The Toxicology Investigators Consortium 2022 Annual Report.

Since 2010, medical toxicology physicians from the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC) have provided reports on their in-hospital and clinic patient consultations to a national case registry, known as the ToxIC Core Registry. De-identified patient data entered into the registry includes patient demographics, reason for medical toxicology evaluation, exposure agents, clinical signs and symptoms, treatments and antidotes administered, and mortality. This thirteenth annual report provides data from 7206 patients entered into the Core Registry in 2022 by 35 participating sites comprising 52 distinct healthcare facilities, bringing the total case count to 94,939. Opioid analgesics were the most commonly reported exposure agent class (15.9%), followed by ethanol (14.9%), non-opioid analgesic (12.8%), and antidepressants (8.0%). Opioids were the leading agent of exposure for the first time in 2022 since the Core Registry started. There were 118 fatalities (case fatality rate of 1.6%). Additional descriptive analyses in this annual report were conducted to describe the location of the patient during hospitalization, telemedicine consultations, and addiction medicine treatments.

Naloxone Use in Novel Potent Opioid and Fentanyl Overdoses in Emergency Department Patients.

Importance: Synthetic opioids, such as the fentanyl analogue and nitazene drug class, are among the fastest growing types of opioids being detected in patients in the emergency department (ED) with illicit opioid overdose (OD). However, clinical outcomes from OD of novel potent opioids (NPOs), specifically nitazenes, are unknown aside from small case series. Objective: To determine naloxone administration and clinical sequelae of patients who were in the ED with NPO overdose compared with fentanyl OD. Design, Setting, and Participants: This is a cohort study subgroup analysis of adults admitted to the ED and tested positive for NPOs among in the ongoing nationwide ToxIC Fentalog cohort study from 2020 to 2022. Patients who were in the ED with a presumed acute opioid OD and residual blood samples were included, and those testing positive for NPOs were analyzed. Patients were included in this analysis if their confirmatory testing was positive for an NPO analyte, such as brorphine, isotonitazene, metonitazene, and/or N-piperidinyl etonitazene. A comparison group included patients that were positive for fentanyl and devoid of any other analytes on toxicologic analysis. Exposures: Patients were exposed to NPOs, including brorphine, isotonitazene, metonitazene and/or N-piperidinyl etonitazene. Main Outcomes and Measures: The primary outcome was the total number of naloxone doses and total cumulative naloxone dose administered as part of routine clinical care following the OD. Naloxone requirements and clinical sequelae of NPO-positive patients were compared with those testing positive for fentanyl only. Results: During the study period, 2298 patients were screened, of whom 717 met inclusion criteria, 537 had complete laboratory testing data, with 11 (2.0%) positive for only fentanyl and 9 (1.7%) positive for NPOs (brorphine, isotonitazene, metonitazene, or N-piperidinyl etonitazene). The age range of patients was aged 20 to 57 years (4 males [44.4%] and 5 females [55.6%]). The NPO group received a statistically significantly higher mean (SD) number of naloxone boluses in-hospital (1.33 [1.50]) compared with the fentanyl group (0.36 [0.92]) (P = .02), which corresponded to a moderately large effect size (Cohen d = 0.78). Metonitazene overdose was associated with cardiac arrest and more naloxone doses overall. Metonitazene cases had a mean (SD) number of 3.0 (0) naloxone doses, and 2 of 2 patients (100%) with metonitazene overdoses were administered cardiopulmonary resuscitation. Conclusions and Relevance: In this cohort study of patients admitted to the ED with confirmed opioid overdose testing positive for NPOs, in-hospital naloxone dosing was high compared with patients who tested positive for fentanyl alone. Further study is warranted to confirm these preliminary associations.

The Toxicology Investigators Consortium Case Registry-the 2021 Annual Report.

The Toxicology Investigators Consortium (ToxIC) Core Registry was established by the American College of Medical Toxicology in 2010. The Core Registry collects data from participating sites with the agreement that all bedside and telehealth medical toxicology consultations will be entered. This twelfth annual report summarizes the registry's 2021 data and activity with its additional 8552 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from January 1 to December 31, 2021. Detailed data was collected from these cases and aggregated to provide information, which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. Gender distribution included 50.4% of cases in females, 48.2% of cases in males, and 1.4% of cases in transgender or gender non-conforming individuals. Non-opioid analgesics were the most commonly reported agent class (14.9%), followed by opioids (13.1%). Acetaminophen was the most common agent reported. Fentanyl was the most common opioid reported and was responsible for the greatest number of fatalities. There were 120 fatalities, comprising 1.4% of all cases. Major trends in demographics and exposure characteristics remained similar to past years' reports. Sub-analyses were conducted to describe new demographic characteristics, including marital status, housing status and military service, the continued COVID-19 pandemic and related toxicologic exposures, and novel substances of exposure.

Predictors of severe outcome following opioid intoxication in children.

INTRODUCTION: While the opioid crisis has claimed the lives of nearly 500,000 in the U.S. over the past two decades, and pediatric cases of opioid intoxications are increasing, only sparse data exist regarding risk factors for severe outcome in children following an opioid intoxication. We explore predictors of severe outcome (i.e., intensive care unit [ICU] admission or in-hospital death) in children who presented to the Emergency Department with an opioid intoxication. METHODS: In this prospective cohort study we collected data on all children (0-18 years) who presented with an opioid intoxication to the 50 medical centers in the US and two international centers affiliated with the Toxicology Investigators Consortium (ToxIC) of the American College of Medical Toxicology, from August 2017 through June 2020, and who received a bedside consultation by a medical toxicologist. We collected relevant demographic, clinical, management, disposition, and outcome data, and we conducted a multivariable logistic regression analysis to explore predictors of severe outcome. The primary outcome was a composite severe outcome endpoint, defined as ICU admission or in-hospital death. Covariates included sociodemographic, exposure and clinical characteristics. RESULTS: Of the 165 (87 females, 52.7%) children with an opioid intoxication, 89 (53.9%) were admitted to ICU or died during hospitalization, and 76 did not meet these criteria. Seventy-four (44.8%) children were exposed to opioids prescribed to family members. Fentanyl exposure (adjusted OR [aOR] = 3.6, 95% CI: 1.0-11.6; p = 0.03) and age ≥10 years (aOR = 2.5, 95% CI: 1.2-4.8; p = 0.01) were independent predictors of severe outcome. CONCLUSIONS: Children with an opioid toxicity that have been exposed to fentanyl and those aged ≥10 years had 3.6 and 2.5 higher odds of ICU admission or death, respectively, than those without these characteristics. Prevention efforts should target these risk factors to mitigate poor outcomes in children with an opioid intoxication.

The Toxicology Investigators Consortium 2020 Annual Report.

The Toxicology Investigators Consortium (ToxIC) Registry was established by the American College of Medical Toxicology in 2010. The registry collects data from participating sites with the agreement that all bedside and telehealth medical toxicology consultation will be entered. This eleventh annual report summarizes the Registry's 2020 data and activity with its additional 6668 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from January 1 to December 31, 2020. Detailed data was collected from these cases and aggregated to provide information which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. Gender distribution included 50.6% cases in females, 48.4% in males, and 1.0% identifying as transgender. Non-opioid analgesics were the most commonly reported agent class, followed by opioid and antidepressant classes. Acetaminophen was once again the most common agent reported. There were 80 fatalities, comprising 1.2% of all registry cases. Major trends in demographics and exposure characteristics remained similar to past years' reports. Sub-analyses were conducted to describe race and ethnicity demographics and exposures in the registry, telemedicine encounters, and cases related to the COVID-19 pandemic.

The Toxicology Investigators Consortium Case Registry-the 2019 Annual Report.

The Toxicology Investigators Consortium (ToxIC) Registry was established by the American College of Medical Toxicology (ACMT) in 2010. The Registry collects data from participating sites with the agreement that all bedside medical toxicology consultation will be entered. This tenth annual report summarizes the Registry's 2019 data and activity with its additional 7177 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from 1 January to 31 December 2019. Detailed data was collected from these cases and aggregated to provide information which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. 50.7% of cases were female, 48.5% were male, and 0.8% were transgender. Non-opioid analgesics was the most commonly reported agent class, followed by opioid and antidepressant classes. Acetaminophen was once again the most common agent reported. There were 91 fatalities, comprising 1.3% of all Registry cases. Major trends in demographics and exposure characteristics remained similar to past years' reports. Sub-analyses were conducted to describe exposures in cases of self-harm, gender differences in substance use disorder, and trends in addiction medicine and pain management consultations.

Drug-specific risk of severe QT prolongation following acute drug overdose.

Background: Severe QT prolongation (SQTP) has been identified as a strong predictor of adverse cardiovascular events in acute drug overdose, but drug-specific causes of SQTP in the setting of acute drug overdose remain unclear. We aimed to perform the most definitive study to date describing drug-specific risk of SQTP following acute drug overdose.Methods: This was a prospective multicenter cohort study at >50 hospital sites across the US using the ToxIC Registry between 2015 and 2018. Inclusion criteria were adults (≥18 years) receiving medical toxicology consultation for acute drug overdose. The primary outcome was SQTP, which was defined using the computer automated Bazett QT correction (QTc) on the ECG with the previously validated cut point of 500 milliseconds. Mean difference in QTc was also calculated for specific drugs. Drugs associated with SQTP were analyzed using multivariable logistic regression to control for known confounders of QT risk (age, sex, race, cardiac disease).Results: From 25,303 patients screened, 6473 met inclusion criteria with SQTP occurring in 825 (13%). Drugs associated with increased adjusted odds of SQTP included Class III antidysrhythmics (sotalol), sodium channel blockers (amitriptyline, diphenhydramine, doxepin, imipramine, nortriptyline), antidepressants (bupropion, citalopram, escitalopram, trazodone), antipsychotics (haloperidol, quetiapine), and the antiemetic serotonin antagonist ondansetron.Conclusions: This large US cohort describes drug-specific risk of SQTP following acute drug overdose. Healthcare providers caring for acute drug overdoses from any of these implicated drugs should pay close attention to cardiac monitoring for occurrence of SQTP.

Fatalities in poisoned patients managed by medical toxicologists.

Background: Poisoning is a leading cause of injury-related death in the United States. The Toxicology Investigators Consortium (ToxIC) Case Registry, established by the American College of Medical Toxicology, prospectively captures patients who were directly cared for and managed at the bedside by medical toxicology services. We sought to describe exposure cases who presented to Emergency Departments (EDs) across ToxIC sites, received direct bedside care by medical toxicologists; however, the intoxication resulted in fatality.Methods: We identified all cases in the ToxIC Case Registry that resulted in fatality after hospital presentation over the 6-year study period. We collected data on patient demographics and clinical information including age group, sex, circumstances of exposure, route of exposure, substances involved, presenting signs and symptoms and management prior to death.Results: Of 44,567 recorded cases in the registry over the study period, 268 (0.6%) fatalities met the inclusion criteria and comprise the study cohort. There was no sex predominance (138 females; 51.5%) and 27 (10.1%) were pediatric fatalities. In 195 (72.7%) patients, exposure was intentional. In 175 (65.3%) patients, fatality was associated with exposure to pharmaceuticals. The leading substances resulting in death were non-opioid analgesics, followed by opioids (72% prescription opioids), cardiovascular medications, sedatives, antipsychotics, antidepressants, and sympathomimetics. At time of consult, the central nervous system was the most common system affected in both fatal and non-fatal cases. Compared with non-fatal ToxIC cases (n = 44,299), fatal cases involved significantly less children (27.7% vs. 10.1%, respectively; p < .001), and were managed more aggressively (e.g., mechanical ventilation 8.3% vs. 69.8%, p < .001). Both non-opioid analgesics (25.3% vs. 14.7%; p < .001) and opioids (17.8% vs. 7.5%; p < .001) were significantly more likely to be ingested in fatal compared with non-fatal cases, although analgesics, opioids, and non-opioids, were the most common agents implicated in both groups.Conclusions: Most ToxIC registry exposures resulting in death involve intentional exposure, without sex predominance. One in 10 fatalities involved a child. Analgesics, non-opioids, and opioids are the most commonly implicated agents in both fatal and non-fatal intoxications, which highlights the centrality of these agents as major sources of both morbidity and mortality.

The Toxicology Investigators Consortium Case Registry-the 2018 Annual Report.

The Toxicology Investigators Consortium (ToxIC) Registry was established by the American College of Medical Toxicology (ACMT) in 2010. The Registry collects data from participating sites with the agreement that all bedside medical toxicology consultation will be entered. The objective of this ninth annual report is to summarize the Registry's 2018 data and activity with its additional 7043 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from 1 January to 31 December 2018. Detailed data was collected from these cases and aggregated to provide information which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. A total of 51.5% of cases were female, 48% were male, and 0.6% transgender. Non-opioid analgesics were the most commonly reported agent class, followed by antidepressants and opioids. Acetaminophen was once again the most common agent reported. There were 106 fatalities, comprising 1.5% of all registry cases. Major trends in demographics and exposure characteristics remained similar to past years' reports. Sub-analyses were conducted to describe exposures in elderly patients, addiction consultation practices, and risk factors for bupropion-induced seizures. The launch of the ToxIC Qualified Clinical Data Registry (TQCDR) is also described.

Correction to: The Toxicology Investigators Consortium Case Registry-The 2017 Annual Report.

Please note the Collaborators for this article listed in the Acknowledgements.

The Toxicology Investigators Consortium Case Registry-the 2017 Annual Report.

The Toxicology Investigators Consortium (ToxIC) Case Registry was established by the American College of Medical Toxicology in 2010. The Registry collects data from participating sites with the agreement that all bedside medical toxicology consultations will be entered. The objective of this eighth annual report is to summarize the Registry's 2017 data and activity with its additional 7577 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from 1 January to 31 December 2017. Detailed data was collected from these cases and aggregated to provide information which includes demographics (e.g., age, gender, race, ethnicity), reason for medical toxicology evaluation (e.g., intentional pharmaceutical exposure, envenomation, withdrawal from a substance), agent and agent class, clinical signs and symptoms (e.g., vital sign abnormalities, organ system dysfunction), treatments and antidotes administered, fatality, and life support withdrawal data. Females were involved in 50.4% of cases. Transgender demographic information collection was initiated in 2017 to better represent the population and there were 36 cases involving transgender patients. Adults aged 19-65 were the most commonly reported age group. Non-opioid analgesics were the most commonly reported agent class, with acetaminophen again the most common agent reported. There were 93 fatalities reported in 2017. Treatment interventions were frequently reported with 30.6% receiving specific antidotal therapy. Major trends in demographics and exposure characteristics remained similar to past years' reports. While treatment interventions were commonly required, fatalities were rare.

The Toxicology Investigators Consortium Case Registry-the 2016 Experience.

The Toxicology Investigators Consortium (ToxIC) Case Registry was established by the American College of Medical Toxicology in 2010. The Registry contains data from participating sites with the agreement that all bedside medical toxicology consultations will be entered. Currently, 83% of accredited medical toxicology fellowship programs in the USA participate. The Registry continues to grow each year, and as of 31 December 2016, a new milestone was reached, with more than 50,000 cases reported since its inception. The objective of this seventh annual report is to summarize the Registry's 2016 data and activity with its additional 8529 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from 1 January to 31 December 2016. Detailed data was collected from these cases and aggregated to provide information which includes the following: demographics (age, gender, race, ethnicity, HIV status), reason for medical toxicology evaluation (intentional pharmaceutical exposure, envenomation, withdrawal from a substance), agent and agent class, clinical signs and symptoms (vital sign abnormalities, organ system dysfunction), treatments and antidotes administered, fatality and life support withdrawal data. Fifty percent of cases involved females, and adults aged 19-65 were the most commonly reported. There were 86 patients (1.0%) with HIV-positive status known. Non-opioid analgesics were the most commonly reported agent class, with acetaminophen the most common agent reported. There were 126 fatalities reported in 2016 (1.5% of cases). Major trends in demographics and exposure characteristics remained similar overall with past years' reports. While treatment interventions were commonly required, fatalities were rare.

Characteristics and Treatment of Patients with Clinical Illness Due to Synthetic Cannabinoid Inhalation Reported by Medical Toxicologists: A ToxIC Database Study.

INTRODUCTION: Synthetic cannabinoid (SC) abuse has resulted in numerous outbreaks of severe clinical illness across the United States over the past decade. The primary objective of this study was to determine the clinical characteristics of patients abusing SC requiring bedside consultation by medical toxicologists. METHODS: This was a multicenter analysis from a prospectively collected cohort of patients presenting to medical care after synthetic cannabinoid exposure, utilizing the ToxIC Registry. Management of cases by medical toxicologists in this cohort occurred in emergency departments, inpatient medical floors, and intensive care units. Cases were identified from January 5, 2010 - July 31, 2015. We characterized the clinical presentations, treatments, outcomes, and sociologic factors associated with SC use in these patients. RESULTS: Medical toxicologists participating in the ToxIC Registry cared for 39,925 cases between 2010 and 2015. Three hundred fifty three of these cases were determined to be SC toxicity. The median age of patients was 25 (IQR: 18, 36) and the majority were males (84%). The most common symptoms were agitation, delirium and toxic psychosis, n=146 (41%). Forty-four (12.5%) had heart rates above 140 beats per minute. Bradycardia was the second most commonly reported severe vital sign abnormality with 20 (5.7%) having heart rates of less than 50 beats per minute. Fifteen (4.2%) patients had hypotension. Fifty-nine (17%) had seizures. The most common pharmacologic treatment provided was benzodiazepines (n=131, 37%) followed by antipsychotics (n=36, 10%).Disposition was available for 276; of these 167 (61%) were managed in the emergency department, 42 (15%) were admitted to the hospital floor, and 67 (24%) were admitted to the ICU. CONCLUSIONS: Synthetic cannabinoids are associated with severe central nervous system and cardiovascular effects.

The Toxicology Investigators Consortium Case Registry-the 2015 Experience.

The American College of Medical Toxicology established the Toxicology Investigators Consortium (ToxIC) Case Registry in 2010. The Registry contains all medical toxicology consultations performed at participating sites. The Registry has continued to grow since its inception, and as of December 31, 2015, contains 43,099 cases. This is the sixth annual report of the ToxIC Registry, summarizing the additional 8115 cases entered in 2015. Cases were identified by a query of the Registry for all cases entered between January 1 and December 31, 2015. Specific data reviewed for analysis included demographics (age, race, gender), source of consultation, reason for consultation, agents and agent classes involved in exposures, signs, symptoms, clinical findings, fatalities, and treatment. By the end of 2015, there were 50 active sites, consisting of 101 separate health-care facilities; 51.2 % of cases involved females. Adults between the ages of 19 and 65 made up the majority (64.2 %) of Registry cases. Caucasian race was the most commonly reported (55.6 %); 9.6 % of cases were identified as Hispanic ethnicity. Inpatient and emergency department referrals were by far the most common referral sources (92.9 %). Intentional pharmaceutical exposures remained the most frequent reason for consultation, making up 52.3 % of cases. Of these intentional pharmaceutical exposures, 69 % represented an attempt at self-harm, and 85.6 % of these were a suicide attempt. Nonopioid analgesics, sedative-hypnotics, and antidepressant agents were the most commonly reported agent classes in 2015. Almost one-third of Registry cases involved a diagnosed toxidrome (32.8 %), with a sedative-hypnotic toxidrome being the most frequently described. Significant vital sign abnormalities were recorded in 25.3 % of cases. There were 98 fatalities reported in the Registry (1.2 %). Adverse drug reactions were reported in 4.3 % of cases. Toxicological treatment was given in 65.3 % of cases, with 33.0 % receiving specific antidotal therapy. Exposure characteristics and trends overall were similar to prior years. While treatment interventions were required in the majority of cases, fatalities were rare.

Acute Poisonings from Synthetic Cannabinoids - 50 U.S. Toxicology Investigators Consortium Registry Sites, 2010-2015.

Recent reports suggest that acute intoxications by synthetic cannabinoids are increasing in the United States (1,2). Synthetic cannabinoids, which were research compounds in the 1980s, are now produced overseas; the first shipment recognized to contain synthetic cannabinoids was seized at a U.S. border in 2008 (3). Fifteen synthetic cannabinoids are Schedule I controlled substances (3), but enforcement is hampered by the continual introduction of new chemical compounds (1,3). Studies of synthetic cannabinoids indicate higher cannabinoid receptor binding affinities, effects two to 100 times more potent than Δ(9)-tetrahydrocannabinol (the principal psychoactive constituent of cannabis), noncannabinoid receptor binding, and genotoxicity (4,5). Acute synthetic cannabinoid exposure reportedly causes a range of mild to severe neuropsychiatric, cardiovascular, renal, and other effects (4,6,7); chronic use might lead to psychosis (6,8). During 2010-2015, physicians in the Toxicology Investigators Consortium (ToxIC) treated 456 patients for synthetic cannabinoid intoxications; 277 of the 456 patients reported synthetic cannabinoids as the sole toxicologic agent. Among these 277 patients, the most common clinical signs of intoxication were neurologic (agitation, central nervous system depression/coma, and delirium/toxic psychosis). Relative to all cases logged by 50 different sites in the ToxIC Case Registry, there was a statistically significant association between reporting year and the annual proportion of synthetic cannabinoid cases. In 2015, reported cases of synthetic cannabinoid intoxication increased at several ToxIC sites, corroborating reported upward trends in the numbers of such cases (1,2) and underscoring the need for prevention.

The Toxicology Investigators Consortium Case Registry--the 2014 Experience.

The Toxicology Investigators Consortium (ToxIC) Case Registry was established in 2010 by the American College of Medical Toxicology. The Registry includes all medical toxicology consultations performed at participating sites. The Registry was queried for all cases entered between January 1 and December 31, 2014. Specific data reviewed for analysis included demographics (age, gender, ethnicity), source of consultation, reasons for consultation, agents involved in toxicological exposures, signs, symptoms, clinical findings, fatalities, and treatment. In 2014, 9172 cases were entered in the Registry across 47 active member sites. Females accounted for 51.1 % of cases. The majority (65.1 %) of cases were adults between the ages of 19 and 65. Caucasians made up the largest identified ethnic group (48.9 %). Most Registry cases originated from the inpatient setting (93.5 %), with a large majority of these consultations coming from the emergency department or inpatient admission services. Intentional and unintentional pharmaceutical exposures continued to be the most frequent reasons for consultation, accounting for 61.7 % of cases. Among cases of intentional pharmaceutical exposure, 62.4 % were associated with a self-harm attempt. Non-pharmaceutical exposures accounted for 14.1 % of Registry cases. Similar to the past years, non-opioid analgesics, sedative-hypnotics, and opioids were the most commonly encountered agents. Clinical signs or symptoms were noted in 81.9 % of cases. There were 89 recorded fatalities (0.97 %). Medical treatment (e.g., antidotes, antivenom, chelators, supportive care) was rendered in 62.3 % of cases. Patient demographics and exposure characteristics in 2014 Registry cases remain similar to prior years. The majority of consultations arose in the acute care setting (emergency department or inpatient) and involved exposures to pharmaceutical products. Among exposures, non-opioid analgesics, sedative/hypnotics, and opioids were the most frequently encountered. A majority of cases required some form of treatment, but fatalities were rare.

Potential Occupational Exposures and Health Risks Associated with Biomass-Based Power Generation.

Biomass is increasingly being used for power generation; however, assessment of potential occupational health and safety (OH&S) concerns related to usage of biomass fuels in combustion-based generation remains limited. We reviewed the available literature on known and potential OH&S issues associated with biomass-based fuel usage for electricity generation at the utility scale. We considered three potential exposure scenarios--pre-combustion exposure to material associated with the fuel, exposure to combustion products, and post-combustion exposure to ash and residues. Testing of dust, fungal and bacterial levels at two power stations was also undertaken. Results indicated that dust concentrations within biomass plants can be extremely variable, with peak levels in some areas exceeding occupational exposure limits for wood dust and general inhalable dust. Fungal spore types, identified as common environmental species, were higher than in outdoor air. Our review suggests that pre-combustion risks, including bioaerosols and biogenic organics, should be considered further. Combustion and post-combustion risks appear similar to current fossil-based combustion. In light of limited available information, additional studies at power plants utilizing a variety of technologies and biomass fuels are recommended.

Assessment of the mode of action for hexavalent chromium-induced lung cancer following inhalation exposures.

Inhalation of hexavalent chromium [Cr(VI)] is associated with increased lung cancer risk among workers in several industries, most notably chromate production workers exposed to high concentrations of Cr(VI) (≥100 µg/m(3)), for which clear exposure-response relationships and respiratory irritation and tissue damage have been reported. Data from this industry are used to assess lung cancer risk associated with environmental and current occupational exposures, occurring at concentrations that are significantly lower. There is considerable uncertainty in the low dose extrapolation of historical occupational epidemiology data to assess risk at current exposures because no published or well recognized mode of action (MOA) for Cr(VI)-induced lung tumors exists. We conducted a MOA analysis for Cr(VI)-induced lung cancer evaluating toxicokinetic and toxicological data in humans and rodents and mechanistic data to assess plausibility, dose-response, and temporal concordance for potential MOAs. Toxicokinetic data support that extracellular reduction of Cr(VI), which limits intracellular absorption of Cr(VI) and Cr(VI)-induced toxicity, can be overwhelmed at high exposure levels. In vivo genotoxicity and mutagenicity data are mostly negative and do not support a mutagenic MOA. Further, both chronic bioassays and the epidemiologic literature support that lung cancer occurs at exposures that cause tissue damage. Based on this MOA analysis, the overall weight of evidence supports a MOA involving deposition and accumulation of particulate chromium in the bifurcations of the lung resulting in exceedance of clearance mechanisms and cellular absorption of Cr(VI). Once inside the cell, reduction of Cr(VI) results in oxidative stress and the formation of Cr ligands. Subsequent protein and DNA damage lead to tissue irritation, inflammation, and cytotoxicity. These effects, concomitant with increased cell proliferation, result in changes to DNA sequences and/or methylation status that can lead to tumorigenesis. This MOA supports the use of non-linear approaches when extrapolating lung cancer risk occurring at high concentration occupational exposures to environmentally-relevant exposures.

Speciated arsenic in air: measurement methodology and risk assessment considerations.

Accurate measurement of arsenic (As) in air is critical to providing a more robust understanding of arsenic exposures and associated human health risks. Although there is extensive information available on total arsenic in air, less is known on the relative contribution of each arsenic species. To address this data gap, the authors conducted an in-depth review of available information on speciated arsenic in air. The evaluation included the type of species measured and the relative abundance, as well as an analysis of the limitations of current analytical methods. Despite inherent differences in the procedures, most techniques effectively separated arsenic species in the air samples. Common analytical techniques such as inductively coupled plasma mass spectrometry (ICP-MS) and/or hydride generation (HG)- or quartz furnace (GF)-atomic absorption spectrometry (AAS) were used for arsenic measurement in the extracts, and provided some of the most sensitive detection limits. The current analysis demonstrated that, despite limited comparability among studies due to differences in seasonal factors, study duration, sample collection methods, and analytical methods, research conducted to date is adequate to show that arsenic in air is mainly in the inorganic form. Reported average concentrations of As(III) and As(V) ranged up to 7.4 and 10.4 ng/m3, respectively, with As(V) being more prevalent than As(III) in most studies. Concentrations of the organic methylated arsenic compounds are negligible (in the pg/m3 range). However because of the variability in study methods and measurement methodology, the authors were unable to determine the variation in arsenic composition as a function of source or particulate matter (PM) fraction. In this work, the authors include the implications of arsenic speciation in air on potential exposure and risks. The authors conclude that it is important to synchronize sample collection, preparation, and analytical techniques in order to generate data more useful for arsenic inhalation risk assessment, and a more robust documentation of quality assurance/quality control (QA/QC) protocols is necessary to ensure accuracy, precision, representativeness, and comparability.