross-sectional study in agricultural workers from Peru

Kaur S., Chowdhary S., Kumar D., Bhattacharyya R., Banerjee D.

Population and food requirements are increasing daily throughout the world. To fulfil these requirements application of pesticides is also increasing. Organophosphorous (OP) and Organocarbamate (OC) compounds are widely used pesticides. These pesticides are used for suicidal purposes too. Both inhibit Acetylcholinesterase (AChE) and cholinergic symptoms are mainly used for the diagnosis of pesticide poisoning. Although the symptoms of the intoxication of OP and OC are similar, recent research has described different targets for OP and OC pesticides. Researchers believe the distinction of OP/OC poisoning will be beneficial for the management of pesticide exposure. OP compounds produce adducts with several proteins. There is a new generation of OP compounds like glyphosate that do not inhibit AChE. Therefore, it’s high time to develop biomarkers that can distinguish OP poisoning from OC poisoning.

Tudi M., Daniel Ruan H., Wang L., Lyu J., Sadler R., Connell D., Chu C., Phung D.T.

Pesticides are indispensable in agricultural production. They have been used by farmers to control weeds and insects, and their remarkable increases in agricultural products have been reported. The increase in the world’s population in the 20th century could not have been possible without a parallel increase in food production. About one-third of agricultural products are produced depending on the application of pesticides. Without the use of pesticides, there would be a 78% loss of fruit production, a 54% loss of vegetable production, and a 32% loss of cereal production. Therefore, pesticides play a critical role in reducing diseases and increasing crop yields worldwide. Thus, it is essential to discuss the agricultural development process; the historical perspective, types and specific uses of pesticides; and pesticide behavior, its contamination, and adverse effects on the natural environment. The review study indicates that agricultural development has a long history in many places around the world. The history of pesticide use can be divided into three periods of time. Pesticides are classified by different classification terms such as chemical classes, functional groups, modes of action, and toxicity. Pesticides are used to kill pests and control weeds using chemical ingredients; hence, they can also be toxic to other organisms, including birds, fish, beneficial insects, and non-target plants, as well as air, water, soil, and crops. Moreover, pesticide contamination moves away from the target plants, resulting in environmental pollution. Such chemical residues impact human health through environmental and food contamination. In addition, climate change-related factors also impact on pesticide application and result in increased pesticide usage and pesticide pollution. Therefore, this review will provide the scientific information necessary for pesticide application and management in the future.

Boedeker W., Watts M., Clausing P., Marquez E.

Human poisoning by pesticides has long been seen as a severe public health problem. As early as 1990, a task force of the World Health Organization (WHO) estimated that about one million unintentional pesticide poisonings occur annually, leading to approximately 20,000 deaths. Thirty years on there is no up-to-date picture of global pesticide poisoning despite an increase in global pesticide use. Our aim was to systematically review the prevalence of unintentional, acute pesticide poisoning (UAPP), and to estimate the annual global number of UAPP. We carried out a systematic review of the scientific literature published between 2006 and 2018, supplemented by mortality data from WHO. We extracted data from 157 publications and the WHO cause-of-death database, then performed country-wise synopses, and arrived at annual numbers of national UAPP. World-wide UAPP was estimated based on national figures and population data for regions defined by the Food and Agriculture Organization (FAO). In total 141 countries were covered, including 58 by the 157 articles and an additional 83 by data from the WHO Mortality Database. Approximately 740,000 annual cases of UAPP were reported by the extracted publications resulting from 7446 fatalities and 733,921 non-fatal cases. On this basis, we estimate that about 385 million cases of UAPP occur annually world-wide including around 11,000 fatalities. Based on a worldwide farming population of approximately 860 million this means that about 44% of farmers are poisoned by pesticides every year. The greatest estimated number of UAPP cases is in southern Asia, followed by south-eastern Asia and east Africa with regards to non-fatal UAPP. Our study updates outdated figures on world-wide UAPP. Along with other estimates, robust evidence is presented that acute pesticide poisoning is an ongoing major global public health challenge. There is a need to recognize the high burden of non-fatal UAPP, particularly on farmers and farmworkers, and that the current focus solely on fatalities hampers international efforts in risk assessment and prevention of poisoning. Implementation of the international recommendations to phase out highly hazardous pesticides by the FAO Council could significantly reduce the burden of UAPP.

Manfo F.P., Mboe S.A., Nantia E.A., Ngoula F., Telefo P.B., Moundipa P.F., Cho-Ngwa F.

Agro pesticides are increasingly used worldwide to increase crop production. However, health hazards resulting from human exposure to these chemicals, especially from agricultural areas of developing countries have been a growing concern. The objective of this study was to evaluate the impact of occupational exposure to agro pesticides on the health of farmers in the Buea subdivision, which is one of the major agrarian areas in Cameroon. The study was transversal and involved 90 participants including 58 farmers using pesticides and a reference population of 32 men not involved in occupational use of agro pesticides. The participants were interviewed on agro pesticide use and their health status. Thereafter, blood samples were collected from the participants and used for the assessment of biochemical markers of the liver (alanine aminotransferase and aspartate aminotransferase) and the kidney (creatinine and uric acid) function. Results revealed that farmers frequently used insecticides, fungicides, and herbicides in their farming activities. Farmers reported several acute health symptoms related to pesticides use with the common ones being skin rash, eye irritation, and face burn. When compared to the reference population, the farmers showed significantly elevated (p<0.01) alanine aminotransferase activity. However, other parameters investigated were not affected significantly. These results suggested that farmers were exposed to 3 different classes of agro pesticides, which induced eye and skin affections. Pesticides exposure resulted in alterations of the liver function hence the increased serum alanine aminotransferase activity. Therefore, there is a need to sensitize the farmers on toxicity and liver alteration potential of agro pesticides and the importance of appropriate protective equipment that may minimize exposure.

Sharma A., Kumar V., Shahzad B., Tanveer M., Sidhu G.P., Handa N., Kohli S.K., Yadav P., Bali A.S., Parihar R.D., Dar O.I., Singh K., Jasrotia S., Bakshi P., Ramakrishnan M., et. al.

Pesticides are extensively used in modern agriculture and are an effective and economical way to enhance the yield quality and quantity, thus ensuring food security for the ever-growing population around the globe. Approximately, 2 million tonnes of pesticides are utilized annually worldwide, where China is the major contributing country, followed by the USA and Argentina, which is increasing rapidly. However, by the year 2020, the global pesticide usage has been estimated to increase up to 3.5 million tonnes. Although pesticides are beneficial for crop production point of view, extensive use of pesticides can possess serious consequences because of their bio-magnification and persistent nature. Diverse pesticides directly or indirectly polluted air, water, soil and overall ecosystem which cause serious health hazard for living being. In the present manuscript, an attempt has been made to critically review the global usage of different pesticides and their major adverse impacts on ecosystem, which will provide guidance for a wide range of researchers in this area.

Guerrero Padilla A.M.

Karami-Mohajeri S., Ahmadipour A., Rahimi H., Abdollahi M.

Abstract Organophosphorus pesticides (OPs) are widely used volatile pesticides that have harmful effects on the liver in acute and chronic exposures. This review article summarises and discusses a wide collection of studies published over the last 40 years reporting on the effects of OPs on the liver, in an attempt to propose general mechanisms of OP hepatotoxicity and possible treatment. Several key biological processes have been reported as involved in OP-induced hepatotoxicity such as disturbances in the antioxidant defence system, oxidative stress, apoptosis, and mitochondrial and microsomal metabolism. Most studies show that antioxidants can attenuate oxidative stress and the consequent changes in liver function. However, few studies have examined the relationship between OP structures and the severity and mechanism of their action. We hope that future in vitro, in vivo, and clinical trials will answer the remaining questions about the mechanisms of OP hepatotoxicity and its management.

Li B., Ma Y., Zhang Y.H.

Trichlorfon is an organophosphate insecticide that is widely used in aquaculture and agriculture against parasitic infestations and has caused aquatic toxicity to non-target organisms. To evaluate the effects of low doses of trichlorfon on the oxidative stress and hepatotoxicity in amphibians, Chinese brown frogs (Rana chensinensis) were exposed to trichlorfon at concentrations of 0, 0.01, 0.1, and 1.0 mg/L for 2 and 4 weeks. Then, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and the content of malondialdehyde (MDA) in hepatic tissue were examined to evaluate the effects of oxidative stress and lipid peroxidation. The histopathological alternations to the liver were observed through light and transmission electron microscopy (TEM). The results showed that SOD and CAT activities were increased in the livers of frogs exposed to various concentrations of trichlorfon. The GST activity showed no significant changes at any concentration after 2 weeks of exposure, whereas there was an initial increase after exposure to 0.1 mg/L of trichlorfon at 4 weeks. The content of MDA revealed a significant decrease after exposure. Histopathological and ultrastructural studies showed that trichlorfon induced hyalinization, vacuolation, nucleus necrosis, and cellular swelling in hepatocytes. These results suggest that low doses of trichlorfon could induce oxidative stress, lipid peroxidation, and hepatic lesions in frogs, which shows that even lower, non-lethal doses of trichlorfon are potentially toxic to amphibians.

Thetkathuek A., Yenjai P., Jaidee W., Jaidee P., Sriprapat P.

In this study, we examined the effects of pesticides in migrant farm workers from Cambodia after workplace exposure on fruit plantations in eastern Thailand.We studied 891 migrant farm workers employed on pineapple, durian, and rambutan plantations in Thailand. Data were collected via a detailed questionnaire survey and measurements of serum cholinesterase level (SChE).The majority of subjects was male (57.7%), with an average age of 30.3 years. Most subjects (76.8%) were moderately aware of good industrial hygiene practices. SChE level was divided into four groups based on the results. Only 4.4% had normal levels of cholinesterase activity, 20.5% had slightly reduced levels, 58.5% had markedly reduced levels and were "at risk," and 16.6% who had highest levels of cholinesterase inhibition were deemed to be in an "unsafe" range. SChE was classified into two groups, SChE value of 87.5 was "normal" and 39 acres, use a backpack sprayer, or have a low level of compliance with accepted industrial hygiene practices. These three classes of workers are at increased risk of chemical exposures and developing acute or chronic illness from pesticide exposures.

Kofod D.H., Jørs E., Varma A., Bhatta S., Thomsen J.F.

Previous studies stating a high prevalence of occupational acute pesticide poisoning in developing countries have mainly relied on measurements of the rather non-specific self-reported acute pesticide poisoning symptoms. Only a few studies have measured the biomarker plasma cholinesterase (PchE) activity, in addition to the symptoms, when assessing occupational acute pesticide poisoning. This study evaluated self-reported symptoms as a proxy for acute organophosphate poisoning among Nepali farmers by examining self-reported acute organophosphate poisoning symptoms and PchE activity in response to occupational acute organophosphate exposure. We performed a randomized, double-blind, placebo-controlled, crossover trial among 42 Nepali commercial vegetable farmers. The farmers were randomly assigned (ratio 1:1) to a 2-h organophosphate (chlorpyrifos 50% plus cypermethrin 5%: moderately hazardous) spray session or a 2-h placebo spray session, and after 7 days’ washout, the farmers were assigned to the other spray session. Before and after each spray session farmers were interviewed about acute organophosphate poisoning symptoms and PchE activity was measured. Analyses were conducted with a Two Sample T-test and Mann Whitney U-test. We found no difference in the symptom sum or PchE activity from baseline to follow up among farmers spraying with organophosphate (symptom sum difference −1, p = 0.737; PchE mean difference 0.02 U/mL, p = 0.220), placebo (symptom sum difference 9, p = 0.394; PchE mean difference 0.02 U/mL, p = 0.133), or when comparing organophosphate to placebo (symptom p = 0.378; PchE p = 0.775). However, a high percentage of the farmers reported having one or more symptoms both at baseline and at follow up in the organophosphate spray session (baseline 47.6%, follow up 45.2%) and placebo spray session (baseline 35.7%, follow up 50.0%), and 14.3% of the farmers reported three or more symptoms after the organophosphate spray session as well as after the placebo spray session. We found a general presence of acute organophosphate symptoms among the farmers regardless of organophosphate exposure or poisoning. Thus, self-reported acute organophosphate symptoms seem to be a poor proxy for acute organophosphate poisoning as the occurrence of these symptoms is not necessarily associated with acute organophosphate poisoning. ClinicalTrials.gov, NCT02838303 . Registered 19 July 2016. Retrospectively registered.

García-García C.R., Parrón T., Requena M., Alarcón R., Tsatsakis A.M., Hernández A.F.

Although epidemiological studies have investigated associations between occupational pesticide exposures and different adverse health outcomes, they have rarely assessed individuals at two time-points of a same crop season with different pesticide use.Clinical symptoms, physical examination signs, hematological and clinical chemistry parameters were measured in 189 intensive agriculture workers and 91 healthy control subjects from Almeria coastline (Southeastern Spain) to evaluate potential effects of pesticide exposure.Greenhouse workers showed an increased risk of ocular and skin signs relative to controls at the period of high pesticide exposure (OR: 4.80 and 2.87, respectively); however, no differences were observed for clinical symptoms. A greater risk for ECG changes (OR: 3.35) and altered spirometry (OR: 5.02) was found at the period of low exposure. Erythrocyte acetylcholinesterase was significantly decreased in greenhouse workers relative to controls in both periods. Assessment of hematological parameters revealed increased counts of erythrocytes, leukocytes, platelets and hemoglobin in greenhouse workers relative to controls, and also in the period of high versus low pesticide exposure. Changes in clinical chemistry parameters included decreased levels of glucose, creatinine, total cholesterol, triglyceride and alkaline phosphatase in greenhouse workers relative to controls; however, these parameters were raised in the period of high versus low pesticide exposure.These findings suggest that chronic occupational exposure to pesticides of lower toxicity than former compounds under integrated production systems elicit mild toxic effects, particularly targeting the skin and eyes, as well as subtle subclinical (biochemical) changes of unknown long-term consequences.

Zhang Y., Lu M., Zhou P., Wang C., Zhang Q., Zhao M.

The widespread use of pesticides, such as pyrethroids, increases health risks to non-target organisms. The potential toxicity of pyrethroids to the liver remains unclear and could be easily overlooked if only the common clinical indicators of liver disease are examined. In the present study, BALB/c mice were given intraperitoneal injections of 0, 2, 4, or 8 mg/kg bifenthrin (BF) for 7 days. The potential liver injury of BF and its underlying mechanism were then investigated through multilevel evaluations. Histological analyses and serum enzyme activities showed no obvious clinical evidence of liver damage. Oxidative stress was induced and caspases were activated in response to increased BF concentrations. Exposure to BF also significantly altered the expression levels of mitochondrial apoptosis-related genes in dose-dependent relationships. The microarray results showed that BF could disturb the metabolic profile and extensively induce genes related to oxidative stress, including the cytochrome P450 family, glutathione peroxidases, glutathione s-transferases and kinases. In the in vivo model, BF induced liver injury through caspase-mediated mitochondrial-dependent cell death, a process that is closely related to oxidative stress, even in the absence of classical clinical biomarkers of liver dysfunction. The results of this study suggest that classical evaluations are not adequate for liver toxicity of pyrethroids, and highlight the need for more comprehensive assessment of health risks of these widely used pesticides.

Mohan V., Mathew P., Jose A., Alex R.

Mohammadyan M., Baharfar Y.

<div> <p>human health and the environment. The study aimed to explore the effects of exposure to pesticides on the liver functions and acetycholinesterase levels in serum (AChES) and red blood cells (AChER) of 100 male participating in agricultural work ranging in age between 20 and 60 year with mean age 37.11&plusmn;9.3. One hundred males matched for age and socio economic status were recruited as a control group to compare levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilriubin, alkaline phosphatase (ALP), total protein, AChES and AChER. The results indicate that AST, ALT and ALP were significantly (<em>P</em>&lt;0.05) increased in pesticide-exposed workers compared with control. There was also a highly significantly (<em>P</em>&lt;0.01) decrease in AChER among male agriculture workers compared with controls. At 10 - 50 times of pesticides applications there was a significantly (<em>P&lt;</em>0.05) decrease in AChER and increase in AST, ALT and ALP activity among exposed group. However, there was a negative correlation between AST, ALT, direct bilirubin, and AChES and age among control group and a positive correlation between ALT and AST and age among exposed group. According to the number of pesticide application, there was a positive correlation between AST, ALP, total and direct bilirubin and number of pesticide application. Agricultural villages in Egypt require more attention to decrease the percentage of literacy among the farmers and raise their health awareness.&nbsp;</p> </div> <p>&nbsp;</p>