Abstract
Introduction
The primary objective of this study was to compare the mortality rates and clinical severity of aluminum phosphide (AlP) versus zinc phosphide (ZnP) poisoning. The secondary objectives were to identify specific prognostic factors such as method of ingestion and clinical markers (hypotension, acidosis) and to describe the epidemiological profile of these cases in Khorramabad, Iran.
Methods
A retrospective, cross-sectional study was conducted by reviewing the medical records of 59 patients admitted for AlP or ZnP poisoning to Shahid Rahimi Hospital in Khorramabad during 2021–2022. Data on demographic characteristics, poisoning details, clinical course, and outcomes were collected. Statistical analysis was performed using SPSS version 20, employing descriptive statistics, Chi-square, Fisher’s exact, and independent t-tests.
Results
The majority of patients were male (52.5%), with a mean age of 30.12 ± 11.96 years. AlP poisoning accounted for 69.5% of cases, with a significantly higher mortality rate (29.3%) compared to ZnP, which had a single fatality. The method of ingestion was a critical prognostic factor for AlP; patients who consumed it without dissolving it in water had a markedly higher mortality rate (50%) than those who dissolved it first (6.7%). The development of hypotension (P < 0.001) and metabolic acidosis (P = 0.003) within the first 48 h were strongly associated with mortality in AlP poisoning. AlP poisoning accounted for 69.5% of cases, with a significantly higher mortality rate (29.3%) compared to ZnP, which had no fatalities (0%). The method of ingestion was a critical prognostic factor for AlP. Intensive care unit (ICU) admission was also a significant predictor of poor outcome. In contrast, no significant association was found between prognosis and gender, psychiatric history, physical form of the poison, or time to hospital presentation. Aluminum phosphide is significantly more lethal than zinc phosphide, largely due to its form, leading to internal phosphine gas release. The consumption method, along with the development of hypotension and metabolic acidosis, are crucial prognostic indicator for AlP poisoning.
Conclusion
These findings underscore the need for aggressive management of metabolic acidosis and hypotension. Stricter enforcement of pesticide sales bans, enhanced safety protocols to prevent accidental exposures, and further research on ZnP poisoning are strongly recommended.
Keywords: Aluminum phosphide, Zinc phosphide, Poisoning, Toxicological, Hypotension
Introduction
Overall, a pesticide is a substance used to control unwanted plants, pests, rodents, or plant diseases [1]. Pesticides include herbicides, insecticides, rodenticides, and fungicides, and are highly important in the agricultural sector [2]. By protecting crops from pests and weeds, and also increasing productivity per hectare, they help farmers produce more food on smaller areas of land [3]. For example, rice, which provides food for more than half of the world’s population, has more than double the yield when pesticides are used [4]. One famous pesticide that is widely used in our country is rice tablets, which are highly toxic and lethal substances [5].
Rice tablets, known scientifically as aluminium phosphide with the chemical formula AlP, were first introduced in 1973 as an ideal pesticide [6]. Since then, they have been used to prevent pest infestation in stored rice, to eliminate pests in other stored grains, and to prevent mold in animal feed, tobacco, etc [7]. The rice tablet available in Iran is sold under the trade name Phostoxin. This tablet contains aluminium phosphide, hydrogen phosphide, carbamide, and ammonia [8]. It is sold as dark gray 3-gram tablets in packages of 10 at a low price [9]. The high lethality of this toxic substance and its availability are reasons why it is widely used for suicide in our country; therefore, its sale in pharmacies and herbal shops has been prohibited since 2013 [10, 11].
It is worth mentioning that another type of rice tablet pesticide exists in our country which is used for household purposes [12]. It does not contain any metallic phosphide and contains garlic extract, sodium chloride, talc, and starch, and naturally lacks the toxic effects of metallic phosphides [13, 14].
On the other hand, rodents, which comprise half of mammalian species, are themselves considered pests of agricultural products, especially in warehouses and food storage sheds [15]. In addition to damaging agricultural products, they have high reproductive rates and widespread distribution, and are also significant from a health and disease perspective [16]. Methods for controlling rodents are varied and include trapping and hunting, poisoning, and fumigating their nests with fumigant poisons (poisons that exist as gas or vapor; if they are in liquid form, like ethylene dibromide and formaldehyde, they can vaporize, and if they are solid, like aluminium phosphide, sodium cyanide, and zinc phosphide, they can release toxic gas when mixed with water) [17, 18]. Among these, the poisoning method is considered the most common, effective, and economical [19].
Rodenticides, commonly referred to as rat poison, are chemicals whose aim is to eliminate small rodents [20]. Common target species for their use are household rodents like mice, squirrels, gophers, etc [21]. Rodent control is necessary because they are vectors for spreading disease, destroy crops/grains, and reproduce rapidly [22]. In India, which is considered an agricultural hub, rodenticides are widely used and also freely available [23]. They are available in various formulations and forms including powder, paste, pellets, grain baits, or blocks [24]. Developing a rodenticide has its own challenges because rodents will not eat what seems toxic to them or what they suspect is toxic [25]. An ideal rodenticide is highly toxic to rodents in small quantities and non-toxic to non-target species [26].
Rodenticides include the categories of inorganic poisons (white phosphorus or zinc phosphide, thallium) [8], coumarin-based poisons (anticoagulants), and cholecalciferol poison, whose mechanism is based on increasing vitamin D, and organic compounds (organophosphorus-based poisons like temephos, whose average lethal dose for rats is 1300 to 8600 mg, and poisons in this category are mostly insecticides) [27, 28].
Based on their toxicity severity, rodenticides are classified into three categories: high, moderate, and low toxicity [29]. The high toxicity category includes substances such as strychnine, thallium, organophosphorus-based poisons, metallic phosphides, and arsenic [30]. Rodenticides with moderate toxicity are defined as those based on cholecalciferol (vitamin D) and alpha-naphthyl thiourea [31]. Finally, the low toxicity classification encompasses warfarin-based poisons like brodifacoum, bromadiolone, and bromethalin, as well as red squill [32].
Despite the significant public health burden of metal phosphide poisoning in Iran, a critical gap remains in the literature. Most Iranian studies have focused almost exclusively on the high mortality rates associated with AlP due to its frequent use in suicide attempts. In contrast, ZnP is often relegated to a secondary consideration, with limited data available regarding its specific clinical progression, comparative complications, and the potential for severe toxicity when compared directly to AlP under similar conditions. Furthermore, there is a lack of localized comparative research in the Lorestan province (Khorramabad) that evaluates how these two agents differ in prognostic indicators like hypotension and metabolic acidosis within the same clinical setting. Given the high prevalence of intentional metal phosphide poisoning in our country and the relative neglect of ZnP in toxicological research, we decided to conduct a retrospective cross-sectional study to investigate the specific mortality, clinical complications, and prognostic differences between zinc phosphide and aluminum phosphide poisoning.
Materials and methods
A retrospective, cross-sectional study was conducted by reviewing the medical records of all patients admitted for AlP or ZnP poisoning to Shahid Rahimi Hospital in Khorramabad during 2021–2022. The study protocol was approved by the Ethics Committee of Lorestan University of Medical Sciences (IR.LUMS.REC.1401.124). Data were collected using a structured checklist under the supervision of a senior toxicologist.
The initial database query identified 72 admissions coded for phosphide/rodenticide poisoning. After manual review, 13 cases were excluded: 10 for poisoning by other agents (e.g., organophosphates) and 3 for grossly incomplete records lacking outcome or core clinical data. The final cohort comprised 59 patients with confirmed AlP (n = 41) or ZnP (n = 18) poisoning.
The inclusion criteria for the study comprise the records of all individuals who were admitted to the Toxicology Department of Shahid Rahimi Hospital in Khorramabad in 2021–2022 due to poisoning with zinc phosphide or aluminum phosphide. Exclusion criteria were explicitly applied and included: Poisoning with any agent other than AlP or ZnP; Medical records missing critical data for analysis, defined as the absence of a documented outcome (death/discharge) OR the absence of key clinical parameters (e.g., no recorded blood pressure or pH/base excess values within the first 48 h for survivors); Cases where the diagnosis of AlP or ZnP poisoning was uncertain or not corroborated by history or clinical presentation.
The information related to individuals will be considered confidential, and the researchers will take action to preserve and not disclose it. Subsequently, the patients’ demographic and clinical information including gender, age, marital status, education level, place of residence, employment status, economic status, method of poison consumption, cause of poisoning, intention behind poisoning, history of mental illness, type of mental illness, history of drug abuse, type of substance abused, and the patient’s outcome will be extracted from the patient records and entered into a researcher-made form.
Treatment protocol
All patients were managed per institutional protocol. Supportive care included immediate resuscitation, continuous monitoring, and correction of electrolyte imbalances. Gastric lavage with a soft tube was considered for conscious patients presenting within 1–2 h. Activated charcoal was not routinely administered. The cornerstone of medical management was aggressive correction of metabolic acidosis with intravenous sodium bicarbonate (targeting pH > 7.2) and support of circulation with fluid resuscitation and vasopressors (e.g., norepinephrine) for refractory hypotension. There is no specific antidote for phosphine poisoning.
For gastric decontamination, patients typically underwent gastric lavage (often with non-water-based solutions such as diluted potassium permanganate 1:10,000, coconut oil, or sodium bicarbonate slurry to minimize phosphine release and absorption), followed by administration of activated charcoal (≈ 1 g/kg) in selected cases if presentation was early (< 1–2 h) and the patient was stable. Sodium bicarbonate infusion was routinely used for correction of severe metabolic acidosis (targeting pH > 7.2–7.3). Aggressive fluid resuscitation with crystalloids, vasopressor support (e.g., norepinephrine for refractory hypotension), mechanical ventilation for respiratory failure, and monitoring/correction of electrolytes were provided as needed. Magnesium sulfate, trimetazidine, or other adjunctive therapies were not systematically administered during the study period.
This protocol aligns with supportive measures reported in prior literature on AlP and ZnP poisoning, emphasizing early resuscitation and management of life-threatening complications (hypotension, acidosis) rather than decontamination alone, given the rapid systemic toxicity of liberated phosphine gas.
Sampling method
A census method was employed, including all eligible medical records from 2021 to 2022 to ensure the largest possible study population. While this resulted in a lack of numerical homogeneity between the AlP (n = 41) and ZnP (n = 18) cohorts, it accurately represents the local epidemiological burden. Conversely, the exclusion criteria encompassed instances of poisoning caused by other types of drugs or toxins, as well as any patient records with incomplete information.
The study faced several limitations and challenges, including the existence of incomplete medical histories, which provided insufficient information on key patient details such as the method and timing of poison consumption and psychiatric history. Additionally, a lack of honesty from either patients or their companions concerning whether the poisoning was intentional (suicidal) or accidental posed a significant constraint. Furthermore, the inaccessibility of patient contact details to complete missing information in the records, coupled with their unwillingness to cooperate in providing accurate data, further complicated the research process.
Data analysis method
After data collection, the data will be entered into SPSS software version 20 and subjected to statistical analysis. For data analysis and description, descriptive statistics along with the Chi-square test, Fisher’s exact test, and the independent t-test will be used. A significance level of less than 0.05 will be considered.
To evaluate the adequacy of our sample size for the primary objective, a post-hoc power analysis was performed for the comparison of mortality rates between the AlP and ZnP groups. With the observed mortality rates (29.3% for AlP and 5.5% for ZnP) and a total sample size of 59 (n1 = 41, n2 = 18), the calculated statistical power was 78.4% (α = 0.05). This indicates that the study was sufficiently powered to detect the primary difference in lethality between the two poisons, though it may have been underpowered for secondary bivariate analyses involving smaller sub-groups or variables with high missingness.
Results
Patient selection and data completeness
The initial electronic and archival record search for the period 2021–2022 identified 72 admissions with a suspected or documented code of phosphide or rodenticide poisoning. Upon detailed manual review, 13 cases were excluded before analysis: 10 were poisoned by other agents (e.g., organophosphates, unknown toxins), and 3 were excluded due to grossly incomplete records lacking both outcome and core clinical data. Thus, 59 patients with confirmed AlP (n = 41) or ZnP (n = 18) poisoning constituted the final study cohort.
Regarding data completeness within the final cohort, all 59 records contained definitive outcome data. For the analysis of 48-hour clinical parameters (hypotension, metabolic acidosis), data from 6 patients (5 AlP, 1 ZnP) who died within 6 hours of admission were necessarily excluded from that specific bivariate analysis (Table 1). The variable with the highest degree of missingness was the precise ‘time to hospital presentation,’ which was undocumented or unreliable in 8 records (13.6%); these were treated as a separate ‘unknown’ category in the analysis, which showed no significant association with outcome.
Table 1.
Baseline characteristics, clinical outcomes, and prognostic factors of patients with aluminum phosphide and zinc phosphide poisoning
| Poison Type | Category | Expired (n, %) | Recovered (n, %) | P-Value |
|---|---|---|---|---|
| Gender | ||||
| AlP | Female | 3 (16.7%) | 15 (83.3%) | 0.19 a |
| Male | 8 (34.8%) | 15 (65.2%) | ||
| Zinc Phosphide | Female | 0 (0%) | 10 (100%) | 0.71 a |
| Male | 1 (12.5%) | 7 (87.5%) | ||
| Psychiatric History | ||||
| AlP | Yes | 4 (40%) | 6 (60%) | 0.28 a |
| No | 7 (22.6%) | 24 (77.4%) | ||
| Zinc Phosphide | Yes | 0 (0%) | 6 (100%) | 0.529 b |
| No | 1 (8.3%) | 11 (91.6%) | ||
| Form of Toxin | ||||
| AlP | Tablets | 11 (28.2%) | 28 (71.8%) | 0.598 b |
| Powder | 0 (0%) | 2 (100%) | ||
| Zinc Phosphide | Tablets | - | - | - |
| Powder 1 | 1 (5.5%) | 17 (94.4%) | ||
| Method of Toxin Consumption 2 | ||||
| AlP | Dissolved in Water | 1 (6.7%) | 14 (93.3%) | 0.006 a |
| Not Dissolved in Water | 10 (50%) | 10 (50%) | ||
| Unknown | 0 (0%) | 5 (100%) | ||
| Zinc Phosphide | Dissolved in Water | 0 (0%) | 16 (100%) | 0.216 b |
| Not Dissolved in Water | 1 (50%) | 1 (50%) | ||
| Unknown | - | - | ||
| Hypotension in First 48 h 3 | ||||
| AlP | No Response to Treatment | 3 (23.1%) | 10 (76.9%) | < 0.001 b |
| Responded to Treatment | 3 (21.4%) | 11 (78.6%) | ||
| No Hypotension | 0 (0%) | 9 (100%) | ||
| Zinc Phosphide | No Response to Treatment | 0 (0%) | 5 (100%) | 0.15 b |
| Responded to Treatment | 0 (0%) | 8 (100%) | ||
| No Hypotension | 0 (0%) | 4 (100%) | ||
| Metabolic Acidosis Progression in First 48 h 3 | ||||
| AlP | No Response to Treatment | 4 (66.7%) | 2 (33.3%) | 0.003 b |
| Responded to Treatment | 2 (11.8%) | 15 (88.2%) | ||
| No Metabolic Acidosis | 0 (0%) | 13 (100%) | ||
| Zinc Phosphide | No Response to Treatment | 0 (0%) | 3 (100%) | 0.97 b |
| Responded to Treatment | 0 (0%) | 9 (100%) | ||
| No Metabolic Acidosis | 0 (0%) | 5 (100%) | ||
| Hospitalization Unit 4 | ||||
| AlP | General Ward | 0 (0%) | 17 (100%) | 0.009 b |
| ICU | 7 (35%) | 13 (65%) | ||
| Zinc Phosphide | General Ward | 0 (0%) | 16 (100%) | < 0.001b |
| ICU | 1 (100%) | 0 (0%) | ||
| Time Interval from Poison Ingestion to Hospital Admission | ||||
| AlP | < 1 h | 3 (33.3%) | 6 (66.7%) | 0.738 b |
| 1 ≤ Time < 2 h | 5 (29.4%) | 12 (70.6%) | ||
| ≥ 2 h | 3 (20%) | 12 (80%) | ||
| Zinc Phosphide | < 1 h | 0 (0%) | 4 (100%) | 0.706 b |
| 1 ≤ Time < 2 h | 0 (0%) | 5 (100%) | ||
| ≥ 2 h | 1 (11.11%) | 8 (88.88%) |
a: chi-square test
b: Fisher’s exact test
1: As zinc phosphide is only available in powder form, no statistical comparison was possible for this subgroup
2: In 5 cases (8.4%), the method of toxin consumption was unknown due to altered consciousness at the time of presentation
3: Five patients with AlP poisoning and one patient with zinc phosphide poisoning expired within six hours of hospitalization, precluding the assessment of their hypotensive status and metabolic acidosis progression
4: Four patients with AlP poisoning and one patient with zinc phosphide poisoning expired during the initial hours of hospitalization in the emergency department. Therefore, they were excluded from the analysis of hospitalization location
A total of 59 patient medical records were reviewed. The study population had a mean age of 30.12 ± 11.96 years and consisted of 28 females (47.5%) and 31 males (52.5%). The majority of patients were married (59.3%) and resided in Khorramabad city (64.4%). A history of psychiatric illness was reported in 16 patients (27.1%).
Regarding the poisoning characteristics, AlP was the most common agent, ingested by 41 patients (69.5%), while 18 patients (30.5%) ingested ZnP. The poison was most frequently consumed in tablet form (39 patients), and 32 patients (54.2%) reported dissolving the substance in water before ingestion. Time to hospital presentation varied: 22.0% arrived within one hour, 37.3% within one to two hours, and the remainder after more than two hours. The overall mortality rate was 20.3% (12 patients), with all fatalities occurring in the AlP group, resulting in a mortality rate of 29.3% for AlP poisoning specifically. All 47 surviving patients were discharged without major physical complications.
Bivariate analyses revealed several key findings. No significant association was found between patient prognosis and gender, history of psychiatric illness, or the physical form of the poison (tablet vs. powder) for either toxic agent.
However, the method of ingestion was a significant factor for AlP poisoning. Patients who consumed AlP without dissolving it in water had a significantly higher mortality rate (50%, 10/20) compared to those who dissolved it first (6.7%, 1/15) (P = 0.006). This relationship was not significant for ZnP poisoning (P = 0.216) (Table 1).
Clinical course was also a critical differentiator. The development of hypotension and metabolic acidosis within the first 48 h was strongly associated with a poorer prognosis in AlP poisoning (P < 0.001 and P = 0.003, respectively). This relationship was not observed in ZnP poisoning. Furthermore, the need for ICU admission was a significant prognostic indicator, with AlP-poisoned patients admitted to the ICU having a mortality rate of 35% (7/20), compared to 0% for those in the general ward (P < 0.05) (Table 2).
Table 2.
Association between clinical/demographic variables and mortality in alp patients
| Variable | Total Cases (n) | Survivors (n = 29) | Mortality (n = 12) | Mortality Rate (%) | P-value |
|---|---|---|---|---|---|
| Ingestion Method | 0.006* | ||||
| Not Dissolved (Direct) | 20 | 10 | 10 | 50.0% | |
| Dissolved in Water | 15 | 14 | 1 | 6.7% | |
| Unknown | 6 | 5 | 1 | 16.7% | |
| Clinical Course (within 48 h)† | < 0.001* | ||||
| Hypotension | |||||
| Present | 18 | 6 | 12 | 66.7% | |
| Absent | 17 | 17 | 0 | 0.0% | |
| Metabolic Acidosis | 0.003* | ||||
| Present | 19 | 10 | 9 | 47.4% | |
| Absent | 16 | 16 | 0 | 0.0% | |
| ICU Admission | < 0.05* | ||||
| Required | 20 | 13 | 7 | 35.0% | |
| General Ward | 21 | 16 | 5 | 23.8% | |
| Demographics | |||||
| Gender | 0.65 (NS) | ||||
| Male | 22 | 15 | 7 | 31.8% | |
| Female | 19 | 14 | 5 | 26.3% | |
Finally, neither the time to hospital presentation nor the mean age of the patients showed a statistically significant association with clinical outcome (P > 0.05 for all poisons). It is important to note that six patients (five from AlP and one from ZnP) died within 6 h of admission, precluding their inclusion in the 48-hour clinical course analysis for hypotension and metabolic acidosis (Table 1).
Predictors of mortality: regression analysis
To further evaluate the clinical and demographic factors associated with mortality in AlP poisoning, a logistic regression analysis was conducted.
In the univariate analysis, the method of ingestion (undissolved vs. dissolved), presence of metabolic acidosis, development of hypotension, and ICU admission were all significantly associated with increased odds of mortality.
In the multivariate model (adjusting for age and sex), the presence of hypotension and metabolic acidosis remained independent predictors of death. Notably, patients who consumed AlP without dissolving it in water had significantly higher odds of mortality compared to those who dissolved it, even after adjusting for potential confounders.
Discussion
This study investigated the epidemiology, mortality, and complications of AlP and ZnP poisoning in 59 patients. The majority of cases (69.5%) involved AlP poisoning, with an overall mortality rate of 20.3%. All fatalities occurred in the AlP group, resulting in a specific mortality rate of 29.3% for this poison.
Key findings indicate that the clinical method of ingestion was significant for AlP; patients who consumed it without first dissolving it in water had a markedly higher mortality rate (50%) compared to those who dissolved it (6.7%) [33]. The development of hypotension and metabolic acidosis were strong, significant predictors of a poor prognosis in AlP poisoning [34]. The need for ICU admission was also a significant indicator of a worse outcome. However, factors such as the physical form of the poison (tablet vs. powder), gender, history of psychiatric illness, time to hospital presentation, and patient age did not show a statistically significant relationship with survival [35, 36].
The multivariate analysis reinforces that while ICU admission and ingestion methods are critical, the physiological markers of refractory hypotension and metabolic acidosis are the strongest independent predictors of a fatal outcome. This suggests that aggressive early hemodynamic and biochemical stabilization may be more impactful than the mere setting of care.
The high statistical significance of hypotension (P < 0.001) and metabolic acidosis (P = 0.003) as prognostic factors reflects the underlying pathophysiology of phosphine toxicity. Phosphine-induced inhibition of cytochrome c oxidase leads to immediate cellular hypoxia and anaerobic metabolism, manifesting clinically as lactic acidosis and profound, often refractory, circulatory collapse.
The study’s results regarding the importance of hypotension and metabolic acidosis align with previous research on AlP poisoning, but it did not confirm the finding from other studies that the time to treatment is a significant prognostic factor. The small sample size for the ZnP group limited the analysis for that specific toxin [37–39].
The toxicity of both AlP and ZnP is primarily mediated by the liberation of phosphine gas (PH3) upon contact with moisture or gastric acid. Once absorbed, phosphine acts as a potent systemic toxin with a high affinity for heme-containing enzymes. Its primary mechanism involves the inhibition of cytochrome c oxidase in the mitochondrial electron transport chain, effectively halting oxidative phosphorylation.
The stark difference in mortality between AlP and ZnP, despite both being metal phosphides, can be attributed fundamentally to their distinct physicochemical properties and the consequent kinetics of phosphine (PH₃) gas liberation. Zn₃P₂ is typically encountered as a dark gray powder. Its reaction with hydrochloric acid in the stomach (Zn₃P₂ + 6HCl → 2PH₃ + 3ZnCl₂) is rapid but can also be initiated by ambient moisture, potentially leading to significant pre-ingestion gas release. This often results in prominent early gastrointestinal irritation (nausea, vomiting) which may limit further ingestion and promote the expulsion of unreacted poison. In contrast, AlP is commonly formulated as solid, compacted tablets. While it reacts similarly (AlP + 3 H₂O → PH₃ + Al(OH)₃), the tablet form and the lower reactivity of aluminum hydroxide formation can slow the hydrolysis process. This allows for more complete gastric absorption and a more sustained, systemic release of phosphine. The liberated PH₃ is a potent mitochondrial toxin, uncoupling oxidative phosphorylation by inhibiting cytochrome c oxidase, leading to catastrophic cellular energy failure, multi-organ dysfunction, and profound circulatory collapse. The delayed, internal release from AlP tablets likely leads to higher systemic absorption of PH₃ before emetic reflexes can clear the stomach contents, explaining the markedly higher incidence of refractory hypotension, severe metabolic acidosis, and mortality observed in our AlP cohort compared to the ZnP group, where earlier emesis may serve as a partial protective mechanism.
The observed lack of homogeneity between the AlP and ZnP groups reflects the regional availability and use of these agents. The significantly smaller ZnP cohort and its low mortality rate (5.5%) limit the power of bivariate analyses for this specific group. However, the disparity in outcomes remains scientifically rigorous when considering the rate of phosphine gas release.
ZnP is typically ingested as a powder, which often allows for pre-ingestion hydrolysis and early emetic responses, effectively “self-limiting” the dose. Conversely, AlP is formulated as a compacted tablet that ensures sustained, internal liberation of phosphine gas. This mitochondrial toxin inhibits cytochrome c oxidase, leading to the refractory hypotension and metabolic acidosis that were the primary drivers of mortality in the AlP group (P < 0.001).
A 2009 Indian study by Jaiswal et al. on 40 aluminum phosphide poisoning patients found that immediate ICU admission and aggressive correction of metabolic acidosis with sodium bicarbonate resulted in a 55% survival rate [40]. The study reported a significant link between metabolic acidosis and prognosis. Unmeasurable systolic blood pressure was also a critical finding, with only 2 of 14 such patients surviving.
In contrast, our study of 59 phosphide poisoning cases (41 aluminum phosphide) had a different patient distribution: only 48.7% were admitted to the ICU, and 9.7% died in the emergency department within six hours.
Our study of 41 aluminum phosphide patients found a significant link between patient survival and both hypotension (P < 0.001) and metabolic acidosis (P = 0.003), mirroring results from a 2014 Tehran study on fatalities [41–42].
However, a key difference emerged regarding the time to hospital presentation. Unlike the Tehran study, which found it significant, our research showed no statistically significant association between the time from ingestion to arrival and patient prognosis (P = 0.73).
While time to hospital arrival is traditionally a cornerstone of emergency toxicology, its lack of statistical significance in our study (P = 0.73) warrants closer examination. This ‘non-significance’ may be attributed to a clinical threshold effect. Aluminum phosphide poisoning is characterized by an extremely rapid transition from ingestion to systemic cellular toxicity. Phosphine gas causes near-instantaneous and irreversible inhibition of mitochondrial respiration.
The majority of our patients may have already passed a critical physiological ‘point of no return’ before arrival, rendering the exact timing of their presentation secondary to the sheer magnitude of the initial dose. Furthermore, because a significant portion of our AlP cohort arrived more than 1 h after admission, the window for effective gastric lavage which might otherwise have created a time-dependent survival benefit had likely closed.
This allows for more complete gastric absorption and a more sustained, systemic release of phosphine. This is clinically evidenced by our finding that ‘dry’ ingestion (without prior dissolution) resulted in a 50% mortality rate, suggesting that the intact tablet acts as a more potent delivery system for the toxin than the partially pre-hydrolyzed dissolved form.
Additionally, the reliance on self-reported or bystander-reported ingestion times in the context of intentional self-harm introduces a potential for recall bias, which may have obscured a true correlation. In cases of high-dose AlP ingestion, the severity of the biochemical insult (evidenced by early metabolic acidosis and hypotension) appears to be a more robust predictor of mortality than the chronological interval between ingestion and hospital entry.
Furthermore, while the method of consuming the poison (e.g., dissolving it) was significantly linked to mortality in our study, its physical form (tablet vs. powder) was not. The smaller sample size and potential unreliability of patient histories regarding ingestion time suggest this variable needs further investigation in larger studies [43, 44].
Comparative studies on zinc phosphide poisoning show varying results. An Egyptian studyreported high ICU admission (67%) but low mortality (0.6%), while our study on 18 patients had only one ICU admission and one death. Neither our study nor a similar Iranian one found a significant link between zinc phosphide prognosis and metabolic acidosis or hypotension [45].
In contrast, a large 2018 study on both aluminum and zinc phosphides confirmed findings from our aluminum phosphide analysis: ICU need, poison type (AlP being deadlier), hypotension, and metabolic acidosis were all significant prognostic factors. A key difference was that the 2018 study found time to hospital arrival was a significant factor for mortality, which our study did not. Both studies agreed that demographic factors like age and gender were not significant predictors [46, 47].
Our study, like the one by Hegazy et al., confirmed that aluminum phosphide is significantly more lethal than zinc phosphide. We also found similar significant links between patient prognosis and ICU admission, hypotension, and metabolic acidosis for aluminum phosphide.
However, our results differed in key areas. Unlike Hegazy’s study, we found no significant association between prognosis and the time to hospital arrival or the physical form of the poison.
A major distinction was our separate analysis for each poison [48].
We found that hypotension and metabolic acidosis were significant prognostic factors for aluminum phosphide but not for zinc phosphide. This specific finding is hard to compare directly with the Hegazy study, which did not stratify its results by poison type.
Despite these insights, several limitations must be acknowledged. First, this was a retrospective, single-center study, which inherently limits the generalizability of the results to other regions with different poisoning patterns or healthcare infrastructures. Second, the sample size, particularly for the ZnP cohort (n = 18), was relatively small. While our post-hoc power analysis (78.4%) suggests the study was sufficiently powered to detect the primary difference in mortality between the two poisons, it may have been underpowered to identify more subtle associations among secondary variables or within the ZnP group itself.
Additionally, as with most retrospective chart reviews, we encountered challenges with incomplete medical records. Data regarding the exact time of ingestion and psychiatric history were often based on self-reports or bystander accounts, which are susceptible to recall bias or intentional misinformation in cases of self-harm. These limitations underscore the need for larger, multi-center prospective studies to validate our findings and further explore the nuances of metal phosphide toxicity.
Conclusion
AlP is significantly more lethal than ZnP. A critical clinical takeaway is that the method of ingestion specifically consuming AlP without prior dissolution serves as a primary ‘red flag’ for mortality. While ZnP often allows for pre-ingestion gas release or early emesis, AlP tablets ensure maximum internal liberation of phosphine gas, leading to the refractory hypotension and metabolic acidosis observed in our study.
Our findings confirm that the consumption method significantly impacted prognosis for AlP, but not for ZnP, potentially due to a small sample size or unreliable patient histories. Significant associations were found between mortality and both hypotension and metabolic acidosis in AlP poisoning, highlighting the importance of treating these complications. Unlike other studies, we found no significant link between the time to hospital arrival and outcome, possibly due to data limitations. Consistent with other research, ICU admission was a strong predictor of mortality.
Based on the findings of this study, several key recommendations are proposed. There is a critical need for further research on zinc phosphide poisoning, which remains significantly understudied in the global literature. To address the high incidence of suicide using toxic agents, it is imperative to implement and enforce stricter regulations, including an effective ban on the public sale of highly lethal pesticides like aluminum phosphide. Concurrently, public health initiatives must be strengthened to increase safety awareness among farmers and warehouse workers, providing clear guidelines to prevent accidental inhalation of phosphine gas. Finally, to enhance the quality of future research, clinical protocols should mandate the collection of more accurate patient histories during hospital admission for poisoning, with physicians explicitly documenting their assessment of the reliability of the history for use in larger, more robust studies.
Acknowledgements
N/A.
Abbreviations
- AlP
aluminum phosphide
- ZnP
zinc phosphide
- ICU
intensive care unit
Author contributions
The authors confirm their contributions to the paper as follows: Dr. Peyman Astaraki conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript. Dr. Ali Hassan Rahmani and Dr. Farkhondeh Jamshidi designed the data collection instruments, collected data, carried out the initial analyses, and reviewed and revised the manuscript. Dr. Maryam Ahadi, Dr.Kiandokht Khorshidi and Dr.Parmida Etebarfarshi coordinated and supervised data collection and critically reviewed the manuscript for important intellectual content. All authors reviewed the results and approved the final version of the manuscript.
Funding
None.
Data availability
The data and supportive information are available within the article.
Declarations
Ethics approval and consent to participate
Permission was taken from the Ethics Committee and Research Committee of Lorestan University of Medical Sciences (IR.LUMS.REC.1401.124).
Human and animal rights
All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Consent for publication
Informed consent was obtained (the under 16 years old was given by a parent or legal guardian).
Standards of reporting
Strobe guidelines were followed.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.Abbaspour A, Nasri Nasrabadi Z, Ghorbani A, Mahdi Marashi S. Successful treatment of acute aluminum phosphide poisoning induced heart failure: a case report. Razi J Med Sci. 2013;20(107).
- 2.Shokrzadeh M, Alizadeh A, Veisi F, Nasri-Nasrabadi N. The mortality rate of aluminum phosphide poisoning; a comparison with other poisonings recorded in Mazandaran department of forensic Medicine, Iran, 2009–2011. J Isfahan Med School. 2015;33(322).
- 3.Khodabandeh F, Kahani A, Soleimani G. The study of fatal complications of rice tablet poisoning. Sci J Forensic Med. 2014;20(2):27–36. [Google Scholar]
- 4.Rahbar Taromsari M, Teymourpour P, Jahanbakhsh R. Survey the histopathological findings in autopsy of poisoned patients with rice tablet (Aluminium Phosphide). J Guilan Univ Med Sci. 2011;19(76):56–63. [Google Scholar]
- 5.D’Silva C, Krishna B, Society of Critical Care Medicine. Rodenticide poisoning. Indian journal of critical care medicine: peer-reviewed, official publication of Indian. 2019;23(Suppl 4):S2728- Rahbar Taramsari M, Orangpour R, Zarkami T, Palizkar M, Mousavian SA. Autopsy results poisoned with rice tablet. J Guilan Univ Med Sci. 2022;36-9.
- 6.Trakulsrichai S, Kosanyawat. N, Atiksawedparit P, Sriapha C, Tongpoo A, Udomsubpayakul U, Rittilert P, Wananukul W. Clinical characteristics of zinc phosphide poisoning in Thailand. Ther Clin Risk Manag. 2017;13(56):42–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Chan LTF, Crowley. RJ, Delliou D, Geyer R. Phosphine analysis in post mortem specimens following ingestion of aluminium phosphide. J Anal Toxicol. 1983;7(4):165–7. [DOI] [PubMed] [Google Scholar]
- 8.Navabi SM, Navabi J, aghaei A, Shaahmadi Z, Heydari R. Mortality from aluminum phosphide poisoning in Kermanshah Province, Iran: characteristics and predictive factors. Epidemiol Health. 2018;40. [DOI] [PMC free article] [PubMed]
- 9.Shadnia S, Sasanian. G, Allami P, Hosseini A, Ranjbar A, Amini-Shirazi N, Abdollahi M. A retrospective 7-years study of aluminum phosphide poisoning in tehran: opportunities for prevention. Hum Exp Toxicol. 2009;28(4):209–13. [DOI] [PubMed] [Google Scholar]
- 10.Chomchai S. Phosphine and phosphides. In: Olson KR, Editor. Poisoning and drug overdose. 4th ed. New York, NY: McGraw-Hill Medical. 2004:306–307.
- 11.Phosphine, Poisindex, Micromedex Healthcare Series. 120 Thomson Healthcare Inc. 2004;120.
- 12.Pajoumand A, Shariat Tarbaghani A. Diagnosis and Treatment of Poisoning. Tehran, Iran: Chehr Publication. 1998:442–444.
- 13.Montazer H, Laali. A, Khosravi N, Amini Ahidashti H, Rahiminezhad M, Mohamadzadeh A. Epidemiological, clinical and laboratory features in patients poisoned with aluminum phosphide. J Mazandaran Univ Med Sci. 2016;26(137):188–95. [Google Scholar]
- 14.Ecocichon D. Toxic effects of pesticides. Casarett and Doull’s toxicology: The basic science of poisons: Companion handbook. 1999.
- 15.Shahi M. Study of epidemiology of poisoning lead to death by carbon monoxide gas in Tehran. Sci J Forensic Med. 1995;5:21–6. [Google Scholar]
- 16.Etemadi-Aleagha A, Akhgari M, Iravani FS. Aluminum phosphide poisoning-related deaths in Tehran, Iran, 2006 to 2013. Medicine. 2015;94(38). [DOI] [PMC free article] [PubMed]
- 17.Singh D, Jit I, Tyagi S. Changing trends in acute poisoning in Chandigarh zone: A 25-year autopsy experience from a tertiary care hospital in Northern India. Am J Forensic Med Pathol. 1999;20(2):203–10. [DOI] [PubMed] [Google Scholar]
- 18.Hegazy MM, Elagamy SE, Salem EA. Pattern and predictors of death from aluminum and zinc phosphide poisoning: a two years prospective study. Egypt J Forensic Sci Appl Toxicol. 2019;19(2):73–8621. [Google Scholar]
- 19.Raman R, Dubey M. The electrocardiographic changes in quick phos poisoning. Indian Heart J. 1985;37(3):193–5. [PubMed] [Google Scholar]
- 20.Haddad LM, Shannon MW, Winchester JF. Clinical management of poisoning and drug overdose. Philadelphia, PA: Saunders; 1998. [Google Scholar]
- 21.Pokhrel D, Pant S, Pradhan A, Mansoor S. A comparative retrospective study of poisoning cases in central, zonal and district hospitals. Kathmandu Univ J science, Eng Technol. 2008;4(1):40–8. [Google Scholar]
- 22.Mehrpour O, Alfred S, Shadnia S, Keyler D, Soltaninejad K, Chalaki N, et al. Hyperglycemia in acute aluminum phosphide poisoning as a potential prognostic factor. Human & Experimental Toxicology. 2008;27(7):591–595. [DOI] [PubMed]
- 23.Asadzadeh R, Khalighi Z, Mohammadi F, Malekshahi M, Shafiei E. Investigating the factors affecting mortality in users of Phostoxin tablet. Iran J Forensic Med. 2022;27(4):254–61. [Google Scholar]
- 24.Astaraki P, Ahadi M,. Salehinejad F, Honardoost V. Fatalities due to poisoning with aluminum phosphide (Rice Pill) and methadone. Drug Res. 2022;72(02):82–5. [DOI] [PubMed] [Google Scholar]
- 25.Pishbin S, Vaziri Nejad R, Khalili P, Ahmadinia H, Arabi M, Ahmadi AK, et al. Geographical Epidemiology of Suicide (Completed and Attempted) in the Townships Covered by Mazandaran University of Medical Sciences during the Years 2012 to 2016: An Ecological Study. Journal of Rafsanjan University of Medical Sciences. 2021;20(3):259–276.
- 26.Shokrzadeh M, Zarei H, Jalilian J, Badeli A, Ebrahimi Falahtalab F, Shayeste Y. A comparison of mortality rate caused by aluminum phosphide with other poisonings in Golestan Province, Iran, 2010–2016. Med J Mashhad Univ Med Sci. 2017;60(5):689–90. [Google Scholar]
- 27.Shayesteh Y, Farzad A, Zarei H, Badali A, Ebrahimi F. Poisoning resulting in death by suicide in Golestan Province in 2010–2016. Nurs Vulnerable J. 2018;5(14):13–23. [Google Scholar]
- 28.Shokrzadeh M, Yaghubi beklar S. Epidemiology of Drug-poisoning death in central cities of Mazandaran, Iran 2011–2016. J Mazandaran Univ Med Sci. 2017;27(153):140–5. [Google Scholar]
- 29.Pourhossein M, Mir Mohammdi SM, Alizadeh A. Evaluation of demography & methods of successful suicide in corpses referred to Sari legal medicine center during 2009–2010. Iran J Forensic Med. 2015;21(3):199–205. [Google Scholar]
- 30.Shokrzadeh M, Alizadeh A, Veisi F, Nasri-Nasrabadi N. The mortality rate of aluminum phosphide Poisoning; A comparison with other poisonings recorded in Mazandaran department of forensic Medicine, Iran, 2009–2011. J Isfahan Med School. 2015;33(322):114–24. [Google Scholar]
- 31.Khodabandeh F, Kahani A, Soleimani G. The study of fatal complications of rice tablet poisoning. Iran J Forensic Med. 2014;20(2):27–36. [Google Scholar]
- 32.Mahmudi GA, Astaraki P, Farhadi A, Nazari Y. The evaluation of poisoning mortality in the admitted patients in Shohada Ashayer hospital of Khorramabad from 2006 to 2010. Sci Magazine Yafte. 2013;15(1):43–50. [Google Scholar]
- 33.Farnaghi F, Hassanian-Moghaddam. H, Faghihi langroodi T. Fatal poisoning and its related factors among children admitted in Loghman Hospital, 1995–2004. Pajoohande. 2009;13(6):529–35. [Google Scholar]
- 34.Gokdemir MT, Kaya. H, Sogut O, Orak M, Ustundag M, Karasu M. A rare type of suicide attempt in East turkey: acute zinc phosphide poisoning. J Acad Emerg Med. 2013;12(2):76–9. [Google Scholar]
- 35.Ghasempouri SK, Zakariaei. Z, Hoseininejad SM, Chinian F, soleymanii M, Pashaei SM, Sadeghi M. Clinical manifestations and treatment management of hospitalized patients with zinc phosphide poisoning, Mazandaran Province, Northern Iran. BMC Emerg Med. 2022;22(1):1–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Ibraheem M, Battah AH, Rahman HA, Batainch-el N, Shomaf MS. Law science and medical experience: local new fatalities. e-Aluminum. 2020;8:164–40. [DOI] [PubMed]
- 37.Bagherian F, Kalani. N, Rahmanian F, abiri S, Hatami N, Foroughian M, Mehramiz NJ, Shahi B. Aluminum phosphide poisoning mortality rate in Iran; a systematic review and meta-analysis. Archives Acad Emerg Med. 2021;9(1). [DOI] [PMC free article] [PubMed]
- 38.Pajoumand A, Jalali N, Abdollah M, Shadnia S. Survival following severe aluminium phosphide poisoning. J Pharm Pract Res. 2002;32(4):297–9. [Google Scholar]
- 39.Naddafi M, Mehrizi. AA, Eghbal MA, Khansari MG, Azarmi Y, sattari MR, Karaman C, Karimi F, Alizadeh M, Yazdani MN, hosseinpour P. Reducing the risk of death induced by aluminum phosphide poisoning: the new therapies. Chemosphere. 2022;294:133800. [DOI] [PubMed] [Google Scholar]
- 40.Jaiswal S, Verma RK, Tewari N. Aluminum phosphide poisoning: effect of correction of severe metabolic acidosis on patient outcome. Indian J Crit Care Medicine: peer-reviewed, Official Publication Indian Soc Crit Care Med. 2009;13(1):21. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41.El Naggar AR, El Mahdy NM. Zinc phosphide toxicity with a trial of Tranexamic acid in its management. J Adv Res. 2011;2(2):149–56. [Google Scholar]
- 42.Chugh SN, Aggarwal HK, Mahajan SK. Zinc phosphide intoxication symptoms: analysis of 20 cases. Int J Clin Pharmacol Ther. 1998;36(7):406–7. [PubMed] [Google Scholar]
- 43.Rodenberg HD, Chang CC, Watson WA. Zinc phosphide ingestion: a case report and review. Vet Hum Toxicol. 1989;31(6):559–62. [PubMed] [Google Scholar]
- 44.Lauterbach M, Solak. E, Kaes J, Wiechelt J, von Mach MA, Weilemann LS. Epidemiology of hydrogen phosphide exposures in humans reported to the poison center in Mainz, Germany, 1983–2003. Clin Toxicol. 2005;43(6):575–81. [DOI] [PubMed] [Google Scholar]
- 45.Bogle RG, Theron. P, Brooks P, Dargan PI, redhead J. Aluminium phosphide poisoning. Emerg Med J. 2006;23(1):e03. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 46.Ng WY, Ching. CK, Chong YK, Ng SW, Cheung WL, Mak TW. Retrospective study of the characteristics of anticoagulant-type rodenticide poisoning in Hong Kong. J Med Toxicol. 2018;14(3):218–28. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 47.Trakulsrichai S, Kosanyawat. N, Atiksawedparit P, Sriapha C, Tongpoo A, Udomsubpayakul U, Rittilert P, Wananukul W. Clinical characteristics of zinc phosphide poisoning in Thailand. Ther Clin Risk Manag. 2017;13:335. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 48.Hegazy MM, Elagamy SE, Salem EA. Pattern and predictors of death from aluminum and zinc phosphide poisoning: a two years prospective study. The Egyptian Journal of Forensic Sciences and Applied Toxicology. 2019;19(2):73-8621- Raman R, Dubey M. The electrocardiographic changes in quick phos poisoning. Indian Heart Journal. 1985;37(3):193–195. [PubMed]
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