Methemoglobinemia Following Monolinuron Ingestion: A Case Report in a Child.

CASE: We describe a case report of a 2-year-old boy presenting to the emergency department with cyanosis and agitation. There was no suggestive history of poisoning but parents reported the presence of an aquarium at the family dinner the night before, with an aquarium cleaner beside it. Physical examination at admission revealed central cyanosis without signs of respiratory distress. Oxygen saturation measured by pulse oximetry (SpO2) was at 80% in room air. Plasma level of methemoglobin was measured at 11.8%. After 6 hours, methemoglobin decreased spontaneously to 5% and pulse oximetry saturation reached 98% in room air. Consciousness, weakness, and behavior were concomitantly improved. Because of rapid and spontaneous improvement, no specific treatment such as methylene blue was administered. A mass spectrometry toxicological analysis was performed in a blood sample taken the day of admission. Screening procedure of pesticides based on liquid chromatography coupled with mass spectrometry identified monolinuron, a phenylurea herbicide. CONCLUSIONS: We recommend considering acquired methemoglobinemia after ingestion of industrial products and drugs in children with cyanosis, mental status alteration, and without respiratory distress symptoms.

PBPK modeling of the cis- and trans-permethrin isomers and their major urinary metabolites in rats.

Permethrin, a pyrethroid insecticide, is suspected to induce neuronal and hormonal disturbances in humans. The widespread exposure of the populations has been confirmed by the detection of the urinary metabolites of permethrin in biomonitoring studies. Permethrin is a chiral molecule presenting two forms, the cis and the trans isomers. Because in vitro studies indicated a metabolic interaction between the trans and cis isomers of permethrin, we adapted and calibrated a PBPK model for trans- and cis-permethrin separately in rats. The model also describes the toxicokinetics of three urinary metabolites, cis- and trans-3-(2,2 dichlorovinyl)-2,2-dimethyl-(1-cyclopropane) carboxylic acid (cis- and trans-DCCA), 3-phenoxybenzoic acid (3-PBA) and 4'OH-phenoxybenzoic acid (4'-OH-PBA). In vivo experiments performed in Sprague-Dawley rats were used to calibrate the PBPK model in a Bayesian framework. The model captured well the toxicokinetics of permethrin isomers and their metabolites including the rapid absorption, the accumulation in fat, the extensive metabolism of the parent compounds, and the rapid elimination of metabolites in urine. Average hepatic clearances in rats were estimated to be 2.4 and 5.7 L/h/kg for cis- and trans-permethrin, respectively. High concentrations of the metabolite 4'-OH-PBA were measured in urine compared to cis- and trans-DCCA and 3-PBA. The confidence in the extended PBPK model was then confirmed by good predictions of published experimental data obtained using the isomers mixture. The extended PBPK model could be extrapolated to humans to predict the internal dose of exposure to permethrin from biomonitoring data in urine.

Determination of dodine in fruit samples by liquid chromatography electrospray ionization-tandem mass spectrometry.

A rapid and sensitive LC/electrospray ionization-MS/MS method has been developed for the determination of dodine in fruit samples. Based on a liquid-liquid extraction of 10 g solid fruit homogenate using an acetone-dichloromethane-hexane mixture and acetate ammonium buffer (pH 4.5), this LC/MS/MS procedure was characterized by recoveries above 50%, with good intra-assay precision (RSD < 13%) and interassay precision (RSD < 18%) for seven different matrixes (apple, apricot, cherry, peach, pear, plum, and quince). This method was validated from 5 to 500 microg/kg according to standard guidelines. Its LOD (1 microg/kg) and LOQ (5 microg/kg) were in accordance with recommendations of the European legislation defined for infant food [maximum residue level (MRL) = 10 microg/kg]. The whole procedure was finally tested on 1022 fruit samples intended for commercialization, both infant food samples and samples not intended in particular for babies. In this study, dodine was detected in 27 samples; none exhibited a concentration higher than the MRL.

Screening of pesticides in blood with liquid chromatography-linear ion trap mass spectrometry.

In clinical or forensic toxicology, general unknown screening procedures are used to identify as many xenobiotics as possible, belonging to numerous chemical classes. We present here a general unknown screening procedure based on liquid chromatography coupled with use of a single linear ion trap mass spectrometer, and focus on the identification of pesticides and/or metabolites in whole blood. After solid-phase extraction (SPE), the compounds of interest were separated using a reversed-phase column and identified by the mass spectrometer operated first in the full-scan mass spectrometry (MS) mode, in the positive and negative polarities, followed by MS(2) and MS(3) scanning of ions selected in data-dependent acquisition. The total scan time was 2.45 s. Two mass spectral libraries (MS(2) and MS(3)), each of 450 spectra, were created for the 320 pesticides and metabolites detected after injection of pure solutions. Robustness of the spectra and matrix effects were studied and were satisfactory for the present application. Detection limits for the 320 compounds were studied by extracting 1 mL spiked blood at concentrations between 10 microg/L and 10 mg/L. If necessary, it was possible to decrease the detection limits of some compounds by 10-100-fold by scanning MS(2) in only one polarity, owing to a shorter total scan time. However, at the same time, the detection specificity decreased as no confirmation could be recorded in the following MS(3) scan and no information could be registered in the other polarity. So, in these rare cases, confirmation by another method was required.

Combined effect of copper and hydrodynamic conditions on Myriophyllum alterniflorum biomarkers.

The aim of this study is to determine the combined effect of copper and hydrodynamic conditions on the response of certain biomarkers of an aquatic macrophyte, namely Myriophyllum alterniflorum. Watermilfoil biomarkers are monitored in a synthetic medium enriched or not with copper (100 µg.L-1) for 21 days in aquarium systems (150 L), under three hydrodynamic conditions: laminar, turbulent, and calm. The studied biomarkers are: respiratory and photosynthetic activities; concentrations of chlorophyll a, b and carotenoids; osmotic potential; hydrogen peroxide content; and growth. In addition, Cu contents in water and in Myriophyllum alterniflorum (roots and shoots) are investigated. The hydrodynamic conditions only affect watermilfoil morphology. Copper accumulates less in turbulent zones; moreover, it is more likely to accumulate in shoots than in roots, except within the calm zone. Cu leads to: i) a significant increase in H2O2 content, ii) a decrease in root growth, pigment content, osmotic potential, photosynthesis and respiration rates, and iii) an inhibition of shoot branching. Differential effects are also observed between younger and older parts, thus indicating the benefit of considering these two plant parts separately in water quality biomonitoring.

Biomonitoring of 29 trace elements in whole blood from inhabitants of Cotonou (Benin) by ICP-MS.

This study aimed to investigate the blood concentration of 29 trace elements, metals or metalloids, in a healthy population of Cotonou not directly exposed to metals in order to propose reference values. Blood samples from 70 blood donors were collected in K2 EDTA tubes for trace elements during September 2015 and a questionnaire was used to assess lifestyle exposure. Blood metal concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS) equipped with a quadrupole-based reaction cell. Among the selected blood donors 51.4% were aged from 18 to 36 years and 49.6% from 37 to 65 years. Among the 29 elements analyzed As, Pb, Mn, Pd, Sb, Co, Se, Sr showed blood concentrations higher than the reference values found in the literature for non-exposed healthy European populations and their geometric means were respectively 5.81; 47.39; 19.71; 1.91; 7.50; 0.66; 163.01; 30.53µg/L. This study provides the first reference value (5th-95th percentiles) for each element in Cotonou, which enables us to carry out further investigations on environmental and occupational exposure.

Axonal degeneration with unusual lesions of the myelin in an occupational neuropathy.

A 35-year-old man had prolonged occupational exposure to lead carboxylate, triethylbenzene, xylene, and dichloromethane, when he developed a subacute predominantly sensory neuropathy. Ultrastructural examination of a peripheral nerve biopsy showed axonal degeneration and unusual lesions of the myelin, with Schwann cell sequestration of vesicular and lamellar debris. Biochemical analysis of lead in a frozen peripheral nerve specimen revealed no significant difference between the propositus and a control. The authors were unable to find any similar peripheral nerve lesions in the literature dealing with neurotoxic chemicals. Any of the several organic solvents could have equally caused the neuropathy and may have been potentialized by the other chemicals.

Evaluation of iodine intake and status using inductively coupled plasma mass spectrometry in urban and rural areas in Benin, West Africa.

OBJECTIVE: Iodine deficiency has severe pathological repercussions. The aim of this study was to evaluate iodine intake and status in adults in Benin, West Africa. METHODS: We randomly selected 420 participants ages 25 to 64 y and free of visible goiter from urban and rural settings of South Benin. The participants had a diet based on carbohydrates and fish. Urine was collected over a 24-h period and samples were assayed for iodine analysis using inductively coupled plasma mass spectrometry. RESULTS: We studied 401 urinary iodine samples. The overall median urinary iodine concentration (UIC) in 24-h urine was 62.9 µg/L (interquartile range: 40-96.2 µg/L). UIC was significantly lower in women than men (56.5 versus 78.6 µg/L; P < 0.001) and in rural versus urban areas (54.7 versus 77.8 µg/L; P < 0.001). In multivariate analysis, low UIC (<100 µg/L) was positively associated with women (odds ratio, 2.48; 95% confidence interval, 1.44-4.26; P = 0.001) and body mass index <25 kg/m(2) (odds ratio, 2.06; 95% confidence interval, 1.20-3.54; P = 0.008). CONCLUSION: Iodine intake appeared to be fairly low in the Beninese population, according to World Health Organization criteria, and factors associated with low iodine intake were identified. Public health interventions to increase iodine intake, such as iodization of commercial salt and/or fortification of selected nutrients, should be strengthened at the national level.

Micropropagation of Myriophyllum alterniflorum (Haloragaceae) for stream rehabilitation: first in vitro culture and reintroduction assays of a heavy-metal hyperaccumulator immersed macrophyte.

Nowadays, submersed aquatic macrophytes play a key role in stream ecology and they are often used as biomonitors of freshwater quality. So, these plants appear as natural candidates to stream rehabilitation experiments. Among them, the stream macrophyte Myriophyllum alterniflorum is used recently as biomonitor and is potentially useful for the restoration of heavy-metal contaminated localities. The best way to obtain a mass production of watermilfoil plants is micropropagation. We developed in vitro culture of M. alterniflorum and the effects of five media on the plant development were assessed. Five morphological and four physiological endpoints were examined leading to the recommendation of the Murashige and Skoog medium for ecotoxicological studies on chlorophyllous parts, and of the Gaudet medium for root cytotoxicity and phytoremediation studies. Micropropagated clones were acclimatized in a synthetic medium and in situ reintroduction was performed efficiently. This is the first report of micropropagated plants transplantation in streams. The successful establishment of watermilfoil beds even in polluted areas strongly suggested that ecological restoration using micropropagated watermilfoil is a promising biotechnology for phytoremediation and rehabilitation of degraded areas. Moreover, high bioconcentration factors evidenced that watermilfoil hyperaccumulates Cd and Cu, and could be potentially used in phytoremediation studies.

Severe and prolonged neurologic toxicity following subcutaneous chlorpyrifos self-administration: a case report.

INTRODUCTION: Organophosphate poisoning by oral or inhalation routes is characterized by a typical time-course of clinical features. CASE PRESENTATION: We report a case of subcutaneous chlorpyrifos self-injection leading to a delayed cholinergic phase, prolonged coma, and severe permanent neurologic injury with electrophysiological patterns suggestive of overlapping intermediate syndrome and distal peripheral neuropathy. Time-course and severity of clinical features were not altered by either atropine or pralidoxime administration. Due to prolonged and severe alteration in consciousness, we used brain multimodal nuclear magnetic imaging and auditory cognitive event-related potentials to assess the patient's potential for awakening. Electrophysiological testing used to monitor muscle weakness showed the coexistence of 20 Hz-decremental responses in proximal muscles and severe denervation in distal muscles. Red blood cell acetylcholinesterase activity progressively normalized on day 60, while plasma butyrylcholinesterase activity remained low until day 100. Chlorpyrifos was detectable in serum until day 30 and urine metabolites for up to three months, supporting the hypothesis of a continuous chlorpyrifos release despite repeated surgical debridement. We suggest that adipose and muscle tissues acted as a chlorpyrifos reservoir. At one-year follow-up, the patient exhibited significant neuromuscular sequelae. CONCLUSION: Subcutaneous chlorpyrifos self-injection may result in severe toxicity with prolonged neurologic injury, atypical overlapping electrophysiological patterns, and a poor final outcome.