Roberto Fanelli

Presence of therapeutic drugs in the environment

Therapeutic drugs can contaminate the environment because of metabolic excretion, improper disposal, or industrial waste. To assess the extent of this contamination, we listed drugs thought to be putative priority pollutants according to selected criteria, and measured them in Lombardy, Italy. Most drugs were measurable in drinking or river waters and sediments, suggesting that pharmaceutical products are widespread contaminants, with possible implications for human health and the environment.

Cocaine in surface waters: a new evidence-based tool to monitor community drug abuse

BackgroundCocaine use seems to be increasing in some urban areas worldwide, but it is not straightforward to determine the real extent of this phenomenon. Trends in drug abuse are currently estimated indirectly, mainly by large-scale social, medical, and crime statistics that may be biased or too generic. We thus tested a more direct approach based on field evidence of cocaine use by the general population.MethodsCocaine and its main urinary metabolite (benzoylecgonine, BE) were measured by mass spectrometry in water samples collected from the River Po and urban waste water treatment plants of medium-size Italian cities. Drug concentration, water flow rate, and population at each site were used to estimate local cocaine consumption.ResultsWe showed that cocaine and BE are present, and measurable, in surface waters of populated areas. The largest Italian river, the Po, with a five-million people catchment basin, steadily carried the equivalent of about 4 kg cocaine per day. This would imply an average daily use of at least 27 ± 5 doses (100 mg each) for every 1000 young adults, an estimate that greatly exceeds official national figures. Data from waste water treatment plants serving medium-size Italian cities were consistent with this figure.ConclusionThis paper shows for the first time that an illicit drug, cocaine, is present in the aquatic environment, namely untreated urban waste water and a major river. We used environmental cocaine levels for estimating collective consumption of the drug, an approach with the unique potential ability to monitor local drug abuse trends in real time, while preserving the anonymity of individuals. The method tested here – in principle extendable to other drugs of abuse – might be further refined to become a standardized, objective tool for monitoring drug abuse.

Estimating community drug abuse by wastewater analysis.

Background The social and medical problems of drug abuse are a matter of increasing global concern. To tackle drug abuse in changing scenarios, international drug agencies need fresh methods to monitor trends and patterns of illicit drug consumption. Objective We tested a sewage epidemiology approach, using levels of excreted drug residues in wastewater, to monitor collective use of the major drugs of abuse in near real time. Methods Selected drug target residues derived from use of cocaine, opiates, cannabis, and amphetamines were measured by mass spectrometry in wastewater collected at major sewage treatment plants in Milan (Italy), Lugano (Switzerland), and London (United Kingdom). The amounts of drug residues conveyed to the treatment plants, reflecting the amounts collectively excreted with urine, were used to estimate consumption of the active parent drugs. Results Reproducible and characteristic profiles of illicit drug use were obtained in the three cities, thus for the first time quickly revealing changes in local consumption (e.g., cocaine consumption rose significantly on weekends in Milan). Profiles of local drug consumption based on waste-water measurements are in line with national annual prevalence estimates. Conclusions Patterns and trends of drug abuse in local communities can be promptly monitored by this tool, a convenient new complement to more complex, lengthy survey methods. In principle, searching the sewage for excreted compounds relevant to public health issues appears to have the potential to become a convenient source of real-time epidemiologic information.

Source, occurrence and fate of antibiotics in the Italian aquatic environment

Aim of this study was to provide an up-to-date assessment of the antibiotics contaminating the aqueous environment in Italy, for a better understanding of risks for the ecosystem and human health. Antibiotics were first listed in order of their theoretical environmental loads, then were measured in wastewater of some sewage treatment plants (STPs) and in rivers in Italy. Macrolides, particularly clarithromycin and spiramycin, and quinolones, particularly ciprofloxacin and L-floxacin/ofloxacin, were the most abundant antibiotics in untreated wastewater. Several of them were not removed in STPs and still remained in the treated wastewater, and a total estimate of 7-14 tons of active principles were discharged annually into the aqueous environment in Italy through this route. Results of the analysis of rivers in northern Italy agreed with these figures, with an average load of 5 kg/day, or about 1.8 tons/year, of antibiotics flowing in the River Po, at sampling sites covering a basin comprising about one-fifth of the Italian population. In conclusion, antibiotics, particularly macrolides and quinolones, are widespread environmental contaminants, and urban STPs are confirmed a major source of the contamination.

Mass spectrometric analysis of illicit drugs in wastewater and surface water.

Residues of illicit drugs have been recently found in urban wastewater and surface water. Their levels reflect the amount of drugs collectively excreted by consumers and can therefore be used to estimate drug abuse. An overview of the most widely used illicit drugs and of the analytical methods used for their detection in wastewater and surface water is presented here. Solid-phase extraction and high performance liquid chromatography-tandem mass spectrometry are the techniques that have been used for these investigations. Instrumental conditions and fragmentation patterns of illicit drugs and their metabolites are described.

Changes in illicit drug consumption patterns in 2009 detected by wastewater analysis

BACKGROUNDnWastewater analysis can provide estimates of illicit drug (ID) consumption in local communities.nnnMETHODSnWe used repeated raw wastewater analysis in urban wastewater treatment plants to estimate loads of cocaine, heroin, methamphetamine, and cannabis consumed daily by the inhabitants of two cities in Northern Italy, Milan and Como, from 2005 to 2009.nnnRESULTSnDaily cocaine loads did not change in Milan from 2005 to 2008 but fell 45% in 2009 (ANOVA, p<0.001, followed by Tukey-Kramer HSD test [2009 vs. others], p<0.05), and there was a similar drop in Como (41%, p<0.0001, t-test). Heroin also fell from 2008 to 2009 in Milan (66%, ANOVA, p<0.001, followed by Tukey-Kramer [2009 vs. others], p<0.05) and Como (26%, p=0.017, t-test). However, methamphetamine, which had risen in Milan from 2005 to 2008, rose further in 2009 (Kruskal-Wallis test, p<0.001, followed by Steel-Dwass [2009 or 2008 vs. previous], p<0.05), and cannabis, which was falling from 2005 to March 2009, rose again in September 2009 (40%, p=0.027, t-test).nnnCONCLUSIONSnResults suggest a trend toward a decrease in consumption of costly ID, such as cocaine and heroin. This might be due to a reduction in the number of consumers and/or to a change in their behaviour since there was also an increase in the consumption of less expensive ID. This itself might reflect a drop in consumers money supply, caused by the economic crisis. Wastewater analysis was useful to estimate ID consumption levels in local communities in real time and promptly identify changes in trends.

Assessment of the dietary exposure to non-dioxin-like PCBs of the Italian general population

The dietary intake of non-dioxin-like polychlorinated biphenyls (NDL-PCBs) has been estimated using the sum of six indicator PCBs (Sigma(6)(PCBs)) in the Italian general population. Data from a national food consumption survey were combined with the mean concentration values of the individual six indicator PCBs (IUPAC Nos. 28, 52, 101, 138, 153, and 180) in foodstuffs available on the European market. Mean concentrations were estimated from the raw data set provided by the European Commission (DG SANCO). The purpose was to describe the distribution of NDL-PCB dietary intake in the Italian population, and to investigate to what extent the variability in dietary habits may cause higher exposures to the aforesaid contaminants. Results indicated a mean dietary intake of Sigma(6)(PCBs) corresponding to 24.6, 16.1, and 10.9 ng kg-bw(-1) day(-1) for toddlers (0.5-6 years old, excluding breastfeeding), children (7-12 year old), and adults (13-94 years old), respectively. Fish and fishery products and milk and dairy products were the major contributors to the total dietary intake. The highest exposures due to variation in dietary habits were in general two-three times higher than the corresponding mean values and they were generally due to a higher fish consumption rate. The NDL-PCB dietary intake decreased with age until about 10-12 years; afterwards it appeared to remain constant. The tolerable daily intake (TDI) has not been established for these contaminants; however, action and maximum allowed levels in feeding stuffs and food recently established by the European Commission for dioxin-like PCBs could also protect consumers from exposure to NDL-PCBs.

Identification of cocaine and its metabolites in urban wastewater and comparison with the human excretion profile in urine

The most relevant human urinary metabolites of cocaine (nine metabolites) were measured in urban wastewater in Italy and USA. A novel analytical method based on liquid chromatography tandem mass spectrometry allowed the identification of ecgonine, ecgonine methyl ester and the pyrolytic derivatives of cocaine in untreated wastewater. The aim of this study was to verify whether the pattern of cocaine metabolites in wastewater reflected the human excretion profile in urine. The performance of the method was good, with recoveries higher than 60% and limits of quantifications in the low ng/L range. The stability in untreated wastewater was assessed for all metabolites and the best storage condition resulted freezing samples immediately after collection and keep them frozen until analysis. All the selected compounds were measured in wastewater at concentrations up to 1.5xa0μg/L and their weekly loads were calculated during a five weeks monitoring campaign in Milan (Italy). The profiles of cocaine metabolites in wastewater matched with those in human urine reported in the literature, suggesting that measures in wastewater reflect the real human excretion and that wastewater analysis is suitable for assessing drug consumption. Benzoylecgonine was confirmed as the best target for estimating cocaine use by wastewater analysis, while cocaine itself should not be considered because its amount in wastewater is affected by other environmental sources such as transport, handling and consumption. Results suggested that the measurement of other metabolites in combination with benzoylecgonine might reflect 60% of an administered dose of cocaine providing also information on different patterns of use.

Illicit Drugs in the Environment: Occurrence, Analysis, and Fate Using Mass Spectrometry

PREFACE. CONTRIBUTORS. I INTRODUCTION. 1 ILLICIT DRUGS AND THE ENVIRONMENT (Christian G. Daughton). II THE PHYSIOLOGY OF ILLICIT DRUGS. 2 METABOLISM AND EXCRETION OF ILLICIT DRUGS IN HUMANS (Manuela Melis, Sara Castiglioni, and Ettore Zuccato). III MASS SPECTROMETRY IN ILLICIT DRUGS DETECTION AND MEASUREMENT CURRENT AND NOVEL ENVIRONMENTAL APPLICATIONS. 3 ANALYTICAL METHODS FOR THE DETECTION OF ILLICIT DRUGS IN WASTEWATERS AND SURFACE WATERS (Renzo Bagnati and Enrico Davoli). 4 WIDE-SCOPE SCREENING OF ILLICIT DRUGS IN URBAN WASTEWATER BY UHPLC-QTOF MS (Felix Hernadez, Juan V. Sancho, and Lubertus Bijlsma). 5 DETERMINATION OF ILLICIT DRUGS IN THE WATER CYCLE BY LC ORBITRAP MS (Pim de Voogt, Erik Emke, Rick Helmus, Pavlos Panteliadis, and Jan A. van Leerdam). IVA MASS SPECTROMETRIC ANALYSIS OF ILLICIT DRUGS IN THE ENVIRONMENT: OCCURRENCE AND FATE IN WASTEWATER AND SURFACE WATER. 6 OCCURRENCE OF ILLICIT DRUGS IN WASTEWATER IN SPAIN (Cristina Postigo, Miren Lopez de Alda, and Damia Barcelo). 7 OCCURRENCE OF ILLICIT DRUGS IN WASTEWATER AND SURFACE WATER IN ITALY (Sara Castiglioni and Ettore Zuccato). 8 OCCURRENCE OF ILLICIT DRUGS IN SURFACE WATER AND WASTEWATER IN THE UK (Barbara Kasprzyk-Hordern). 9 ON THE FRONTIER: ANALYTICAL CHEMISTRY AND THE OCCURRENCE OF ILLICIT DRUGS INTO SURFACE WATERS IN THE UNITED STATES (Tammy Jones-Lepp, David Alvarez, and Bommanna Loganathan). 10 MONITORING NONPRESCRIPTION DRUGS IN SURFACE WATER IN NEBRASKA (USA) (Shannon Bartelt-Hunt, and Daniel D. Snow). IVB MASS SPECTROMETRIC ANALYSIS OF ILLICIT DRUGS IN THE ENVIRONMENT: ILLICIT DRUGS IN DRINKING WATER. 11 PRESENCE AND REMOVAL OF ILLICIT DRUGS IN CONVENTIONAL DRINKING WATER TREATMENT PLANTS (Maria Huerta-Fontela, Maria Teresa Galceran, and Francesc Ventura). 12 ANALYSIS OF ILLICIT DRUGS IN WATER USING DIRECT-INJECTION LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY (Rebecca A. Trenholm and Shane A. Snyder). IVC MASS SPECTROMETRIC ANALYSIS OF ILLICIT DRUGS IN THE ENVIRONMENT: PRESENCE IN AIR AND SUSPENDED PARTICULATE MATTER. 13 PSYCHOTROPIC SUBSTANCES IN URBAN AIRBORNE PARTICULATES (Angelo Cecinato and Catia Balducci). V APPLICATIONS OF ILLICIT DRUG ANALYSIS IN THE ENVIRONMENT. 14 ILLICIT DRUGS IN THE ENVIRONMENT: IMPLICATION FOR ECOTOXICOLOGY (Guido Domingo, Kristin Schirmer, Marcella Bracale, and Francesco Pomati). 15 DRUG ADDICTION POTENTIAL OF A NEW APPROACH TO MONITORING DRUG CONSUMPTION (Norbert Frost). 16 ASSESSING ILLICIT DRUG CONSUMPTION BY WASTEWATER ANALYSIS: HISTORY, POTENTIAL, AND LIMITATION OF A NOVEL APPROACH (Ettore Zuccato and Sara Castiglioni). 17 COCAINE AND METABOLITES IN WASTEWATER AS A TOOL TO CALCULATE LOCAL AND NATIONAL COCAINE CONSUMPTION PREVALENCE IN BELGIUM (Alexander L.N. van Nuijs, Lieven Bervoets, Philippe G. Jorens, Ronny Blust, Hugo Neels, and Adrian Covaci). 18 MEASUREMENT OF ILLICIT DRUG CONSUMPTION IN SMALL POPULATIONS: PROGNOSIS FOR NONINVASIVE DRUG TESTING OF STUDENT POPULATIONS (Deepika Panawennage, Sara Castiglioni, Ettore Zuccato, Enrico Davoli, and M. Paul Chiarelli). VI CONCLUSIONS. 19 CONCLUSIONS AND FUTURE PERSPECTIVES (Roberto Fanelli). INDEX.

Bone mineral density changes in relation to environmental PCB exposure

Background Bone toxicity has been linked to organochlorine exposure following a few notable poisoning incidents, but epidemiologic studies in populations with environmental organochlorine exposure have yielded inconsistent results. Objectives The aim of this study was to investigate whether organochlorine exposure was associated with bone mineral density (BMD) in a population 60–81 years of age (154 males, 167 females) living near the Baltic coast, close to a river contaminated by polychlorinated biphenyls (PCBs). Methods We measured forearm BMD in participants using dual energy X-ray absorptiometry; and we assessed low BMD using age- and sex-standardized Z-scores. We analyzed blood samples for five dioxin-like PCBs, the three most abundant non-dioxin-like PCBs, and p,p′-dichloro-phenyldichloroethylene (p,p′-DDE). Results In males, dioxin-like chlorobiphenyl (CB)-118 was negatively associated with BMD; the odds ratio for low BMD (Z-score less than −1) was 1.06 (95% confidence interval, 1.01–1.12) per 10 pg/mL CB-118. The sum of the three most abundant non-dioxin-like PCBs was positively associated with BMD, but not with a decreased risk of low BMD. In females, CB-118 was positively associated with BMD, but this congener did not influence the risk of low BMD in women. Conclusions Environmental organochlorine exposures experienced by this population sample since the 1930s in Sweden may have been sufficient to result in sex-specific changes in BMD.