Environmental exposure to melamine and its derivatives and kidney outcomes in children.

Melamine caused acute nephrotoxicity in a past food adulteration incident, but it is unclear whether and how widespread ambient exposure to melamine and related compounds might affect pediatric kidney health. We assessed cross-sectional associations between childhood exposure to melamine and its derivatives and biomarkers of kidney injury and health and explored potential heterogeneity by sex suggested by sex-dependent differences in renal physiology. We measured melamine and its derivatives ammeline, ammelide, and cyanuric acid (CYA) in spot urine samples collected from 192 children from an urban site (Seattle, WA) and 187 children from a rural site (Yakima, WA) aged 4-8 years in the Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) Study. In addition, biomarkers of kidney injury were measured in the same urine samples, including albumin, total protein, KIM-1, NAG, NGAL, and EGF. We utilized linear regressions to examine associations between individual chemical exposures and kidney biomarkers. Interaction terms examined association modification by sex, as well as potential interactions between melamine and CYA. Despite comparable exposures, girls had higher levels of many kidney injury biomarkers compared to boys. A ten-fold higher melamine concentration was associated with a 18% (95% CI: 5.6%, 31%) higher EGF in the full sample, while ten-fold higher melamine was associated with a 76% (14.1%, 173%) higher KIM-1 in boys but not in girls (-10.1% (-40.6%, 36.1%), interaction p = 0.026). Melamine exhibited significant negative interactions with CYA in association with total protein and NAG that appeared to be specific to girls. Our results suggest possible associations between melamine exposure and markers of kidney injury that may be more pronounced in boys. These findings provide novel insights into melamine and related derivative compound health effects at low levels of exposure in children and emphasize the role of sex in mediating the relationship between nephrotoxicant exposure and kidney injury.

Removal of Remdesivir's Metabolite GS-441524 by Hemodialysis in a Double Lung Transplant Recipient with COVID-19.

Remdesivir has reported efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and in vivo Drug-drug interactions limit therapeutic options in transplant patients. Remdesivir and its metabolite GS-441524 are excreted principally in urine. In intensive care unit (ICU) settings, in which multiple-organ dysfunctions can occur rapidly, hemodialysis may be a viable option for maintaining remdesivir treatment, while improving tolerance, by removing both remdesivir's metabolite (GS-441524) and sulfobutylether ß-cyclodextrin sodium (SEBCD). Additional studies may prove informative, particularly in the evaluations of therapeutic options for coronavirus disease 2019 (COVID-19).

Development of analytical method of melamine in placenta from pregnant women by isotope-dilution liquid chromatography/tandem mass spectrometry.

RATIONALE: Melamine is ubiquitously present in our daily life. It has a known effect on the kidneys, but it may also adversely affect the reproduction system. We have developed an analytical method for measuring melamine levels in maternal placenta and correlated these levels with melamine concentrations in urine, a necessary step in finding out if melamine might cross the placenta and enter the circulation of the fetus. METHODS: We used liquid-liquid extraction, clean up by solid-phase extraction (SPE), and isotope-dilution liquid chromatography/tandem mass spectrometry (LC/MS/MS) to measure melamine in placenta specimens. The results of this method were assessed for linearity, limits of quantitation (LOQs), and intra- and inter-assay precision as well as accuracy, matrix effect, and recovery rate. RESULTS: Calibration curves indicated good linearity (r >0.995) over concentrations ranging from 5 to 500 ng/mL in placenta specimens, intra- and inter-assay precision from 0.89% to 27.07%, and accuracy from 92.4% to123.5%. Recovery ranged from 63.9 to 83.9%, and the LOQ was 5 ng/mL in placenta (0.2 g). Placental melamine levels ranged from 7.87 to19.64 ng/mL, all detectable (n = 8). Pregnant women with higher levels of urinary melamine had higher placenta melamine levels than those with non-detectable urinary melamine, though the results were not significantly different (p = 0.149, n = 4 in each group). CONCLUSIONS: The results of this study suggest that pregnant women were exposed to low doses of melamine in their daily lives as measured in urine samples and placenta specimens. It is unclear whether placenta melamine concentrations can better represent long-term exposure than urine or whether melamine in the uterus can enter the fetus via this route.

A probabilistic approach for benchmark dose of melamine exposure for a marker of early renal dysfunction in patients with calcium urolithiasis.

Environmental exposure to melamine has been associated with early renal injury in urolithiasis patients even when urinary concentrations of melamine are low. The aim of this study was to derive a benchmark dose (BMD) for melamine for urolithiasis patients. To do this, one-spot urine sample from 309 participants was obtained to measure urinary melamine and N-acetyl ß-D-glucosaminidase (NAG), an early renal damage biomarker. The participants were then classified into four exposure groups based on the outcomes of melamine tableware usage questionnaire. A beta distribution of urinary excretion fraction for each group was assumed to estimate their average daily intakes (AvDIs) of melamine. The BMD and the corresponding one-sided 95% lower bound (BMDL) was then derived based on Bayesian model averaging of alternative regression models between the participants' NAG levels and their estimated AvDIs, adjusting for age, gender, and other covariates. Bayesian Markov chain Monte Carlo simulations were used for all the estimates. With a benchmark response of 0.10, the simulated BMDL of 4.89 µg/kg-bw/day for melamine exposure threshold was much lower than the WHO's current recommended tolerable daily intake of 200 µg/kg_bw/day and the US FDA's 63 µg/kg_bw/day. The current regulation level of melamine might not safeguard urolithiasis patients from further deterioration of renal function.

Investigating the interaction between melamine and cyanuric acid using a Physiologically-Based Toxicokinetic model in rainbow trout.

Following outbreaks of feed and food adulterations with a melamine and cyanuric acid mixture in 2007 and melamine in 2008 respectively, the kinetics and toxicodynamics of the mixture have been investigated particularly in sensitive species such as the rainbow trout. Tissue concentrations and intensity of the adverse effect, melamine-cyanurate crystal formation in kidney, were reported in similar experimental conditions. Here, a recent PBTK model for rainbow trout has been applied to model the kinetics of both single compounds based on residue levels in tissues. Both PBTK models for the single compounds were combined and a model of crystal formation for the mixture melamine-cyanuric acid was also added to predict the intensity of crystal formation under the assumptions that crystals formed either in urine or in kidney tissue. Modelling the kinetics of melamine and cyanuric acid provided a better understanding and prediction of intensity of crystal formation in case of sequential exposures with varying intensity or co-exposure. This study demonstrates, for the first time, how fish PBTK models can play a key role in the understanding and prediction of toxicokinetics and toxicodynamics of mixtures. This study also illustrates how adverse effects may potentially occur even when the compounds are not administered together as a mixture.

Absorption, distribution, metabolism and excretion of an isocitrate dehydrogenase-2 inhibitor enasidenib in rats and humans.

1. The absorption, distribution, metabolism and excretion of enasidenib were studied following a single oral dose of [14C]enasidenib to rats (10 mg/kg; 100 µCi/kg) and healthy volunteers (100 mg; 318 nCi). 2. Enasidenib was readily absorbed, extensively metabolized and primarily eliminated via the hepatobiliary pathway. Enasidenib-derived radioactivity was widely distributed in rats. Excretion of radioactivity was approximately 95-99% of the dose from rats in 168 h post-dose and 82.4% from human volunteers in 504 h post-dose. In rat bile, approximately 35-42% of the administered dose was recovered, with less than 5% of the dose excreted as the parent drug. Renal elimination was a minor pathway, with <12% of the dose excreted in rat urine and <10% of the dose excreted in human urine. 3. Enasidenib was the prominent radioactive component in rat and human systemic circulation. Enasidenib was extensively metabolized in rats and human volunteers through N-dealkylation, oxidation, direct glucuronidation and combinations of these pathways. Glucuronidation was the major metabolic pathway in rats while N-dealkylation was the prominent metabolic pathway in human volunteers. All human metabolites were detected in rats.

Ingestion of swimming pool water by recreational swimmers.

The volume of water ingested by swimmers while swimming is of great interest to individuals who develop risk assessments using quantitative microbial risk assessment or epidemiological approaches. We have used chloroisocyanurate disinfected swimming pool waters to determine the amount of water swallowed by swimmers during swimming activity. The chloroisocyanurate, which is in equilibrium with chlorine and cyanuric acid in the pool water, provides a biomarker, cyanuric acid, that once swallowed passes through the body into the urine unchanged. The concentration of cyanuric acid in a 24 hour urine specimen and the concentration in pool water can be used to calculate the amount of water swallowed. Our study population of 549 participants, which was about evenly divided by gender, and young and adult swimmers, indicated that swimmers ingest about 32 mL per hour (arithmetic mean) and that children swallowed about four times as much water as adults during swimming activities. It was also observed that males had a tendency to swallow more water than females during swimming activity and that children spent about twice as much time in the water than adults.

Paracetamol decreases steady-state exposure to lamotrigine by induction of glucuronidation in healthy subjects.

AIM: Patients receiving lamotrigine therapy frequently use paracetamol concomitantly. While one study suggests a possible, clinically relevant drug-drug interaction, practical recommendations of the concomitant use are inconsistent. We performed a systematic pharmacokinetic study in healthy volunteers to quantify the effect of 4 day treatment with paracetamol on the metabolism of steady-state lamotrigine. METHODS: Twelve healthy, male volunteers participated in an open label, sequential interaction study. Lamotrigine was titrated to steady-state (100 mg daily) over 36 days, and blood and urine sampling was performed in a non-randomized order with and without paracetamol (1 g four times daily). The primary endpoint was change in steady-state area under the plasma concentration-time curve of lamotrigine. Secondary endpoints were changes in total apparent oral clearance, renal clearance, trough concentration of lamotrigine and formation clearance of lamotrigine glucuronide conjugates. RESULTS: Co-administration of lamotrigine and paracetamol decreased the steady-state area under the plasma concentration-time curve of lamotrigine by 20% (95% CI 10%, 25%; P < 0.001) from 166 to 127 µmol l(-1) . Concomitant administration of paracetamol increased the formation clearance of lamotrigine glucuronide conjugates by 45% (95% CI 18%, 79%, P = 0.005) from 1.7 to 2.8 l h(-1) , while the trough value of lamotrigine was reduced by 25% (95% CI 12%, 36%, P = 0.003) from 5.3 to 3.9 µmol l(-1) . CONCLUSION: Paracetamol statistically significantly induced steady-state lamotrigine glucuronidation, resulting in a 20% decrease in total systemic exposure and a 25% decrease in trough value of lamotrigine. This interaction may be of clinical relevance in some patients.

Human Metabolite Lamotrigine-N(2)-glucuronide Is the Principal Source of Lamotrigine-Derived Compounds in Wastewater Treatment Plants and Surface Water.

Wastewater and surface water samples, extracted with four solid-phase extraction cartridges of different chemistries, were suspect-screened for the anticonvulsant lamotrigine (LMG), its metabolites, and related compounds. LMG, three human metabolites, and a LMG synthetic impurity (OXO-LMG) were detected. Preliminary results showed significantly higher concentrations of OXO-LMG in wastewater effluent, suggesting its formation in the wastewater treatment plants (WWTPs). However, biodegradation experiments with activated sludge demonstrated that LMG is resistant to degradation and that its human metabolite lamotrigine-N(2)-glucuronide (LMG-N2-G) is the actual source of OXO-LMG in WWTPs. In batch reactors, LMG-N2-G was transformed, following pseudo-first-order kinetics to OXO-LMG and LMG, but kinetic experiments suggested an incomplete mass balance. A fragment ion search applied to batch-reactor and environmental samples revealed another transformation product (TP), formed by LMG-N2-G oxidation, which was identified by high-resolution mass spectrometry. Accounting for all TPs detected, a total mass balance at two concentration levels in batch reactors was closed at 86% and 102%, respectively. In three WWTPs, the total mass balance of LMG-N2-G ranged from 71 to 102%. Finally, LMG-N2-G and its TPs were detected in surface water samples with median concentration ranges of 23-139 ng L(-1). The results of this study suggest that glucuronides of pharmaceuticals might also be sources of yet undiscovered, but environmentally relevant, transformation products.

Variability in 24 hour excretion of cyanuric acid: implications for water exposure assessment.

Cyanuric acid (CYA) excretion in urine has been used to estimate the volume of water ingested during swimming and other recreational activities in outdoor pools containing this chemical. These estimates of water ingestion are based on the assumption of 100% excretion within 24 hours, but the supporting evidence for this is scant. While adapting this methodology to investigate other water ingestion scenarios, we observed a high degree of variability in cyanuric acid excretion among experimental subjects, with over 25% of individuals excreting less than 80% of an ingested dose. Use of cyanuric acid to measure inadvertent water ingestion may be a valuable tool to generate data for health risk assessment of non-potable water sources, but our observations indicate that this technique carries an inherent degree of underestimation that should be taken into account when calculating water exposure.

Behavioral Intervention and Decreased Daily Melamine Exposure from Melamine Tableware.

This study aims to examine whether behavior intervention can decrease total urinary melamine excretion. A total of 16 healthy subjects were recruited from two university buildings (eight subjects each). By using a stepped-wedge cluster randomized and controlled trial design, we randomly assigned eight subjects from the same building to the serial steps of either control-intervention-intervention or control-control-intervention. Each step lasted for 3 days. Subjects in the intervention step carried one bag containing stainless steel tableware as meal boxes and used them for each meal during the trial, whereas those in the control step carried one empty bag. The 24 h urine samples for 9 consecutive days were collected. In the control-intervention-intervention group, after excluding two subjects with missing data, the median absolute difference of the total 3 day melamine excretion between the seventh to the ninth day and from the first to the third day was -19.9 µg (a range from -160.6 to -7.2 µg, p = 0.028, n = 6). The median protection percent of the total 3 day melamine exposure (the amount from the seventh to the ninth day minus the amount from the first to the third day, divided by the amount from the first to the third day) was 68.4%, ranging from 41.8% to 91.8%. Regular use of stainless steel-made meals boxes can mitigate melamine exposure from melamine tableware.

Simultaneous extraction and quantification of lamotrigine, phenobarbital, and phenytoin in human plasma and urine samples using solidified floating organic drop microextraction and high-performance liquid chromatography.

A novel and simple method based on solidified floating organic drop microextraction followed by high-performance liquid chromatography with ultraviolet detection has been developed for simultaneous preconcentration and determination of phenobarbital, lamotrigine, and phenytoin in human plasma and urine samples. Factors affecting microextraction efficiency such as the type and volume of the extraction solvent, sample pH, extraction time, stirring rate, extraction temperature, ionic strength, and sample volume were optimized. Under the optimum conditions (i.e. extraction solvent, 1-undecanol (40 µL); sample pH, 8.0; temperature, 25°C; stirring rate, 500 rpm; sample volume, 7 mL; potassium chloride concentration, 5% and extraction time, 50 min), the limits of detection for phenobarbital, lamotrigine, and phenytoin were 1.0, 0.1, and 0.3 µg/L, respectively. Also, the calibration curves for phenobarbital, lamotrigine, and phenytoin were linear in the concentration range of 2.0-300.0, 0.3-200.0, and 1.0-200.0 µg/L, respectively. The relative standard deviations for six replicate extractions and determinations of phenobarbital, lamotrigine, and phenytoin at 50 µg/L level were less than 4.6%. The method was successfully applied to determine phenobarbital, lamotrigine, and phenytoin in plasma and urine samples.

Application of a magnetic molecularly imprinted polymer for the selective extraction and trace detection of lamotrigine in urine and plasma samples.

Magnetic molecularly imprinted polymers have been synthesized for the selective preconcentration and trace determination of lamotrigine (LTG) in urine and plasma samples. The magnetic nanoparticles were modified by tetraethyl orthosilicate and 3-methacryloxypropyl trimethoxysilane before imprinting. The magnetic molecularly imprinted polymers were prepared via surface molecular imprinting technique, using Fe3 O4 as a magnetic component, LTG as template molecule, methacrylic acid as a functional monomer, ethylene glycol dimethacrylate as a cross-linker, and 2,2'-azobisisobutyronitrile as a radical initiator in methanol/acetonitrile (50:50, v/v) as the porogen. The obtained sorbent was characterized using scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, and thermal analysis. Separation of the sorbent from the sample solution was simply achieved by applying an external magnetic field. Determination of the extracted drug was performed by high-performance liquid chromatography with UV detection. Under the optimum extraction conditions, the method detection limits were 0.7 µg/L (based on S/N of 3) for urine samples and 0.5 µg/L for plasma samples. A linear dynamic range of 1-1000 µg/L was obtained for LTF in plasma and urine samples. Finally, the applicability of the proposed method was evaluated by extraction and determination of LTG in urine and plasma samples.

Assessment of swimmer behaviors on pool water ingestion.

Enteric pathogens in pool water can be unintentionally ingested during swimming, increasing the likelihood of acute gastrointestinal illness (AGI). AGI cases in outbreaks are more likely to submerge heads than non-cases, but an association is unknown since outbreak data are self-reported and prone to bias. In the present study, head submersion frequency and duration were observed and analyzed for associations with pool water ingestion measured using ultra high pressure liquid chromatography - tandem mass spectrometry. Frequency of splashes to the face was also quantified. Reliable tools that assess activities associated with pool water ingestion are needed to identify ingestion risk factors and at-risk populations. Objectives were to determine if the observed activities were associated with ingestion, and to test environmental sensor and videography assessment tools. Greater frequency and duration of head submersion were not associated with ingestion, but frequency of splashes to the face, leisurely swimming, and being ≤18 were. Videography was validated for assessing swimmer head submersion frequency. Results demonstrate ingestion risk factors can be identified using videography and urine analysis techniques. Expanding surveys to include questions on leisure swimming participation and frequency of splashes to the face is recommended to improve exposure assessment during outbreak investigations.

A simple and sensitive HPLC-UV determination of 7-O-succinyl macrolactin A in rat plasma and urine and its application to a pharmacokinetic study.

A simple, sensitive and reproducible isocratic reversed-phase (C(18) ) high-performance liquid chromatography (HPLC) method was developed to determine 7-O-succinyl macrolactin A (SMA) in rat plasma and urine samples using UV detector set at 230 nm. Lamotrigine was used as internal standards (IS) to ensure the precision and accuracy of the method. The retention times of SMA and IS for the plasma sample were 9.2 and 4.4 min, respectively, and those for the urine samples were 7.9 and 4.3 min, respectively. The intra- and inter-day variations of the analytical responses, expressed in terms of relative standard deviation, were less than 14.9%. The accuracy, in terms of average analytical recovery, ranged from 90.4 to 119%. The lower limits of quantification of SMA in rat plasma and urine samples were 0.02 and 0.1 µg/mL, respectively. This method is applicable for the pharmacokinetic studies of SMA in rats.

[Simultaneous determination of melamine and cyanuric acid residues in water and urine by solid phase extraction-hydrophilic interaction liquid chromatography-electrospray tandem mass spectrometry method].

OBJECTIVE: We aimed to establish a sensitive quantified method for the simultaneous determination of melamine and cyanuric acid residues in water and urine by hydrophilic interaction liquid chromatography coupled with electrospray tandem mass spectrometry (HILIC-ESI-MS/MS) with the pretreatment of hydrophilic functional silica gel and cation exchange resin mixed solid phase extraction column(MCT), and to investigate the melamine and cyanuric acid residues in 501 water and 216 urine from several province and city. METHODS: About 100 ml water (or 10 ml urine) was adjusted to pH 3.0 with concentrated hydrochloric acid, and then mixed with the internal standard solution((15)N3-melamine and (15)N3-(13)C3 -cyanuric acid) and 100 ml acetonitrile (10 ml for urine). The solution was cleaned with MCT solid-phase extraction column, and eluted once by 3 ml methanol and twice by 2.5 ml methanol (containing 5% ammonia water). The effluent was collected and dried by N2 flow at 40 °C, and then diluted to 2 mmol/L ammonium acetate containing 90% volume fraction acetonitrile. The completely dissolved solution was then filtered with 0.22 µm organic membrane; and the filtrate was detected by high performance liquid chromatography-tandem mass spectrometry and quantified with internal standards. The repeatability and sensitivity of the assay were evaluated. Then we detected the melamine and cyanuric acid residues in 501 water and 216 urine samples collected from several province and city. RESULTS: By the quantification of internal standard (15)N3-melamine and (15)N3-(13)C3-cyanuric acid, the melamine and cyanuric acid were linear in the range of 2.0-1000.0 µg/L with correlation coefficient of 0.9998 and 0.9997. The detection limits of the method were separately 0.4 ng/L (melamine) and 0.3 ng/L (cyanuric acid) for water, and 4.0 ng/L (melamine) and 3.0 ng/L (cyanuric acid) for urine. The average recovery rate was around 95.3%-100.1% with the relative standard deviation (RSD) was <4.02%. Out of the 501 water samples, melamine was detected out in 19.9% (100/501) and cyanuric acid was detected out in 5.2% (26/501). The content was around 0.03-5.00 g/L. Melamine or cyanuric acid was detected out in 24.5% of the urine samples (53/216), with the content around 0.01-1.00 g/L. CONCLUSION: The established method of solid phase extraction-hydrophilic interaction liquid chromatography-electrospray tandem mass spectrometry can satisfy the requirement for detection of melamine and cyanuric acid residues in all sorts of water and urine. Meanwhile, the two substances widely existed in water and Chinese population.

Melamine crystallization: physicochemical properties, interactions with other lithogenic salts and response to therapeutic agents.

PURPOSE: There were reports of children in the People's Republic of China being hospitalized with renal stones and/or failure by September 2008, which were caused by melamine and its co-contaminant cyanurate. We investigated the physicochemical behavior of melamine, its interaction with other endogenous urine factors and the response to therapeutic agents in the renal environment in vitro. MATERIALS AND METHODS: A mixed suspension, mixed product removal system was set up for crystallization studies of melamine in urine. Crystallization kinetic parameters, including the nucleation and growth rates, and suspension density, were determined according to crystal number and size, as measured by a Coulter particle counter. RESULTS: Melamine crystallized out from urine under normal urinary conditions (pH 5.0 to 6.5) but crystallization was strongly inhibited at pH 4.5 or lower. Melamine significantly enhanced calcium oxalate precipitation while uric acid significantly decreased melamine crystallization. Bacteria mimicking urinary tract infection promoted melamine crystallization. Clinical relevant drugs, such as citrate and bicarbonate, significantly decreased melamine crystallization. CONCLUSIONS: This implies that melamine crystallizes under normal urinary conditions and can interact with other lithogenic salts and pose a significant risk for other stones. Urinary tract infection promotes melamine crystallization. Citrate and bicarbonate therapy are effective prophylactic agents against melamine induced crystallization.

Pathway for the elimination of melamine in lactating dairy cows.

Melamine might be degraded into cyanuric acid and some other analogs by the rumen microorganism. Thus, the metabolism of melamine in ruminants may be different from that in monogastric animals. The objective of this study was to investigate the pathway for the elimination of melamine in lactating dairy cows. Four late-lactation dairy cows (body weight=524±17 kg, days in milk=265±14 d) fitted with ruminal cannulas were dosed with melamine (purity ≥99.5%) at 800 mg/d per cow that divided into 2 equal daily doses. The trial lasted for 20 d (13-d preliminary period, followed by a 7-d sample-collecting period). The method of liquid chromatography and tandem mass spectrometry was used to determine melamine and cyanuric acid contents simultaneously. Before the trial started, no melamine or cyanuric acid was detected in samples of total mixed ration, milk, plasma, urine, and feces. The melamine concentration in rumen fluid (Y, mg/L) decreased exponentially after the morning feeding (X, h) (Y=3.85591e(-X/9.25674)+1.35924, R(2)=0.99), but no cyanuric acid was detected. Plasma melamine concentration (0.296±0.014 mg/L) was relatively stable in the 3 different sampling times. The percentages of melamine excreted through milk, urine, and feces were 0.48±0.06, 44.07±10.79 and 10.98±3.88%, respectively. It could be inferred that 44.47±7.98% of ingested melamine was degraded in the rumen, because cyanuric acid was detected in plasma, urine, and feces on the condition that no melamine was contained in the total mixed ration fed to the dairy cows. The results of the present study implied that the elimination pathway of melamine in lactating dairy cows was different from that in monogastric animals. A high percentage of melamine was degraded into cyanuric acid gradually by rumen microorganisms. Most ingested melamine was excreted in urine and feces, which are the main elimination pathways for melamine in lactating dairy cows.

Flow-injection chemiluminescence determination of melamine in urine and plasma.

A novel flow-injection chemiluminescence method for the determination of melamine in urine and plasma was developed. It was found that melamine can remarkably enhance chemiluminescence emission from the luminol-K(3) Fe(CN)(6) system in an alkaline medium. Under the optimum conditions, chemiluminescence intensity had a good linear relationship with the concentration of melamine in the range 9.0 × 10(-9) -7.0 × 10(-6) g/mL, with a correlation coefficient of 0.9992. The detection limit (3σ) was 3.5 ng/mL. The method has been applied to determine the concentration of melamine in samples using liquid-liquid extraction. Average recoveries of melamine were 102.6% in urine samples and 95.1% in plasma samples. The method provided a reproducible and stable approach for the sensitive detection of melamine in urine and plasma samples.

[Identification of biomarkers of short- and medium-term exposure in urine and hair of subjects exposed to terbuthylazine]. / Identificazione di indici biologici di esposizione a breve e medio termine nelle urine e nei capelli di soggetti esposti a terbutilazina.

Terbuthylazine (TBA) is a herbicide widely used for weed control in corn crop. In mammals it is completely metabolized and excreted in urine, mostly as desetilterbutilazina (DET). This work aims to evaluate the use of urine and hair as matrices for monitoring short- and medium-term exposure to TBA. Levels of TBA and DET have been evaluated in hair and urine samples of 12 exposed farmers, 14 rural residents, 17 urban residents. In hair TBA was quantified in all samples of farmers and rural residents, but not of urban residents. In urine DET was detected in post-application samples of farmers but not in rural and urban residents. These results suggest that TBA in hair can be used as an index of cumulative exposure to TBA, while DET in the urine can be used as an index of short-term exposure in farmers.