Aluminum Phosphide Poisoning Research Articles

Insulin in aluminum phosphide poisoning: A systematic review of the current literature.

Aluminum phosphide (AlP) is a commonly used fumigant in agriculture and grain preservation because of its high potency and low cost. Due to the absence of a specific antidote and promising treatment modality, poisoning with this substance is deadly. Amid multiple studies in different parts of the world, each exploring options like lavage, inotropes, antioxidants, etc, we conducted a systematic review to find the possible role of exogenous insulin in treating symptomatic cases of AlP poisoning. Experimental studies released before February 15, 2024, that reported the use of exogenous insulin were systematically reviewed following the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. The search was done on PubMed Central, Cochrane Library, and Google Scholar. After applying the inclusion and exclusion criteria, we finalized a few scientific papers for the review. Studying data from 4 scientific papers (3 quasi-experimental studies and 1 randomized controlled trial), we could postulate the significant improvement in survivability after the inclusion of exogenous insulin in the treatment of poisoned cases of AlP. Studies showed divergent results for the blood pressure, blood gases, and need for mechanical ventilation. Hypoglycemia, hyperglycemia, and hypokalemia were the reported adverse effects of this therapy. Our review found that the use of exogenous insulin in AlP poisoning reduced mortality rates, which was consistent across all studies. With available knowledge, its inclusion as a part of therapy might be beneficial in AlP poisoning, but to put it forward confidently, we still need high-quality randomized control trials. It is indeed a subject of interest for future research.

Clinico-Epidemiological Profile and Outcome of Acute Poisoning Patients admitted to Intensive Care Unit in A Tertiary Level Private Hospital in Bangladesh

Background: Acute poisoning is a prevalent health issue necessitating Intensive Care Unit (ICU) admission in developing countries. This study evaluates the socio-demographic characteristics, clinical parameters, and outcomes of acute poisoning patients admitted to the ICU in a tertiary level private hospital in Bangladesh. Method: This retrospective cohort study was conducted at tertiary care private hospital in Narayanganj, Bangladesh. Data was collected from ICU medical records from January 2023 to April 2024, enrolling a total of 57 patients aged 18 years or more who presented with acute poisoning. Data analysis was performed using Stata (Statistical Software for Data Science) 17.0(p < 0.05) Results: Out of 57 patients, 52.63% were females, with mean age of 27.84 years. Suicidal intent accounted for 84.21% of cases, and the primary reasons for poisoning included marital (61.40%) and familial disharmony (15.79%). The predominant type of poisoning was due to sedatives (17.54%) followed by aluminium phosphide (14.04%), and stupefying agents (14.04%). Aluminium phosphide poisoning had a 100% fatality rate, while sedatives and several other agents had 100% recovery rate. Statistical analysis showed a significant association between the type of poison and the final outcome (χ2(15) = 38.7996, p = 0.001). Conclusion: The study highlights the prevalence of intentional poisoning among young adults, especially females, with sedatives, aluminium phosphide, and stupefying agents being the most common. The high mortality rate from aluminium phosphide underscores the need for strict regulations and public awareness to control access to these substances. Bangladesh Crit Care J September 2024; 12 (2): 89-95

Incidental detection of aluminum phosphide in abdominal subcutaneous fat- a rare reporting of chemical analysis findings in poisoning cases.

Aluminum phosphide (AlP) poses a significant health challenge in developing countries, primarily because of its accessibility to the unregulated market and the absence of specific antidotes. Although chemical analysis of routine viscera can provide valuable information regarding the type of poison present in the body during poisoning incidents, numerous factors can alter the test results of chemical analysis, such as decomposition changes, postmortem redistribution, and the chemical nature of drugs. Analytical methods are frequently impeded by the interference caused by coextracted putrefactive compounds, which can mask or alter the detection of drugs. This series of three cases is particularly noteworthy because it involves the postmortem detection of AlP in the abdominal subcutaneous fat of the deceased, a previously unreported occurrence. In the first case, the body showed findings of late postmortem changes, with stomach mucosa being congested and hemorrhagic, along with routine viscera, and abdominal subcutaneous fat was sent for toxicological analysis. To confirm these findings, in two further cases of suspected AlP poisoning, subcutaneous fat was sent along with routine viscera. Stomach mucosa in the other two cases showed findings similar to those in the first. In the third case, black paste-like material was noted as stomach content. All the cases revealed the presence of AlP in routine viscera samples and abdominal subcutaneous fat on gas chromatography-mass spectrometry (GC‒MS) analysis. Therefore, abdominal fat can serve as a suitable sample for toxicological analysis to identify the presence of AlP, even in cases with advanced putrefactive changes.

An Oxidative Stress Study on Curcumin and NanoCurcumin against Aluminum Phosphide-induced Kidney Injury in Rats: The Role of SIRT1/FOXO3 Signaling Pathway in Nephrotoxicity.

In this study, we have investigated the aluminium phosphide (ALP) toxicity on Renal Function and oxidative stress in kidney tissue of male rats and the possible protective role of Curcumin and nanoCurcumin against ALP-induced nephrotoxicity. Thirty-six adult male rats were divided into 6 groups (n=6). ALP (2 mg/kg oral administration) and control groups received Curcumin and nanoCurcumin (oral administration 100 mg/kg) or without it. After seven days of treatment, kidney parameters, oxidative stress biomarkers, and expression level of sirtuins1 (SIRT1)/Forkhead box protein O1 (FoxO1) pathway genes were evaluated in kidney tissue. In addition, histopathological changes in the kidney tissues were assayed. In the ALP group, compared to the control group, lipid peroxidation levels, urea, and creatinine were increased, and total antioxidant capacity and thiol groups decreased significantly p < 0.05. In Curcumin and nanoCurcumin groups compared to the ALP group, lipid peroxidation and creatinine decreased significantly p < 0.05. Also, Curcumin and nanoCurcumin improved the tissue damage caused by ALP. NanoCurcumin modulated the effect of ALP on the gene expression levels in SIRT1/FoxO1. The present study showed that ALP intoxication in kidney tissue can induce oxidative damage. Moreover, Curcumin and nanocurcumin, as potential antioxidants, can be effective therapeutics in ALP-induced nephrotoxicity.

Prognostic value of PGI score compared to poison severity score (PSS) and simplified acute physiology score (SAPS) II as predictors of mortality and other adverse outcomes in acute poisoning with aluminum phosphide

Aluminum phosphide (AlP) poisoning is a life-threatening emergency prevalent in the Middle East region including Egypt. Early prediction of prognosis is critical for initiating the utmost intensive interventions. Though many scoring systems were studied for predicting the prognosis of AlP poisoning, these scores received wide criticism. Complexity and reliability were the main concerns. Therefore, this retrospective cross-sectional study aimed to evaluate the performance of the recently introduced PGI score as a predictor of case fatality, the need for mechanical ventilation and vasopressor therapy in acute AlP poisoning. Moreover, it compares the performance of PGI with the known poison severity score (PSS), and the simplified acute physiology score (SAPS) II. Among 144 exposed patients, we reported a mortality rate of 61.1%. Non-survivors exhibited significantly higher PGI, PSS, and SAPS II than survivors. Though the PGI, PSS, and SAPS II proved their significance as predictors of mortality and, the need for MV and vasopressors, the PGI score showed a significantly higher area under the curve (AUC) as a predictor of MV (AUC = 0.848) compared to PSS (AUC = 0.731) and SAPS II (AUC = 0.749). Additively, PGI of 2 or more was a significant predictor of mortality (AUC = 0.831, sensitivity = 65.9%, and specificity = 89.3 %) and MV (p < 0.001), while PGI of 1 or more was another predictor of vasopressor need (AUC = 0.881, sensitivity = 89.0% and specificity = 79.4%). Given the PGI score's high AUCs across all outcomes, coupled with its balanced sensitivity and specificity, the PGI score could be a simple, and robust tool replacing the PSS and SAPS II for predicting mortality, clinical decision-making including the need for MV and vasopressor therapy in acute AlP exposure. Adopting the PGI score seems substantially useful in managing acute AlP poisoning, notably in resource-restricted countries.

Toxic Myocarditis with Brugada Phenocopy in a Case of Aluminum Phosphide Poisoning

Brugada phenocopy is considered when a Brugada-type ECG pattern is present but with a low likelihood of true Brugada syndrome, as indicated by negative family history, genetic testing, or provocative testing with drugs, or ECG normalization after the removal of precipitants. Brugada phenocopy has been reported due to various causes such as fever and electrolyte imbalance. We describe a 22-year-old man who presented with aluminum phosphide poisoning, resulting in severe metabolic acidosis, myocarditis, and profound myocardial depression. He developed transient Brugada-like ECG changes and multiorgan dysfunction, requiring intensive management, including mechanical ventilation and inotropes. Brugada phenocopy is a rare manifestation of aluminum phosphide-associated toxic myocarditis. After a week of treatment, there was a significant improvement in cardiac function and overall clinical status.

The Protective Effect of Ethanolic Extract of Olive Leaf on Aluminum Phosphide-Induced Cardiac Toxicity in Rats

Background: The purpose of this study is to evaluate a treatment for aluminum phosphide (ALP) poisoning, which is known as “rice tablet”. Methods: In the present study, the impact of different doses of ethanolic extract of olive leaves (100, 200, and 400 mg/kg) on ALP (120 mg/kg)-induced cardiotoxicity was evaluated in anesthetized-gastrotomized adult male Wistar rats. Thirty-five rats were randomly assigned into five groups (n=7) as follows: control (AC) and treatment groups [ALP+Olea100 (AO100), ALP+Olea 200 (AO200), and ALP+Olea 400 (AO400)]. Physiological data including blood pressure, heart rate, electrocardiogram (ECG), as well as oxidative stress markers were measured in heart tissues. Results: ALP-intoxication led to perturbed normal ECG and increased oxidative stress. Administration of olive leaf extract at various concentrations, however, mitigated bradycardia after 90 minutes, following ALP-intoxication (in AO200), hypotension (in AO100), and cardiac conduction disturbances (decreased QTC in the AO200 30 (P&lt;0.05), 60 (P&lt;0.001), and 90 (P&lt;0.05) minutes after intoxication) and decreased PR 60 (P&lt;0.05) and 90 minutes (P&lt;0.01) after intoxication. This was compared with baseline as well as detrimental changes in cardiac electrophysiology [mitigated ST-segment elevation in AO200 and depressed T-wave in the AO200 (P&lt;0.05) and AO400 (P&lt;0.01) groups 90 minutes after intoxication] Conclusion: Based on these authentic results, it seems that olive leaf extracts can be useful in reducing the severity of symptoms in ALP-poisoned individuals and could be utilized in a poisoning emergency.

Examining the effectiveness of prognostic scoring systems and mortality predictors in aluminum phosphide poisoning: insights from emergency department settings

Aluminum Phosphide (AlP), a potent rodenticide and fumigant pesticide, poses a significant health threat, especially in agricultural communities. This study aimed to investigate demographic trends and predictive factors influencing outcomes in AlP poisoning patients presenting to the Emergency Department (ED). With an alarming mortality rate of 80.4%, identifying predictors of mortality became imperative. Non-survivors tended to be older and presented with distinct vital signs, such as tachycardia and shock upon ED arrival. Prognostic scoring systems like the Modified Early Warning Score (MEWS), Shock Index (SI), Mean Arterial Pressure (MAP), Glasgow Coma Scale (GCS), and serum lactate emerged as robust mortality predictors, with good accuracy (Area Under the Curve, AUC, MEWS=0.904, SI=0.914, MAP=0.869, GCS=0.829, lactate=0.962). This study favors integrating these predictors into routine ED practices, particularly in Low- and Middle-Income Countries (LMICs), to prognosticate and enhance management outcomes in patients with AlP poisoning, offering essential guidance for emergency physicians.

Pattern of poisoning cases in Bir Hospital

Background: Poisoning is one of the major causes of hospitalization through emergency and is a major public health problem in the country. For starting preventive measures, information on nature and extent of poisoning is required. For some years, there has been no study on poisoning at Bir hospital. Objectives: To find out the patient profile, the common poisons and outcome of poisoning cases. Materials and Methods: A retrospective analysis of all acute poisoning cases admitted to the emergency department of Bir Hospital from January 2005 to June 2005 was done to study the pattern of acute poisoning. Data on age, sex, time elapsed after intake, circumstances of poisoning, name of the poisonous substance, actual use, chemical type, hospitalization days, severity and outcome were collected and analyzed. Results: The age of the patients varied from 16 to 65 years. The male female ratio was 1:1.3. More than three-fourth (76.8%) of the female patients were from 16 to 25 years age group. Similarly, 46.5% of the male patients were from 16 to 25 years age group. In more than 25 years of age, there was malepredominance in all the age group. The common insecticides used for poisoning were organophosphorus compounds mainly Methyl Parathion (Metacid) and Dichlorovos (Nuvan). Paracetamol alone or combination preparations with antihistamines were the most common analgesic used. Benzodiazepines were the most commonly used anxiolytics. Ninety-seven percent of caseswere intentional poisoning for suicidal attempt. Most of the cases (61.6%) had arrived hospital within 3 hours after exposure to the poison. The hospital stay of the admitted patients with poisoningranged from one to sixteen days. The mean hospital stay was 5.9 days. During the hospital stay, six (6.0%) cases were managed in Intensive Care Unit (ICU) service. In this study, only 3% cases had mortality. There were 5 cases of Aluminium Phosphide poisoning but surprisingly, none of them died from this highly toxic poison. Conclusion: Suicide among adolescents and young adults is a common public health problem. Patients with intentional poisoning must undergo psychiatric consultation during their stay in the hospital for the treatment poisoning. This will minimize the risk of next attempt of self harm. In addition, strict rules must be followed regarding sale of psychotropic medicines and pesticides. Effective clinical management of poisoning can minimize the mortality.

Mitotherapy with Fresh Isolated Cardiac Mitochondria Via Injection Into Blood Reduces Aluminum Phosphide-Induced Mortality and Protects Cardiac Tissue Against Oxidative Stress and Mitochondrial Damages.

The hallmark of aluminum phosphide (AlP) poisoning is heart failure in victims which is associated with reactive oxygen species (ROS), mitochondrial dysfunction, oxidative stress, alteration in antioxidant defense system and depletion of ATP in cardiomyocytes. In the present study, we hypothesized that the injection of isolated mitochondria into blood or mitochondrial transplantation can likely create a primary target for phosphine released from AlP and inhibit AlP-induced mortality and cardiotoxicity in rat. Male, Wistar, healthy and adult rats were randomly divided into 5 groups as control, AlP (12.5 mg/kg, orally), AlP + mitochondria (125 µg/kg), AlP + mitochondria (250 µg/kg) and mitochondria (250 µg/kg) alone. Functional and intact mitochondria isolated from rat heart and transplantation was carried out via tail vein, 30 min after exposure to AlP. Survival rate, histopathological alterations, cardiac biochemical markers, oxidative stress and mitochondrial toxicity parameters were monitored and analyzed during 30 days. We found that injection of healthy mitochondria into blood at concentrations of 125 and 250 125 µg/ml significantly increased the survival of rats up to 40% and 56.25% respectively, during 30 days. Moreover, we observed that mitochondria injection into blood decreased histopathological damages, cardiac biochemical markers, oxidative stress and mitochondrial toxicity parameters. To our knowledge, the current study is the first report in the literature that demonstrated good therapeutic effects of mitochondrial transplantation in AlP-induced mortality and cardiotoxicity. The findings of the present study suggests that injection of exogenous mitochondria into blood could be an effective therapeutic strategy in treating AlP poisoning.

Construction of a Crucial Score to predict the Outcome of Patients with Aluminum Phosphide Poisoning at the Poison Control Center - Ain Shams University Hospitals

Construction of a Crucial Score to predict the Outcome of Patients with Aluminum Phosphide Poisoning at the Poison Control Center - Ain Shams University Hospitals

Hemolytic Uremic Syndrome Following the Aluminum Phosphide Poisoning: A Case Report

Aluminum Phosphide (ALP) is an effective, cheap, and highly toxic pesticide. ALP poisoning can have destructive effects on the human body, such as the heart, lungs, gastrointestinal tract, kidneys, and central nervous system, although all organs can be involved. We describe a 53-year-old Iranian Kurdish man with Hemolytic Uremic Syndrome (HUS) and Acute Kidney Injury (AKI). Supportive treatments such as hemodialysis and plasmapheresis were performed. After 23 days of hospitalization, the patient fully recovered and was discharged. Thrombotic microangiopathy such as HUS should be considered in patients with ALP toxicity that has a genetic defect in complement proteins. Combined use of hemodialysis and plasmapheresis improve outcomes in these patients.

Effective Management of Acute Aluminum Phosphide Poisoning in Pregnancy: A Case Study of Dual Therapy Efficacy and Collaborative Care

Effective Management of Acute Aluminum Phosphide Poisoning in Pregnancy: A Case Study of Dual Therapy Efficacy and Collaborative Care

The possible therapeutic role of intravenous lipid emulsion in acute aluminium phosphide poisoning: a randomized controlled clinical trial.

Aluminum phosphide (ALP) is a highly toxic rodenticide and the mortality rates caused by it have been demonstrated up to 70-100% in various studies. Unfortunately, there is no specific antidote to manage its toxic effects. This study aimed to assess the biochemical and clinical efficacy and safety of intravenous lipid emulsion as an adjuvant therapy in acute aluminum phosphide poisoning. Sixty-four cases with acute ALP poisoning were stratified according to severity by the Poison Severity Score into severe and moderate groups (32 patients each). Patients were then randomly allocated into either receiving intravenous lipid emulsion in addition to the conventional treatment or receiving the conventional treatment only by using block randomization. Treatment by ILE resulted in a significant improvement in the survival time, the mean arterial blood pressure, arterial blood gases, and a significant reduction in serum lactate levels. The need for intubation and mechanical ventilation was insignificantly lower in the intervention groups compared to control groups. However, the reduction in mortality rate in the patients of intervention groups compared with control groups was found to be non-significant. Intravenous lipid emulsion use in acute ALP poisoning significantly prolonged the survival time, improved the metabolic acidosis, decreased the serum lactate levels and increased the mean arterial blood pressure and hospital stay in the intervention groups. And insignificantly decreased the mortality rate, need of intubation and mechanical ventilation, and the total dose of vasopressors.

The possible link between aluminum phosphide poisoning and NLRP3 inflammasome

Aluminum phosphide (AlP) is a fumigant used to control pests. However, human exposure to this substance can lead to poisoning. AlP reacts with gastric acid and water to release phosphine (PH3). This toxic gas affects the mitochondria and quickly enters the bloodstream. This gas impairs the mitochondria's ability to generate ATP, leading to oxidative stress, mitochondrial dysfunction, and damage to mitochondrial DNA (mt-DNA). Mitochondria release damage-associated molecular patterns (DAMPs) to shield cells from stress and stimulate the innate immune system.Nonetheless, if mitochondrial homeostasis is disrupted, an excessive immune response can occur, causing organ dysfunction. Mitochondrial reactive oxygen species (mt-ROS) and mt-DNA act as DAMPs. Upon recognition of DAMPs, the inflammasome is activated, causing inflammation. The nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP3) gene on chromosome 1's extended arm encodes a protein that triggers the human inflammasome. NLRP3 is the most extensively researched inflammasome subfamily. It is essential to recognize that the pathophysiology of mitochondrial dysfunction and NLRP3 activation is complex and multifactorial, and a comprehensive approach may be needed to address both the underlying causes and downstream inflammatory responses effectively. The cGAS-STING pathway is essential for immune responses, and targeting specific nodes can be beneficial. Therapeutic approaches include small molecule drugs, biologics, vaccines, and combination therapies. Since there is a significant relationship between mitochondrial events and NLRP3 activation, targeting this inflammasome could be a promising strategy for developing antidotes for AlP poisoning.

Expression of Concern: Reducing the risk of death induced by aluminum phosphide poisoning: The new therapies

Expression of Concern: Reducing the risk of death induced by aluminum phosphide poisoning: The new therapies

The adjuvant effect of oil-based gastric lavage on the outcome of acute Aluminum phosphide poisoning: a systematic review and meta-analysis.

Aluminum Phosphide (AlP) poisoning constituted the most common cause of poisoning death in some low- and middle-income countries (LMICs). This study aimed to evaluate the safety and efficacy of oil-based gastric lavage (GL) compared with standard therapy for the treatment of AlP poisoning. Materials and methods. This systematic review complied with "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) Protocols. A comprehensive search was carried out, identifying randomized controlled trials (RCTs), including anyone presenting within 6h of exposure to AlP, and the administration of GL with oils, including liquid paraffin or coconut oil. We identified 7 RCTs. The evidence from 4 RCTs indicates that GL with paraffin oil is an effective treatment for acute AlP poisoning, decreasing the mortality rate (RR=0.62; 95% CI=0.48 to 0.81; participants=226; I 2=10%; low-quality evidence). We estimate the Number Needed to Treat of 4. Likewise, this intervention reduces the need for intubation and mechanical ventilation (RR=0.62; 95% CI=0.40 to 0.79; I2=0%; low-quality evidence). Regarding GL with coconut oil, the evidence from 4 RCTs, indicates a slight reduction in mortality (RR=0.82; 95% CI=0.69 to 0.98; participants=112; I2=0%; very low-quality evidence). Limited evidence suggests that GL with paraffin oil is effective in reducing the mortality rate. Likewise, limited evidence showed in favor of paraffin oil concerning the need for intubation and mechanical ventilation. Very limited evidence suggests that GL with coconut oil could reduce mortality. Both interventions would have a benign safety profile.

Evaluation of the protective effect of coenzyme Q10 on hepatotoxicity caused by acute phosphine poisoning.

Background: Aluminum phosphide (AlP) poisoning is prevalent in numerous countries, resulting in high mortality rates. Phosphine gas, the primary agent responsible for AlP poisoning, exerts detrimental effects on various organs, notably the heart, liver and kidneys. Numerous studies have documented the advantageous impact of Coenzyme Q10 (CoQ10) in mitigating hepatic injuries. The objective of this investigation is to explore the potential protective efficacy of CoQ10 against hepatic toxicity arising from AlP poisoning. Method: The study encompassed distinct groups receiving almond oil, normal saline, exclusive CoQ10 (at a dosage of 100mg/kg), AlP at 12mg/kg; LD50 (lethal dose for 50%), and four groups subjected to AlP along with CoQ10 administration (post-AlP gavage). CoQ10 was administered at 10, 50, and 100mg/kg doses via Intraparietal (ip) injections. After 24h, liver tissue specimens were scrutinized for mitochondrial complex activities, oxidative stress parameters, and apoptosis as well as biomarkers such as aspartate transaminase (AST) and alanine transaminase (ALT). Results: AlP induced a significant decrease in the activity of mitochondrial complexes I and IV, as well as a reduction in catalase activity, Ferric Reducing Antioxidant Power (FRAP), and Thiol levels. Additionally, AlP significantly elevated oxidative stress levels, indicated by elevated reactive oxygen species (ROS) production, and resulted in the increment of hepatic biomarkers such as AST and ALT. Administration of CoQ10 led to a substantial improvement in the aforementioned biochemical markers. Furthermore, phosphine exposure resulted in a significant reduction in viable hepatocytes and an increase in apoptosis. Co-treatment with CoQ10 exhibited a dose-dependent reversal of these observed alterations. Conclusion: CoQ10 preserved mitochondrial function, consequently mitigating oxidative damage. This preventive action impeded the progression of heart cells toward apoptosis.

The comparative study of mortality rate on Aluminium phosphide poisoning in three districts of Himachal Pradesh

The comparative study of mortality rate on Aluminium phosphide poisoning in three districts of Himachal Pradesh

Death Due To 2, 4-DI-Ethyl Ester Poisoning –A Rarely Documented Compound in Clinical and Forensic Practice

Poisoning with Herbicides, Pesticides and Rodenticides etc. is very common nowadays especially in the northern parts of India due to their easy availability from market. Such compounds are available in the houses of farmers, persons dealing in agriculture sectors. Most of the time the cases of poisoning which are brought to our hospitals or are brought for autopsy in the mortuaries are of Organo phosphates, Organo chloro compounds or Aluminum Phosphide poisoning. In this case, we will discuss about the poisoning with a rarely documented compound 2, 4 Di Ethyl Ester which is a compound of Phenoxy acetic group. 2,4 Dichlorophenoxyacetic acid (2,4-D) is a selective herbicide used to kill broad leafed plants. The signs and symptoms of this compound mimics with anti-cholinesterase compounds which might be the reason for under reporting of this compound as a potential cause of poisoning. The role of preserving blood sample during post-mortem to look for myoglobin and creatine phsphokinase levels may be of help in giving opinion regarding cause of death in case of negative FSL's reports.