Acute Inhalation Research Articles

Guideline of Management of Acute Smoke Inhalation Injury: Systematic Review and Meta-Analysis of Last 10 Years

Guideline of Management of Acute Smoke Inhalation Injury: Systematic Review and Meta-Analysis of Last 10 Years

PBPK modeling demonstrates that exposure time adjustment is unnecessary for setting an acute manganese inhalation exposure guideline

PBPK modeling demonstrates that exposure time adjustment is unnecessary for setting an acute manganese inhalation exposure guideline

Release of ATP in the lung evoked by inhalation of irritant gases in rats.

Adenosine triphosphate (ATP) can be released into the extracellular milieu from various types of cells in response to a wide range of physical or chemical stresses. In the respiratory tract, extracellular ATP is recognized as an important signal molecule and trigger of airway inflammation. Chlorine (Cl2), sulfur dioxide (SO2), and ammonia (NH3) are potent irritant gases and common industrial air pollutants due to their widespread uses as chemical agents. This study was carried out to determine if acute inhalation challenges of these irritant gases, at the concentration and duration simulating the accidental exposures to these chemical gases in industrial operations, triggered the release of ATP in the rat respiratory tract; and if so, whether the level of ATP in bronchoalveolar lavage fluid (BALF) evoked by inhalation challenge of a given irritant gas was elevated by chronic allergic airway inflammation. Our results showed: 1) inhalation of these irritant gases caused significant increases in the ATP level in BALF, and the magnitude of evoked ATP release was in the order of Cl2 > SO2 > NH3. 2) Chronic airway inflammation induced by ovalbumin-sensitization markedly elevated the ATP level in BALF during baseline (breathing room air) but did not potentiate the release of ATP in the lung triggered by inhalation challenges of these irritant gases. These findings suggested a possible involvement of the ATP release in the lung in the regulation of overall airway responses to acute inhalation of irritant gases and the pathogenesis of chronic allergic airway inflammation.NEW & NOTEWORTHY Extracellular adenosine triphosphate (ATP) is a contributing factor and signaling molecule of airway inflammation. This study demonstrated for the first time that the ATP release in the lung was markedly elevated after acute inhalation challenges of three common industrial air pollutants; the order of the response magnitude was chlorine > sulfur dioxide > ammonia. These findings provided new information and improved our understanding of the adverse pulmonary effects caused by accidental inhalation exposures to these irritant gases.

P20-27 Zinc suphide – considerations and challenges for acute inhalation toxicity testing and classification under REACH

P20-27 Zinc suphide – considerations and challenges for acute inhalation toxicity testing and classification under REACH

A Rare Case Of Inhalational Organophosphorus Toxicity

Organophosphorus poisoning is commonly encountered in agricultural settings where the usage of pesticides is more. These compounds are also known for their potential as chemical warfare agents due to their toxic effects on the nervous system. This case report highlights a rare incident of acute inhalation organophosphorus poisoning in a 38-year-old male, who presented to the emergency department with symptoms of giddiness, nausea, vomiting and generalized fatigue. Early diagnosis and treatment are important in managing this potential life-threatening condition. The patient's clinical presentation, diagnostic findings and treatment are discussed here

Acute exposure to carbon monoxide inhalation and/or hot water immersion transiently increases erythropoietin in females but not in males.

The use of acute carbon monoxide inhalation (COi) and hot water immersion (HWI) are of growing interest as interventions to stimulate erythropoietin (EPO) production. However, whether EPO production is further augmented when combining these stressors and whether there are sex differences in this response are poorly understood. Therefore, we measured circulating EPO concentration in response to acute COi and HWI independently and in combination and determined whether the responses were altered by sex. Participants completed three study visits-COi, HWI, and combined COi and HWI-separated by 1 week in a randomized, balanced, crossover design. Renal blood velocity was measured during all interventions, and carboxyhaemoglobin was measured during and after COi. Serum samples were analysed every hour for 6h post-intervention for EPO concentration. HWI decreased renal blood velocity (46.2cm/s to 36.2cm/s) (P<0.0001), and COi increased carboxyhaemoglobin (1.5%-12.8%) (P<0.0001) without changing renal blood velocity (46.4-45.2cm/s) (P=0.4456). All three interventions increased peak EPO concentration from baseline (COi: 6.02-9.74mIU/mL; HWI: 6.80-11.10mIU/mL; COi + HWI: 6.71-10.91mIU/mL) (P=0.0048) and to the same extent (P=0.3505). On average, females increased EPO while males did not in response to COi (females: 6.17mIU/mL; males: 1.27mIU/mL) (P=0.0010), HWI (females: 6.47mIU/mL; males: 2.14mIU/mL) (P=0.0104), and COi and HWI (females: 6.65mIU/mL; males: 1.76mIU/mL) (P=0.0256). These data emphasize that combining these interventions does not augment EPO secretion and that these interventions may work better in females.

Inhalation Toxicity Screening of Consumer Products Chemicals using OECD Test Guideline Data-based Machine Learning Models

This study aimed to screen the inhalation toxicity of chemicals found in consumer products such as air fresheners, fragrances, and anti-fogging agents submitted to K-REACH using machine learning models. We manually curated inhalation toxicity data based on OECD test guideline 403 (Acute inhalation), 412 (Sub-acute inhalation), and 413 (Sub-chronic inhalation) for 1709 chemicals from the OECD eChemPortal database. Machine learning models were trained using ten algorithms, along with four molecular fingerprints (MACCS, Morgan, Topo, RDKit) and molecular descriptors, achieving F1 scores ranging from 51 % to 91 % in test dataset. Leveraging the high-performing models, we conducted a virtual screening of chemicals, initially applying them to data-rich chemicals generally used in occupational settings to determine the prediction uncertainty. Results showed high sensitivity (75 %) but low specificity (23 %), suggesting that our models can contribute to conservative screening of chemicals. Subsequently, we applied the models to consumer product chemicals, identifying 79 as of high concern. Most of the prioritized chemicals lacked GHS classifications related to inhalation toxicity, even though they were predicted to be used in many consumer products. This study highlights a potential regulatory blind spot concerning the inhalation risk of consumer product chemicals while also indicating the potential of artificial intelligence (AI) models to aid in prioritizing chemicals at the screening level.

Acute Neurobehavioral and Glial Responses to Explosion Gas Inhalation in Rats.

Military personnel, firefighters, and fire survivors exhibit a higher prevalence of mental health conditions such as depression and post-traumatic stress disorder (PTSD) compared to the general population. While numerous studies have examined the neurological impacts of physical trauma and psychological stress, research on acute neurobehavioral effects of gas inhalation from explosions or fires is limited. This study investigates the early-stage neurobehavioral and neuronal consequences of acute explosion gas inhalation in Sprague-Dawley rats. Rats were exposed to simulated explosive gas and subsequently assessed using behavioral tests and neurobiological analyses. The high-dose exposure group demonstrated significant depression-like behaviors, including reduced mobility and exploration. However, neuronal damage was not evident in histological analyses. Immunofluorescence revealed increased density of radial glia and oligodendrocytes in specific brain regions, suggesting hypoxia and axon damage induced by gas inhalation as a potential mechanism for the observed neurobehavioral changes. These findings underscore the acute impact of explosion gas inhalation on mental health, highlighting the habenula and dentate gyrus of hippocampus as the possible target regions. The findings are expected to support early diagnosis and treatment strategies for brain injuries caused by explosion gas, offering insights into early intervention for depression and PTSD in affected populations.

Modeling Plutonium Decorporation in a Female Nuclear Worker Treated with Ca-DTPA after Inhalation Intake.

The present work models plutonium (Pu) biokinetics in a female former nuclear worker. Her bioassay measurements are available at the US Transuranium and Uranium Registries. The worker was internally exposed to a plutonium-americium mixture via acute inhalation at a nuclear weapons facility. She was medically treated with injections of 1 g Ca-DTPA on days 0, 5, and 14 after the intake. Between days 0 and 20, fecal and urine samples were collected and analyzed for 239Pu and 241Am. Subsequently, she was followed up for bioassay monitoring over 14 y, with additional post-treatment urine samples collected and analyzed for 239Pu. The uniqueness of this dataset is due to the availability of: (1) both early and long-term bioassay data from a female with plutonium intake; (2) data on chelation therapy for a female; and (3) fecal measurement results. Chelation therapy with Ca- and/or Zn-salts of DTPA is known to aid in reducing the internal radiation dose by enhancing the excretion of plutonium and americium from the body. Such enhancement affects plutonium biokinetics in the human body, posing a challenge to the internal dose assessment. The current radiation dose assessment practice is to exclude the data affected by Ca-DTPA from the analysis. The present analysis is the first to explicitly model the chelation-affected bioassay data in a female by using a newly developed chelation model. Thus, the bioassay data collected during and after the Ca-DTPA administrations were used for biokinetic modeling and dose assessment. The Markov Chain Monte Carlo method was used to investigate model parameter uncertainty, based on the bioassay data and assumed prior probability distributions. A χ2/nData (number of data points) ≈ 1 was observed in this study, which indicates self-consistency of the data with the model. Results of this study show that the worker's 239Pu intake was 12 Bq, with a committed effective dose to the whole-body of 1.2 mSv and a committed equivalent dose to the bone surfaces, liver, and lungs of 37.8, 9.1, and 0.8 mSv, respectively. This study also discusses the worker's dose reduction due to chelation treatment.

Cardiorespiratory failure induced by inhalation of aerosolized fentanyl in anesthetized rats

Intravenous rapid injection of fentanyl causes respiratory depression (severe apneas), leading to sudden death, which constitutes the deadliest drug reaction among overdoses of synthetic opioids. Here we asked whether acute inhalation of overdose fentanyl would also result in similar respiratory failure and death. The anesthetized and spontaneously breathing rats with tracheal cannulation were exposed to aerosolized fentanyl at 100 mg/m3 (FNTH) or 30 mg/m3 (FNTL) for 10 min. Minute ventilation (VE), electromyography (EMG) of the internal and external intercostal muscles and thyroarytenoid muscles (EMGII, EMGEI, and EMGTA), heart rate and arterial blood pressure were recorded. During the exposure, FNTH and FNTL immediately triggered bradypnea (40 % reduction, p < 0.05) with TE prolonged and then gradually decreased VE by 40 % (P < 0.05) after a brief VE recovery. The initial TE prolongation (apneas) were characterized by the cessation of EMGEI activity with enhanced tonic discharges of EMGTA and EMGII. After termination of the exposure, the cardiorespiratory responses to FNTL returned to the baseline values 30 min later, while those to FNTH were greatly exacerbated (P < 0.05), leading to ventilatory and cardiac arrest occurred 16.4 ± 4.7 min and 19.3 ± 4.5 min respectively after the onset of FNTH. The ventilatory arrest was featured by cessation of both EMGEI and EMGII and augmentation of tonic EMGTA. Our results suggest that acute exposure to an overdose of fentanyl aerosol leads to death through initially inducing a brief central and upper airway obstructive apnea as well as chest wall rigidity followed by gradual severe hypoventilation, bradycardia and hypotension, and eventual cardiorespiratory arrest in anesthetized rats.

Toxicological Assessment of Pesticide Exposure in Wistar Rats: An Acute and Sub-Acute Inhalation Study

Background: Pesticide ubiquity and extensive applications have attendant public health implications. This study examines the immediate and prolonged inhalation toxicity of various commonly used insecticides in male Wistar rats. Methods: 192 male Wistar rats were utilized and kept in regular housing. The study was carried out in three stages: a preliminary test, an acute test, and a sub-acute. Wistar rats, housed in an improvised chamber, were exposed to varying doses of insecticides in each phase to assess their toxicities to insecticides. For comparativeness, we withdrew 57 of the rats from exposure to ascertain possible recovery. The study included monitoring behavioral changes, recording mortality rates, and conducting necropsies to evaluate organ pathology. Dose-response relationships were analyzed to determine lethal doses (LD50) and potential sublethal effects. Results: Overall, we found a dose-related increase in the severity of the response, which potentially indicates an alteration of a specific biochemical process. The range-finding test assessed the effects of DD Force, Sniper, Industrial Camphor, Edible Camphor, Kerosene, and combined pesticides. It revealed significant physiological impacts followed by mortalities at specific dosage levels. Subsequent acute toxicity testing determined LC50 values for each insecticide. Rats showed a dose-dependent health deterioration following sub-acute exposure, particularly in the combined pesticide group, indicating synergistic toxicity. Conclusion: Exposure to the combined pesticide at high doses was associated with severe toxicities in the tested rats. This evidence suggests that commonly used pesticides could potentiate adverse health outcomes when results are extrapolated in humans.

Transcriptome changes in humans acutely exposed to nanoparticles during grinding of dental nanocomposites.

Aim: Today, there is a lack of research studies concerning human acute exposure to nanoparticles (NPs). Our investigation aimed to simulate real-world acute inhalation exposure to NPs released during work with dental nanocomposites in a dental office or technician laboratory. Methods: Blood samples from female volunteers were processed before and after inhalation exposure. Transcriptomic mRNA and miRNA expression changes were analyzed. Results: We detected large interindividual variability, 90 significantly deregulated mRNAs, and 4 miRNAs when samples of participants before and after dental nanocomposite grinding were compared. Conclusion: The results suggest that inhaled dental NPs may present an occupational hazard to human health, as indicated by the changes in the processes related to oxidative stress, synthesis of eicosanoids, and cell division.

CURRENT STATUS OF THE LEGAL FRAMEWORK IN THE PLANT PROTECTION AND ECOLOGY AND HYGIENE MONITORING DOMAIN IN UKRAINE

Presently chemical plant protection products are an inseparable part of agriculture. They have not only their main purpose of plant assistance, but they also have the potential risk of negative impact on biocenosis species (birds, bees, soil microflora, algae, etc.) and the human body and its health respectively. The purpose of our study was to aggregate data on the existing legal framework of plant protection products in Ukraine and assess their ecology and hygiene monitoring. For analysis of the plant chemical protection, we used as the basic documents the regulatory framework of domestic legislation in toxicological and hygiene, ecology assessment, and ecology and hygiene monitoring domains. Currently, many laws and legal acts regulate the use of pesticides by state and private agricultural farms in Ukraine. This number of documents covers not only pre-registration studies of pesticides but also their post-registration monitoring in the environment. The key entities that control potential negative risks of these products through the regulations are the State Emergency Service, Ministry of Environmental Protection, Ministry of Health, Ministry of Housing and Communal Services, Ministry of Agriculture Policy, State Agency of Water Resources, State Committee of Land Resources, State Agency of the Forest Resources. However, the impact of xenobiotics on non-target species of the ecosystem is currently quite underestimated. The decline in biodiversity directly depends on the condition of the environment and the negative impact on it. Instances of acute oral, inhalation, or dermal poisoning of birds, bees, and aquatic invertebrates with pesticides are quite common and among the factors that affect public health. That is why ecology and hygiene monitoring is essential in line with the assessment of the risks of the inappropriate release of pesticides. These should be treated as a critical component of managing environmental sustainability and safety for public health. The implementation of global approaches to monitoring and controlling the post- registration impact of pesticides on the ecology and hygiene in Ukraine can also take into account the far-reaching consequences of their negative impact, accumulation, and environmental pollution. As a result, this will help to avoid adverse impacts on animal, insect, and bird populations, as well as human health.

The Extraction of Organic Silica from Agricultural Waste: A Mini Review

Inorganic silica precursors, also known as alkoxysilanes, have been used commercially in many applications and synthetizations. However, it has been reported that these inorganic silicas can harm human health, causing stomach, bladder, and kidney failure, as well as death in the case of an acute inhalation. Due to this reason, organic silica from agricultural waste such as coconut husks, corncobs, sugarcane bagasse, rice husks, and bamboo leaves is being reviewed as an alternative source to replace the risky inorganic silica. This work discussed the extraction method, silica percentage obtained, and applications involving the use of organic silica, demonstrating that green waste can replace inorganic silica and provide good value to society.

Improving the reliability of internal dosimetry for uranium workers: Application of the ICRP/OIR uranium model to long-term occupational intakes

In the Occupational Intakes of Radionuclides (OIR) report series, the International Commission on Radiological Protection (ICRP) published updated biokinetic models and dosimetric data associated with the internal exposure of workers, which are consistent with the recommendations of ICRP Publication 103. The present study focused on the application of the new OIR uranium model published in ICRP Publication 137, which is relevant for the interpretation of measurements of activity in the body and in excreta, and for calculating the committed effective dose. The main objective of this study was to assess the impacts of the new OIR biokinetic models and dose coefficients compared with the old ones based on ICRP Publications 60/78/119. CIEMAT and the University of Salamanca in Spain have been working on re-interpreting in vitro bioassay data obtained from workers with long-term exposure to inhaling uranium oxides during the fabrication of nuclear fuel elements using low enriched uranium, which is now classified as OIR type M/S material. The effects on the retention/excretion models and dose coefficients were studied for 234U, 235U, 238U, and the uranium mixture. Committed effective doses were re-assessed using BIOKMOD code by applying the new OIR excretion model and dose coefficients considering acute and/or chronic inhalation intake scenarios. A reduction by roughly a factor of four was obtained compared with former doses based on ICRP Publications 60/78/119, which is an important effect to take into consideration.

Bis-(2-Chloroisopropyl) ether.

Bis-(2-Chloroisopropyl) ether (BCIPE) was used as a solvent for fats, greases, paint, varnish removers, and in spotting and cleaning solutions. However, BCIPE has not been commercially manufactured or used for numerous years. In experimental animal studies, BCIPE is moderately toxic following acute oral, dermal, and inhalation routes of exposure. BCIPE is a severe eye irritant but not a dermal irritant or dermal sensitizer. BCIPE was not genotoxic or mutagenic in in vitro and in vivo assays; it was not toxic in a 3-generation reproductive dietary study in rats. Short-term, repeated inhalation and oral exposure in rats produced increased liver and kidney weights and congestion; dermal exposure in rabbits did not produce any observable adverse effects. BCIPE did not produce a statistically significant increase in tumors in two different 2-year dietary studies in mice and rats. In mice, technical grade BCIPE produced increased incidences of alveolar/bronchiolar adenomas in females, hepatocellular carcinomas in males, and a low incidence of forestomach hyperplasia (in both sexes at the high-dose). Further investigation with technical grade BCIPE concluded that these effects were species- and dose-specific with limited, if any, relevance to humans. The NOAEL of 400 ppm (15 mg/kg/day) from the 2-year dietary study in female rats was considered the point of departure for the health-based WEEL derivation. After adjustment for duration of exposure, interindividual variability, and intraindividual variability, an 8-h time-weighted average (TWA) WEEL value of 3 ppm (21 mg/m3) was derived. This exposure limit is expected to provide a significant margin of safety against any potential adverse health effects in workers.

A theoretical investigation of the competition between σ- and π-holes on the stability of the complexes resulting from the interaction between the COCl2 and OCY molecules (Y = S, Se, and Te)

Carbonyl dichloride (COCl2), also known as phosgene, is a highly toxic gas, whose exposure or acute inhalation causes severe respiratory complications, such as pulmonary edema, pulmonary emphysema, and even death. In this study, we theoretically investigated the complexes formed by the interaction between the COCl2 (phosgene) and OCY molecules (Y = S, Se, and Te). Complex geometry optimization yielded three distinct types of conformations. Conformation-I complexes were stabilized by two concurring chalcogen-bonding interactions (i.e. O⋯Y and Cl⋯Y) by forming a ring structure. However, only a single linear interaction (O⋯C) or (O⋯Cl) occurred in conformation-II and III complexes, forming complexes with the nature of tetrel and halogen bonds, respectively. According to the results of the molecular electrostatic potential (MEP), interaction energy (ΔET), natural bond orbital (NBO), and so on, the σ-hole of the Y atom in the OCY molecule exhibited higher acidic strength and formed more stable complexes than those resulting from the σ- and π-holes of the COCl2 molecule.

Improving approaches to hygienic rationing of antimicrobial drugs

Introduction. Currently, the production of medicines, including those with antimicrobial properties, is expanding at chemical and pharmaceutical enterprises. However, scientific approaches to hygienic regulation of the content of specific antimicrobials in the air of the work area are not yet available. The study aims to substantiate approaches to predicting approximate safe levels of exposure (ASLE) to substances with a specific antimicrobial effect. Materials and methods. The scientists have carried out the research in two stages. The first stage is an experimental study of the single inhalation effect of an antibiotic clarithromycin at concentrations of 54.2; 25.4; 15.3; 9.1; 2.8 and 0.9 mg/m3 on mongrel female rats weighing 230–250 g. The authors have evaluated the indicators of toxic (morphological and functional parameters of the nervous, cardiovascular and respiratory systems, biochemical parameters of the liver and kidneys, as well as the composition of peripheral blood) and specific effects (qualitative and quantitative composition of the microbiota of the large intestine of rats). The second stage was the analysis of the database on hygienic rationing of chemicals, which consisted in searching for hygienic standards (ASLE, MPC), threshold concentrations for the general toxic (Limint) and specific (Limbact) effects of antimicrobials. Results. During the experiment, experts have established the threshold of acute inhalation exposure (Limac int) of clarithromycin at a concentration of 25.4 mg/m3 according to the total toxic effects (peripheral blood counts, liver and kidney function). When exposed to an antibiotic at a concentration of 2.8 mg/m3, there was an imbalance of the intestinal microflora in the absence of a general toxic effect, which indicated a specific and selective antimicrobial effect of the drug. Based on the analysis of literature data, the parameters of toxicometry of 21 substances with antimicrobial effect were determined, their representative sample was justified and its regression analysis was carried out. Conclusion. Based on experimental and literary data, the authors established a significantly strong correlation (r=0.729) between the values of MPC (ASLE) and the threshold of antimicrobial action (Limbact). They also developed a mathematical equation to predict safe levels of antimicrobials based on their specific and selective activity.

DEVELOPMENT OF THE DERMAL EFFECT OF PESTICIDES ON PROFESSIONAL CONTINGENTS USING INNOVATIVE 3RIVE 3D TECHNOLOGY

The skin is the most vulnerable organ when spraying pesticides on fields. Farmers are also exposed to pesticides during mixing, loading of pesticides, and when cleaning equipment and disposing of empty containers. The aim. To study and analyze the features of the risk of pesticides dermal exposure to professional contingents during treatments using the innovative 3RIVE 3D pesticide application technology. Materials and methods. The 3RIVE 3D innovative technological system of introducing was used to applicate Brigade 3Rive 3D, SC formulation. Field experiments on the study of working conditions when using the pesticide were conducted in various soil and climatic regions of Eastern Europe. Statistical processing of the results was carried out using a package of licensed statistical programs IBM SPSS StatisticsBase v.22 and MS Excel. Research results and discussion. During the conducted research, no bifenthrin contamination was found on the open skin of the operator and the tractor driver, who were processing corn crops with the Brigade 3Rive 3D, SC formulation. However, the operator's gloves were found to contain 0.025 mg of bifenthrin. Calculation of the unitless CASd value on the possibility of skin acute effects when applying the formulation showed that bifenthrin and the Brigade 3Rive 3D, SC formulation based on it are characterized by sufficient selectivity of action on the target object (CASd – 645 and 162, respectively, i.e. &gt; 100) and a low level of danger acute dermal toxic effects for workers, which is due to low values of effective consumption rates. The real dermal risk of bifenthrin exposure when using the Brigade 3Rive3D, SC formulation was significantly lower compared to the risk of workers involved in “traditional” air treatment and treatment with unmanned aerial vehicles (UAVs) (p=0.009-0.048 according to Wilcoxon's W-criterion); in comparison with rod and fan processing – it is non-significantly lower (р=0.262-1.000). There was a similar picture in comparison with the dermal aggravated risk – significantly lower in comparison with the risk of workers involved in “traditional” air treatment and processing with the help of UAVs (p=0.009 according to Wilcoxon's W-criterion); in comparison with rod and fan treatment – non-significantly lower (р=0.262-1.000). Conclusion. It was established that the studied active substance bifenthrin and the Brigade 3Rive 3D, SC formulation based on it are characterized by sufficient selectivity of dermal action on the target object and a low probability of acute dermal effects. A higher probability of acute inhalation poisoning than dermal exposure was revealed.

Role of Opioid Mu1-Recptors (μ1Rs) in The Inhalation of Carfentanil (CRF) Aerosol-Induced Respiratory Disorder in Awake Rats

Our previous study has shown that inhalation of fentanyl (100 mg/m3) for 10 min initially induces apnea, hypotension and bradycardia, leading to ventilatory and then cardiac arrest within 15 min in anesthetized rats (Zhuang J., et al, 2024). CRF acts on opioid mu-receptors (MORs) with a potency 100 times that of fentanyl. Inhalation of aerosolized CRF as a chemical weapon has been reported to cause sudden death in humans (Wax PM et al, 2003), but the cause of the death is not fully understood. Moreover, though the opioid-induced respiratory disorder is known to mainly result from the action of μ1Rs, the contribution of μ1Rs to the CRF-induced cardiorespiratory disorder remains unknown. Therefore, we asked whether acute inhalation of overdose CRF would induce cardiorespiratory disorder and sudden death via acting on μ1R in awake rats. The rats were exposed to aerosolized vehicle and CRF at 12.86 (low dose) or 20 mg/m3 (high dose) for 15 min with cardiorespiratory (VE, VT, fR, and HR) responses recorded for 60 min. The low and high doses of CRF induced sudden death in 1/6 and 2/2 rats respectively. Compared to aerosolized vehicle, the low dose of CRF initially decreased VE and HR by ~50% within 3 min exposure, which were maintained to the end of experiment, and all responses disappeared on the next day in the survived rats. Interestingly, the responses of breathing pattern to the CRF exposure were sequentially characterized by the rapid shallow breathing (within several seconds of the exposure), slow and deep breathing and then only slow breathing. In comparison, the dVE and bradycardia became much more aggravated after 15 min CRF aerosol-delivery in the dead rats than the survived ones, resulting in ventilatory and cardiac arrest within ~25 min post exposure. The cardiorespiratory responses to the low dose of CRF aerosol exposure were also performed after pretreatment with naloxone hydrochloride (NLX to systemically antagonize opioid receptors) or naloxonazine (NALZ to selectively antagonize μ1Rs). The CRF-induced dVE and bradycardia were fully blocked by NLX and largely alleviated by NALZ. In conclusion, our experiments not only establish a rat model of acute inhalation of CRF-induced cardiorespiratory disorder and sudden death, but also demonstrate a key role of opioid receptors, especially μ1Rs, in the CRF-induced cardiorespiratory disorder. Supported by NIH R01 grants HL163512 and DA059063. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.