Human Exposure Research Articles

Nylon 6 film coated with poly-tetrahydrofuran sol–gel solution in face mask as a non-invasive in vivo sampling device for caffeine in human exhaled breath aerosol

Caffeine is an alkaloid compound that can excite the central nervous system and effectively relieve fatigue in moderation. However, excessive caffeine consumption can block blood vessels, raising blood pressure and increasing the risk of atherosclerosis. The International Agency for Research on Cancer of the World Health Organization has listed caffeine in category 3 carcinogens, so it is crucial that caffeine be detected easily and accurately. Exhaled breath aerosol (EBA), which consists of a large number of volatile substances and complex biological matrices, can not only reflect the physiological state of the human body, ingested substances, and environmental exposures; on the other hand, the characteristics of non-invasive sampling also make EBA analysis has a broad application prospect in the field of human health monitoring and disease diagnosis. This paper used a combination of nylon 6 film coated with poly-tetrahydrofuran (PTHF) and a medical N95 mask to construct a convenient and direct sampling device, which can be used to collect caffeine ingested by humans non-invasively from EBA. Volunteers wore a mask for a defined period of time after consuming a certain amount of caffeine. The samples were next back-extracted with methanol and detected and analyzed using gas chromatography-high resolution mass spectrometry (GC-HRMS). The results showed that under the optimized analytical conditions, the PTHF-coated nylon 6 film was effective in collecting caffeine from human EBA, and the peak time of caffeine was 23.44 min. The mask-loaded coated device in this study has the advantages of being comfortable and efficient, safe and non-invasive as well as easy to operate, and by combining with mass spectrometry molecular techniques it can achieve high sensitivity and specificity analysis of trace components, which is expected to be used for the early diagnosis of respiratory diseases in clinical analysis.

Toxicity of Waterpipe Tobacco Smoking: The Role of Flavors, Sweeteners, Humectants, and Charcoal.

Waterpipe tobacco (WPT) smoking is a public health concern, particularly among youth and young adults. The global spread of WPT use has surged since the introduction of pre-packaged flavored and sweetened WPT, which is widely marketed as a safer tobacco alternative. Besides flavorants and sugars, WPT additives include humectants, which enhance the moisture and sweetness of WPT, act as solvents for flavors, and impart smoothness to the smoke, thus increasing appeal to users. In the United States (U.S.), unlike cigarette tobacco flavoring (with the exception of menthol), there is no FDA product standard or policy in place prohibiting sales of flavored WPT. Research has shown that the numerous fruit, candy, and alcohol flavors added to WPT entice individuals to experience those flavors, putting them at an increased risk of exposure to WPT smoke-related toxicants. Additionally, burning charcoal briquettes-used as a heating source for WPT-contributes to the harmful health effects of WPT smoking. This review presents existing evidence on the potential toxicity resulting from humectants, sugars, and flavorants in WPT, and from the charcoal used to heat WPT. The review discusses relevant studies of inhalation toxicity in animal models and of biomarkers of exposure in humans. Current evidence suggests that more data are needed on toxicant emissions in WPT smoke to inform effective tobacco regulation to mitigate the adverse impact of WPT use on human health.

Neuroprotective effect of sea urchins (Diadema savignyi) extract in an animal model of aluminum neurotoxicity

Human exposure to heavy metals causes major health consequences. Aluminum (Al) toxicity primarily affects the brain and has been implicated in neurodegenerative disorders. Natural products offer a cheap and safe source of protective agents against heavy metal toxicity. This study investigates the neuroprotective role of the shell extract (SH) from the Sea urchin (Diadema savignyi) collected from the Red Sea in an Aluminum-induced neurotoxicity model.Aluminum (Al, 250 µg/ml) caused cell death in a dose-dependent manner on neuroblastoma (SH-SY5Y) cells. The shell extract (50, 100, and 200 µg/ml) improved cell viability of the neuroblastoma cells. In vivo, toxicity assessment showed that Aluminum administration increased the levels of blood Urea, creatinine, and liver enzymes. Treatment with Shell extract reversed the levels back to normal.Oxidative stress assessment in vitro and in vivo showed that Al caused an increase in Nitric Oxide (NO) concentration and a significant reduction in Catalase and Glutathione (GSH) activity. Treatment with Shell extract (SH) improved these changes.Microscopic examination of the cerebral cortex showed that Aluminum-treated animals had significant neuronal damage, as evidenced by the degenerated neurons and increased apoptosis marker Caspase 3. There was also an increase in glial activation seen by an increase in the expression of Glial fibrillary Acidic Protein (GFAP). Treatment with Shell extract (100 and 200 µg/kg) showed neuroprotective effects all over cortical layers with minimal neuronal degenerative changes.The current work proves the potential antitoxic and neuroprotective properties of Sea Urchins (Diadema savignyi) extract as a cheap and safe therapeutic alternative against heavy metal toxicity.

Correspondence on "Per- and Polyfluoroalkyl Substances in Personal Hygiene Products: The Implications for Human Exposure and Emission to the Environment".

Correspondence on "Per- and Polyfluoroalkyl Substances in Personal Hygiene Products: The Implications for Human Exposure and Emission to the Environment".

Internalization of nano- and micro-plastics in human erythrocytes leads to oxidative stress and estrogen receptor-mediated cellular responses

Plastic material versatility has resulted in a substantial increase in its use in several sectors of our everyday lives. Consequently, concern regarding human exposure to nano-plastics (NPs) and micro-plastics (MPs) has recently increased. It has been shown that plastic particles entering the bloodstream may adhere to the erythrocyte surface and exert adverse effects following erythrocyte aggregation and adhesion to blood vessels. Here, we explored the effects of polystyrene nano-plastics (PS-NPs) and micro-plastics (PS-MPs) on human erythrocytes. Cellular morphology, binding/internalization of PS-NPs and PS-MPs, oxidative stress parameters, as well as the distribution and anion exchange capability of band 3 (anion exchanger 1; SLC4A1) have been analyzed in human erythrocytes exposed to 1 μg/mL PS-NPs or PS-MPs for 3 and 24 h, respectively. The data obtained showed significant modifications of the cellular shape after exposure to PS-NPs or PS-MPs. In particular, a significantly increased number of acanthocytes, echinocytes and leptocytes were detected. However, the percentage of eryptotic cells (<1 %) was comparable to physiological conditions. Analytical cytology and confocal microscopy showed that PS-NPs and PS-MPs bound to the erythrocyte plasma membrane, co-localized with estrogen receptors (Erα/ERβ), and were internalized. An increased trafficking from the cytosol to the erythrocyte plasma membrane and abnormal distribution of ERs were also observed, consistent with ERα-mediated binding and internalization of PS-NPs. An increased phosphorylation of ERK1/2 and AKT kinases indicated that an activation of the ER-modulated non-genomic pathway occurred following exposure to PS-NPs and PS-MPs. Interestingly, PS-NPs or PS-MPs caused a significant production of reactive oxygen species, resulting in an increased lipid peroxidation and protein sulfhydryl group oxidation. Oxidative stress was also associated with an altered band 3 ion transport activity and increased oxidized haemoglobin, which led to abnormal clustering of band 3 on the plasma membrane. Taken together, these findings identify cellular events following the internalization of PS-NPs or PS-MPs in human erythrocytes and contribute to elucidating potential oxidative stress-related harmful effects, which may affect erythrocyte and systemic homeostasis.

Perchlorate in foodstuffs from South China and its implication for human dietary exposure

Perchlorate, an aqueous-soluble compound resistant to degradation, is mainly used in the synthesis of pyrotechnics, herbicides, and other products. It serves as a pivotal component in the production of fireworks, rocket fuel, and explosives. Perchlorate was recognized as a pollutant owing to the potential toxic risk to thyroid function, which could pose a potential threat to the nervous system of infants and pregnant women. Some study had found that perchlorate existed in food, water and air. This study aimed to investigate the levels of perchlorate in six types of foods (n=570) from South China, and evaluate potential exposure risks for residents. Vegetables were found to have the highest median levels of foods, attributed to elevated water content in leafy vegetables and facile solubility of perchlorate in water. The relatively low levels of perchlorate in food compared to other studies could attribute to the fact that the period of food we purchased in this study was during the wet season while the contaminants, such as perchlorate, were diluted. The maximum hazard quotient (HQ) values for all residents consuming different foods and water were all higher than 1 This suggested that there is a potential health risk of perchlorate to residents in South China. Those may be attributed to the high levels of perchlorate in some individual samples of meat and eggs. However, the 95th percentile of HQ values in all residents was less than 1, indicating that there is no potential health risk of perchlorate to most residents in South China.

Tissue distribution and exposure risk assessment of dioxins, dioxin-like polychlorinated biphenyls and perfluoroalkyl substances in red swamp crayfish

Significant attention has been paid to the adverse effects of dioxins, dioxin-like polychlorobiphenyls (DL-PCBs) and per-and polyfluoroalkyl substances (PFAS) in environment and food on ecosystem and human health. However, limited information exists regarding the occurrence, tissue distribution and exposure risk of these pollutants in crayfish. This study investigated tissue-specific distribution characteristics, influence factors and exposure risk of dioxins, DL-PCBs and PFAS in crayfish. Dioxins, DL-PCBs, and PFAS were detected in crayfish samples, with concentrations ranging from 0.361 to 1.91 pg TEQ g−1 for sum dioxins and DL-PCBs, and 1.54–21.2 ng g−1 for sum PFAS. The highest concentrations of dioxins, DL-PCBs TEQ and total PFAS were found in crayfish viscera and accounting for over 69% of the relative body burden (RBBs) of these pollutants. The specific-tissue distribution of these pollutants linked to tissue fat and protein content and log Kow and molecular weights of homologues. The consumption of crayfish edible tissue posed no health risks from exposure to dioxins and DL-PCBs as well as sum 4 PFAS in adults. However, consumption of crayfish viscera significantly increased exposure risk. This study can provide valuable insights into the tissue-specific distribution and human exposure risks associated with dioxins, DL-PCBs and PFAS in crayfish.

Dietary Intake of Minerals and Potential Human Exposure to Toxic Elements via Coffee Consumption.

In this study, we investigated the levels of macro, minor, and trace elements in roasted ground and instant coffees (n = 56). We assessed dietary mineral intake and health risks associated with potentially toxic elements (PTEs) using deterministic and probabilistic approaches. The limits of detection (LOD) ranged from 0.13 µg/kg for Be to 3.7 mg/kg for K, with corresponding limits of quantification (LOQ) at 0.43 µg/kg and 12.2 mg/kg. The recovery values (R%) ranged from 89 to 107%. The most abundant element was K, followed by Mg, Ca, and Na. Other elements followed this order: Fe > Mn > B > Cu > Sr > Zn > Al > Ba > Ni > Cr > Co > Se > Sn > Pb > Li > Ag > V > As > Cd > Hg > Be. Instant coffees generally exhibited higher K, Mg, and Na levels than ground-roasted coffees. Notably, Hg, Li, and Se were not detected in 34, 2, and 1 samples, respectively. Coffee samples were generally a good source of dietary elements such as Cu, Mn, Cr, and Se. The PTEs found in coffee products posed negligible risks to human health. The total target hazard quotient (TTHQ) remained below 1, and the incremental lifetime cancer risk (ILCR) did not exceed the threshold of 1 × 10-6. Nevertheless, coffee consumption contributed to Pb and As levels below 15% of the benchmark dose lower confidence limit (BMDL) values, and Sn, Hg, and Cd levels below 0.90% of the provisional tolerable weekly intake (PTWI).

Polybrominated diphenyl ethers in indoor dust from Brazil: assessing demographic differences and human health exposure.

Indoor house dust is considered an important human exposure route to polybrominated diphenyl ethers (PBDEs), which has raised concern about their environmental persistence and toxicity properties. In this study, eight PBDEs (BDE-28, -47, -99, -100, -153, -154, -183, and -209) were determined in house dust from two cities with different socio-demographic characteristics from Brazil, examining possible relationships with factors that potentially influence contamination (population density, economic activities, presence of electronic equipment, and so on) and also estimating the risk of human exposure through oral ingestion and dermal contact. The Σ8PBDE concentration in Sorocaba city ranged between 380 and 4269ng/g dw, while in Itapetininga city ranged from 106 to 1000ng/g dw. In both regions, BDE-209 was the most abundantly found congener, followed by BDE-99. House dust from Sorocaba presented significantly greater concentrations of BDE-183 and BDE-209 than Itapetininga. Regarding risk exposure assessment, the estimated daily intake (EDI) of PBDEs was much lower than their respective reference doses (RfDs) in all pathways estimated (non-dietary ingestion and dermal contact). This study provided valuable data to improve the knowledge about the presence and exposure to PBDEs in Brazilian house dust in comparison to other developing countries and the need to control environmental pollution and protect human health.

Analytical methods, source, concentration, and human risks of microplastics: a review.

Microplastics (MPs) as an atmospheric pollutant are currently receiving widespread attention. Although atmospheric MPs have been extensively studied, due to different research methods, systematic comparisons of atmospheric MPs are still needed. This review critically reviewed the analytical methods, research status and potential human exposure. In this review, the detection principles, advantages and limitations of different visual andchemical analysis methods are reported, and the potential risks of MPs to the human are also introduced. Based on future research about the human risks, emphasized the importance of establishing standardized research methods.

One Health Threat of Treated Wastewater Discharge in Urban Ohio Rivers: Implications for Surface Water and Fish Gut Microbiome and Resistome.

Wastewater treatment plants (WWTPs) are thought to be a major disseminating source of antibiotic resistance (AR) to the environment, establishing a crucial connection between human and environmental resistome. The objectives of this study were to determine how wastewater effluents impact microbiome and resistome of freshwater and fish, and identify potential AR-carrying clinically relevant pathogens in these matrices. We analyzed wastewater influent and effluent from four WWTPs in three metropolitan areas of Ohio, USA via shotgun metagenomic sequencing. We also sequenced river water and fish guts from three reaches (upstream, at the WWTP outfall, and downstream). Notably, we observed a decline in microbiome diversity and AR gene abundance from wastewater to the receiving river. We also found significant differences by reach and trophic level (diet) in beta-diversity of the fish gut microbiomes. SourceTracker revealed that 0.443 and 0.248 more of the of the fish gut microbiome was sourced from wastewater effluent in fish from the outfall and downstream locations, respectively, compared to upstream fish. Additionally, AR bacteria of public health concern were annotated in effluent and river water samples, indicating potential concern for human exposure. In summary, our findings show the continued role of wastewater as a significant AR reservoir and underscores the considerable impact of wastewater discharge on aquatic wildlife, which highlights the One Health nature of this issue.

Occupational Hazard Exposure: Assessment of Hypogonadism and Dyslipidemia in House and Automobile Painters in Ilorin, Nigeria

Aims: To investigate the impact of human exposure to the constituents of paint on serum reproductive hormone and Lipid profile among occupationally exposed House and Automobile spray painters in Yakuba district of Ilorin East Local Government area of Kwara State. Nigeria. Study Design: Experimental./ Cross sectional. Place and Duration of Study: Yakuba district of Ilorin East Local Government area of Kwara State. Nigeria, 6months; between July 23 and January 2024. Methodology: 120 male participants were recruited for this study with the mean age 33.15±0.86 years. The participants included 40 automobile painters, 40 house painters, and male artisans who were not painters and served as the control group .Venous Blood samples were collected from both the test and control subjects for the measurement of serum lipids and testosterone using reference techniques. Results: Total Cholesterol, Triglyceride, HD and LDL cholesterol were significantly higher (P&lt;0.05) in the exposed automobile and house painters than the control groups. There was no significant difference (P&gt;0.05) between the serum lipid values of the automobile and the house painters. The serum testosterone level in both group of exposed painters was statistically similar(P&gt;0.05). There was no significant correlation (P&gt;0.05) between the frequency of cars or houses painted per month and work experience with the lipid profile parameters and testosterone levels in the occupationally exposed house and automobile painters. Conclusion: Occupational exposure to some chemical constituents of paint is associated with dyslipidemia and decrease serum testosterone which may precipitate adverse ill health among the painters.

Low levels of per- and polyfluoroalkyl substances (PFAS) detected in drinking water in Norway, but elevated concentrations found near known sources

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous contaminants which are also found in drinking water. Concentration levels in drinking water vary widely and range from a very low contribution to total daily exposure for humans to being the major source of uptake of PFAS. PFAS concentrations in Norwegian drinking water has been rarely reported. We investigated concentrations of 31 PFAS in 164 water samples, representing both source water (i.e., before drinking water treatment) and finished drinking water. Samples were taken from 18 different water bodies across Norway. The 17 waterworks involved supply drinking water to 41 % of the Norwegian population. Only four of the waterworks utilised treatment involving activated carbon which was able to significantly reduce PFAS from the source water. Samples of source water from waterworks not employing activated carbon in treatment were therefore considered to represent drinking water with regards to PFAS (142 samples). All samples from one of the water bodies exceeded the environmental quality standard (EQS) for perfluorooctane sulfonic acid (PFOS) according to the water framework directive (0.65 ng/L). No concentrations exceeded the sum of (20) PFAS (100 ng/L) specified in the EU directive 2020/2184 for drinking water. Several EU countries have issued lower guidelines for the sum of the four PFAS that the European Food Safety Authority (EFSA) has established as the tolerable weekly intake (TWI) for PFOS, perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS). Denmark and Sweden have guidelines specifying 2 and 4 ng/L for the sum of these PFAS. Only one of the 142 drinking water samples exceeded the Danish TWI and contained a sum of 6.6 ng/L PFAS. A population exposure model, for individuals drinking water from the investigated sources, showed that only 0.5 % of the population was receiving PFAS concentrations above the Danish limit of 2 ng/L.

Metabolomics highlights biochemical perturbations occurring in the kidney and liver of mice administered a human dose of colistin

Introduction: Colistin (CMS) is used for the curation of infections caused by multidrug-resistant bacteria. CMS is constrained by toxicity, particularly in kidney and neuronal cells. The recommended human doses are 2.5–5 mg/kg/day, and the toxicity is linked to higher doses. So far, the in vivo toxicity studies have used doses even 10-fold higher than human doses. It is essential to investigate the impact of metabolic response of doses, that are comparable to human doses, to identify biomarkers of latent toxicity. The innovation of the current study is the in vivo stimulation of CMS's impact using a range of CMS doses that have never been investigated before, i.e., 1 and 1.5 mg/kg. The 1 and 1.5 mg/kg, administered in mice, correspond to the therapeutic and toxic human doses, based on previous expertise of our team, regarding the human exposure. The study mainly focused on the biochemical impact of CMS on the metabolome, and on the alterations provoked by 50%-fold of dose increase. The main objectives were i) the comprehension of the biochemical changes resulting after CMS administration and ii) from its dose increase; and iii) the determination of dose-related metabolites that could be considered as toxicity monitoring biomarkers.Methods: The in vivo experiment employed two doses of CMS versus a control group treated with normal saline, and samples of plasma, kidney, and liver were analysed with a UPLC-MS-based metabolomics protocol. Both univariate and multivariate statistical approaches (PCA, OPLS-DA, PLS regression, ROC) and pathway analysis were combined for the data interpretation.Results: The results pointed out six dose-responding metabolites (PAA, DA4S, 2,8-DHA, etc.), dysregulation of renal dopamine, and extended perturbations in renal purine metabolism. Also, the study determined altered levels of liver suberylglycine, a metabolite linked to hepatic steatosis. One of the most intriguing findings was the detection of elevated levels of renal xanthine and uric acid, that act as AChE activators, leading to the rapid degradation of acetylcholine. This evidence provides a naïve hypothesis, for the potential association between the CMS induced nephrotoxicity and CMS induced 39 neurotoxicity, that should be further investigated.

Mathematical-model Analysis of the Potential Exposure to Lead, Zinc and Iron Emissions from Consumption of Premium Motor Spirit in Nigeria

Environmental pollution has been on the increase due to emission from vehicles using fossil fuels. This research investigated the exposure of air, soil and water bodies to trace metal emissions: Pb, Zn and Fe, as a result of the consumption of premium motor spirit (PMS) in Nigeria. The exposure of air, soil, and water bodies to these emissions also lead to exposure of humans, food and animals to the emissions. This was done to estimate the emission rates, emission rate per capita, and emission rates per land areas (or land distribution). The results showed that: the annual emission rates ranged between 4.66 kg/y for Pb in 2012 in Jigawa State and 5.050∙103 kg/y for Fe in 2015 in Lagos State; the emission rates per capita ranged between 0.52∙10−6 kg/(y∙person) for Pb in 2012 in Kwara State and 2.33∙10−3 kg/(y∙person) and this was recorded in Lagos State in the year 2015; while the rate per land area ranged between 0.093∙10−3 kg/(y∙km2) for Pb in 2012 in Taraba State and 1.38 kg/(y∙km2) for Fe in 2015 in Lagos State. Results showed that residents of Lagos are at the highest risk of trace metal poisoning because they had the highest emission rates per capita, followed by Abuja, Osun, and Ogun. The states at the lowest risk are Yobe and Taraba, with Yobe as the lowest. It is recommended that regulations concerning the trace metal contents of fuels imported and distributed in Nigeria should be created and implemented to curb these risks.

Per- and Polyfluorinated Substances (PFAS); a Literature Review

This literature review aims to assess contemporary research on human exposure to Per- and Polyfluorinated Substances (PFAS) using the PubMed database. A series of research papers were acquired and examined, revealing novel exposure routes (firefighting, blood transfusions), associations with renal cell carcinoma, impact on DNA methylation, and links to pregnancy and early infant health. PFAS is also associated with adiposity, heart disease, and impaired immune response post-vaccination. The literature suggests potential interventions through blood and plasma donations. Limitations in the scope and scale of research, along with gaps in the understanding of the carcinogenic potential of PFAS and the efficacy of interventions in reducing PFAS exposure, were identified. Further public health research should address these gaps and limitations to enhance our understanding and address the negative health outcomes associated with PFAS exposure.

Chlorfenapyr poisoning: a systematic review

Introduction Chlorfenapyr, a N-substituted halogenated pyrrole, is a broad-spectrum insecticide. The insecticidal activity of chlorfenapyr depends on its biotransformation by hepatic cytochrome P450 monooxygenases to tralopyril, which uncouples mitochondrial oxidative phosphorylation and disrupts adenosine triphosphate production. Neither the metabolism of chlorfenapyr nor the mechanism of tralopyril is completely elucidated. Acute human chlorfenapyr poisoning is not well characterized, and best practice in management following acute exposure is unclear. The purpose of this review is to characterize acute human chlorfenapyr poisoning by its clinical course, laboratory investigations, and imaging findings and propose a management plan for acute human chlorfenapyr exposure. Methods We systematically searched PubMed, Web of Science, Google Scholar, and EMBASE from inception to April 2024 across all languages for human chlorfenapyr and tralopyril cases, with descriptions of exposure, clinical manifestations, and clinical course included. Only manuscripts and abstracts from scientific conferences with sufficient clinical data following acute human exposures were included. In vitro studies, animal studies, agricultural studies, environmental impact studies, and non-clinical human studies were excluded. We then reviewed citations of included studies for additional eligible publications. Non-English publications were translated using Google Translate or primarily translated by our authors. The study adhered to Preferred Reporting for Systematic Reviews and Meta-analyses (PRISMA) guidelines for systematic reviews. Results We identified 3,376 publications of which 48 met study inclusion criteria, describing 75 unique cases of human poisoning from ingestion, inhalation, dermal exposure, and intra-abdominal injection of chlorfenapyr. No cases of tralopyril exposure were identified. The median time from exposure to symptom onset was six hours (interquartile range 1–48 hours). The most frequent initial or presenting signs/symptoms included diaphoresis, nausea and/or vomiting, and altered mental status. While hyperthermia (≥38 degrees centigrade) was less common at presentation, hyperthermia developed in 61 percent of all patients and was temporally associated with clinical deterioration and death. Most common laboratory abnormalities included elevated blood creatine kinase activity, hepatic aminotransferase activities, and lactate concentration. Imaging studies of the central nervous system often showed extensive symmetrical white matter abnormalities with swelling. Case fatality was 76 percent, and survivors commonly experienced sustained neurological sequelae. Management strategies were highly varied, and the effectiveness of specific medical interventions was unclear. Discussion Acute human chlorfenapyr poisoning is characterized by a latent period as long as 14 days, deterioration over hours to days, and can result in serious morbidity and mortality. Development of hyperthermia, likely driven by oxidative phosphorylation uncoupling by tralopyril, is an ominous clinical sign and is temporally associated with clinical decompensation and death. Laboratory abnormalities, particularly elevated creatine kinase activity, hepatic aminotransferase activities, and lactate concentration, were common, but only creatine kinase activity differed amongst survivors and fatalities. Best clinical practice in the management of patients exposed to chlorfenapyr is unclear, and we opine that a conservative approach with close clinical monitoring and supportive care is prudent. Limitations The limitations of all reviews include their inherent retrospective and observational nature as well as publication bias that emphasizes severe outcomes, thus impacting the spectrum of illness and skewing mortality percentage. In addition, we interrogated a finite number of databases for publications on human chlorfenapyr exposure and there were limited cases with laboratory testing to confirm chlorfenapyr poisoning. Analysis of our systematic review was not powered to detect differences between groups, comparative statistics were not performed, and significance is not reported. Conclusions Acute human chlorfenapyr toxicity is characterized by a latent period following exposure, development of new or progression of established signs/symptoms, potential for critical illness, rapid deterioration, serious morbidity, and mortality. A conservative approach to patient management is prudent.

Chlorfenapyr poisoning: a systematic review

Introduction Chlorfenapyr, a N-substituted halogenated pyrrole, is a broad-spectrum insecticide. The insecticidal activity of chlorfenapyr depends on its biotransformation by hepatic cytochrome P450 monooxygenases to tralopyril, which uncouples mitochondrial oxidative phosphorylation and disrupts adenosine triphosphate production. Neither the metabolism of chlorfenapyr nor the mechanism of tralopyril is completely elucidated. Acute human chlorfenapyr poisoning is not well characterized, and best practice in management following acute exposure is unclear. The purpose of this review is to characterize acute human chlorfenapyr poisoning by its clinical course, laboratory investigations, and imaging findings and propose a management plan for acute human chlorfenapyr exposure. Methods We systematically searched PubMed, Web of Science, Google Scholar, and EMBASE from inception to April 2024 across all languages for human chlorfenapyr and tralopyril cases, with descriptions of exposure, clinical manifestations, and clinical course included. Only manuscripts and abstracts from scientific conferences with sufficient clinical data following acute human exposures were included. In vitro studies, animal studies, agricultural studies, environmental impact studies, and non-clinical human studies were excluded. We then reviewed citations of included studies for additional eligible publications. Non-English publications were translated using Google Translate or primarily translated by our authors. The study adhered to Preferred Reporting for Systematic Reviews and Meta-analyses (PRISMA) guidelines for systematic reviews. Results We identified 3,376 publications of which 48 met study inclusion criteria, describing 75 unique cases of human poisoning from ingestion, inhalation, dermal exposure, and intra-abdominal injection of chlorfenapyr. No cases of tralopyril exposure were identified. The median time from exposure to symptom onset was six hours (interquartile range 1–48 hours). The most frequent initial or presenting signs/symptoms included diaphoresis, nausea and/or vomiting, and altered mental status. While hyperthermia (≥38 degrees centigrade) was less common at presentation, hyperthermia developed in 61 percent of all patients and was temporally associated with clinical deterioration and death. Most common laboratory abnormalities included elevated blood creatine kinase activity, hepatic aminotransferase activities, and lactate concentration. Imaging studies of the central nervous system often showed extensive symmetrical white matter abnormalities with swelling. Case fatality was 76 percent, and survivors commonly experienced sustained neurological sequelae. Management strategies were highly varied, and the effectiveness of specific medical interventions was unclear. Discussion Acute human chlorfenapyr poisoning is characterized by a latent period as long as 14 days, deterioration over hours to days, and can result in serious morbidity and mortality. Development of hyperthermia, likely driven by oxidative phosphorylation uncoupling by tralopyril, is an ominous clinical sign and is temporally associated with clinical decompensation and death. Laboratory abnormalities, particularly elevated creatine kinase activity, hepatic aminotransferase activities, and lactate concentration, were common, but only creatine kinase activity differed amongst survivors and fatalities. Best clinical practice in the management of patients exposed to chlorfenapyr is unclear, and we opine that a conservative approach with close clinical monitoring and supportive care is prudent. Limitations The limitations of all reviews include their inherent retrospective and observational nature as well as publication bias that emphasizes severe outcomes, thus impacting the spectrum of illness and skewing mortality percentage. In addition, we interrogated a finite number of databases for publications on human chlorfenapyr exposure and there were limited cases with laboratory testing to confirm chlorfenapyr poisoning. Analysis of our systematic review was not powered to detect differences between groups, comparative statistics were not performed, and significance is not reported. Conclusions Acute human chlorfenapyr toxicity is characterized by a latent period following exposure, development of new or progression of established signs/symptoms, potential for critical illness, rapid deterioration, serious morbidity, and mortality. A conservative approach to patient management is prudent.

Design Considerations and Experimental Testing of a Wide-Area Inductive Power Transfer (IPT) System for Body-Worn Electronics

The provision of wireless and battery-free power is key to extending the applications of body-worn sensing electronics. This paper investigates the design of an IPT system for a body-worn scenario where the challenges include highly variable coupling, the requirement for the coil/s to be flexible, and close proximity to the body. Variable coupling results in a system that must operate with received powers ranging over orders of magnitude, whilst the use of flexible coils reduces the Q-factor and results in the potential for inductance variation. The human exposure considerations limit both the maximum field strengths that the wearer of a receiver coil might experience and the field strengths that a third party might be exposed to. In this paper, analytical models are used to identify key design variables and to guide the design synthesis of an IPT system for a wrist-worn medical sensor. Practical circuits to drive the transmit coil and to interface the receive coil with the load electronics are described. A prototype system is tested to validate the theoretical analysis, providing power greater than 2 mW to the sensor over a hemispherical region up to 250 mm in radius from the transmit coil.

Clinical Ocular Exposure Extrapolation for a Complex Ophthalmic Suspension Using Physiologically Based Pharmacokinetic Modeling and Simulation

The development of generic ophthalmic drug products with complex formulations is challenging due to the complexity of the ocular system and a lack of sensitive testing to evaluate the interplay of its physiology with ophthalmic drugs. New methods are needed to facilitate the development of ophthalmic generic drug products. Ocular physiologically based pharmacokinetic (O-PBPK) models can provide insight into drug partitioning in eye tissues that are usually not accessible and/or are challenging to sample in humans. This study aims to demonstrate the utility of an ocular PBPK model to predict human exposure following the administration of ophthalmic suspension. Besifloxacin (Bes) suspension is presented as a case study. The O-PBPK model for Bes ophthalmic suspension (Besivance® 0.6%) accounts for nasolacrimal drainage, suspended particle dissolution in the tears, ocular absorption, and distribution in the rabbit eye. A topical controlled release formulation was used to integrate the effect of Durasite® on Bes ocular retention. The model was subsequently used to predict Bes exposure after its topical administration in humans. Drug-specific parameters were used as validated for rabbits. The physiological parameters were adjusted to match human ocular physiology. Simulated human ocular pharmacokinetic profiles were compared with the observed ocular tissue concentration data to assess the OCAT models’ ability to predict human ocular exposure. The O-PBPK model simulations adequately described the observed concentrations in the eye tissues following the topical administration of Bes suspension in rabbits. After adjustment of physiological parameters to represent the human eye, the extrapolation of clinical ocular exposure following a single ocular administration of Bes suspension was successful.