Variability in urinary neonicotinoid concentrations in single-spot and first-morning void and its association with oxidative stress markers

Li, Adela Jing; Martinez-Moral, Maria-Pilar

doi:10.1016/j.envint.2019.105415

Cited by 74 publications

(30 citation statements)

References 46 publications

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“…For mice, treated with NOAEL levels of Imida and Aceta (10 mg/kg), the brain levels were around 3–6 ppm, and plasma concentrations were in a similar range (15–30 µM) (Ford and Casida 2006 ). Human data are mostly available for urinary metabolites used for biomonitoring, and the concentrations were maximally in the low nM range (Zhang et al 2019 ; Li et al 2020 ; Li and Kannan 2020 ). Due to the lack of more direct data, we built physiology-based toxicokinetic (PBTK) models to predict plasma and brain concentrations (Table S11).…”

Section: Resultsmentioning

confidence: 99%

Functional alterations by a subgroup of neonicotinoid pesticides in human dopaminergic neurons

et al. 2021

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Neonicotinoid pesticides, originally developed to target the insect nervous system, have been reported to interact with human receptors and to activate rodent neurons. Therefore, we evaluated in how far these compounds may trigger signaling in human neurons, and thus, affect the human adult or developing nervous system. We used SH-SY5Y neuroblastoma cells as established model of nicotinic acetylcholine receptor (nAChR) signaling. In parallel, we profiled dopaminergic neurons, generated from LUHMES neuronal precursor cells, as novel system to study nAChR activation in human post-mitotic neurons. Changes of the free intracellular Ca2+ concentration ([Ca2+]i) were used as readout, and key findings were confirmed by patch clamp recordings. Nicotine triggered typical neuronal signaling responses that were blocked by antagonists, such as tubocurarine and mecamylamine. Pharmacological approaches suggested a functional expression of α7 and non-α7 nAChRs on LUHMES cells. In this novel test system, the neonicotinoids acetamiprid, imidacloprid, clothianidin and thiacloprid, but not thiamethoxam and dinotefuran, triggered [Ca2+]i signaling at 10–100 µM. Strong synergy of the active neonicotinoids (at low micromolar concentrations) with the α7 nAChR-positive allosteric modulator PNU-120596 was observed in LUHMES and SH-SY5Y cells, and specific antagonists fully inhibited such signaling. To provide a third line of evidence for neonicotinoid signaling via nAChR, we studied cross-desensitization: pretreatment of LUHMES and SH-SY5Y cells with active neonicotinoids (at 1–10 µM) blunted the signaling response of nicotine. The pesticides (at 3–30 µM) also blunted the response to the non-α7 agonist ABT 594 in LUHMES cells. These data show that human neuronal cells are functionally affected by low micromolar concentrations of several neonicotinoids. An effect of such signals on nervous system development is a toxicological concern.

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Section: Resultsmentioning

confidence: 99%

Functional alterations by a subgroup of neonicotinoid pesticides in human dopaminergic neurons

et al. 2021

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“…suggested that the high variance of detected creatinine corrected level of urinary neonicotinoids [104], but the level of DMAP was rather consistent. CKD patients frequently complained of typical symptoms previously observed in subacute neonicotinoid intoxication in Japan [75].…”

Section: Discussionmentioning

confidence: 98%

Urinary Concentrations of Neonicotinoid Insecticides and Tubular Biomarkers, and Clinical Symptoms in Chronic Kidney Disease Patients, Their Family Members and Others in Dry-zone of Sri Lanka: a Small Scale Field-based Case-Control Study

Taira

Kawakami

Weragoda

et al. 2021

Preprint

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Background: The growing worldwide prevalence of chronic kidney disease of unknown etiology (CKDu) has been reported since the 1990’s. Neonicotinoids are systemic insecticides started to use in 1990’s with nicotinic acetylcholine receptor competitive modulator action, which may cause renal dysfunction as well as neurological symptoms.Methods: We conducted a field-based case-control study in the North Central Dry-zone of Sri Lanka where CKDu was prevailing. We collected spot urine samples of 92 residents, including 15 CKD patients, 15 CKD family members, and 62 neighbors in May or in December 2015, and analyzed seven neonicotinoids and a metabolite by LC-ESI/MS/MS, in addition to two biomarkers of renal tubule activity, Cystatin-C and L-FABP. The symptoms they complained of were also investigated by interview.Results: Urine was almost acidic and significant correlation was found in urinary concentration of Cystatin-C and L-FABP (r=0.71, p<0.001). In CKD patients in compare to non-CKD participants, urine Cystatin-C and L-FABP were significantly higher (p=0.0013, p<0.001, respectively) and more symptoms complained, e.g. finger tremor, fever, and abnormal behavior, as well as high urine volume, appetite loss, and reduced body weight. The detection rates of neonicotinoids were highest in N-desmethyl-acetamiprid 92.4 %, following dinotefuran 17.4 %, thiamethoxam 17.4 %, clothianidin 9.8%, thiacloprid 3.3%, imidacloprid 2.2%, nitenpyram and acetamiprid 0%. Dinotefuran and thiacloprid had not registered in 2015 in Sri Lanka. Between the concentration of urine Cystatin-C and N-desmethyl-acetamiprid, weak negative correlation was observed (r=-0.19, p=0.077)Conclusions: In CKD patients in the area, high urine Cystatin-C/L-FABP and more neurological symptoms were observed. Neonicotinoids exposure of people living in CKDu-epidemic area in Sri Lanka was common. Further investigation is needed to elucidate that occupational neonicotinoid exposure is one of the causes of CKDu and some neurological symptoms, e.g. appropriate timing of urine sampling.

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“…Data regarding historic pesticide use must be collected. Previous studies found that urinary concentrations of DAP metabolites and some NEO/m do not adequately reflect exposure for over 1 month [ 57 , 58 ]. Spot urine and blood samples were collected after breakfast and before lunch to keep the sampling period short.…”

Section: Discussionmentioning

confidence: 99%

Exposure to Organophosphate and Neonicotinoid Insecticides and Its Association with Steroid Hormones among Male Reproductive-Age Farmworkers in Northern Thailand

Suwannarin

Prapamontol

Isobe

et al. 2021

IJERPH

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Several studies indicated organophosphate (OP) and neonicotinoid (NEO) insecticides are endocrine disruptors; however, data are scarce. This cross-sectional study recruited 143 male farmworkers aged 18–40 years in Fang district, Chiang Mai province, northern Thailand. OP exposure was assessed by measuring urinary dialkylphosphate (DAPs) using a gas-chromatography flame photometric detector. Urinary NEOs, their metabolites (NEO/m) and serum steroid hormones were measured using liquid chromatography–tandem mass spectrometry. Characteristics of participants were determined by face-to-face interviews. DAPs and five NEO/m were detected in more than 60% of samples. The concentration of diethylphosphate was highest among DAP metabolites (geometric mean concentration (GM: 23.9 ng/mL) and the concentration of imidacloprid (IMI) was highest among NEO/m (GM: 17.4 ng/mL). Linear regression models showed that the IMI level was positively associated with testosterone, dehydrocorticosterone (DHC) and dehydroepiandrosterone (DHEA) levels. Imidacloprid-olefin and DHEA levels were positively associated. Thiamethoxam (THX) were inversely associated with DHC and deoxycorticosterone levels. Clothianidin (CLO), THX and N-desmethyl-acetamiprid levels were positively associated with the androstenedione level. CLO and THX levels were inversely associated with the cortisone level. In conclusion, the association between NEO insecticides exposure and adrenal androgens, glucocorticoids and mineralocorticoids, suggest potential steroidogenesis activities. Our findings warrant further investigation.

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Variability in urinary neonicotinoid concentrations in single-spot and first-morning void and its association with oxidative stress markers

Cited by 74 publications

References 46 publications

Functional alterations by a subgroup of neonicotinoid pesticides in human dopaminergic neurons

Functional alterations by a subgroup of neonicotinoid pesticides in human dopaminergic neurons

Urinary Concentrations of Neonicotinoid Insecticides and Tubular Biomarkers, and Clinical Symptoms in Chronic Kidney Disease Patients, Their Family Members and Others in Dry-zone of Sri Lanka: a Small Scale Field-based Case-Control Study

Exposure to Organophosphate and Neonicotinoid Insecticides and Its Association with Steroid Hormones among Male Reproductive-Age Farmworkers in Northern Thailand

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