Prognostic Significance of Blood Glucose Levels and Alterations Among Patients with Aluminium Phosphide Poisoning.

OBJECTIVES: This study aimed to assess the prognostic significance of blood glucose levels and blood glucose alterations (i.e. hyper- or hypoglycaemia) among patients with aluminium phosphide (AlP) poisoning. METHODS: This prospective observational study was conducted at the Postgraduate Institute of Medical Education & Research, Chandigarh, India, between January 2010 and June 2011. All patients presenting to the emergency department with a definitive history of AlP ingestion or symptoms compatible with AlP poisoning were included in the study. Blood glucose levels were recorded at presentation and every six hours thereafter. Alterations in blood glucose levels and other clinical and laboratory variables were subsequently compared between survivors and non-survivors. RESULTS: A total of 116 patients with AlP poisoning were identified. Of these, 57 patients (49%) survived and 59 patients (51%) died. At presentation, the mean blood glucose levels of survivors and non-survivors were 119.9 ± 35.7 mg/dL and 159.7 ± 92.5 mg/dL, respectively (P <0.001). In comparison to the survivors, non-survivors had significantly higher heart rates, total leukocyte counts, blood glucose level alterations and serum creatinine levels (P <0.050). In addition, systolic blood pressure, Glasgow coma scale scores, arterial blood gas pH and bicarbonate values and duration of hospital stay was significantly lower compared to survivors (P <0.001). However, neither blood glucose levels at admission nor blood glucose alterations correlated independently with mortality in a multivariate analysis. CONCLUSION: The role of blood glucose level alterations in predicting patient outcomes in AlP poisoning cases remains inconclusive. Further studies with larger sample sizes are required.

A review of the protective role of melatonin during phosphine-induced cardiotoxicity: focus on mitochondrial dysfunction, oxidative stress and apoptosis.

OBJECTIVES: Acute poisoning with aluminium phosphide (AlP) is a major cause of mortality in developing countries. AlP mortality is due to cardiac dysfunction leading to cardiomyocyte death. The main mechanism is an inhibition of cytochrome c oxidase in the cardiomyocyte mitochondria, resulting in a decreased ATP production and oxidative stress. Unfortunately, the administration of exogenous drugs does not meet the desired requirements of an effective therapy. Melatonin is an amphiphilic molecule and can easily pass through all cellular compartments with the highest concentration recorded in mitochondria. It is known as a vigorous antioxidant, acting as a potent reactive oxygen species (ROS) scavenger. Our aim is to summarize the mechanisms by which melatonin may modulate the deteriorating effects of AlP poisoning on cardiac mitochondria. KEY FINDINGS: Melatonin not only mitigates the inhibition of respiratory chain complexes, but also increases ATP generation. Moreover, it can directly inhibit the mitochondrial permeability transition pore (mPTP) opening, thus preventing apoptosis. In addition, melatonin inhibits the release of cytochrome c from mitochondria to hinder caspase activation leading to cell survival. SUMMARY: Based on the promising effects of melatonin on mitochondria, melatonin may mitigate AlP-induced cardiotoxicity and might be potentially suggested as cardioprotective in AlP-intoxicated patients.

Exposure to hardly soluble indium compounds in ITO production and recycling plants is a new risk for interstitial lung damage.

OBJECTIVES: To identify the effects of indium on the lung and to assess exposure-effect and exposure-response relations between indium exposure and effects on the lungs. METHODS: Ninety three male indium exposed and 93 male non-exposed workers from four ITO manufacturing or ITO recycling plants were analysed in a cross-sectional study. Indium in serum (In-S) was determined as a biological exposure index. Geometric means (GSD) of In-S were 8.25 ng/ml (4.55) in the exposed workers and 0.25 (2.64) in the non-exposed workers. The maximum concentration of In-S was 116.9 ng/ml. A questionnaire for respiratory symptoms and job histories, spirometry, high-resolution computerised tomography (HRCT) of the chest, serum KL-6, serum SP-A, serum SP-D and serum CRP were measured as the effect indices. RESULTS: Spirometry, subjective symptoms and the prevalence of interstitial or emphysematous changes on lung HRCT showed no differences between exposed and non-exposed workers. Geometric means (GSD) of KL-6, SP-D and SP-A in the exposed workers were 495.4 U/ml (2.26), 85.2 ng/ml (2.02) and 39.6 ng/ml (1.57), and were significantly higher than those in the non-exposed workers. The prevalence (%) of the exposed and non-exposed workers exceeding the reference values were also significantly higher in KL-6 (41.9 vs 2.2), SP-D (39.8 vs 7.5), and SP-A (43.0 vs 24.7). Very sharp exposure-effect and exposure-response relations were discovered between In-S and KL-6 and between In-S and SP-D when the exposed workers were classified into seven groups by In-S. CONCLUSIONS: The study outcomes with regard to the basis of serum immunochemistry biomarkers and HRCT indicate that exposure to hardly soluble indium compound dust may represent a risk for interstitial lung damage.

Occupational exposure to aluminium phosphide and phosphine gas? A suspected case report and review of the literature.

The manufacture and application of aluminium phosphide fumigants pose risks of inhalation exposure to phosphine gas. This article presents a case report of suspected inhalation exposure to phosphine gas in a manufacturing facility for aluminium phosphide fumigants, which was associated with acute dyspnoea, hypotension, bradycardia and other signs of intoxication. These symptoms resolved within several hours after removal from exposure. A review of the data on human exposures to phosphide fumigants identifies both pesticide applicators and individuals in the vicinity of application to be at risk of accidental exposure and injury from phosphine inhalation. More recent reports have identified risks of phosphine gas inhalation in association with the clandestine production of methamphetamine. Toxicodynamic effects of phosphine result from the inhibition of cytochrome c oxidase and subsequent generation of reactive oxygen species. There remain unanswered questions relating to the toxicokinetics of phosphine, as well as the assessment of human exposure utilizing biomarkers. As initial signs and symptoms of intoxication from phosphine gas may be nonspecific and transient, there is a need for improved recognition of the potential hazards associated with phosphide fumigants and phosphine gas.

Multi-endpoint biological monitoring of phosphine workers.

The pesticide phosphine (PH(3)) is a suspected carcinogen and a known clastogen which has been shown to produce chromosome damage in agricultural workers. To confirm and extend these results we evaluated 22 phosphine appliers and 26 controls matched for age and smoking status. Two independent methods were used to evaluate exposure: fluorescence in situ hybridization (FISH) with whole-chromosome paints of chromosomes 1, 2, and 4 labeled in a single color to quantify translocations in peripheral lymphocytes, and the glycophorin A (GPA) assay to quantify phenotypically mutant (NØ or NN) erythrocytes. No differences in the frequency of translocations were found in the phosphine appliers compared to the controls, and no effect of cigarette smoking was observed. However, a significant increase in the frequency of translocations with age (P<0.0001) was seen. No effect of phosphine exposure or cigarette smoking was observed in the GPA assay. These results are in contrast to previous findings from this same population which showed an increase in chromosome aberrations among phosphine appliers. The results are most easily interpreted as supporting the effectiveness of the personal protective equipment that is now worn by the workers but which was not employed prior to and during the earlier studies.

Phosphine toxicity: report of two cases and review of the literature.

Aluminum phosphide is a commonly used fumigant in the agricultural community. This article reviews the toxic effects of phosphine on the lungs and central nervous system in two workers and reviews the available scientific literature. Education for prevention of exposure and more frequent monitoring for exposure are recommended.

Influence of environmental, structural, and behavioral factors on the presence of phosphine in worker areas during fumigations in grain elevators.

Data-logging gas monitors with electrochemical cells sensitive to phosphine (PH3) were used to characterize concentrations of this common grain fumigant in and around grain elevators during fumigations. Twenty-four grain fumigations were observed, and each was monitored over a 5- to 8-day period. Phosphine gas, generated from aluminum phosphide fumigant applied to the grain, generally moved upward toward the grain surface and exited the bin at bin-top openings to the outside air or to enclosed worker areas. The upward air currents appeared to be the result of chimney effects, e.g., pressure differences resulting from buoyant air inside the warm grain and cooler, denser, ambient air. Significant wind effects on the PH3 concentration were also observed in the air between the grain surface and the bin roof. In enclosed areas located at the bin-top level, monitors located near the fill port or the fumigant dispenser recorded PH3 concentrations in excess of the exposure limit of 0.3 parts per million (ppm) about 35% of the time during grain fumigations. Phosphine concentrations between 0.31 and 1.0 ppm were observed 17.3% of the time, and concentrations in the ranges of 1.01-3.0, 3.01-10.0, and >10 ppm constituted 11.8%, 5.5%, and 0.3% of all readings, respectively, in bin-top worker areas. The likelihood of recording PH3 concentrations >0.3 ppm depended on ventilation practices. Fans in tunnels and open windows at aboveground locations appeared to greatly reduce the likelihood of high PH3 concentrations in enclosed areas.

Fumigant-related illnesses: Washington State's five-year experience.

OBJECTIVE: Exposure to fumigants may have severe or persistent health effects. Washington State's fumigant-related illnesses were reviewed to better understand the circumstances surrounding exposure and resultant health effects. METHODS: Fumigant-related illnesses reported to and investigated by the Washington State Department of Health were reviewed. Illnesses considered by Department of Health to be definitely, probably, or possibly related to pesticide exposure were then analyzed. RESULTS: From 1992-1996, 39 (3.3%) of 1192 definite, probable, or possible cases of pesticide-related illnesses involved exposures to fumigants. Fumigant exposures during this period were to aluminum phosphide (15), methyl bromide (12), metam-sodium (9), and zinc phosphide (3). Symptoms included respiratory problems and eye and/or skin irritation for the majority of exposures, and no deaths were reported. The nature of exposure for these cases included exposure to applicators (17), reentry into a fumigated structure (9), improper storage or disposal (6), reentry into treated agricultural fields (4), drift from treated fields (2), and other (1). CONCLUSIONS: Review of fumigant exposures should be used to prevent future events through continued enforcement of established regulations and training of applicators.

Spontaneous emission of phosphane from animal slurry treatment processing.

The degree of the emission of the mutagenic phosphane from animal slurry have become an issue of hygienic which so far has not been investigated. This work clearly detects spontaneously emitted free phosphane from animal slurry for the first time and correlates the degree of its emission with different disposal technologies. The subjects of the investigations are the simple storage process and processes involving biogas plants for the digestion both of pig and cattle slurry. Pig slurry generates about one magnitude more phosphane than cattle slurry. The maximum concentration detected in putrefaction gas was 14621 ppt(v/v). Putrefaction gas samples from fresh fecal slurry in primary (mediary storage) tanks followed by storage basins and sedimenters contains the highest concentrations. The mainly methanogenic biogas process generates the smallest concentrations but the highest fluxes of phosphane. Fluxes and concentrations in open basins are significantly higher during summer than in winter. The correlation of phosphane and dimethyldisulfide concentrations indicates that primary lytic processes play a role in the liberation of phosphane. Individual samples of the emission in air give a maximum value of 35 ppt. By comparison, measurement of phosphane in Hungarian digester gas from municipal sewage treatment show that maximum concentrations could be some orders of magnitude higher. Therefore the data base for phosphane from animal slurry must in future be expanded. The results of analysis so far achieved cannot be interpreted from either a human or veterinary medical viewpoint.

Evaluation of phosphine genotoxicity at occupational levels of exposure in New South Wales, Australia.

Phosphine has been claimed to cause chromosomal damage at exposures close to the current time weighted average exposure standard of 0.3 ppm (0.4 mg/m3). The current study involved 31 phosphine fumigators and 21 controls during the high fumigation season. All were volunteers and were evaluated for genotoxicity variables, including micronuclei in peripheral blood lymphocytes and urine mutagenicity. In parallel, all fumigators and 17 controls were evaluated for full haematology, multiple biochemical analysis, whole blood organochlorines, and whole blood and serum cholinesterase activity. The results for micronuclei showed no significant differences between fumigators and controls, but detected a strong association between age and increased frequency of micronuclei. Measurement of urine mutagenicity did not show any significant difference between fumigators and controls, but did show increased excretion of mutagens in smokers. All haematological and biochemical variables were within normal ranges, except for some non-specific changes in biochemistry. At monitored occupational exposures of < 2.4 ppm/h our results show no association between phosphine exposure and genotoxic or toxicological effects in fumigators.

Radiometric assay of red cell and plasma cholinesterase in pesticide appliers from Minnesota.

In this study we demonstrate the uses of radiometric assay to detect anticholinesterases in a human population (N = 80) exposed to a broad spectrum of pesticides. The assay is nondilutional. Therefore, anticholinesterase (AChE) agents with low binding affinity can be detected. Our initial results show statistically significant exposure-related decreases in either red cell (AChE) or plasma cholinesterase activity ((butyrl)cholinesterase; BuChE) occurred not only among pesticide appliers who use organophosphates, but also among appliers of the fumigant phosphine. These data extend earlier observations made in laboratory animals exposed to this fumigant. Significant exposure-related decreases in AChE activity were seen in herbicide appliers and appear to be associated with exposure to the herbicide 2-methoxy-3,6-dichlorobenzoic acid. There was no evidence of exposure-related decreases in BuChE activity in herbicide appliers. Our in vivo data, coupled with preliminary in vitro studies of phosphine (50% AChE inhibition, 10 ppm) and 2-methoxy-3,6-chlorobenzoic acid (50% AChE and BuChE inhibition, 70 ppm), suggest that the radiometric assay may be used to detect a broader spectrum of biologically active anticholinesterase agents.

Unusual occupational toxins.

Occupational and environmental medicine affords encounters with many unusual toxins, ranging from exotic metals to rocket fuels. Twelve of the most unusual industrial toxins are reviewed here and their clinical manifestations and treatments explored: acetonitrile, acrylonitrile, boron hydrides, dimethylaminopropionitrile, dimethylformamide, hydrazines, methyl isocyanate, 2-nitropropane, phosphine, Stalinon, tellurium, and vanadium.

Chromosome rearrangements in fumigant appliers: possible relationship to non-Hodgkin's lymphoma risk.

Appliers of pesticides (n = 18) who are exposed to the fumigant phosphine or who have a mixed exposure to other pesticides and phosphine demonstrate a significant increase in chromosome rearrangements in G-banded chromosomes from peripheral blood compared to control subjects (n = 26). Appliers who had discontinued using phosphine for at least 8 months prior to specimen collection (n = 5) do not demonstrate significant increases in chromosome rearrangements compared to controls. Breakpoint analysis of 6,138 metaphases from all subjects demonstrates 196 breaks per 3605 metaphases in exposed subjects and 102 breaks per 2,533 metaphases in control subjects. Bands with significantly more breaks than expected based on band length in all study subjects were 1q32, 3p14, 7p15, and 14q11. Three of these four bands had significantly more breaks than expected in the exposed group, and all four bands had a significant excess of breaks in the control group. There are four bands with a significant excess of breaks in the exposed group and no breaks in the control group; each of these occurs in a known protooncogene region. These are 1p13 (NRAS), 2p23 (NMYC), 14q32 (ELK2), and 21q12 (ETS-2). Most breaks at bands 1p13, 14q32, and 21q22 are associated with chromosome rearrangements and occurred in appliers who have a mixed exposure to phosphine and other pesticides. Cytogenetic abnormalities, i.e., rearrangements and/or deletions involving bands 1p13, 2p23, and 14q32, are associated with non-Hodgkin's lymphoma. We speculate that these findings could relate to the risk of evolution of a neoplastic clone in these workers. Epidemiological studies of similarly exposed workers indicate an excess of non-Hodgkin's lymphoma.

Multiple-episode conjunctivitis outbreak among workers at a nut-processing facility.

Workers in a Kern County almond and pistachio nut-packing facility sought medical care for eye irritation (conjunctivitis) on three separate occasions in 1987 and 1988. These incidents were investigated by the California Department of Health Services to identify the agent responsible for the eye irritation outbreak and to suggest possible remediation. The eye irritation incidents involved only the 30 to 35 workers in the preprocessor shed. Each of the three eye irritation incidents followed phosphine (Gastoxin) fumigation. Four plausible hypotheses were tested as explanations of the outbreaks of eye irritation: phosphine gas exposure, ammonia gas exposure, aluminum hydroxide dust exposure, and almond cleaning and hulling dust exposure, with or without contamination by propargite residues (Omite 6-E). None of these hypotheses received enough consistent support to be viewed as a probable cause for the illness outbreaks.