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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.

Adult↗

Biodegradation of 1,3,5-trinitro-1,3,5-triazine (RDX).

Two bacteria were isolated from 1,3,5-trinitro-1,3,5-triazine (RDX) contaminated soil at Picatinny Arsenal, New Jersey. These organisms were subsequently identified as Rhiziobium rhizogenes BL and Burkholderia sp.BL by the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ, German Collection of Microorganisms and Cell Cultures). In addition a fungus, identified as Cladosporium cladosporioides by DSMZ, was found to be growing on water wet RDX. All of these organisms were found to degrade RDX. The two bacteria were found to represent new species that have not been reported before. It was found that these organisms along with an added carbon source could degrade RDX to simple gaseous products. Data are presented that elucidate the mechanisms of RDX biodegradation for these organisms.

Biodegradation, Environmental↗

Determination of sodium monofluoroacetate (compound 1080) in tissues and baits as its benzyl ester by reaction-capillary gas chromatography.

A reaction-capillary gas-chromatographic procedure using photo-ionization (PID) or flame-ionization (FID) detection was developed for the determination of sodium monofluoroacetate (compound 1080), a pesticide, in tissues and baits. Fluoroacetic acid from tissue (1 g) and bait (10 g) extracts was first partitioned into ethyl acetate and then into 0.5 M benzyldimethylphenylammonium hydroxide. Benzylation was achieved by pyrolysis of the quaternary ammonium salt in the injection port. Chloroacetic acid was used as the internal standard. A linear relationship (r = 0.999) was observed between the peak area ratio of the substrate/internal standard and the fluoroacetic acid concentration. The detection limit for compound 1080 using the described analytical procedure, was 15 micrograms/kg with PID and 100 micrograms/kg with FID.

Animals↗

Quantification of brodifacoum in plasma and liver tissue by HPLC.

A simple high-performance liquid chromatographic method has been developed for detection and quantification of brodifacoum in plasma and liver tissue. After adding difenacoum as the internal standard, brodifacoum and difenacoum are extracted from 2 mL of plasma with two sequential 10-mL volumes of acetonitrile-ethyl ether (9:1) and from 2 g of liver tissue by grinding the tissue with 10 mL acetonitrile. The extracts are evaporated to dryness under nitrogen, 2 mL of acetonitrile is added to reconstitute the residues, and the resulting solution is analyzed using reversed-phase chromatography and fluorescence detection. The limits of detection for plasma and tissue are 2 micrograms/L and 5 ng/g, respectively. Using internal standardization, the mean intra-assay recovery from plasma is 92% and the mean inter-assay recoveries is 109%. The mean intra-assay and inter-assay recoveries from tissue are 96%. No interferences were observed with any of the following related compounds: brodifacoum, bromadiolone, coumarin, difenacoum, diphacinone, warfarin, and vitamin K1.

4-Hydroxycoumarins↗

Evaluation of an HPTLC method for the determination of strychnine and crimidine in biological samples.

In an attempt to improve the sensitivity and selectivity of thin-layer chromatographic analysis for the detection of strychnine and crimidine in biological samples, a rapid high-performance thin-layer chromatographic (HPTLC) method with densitometry is described. Fortified dog serum and stomach content samples were analyzed after extraction with chloroform. Quantitation was achieved by densitometry in the ultraviolet (UV) range (260 nm) of HPTLC silica gel 60 plates. Detection of trace levels as low as 5 ng proved feasible. Linearity was obtained over a range of 10-250-ng deposits for crimidine and 12.5-250-ng deposits for strychnine with simple or F254 plates. No interferences were observed in the UV spectra (220-380 nm) when peaks obtained with HPTLC of the standard substances and positive biological contents were scanned.

Animals↗

GC and GC-MS determination of fluoroacetic acid and phenoxy acid herbicides via triphasal extractive pentafluorobenzylation using a polymer-bound phase-transfer catalyst.

A simple and sensitive gas chromatography and gas chromatography-mass spectrometry (GC-MS) procedure has been developed for fluoroacetic acid (FA) and phenoxy acid herbicides (PAHs) via triphasal extractive pentafluorobenzylation. The triphasal system consisted of an aqueous sample, the extraction solvent toluene containing pentafluorobenzyl bromide as the derivatization reagent, and polymer-bound tri-n-butyl-methylphosphonium bromide as a phase-transfer catalyst, FA spiked in beverages, such as orange juice and milk, was extracted as its pentafluorobenzyl (PFB) derivative under moderate conditions (i.e., at a pH value of 6.5 at 60 degrees C). The detection limits were 0.10-0.20 microgram/mL by GC with electron-capture detection (GC-ECD), and 0.42-0.50 microgram/mL by full-scan GC-MS. PAHs were also detectable in the same manner within the detection limits of 0.05-0.10 microgram/mL by GC-ECD and 0.13-0.25 microgram/mL by full-scan GC-MS. Urine and serum which both contained 2,4-dichlorophenoxyacetic acid could also be analyzed by GC-MS after the triphasal pentafluorobenzylation. The detection limit was 0.20 microgram/mL in the full-scan mode and 10 ng/mL in the selected ion monitoring mode both for the urine and serum.

2,4-Dichlorophenoxyacetic Acid↗

Keratinocyte growth factor attenuates lung leak induced by alpha-naphthylthiourea in rats.

OBJECTIVE: To investigate the effect of pretreatment with keratinocyte growth factor on acute permeability pulmonary edema. DESIGN: Prospective, randomized, controlled animal study. SETTING: University research laboratory. SUBJECTS: Specific pathogen-free Sprague-Dawley rats. INTERVENTION: Acute permeability pulmonary edema was induced with an injection of alpha-naphthylthiourea, and lung leak was assessed in an isolated perfused lung model over 180 mins. Leak was confirmed with wet/dry lung weight ratios, and the alveolar fluid protein concentration was measured after bronchoalveolar lavage. The effect of pretreatment with keratinocyte growth factor (injected intratracheally 48 hrs before the experiment) on alpha-naphthylthiourea-induced pulmonary edema was assessed (keratinocyte growth factor/alpha-naphthylthiourea group). Control groups (Control and keratinocyte growth factor/Control) were also studied. Histopathology was performed for each of the four groups. MEASUREMENTS AND MAIN RESULTS: The alpha-naphthylthiourea produced an acute permeability pulmonary edema detected by lung leak over the 180-min ex vivo period of monitoring the isolated perfused lung (leak = 8+/-mL; wet/dry weight ratio 14.7+/-2; lavage protein 3.1+/-1 mg/mL). Pretreatment with keratinocyte growth factor significantly attenuated these parameters (leak = 2.3+/-0.4 mL; wet/dry weight ratio 7.1 +/- 0.5; lavage protein 0.28 +/-0.03 mg/mL), which were not significantly different from the control group and the keratinocyte growth factor/control group. Histopathology showed abundant type II pneumocyte hyperplasia in the lungs of animals pretreated with keratinocyte growth factor, and marked pulmonary edema in animals pretreated with alpha-naphthylthiourea. Less edema was apparent in the keratinocyte growth factor/alpha-naphthylthiourea group. All data are expressed as mean +/- SEM. CONCLUSIONS: Pretreatment with keratinocyte growth factor significantly attenuates pulmonary edema induced by alpha-naphthylthiourea. The mechanisms of this protection are likely related to type II pneumocyte hyperplasia, but remain to be specifically elucidated.

Animals↗

Exacerbation by granulocyte colony-stimulating factor of prior acute lung injury: implication of neutrophils.

OBJECTIVE: Granulocyte colony-stimulating factor is widely prescribed to hasten recovery from cancer chemotherapy-induced neutropenia and has been reported to induce pulmonary toxicity. However, circumstances and mechanisms of this toxicity remain poorly known. DESIGN: To reproduce a routine situation in cancer patients receiving chemotherapy, we investigated the mechanisms underlying granulocyte colony-stimulating factor-induced exacerbation of alpha-naphthylthiourea-related pulmonary edema. SETTING: Laboratory research unit. SUBJECTS: Male specific-pathogen-free Sprague-Dawley rats. INTERVENTIONS: The effects of granulocyte colony-stimulating factor given alone or after alpha-naphthylthiourea used to induce acute lung injury were investigated. MEASUREMENTS AND MAIN RESULTS: Lung injury was assessed based on neutrophil sequestration (myeloperoxidase activity in lung tissue) and influx into alveolar spaces (bronchoalveolar lavage fluid cell quantification) and on edema formation (wet/dry lung weight ratio) and alveolar protein concentration into bronchoalveolar lavage fluid. Tumor necrosis factor-alpha and interleukin-1beta were measured in serum, lung homogenates, and isolated alveolar macrophage supernatants. In control rats, granulocyte colony-stimulating factor (25 microg/kg) significantly elevated circulating neutrophil counts without producing alveolar recruitment or pulmonary edema. alpha-Naphthylthiourea significantly increased the wet/dry lung weight ratio (4.68 +/- 0.04 vs. 4.38 +/- 0.07 in controls, p=.04) and induced alveolar protein leakage. Adding granulocyte colony-stimulating factor to alpha-naphthylthiourea exacerbated pulmonary edema, causing neutrophil sequestration in pulmonary vessels, significantly increasing lung myeloperoxidase activity (12.7 +/- 2.0 mOD/min/g vs. 1.1 +/- 0.4 mOD/min/g with alpha-naphthylthiourea alone; p<.0001), and increasing proinflammatory cytokine secretion. alpha-Naphthylthiourea-related pulmonary edema was not exacerbated by granulocyte colony-stimulating factor during cyclophosphamide-induced neutropenia or after lidocaine, which antagonizes neutrophil adhesion to endothelial cells. Tumor necrosis factor-alpha and interleukin-1beta concentrations in alveolar macrophage supernatants and lung homogenates were significantly higher with alpha-naphthylthiourea + granulocyte colony-stimulating factor than with either agent alone, and anti-tumor necrosis factor-alpha antibodies abolished granulocyte colony-stimulating factor-related exacerbation of alpha-naphthylthiourea-induced pulmonary edema. In rats with cyclophosphamide-induced neutropenia, tumor necrosis factor-alpha concentrations in alveolar macrophage supernatants and lung homogenates were significantly decreased compared with rats without neutropenia. CONCLUSION: Granulocyte colony-stimulating factor-related pulmonary toxicity may involve migration of neutrophils to vascular spaces, adhesion of neutrophils to previously injured endothelial cells, and potentiation of proinflammatory cytokine expression.

Animals↗

Effect of iron(III), humic acids and anthraquinone-2,6-disulfonate on biodegradation of cyclic nitramines by Clostridium sp. EDB2.

AIMS: To determine the biodegradation of cyclic nitramines by an anaerobic marine bacterium, Clostridium sp. EDB2, in the presence of Fe(III), humic acids (HA) and anthraquinone-2,6-disulfonate (AQDS). METHODS AND RESULTS: An obligate anaerobic bacterium, Clostridium sp. EDB2, degraded RDX and HMX, and produced similar product distribution including nitrite, methylenedinitramine, nitrous oxide, ammonium, formaldehyde, formic acid and carbon dioxide. Carbon (C) and nitrogen (N) mass balance for RDX products were 87% and 82%, respectively, and for HMX were 88% and 74%, respectively. Bacterial growth and biodegradation of RDX and HMX were stimulated in the presence of Fe(III), HA and AQDS suggesting that strain EDB2 utilized Fe(III), HA and AQDS as redox mediators to transfer electrons to cyclic nitramines. CONCLUSIONS: Strain EDB2 demonstrated a multidimensional approach to degrade RDX and HMX: first, direct degradation of the chemicals; second, indirect degradation by reducing Fe(III) to produce reactive-Fe(II); third, indirect degradation by reducing HA and AQDS which act as electron shuttles to transfer electrons to the cyclic nitramines. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study could be helpful in determining the fate of cyclic nitramine energetic chemicals in the environments rich in Fe(III) and HA.

Anthraquinones↗

Covert self poisoning with brodifacoum, a 'superwarfarin'.

The clinical course of a patient poisoned with the 'superwarfarin' brodifacoum and a method for estimation of plasma levels is described. It was characterised by prolonged depression of Vitamin K-dependent clotting factors poorly responsive to Vitamin K administration.

4-Hydroxycoumarins↗