Psilocybine services in Oregon: a call for awareness among clinical toxicologists.

BACKGROUND: In 2023, Oregon enacted laws regulating the manufacture and use of psilocybine products in licensed facilities for supervised sessions with trained facilitators. COMMENTARY: This commentary summarizes the final rules for psilocybine services in Oregon, and provides perspectives from a clinical toxicologist on some of the issues that may arise. These include the scope of practice for non-clinical facilitators, prevention and management of adverse drug reactions, and toxicological uncertainties with regards to dose considerations for people with mental health and other medical conditions. CONCLUSION: This commentary addresses some common misperceptions relating to the program, and provides perspective on some of the challenges that clinical toxicologists may encounter as legislative reform initiatives for psilocybine move forward throughout the United States.

Naphthalene biomarkers and relationship with hemoglobin and hematocrit in White, Black, and Hispanic adults: results from the 2003-2004 National Health and Nutrition Examination Survey.

Naphthalene is an important contaminant in indoor and outdoor air. Acute overexposure can have toxic effects, resulting in hemolysis. There have been no studies evaluating the impact of environmental exposure on red blood cell indices. We examined 1- and 2-hydroxynaphthalene urinary metabolites (NAP1 and NAP2) in non-Hispanic White, non-Hispanic Black, and Mexican-American adults in the USA and their relationship with hemoglobin (Hb) and hematocrit (HCT). Using the 2003-2004 National Health and Nutrition Examination Survey data, weighted generalized linear regression analyses were used to examine the association between Hb (in grams per deciliter) and HCT (in percent) with NAP1 and NAP2 (per 100,000 ng/L). Beta coefficients ± SE are reported. NAP1 and NAP2 were highest in non-Hispanic Blacks, followed by non-Hispanic Whites, and lowest in Mexican-American adults. There was a positive association between NAP1 and Hb (0.39 ± 0.11, p = 0.0034) and HCT (1.14 ± 0.28, p = 0.0009) after adjusting for age, gender, race, education, and smoking. Stratified analysis by smoking showed similar results with the association being stronger for smokers (Hb 0.63 ± 0.23, p = 0.02; HCT 1.43 ± 0.79, p = 0.09) than nonsmokers (Hb 0.34 ± 0.14, p = 0.03; HCT 1.08 ± 0.42, p = 0.02). The association was also stronger for non-Hispanic blacks (Hb 0.54 ± 0.20, p = 0.02; HCT 1.43 ± 0.55, p = 0.02) than for non-Hispanic whites (Hb 0.37 ± 0.18, p = 0.06; HCT 1.20 ± 0.51, p = 0.03) and was not significant for Mexican-Americans (Hb 0.30 ± 1.7, p = 0.10; HCT 0.99 ± 0.52, p = 0.08). NAP2 was not significantly associated with Hb or HCT. The observed disparity in NAP1 and NAP2 levels by race/ethnicity is consistent with published literature. The origin of these differences in exposure is unclear but may reflect differences in environmental exposure as well as genetic susceptibility. The positive association between NAP1 with HCT and Hb is an unexpected finding. Further research is needed to understand the possible biological mechanisms or other explanations for this association.

Age and gender dependent bioavailability of R- and R,S-α-lipoic acid: a pilot study.

Lipoic acid (LA) shows promise as a beneficial micronutrient toward improving elder health. Studies using old rats show that (R)-α-LA (R-LA) significantly increases low molecular weight antioxidants that otherwise decline with age. Despite this rationale for benefiting human health, little is known about age-associated alterations in absorption characteristics of LA, or whether the commercially available racemic mixture of LA (R,S-LA) is equally as bioavailable as the naturally occurring R-enantiomer. To address these discrepancies, a pilot study was performed to establish which form of LA is most effectively absorbed in older subjects relative to young volunteers. Young adults (average age=32 years) and older adults (average age=79 years) each received 500 mg of either R- or R,S-LA. Blood samples were collected for 3h after supplementation. After a washout period they were given the other chiral form of LA not originally ingested. Results showed that 2 out of 6 elder males exhibited greater maximal plasma LA and area under the curve for the R-form of LA versus the racemic mixture. The elder subjects also demonstrated a reduced time to reach maximal plasma LA concentration following R-LA supplementation than for the racemic mixture. In contrast, young males had a tendency for increased bioavailability of R,S-LA. Overall, bioavailability for either LA isoform was much more variable between older subjects compared to young adults. Plasma glutathione levels were not altered during the sampling period. Thus subject age, and potential for varied response, should be considered when determining an LA supplementation regimen.

Dialkyl phosphates as biomarkers of organophosphates: the current divide between epidemiology and clinical toxicology.

CONTEXT: Organophosphate insecticides are widely utilized throughout the world. The cholinergic toxidrome, resulting from cholinesterase inhibition, is the clinically relevant endpoint in organophosphate poisoning. In recent years, urinary dialkyl phosphates (DAPs) have emerged as a common method of assessing exposure to organophosphates in epidemiological investigations. Using dialkyl phosphates as biomarkers of exposure to organophosphates, several recent epidemiological studies have reported associations with adverse health outcomes. The purpose of this article is to review the application and limitations of urinary DAPs as biomarkers of exposure to organophosphate insecticides. METHODS: A literature search was conducted of the PubMed database, using keywords "dialkylphosphate" and "dialkyl phosphate." The scientific literature was reviewed to identify sources of dialkyl phosphate metabolites from in vivo metabolism of organophosphates, and as environmental degradation products. Epidemiological investigations were reviewed to summarize the use of use of DAPs as biomarkers in cross-sectional studies, occupational exposures, acute poisonings, and in health outcome studies. Emphasis was placed on the assessment of DAPs in the context of existing biomarker frameworks, as defined by the National Research Council. Studies were assessed for concurrent use of cholinesterase activity as a biomarker of effect, and whether a dose-response relationship could be determined between DAPs and cholinesterase depression or cholinergic effects. RESULTS: Over 184 publications were identified, describing dialkyl phosphates and their use as biomarkers of exposure. The in vivo metabolism of organophosphates yields different DAPs, depending upon whether they undergo bioactivation or detoxification. The detection of urinary DAPs does not provide specificity with respect to the organophosphate from which they were derived, or their toxicological potency. Several recent studies documented the common presence of DAPs in residential environments and foods. Experimental studies support that DAPs have significant oral bioavailability, and undergo little to no metabolism prior to urinary excretion. Cross-sectional studies in multiple countries confirm that urinary DAPs are commonly detectable in the general population. No occupational studies were identified supporting a dose-response relationship between DAPs and significant cholinesterase inhibition. No occupational studies were identified supporting evidence of a threshold level of DAPs excretion at which clinical cholinergic signs or symptoms have been observed. Recent prospective epidemiological studies using DAPs as biomarkers have not concurrently assessed effects on cholinesterase activity, or conducted analyses that distinguish different DAPs that reflect bioactivation versus detoxification pathways. DISCUSSION: There are numerous limitations to the use of DAPs as biomarkers of exposure. These include a lack of specificity with respect to the organophosphate from which they were derived, and a growing body of evidence that toxicologically irrelevant DAPs are commonly encountered in food and the environment. Substantial intra- and inter-day variability has been reported for dialkyl phosphate excretion in humans, which is problematic for studies that rely on single measurements to assess exposure. The toxicological distinction between different DAPs reflecting biomarkers of activation and detoxification processes has not been considered in some prospective epidemiological studies. A relationship between DAPs as biomarkers of exposure and the critical biomarker of effect, cholinesterase activity, has not been established. CONCLUSIONS: The science of exposure assessment using DAPs as biomarkers is not advancing, and this complicates the interpretation of epidemiological studies. At the current time, DAPs have very limited utility in clinical toxicology or in the risk assessment process for organophosphates. Until these limitations are addressed, the appropriate role of DAPs in the assessment of human health risks from organophosphates is unclear.

Naphthalene Mothballs: Emerging and Recurring Issues and their Relevance to Environmental Health.

Naphthalene is a polycyclic aromatic hydrocarbon that is commonly encountered in indoor and outdoor environments. There is growing awareness of the environmental health risks associated with inhalation exposure to naphthalene in the indoor environment. While there are numerous potential sources of naphthalene indoors, the use of mothballs can be a significant contributor to ambient concentrations. This review article describes recurring and emerging environmental health issues relating to mothballs containing naphthalene. The toxicology and health effects of naphthalene exposure are reviewed, with discussion of high-risk populations and risk mitigation strategies. Environmental health professionals should be aware of mothball use in the home, and recognize risks associated with accidental exposure and misuse.

The spatial epidemiology of cocaine, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) use: a demonstration using a population measure of community drug load derived from municipal wastewater.

AIMS: To determine the utility of community-wide drug testing with wastewater samples as a population measure of community drug use and to test the hypothesis that the association with urbanicity would vary for three different stimulant drugs of abuse. DESIGN AND PARTICIPANTS: Single-day samples were obtained from a convenience sample of 96 municipalities representing 65% of the population of the State of Oregon. MEASUREMENTS: Chemical analysis of 24-hour composite influent samples for benzoylecgonine (BZE, a cocaine metabolite), methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA). The distribution of community index drug loads accounting for total wastewater flow (i.e. dilution) and population are reported. FINDINGS: The distribution of wastewater-derived drug index loads was found to correspond with expected epidemiological drug patterns. Index loads of BZE were significantly higher in urban areas and below detection in many rural areas. Conversely, methamphetamine was present in all municipalities, with no significant differences in index loads by urbanicity. MDMA was at quantifiable levels in fewer than half the communities, with a significant trend towards higher index loads in more urban areas. CONCLUSION; This demonstration provides the first evidence of the utility of wastewater-derived community drug loads for spatial analyses. Such data have the potential to improve dramatically the measurement of the true level and distribution of a range of drugs. Drug index load data provide information for all people in a community and are potentially applicable to a much larger proportion of the total population than existing measures.

Longitudinal trends in organophosphate incidents reported to the National Pesticide Information Center, 1995-2007.

BACKGROUND: Regulatory decisions to phase-out the availability and use of common organophosphate pesticides among the general public were announced in 2000 and continued through 2004. Based on revised risk assessments, chlorpyrifos and diazinon were determined to pose unacceptable risks. To determine the impact of these decisions, organophosphate (OP) exposure incidents reported to the National Pesticide Information Center (NPIC) were analyzed for longitudinal trends. METHODS: Non-occupational human exposure incidents reported to NPIC were grouped into pre- (1995-2000) and post-announcement periods (2001-2007). The number of total OP exposure incidents, as well as reports for chlorpyrifos, diazinon and malathion, were analyzed for significant differences between these two periods. The number of informational inquiries from the general public was analyzed over time as well. RESULTS: The number of average annual OP-related exposure incidents reported to NPIC decreased significantly between the pre- and post-announcement periods (p < 0.001). A significant decrease in the number of chlorpyrifos and diazinon reports was observed over time (p < 0.001). No significant difference in the number of incident reports for malathion was observed (p = 0.4), which was not phased-out of residential use. Similar to exposure incidents, the number of informational inquiries received by NPIC declined over time following the phase-out announcement. CONCLUSION: Consistent with other findings, the number of chlorpyrifos and diazinon exposure incidents reported to NPIC significantly decreased following public announcement and targeted regulatory action.

Regional variation in the severity of pesticide exposure outcomes: applications of geographic information systems and spatial scan statistics.

INTRODUCTION: Geographic information systems and spatial scan statistics have been utilized to assess regional clustering of symptomatic pesticide exposures reported to a state Poison Control Center (PCC) during a single year. In the present study, we analyzed five subsequent years of PCC data to test whether there are significant geographic differences in pesticide exposure incidents resulting in serious (moderate, major, and fatal) medical outcomes. METHODS: A PCC provided the data on unintentional pesticide exposures for the time period 2001-2005. The geographic location of the caller, the location where the exposure occurred, the exposure route, and the medical outcome were abstracted. RESULTS: There were 273 incidents resulting in moderate effects (n = 261), major effects (n = 10), or fatalities (n = 2). Spatial scan statistics identified a geographic area consisting of two adjacent counties (one urban, one rural), where statistically significant clustering of serious outcomes was observed. The relative risk of moderate, major, and fatal outcomes was 2.0 in this spatial cluster (p = 0.0005). CONCLUSIONS: PCC data, geographic information systems, and spatial scan statistics can identify clustering of serious outcomes from human exposure to pesticides. These analyses may be useful for public health officials to target preventive interventions. Further investigation is warranted to understand better the potential explanations for geographical clustering, and to assess whether preventive interventions have an impact on reducing pesticide exposure incidents resulting in serious medical outcomes.

Pyrethrin and pyrethroid exposures in the United States: a longitudinal analysis of incidents reported to poison centers.

INTRODUCTION: Citing the Food Quality Protection Act, the US Environmental Protection Agency (EPA) decided to phase out and eliminate organophosphate insecticide use in residential environments. The phase out process spanned from 2000 to 2005, and it may have resulted in increased consumer use of insecticides containing other active ingredients. This study utilized data from the national Poison Control Center to assess possible changes in exposure incidents involving pyrethrin and pyrethroid insecticides during the phase out of organophosphates from residential uses. METHODS: We extracted pyrethrin and pyrethroid insecticide exposure data from the American Association of Poison Control Centers Toxic Exposure Surveillance System (TESS) annual reports from 2000 to 2005. We examined pyrethrin and pyrethroid incidents by total exposures for each year, and we stratified exposures by age range, reason, number of cases treated in a health care facility, and medical outcome. Cases were examined as a proportion of all insecticide exposures. We calculated the annual incidence rates for exposures involving pyrethrin and pyrethroid insecticides of the population served. RESULTS: Pyrethrin and pyrethroid exposures increased annually in number and as a percentage of all insecticide exposure incidents. The increase in cases was observed for all age categories and exposure reasons. A statistically significant correlation was observed between advancing years (2000-2005) and the number of pyrethrin and pyrethroid incidents (p<.01). While the number of incidents treated in a health care facility increased annually during the study period, the proportion was constant (0.185 +/- 0.012) over the six year period. During the study period, the incidence rate for pyrethrin and pyrethroid exposures increased each year. 44% of all medical outcomes data was recorded, and the majority of outcomes resulted in no symptoms (37%) or minor symptoms (53%). CONCLUSION: TESS data showed a clear increase in cases involving pyrethrins and pyrethroids. The increase was temporally associated with the phase out of organophosphates from residential uses. In the future, medical toxicologists and poison control center personnel should be prepared to respond to an increasing number of pyrethrin and pyrethroid insecticide exposures.

Organophosphate exposures in the United States: a longitudinal analysis of incidents reported to poison centers.

The implementation of the Food Quality Protection Act of 1996 resulted in a decision by the U.S. Environmental Protection Agency to phase out and eliminate the use of organophosphate insecticides in residential environments. The phase-out and cancellation process began in the year 2000 and was complete in 2005. The purpose of this investigation was to utilize national Poison Control Center data to assess whether the risk mitigation decision had an impact on the number of incident cases involving organophosphates in the United States. Organophosphate exposure incident data were extracted from Annual Reports of the American Association of Poison Control Centers Toxic Exposure Surveillance System (TESS) for the years 1995 to 2004. The number of organophosphate exposure incidents peaked at 20,135 in 1997, and declined in each subsequent year. A statistically significant decrease was observed in the average annual number of organophosphate exposure incidents when comparing data from the time periods before (1995-1999) and after (2000-2004) the commencement of the phase-out process. The decrease in organophosphate incident cases was observed for all age categories, as well as for the circumstances surrounding the exposure (unintentional and intentional exposure incidents). TESS data showed a significant decrease in incident cases involving organophosphates in association with the phase-out from residential uses. The results of this investigation are consistent with other studies that have reported that regulatory restriction of access to pesticide formulations may have a significant impact on the number of human exposure incidents.

Fatality after a single dermal application of lindane lotion.

Lindane lotion, approved by the US Food and Drug Administration (FDA) for treatment of scabies and lice, poses risks of serious adverse effects on the nervous system. In 2003, the FDA issued a public health advisory for lindane products, emphasizing the importance of compliance with labeling instructions. The author presents a case in which a fatal outcome followed a single dermal application of lindane. The product was not applied according to the labeling instructions, and the 66-year-old man rapidly developed hypoxemia, seizures, respiratory acidosis, and hypotension. The final diagnosis at autopsy was hypoxic ischemic encephalopathy from lindane. This case is consistent with other reports of severe neurological outcomes from pharmaceutical use of lindane. These factors suggest a need for the FDA to reassess whether the risks of lindane have been effectively communicated to healthcare providers.

Pyrethroid insecticides: advances and challenges in biomonitoring.

Pyrethroid insecticides have a wide variety of applications throughout the world. They are structurally diverse chemicals that are synthetically derived from naturally occurring pyrethrin insecticides. Significant advances in analytical chemistry have led to the development of biomarkers of exposure to pyrethroids, and these methods are currently being applied to study exposure in the general population. This article reviews the chemistry and toxicology of pyrethroid insecticides, with an emphasis on the development of biomarkers to assess environmental exposure. Future challenges in the application of these biomarkers in epidemiological studies are explored, as is a need for improved understanding of the toxicokinetics of pyrethroids in humans.

Pesticides and electronic resources for health care providers.

Agricultural workers are at higher risk of occupational injuries, including pesticide exposures. There is general agreement that the training of health care providers to recognize and manage such exposures is limited and in need of improvement. While the Internet presents opportunities for health care providers to access information and continue their medical education, it can be difficult to identify relevant resources in a timely manner. This case report presents a realistic scenario of a suspected pesticide exposure among symptomatic agricultural workers. The discussion that follows presents Web-based resources that health care providers can rely upon in recognizing, managing, and preventing pesticide-related illness.

DEET: a review and update of safety and risk in the general population.

The emergence of West Nile Virus (WNV) in North America has resulted in increased public awareness and utilization of insect repellents containing N,N-diethyl-m-toluamide (DEET) in the prevention of mosquito-borne disease. Regulatory reassessments in North American countries have recently been completed for insect repellents containing DEET as active ingredient, resulting in labeling changes intended to minimize unnecessary exposure to special populations, including children. This article describes those changes, and summarizes more recent data relating to the pharmacokinetics, toxicology, and epidemiology of adverse effects associated with DEET in humans.

Trichothecenes in the environment: relevance to human health.

Trichothecenes are agriculturally important mycotoxins of relevance to human health. Fungi capable of producing trichothecenes can be found throughout the world, and include certain species of Fusarium, Myrothecium, and Stachybotrys. The production of mycotoxins by these toxigenic species is determined by genetic factors and the environmental conditions of their growth. The environmental fate of trichothecenes may be affected by other microorganisms that can detoxify them. Deoxynivalenol and T-2 toxin are examples of trichothecenes that are detectable as natural and unavoidable contaminants of certain agricultural commodities as well as commercial foods. Current estimates of dietary exposure to deoxynivalenol and T-2 toxin are below thresholds for adverse effects that have been reported in experimental animal studies, although historical epidemics of human illness have rarely been described in association with consumption of food derived from heavily contaminated grains. The toxicodynamic properties of trichothecenes include inhibition of protein synthesis and immunomodulatory effects. Very little information is available relating to their toxicokinetics and toxicodynamics in humans. While there is general agreement that the diet represents an important source of human exposure to trichothecenes, risk assessment from non-dietary routes of exposure is complicated by the limited epidemiological data that are currently available.

Dietary aflatoxin exposure and chemoprevention of cancer: a clinical review.

Exposure to dietary aflatoxins is considered to be an important risk factor for the development of hepatocellular carcinoma in certain regions of the world. Significant advances have recently been made in understanding the clinical toxicology of aflatoxins. These include the development and validation of biomarkers of exposure and genotoxic effect. These biomarkers are currently being utilized to explore the potential that pharmaceutical interventions may have in modifying the toxicokinetics of dietary aflatoxin exposure. Preliminary results of clinical trials with the drug oltipraz suggest that it may modify the genotoxic effects of aflatoxin B1 by inhibiting bioactivation pathways and stimulating detoxification pathways. More recent results of a clinical trial with chlorophyllin suggest that this drug may have a role in preventing dietary exposure to aflatoxin B1 by reducing its oral bioavailability. The preliminary results of these chemoprevention studies may ultimately have implications for cancer prevention in high-risk populations in the future.

Biopesticides.

The term 'biopesticide' encompasses a broad array of microbial pesticides, biochemicals derived from micro-organisms and other natural sources, and processes involving the genetic incorporation of DNA into agricultural commodities that confer protection against pest damage (plant-incorporated protectants). Some microbial pesticides, such as Bacillus thuringiensis, have a long history of safe and effective use as a biological insecticide. More recent developments in microbial pest control include the utilisation of other bacterial and fungal species that may competitively inhibit the growth of pathogenic and toxigenic micro-organisms on important agricultural commodities. The use of microbes and their gene products introduces additional considerations to the toxicological dose-response relationship, including a need to determine the plausibility of infectious and immunological effects in association with human exposure to these biopesticides in food or the environment. Studies of substantial equivalence suggest that foods currently derived from plant-incorporated protectants are not likely to differ from conventional foods. However, there is general consensus that the scientific methods to assess risks from genetically modified foods and micro-organisms will continue to evolve in the future.

Regional variation in the incidence of symptomatic pesticide exposures: applications of geographic information systems.

OBJECTIVE: To evaluate the epidemiology of symptomatic human pesticide exposures using poison control center data and geographic information systems. METHODS: All symptomatic human pesticide exposures reported to the poison center during the period from January 1 to December 31, 2000 were included for analysis using geographic information systems. A space-time scan statistic was utilized to evaluate for clustering of symptomatic human exposures. RESULTS: Of 322 symptomatic pesticide exposures, 297 (92%) contained spatial identifiers that could be further analyzed using geographic information systems. A spatial and temporal cluster of symptomatic pesticide exposures was identified during the periodfrom April 1 to August 31, 2000, covering a large geographic area of eastern and predominantly rural regions of the state. The relative risk of reporting a symptomatic pesticide exposure among individuals living within this geographic area was 1.8 (log likelihood ratio = 18.5, P = 0.0005). CONCLUSIONS: Geographic information systems can be effectively utilized by poison control centers to study regional and temporal variation in the incidence of human pesticide exposures. With the collection of more specific spatial identifiers, geographic information systems may have many additional applications in the surveillance and prevention of pesticide and other sentinel event exposures.