Ca2+ imaging with two-photon microscopy to detect the disruption of brain function in mice administered neonicotinoid insecticides.

Neonicotinoid pesticides are a class of insecticides that reportedly have harmful effects on bees and dragonflies, causing a reduction in their numbers. Neonicotinoids act as neuroreceptor modulators, and some studies have reported their association with neurodevelopmental disorders. However, the precise effect of neonicotinoids on the central nervous system has not yet been identified. Herein, we conducted in vivo Ca2+ imaging using a two-photon microscope to detect the abnormal activity of neuronal circuits in the brain after neonicotinoid application. The oral administration of acetamiprid (ACE) (20 mg/kg body weight (BW) in mature mice with a quantity less than the no-observed-adverse-effect level (NOAEL) and a tenth or half of the median lethal dose (LD50) of nicotine (0.33 or 1.65 mg/kg BW, respectively), as a typical nicotinic acetylcholine receptor (nAChR) agonist, increased anxiety-like behavior associated with altered activities of the neuronal population in the somatosensory cortex. Furthermore, we detected ACE and its metabolites in the brain, 1 h after ACE administration. The results suggested that in vivo Ca2+ imaging using a two-photon microscope enabled the highly sensitive detection of neurotoxicant-mediated brain disturbance of nerves.

Assessment of ameliorative effects of organic dietary interventions on neonicotinoid exposure rates in a Japanese population.

Neonicotinoid insecticides (NNIs) are a popular class of insecticides used in various pest management regimens worldwide. Biomonitoring studies continuously report high exposure rates of NNIs in various human populations across the globe. Yet, there is no validated countermeasure for combating the recent exponential rise in NNI exposure rates observed in human populations. The current study assessed the impacts of organic dietary interventions on NNI exposure rates in a Japanese population. A total of 103 volunteers were recruited into the study. Subjects were either served with Organic diets for 5 and 30 days or conventional diets. A total of 919 repeated urine samples were collected from the participants and then subjected to LC-MS/MS analysis to determine urinary concentrations of 7 NNIs parent compounds and an NNI metabolite. Eight NNIs were detected; with a decreasing detection frequency (%Dfs) pattern; desmethyl-acetamiprid (dm-ACE) (64.96%) > dinotefuran (52.12%), imidacloprid (39.61%) > clothianidin (33.95%) > thiamethoxam (28.51%) > acetamiprid (12.62%) > nitenpyram (5.33%) > thiacloprid (2.83%). Dinotefuran, dm-ACE, and clothianidin recorded the highest concentrations in the subjects. The %Df of NNIs in the 5-days or 30-days organic diet group were lower than those of the conventional diet consumers. The organic diet group showed lower rates of multiple NNI exposures than those of the conventional diet consumers. The mean and median cumulative levels of NNIs (median IMIeq) were significantly lower in the organic diet group than the conventional diet group (p < 0.0001). The estimated daily intakes (EDIs) of NNIs were higher in adults than children, but less than 1% of NNI cRfDs, except for clothianidin, which exhibited a %cRfD of 1.32 in children. Compared to the conventional diet group, the 5- and 30-day organic dietary intervention showed drastic reductions in NNI EDIs. Findings from the present study give credence to organic dietary interventions as potential ameliorative strategies for NNI exposure rates in human populations.

Urinary concentrations of neonicotinoid insecticides were related to renal tubular dysfunction and neuropsychological complaints in Dry-zone of Sri Lanka.

Neonicotinoids are systemic insecticides used since the 1990's , that possess renal tubular toxicity. We conducted a field-based descriptive study in the North Central Dry-zone of Sri Lanka, where chronic kidney disease (CKD) of unknown etiology has been increasing since the 1990's. To elucidate the relationship between renal tubular dysfunctions and urinary neonicotinoids concentrations, we collected spot urine samples from15 CKD patients, 15 family members, and 62 neighbors in 2015, analyzed two renal tubular biomarkers, Cystatin-C and L-FABP, quantified seven neonicotinoids and a metabolite N-desmethyl-acetamiprid by LC-MS/MS; and we investigated their symptoms using a questionnaire. Cystatin-C and L-FABP had a positive correlation (p < 0.001). N-Desmethyl-acetamiprid was detected in 92.4% of the urine samples, followed by dinotefuran (17.4%), thiamethoxam (17.4%), clothianidin (9.8%), thiacloprid and imidacloprid. Dinotefuran and thiacloprid have never been registered in Sri Lanka. In High Cystatin-C group (> 70 µg/gCre, n = 7), higher urinary concentration of dinotefuran (p = 0.009), and in Zero Cystatin-C group (< LOQ, n = 7), higher N-desmethyl-acetamiprid (p = 0.013), dinotefuran (p = 0.049), and thiacloprid (p = 0.035), and more complaints of chest pains, stomachache, skin eruption and diarrhea (p < 0.05) were found than in Normal Cystatin-C group (n = 78). Urinary neonicotinoids may be one of the potential risk factors for renal tubular dysfunction in this area.

Neonicotinoid residues in commercial Japanese tea leaves produced by organic and conventional farming methods.

The current study sought to assess the residual levels of neonicotinoid insecticides (NEO) in organic and conventional green tea leaves produced in Japan. A total of 103 tea leaves (thus, 42 organic and 61 conventional), were sampled from grocery stores in Japan. Concentrations of NEOs in the tea leaves were quantified using LC-MS/MS; and the data was used to estimate maximum daily intakes of NEOs within the Japanese population. Seven native NEO compounds and one NEO metabolite were detected in both organic and conventional tea leaves. Detection frequencies (%Dfs) of NEOs in the tea samples (n = 103) were found in the decreasing order; thiacloprid (84.47 %) > dinotefuran (74.76 %) > imidacloprid (69.90 %) ≈ clothianidin (69.90 %) > dm-acetamiprid (63.11 %) > thiamethoxam (58.25 %) > acetamiprid (4.85 %) > nitenpyram (1.94 %). About 94.20 % of the tea leaves contained two or more NEO compounds simultaneously. The %Dfs of NEOs were relatively lower in organic tea leaves, compared to the conventional tea leaves. Various percentile concentrations of NEOs were far lower in organic tea leaves, compared to the conventional tea leaves. The maximum daily intakes of NEOs through consumption of tea (MDIgt) were also lower for organic tea leaves, compared to the conventional tea samples.

Simultaneous quantification of imidacloprid and its metabolites in tissues of mice upon chronic low-dose administration of imidacloprid.

This study aimed to (i) develop a sensitive method for simultaneous detection and quantification of imidacloprid (IMI) and seven of its metabolites in tissue specimens, and to (ii) determine the biodistribution of the IMI compounds in tissues of C57BL/6J male mice; after exposure to 0.6 mg/kg bw/day of IMI (10% of no observable adverse effect level of IMI) through a powdered diet for 24 weeks. We successfully developed a method which was accurate (recoveries were ≥ 70% for most compounds), sensitive (LODs ≤ 0.47 ng/mL and LOQs ≤ 1.43 ng/mL were recorded for all detected compounds, R2 ≥ 0.99) and precise (RSDs ≤ 20%) for routine analysis of IMI and seven of its metabolites in blood and various tissue matrices. After bio-distributional analysis, IMI and five of its metabolites were detected in mice. Brain, testis, lung, kidney, inguinal white adipose tissue and gonadal white adipose tissue mainly accumulated IMI, blood and mesenteric white adipose tissue mainly accumulated IMI-olefin; liver mainly accumulated desnitro-IMI; pancreas predominately accumulated 4-hydroxy-IMI. The desnitro-dehydro-IMI and the desnitro-IMI metabolites recorded tissue-blood concentration ratios ≥ 1.0 for testis, brain, lung and kidney. The cumulative levels of the six detected IMI compounds (Σ6 IMI compounds) were found in the decreasing order: blood > testis > brain > kidney > lung > iWAT > gWAT > mWAT > liver > pancreas. Altogether, this study provided essential data needed for effective mechanistic elucidation of compound-specific adverse outcomes associated with chronic exposures to IMI in mammalian species.

Human Exposures to Neonicotinoids in Kumasi, Ghana.

Neonicotinoid insecticides (NNIs) are now popular in many agricultural systems across Africa; however, the extent of human exposures to NNIs in African countries is scarcely reported. The present study evaluates neonicotinoid exposures in the consumer population of Kumasi, a cosmopolitan city in Ghana. A total of 75 human urine samples were collected from healthy volunteers (nonfarmers, aged 13-80 yr) and analyzed with a liquid chromatography electrospray ionization tandem mass spectrometry system. Seven NNIs and 3 NNI metabolites were detected in the following pattern (frequency, median concentration, maximum concentration): N-dm-acetamiprid (94.7%, 0.41 µg/L, 8.79 µg/L) > imidacloprid (70.7%, 0.15 µg/L, 211.62 µg/L) > N-(6-chloro-3-pyridylmethyl)-N-ethyl-N'-methylformamidine (62.2%, 0.43 µg/L, 53.85 µg/L) > 2-[N-(6-chloro-3-pyridylmethyl)-N-ethylamino]-2-(methylimino)acetic acid (56.8%, 0.10 µg/L, 3.53 µg/L) > clothianidin (40%, >limit of quantification [LOQ], 0.45 µg/L) > nitenpyram (18.7%, >LOQ, 0.14 µg/L) ≈ thiamethoxam (18.7%, >LOQ, 0.21 µg/L) > dinotefuran (12.0%, >LOQ, 1.01 µg/L) > acetamiprid (2.7%, >LOQ, 0.08 µg/L) ≈ thiacloprid (2.7%, >LOQ, 0.14 µg/L). Approximately 92% of the subjects were found to be exposed to multiple neonicotinoids simultaneously. The mean, median, and maximum imidacloprid equivalent of the relative potency factor of NNIs were found to be 1.6, 0.5, and 22.52, respectively. The median estimated daily intakes of acetamiprid, imidacloprid, and nitenpyram were 0.47, 1.27, and 0.02 µg/kg/d for females and 0.91, 0.66, and 0.08 µg/kg/d for males, respectively. The maximum daily intakes of all the NNIs were <1% of their chronic reference doses (cRfDs), except for imidacloprid and thiacloprid which recorded maximum daily intakes corresponding to 17.97 and 8.28% of cRfDs, respectively. To the best of our knowledge, the present study is the first biomonitoring report on neonicotinoid insecticides in Africa. Environ Toxicol Chem 2021;40:2306-2318. © 2021 SETAC.

Chronic low-dose exposure to imidacloprid potentiates high fat diet-mediated liver steatosis in C57BL/6J male mice.

Hepatic steatosis is known to precede a continuum of events that lead to hepatic metabolic dysfunction, inflammation and carcinogenesis. Recently, studies have linked xenobiotic exposures to hepatic steatogenesis and its associated metabolic disorders; however, the underlying mechanisms remain elusive. This study aimed to elucidate the mechanistic role of imidacloprid in the prevalence of high fat diet (HFD)-induced liver steatosis, using a C57BL/6J mice model. Mice (3 weeks old) were fed with HFD and treated with 0.6 mg/kg bw/day (one-tenth of the NOAEL) of imidacloprid through water or diet, for 24 weeks. In a controlled group, mice were fed with only HFD. At the end of the study, imidacloprid treatment significantly potentiated HFD-induced body weight gain in mice. Also, imidacloprid increased the liver weights of mice, with complimentary reductions in mesenteric and gonadal white adipose tissue weights. Histopathological analysis of liver revealed a drastic steatosis in imidacloprid treated mice. Following a real-time qPCR analysis, imidacloprid upregulated transcriptions of hepatic fatty acid biosynthesis-related transcription factors and genes. Imidacloprid also induced hepatic expression of the gene encoding pregnane X receptor; but had no significant effect on hepatic expressions of liver X receptor and aryl hydrocarbon receptor. The imidacloprid treatment further enhanced serum alanine aminotransferase levels but downregulated hepatic antioxidant mRNA expressions. Ultimately, this study suggested an imidacloprid-potentiation effects on prevalence of HFD-induced liver steatosis via transcriptional modulations of the hepatic FA biosynthesis pathway.

Residues of neonicotinoids in soil, water and people's hair: A case study from three agricultural regions of the Philippines.

Synthetic pesticides such as neonicotinoids are commonly used to treat crops in tropical regions, where data on environmental and human contamination are patchy and make it difficult to assess to what extent pesticides may harm human health, especially in less developed countries. To assess the degree of environmental and human contamination with neonicotinoids we collected soil, water and people's hair in three agricultural regions of the Philippines and analysed them by ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS-MS). Five neonicotinoids, namely acetamiprid, clothianidin, imidacloprid, thiacloprid and thiamethoxam were targeted. Residues of neonicotinoids were found in 78% of 67 soil samples from the three provinces. Total neonicotinoid loads ranged on average between 0.017 and 0.89 µg/kg in soils of rice, banana and vegetable crops, and were 130 times higher (113.5 µg/kg) in soils of a citrus grove. Imidacloprid was the most prevalent compound at an average of 0.56 µg/kg in soil while thiacloprid was below the limit of detection. Half of the eight water samples from a rice field and nearby creek contained residues of imidacloprid (mean 1.29 ng/L) and one contained thiamethoxam (0.15 ng/L). Residues of neonicotinoids were found in 81% of 99 samples of people's hair from the surveyed regions (average total concentrations 0.14 to 1.18 ng/g, maximum 350 ng/g). Hair residue levels correlated well with the concentrations of thiamethoxam and total residues in soils from the same locality (r = 0.98). The presence of thiacloprid in 15% of the hair samples but not in soil samples suggests an additional route of exposure among people, which is most likely to be through ingestion of agricultural food and drinks available in the market.

LC-ESI/MS/MS analysis of neonicotinoids in urine of very low birth weight infants at birth.

OBJECTIVES: Neonicotinoid insecticides are widely used systemic pesticides with nicotinic acetylcholine receptor agonist activity that are a concern as environmental pollutants. Neonicotinoids in humans and the environment have been widely reported, but few studies have examined their presence in fetuses and newborns. The objective of this study is to determine exposure to neonicotinoids and metabolites in very low birth weight (VLBW) infants. METHODS: An analytical method for seven neonicotinoids and one neonicotinoid metabolite, N-desmethylacetamiprid (DMAP), in human urine using LC-ESI/MS/MS was developed. This method was used for analysis of 57 urine samples collected within 48 hours after birth from VLBW infants of gestational age 23-34 weeks (male/female = 36/21, small for gestational age (SGA)/appropriate gestational age (AGA) = 6/51) who were admitted to the neonatal intensive care unit of Dokkyo Hospital from January 2009 to December 2010. Sixty-five samples collected on postnatal day 14 (M/F = 37/22, SGA/AGA = 7/52) were also analyzed. RESULTS: DMAP, a metabolite of acetamiprid, was detected in 14 urine samples collected at birth (24.6%, median level 0.048 ppb) and in 7 samples collected on postnatal day 14 (11.9%, median level 0.09 ppb). The urinary DMAP detection rate and level were higher in SGA than in AGA infants (both p<0.05). There were no correlations between the DMAP level and infant physique indexes (length, height, and head circumference SD scores). CONCLUSION: These results provide the first evidence worldwide of neonicotinoid exposure in newborn babies in the early phase after birth. The findings suggest a need to examine potential neurodevelopmental toxicity of neonicotinoids and metabolites in human fetuses.

Contamination by neonicotinoid insecticides and their metabolites in Sri Lankan black tea leaves and Japanese green tea leaves.

Tea is one of the world's most popular beverages due to health promoting effects. Despite these, there have been concerns about the adverse effects of tea contamination by neonicotinoid insecticides. Only a handful of studies on neonicotinoid insecticides in tea have been carried out and this study was therefore performed to determine the concentrations of seven neonicotinoid insecticides and 20 metabolites in Japanese green tea leaves, and black tea leaves from Sri Lanka; and assess the Maximum Daily Intake (MDI) of neonicotinoid insecticides. From the results, the seven parent compounds were detected in Japanese tea leaves and beverages. Dinotefuran (3004 ng/g) was found at the highest level in green tea leaves. Ten of the 20 metabolites were detected in Japanese tea products. Dinotefuran-urea (92%) and thiacloprid-amide (89%) were most frequently detected in Japanese tea leaves. Clothianidin-urea (100 ng/g) was found at the highest level in green tea leaves. Neonicotinoid insecticides and metabolites were not detected in Sri Lankan black tea leaves. The concentrations and MDI of neonicotinoid insecticides in tea leaves were below the Maximum Residual Levels (MRLs) and Acceptable Daily Intakes (ADIs), respectively.

Relationship between Urinary N-Desmethyl-Acetamiprid and Typical Symptoms including Neurological Findings: A Prevalence Case-Control Study.

Neonicotinoid insecticides are nicotinic acetylcholine receptor agonists used worldwide. Their environmental health effects including neurotoxicity are of concern. We previously determined a metabolite of acetamiprid, N-desmethyl-acetamiprid in the urine of a patient, who exhibited some typical symptoms including neurological findings. We sought to investigate the association between urinary N-desmethyl-acetamiprid and the symptoms by a prevalence case-control study. Spot urine samples were collected from 35 symptomatic patients of unknown origin and 50 non-symptomatic volunteers (non-symptomatic group, NSG, 4-87 year-old). Patients with recent memory loss, finger tremor, and more than five of six symptoms (headache, general fatigue, palpitation/chest pain, abdominal pain, muscle pain/weakness/spasm, and cough) were in the typical symptomatic group (TSG, n = 19, 5-69 year-old); the rest were in the atypical symptomatic group (ASG, n = 16, 5-78 year-old). N-desmethyl-acetamiprid and six neonicotinoids in the urine were quantified by liquid chromatography-tandem mass spectrometry. The detection of N-desmethyl-acetamiprid was the most frequent and highest in TSG (47.4%, 6.0 ppb (frequency, maximum)), followed by in ASG (12.5%, 4.4 ppb) and in NSG (6.0%, 2.2 ppb), however acetamiprid was not detected. Thiamethoxam was detected in TSG (31.6%, 1.4 ppb), in ASG (6.3%, 1.9 ppb), but not in NSG. Nitenpyram was detected in TSG (10.5%, 1.2 ppb), in ASG (6.3%, not quantified) and in NSG (2.0%, not quantified). Clothianidin was only detected in ASG (6.3%, not quantified), and in NSG (2.0%, 1.6 ppb). Thiacloprid was detected in ASG (6.3%, 0.1 ppb). The cases in TSG with detection of N-desmethyl-acetamiprid and thiamethoxam were aged 5 to 62 years and 13 to 62 years, respectively. Detection of N-desmethyl-acetamiprid was associated with increased prevalence of the symptoms (odds ratio: 14, 95% confidence interval: 3.5-57). Urinary N-desmethyl-acetamiprid can be used as a biomarker for environmental exposure to acetamiprid. Further multi-centered clinical research in larger patients groups with more metabolites analysis is needed.

Qualitative profiling and quantification of neonicotinoid metabolites in human urine by liquid chromatography coupled with mass spectrometry.

Neonicotinoid pesticides have been widely applied for the production of fruits and vegetables, and occasionally detected in conventionally grown produce. Thus oral exposure to neonicotinoid pesticides may exist in the general population; however, neonicotinoid metabolites in human body fluids have not been investigated comprehensively. The purpose of this study is the qualitative profiling and quantitative analysis of neonicotinoid metabolites in the human spot urine by liquid chromatography coupled with mass spectrometry (LC/MS). Human urine samples were collected from three patients suspected of subacute exposure to neonicotinoid pesticides. A qualitative profiling of urinary metabolites was performed using liquid chromatography/time-of-flight mass spectrometry (LC/TOFMS) with a database of nominal molecular weights of 57 known metabolites of three neonicotinoid pesticides (acetamiprid, Imidacloprid, and clothianidin), as well as the parent compounds. Then a quantitative analysis of selected urinary metabolites was performed using liquid chromatography/tandem mass spectrometry (LC/MS/MS) with a standard pesticide and metabolite, which were detected by the qualitative profiling. The result of qualitative profiling showed that seven metabolites, i.e. an acetamiprid metabolite, N-desmethyl-acetamiprid; three Imidacloprid metabolites, 5-hydroxy-Imidacloprid, 4,5-dihydroxy-imidacloprid, 4,5-dehydro-Imidacloprid; a common metabolite of acetamiprid and Imidacloprid, N-(6-chloronicotinoyl)-glycine; and two clothianidin metabolites, N-desmethyl-clothianidin, N-(2-(methylsulfanyl)thiazole-5-carboxyl)-glycine, as well as acetamiprid, were detected in the urine of three cases. The result of the quantitative analysis showed N-desmethyl-acetamiprid was determined in the urine of one case, which had been collected on the first visit, at a concentration of 3.2 ng/mL. This is the first report on the qualitative and quantitative detection of N-desmethyl-acetamiprid in the human urine. The results suggest that the one case with detection of N-desmethyl-acetamiprid was exposed to acetamiprid through the consumption of contaminated foods. Urinary N-desmethyl-acetamiprid, as well as 5-hydroxy-Imidacloprid and N-desmethyl-clothianidin, may be a good biomarker for neonicotinoid exposure in humans and warrants further investigation.

[The correlation of middle ear pressure variations with mastoid pneumatization during nitrous oxide administration].

BACKGROUND: The present study evaluated the relationship between the middle ear (ME) pressure increase rate (PIR) and the mastoid size as well as the effect of mastoid size on the incidence of nausea and vomiting during nitrous oxide (N2O) anesthesia. METHODS: Twelve healthy male volunteers were recruited. The extent of mastoid pneumatization was measured planimetrically using a mastoid X-ray (Schuller's view). The ears were then divided into a small or large mastoid group according to the median value. The ME pressure was compared just before each increase to 33%, 50%, and 67% N2O. Using the ME pressure curve, the PIR for the first peak of the curve steepness was calculated. RESULTS: Increasing the end-tidal N2O concentration to 50% and 67% in the large mastoid group and to 33%, 50%, and 67% in the small mastoid group significantly increased the ME pressure. The PIR in the ears in the large mastoid group was significantly lower and the incidence of nausea was 33% in the small mastoid group during 33% N2O anesthesia. CONCLUSIONS: A higher PIR in the ears and a higher incidence of nausea were observed in the small mastoid group, compared with the large mastoid group.

Auditory evoked potential index does not correlate with observer assessment of alertness and sedation score during 0.5% bupivacaine spinal anesthesia with nitrous oxide sedation alone.

PURPOSE: The aim of this study was to evaluate the auditory evoked potential (AEP) index as a hypnosis monitor during nitrous oxide (N(2)O) sedation added to spinal analgesia. METHODS: Forty-five patients scheduled to undergo surgery under spinal anesthesia were recruited after giving informed consent. Adequate anesthesia levels were confirmed, and a disposable AEP index sensor (aepEX, Medical Device Management) was placed. A tight facemask was fitted, and a fresh gas flow of 100% oxygen 10 L/min was provided. AEP index monitoring was then initiated, and measurements and observer assessment of alertness/sedation (OAA/S) scores were recorded manually. N(2)O was administered in stepwise increases in the end-tidal concentration of 33%, 50%, and 67%. Paired AEP index and OAA/S scores were obtained immediately before each change in N(2)O concentration. RESULTS: Sixteen patients were excluded from final analysis because of nausea, vomiting, or abnormal excitatory behaviors. The increases in N(2)O concentration induced significant decreases in OAA/S scores and no substantial AEP index changes. Although OAA/S scores of 1 and 2 were observed in only two and five patients, respectively, a reduction in the OAA/S score from 5 to 1 was associated with a significant decrease in AEP index to the level indicative of moderate sedation. CONCLUSION: The AEP index might not be a suitable indicator of light hypnosis as defined by an OAA/S score of ≥3 during sedation with N(2)O alone.

[Detection of chloropyridinyl neonicotinoid insecticide metabolite 6-chloronicotinic acid in the urine: six cases with subacute nicotinic symptoms].

Neonicotinoid is a recently developed insecticide with worldwide use that has been increasing. It acts as a nicotinic acetylcholine receptor agonist. Chloropyridinyl neonicotinoid is a subgroup of neonicotinoid, and are commercially available as imidacloprid, nitenpyram, acetamiprid, and thiacloprid. The maximum residue limits of acetamiprid for fruits and tea leaves are high in Japan, e.g. 5 ppm for grapes and 30 ppm for tea leaves. 6-chloronicotinic acid (6 CNA) is a common metabolite in animals after exposure to chloropyridinyl neonicotinoids, but has not yet been detected in human urine. 'Spot' urine samples on the first visit and after were collected from eleven patients 6-52 years-old, who visited X-clinic from August to December in 2008, within 24 hours after symptom onset with unknown origin. Urinary 6 CNA was detected in six out of the eleven patients (IC positive group), by ion chromatography and identified in twenty specimens of these six patients by liquid chromatography-mass spectrometry (LC/MS), maximum 84.8 microg/L from the first visit to the 20th visit. The sensitivity of ion chromatography for LC/MS was 45%, and the specificity was 100%. The IC positive group showed headache, general fatigue, finger tremor, and short time memory disturbance in 100%, fever (> 37.0 degrees C), cough, palpitation, chest pain, stomachache, myalgia/muscle spasm/muscle weakness in 83%, heart rate abnormality (sinus tachycardia, sinus bradycardia, or intermittent WPW syndrome) in 83%, high domestic fruits intake (> 500 g/day) in 83%, high tea beverage intake (> 500 mL/day) in 66%. Five patients who were not among the IC positive group showed < 80%, < 40%, 60%, 60%, 20%, respectively. The patients gradually recovered through supportive therapy and the restriction of fruits and tea intake within several days to two months. In conclusion, urinary 6-chloronicotinic acid, a common metabolite of chloropyridinyl neonicotinoid insecticide, was detected for the first time, from six patients with subacute nicotinic symptoms.

Long QT and ST-T change associated with organophosphate exposure by aerial spray.

The relation between the electrocardiographic manifestation and the subjective symptoms accompanying organophosphate pesticide exposure caused by aerial spray was investigated. The study included 39 patients with a diagnosis of organophosphate poisoning, who visited A-clinic within 24h of exposure to aerial spray of organophosphate pesticide in Gumma Prefecture, from July 2001 to September 2001. Ages ranged from 3 to 82 years. Thirty-five patients were female. Three were diagnosed as severe, 11 moderate, and 25 mild, judged from the score of subjective symptoms. Electrocardiographic abnormalities were bradycardia (<50) 2; prolonged PQ interval 4; prolonged QTc interval (>430ms) 22; nonspecific ST-T change 35; supraventricular arrhythmia 13; and ventricular premature complex with R on T 1. Prolonged QTc interval developed in 2-3 severe cases, 4-11 moderate cases, and 16-25 mild cases. QT prolongation, ST-T change and arrhythmia were detected for some patients exposed to organophosphate by aerial spray.