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Exploring cancer development in adulthood: cholinesterase depression and genotoxic effect from chronic exposure to organophosphate pesticides among rural farm children

How V, Hashim Z, Ismail P, Md Said S, Omar D, Bahri Mohd Tamrin S

J Agromedicine, 2014;19(1):35-43.
PMID: 24417530 DOI: 10.1080/1059924X.2013.866917

Children are the vulnerable group in the agricultural community due to their early exposure to pesticides through the dynamic interplay between genetic predisposition, environment, and host-related factors. This study aims to identify the possible association between the depression in blood cholinesterase level and genotoxic effect among farm children. The results of micronuclei assay and comet assay showed that the reduced blood cholinesterase level from organophosphate pesticide exposure is significantly associated with an increase in chromosome breakage and DNA strand breaks. These genotoxicity end points suggest that farm children's cells experience early DNA damage that may lead to uncontrolled cell proliferation during their adulthood. Thus, farm children who grow up near pesticide-treated farmland have a higher probability of developing cancer than children with minimal or zero exposure to pesticides.

Matched MeSH terms: Pesticides/toxicity*
Fulltext Toxicity of buprofezin on the survival of embryo and larvae of African catfish, Clarias gariepinus (Bloch)

Marimuthu K, Muthu N, Xavier R, Arockiaraj J, Rahman MA, Subramaniam S

PLoS One, 2013;8(10):e75545.
PMID: 24098390 DOI: 10.1371/journal.pone.0075545

Buprofezin is an insect growth regulator and widely used insecticide in Malaysia. The present study evaluated the toxic effects of buprofezin on the embryo and larvae of African catfish (Clarias gariepinus) as a model organism. The embryos and larvae were exposed to 7 different concentrations (0, 0.05, 0.5, 5, 25, 50 and 100 mg/L) of buprofezin. Each concentration was assessed in five replicates. Eggs were artificially fertilized and 200 eggs and larvae were subjected to a static bath treatment for all the concentrations. The mortality of embryos was significantly increased with increasing buprofezin concentrations from 5 to 100 mg/L (p< 0.05). However, the mortality was not significantly different (p<0.05) among the following concentrations: 0 (control), 0.05, 0.5 and 5 mg/L. Data obtained from the buprofezin acute toxicity tests were evaluated using probit analysis. The 24 h LC50 value (with 95% confidence limits) of buprofezin for embryos was estimated to be 6.725 (3.167-15.017) mg/L. The hatching of fish embryos was recorded as 68.8, 68.9, 66.9, 66.4, 26.9, 25.1 and 0.12% in response to 7 different concentrations of buprofezin, respectively. The mortality rate of larvae significantly (p<0.05) increased with increasing buprofezin concentrations exposed to 24-48 h. The 24 and 48 h LC50 values (with 95% confidence limits) of buprofezin for the larvae was estimated to be 5.702 (3.198-8.898) and 4.642 (3.264-6.287) mg/L respectively. There were no significant differences (p>0.05) in the LC50 values obtained at 24 and 48 h exposure times. Malformations were observed when the embryos and larvae exposed to more than 5 mg/L. The results emerged from the study suggest that even the low concentration (5 mg/L) of buprofezin in the aquatic environment may have adverse effect on the early embryonic and larval development of African catfish.

Matched MeSH terms: Pesticides/toxicity*
Toxicological and hematological effect of Terminalia arjuna bark extract on a freshwater catfish, Heteropneustes fossilis

Suely A, Zabed H, Ahmed AB, Mohamad J, Nasiruddin M, Sahu JN, et al.

Fish Physiol Biochem, 2016 Apr;42(2):431-44.
PMID: 26501361 DOI: 10.1007/s10695-015-0149-3

Increasing demand for eco-friendly botanical piscicides and pesticides as replacements for harmful synthetic chemicals has led to investigation of new sources of plant materials. Stem bark of Terminalia arjuna, which has been used as a popular folk medicine since ancient time, was examined for its piscicidal activity. This study aims to determine toxicity of ethanol extract of T. arjuna bark on fresh water stinging catfish (Heteropneustes fossilis), along with evaluation of changes in hematological parameters of the fishes exposed to a lethal concentration. The percent mortality of fishes varied significantly in response to concentrations of the extract and exposure times (between exposure time F = 36.57, p < 0.001; between concentrations F = 39.93, p < 0.001). The lethal concentrations (LC50) of ethanol extract were found to be 12.7, 8.94, 5.63 and 4.71 mg/l for 24, 48, 72 and 96 h, respectively. During acute toxicity test, blood samples of treatment fishes showed significant decreases in the red blood cells count, hematocrit content, hemoglobin concentration, mean corpuscular hemoglobin concentration and plasma protein level when compared to those of the control group, while there were significant increases in the mean corpuscular volume, mean corpuscular hemoglobin, white blood cells count and plasma glucose concentration. These results suggest that T. arjuna bark extract could be considered as a potent piscicide due to its toxic effect on fish, particularly fish hematology.

Matched MeSH terms: Pesticides/toxicity*
Diploid and triploid African catfish (Clarias gariepinus) differ in biomarker responses to the pesticide chlorpyrifos

Karami A, Goh YM, Jahromi MF, Lazorchak JM, Abdullah M, Courtenay SC

Sci Total Environ, 2016 07 01;557-558:204-11.
PMID: 26994807 DOI: 10.1016/j.scitotenv.2016.03.030

The impacts of environmental stressors on polyploid organisms are largely unknown. This study investigated changes in morphometric, molecular, and biochemical parameters in full-sibling diploid and triploid African catfish (Clarias gariepinus) in response to chlorpyrifos (CPF) exposures. Juvenile fish were exposed to three concentrations of CPF (mean measured μg/L (SD): 9.71 (2.27), 15.7 (3.69), 31.21 (5.04)) under a static-renewal condition for 21days. Diploid control groups had higher hepatosomatic index (HSI), plasma testosterone (T), and brain GnRH and cyp19a2 expression levels than triploids. In CPF-exposed groups, changes in HSI, total weight and length were different between the diploid and triploid fish. In contrast, condition factor did not alter in any of the treatments, while visceral-somatic index (VSI) changed only in diploids. In diploid fish, exposure to CPF did not change brain 11β-hsd2, ftz-f1, foxl2, GnRH or cyp19a2 mRNA levels, while reduced tph2 transcript levels compared to the control group. In contrast, 11β-hsd2 and foxl2 expression levels were changed in triploids following CPF exposures. In diploids, plasma T levels showed a linear dose-response reduction across CPF treatments correlating with liver weight and plasma total cholesterol concentrations. In contrast, no changes in plasma cholesterol and T concentrations were observed in triploids. Plasma cortisol and 17-β estradiol (E2) showed no response to CPF exposure in either ploidy. Results of this first comparison of biomarker responses to pesticide exposure in diploid and polyploid animals showed substantial differences between diploid and triploid C. gariepinus.

Matched MeSH terms: Pesticides/toxicity*
Fulltext Evaluation of types of poisoning exposure calls managed by the Malaysia National Poison Centre (2006-2015): A retrospective review

Tangiisuran B, Jiva M, Ariff AM, Abdul Rani NA, Misnan A, Rashid SM, et al.

BMJ Open, 2018 12 31;8(12):e024162.
PMID: 30598487 DOI: 10.1136/bmjopen-2018-024162

OBJECTIVE: Accidental or intentional poisoning is a public health concern requiring intervention. The current study designs to evaluate the types of poisoning exposure calls received by the Malaysia National Poison Centre (NPC) over a 10-year period.
SETTINGS AND DATA SOURCES: The poisoning enquiries database (2006-2015) from the Malaysia NPC was used for the analysis.
PARTICIPANTS: The NPC records all telephone calls that it manages using a validated and standardised form. Demographics and types of the poisoning exposure calls were extracted and descriptive analysis was applied.
PRIMARY AND SECONDARY OUTCOMES: The primary outcome of this study is to evaluate NPC data for trends in the poisoning exposure calls based on the types and modes of poisoning over a 10-year period. The secondary outcome is to evaluate the characteristics of human exposure cases based on the calls received by the NPC.
RESULTS: There was a notable increase in the number of poisoning exposure calls noticed during the 10-year period but dropped significantly in 2012. The highest number of poisoning exposure calls came from Selangor (21.0%), Perak (18.0%) and Negeri Sembilan (9.8%). More than half of the exposure was intentional (53.8%) involving more women (50.3%) as compared with men (41.9%), and in the 20-29 years age group category (33.5%). Exposure mostly occurred at home (96%) through the ingestion route (94.1%). Pharmaceutical products (40.5%), pesticides (31.7%) and household products (20.1%) were the common agents implicated for intentional exposure.
CONCLUSIONS: There is an increasing trend in enquiries on poisoning exposure calls made to the NPC. Most of the intentional poisoning exposures occurred among younger women and involved pharmaceuticals, pesticides or household products. Poisoning safety education and other interventions are needed to curb poisoning incidents.

Matched MeSH terms: Pesticides/toxicity*
Ecological risk estimation of organophosphorus pesticides in riverine ecosystems

Wee SY, Aris AZ

Chemosphere, 2017 Dec;188:575-581.
PMID: 28917209 DOI: 10.1016/j.chemosphere.2017.09.035

Pesticides are of great concern because of their existence in ecosystems at trace concentrations. Worldwide pesticide use and its ecological impacts (i.e., altered environmental distribution and toxicity of pesticides) have increased over time. Exposure and toxicity studies are vital for reducing the extent of pesticide exposure and risk to the environment and humans. Regional regulatory actions may be less relevant in some regions because the contamination and distribution of pesticides vary across regions and countries. The risk quotient (RQ) method was applied to assess the potential risk of organophosphorus pesticides (OPPs), primarily focusing on riverine ecosystems. Using the available ecotoxicity data, aquatic risks from OPPs (diazinon and chlorpyrifos) in the surface water of the Langat River, Selangor, Malaysia were evaluated based on general (RQm) and worst-case (RQex) scenarios. Since the ecotoxicity of quinalphos has not been well established, quinalphos was excluded from the risk assessment. The calculated RQs indicate medium risk (RQm = 0.17 and RQex = 0.66; 0.1 ≤ RQ 1 (high risk) was observed for both the general and worst cases of chlorpyrifos, but only for the worst cases of diazinon at all sites from downstream to upstream regions. Thus, chlorpyrifos posed a higher risk than diazinon along the Langat River, suggesting that organisms and humans could be exposed to potentially high levels of OPPs.

Matched MeSH terms: Pesticides/toxicity
Pesticide risk assessment: A study on inhalation and dermal exposure to 2,4-D and paraquat among Malaysian paddy farmers

Baharuddin MR, Sahid IB, Noor MA, Sulaiman N, Othman F

J Environ Sci Health B, 2011;46(7):600-7.
PMID: 21749249 DOI: 10.1080/03601234.2011.589309

A cross-section analytical study was conducted to evaluate the risk of pesticide exposure to those applying the Class II pesticides 2,4-D and paraquat in the paddy-growing areas of Kerian, Perak, Malaysia. It investigated the influence of weather on exposure as well as documented health problems commonly related to pesticide exposure. Potential inhalation and dermal exposure for 140 paddy farmers (handlers of pesticides) were assessed. Results showed that while temperature and humidity affected exposure, windspeed had the strongest impact on pesticide exposure via inhalation. However, the degree of exposure to both herbicides via inhalation was below the permissible exposure limits set by United States National Institute of Occupational Safety and Health (NIOSH). Dermal Exposure Assessment Method (DREAM) readings showed that dermal exposure with manual spraying ranged from moderate to high. With motorized sprayers, however, the level of dermal exposure ranged from low to moderate. Dermal exposure was significantly negatively correlated with the usage of protective clothing. Various types of deleterious health effects were detected among users of manual knapsack sprayers. Long-term spraying activities were positively correlated with increasing levels of the gamma-glutamyl transpeptidase (GGT) liver enzyme. The type of spraying equipment, usage of proper protective clothing and adherence to correct spraying practices were found to be the most important factors influencing the degree of pesticide exposure among those applying pesticides.

Matched MeSH terms: Pesticides/toxicity*
The effect of organochlorines and heavy metals on sex steroid-binding proteins in vitro in the plasma of nesting green turtles, Chelonia mydas

Ikonomopoulou MP, Olszowy H, Hodge M, Bradley AJ

J. Comp. Physiol. B, Biochem. Syst. Environ. Physiol., 2009 Jul;179(5):653-62.
PMID: 19247670 DOI: 10.1007/s00360-009-0347-3

In this study on green turtles, Chelonia mydas, from Peninsular Malaysia, the effect of selected environmental toxicants was examined in vitro. Emphasis was placed on purported hormone-mimicking chemicals such as dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene, dieldrin, lead, zinc and copper. Five concentrations were used: high (1 mg/L), medium (10(-1) mg/L), low (10(-2) mg/L), very low (10(-6) mg/L) and control (diluted carrier solvent but no toxicants). The results suggest that environmental pesticides and heavy metals may significantly alter the binding of steroids [i.e. testosterone (T) and oestradiol] to the plasma proteins in vitro. Competition studies showed that only Cu competed for binding sites with testosterone in the plasma collected from nesting C. mydas. Dieldrin and all heavy metals competed with oestradiol for binding sites. Furthermore, testosterone binding affinity was affected at various DDT concentrations and was hypothesised that DDT in vivo may act to inhibit steroid-protein interactions in nesting C. mydas. Although the precise molecular mechanism is yet to be described, DDT could have an effect upon the protein conformation thus affecting T binding (e.g. the T binding site on the steroid hormone binding protein molecule).

Matched MeSH terms: Pesticides/toxicity*
Is plasma beta-glucuronidase a novel human biomarker for monitoring anticholinesterase pesticides exposure? A Malaysian experience

Inayat-Hussain SH, Lubis SH, Sakian NI, Ghazali AR, Ali NS, El Sersi M, et al.

Toxicol Appl Pharmacol, 2007 Mar;219(2-3):210-6.
PMID: 17140616

A cross-sectional study was conducted to investigate the effects of acute and chronic pesticide exposure on the plasma beta-glucuronidase enzyme activity among five patients of acute pesticide poisoning in Tengku Ampuan Rahimah Hospital, Klang, 230 farmers in the MADA area, Kedah and 49 fishermen in Setiu, Terengganu. The duration of pesticide exposure among the patients was unknown, but the plasma samples from patients were collected on day one in the hospital. The duration of pesticide exposure among the farmers was between 1 and 45 years. The beta-glucuronidase activity was compared with plasma cholinesterase activity in the same individual. The plasma cholinesterase activity was measured using Cholinesterase (PTC) Reagent set kit (Teco Diagnostics, UK) based on colorimetric method, while the plasma beta-glucuronidase activity was measured fluorometrically based on beta-glucuronidase assay. The plasma cholinesterase activity was significantly reduced (p<0.05) among the patients (1386.786+/-791.291 U/L/min) but the inhibition in plasma cholinesterase activity among the farmers (7346.5+/-1860.786 U/L/min) was not significant (p>0.05). The plasma beta-glucuronidase activity among the farmers was significantly elevated (p<0.05) (0.737+/-0.425 microM/h) but not significant among the patients (p>0.05). The plasma cholinesterase activity was positively correlated with the plasma beta-glucuronidase activity among the farmers (r=0.205, p<0.01) but not among the patients (r=0.79, p>0.05). Thus, plasma beta-glucuronidase enzyme activity can be measured as a biomarker for the chronic exposure of pesticide. However, further studies need to be performed to confirm whether plasma beta-glucuronidase can be a sensitive biomarker for anticholinesterase pesticide poisoning.

Matched MeSH terms: Pesticides/toxicity*
Fulltext Occupational Health and Safety in the Palm Oil Industry: A Systematic Review

Myzabella N, Fritschi L, Merdith N, El-Zaemey S, Chih H, Reid A

Int J Occup Environ Med, 2019 10;10(4):159-173.
PMID: 31586381 DOI: 10.15171/ijoem.2019.1576

BACKGROUND: The palm oil industry is the largest contributor to global production of oils and fats. Indonesia and Malaysia are the largest producers of palm oil. More than a million workers are employed in this industry, yet there is a lack of information on their occupational health and safety.
OBJECTIVE: To identify and summarize occupational hazards among oil palm plantation workers.
METHODS: A search was carried out in June 2018 in PubMed, Web of Science, Scopus, and Ovid. Relevant publications were identified by a systematic search of four databases and relevant journals. Publications were included if they examined occupational hazards in oil palm plantation workers.
RESULTS: 941 publications were identified; of these, 25 studies were found eligible to be included in the final review. Of the 25 studies examined, 19 were conducted in Malaysia, 2 in Costa Rica, and one each in Ghana, Indonesia, Myanmar, Papua New Guinea, and Cameroon. Oil palm plantation workers were found to be at risk of musculoskeletal conditions, injuries, psychosocial disorders, and infectious diseases such as malaria and leptospirosis. In addition, they have potential exposure to paraquat and other pesticides.
CONCLUSION: In light of the potential of palm oil for use as a biofuel, this is an industry with strong growth potential. The workers are exposed to various occupational hazards. Further research and interventions are necessary to improve the working conditions of this already vast and growing workforce.

Matched MeSH terms: Pesticides/toxicity
Tradescantia-micronucleus and -stamen hair mutation assays on genotoxicity of the gaseous and liquid forms of pesticides

Mohammed KB, Ma TH

Mutat Res, 1999 May 19;426(2):193-9.
PMID: 10350597

The clastogenic and mutagenic effects of the insecticide Dimethoate (Cygon-2E), herbicides Atrazine, Simazine (Princep), Dicamba (Banvel D) and Picloram (Tordon) were studied using the Tradescantia-micronucleus (Trad-MCN) and Tradescantia-stamen hair mutation (Trad-SHM) assays. In clone 4430, dimethoate fumes both significantly increased the pink mutation events and reduced the number of stamen hairs per filament with increasing dosages. The pink mutation events were elevated by the liquid treatment with Picloram at 100 ppm concentration. The result of Trad-MCN test on Dimethoate fumes was not significantly different between the control and treated groups. The herbicide Atrazine showed positive effects at 10-50 ppm dose (liquid) and signs of overdose at 100 and 500 ppm concentrations. Simazine was mildly positive in elevating the MCN frequencies in the dose range of 5 to 200 ppm (liquid doses). Both Dicamba and Picloram induced a dosage-related increase in MCN frequencies in the Trad-MCN tests using Tradescantia clone 03. However, in higher dosages (200 ppm or higher), there were signs of overdose, reduction of MCN frequencies and physical damage of the leaves and buds of plant cuttings.

Matched MeSH terms: Pesticides/toxicity*
Fulltext How does exposure to pesticides vary in space and time for residents living near to treated orchards?

Wong HL, Garthwaite DG, Ramwell CT, Brown CD

Environ Sci Pollut Res Int, 2017 Dec;24(34):26444-26461.
PMID: 28948535 DOI: 10.1007/s11356-017-0064-5

This study investigated changes over 25 years (1987-2012) in pesticide usage in orchards in England and Wales and associated changes to exposure and risk for resident pregnant women living 100 and 1000 m downwind of treated areas. A model was developed to estimate aggregated daily exposure to pesticides via inhaled vapour and indirect dermal contact with contaminated ground, whilst risk was expressed as a hazard quotient (HQ) based on estimated exposure and the no observed (adverse) effect level for reproductive and developmental effects. Results show the largest changes occurred between 1987 and 1996 with total pesticide usage reduced by ca. 25%, exposure per unit of pesticide applied slightly increased, and a reduction in risk per unit exposure by factors of 1.3 to 3. Thereafter, there were no consistent changes in use between 1996 and 2012, with an increase in number of applications to each crop balanced by a decrease in average application rate. Exposure per unit of pesticide applied decreased consistently over this period such that values in 2012 for this metric were 48-65% of those in 1987, and there were further smaller decreases in risk per unit exposure. All aggregated hazard quotients were two to three orders of magnitude smaller than one, despite the inherent simplifications of assuming co-occurrence of exposure to all pesticides and additivity of effects. Hazard quotients at 1000 m were 5 to 16 times smaller than those at 100 m. There were clear signals of the impact of regulatory intervention in improving the fate and hazard profiles of pesticides used in orchards in England and Wales over the period investigated.

Matched MeSH terms: Pesticides/toxicity*
Fulltext Performance of a cyanobacteria whole cell-based fluorescence biosensor for heavy metal and pesticide detection

Shing WL, Heng LY, Surif S

Sensors (Basel), 2013;13(5):6394-404.
PMID: 23673679 DOI: 10.3390/s130506394

Whole cell biosensors always face the challenge of low stability of biological components and short storage life. This paper reports the effects of poly(2-hydroxyethyl methacrylate) (pHEMA) immobilization on a whole cell fluorescence biosensor for the detection of heavy metals (Cu, Pb, Cd), and pesticides (dichlorophenoxyacetic acid (2,4-D), and chlorpyrifos). The biosensor was produced by entrapping the cyanobacterium Anabaena torulosa on a cellulose membrane, followed by applying a layer of pHEMA, and attaching it to a well. The well was then fixed to an optical probe which was connected to a fluorescence spectrophotometer and an electronic reader. The optimization of the biosensor using several factors such as amount of HEMA and drying temperature were undertaken. The detection limits of biosensor without pHEMA for Cu, Cd, Pb, 2,4-D and chlorpyrifos were 1.195, 0.027, 0.0100, 0.025 and 0.025 µg/L respectively. The presence of pHEMA increased the limits of detection to 1.410, 0.250, 0.500, 0.235 and 0.117 µg/L respectively. pHEMA is known to enhance the reproducibility of the biosensor with average relative standard deviation (RSD) of ±1.76% for all the pollutants tested, 48% better than the biosensor without pHEMA (RSD = ±3.73%). In storability test with Cu 5 µg/L, the biosensor with pHEMA performed 11.5% better than the test without pHEMA on day-10 and 5.2% better on day-25. pHEMA is therefore a good candidate to be used in whole cell biosensors as it increases reproducibility and enhances biosensor storability.

Matched MeSH terms: Pesticides/toxicity
Occurrence and potential risk of organophosphorus pesticides in urbanised Linggi River, Negeri Sembilan, Malaysia

Zainuddin AH, Wee SY, Aris AZ

Environ Geochem Health, 2020 Nov;42(11):3703-3715.
PMID: 32488800 DOI: 10.1007/s10653-020-00604-4

The application of organophosphorus pesticides (OPPs) increased gradually because of the rise in global food demand that triggered the agriculture sector to increase the production, leading to OPP residues in the surface water. This study elucidated the presence of OPPs and estimated its ecological risk in the riverine ecosystem of the urbanised Linggi River, Negeri Sembilan, Malaysia. The OPP concentration in surface water was determined using solid-phase extraction method and high-performance liquid chromatography coupled with diode array detection. Further, the ecological risk was estimated by using the risk quotient (RQ) method. The three OPPs, i.e. chlorpyrifos, diazinon, and quinalphos were detected with mean concentrations of 0.0275 µg/L, 0.0328 µg/L, and 0.0362 µg/L, respectively. The OPPs were at high risk (in general and worst cases) under acute exposure. The estimated risk of diazinon was observed as medium for general (RQm = 0.5857) and high for worst cases (RQex = 4.4678). Notably, the estimated risk for chlorpyrifos was high for both general and worst cases (RQm = 1.9643 and RQex = 11.5643) towards the aquatic ecosystem of the Linggi River. Chronic risk of quinalphos remains unknown because of the absence of toxicity endpoints. This study presented clear knowledge regarding OPP contamination and possible risk for aquatic ecosystems. Hence, OPPs should be listed as one of the main priority contaminants in pesticide mitigation management in the future.

Matched MeSH terms: Pesticides/toxicity

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