Unintended Exposure Research Articles

Trends and characteristics of ocular exposures related to e-cigarettes and e-liquids reported to Poison Control Centers in the United States, 2010–2019

Introduction Ocular injuries and unintended exposures involving electronic nicotine delivery systems (ENDS), also known as e-cigarettes, have been reported. However, trends and characteristics of ENDS-related ocular exposures at the population level are not well documented. This study was designed to describe trends and characteristics of ENDS-related ocular exposure cases reported to poison control centers (PCCs) in the U.S. Methods We computed descriptive statistics of ENDS-related ocular exposure cases reported to PCCs between January 1, 2010 and December 31, 2019, including number of cases per year and the distribution of characteristics of those cases. We also summarized case narrative review findings. Results A total of 1,393 ENDS-related ocular exposure cases were reported to PCCs during the study period. Overall number of cases increased from two in 2010 to a peak of 389 in 2014, followed by a steady decline in 2015–2018. Of the 1,393 cases, 42.5% occurred among individuals aged 25 years and older; 20.4 and 17.7% occurred among young adults aged 18–24 years and children younger than five years, respectively. Nearly one quarter (23.8%) of the individuals experiencing ocular exposure sought or were recommended to seek medical attention. Case narrative review found that 59 of 127 (46.5%) cases were due, at least in part, to incorrect use or handling of the products. Discussion and conclusions Our study shows that more than 1,000 ENDS-related ocular exposure cases were reported to PCCs during the study period. Many of these cases involved young children; nearly half were due, at least in part, to incorrect use or handling of the products. Future efforts to prevent these exposures may focus on improving the awareness of the potential harmful effects of ENDS products and the importance of appropriate handling of ENDS products. Health care professionals may play an important role in educating patients and improving surveillance of ENDS-related ocular exposure cases.

Approaches for setting occupational exposure limits in the pharmaceutical industry.

The use of pharmaceutical drugs has provided a cure for many diseases. However, unintended exposure to drugs in the manufacturing workplace can cause significant health hazards to workers. It is important to protect the workforce from these deleterious effects by limiting exposure to an acceptable level, the occupational exposure limit (OEL). OEL is defined as airborne concentrations (expressed as a time-weighted average for a conventional 8-h workday and a 40-h work week) of a substance to which nearly all workers may be repeatedly exposed (for a working lifetime) without adverse effects. Determination of OELs has become very challenging over time, requiring an overall assessment of the preclinical and clinical data of the drug being manufactured. Previously, to derive OEL values, toxicologists used animal no-observed-adverse-effect level (NOAEL) data, which have been replaced with the overall assessment of animal and human data, placing a higher emphasis on human health-based data. A major advantage of working with human pharmaceuticals is that sufficient clinical data are available for them in most cases. The present manuscript reviews the latest knowledge regarding the derivation of occupational exposure limits as health-based exposure limits (HBELs) for pharmaceuticals. We have provided examples of OEL calculations for various drugs including levofloxacin (CAS No. 100986-85-4), dienogest (CAS no. 65928-58-7), and acetylsalicylic acid (ASA, CAS no. 50-78-2) using human data. This report will benefit professionals in the OEL domain in understanding this highly important, growing, and challenging field.

Comparison of Mycoplasma hyopneumoniae response to infection by route of exposure

Mycoplasma hyopneumoniae (MHP) is a concern both for pig well-being and producer economic viability. In the absence of fully protective health interventions, producers rely on controlled exposure to induce an immune response in pigs and minimize the clinical outcomes of MHP infection in pig populations. This study compared the effect of route of exposure on MHP infection, antibody response, clinical signs, and pathology. Six-week-old MHP-negative pigs (n = 78) were allocated to negative control (n = 6) or one of three MHP exposure routes: intratracheal (n = 24, feeding catheter), intranasal (n = 24, atomization device), and aerosol (n = 24, fogger). Body weight, cough indices, and samples (serum, oral fluid, tracheal) were collected weekly through 49 days post-exposure (DPE). Intratrachal exposure produced the highest proportion (24/24) of MHP DNA-positive pigs on DPE 7, as well as earlier and higher serum antibody response. Intranasal and aerosol exposures resulted in infection with MHP DNA detected in tracheal samples from 18/24 and 21/24 pigs on DPE 7, respectively. Aerosol exposure had the least impact on weight gain (0.64 kg/day). No difference was observed among treatment groups in coughing and lung lesions at necropsy. While intratracheal inoculation and seeder animals are frequently used in swine production settings, intranasal or aerosol exposure are viable alternatives to achieve MHP infection. Regardless of the route, steps should be taken to verify the purity of the inoculum and, in the case of aerosol exposure, avert the unintended exposure of personnel and animals to other pathogens.

Proposals for the Russian quality assurance program in computed tomography

To ensure the quality assurance of CT-examinations, it is necessary to obtain the high-quality diagnostic information and maintain the optimal exposure levels of patients and medical staff. This paper is focused on the requirements and main aspects of quality assurance of CT-examinations, which include quality control of the equipment, methods of CT-image quality control, optimization of radiation protection, as well as management of the unintended and accidental medical exposure. The paper contains recommendations on quality control of diagnostic equipment, methods for monitoring the quality control of CT-images, values of diagnostic reference levels for the detection of abnormally high patient doses and optimization of the radiation protection of patients, as well as the recommendations for management of radiation and non-radiation accidents. All main sections of the paper represent an unified quality assurance system in computed tomography.

Fugitive aerosols in the intensive care unit: a narrative review.

The risk of unintended inhalation of fugitive aerosols is becoming a topic of increasing interest in the healthcare arena. These fugitive aerosols may be bioaerosols, generated by the patient themselves through cough or sneeze, or they may be therapeutic medical aerosols, generated by therapeutic medical aerosol generators with the intent of delivery to a specific patient's respiratory tract. This review focus' on therapeutic aerosols in the intensive care unit (ICU) only, those typically generated by nebulisers. In the intensive care environment, patients are generally in receipt of ventilatory support, and the literature suggests that these different support interventions influence fugitive therapeutic medical aerosol emissions in a variety of ways. Predominant ventilatory support interventions include, but are not limited to, invasive mechanical ventilation (MV), non-invasive mechanical ventilation (NIV), high flow nasal therapy (HFNT), and supplemental oxygen delivery in spontaneously breathing patients. Further, factors such as nebuliser type, patient interface, patient breathing pattern, nebuliser position in the patient breathing circuit and medication formulation characteristics also have been shown to exert influence on aerosol concentrations and distance from the source. Here we present the state of the art knowledge in this, as yet, poorly described field of research, and identify the key risks, and subsequently, opportunities to mitigate the risks of unintended exposure of both patients and bystanders during and for periods following the administration of therapeutic aerosols.

Fetal Physiologically Based Pharmacokinetic Models: Systems Information on Fetal Cardiac Output and Its Distribution to Different Organs during Development.

Fetal circulation is unique and the parameters describing hemodynamic status during development are critical for constructing a fetal physiologically based pharmacokinetic model. To date, a comprehensive review of circulatory changes during fetal development, with a specific focus on developing these models, has not been reported. The objective of this work was to collate, analyze, and mathematically describe physiological information on fetal cardiac output and tissue blood flows during development. A comprehensive literature search was carried out to collate and evaluate the changes to fetal cardiac output and fetal tissue blood flows during growth. The collated data were assessed, integrated, and analyzed to establish continuous mathematical functions describing the average parameter changes and variability during development. Data were available for fetal cardiac output (14 Doppler studies), blood flow through the fetal umbilical vein (15 studies), ductus venosus (6 studies), liver veins (5 studies), brain (4 studies), lungs (5 studies), and kidneys (2 studies). Fetal cardiac output is described as either an age- or weight-dependent function. The latter is preferred as it generates an individualized cardiac output that is correlated to the fetal body weight. Blood flow as a proportion of fetal cardiac output to the liver, placenta, brain, kidneys, and lungs was age varying, whilst for the adipose, bone, heart, muscle, and skin the blood flow proportions were fixed. The pattern of change (with respect to direction and pace) for each of these parameters was different. Despite limitations in the availability of some values, the collected data provide a useful resource for fetal physiologically based pharmacokinetic modeling. Potential applications of these data include predicting xenobiotic exposure and risk assessment in the fetus following the administration of maternally dosed drugs or unintended exposure to environmental toxicants.

Unintended Self-Inoculation with Bovine Paratuberculosis Vaccine Causing Granulomatous Dermatitis Positive for Acid-Fast Bacilli

ABSTRACT Mycobacterium paratuberculosis causes Johne’s disease in cattle, a chronic granulomatous enteritis for which a killed vaccine is commercially available. We present a case of a veterinarian who had an unintended needle-stick with injection of vaccine material. He developed a granulomatous dermatitis with acid-fast bacilli identified on pathology of affected tissue. It is important for health-care providers who care for patients at risk for unintended vaccine exposure to be aware of the possible sequelae after exposure and provide appropriate treatment based on the severity of the injury and subsequent tissue response.

Nanomaterial-Enabled Sensors and Therapeutic Platforms for Reactive Organophosphates.

Unintended exposure to harmful reactive organophosphates (OP), which comprise a group of nerve agents and agricultural pesticides, continues to pose a serious threat to human health and ecosystems due to their toxicity and prolonged stability. This underscores an unmet need for developing technologies that will allow sensitive OP detection, rapid decontamination and effective treatment of OP intoxication. Here, this article aims to review the status and prospect of emerging nanotechnologies and multifunctional nanomaterials that have shown considerable potential in advancing detection methods and treatment modalities. It begins with a brief introduction to OP types and their biochemical basis of toxicity followed by nanomaterial applications in two topical areas of primary interest. One topic relates to nanomaterial-based sensors which are applicable for OP detection and quantitative analysis by electrochemical, fluorescent, luminescent and spectrophotometric methods. The other topic is directed on nanotherapeutic platforms developed as OP remedies, which comprise nanocarriers for antidote drug delivery and nanoscavengers for OP inactivation and decontamination. In summary, this article addresses OP-responsive nanomaterials, their design concepts and growing impact on advancing our capability in the development of OP sensors, decontaminants and therapies.

Pregnancy screening practices and treatment of pregnant patients among radiation oncologists: results of an international survey.

BackgroundThe human embryo or foetus is susceptible to harmful effects of radiation, which include growth delay, malformations, impaired cognitive function, cancer and foetal demise. The purpose of this study is to describe pregnancy screening practices in radiation oncology, so that potential health effects may be avoided and areas of prevention may be identified.MethodsAn electronic survey was delivered to 6,304 members of the American Society for Radiation Oncology. The survey subjects were radiation oncologists who are currently practicing in the world. Chi-square tests and a multiple logistic regression model were used to analyse the data. All tests were two-sided and the statistical significance level used was 0.05. This study (STUDY00009765) was approved by an Institutional Review Board.ResultsA total of 434 responses from practicing radiation oncologists were received. Of these respondents, 69.1% were practicing in the United States. Of all respondents, 19.8% reported treating paediatric patients and 93.6% reported treating premenopausal patients. Despite 84.8% of radiation oncologists saying they would ‘strongly agree’ or ‘agree’ that one should screen for pregnancy prior to radiation therapy, 29.7% of respondents reported their department has no screening policy and 7.1% of respondents reported they do not screen for pregnancy. Having a departmental policy was associated with screening for pregnancy (p-value = 0.0005).Of all respondents, 93 reported treating a known pregnant patient. Of these 93 respondents, 76 reported intentionally treating and 17 reported accidentally treating a pregnant patient. Respondents who did not screen at time of simulation were significantly more likely to treat a pregnant patient than those who screened at time of simulation (p-value = 0.0459).ConclusionsHeterogeneity exists among practicing radiation oncologists regarding pregnancy screening. Institutional policies should be clear and consistent. All members of the radiation oncology team should make every effort to minimise unintended radiation exposure to the embryo or foetus.

Quantification of Accidental Gluten Contamination in the Diet of Children with Treated Celiac Disease.

A strict gluten-free diet is extremely difficult to maintain. Protracted ingestion of gluten traces (>10 mg/day) is sufficient to cause significant damage in the architecture of the small intestinal mucosa in patients on treatment for celiac disease. The aim of this study was to directly measure the level of contaminating gluten in the daily diet of celiac children following a gluten-free diet. From April 2019 to December 2019, celiac disease children (2–18 years old) on a gluten-free diet for ≥6 months were offered to participate in this prospective-observational study. Patients and their caregivers were invited to provide a representative portion (about 10 g) of all meals consumed during a 24-h period. Participants were requested to weigh all ingested food and report items in a 24-h food diary. The gluten content was quantified by the R5 sandwich enzyme-linked immunosorbent assay method. Sixty-nine children completed the protocol. Overall, 12/448 (2.7%) food samples contained detectable amounts of gluten; of them, 11 contained 5–20 ppm and 1 >20 ppm. The 12 contaminated food samples belonged to 5/69 enrolled patients. In these 5 children, the daily gluten intake was well below the safety threshold of 10 mg/day. The present findings suggest that in a country characterized by high celiac disease awareness, the daily unintended exposure to gluten of treated celiac children on regular follow-up is very low; reassuringly, the presence of gluten traces did not lead to exceed the tolerable threshold of 10 mg/day of gluten intake in the gluten-free diet.

Evanescent Wave Optical Fiber Sensors Using Enzymatic Hydrolysis on Nanostructured Polyaniline for Detection of β-Lactam Antibiotics in Food and Environment.

β-Lactam antibiotics such as penicillins and cephalosporins are extensively used for human infection therapy. Consistent unintended exposure to these antibiotics via food and water is known to promote antibiotic-resistant bacterial pathogenesis with high morbidity and mortality in humans. An optical enzymatic biosensor for rapid and point-of-use detection of these antibiotics in food and water has been developed and tested. Enzymatic hydrolysis of β-lactams, on the electroactive polyaniline nanofibers, altered the polymeric backbone of the nanofibers, from emeraldine base form to emeraldine salt, which was measured as an increase in evanescent wave absorbance at 435 nm. The sensors were calibrated by spiking antibiotic-free milk with ceftazidime (as a model β-lactam analyte) in a linear range of 0.36-3600 nM (R2 = 0.98). The calibration was further validated for packaged milk, local cow milk, and buffalo milk. A similar calibration was devised for chicken meat samples in a linear range of 9-1800 nM (R2 = 0.982) and tap water in a linear range of 0.18-180 nM (R2 = 0.99). Interestingly, it was possible to use the same calibration for the determination of other β-lactam antibiotics (ampicillin, amoxicillin, and cefotaxime), which reflects the usefulness of the sensor for wide-scale deployment. The sensor performance was validated with a wastewater sample, from a wastewater treatment plant (WWTP), qualitatively analyzed by high-resolution liquid chromatography coupled with mass spectroscopy for detection of β-lactams. The sensor scheme developed and tested is of grassroot relevance as a quick solution for measurement of β-lactam residues in food and environment.

Hazard Recognition Patterns Demonstrated by Construction Workers.

Construction workers fail to recognize a large number of safety hazards. These unrecognized safety hazards can lead to unintended hazard exposure and tragic safety incidents. Unfortunately, traditional hazard recognition interventions (e.g., job hazard analyses and safety training) have been unable to tackle the industry-wide problem of poor hazard recognition levels. In fact, emerging evidence has demonstrated that traditional hazard recognition interventions have been designed without a proper understanding of the challenges workers experience during hazard recognition efforts. Interventions and industry-wide efforts designed based on a more thorough understanding of these challenges can yield substantial benefits—including superior hazard recognition levels and lower injury rates. Towards achieving this goal, the current investigation focused on identifying hazard categories that workers are more proficient in recognizing and others that they are less proficient in recognizing (i.e., hazard recognition patterns). For the purpose of the current study, hazards were classified on the basis of the energy source per Haddon’s energy release theory (e.g., gravity, motion, electrical, chemical, etc.). As part of the study, 287 workers representing 57 construction workplaces in the United States were engaged in a hazard recognition activity. Apart from confirming previous research findings that workers fail to recognize a disproportionate number of safety hazards, the results demonstrate that the workers are more proficient in recognizing certain hazard types. More specifically, the workers on average recognized roughly 47% of the safety hazards in the gravity, electrical, motion, and temperature hazard categories while only recognizing less than 10% of the hazards in the pressure, chemical, and radiation hazard categories. These findings can inform the development of more robust interventions and industry-wide initiatives to tackle the issue of poor hazard recognition levels in the construction industry.

Mechanical cues protect against silica nanoparticle exposure in SH-SY5Y neuroblastoma

The increasing appearance of engineered nanomaterials in broad biomedical and industrial sectors poses an escalating health concern from unintended exposure with unknown consequences. Routine in vitro assessments of nanomaterial toxicity are a vital component to addressing these mounting health concerns; however, despite the known role of cell-cell and cell-matrix contacts in governing cell survival, these physical interactions are generally ignored. Herein, we demonstrate that exposure to amorphous silica particles destabilizes mitochondrial membrane potential, stimulates reactive oxygen species (ROS) production and promotes cytotoxicity in SH-SY5Y human neuroblastoma through mechanisms that are potently matrix dependent, with SH-SY5Y cells plated on the softest matrix displaying a near complete recovery in viability compared to dose-matched cells plated on tissue-culture plastic. Cells on the softest matrix (3 kPa) further displayed a 50% reduction in ROS production and preserved mitochondrial membrane potential. The actin cytoskeleton is mechanosensitive and closely related to ROS production. SH-SY5Y cells exposed to a 100 μg/mL dose of 50 nm silica particles displayed distinct cytoskeletal aberrations and a 70% increase in cell stiffness. Overall, this study establishes that the mechanical environment can significantly impact silica nanoparticle toxicity in SH-SY5Y cells. The mechanobiochemical mechanisms behind this regulation, which are initiated at the cell-matrix interface to adjust cytoskeletal structure and intracellular tension, demand specific attention for a comprehensive understanding of nanotoxicity.

Thirdhand Smoke Contamination and Infant Nicotine Exposure in a Neonatal Intensive Care Unit: An Observational Study.

Thirdhand smoke (THS) is ultrafine particulate matter and residue resulting from tobacco combustion, with implications for health-related harm (eg, impaired wound healing), particularly among hospitalized infants. Project aims were to characterize nicotine (THS proxy) transported on neonatal intensive care unit (NICU) visitors and deposited on bedside furniture, as well as infant exposure. Cross-sectional data were collected from participants in a metropolitan NICU. Participants completed a survey and carbon monoxide breath sample, and 41.9% (n = 88) of participants (n = 210) were randomly selected for finger-nicotine wipes during a study phase when all bedside visitors were screened for nicotine use and finger-nicotine levels. During an overlapping study phase, 80 mother-infant dyads consented to bedside furniture-nicotine wipes and an infant urine sample (for cotinine analyses). Most nonstaff visitors' fingers had nicotine above the limit of quantification (>LOQ; 61.9%). Almost all bedside furniture surfaces (93.8%) and infant cotinine measures (93.6%) had values >LOQ, regardless of household nicotine use. Participants who reported using (or lived with others who used) nicotine had greater furniture-nicotine contamination (Mdn = 0.6 [interquartile range, IQR = 0.2-1.6] µg/m2) and higher infant cotinine (Mdn = 0.09 [IQR = 0.04-0.25] ng/mL) compared to participants who reported no household-member nicotine use (Mdn = 0.5 [IQR = 0.2-0.7] µg/m2; Mdn = 0.04 [IQR = 0.03-0.07] ng/mL, respectively). Bayesian univariate regressions supported hypotheses that increased nicotine use/exposure correlated with greater nicotine contamination (on fingers/furniture) and infant THS exposure. Potential furniture-contamination pathways and infant-exposure routes (eg, dermal) during NICU hospitalization were identified, despite hospital prohibitions on tobacco/nicotine use. This work highlights the surreptitious spread of nicotine and potential THS-related health risks to vulnerable infants during critical stages of development. THS contamination is underexplored in medical settings. Infants who were cared for in the NICU are vulnerable to health risks from THS exposure. This study demonstrated that 62% of nonstaff NICU visitors transport nicotine on their fingers to the NICU. Over 90% of NICU (bedside) furniture was contaminated with nicotine, regardless of visitors' reported household-member nicotine use or nonuse. Over 90% of infants had detectable levels of urinary cotinine during NICU hospitalizations. Results justify further research to better protect infants from unintended THS exposure while hospitalized.

Confocal scanning photoluminescence for mapping electron and photon beam-induced microscopic changes in SiNx during nanopore fabrication

Focused electron and laser beams have shown the ability to form nanoscale pores in SiNx membranes. During the fabrication process, areas beyond the final nanopore location will inevitably be exposed to the electron beams or the laser beams due to the need for localization, alignment and focus. It remains unclear how these unintended exposures affect the integrity of the membrane. In this work, we demonstrate the use of confocal scanning photoluminescence (PL) for mapping the microscopic changes in SiNx nanopores when exposed to electron and laser beams. We developed and validated a model for the quantitative interpretation of the scanned PL result. The model shows that the scanning PL result is insensitive to the nanopore size. Instead, it is dominated by the product of two microscopic material factors: quantum yield profile (i.e. variations in electronic structure) and thickness profile (i.e. thinning of the membrane). We experimentally demonstrated that the electron and laser beams could alter the material electronic structures (i.e. quantum yield) even when no thinning of the membrane occurs. Our results suggest that minimizing the unintended e-beam or laser beam to the SiNx during the fabrication is crucial if one desires the microscopic integrity of the membrane.

The Cytotoxicity of Metal Nanoparticles Depends on Their Synergistic Interactions

AbstractWith a steady growth in use of engineered nanoparticles (NPs) in consumer products the unintended exposure to humans has increased. The risks associated with introduction of NPs in the environment have been widely investigated, but mostly for single type of NPs. Herein, a single NP and NP co‐exposure study is reported: the cellular effects of silver and platinum NPs on the main components of the blood–brain barrier, human cerebral microvascular endothelial cells, and human primary astrocytes. The synergy is quantitatively evaluated as per the Chou–Talalay method. NP co‐exposure synergistically inhibits proliferation of both cell types, to a greater extent for endothelial cells. In addition, astrocytes are more tolerant to NPs. The mechanism of synergy with short‐duration incubation time points (up to 30 min) is further explored. Although intracellular trafficking studies and quantitative assessments of NP uptake does not explain the mechanisms of synergistic cytotoxicity, a proteomics analysis suggests that it arises from activation of an immune modulating response and deregulation of the extracellular matrix organization. The substantial synergetic effects in the co‐exposure studies highlight the importance of this work in relation to assessment of the health risks associated with nanomaterials.

Extended-Interval Dosing Strategy of Immune Checkpoint Inhibitors in Lung Cancer: Will it Outlast the COVID-19 Pandemic?

Patients with lung cancer are particularly vulnerable to complications from coronavirus disease-2019 (COVID-19). Recurrent hospital visits and hospital admission are potential risk factors for acquiring infection with its causative pathogen, severe acute respiratory syndrome coronavirus−2 (SARS-CoV-2). As immune checkpoint inhibitors (ICIs) constitute the therapeutic backbone for the vast majority of patients with advanced lung cancer in the absence of actionable driver oncogenes, there have been intense discussions within the oncology community regarding risk-benefit of delaying these treatments or use of alternative extended-interval treatment strategies to minimize the risk of viral transmission secondary to unintended nosocomial exposures. In the midst of the COVID-19 pandemic, the U.S. Food and Drug Administration (FDA) granted accelerated approval for extended-interval strategy of pembrolizumab at a dose of 400 mg every 6 weeks for all already approved oncologic indications. Herein, we summarize the evidence from the in silico pharmacokinetic modeling/simulation studies supporting extended-interval dosing strategies for the ICIs used in lung cancer. We further review the evolving clinical evidence behind these approaches and predict that they will continue to be used in routine practice even long after the pandemic, particularly for patients with durable disease control.

Dicamba Retention in Commercial Sprayers Following Triple Rinse Cleanout Procedures, and Soybean Response to Contamination Concentrations

The commercial launch of dicamba-tolerant (DT) crops has resulted in increased dicamba usage and a high number of dicamba off-target movement complaints on sensitive soybeans (Glycine max L.). Dicamba is a synthetic auxin and low dosages as 0.028 g ae ha−1 can induce injury on sensitive soybean. Tank contamination has been identified as one of the sources for unintended sensitive crop exposure. The labels of new dicamba formulations require a triple rinse cleanout procedure following applications. Cleanout efficacy might vary based on the sprayer type and procedure followed. This study was performed to quantify dicamba retention in commercial sprayers and assess the risk for crop injury from remaining contaminants. The results indicate triple rinse with water was comparable to cleanout procedures utilizing ammonium, commercial tank cleaners, and glyphosate in rinses. Dicamba contaminants in final rinsates resulted in <15% visual injury and no yield response when applied to sensitive soybeans at R1 stage. A survey of 25 agricultural sprayers demonstrated a cleanout efficacy of 99.996% by triple rinsing with water following applications of dicamba at 560 g ae ha−1, with concentrations of less than 1 ug mL−1 detected rinsates from the fourth rinse. A dose response experiment predicted dosages causing 5% visual injury and the yield losses were 0.1185 and 2.8525 g ae ha−1. However, symptomology was observed for all tested dosages, including the rate as low as 0.03 g ae ha−1. The results from this study suggest triple rinsing with sufficient amount of water (≥10% of tank volume) is adequate for the removal of dicamba residues from sprayers to avoid sensitive soybean damage. This study can provide producers with confidence in cleanout procedures following dicamba applications, and aid in minimizing risk for off-target movement through tank contamination.

Metabolism of mono-(2-ethylhexyl) phthalate in Arabidopsis thaliana: Exploration of metabolic pathways by deuterium labeling

Mono-(2-ethylhexyl) phthalate (MEHP) is the primary monoester transformation product of the commonly used plasticizer, di-2-ethylhexyl phthalate (DEHP), and has been frequently detected in various environmental compartments (e.g., soil, biosolids, plants). Plants growing in contaminated soils can take up MEHP, and consumption of the contaminated plants may result in unintended exposure for humans and other organisms. The metabolism of MEHP in plants is poorly understood, but critical for evaluating the potential human and environmental health risks. The present study represents the first attempt to explore the metabolic fate of MEHP in plants. We used Arabidopsis thaliana cells as a plant model and explored metabolic pathways of MEHP using deuterium stable isotope labelling (SIL) coupled with time-of-flight high resolution mass spectrometer (TOF-HRMS). A. thaliana rapidly took up MEHP from the culture medium and mediated extensive metabolism of MEHP. Combining SIL with TOF-HRMS analysis was proved as a powerful method for identification of unknown MEHP metabolites. Four phase Ⅰ and three phase Ⅱ metabolites were confirmed or tentatively identified. Based on the detected transformation products, hydroxylation, oxidation, and malonylation are proposed as the potential MEHP metabolism pathways. In cells, the maximum fraction of each transformation product accounted for 2.8–56.5% of the total amount of metabolites during the incubation. For individual metabolites, up to 2.9–100% was found in the culture medium, suggesting plant excretion. The results in the cell culture experiments were further confirmed in cabbage and A. thaliana seedlings. The findings suggest active metabolism of MEHP in plants and highlight the need to include metabolites in refining environmental risk assessment of plasticizers in the agro-food systems.

Evaluation of Different Quality-Relevant Aspects of Closed System Transfer Devices (CSTDs).

Health care professionals can be exposed to hazardous drugs such as cytostatics during preparation of drugs for administration. Closed sytem transfer devices (CSTDs) were introduced to provide protection for healthcare professional against unintended exposure to hazardous drugs. The interest in CSTDs has significantly increased after USP <800> monograph was issued. The majority of the studies published so far on CSTDs have focused on their "containment" function. However, other important attributes for CSTDs with potential importance for product quality impact are not yet fully evaluated. In the current study, we evaluated four sytems from different suppliers, in combination with different container closure systems (CCS), using solutions of different viscosity and surface tension. The different CSTD / CCS combinations were tested for (a) containment (integrity) using a highly sensitive helium leak test, (b) the force required for mounting the vial adaptor, (c) contribution to visible and subvisible particles as well as (d) the hold-up volume. Results show that the majority of CSTDs may have leaks varying in size, and that some of them generated visible particles due to stopper coring and subvisible particles, both due to silicon oil and particulate contaminations of the Devices. Finally, the holdup volume was up to 1mL depending on the CSTD type, vial size and solution viscosity. These results show that there is a need to evaluate the compatibility of CSTD systems to select the best system for the intended use and that CSTDs may adversely impact product quality and delivered dose.