Sub-acute toxicity, antinociceptive and anti-inflammatory effects of Mucuna pruriens L. leaves in experimental rodents.

ETHNOPHARMACOLOGICAL RELEVANCE: Mucuna pruriens L is a wild and cultivated leguminous plant which have been used as an aphrodisiac, diuretic, nerve tonic, and antiarthritic agent. AIM: To evaluate the toxicity, antinociceptive, and anti-inflammatory activities of M. pruriens (EEMP) ethanol extract in experimental models. METHODS: M. pruriens dried leaves were extracted using aqueous ethanol (30:70). Tests for acute and subacute toxicity were conducted on rats and mice. Mice were used in hotplate, acetic acid, and formalin models to test the antinociceptive activity of EEMP. The anti-inflammatory properties of EEMP (25, 100, and 400 mg/kg) were assessed egg albumin, carrageenan, and formalin-induced oedema models. The study examined the anti-inflammatory mechanism of EEMP (25-400 mg/kg) in rats with an air pouch caused by carrageenan. Air pouch exudates were tested for total leucocytes and differential cell counts, TNF-α, IL-6, myeloperoxidase activity, malondialdehyde, nitrites, and reduced glutathione (GSH). RESULTS: The acute oral toxic dose of EEMP is greater than 2000 mg/kg. There were no significant behavioral, hematological or biochemical alterations seen after 14-days repeated administration of EEMP (200, 400 and 800 mg/kg) in mice. The EEMP demonstrated significant antinociceptive activity in hotplate, acetic acid and formalin-induced nociception in mice. The EEMP significantly and dose dependently reduced paw oedema at 2, 4 and 96 h in the egg-albumin, carrageenan- and formalin-induced paw oedema, respectively. Exudates volume, inflammatory cell counts, TNF-α, IL-6, myeloperoxidase, malondialdehyde and nitrites were significantly reduced, while GSH increased in carrageenan-air pouch of EEMP-treated rats. CONCLUSION: Mucuna pruriens leaves ethanol extract demonstrated good safety profile as well as antinociceptive and anti-inflammatory activity through mechanisms related to inhibition of oxidative stress and pro-inflammatory cytokines as well as lysosomal membrane stability.

Formaldehyde exacerbates inflammation and biases T helper cell lineage commitment through IFN-γ/STAT1/T-bet pathway in asthma.

The correlation between formaldehyde (FA) exposure and prevalence of asthma has been widely reported. However, the underlying mechanism is still not fully understood. FA exposure at 2.0 mg/m3 was found to exacerbate asthma in OVA-induced murine models. IFN-γ, the cytokine produced by T helper 1 (Th1) cells, was significantly induced by FA in serum and bronchoalveolar lavage fluid (BALF) of asthmatic mice, which was different from cytokines secreted by other Th cells. The observation was also confirmed by mRNA levels of Th marker genes in CD4+ T cells isolated from BALF. In addition, increased production of IFN-γ and expression of T-bet in Jurkat T cells primed with phorbol ester and phytohaemagglutinin were also observed with 100 µM FA treatment in vitro. Upregulated STAT1 phosphorylation, T-bet expression and IFN-γ production induced by FA was found to be restrained by STAT1 inhibitor fludarabine, indicating that FA promoted Th1 commitment through the autocrine IFN-γ/STAT1/T-bet pathway in asthma. This work not only revealed that FA could bias Th lineage commitment to exacerbate allergic asthma, but also identified the signaling mechanism of FA-induced Th1 differentiation, which may be utilized as the target for development of interfering strategies against FA-induced immune disorders.

A South African case study on anatomical embalming for human body donation programmes with toxicological considerations.

Body embalming, a practice with deep historical roots across various cultures, forms the backbone of contemporary human body donation educational programmes. In this study, we explored current embalming practices within six South African human anatomical dissection programmes, focusing on the use and volumes of key chemicals-formalin, phenol, and alcohol-and their associated health risks and potential toxicity. We measured and compared aspects of embalming practices such as the duration of body preservation and the annual intake of bodies. Variations in embalming practices and chemical ratios across different South African universities were found. However, the consistent use of formalin, phenol and alcohol were observed across all six programmes. Formaldehyde concentrations used in South African dissection programmes were within the generally acceptable international range. Regarding arterial embalming, South African dissection programmes showed widespread adherence to international embalming practices, with one programme using a substantially lower concentration of formalin. The dual nature of formaldehyde as both an effective preservative and a recognised carcinogen was underscored in relation to human health regarding chemical toxicity. Phenol, like formaldehyde, was consistently used as it is important for the inhibition of bacterial and fungal growth. Alcohol was also consistently used, but there was much greater variation in its volume across South African institutions. Our data showed a slight positive relationship between storage duration and the volumes of formalin and phenol in human embalming fluid. South African regulators enforce stricter exposure limits than those set by the World Health Organisation and various European agencies. While South African institutions operate within internationally acceptable ranges of chemical use that both maximise preservation and minimise toxicity, we acknowledge that these data are preliminary. Further investigation is encouraged to ensure embalming practices effectively protect all those involved and support the educational goals of human anatomical dissection programmes in South Africa.

Residential exposure to air pollution and incidence of leukaemia in the industrial area of Viadana, Northern Italy.

BACKGROUND: Exposure to air pollution has been proposed as one of the potential risk factors for leukaemia. Work-related formaldehyde exposure is suspected to cause leukaemia. METHODS: We conducted a nested register-based case-control study on leukaemia incidence in the Viadana district, an industrial area for particleboard production in Northern Italy. We recruited 115 cases and 496 controls, frequency-matched by age, between 1999 and 2014. We assigned estimated exposures to particulate matter (PM10, PM2.5), nitrogen dioxide (NO2), and formaldehyde at residential addresses, averaged over the susceptibility window 3rd to 10th year prior to the index date. We considered potential confounding by sex, age, nationality, socio-economic status, occupational exposures to benzene and formaldehyde, and prior cancer diagnoses. RESULTS: There was no association of exposures to PM10, PM2.5, and NO2 with leukaemia incidence. However, an indication of increased risk emerged for formaldehyde, despite wide statistical uncertainty (OR 1.46, 95%CI 0.65-3.25 per IQR-difference of 1.2 µg/m3). Estimated associations for formaldehyde were higher for acute (OR 2.07, 95%CI 0.70-6.12) and myeloid subtypes (OR 1.79, 95%CI 0.64-5.01), and in the 4-km buffer around the industrial facilities (OR 2.78, 95%CI 0.48-16.13), although they remained uncertain. CONCLUSIONS: This was the first study investigating the link between ambient formaldehyde exposure and leukaemia incidence in the general population. The evidence presented suggests an association, although it remains inconclusive, and a potential significance of emissions related to industrial activities in the district. Further research is warranted in larger populations incorporating data on other potential risk factors.

Human exposure to formaldehyde and health risk assessment: a 46-year systematic literature review.

After confirming that formaldehyde (FA) is carcinogenic, many studies were conducted in different countries to investigate this finding. Therefore, according to the dispersion of related studies, a bibliometric review of the current literature was performed with the aim of better understanding the exposure to FA and the resulting health risk, for the first time, using the Scopus database and the two open-source software packages, Bibliometrix R package. After screening the documents in Excel, the data was analyzed based on three aspects including performance analysis, conceptual structure, and intellectual structure, and the results were presented in tables and diagrams. A total of 468 documents were analyzed over period 1977-2023, in which 1956 authors from 56 countries participated. The number of scientific publications has grown significantly from 1977 (n = 1) to 2022 (n = 19). Zhang Y., from the Yale School of Public Health (USA), was identified as the most impactful author in this field. The Science of the Total Environment journal was identified as the main source of articles related to exposure to formaldehyde by publishing 25 studies. The United States and China were the most active countries with the most international collaboration. The main topics investigated during these 46 years included "formaldehyde" and "health risk assessment", which have taken new directions in recent years with the emergence of the keyword "asthma". The present study provides a comprehensive view of the growth and evolution of studies related to formaldehyde and the resulting health risks, which can provide a better understanding of existing research gaps and new and emerging issues.

Occupational exposure, carcinogenic and non-carcinogenic risk assessment of formaldehyde in the pathology labs of hospitals in Iran.

Formaldehyde, a known carcinogenic compound, is commonly used in various medical settings. The objective of this study was to assess the carcinogenic and non-carcinogenic risks associated with occupational exposure to formaldehyde. This study was conducted in the pathology labs of four hospitals in Tehran. Cancer and non-cancer risks were evaluated using the quantitative risk assessment method proposed by the United States environmental protection agency (USEPA), along with its provided database known as the integrated risk information system (IRIS). Respiratory symptoms were assessed using the American thoracic society (ATS) questionnaire. The results indicated that 91.23% of exposure levels in occupational groups exceed the NIOSH standard of 0.016 ppm. Regarding carcinogenic risk, 41.03% of all the studied subjects were in the definite carcinogenic risk range (LCR > 10-4), 23.08% were in the possible carcinogenic risk range (10-5 < LCR < 10-4), and 35.90% were in the negligible risk range (LCR < 10-6). The highest index of occupational carcinogenesis was observed in the group of lab technicians with a risk number of 3.7 × 10-4, followed by pathologists with a risk number of 1.7 × 10-4. Furthermore, 23.08% of the studied subjects were within the permitted health risk range (HQ < 1.0), while 76.92% were within the unhealthy risk range (HQ > 1.0). Overall, the findings revealed significantly higher carcinogenic and non-carcinogenic risks among lab technicians and pathologists. Therefore, it is imperative to implement control measures across various hospital departments to mitigate occupational formaldehyde exposure levels proactively. These findings can be valuable for policymakers in the health sector, aiding in the elimination or reduction of airborne formaldehyde exposure in work environments.

Astrocytes in preoptic area regulate acute nociception-induced hypothermia through adenosine receptors.

AIMS: The preoptic area (POA) of the hypothalamus, crucial in thermoregulation, has long been implicated in the pain process. However, whether nociceptive stimulation affects body temperature and its mechanism remains poorly studied. METHODS: We used capsaicin, formalin, and surgery to induce acute nociceptive stimulation and monitored rectal temperature. Optical fiber recording, chemical genetics, confocal imaging, and pharmacology assays were employed to confirm the role and interaction of POA astrocytes and extracellular adenosine. Immunofluorescence was utilized for further validation. RESULTS: Acute nociception could activate POA astrocytes and induce a decrease in body temperature. Manipulation of astrocytes allowed bidirectional control of body temperature. Furthermore, acute nociception and astrocyte activation led to increased extracellular adenosine concentration within the POA. Activation of adenosine A1 or A2A receptors contributed to decreased body temperature, while inhibition of these receptors mitigated the thermo-lowering effect of astrocytes. CONCLUSION: Our results elucidate the interplay between acute nociception and thermoregulation, specifically highlighting POA astrocyte activation. This enriches our understanding of physiological responses to painful stimuli and contributes to the analysis of the anatomical basis involved in the process.

Interventional probability of causation (IPoC) with epidemiological and partial mechanistic evidence: benzene vs. formaldehyde and acute myeloid leukemia (AML).

INTRODUCTION: Causal epidemiology for regulatory risk analysis seeks to evaluate how removing or reducing exposures would change disease occurrence rates. We define interventional probability of causation (IPoC) as the change in probability of a disease (or other harm) occurring over a lifetime or other specified time interval that would be caused by a specified change in exposure, as predicted by a fully specified causal model. We define the closely related concept of causal assigned share (CAS) as the predicted fraction of disease risk that would be removed or prevented by a specified reduction in exposure, holding other variables fixed. Traditional approaches used to evaluate the preventable risk implications of epidemiological associations, including population attributable fraction (PAF) and the Bradford Hill considerations, cannot reveal whether removing a risk factor would reduce disease incidence. We argue that modern formal causal models coupled with causal artificial intelligence (CAI) and realistically partial and imperfect knowledge of underlying disease mechanisms, show great promise for determining and quantifying IPoC and CAS for exposures and diseases of practical interest. METHODS: We briefly review key CAI concepts and terms and then apply them to define IPoC and CAS. We present steps to quantify IPoC using a fully specified causal Bayesian network (BN) model. Useful bounds for quantitative IPoC and CAS calculations are derived for a two-stage clonal expansion (TSCE) model for carcinogenesis and illustrated by applying them to benzene and formaldehyde based on available epidemiological and partial mechanistic evidence. RESULTS: Causal BN models for benzene and risk of acute myeloid leukemia (AML) incorporating mechanistic, toxicological and epidemiological findings show that prolonged high-intensity exposure to benzene can increase risk of AML (IPoC of up to 7e-5, CAS of up to 54%). By contrast, no causal pathway leading from formaldehyde exposure to increased risk of AML was identified, consistent with much previous mechanistic, toxicological and epidemiological evidence; therefore, the IPoC and CAS for formaldehyde-induced AML are likely to be zero. CONCLUSION: We conclude that the IPoC approach can differentiate between likely and unlikely causal factors and can provide useful upper bounds for IPoC and CAS for some exposures and diseases of practical importance. For causal factors, IPoC can help to estimate the quantitative impacts on health risks of reducing exposures, even in situations where mechanistic evidence is realistically incomplete and individual-level exposure-response parameters are uncertain. This illustrates the strength that can be gained for causal inference by using causal models to generate testable hypotheses and then obtaining toxicological data to test the hypotheses implied by the models-and, where necessary, refine the models. This virtuous cycle provides additional insight into causal determinations that may not be available from weight-of-evidence considerations alone.

Endogenous aldehyde-induced DNA-protein crosslinks are resolved by transcription-coupled repair.

DNA-protein crosslinks (DPCs) induced by aldehydes interfere with replication and transcription. Hereditary deficiencies in DPC repair and aldehyde clearance processes cause progeria, including Ruijs-Aalfs syndrome (RJALS) and AMeD syndrome (AMeDS) in humans. Although the elimination of DPC during replication has been well established, how cells overcome DPC lesions in transcription remains elusive. Here we show that endogenous aldehyde-induced DPC roadblocks are efficiently resolved by transcription-coupled repair (TCR). We develop a high-throughput sequencing technique to measure the genome-wide distribution of DPCs (DPC-seq). Using proteomics and DPC-seq, we demonstrate that the conventional TCR complex as well as VCP/p97 and the proteasome are required for the removal of formaldehyde-induced DPCs. TFIIS-dependent cleavage of RNAPII transcripts protects against transcription obstacles. Finally, a mouse model lacking both aldehyde clearance and TCR confirms endogenous DPC accumulation in actively transcribed regions. Collectively, our data provide evidence that transcription-coupled DPC repair (TC-DPCR) as well as aldehyde clearance are crucial for protecting against metabolic genotoxin, thus explaining the molecular pathogenesis of AMeDS and other disorders associated with defects in TCR, such as Cockayne syndrome.

Formaldehyde Exposure of Aquaculture Workers in Korea.

OBJECTIVES: Korea's aquaculture sector primarily cultivates aquatic life, with fish seed production as a focus. Formalin, a parasiticide, consists of 37% formaldehyde mixed with yellow No. 4 dye. Formaldehyde vaporization poses cancer risks, classified as a carcinogen. Korea regulates formaldehyde as a hazardous substance, requiring workplace environment measurements. Few aquaculture farms have conducted these checks in recent years. In this study, we investigated actual formaldehyde exposure levels among Korean aquaculture workers, highlighting a critical safety concern. METHODS: A field survey was conducted to measure formaldehyde exposure at 10 aquaculture farms in areas where Korean aquaculture is concentrated. Short-term and long-term personal samples, local samples, and direct-reading measurements were conducted. Formaldehyde exposure levels were detected in short-term personal samples from six farms and in long-term personal samples from two farms, and formaldehyde was detected in all local samples. In direct-reading measurements, a high concentration of formaldehyde was sustained for short periods. RESULTS: Long-term (8-hour) personal samples were mostly non-detectable, except for farms A and D, which had levels of 0.0009 ppm and 0.0017 ppm, respectively. Short-term (15-minute) samples were non-detectable in four farms, with an average of 0.0158 (±0.0130) ppm in the remaining six farms. Local samples from all farms had an average of 0.0384 (±0.0957) ppm of formaldehyde. For farms A and D, where long-term sampling detected formaldehyde, real-time measurements showed a sustained high concentration in farm A for about 48 minutes before decreasing. Farm D had no detectable formaldehyde throughout the monitoring period. CONCLUSION: According to the formaldehyde exposure level assessment, short term exposure to formaldehyde during and immediately after application of formalin nearly exceeded the ACGIH TLV STEL in one farm. However, concentration of long term samples appeared at 10% of ACGIH TLV TWA. Additional study is recommended to determine whether exposure to formaldehyde poses a health risk for aquaculture workers during application of formalin.

RNA sequencing of formalin fixed paraffin-embedded heart tissue provides transcriptomic information about chemotherapy-induced cardiotoxicity.

Gene expression of formalin-fixed paraffin-embedded (FFPE) tissue may serve for molecular studies on cardiovascular diseases. Chemotherapeutics, such as doxorubicin (DOX) may cause heart injury, but the mechanisms of these side effects of DOX are not well understood. This study aimed to investigate whether DOX-induced gene expression in archival FFPE heart tissue in experimental rats would correlate with the gene expression in fresh-frozen heart tissue by applying RNA sequencing technology. The results showed RNA from FFPE samples was degraded, resulting in a lower number of uniquely mapped reads. However, DOX-induced differentially expressed genes in FFPE were related to molecular mechanisms of DOX-induced cardiotoxicity, such as inflammation, calcium binding, endothelial dysfunction, senescence, and cardiac hypertrophy signaling. Our data suggest that, despite the limitations, RNA sequencing of archival FFPE heart tissue supports utilizing FFPE tissues from retrospective studies on cardiovascular disorders, including DOX-induced cardiotoxicity.

Health risk assessment from inhalation exposure to indoor formaldehyde: A systematic review and meta-analysis.

This systematic review and meta-analysis investigated studies on formaldehyde (FA) inhalation exposure in indoor environments and related carcinogenic (CR) and non-carcinogenic (HQ) risk. Studies were obtained from Scopus, PubMed, Web of Science, Medline, and Embase databases without time limitation until November 21, 2023. Studies not meeting the criteria of Population, Exposure, Comparator, and Outcomes (PECO) were excluded. The 45 articles included belonged to the 5 types of sites: dwelling environments, educational centers, kindergartens, vehicle cabins, and other indoor environments. A meta-analysis determined the average effect size (ES) between indoor FA concentrations, CR, and HQ values in each type of indoor environment. FA concentrations ranged from 0.01 to 1620 µg/m3. The highest FA concentrations were stated in water pipe cafés and the lowest in residential environments. In more than 90% of the studies uncertain (1.00 ×10-6 1.00 ×10-4) due to FA inhalation exposure was reported and non-carcinogenic risk was stated acceptable. The meta-analysis revealed the highest CR values due to inhalation of indoor FA in high-income countries. As 90% of the time is spent indoors, it is crucial to adopt effective strategies to reduce FA concentrations, especially in kindergartens and schools, with regular monitoring of indoor air quality.

The impact of formaldehyde exposure on lung inflammatory disorders: Insights into asthma, bronchitis, and pulmonary fibrosis.

Lung inflammatory disorders are a major global health burden, impacting millions of people and raising rates of morbidity and death across many demographic groups. An industrial chemical and common environmental contaminant, formaldehyde (FA) presents serious health concerns to the respiratory system, including the onset and aggravation of lung inflammatory disorders. Epidemiological studies have shown significant associations between FA exposure levels and the incidence and severity of several respiratory diseases. FA causes inflammation in the respiratory tract via immunological activation, oxidative stress, and airway remodelling, aggravating pre-existing pulmonary inflammation and compromising lung function. Additionally, FA functions as a respiratory sensitizer, causing allergic responses and hypersensitivity pneumonitis in sensitive people. Understanding the complicated processes behind formaldehyde-induced lung inflammation is critical for directing targeted strategies aimed at minimizing environmental exposures and alleviating the burden of formaldehyde-related lung illnesses on global respiratory health. This abstract explores the intricate relationship between FA exposure and lung inflammatory diseases, including asthma, bronchitis, allergic inflammation, lung injury and pulmonary fibrosis.

Assessment of associations between inhaled formaldehyde and lymphohematopoietic cancer through the integration of epidemiological and toxicological evidence with biological plausibility.

Formaldehyde is recognized as carcinogenic for the portal of entry sites, though conclusions are mixed regarding lymphohematopoietic (LHP) cancers. This systematic review assesses the likelihood of a causal relationship between formaldehyde and LHP cancers by integrating components recommended by NASEM. Four experimental rodent bioassays and 16 observational studies in humans were included following the implementation of the a priori protocol. All studies were assessed for risk of bias (RoB), and meta-analyses were conducted on epidemiological studies, followed by a structured assessment of causation based on GRADE and Bradford Hill. RoB analysis identified systemic limitations precluding confidence in the epidemiological evidence due to inadequate characterization of formaldehyde exposure and a failure to adequately adjust for confounders or effect modifiers, thus suggesting that effect estimates are likely to be impacted by systemic bias. Mixed findings were reported in individual studies; meta-analyses did not identify significant associations between formaldehyde inhalation (when measured as ever/never exposure) and LHP outcomes, with meta-SMRs ranging from 0.50 to 1.51, depending on LHP subtype. No associations with LHP-related lesions were reported in reliable animal bioassays. No biologically plausible explanation linking the inhalation of FA and LHP was identified, supported primarily by the lack of systemic distribution and in vivo genotoxicity. In conclusion, the inconsistent associations reported in a subset of the evidence were not considered causal when integrated with the totality of the epidemiological evidence, toxicological data, and considerations of biological plausibility. The impact of systemic biases identified herein could be quantitatively assessed to better inform causality and use in risk assessment.

What are the DNA lesions underlying formaldehyde toxicity?

Formaldehyde is a highly reactive organic compound. Humans can be exposed to exogenous sources of formaldehyde, but formaldehyde is also produced endogenously as a byproduct of cellular metabolism. Because formaldehyde can react with DNA, it is considered a major endogenous source of DNA damage. However, the nature of the lesions underlying formaldehyde toxicity in cells remains vastly unknown. Here, we review the current knowledge of the different types of nucleic acid lesions that are induced by formaldehyde and describe the repair pathways known to counteract formaldehyde toxicity. Taking this knowledge together, we discuss and speculate on the predominant lesions generated by formaldehyde, which underly its natural toxicity.

Sensory irritation and use of the best available science in setting exposure limits: Issues raised by a scientific panel review of formaldehyde human research studies.

As a high production volume chemical with recognized sensory irritation and widespread exposure, the human health risk potential of formaldehyde has been reviewed by many international regulatory agencies and scientific advisory bodies. A scientific panel, the Human Studies Review Board, under the auspices of the EPA's Toxic Substances Control Act (TSCA) program recently reviewed the sensory irritation studies included in the 2022 Draft Integrated Risk Information System (IRIS) Formaldehyde Hazard Assessment in the context of their use in a weight of evidence evaluation of acute inhalation health effects. This panel issued a series of recommendations on the use of these studies for the purposes of calculating exposure limits (e.g., study design preferences; uncertainty adjustment). Considering that these recommendations might reflect topic areas with varying degrees of scientific consensus, this commentary reflects on commonalities and distinctions amongst international formaldehyde exposure limits based on sensory irritation. Notably, each review panel charged with an assessment of the science recommended that no adjustment was needed to account for either exposure duration or human variability. These areas of scientific consensus should be considered as the best available science for the purposes of setting exposure limits in the anticipated TSCA Risk Evaluation on formaldehyde.

Aldehyde dehydrogenase 2 deficiency reinforces formaldehyde-potentiated pro-inflammatory responses and glycolysis in macrophages.

Aldehyde dehydrogenase 2 (ALDH2) deficiency caused by   genetic variant is present in more than 560 million people of East Asian descent, which can be identified by apparent facial flushing from acetaldehyde accumulation after consuming alcohol. Recent findings indicated that ALDH2 also played a critical role in detoxification of formaldehyde (FA). Our previous studies showed that FA could enhance macrophagic inflammatory responses through the induction of HIF-1α-dependent glycolysis. In the present study, pro-inflammatory responses and glycolysis promoted by 0.5 mg/m3 FA were found in mice with Aldh2 gene knockout, which was confirmed in the primary macrophages isolated from Aldh2 gene knockout mice treated with 50 µM FA. FA at 50 and 100 µM also induced stronger dose-dependent increases of pro-inflammatory responses and glycolysis in RAW264.7 murine macrophages with knock-down of ALDH2, and the enhanced effects induced by 50 µM FA was alleviated by inhibition of HIF-1α in RAW264.7 macrophages with ALDH2 knock-down. Collectively, these results clearly demonstrated that ALDH2 deficiency reinforced pro-inflammatory responses and glycolysis in macrophages potentiated by environmentally relevant concentration of FA, which may increase the susceptibility to inflammation and immunotoxicity induced by environmental FA exposure.

Survival of formalin intoxication in a 13-year-old Thoroughbred gelding.

BACKGROUND: Formalin intoxication via the gastrointestinal route has not been previously reported in the horse. Whereas ingestion of formalin in humans, although rare, is well documented. Majority of human cases are either accidental, suicidal or homicidal and often lead to fatality, with a reported lethal formaldehyde dose equating to 0.12 - 0.16 g/kg bwt. OBJECTIVES: To describe a single case report of the clinical management of an adult horse referred to a veterinary teaching hospital following accidental administration of 10% formalin via nasogastric tube. METHODS: A 13-year-old Thoroughbred gelding originally presented to the referring veterinarian for colic where 1.8 L of 10% formalin was accidentally administered instead of mineral oil via nasogastric intubation, a potentially lethal dose of formaldehyde (0.12 g/kg bwt). Approximately 20-hours following 10% formalin administration the horse was admitted to the referral hospital with moderate tachycardia, occasional ectopic beats, tacky and hyperaemic mucous membranes, delayed capillary refill time, reduced borborygmi, and pronounced digital pulses. Diagnostic investigations included laboratory blood analysis, urinalysis, electrocardiogram, abdominal ultrasound, palpation per rectum and gastroscopy. RESULTS: Patient assessment found evidence of toxicity to the gastrointestinal tract, hypovolaemia and risk for laminitis. Intensive care included fluid and electrolyte therapy, anti-inflammatories and analgesia, continuous digital cryotherapy, gastro-protectants and other methods of gastrointestinal support. The horse was discharged from hospital on day 14 with no long-term complications and the client-veterinarian relationship was preserved. DISCUSSION: In human cases of ingestion, gastrointestinal injury is typically accompanied by severe metabolic acidosis and multiple organ dysfunction syndrome due to toxicity of other body systems that can contribute to non-survival. Formaldehyde toxicity in the present case predominantly affected the gastrointestinal tract, most likely a direct result of the route of administration. Aside from gastrointestinal injury, primary toxicity of other body systems was not confirmed. To prevent this medical error recurring, the referring veterinary clinic revised their labelling and storage of 10% formalin. CONCLUSION: This is the first report of systemic formalin intoxication in the horse. Following a high dose of 10% formalin (0.12 g/kg bwt formaldehyde) enterally, the horse survived having received intensive supportive care based on human guidelines for ingested formalin.

Formaldehyde aggravates airway inflammation through induction of glycolysis in an experimental model of asthma exacerbated by lipopolysaccharide.

Formaldehyde (FA) exposure has been reported to induce or aggravate allergic asthma. Infection is also a potential risk factor for the onset and aggravation of asthma. However, no study has addressed the effects of FA exposure on asthmatic patients with respiratory infection. FA is ubiquitous in environment and respiratory infections are common in clinics. Therefore, it is necessary to explore whether FA exposure leads to the further worsening of symptoms in asthma patients with existing respiratory infection. In the present study, ovalbumin (OVA) was used to establish the murine asthma model. Lipopolysaccharide (LPS) was intratracheal administrated to mimic asthma with respiratory infection. The mice were exposed to 0.5 mg/m3 FA. FA exposure did not induce a significant aggravation on OVA induced allergic asthma. However, the lung function of specific airway resistance (sRaw), histological changes and cytokines production were greatly aggravated by FA exposure in OVA/LPS induced murine asthma model. Monocyte-derived macrophages (MDMs) were isolated from asthmatic patients. Exposure of MDMs to FA and LPS resulted in increased TNF-α, IL-6, IL-1ß, and nitric oxide (NO) production. Lactate produciton and lactate dehydrogenase A (LDHA) expression were found to be upregulated by FA in OVA/LPS induced asthmatic mice and LPS stimulated MDMs. Furthermore, glycolysis inhibitor 2-Deoxy-d-glucose attenuated FA and LPS induced TNF-α, IL-6, IL-1ß, and NO production. We conclude that FA exposure can lead to the aggravation of allergic asthma with infection through induction of glycolysis. This study could offer some new insight into how FA promotes asthma development.

Influence of formaldehyde exposure on the molecules of the NO/cGMP-cAMP signaling pathway in different brain regions of Balb/c mice.

This toxicology study was conducted to assess the impact of formaldehyde, a common air pollutant found in Chinese gymnasiums, on the brain function of athletes. In this research, a total of 24 Balb/c male mice of SPF-grade were divided into four groups, each consisting of six mice. The mice were exposed to formaldehyde at different concentrations, including 0 mg/m3, 0.5 mg/m3, 3.0 mg/m3, and 3.0 mg/m3 in combination with an injection of L-NMMA (NG-monomethyl-L-arginine), which is a nitric oxide synthase antagonist. Following a one-week test period (8 h per day, over 7 days), measurements of biomarkers related to the nitric oxide (NO)/cGMP-cAMP signaling pathway were carried out on the experimental animals post-treatment. The study found that: (1) Exposure to formaldehyde can lead to brain cell apoptosis and neurotoxicity; (2) Additionally, formaldehyde exposure was found to alter the biomarkers of the NO/cGMP-cAMP signaling pathway, with some changes being statistically significant (p < 0.05 or p < 0.01); (3) The use of L-NMMA, an antagonist of the NO/cGMP-cAMP signaling pathway, was found to prevent these biomarker changes and had a protective effect on brain cells. The study suggests that the negative impact of formaldehyde on the brain function of mice is linked to the regulation of the NO/cGMP-cAMP signaling pathway.