Genetic Polymorphism in Xenobiotic Metabolising Genes and Increased Oxidative Stress among Pesticides Exposed Agricultural Workers Diagnosed with Cancers.

BACKGROUND: Oxidative stress combined with nullity of xenobiotic metabolizing GSTT1/GSTM1/CYP2E1 genes may increase the susceptibility of agricultural workers to adverse health effects including cancer. The present study was conducted to determine; the prevalence of polymorphisms in GSTM1, GSTT1 and CYP2E1 genes, serum 8-hydroxy-2'-deoxygunosine levels, and the role of these markers in risk of cancer among agricultural workers occupationally exposed to pesticides. METHODS: A total of 360 participants, of which 180 belonging to farming group diagnosed with leukemia (n=60), lymphoma (n=60) and breast cancers (n=60), 90 in non-farming group diagnosed with similar cancers and the other 90 as healthy controls with neither history of occupational exposure nor diagnosed with any type of cancers were recruited. Following the questionnaire survey, serum 8-OHdG and genetic polymorphisms in the three genes were determined using ELISA and PCR methods respectively. RESULTS: The results of the study revealed that farm workers carrying GSTT1 null genotype had increased risk for lymphoma (OR = 5.34; 95% CI = 1.80-15.82) and breast cancer (OR=4.04; 95% CI = 1.24-13.07). For farm workers carrying GSTM1 null genotype, the risk was six-fold for breast cancer (OR = 6.88; 95% CI =1.88-25.99). Further, there found a significant difference between 8-OHdG and nullity of CYP2E1 among the farm workers diagnosed with leukemia. CONCLUSION: The findings of the present study suggest that the polymorphisms in detoxifying genes among farm workers occupationally exposed to pesticides and the oxidative stress may likely be responsible for triggering the mechanism of malignancy.

Mitigation of pesticide residue levels in the exposed dermal regions of occupationally exposed farmworkers by use of personal protective equipment.

Unsafe pesticide handling practices with the limited use of personal protective equipment (PPE) by the Indian farming groups lead to an increased risk of exposure to pesticides. Therefore, a community-based follow-up study based on dosimeters, wipes, and hand-wash technique was carried out to evaluate the dermal exposure to pesticides and to analyze the impact of the usage of PPE on minimizing the exposure among the farmworkers of Rangareddy district, Telangana, India. Risk in terms of hazard quotient (HQ), hazard index (HI), and safety analysis as margins of safety was assessed. Farmworkers averaged 18 years of farming experience and showed resistance to adopting good agricultural practices. Ten pesticide residues were detected in concentrations ranging from 0.000 to 246 mg ml-1 in hand-wash, 0.000 to 198.33 ng cm-2 in patch dosimeter, and 0.000 to 1,740 ng cm-2 in wipe samples collected from farmworkers not using PPE. The second phase includes the intervention study results that revealed a significant reduction both in the concentrations and the number of pesticide residues detected in the hand-wash, patch, and wipe samples of the farmworkers who have used the PPE provided to them (p < 0.01). Furthermore, the probabilistic health risk assessment in terms of the HQ values ranged from 0.02 to 1029.82, and HI was >1, suggesting the non-carcinogenic risks associated with dermal exposure to pesticides among them. Additionally, the safety risk assessment in terms of the margin of safety suggests that they follow risky handling practices. The study confirms that farmworkers are exposed to pesticides and emphasizes the significance of using PPE in reducing the risk.

Residual Dialkyl Phosphate Metabolite Concentrations of Organophosphate Pesticides Among Indian Farmworkers: Implication of Exposure and Hazard Assessment.

OBJECTIVE: Biomonitoring of urinary dialkyl phosphate (DAP) metabolites, a sensitive biomarker to assess pesticides exposure and also to study the impact of the use of personal protective equipment (PPE). METHODS: A preintervention-postintervention study to biomonitor dimethylphosphate, diethylphosphate, diethylthiophosphate, and diethyl-dithiophosphate using liquid chromatography with tandem mass spectrometry among Indian farmworkers (n = 120). RESULTS: Dimethylphosphate was detected in all samples at a mean concentration of 74.91 µg · L -1 (17.616 µg · g -1 creatinine), whereas diethylthiophosphate and diethyl-dithiophosphate were detected in 88% and 82% of samples, respectively, among farmworkers who adopted unsafe pesticide-handling practices. Intervention studies showed a significant reduction in the urinary DAP metabolites detected among the farmworkers using PPE provided to them ( P < 0.01). CONCLUSIONS: Study confirms the exposure to pesticides among farmworkers and highlights the importance of the use of PPE to minimize exposure.

Knowledge, attitude and practices related to pesticide usage among farmers: Findings from a hospital based cross-sectional study.

BACKGROUND: In India, where agriculture is the prime occupation among the rural population, farmers are extensively using pesticides in crop production without taking adequate precautions. OBJECTIVE: The current study aimed to examine pesticide usage patterns, usage of personal protective equipment (PPE), knowledge on pesticide toxicity, and attitude towards occupational safety among farmers diagnosed with leukaemia (n = 60), lymphoma (n = 33), and breast cancer (n = 30) visiting a tertiary cancer care hospital in Hyderabad, India. METHODS: Face-to-face interviews were conducted using a pre-tested questionnaire and the data collected were analysed with statistical software SPSS 23. RESULTS: The survey revealed that the participants had an average of 19.6 years of farming experience and women were predominantly involved in the mixing of pesticides and other agricultural work apart from spraying. All of them were not using any PPE and the majority of them did not have any knowledge on the route of exposure, toxicity symbols, and safe handling of pesticides. Statistical analysis showed no significant association between educational status and knowledge, attitude and practices (p > 0.05). CONCLUSION: Even though the majority of the farmers were educated, their lack of adequate knowledge on pesticides had enabled them to adopt risky behaviours in handling and storage of pesticides. There is a need for continuous training programs for farmers to promote awareness and minimize the hazards of occupational exposure.

The impact of the use of personal-protective-equipment on the minimization of effects of exposure to pesticides among farm-workers in India.

Introduction: Although excessive use of pesticides and unsafe agricultural practices may contribute to numerous intoxications, the role of PPE (personal-protective-equipment) in the minimization of toxicological effects due to pesticide exposure has not been addressed so far. The present study aimed to assess the impact of the use of PPE on the minimization of effects of exposure to pesticides among farm-workers. Methods: A community-based follow-up study with questionnaire-based survey and field observations was undertaken among farm-workers (n = 180) of Rangareddy district, Telangana, India. Biomarkers of exposure such as cholinesterase activity, inflammatory markers (TNF-α, IL-1ß, IL-6, cortisol, and hs-C reactive protein), nutrients (vitamins A, E), liver function (total protein and A/G ratio, AST and ALT levels) were investigated in the laboratory by following the standard protocols. Results: Farm-workers who had a mean farming exposure of 18 years of and who neither followed safe pesticide handling practices nor used PPE and also showed reluctance to obey good agricultural practices (GAPs). Inhibition of AChE (acetylcholine esterase) with increased inflammation was found among farm-workers as compared to their respective normal values when they have not used PPE. Linear regression statistical analysis revealed a profound effect on inhibition in the AChE activity and various inflammatory markers with the increase in the duration of pesticide exposure. Further, there was no effect of the duration of pesticide exposure on the levels of vitamins A, E, ALT, AST, total protein, and A/G ratio. Further, intervention studies carried out on the use of PPE provided (commercially available and cost-effective) for 90 days showed a significant reduction in the biomarker levels (p < 0.01). Conclusion: This study demonstrated the importance of the use of PPE during pesticide applications and other agricultural tasks to minimize pesticide-associated adverse health effects.

Endovascular stenting for malignant superior vena cava syndrome - Case series and review of literature.

The treatment of malignant superior vena cava syndrome (SVCS) revolves around radiotherapy and chemotherapy to relieve symptoms with surgery being ruled out due to the advanced stage of malignancy. Primary placement of endovascular stent for palliation of malignant SVCS is not commonly reported in the literature. Here, we present two cases of malignant superior vena cava syndrome with successful relief of symptoms after the placement of endo vascular stent.

Assessment of dermal exposure to pesticides among farmers using dosimeter and hand washing methods.

Inappropriate use of pesticides followed by unsafe handling practices to control the insect infestation among the farming groups in developing countries has resulted in a high exposure risk. The use of personal protective equipment is also negligible among Indian farmers due to their affordability to access the same. Very little research has been conducted to establish an exposure assessment procedure through dermal penetration of pesticide residues. Therefore, to quantify the contamination of pesticide residues through dermal exposure along with detailed field observations and pesticide management practices, a field study was conducted in Rangareddy district, Telangana, Southern India, to assess the dermal exposure based on dosimeter and hand washing methods. The analytical method was modified and validated in-house for performance parameters such as limit of detection, quantification, linear range, recovery, and precision. The potential dermal exposure values ranged from 0.15 to 13.45 µg, while a reduction was found in exposure levels as actual dermal exposure values ranged from 0 to 0.629 µg. Contamination through hand washing was the major contributor to overall dermal exposure. Statistical analysis revealed a significant difference in the exposed dermal regions of the leg and torso after the use of PPE. Penetration factor for each anatomical region and risk evaluation in terms of the Margin of Safety implies unsafe handling of pesticides. The findings of the present study confirm the increased exposure to organophosphate pesticides among operators and highlight the importance of the use of protective measures, especially among those that focus on dermal exposure mitigation.

Preparation of Rhenium-188-Lipiodol Using Freeze-Dried Kits for Transarterial Radioembolization: An Overview and Experience in a Hospital Radiopharmacy.

Background: Rhenium-188(188Re)-lipiodol is a clinically effective, economically viable radiopharmaceutical for Selective Internal Radiation Therapy of liver cancer. Present study evaluates the performance of three freeze-dried kits with respect to the radiochemistry, quality control, and overall "ease of preparation" aspects in a hospital radiopharmacy. Materials and Methods: Freeze-dried kits of acetylated 4-hexadecyl-4,7-diaza-1,10-decanedithiol (AHDD), super six sulfur (SSS), and diethyl dithiocarbamate (DEDC), obtained commercially or received as gift, were used for the preparation of 188Re-lipiodol using freshly eluted 188Re-sodium perrhenate from commercial Tungsten-188/188Re generator following recommended procedures. Results: The overall yield of 188Re-lipiodol prepared using AHDD Kit, SSS Kit, and DEDC Kit was 74.82% ± 3.3%, 87.55% ± 4.8%, and 76.38% ± 4.6%, respectively. Observed radiochemical purity (RCP) of 188Re-lipiodol prepared using these kits was 88.65% ± 2.8%, 92.92% ± 3.0%, and 91.38% ± 3.0%, respectively. Using a modified version of the DEDC Kits, overall yield of 87.17% ± 2.7% and RCP of 95.43% ± 2.3% could be achieved. Conclusions: While all three freeze-dried kits can be used for the preparation of 188Re-lipiodol in >70% overall yield, the modified version of DEDC Kits has some advantages in terms of preparation time and volume of Rhenium-188 activity that can be added to the kit vial. The latter feature of the DEDC Kit is particularly useful for patient dose preparation with 188Re activity of low radioactive concentration.

Pesticide handling practices and self-reported morbidity symptoms among farmers.

Amid growing concern about the adverse effects of pesticides, a questionnaire-based cross-sectional study was conducted to evaluate farmers' knowledge on pesticides handling. Results of in-depth surveys (n = 217) with field observations revealed that participants had a mean 18 years of farming experience and knapsack-sprays were used for spraying. About 99% were not using any personal-protective-equipments during mixing, loading, application operations. Over 80% reentered the treated farms within two-days of application without following safety protocols and 39% admitted unsafe disposal of empty containers of pesticides. Statistical-analysis revealed a significant association between participant's pesticide handling practices and self-reported morbidity symptoms (p < 0.05). Despite awareness of toxicity, participants were mishandling the pesticides. Training on safe handling practices and incentives in form of personal-protective-equipments could be productive to ensure safety at work.

Empirical 188Re-HDD/lipiodol intra-arterial therapy based on tumor volume, in patients with solitary inoperable hepatocellular carcinoma.

OBJECTIVE: This study aimed to assess the potential benefits and tolerability of an empirical dose of approximately 0.8-1.2 mCi (29.6-44.4 MBq) of Re-4-hexadecyl-1-2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol/lipiodol (Re-HDD/lipiodol) per milliliter of tumor volume, administered after super-selection of the tumor feeding branches of hepatic artery for treatment of inoperable hepatocellular carcinoma (HCC). METHODS: Patients with advanced HCC or classified as inoperable, with no demonstrated extrahepatic disease and no significant comorbidities were eligible. The patients selected for this study had a single tumoral lesion, measuring less than 150 cc. The range of total activity administered was between 30 and 100 mCi (1.2-3.7) GBq Re-HDD/lipiodol, administered in the super selected branches of the hepatic artery supplying the tumor in 42 Patients. Whole-body scintigraphies and single-photon emission computed tomography-computed tomography (SPECT-CT) of the liver including tumor were performed at four-time points after injection. Absorbed doses to the various organs were calculated according to the Medical Internal Radiation Dose formalism. Blood and urine samples were collected at multiple time points until 72 h after injection. Hematological, hepatic and pulmonary toxicity was assessed until 12 weeks after administration using the Common Toxicity Criteria for Adverse Events (version 3.0) scale. Responses were evaluated on contrast enhanced computed tomography (CECT) and by alfa-fetoprotein (AFP) level monitoring. RESULTS: About 40.6 ± 4.8% of the injected activity was excreted in the urine by 72 h after injection. The mean absorbed dose to the liver, lungs, stomach, kidney and intestine was 14.4 ± 1.8, 4.8 ± 0.6, 5.5 ± 1.1, 5.1 ± 0.7, and 6.5 ± 1.0 Gy (mean ± SD), respectively. Up to 6 days after administration, 26 of 44 patients had adverse events consisting of aggravations of preexisting laboratory changes (24 patients), fatigue (5 patients), vomiting (6 patients), fever (2 patients), right hypochondrial pain (8 patients), and pain at site of femoral catheter insertion (8 patients). Toxicity assessment at weeks 6 and 12 revealed two cases of mild worsening of liver function tests and no lung or hematological toxicity noted. Two patients were lost to follow-up after the 6-week visit. The response was assessed on CECT in all the remaining patients and the classification of results was more standardized when using European Association for the Study of the Liver (EASL) criteria rather than response evaluation criteria in solid tumors (RECIST) criteria. According to EASL criteria, 8 patients had a partial response, 28 patients had a complete response, 4 patients had progressive disease and 4 patients with stable disease were reported. Thirty-six patients had a baseline elevated AFP and on follow-up at 6 weeks, 6 of these patients showed stable AFP, progression in 4 patients and 26 showed a reduction. CONCLUSION: After the administration of 1.2-3.7 GBq Re-HDD/lipiodol based on empirical activity calculation of 0.8-1.2 mCi/mL of tumor volume, more than half of the patients in the present study had an objective response on imaging and biochemically. No significant adverse side effects were noted and most of the laboratory markers as well as symptoms returned to normal after 48-72 h post-administration. Selective administration of the radiopharmaceutical into the tumor feeding arteries gives a good anti-tumoral effect with minimal side effects and damage to surrounding normal liver tissue.

Rhenium-188 Hydroxyethane 1,1-Diphosphonic Acid (HEDP) for Bone Pain Palliation Using BARC-HEDP Kits versus Pars-HEDP Kits: A Comparison on Preparation and Performance Aspects at Hospital Radiopharmacy.

PURPOSE OF THE STUDY: Rhenium-188 hydroxyethane 1,1-diphosphonic acid (HEDP) is a clinically established radiopharmaceutical for palliation of bone pain due to osseous metastases. Recently, the Bhabha Atomic Research Centre (BARC) had developed a freeze-dried kit for the preparation of rhenium-188 HEDP. The present study compares the radiochemistry aspects of indigenous BARC-HEDP kits with commercially available HEDP kits from Pars Isotope Company, Iran. MATERIALS AND METHODS: Freeze-dried HEDP kits were obtained from Radiopharmaceuticals Division, BARC, and Pars Isotope Company, Iran. Following recommended procedures, rhenium-188 HEDP was prepared using freeze-dried kits from both sources using freshly eluted rhenium-188 sodium perrhenate obtained from a commercial tungsten-188/rhenium-188 generator. RESULTS: Both kits could be used for the preparation of rhenium-188 HEDP in >95% radiochemical purity (RCP). Rhenium-188 HEDP prepared from both kits showed comparable in vitro stability as well as pharmacokinetic properties. The normal bone-to-soft tissue ratio observed for rhenium-188 HEDP prepared using BARC-HEDP kit and Pars-HEDP kit was 1.993 and 1.416, respectively. CONCLUSIONS: Both HEDP kits provided a user-friendly solution for the preparation of rhenium-188 HEDP. While Pars-HEDP-kit permits the addition of only 2 mL of rhenium-188 perrhenate solution per kit vial, BARC-HEDP-kit allows up to 5 mL. This feature permits the preparation of patient dose of rhenium-188 HEDP even with older generators providing rhenium-188 perrhenate having a low radioactive concentration (activity/mL). In addition, availability of an indigenous product is always preferable over imported options.