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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 188Re-4-hexadecyl-1-2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol/lipiodol (188Re-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 188Re-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 188Re-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.

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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.

IntroductionAlthough 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.MethodsA 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-1β, 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.ResultsFarm-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).ConclusionThis study demonstrated the importance of the use of PPE during pesticide applications and other agricultural tasks to minimize pesticide-associated adverse health effects.