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CORK Bibliography: Contaminants and Adulterants

69 citations. January 2009 to present

Prepared: March 2012

Agrawal SS; Rajagopal K. Nicotine contents in various toothpowders (dant manjans): Measurement and safety evaluation. Food and Chemical Toxicology 47(3): 511-524, 2009. (24 refs.)

The use of tobacco products as dentrifice is prevalent in various parts of India. Among them toothpowder (dant manjan) is very common. These nicotine containing toothpastes/tooth powders are health hazards and is also habit forming. Health experts of India rightly banned use of nicotine containing toothpowder as early as 1992 by making proper legislation. We just made an attempt to verify whether the manufacturers complying the legislation or not. Eight leading brands of toothpowders were analyzed qualitatively by gas chromatography-mass spectrum detector and also quantitatively by gas chromatography-nitrogen phosphorus detector. Our results indicated four brands were found to contain nicotine in the range of 2.53 mu g/g to 11.50 mg/g of toothpowder. This finding further confirms that addition of nicotine in dentifrice violates the regulatory norms. Regulatory authorities should give more attention to ensure that all toothpowders are free from nicotine which is also a statutory requirement.

Aitken CK; Fry TRL; Farrell L; Pellegrini B. Smokers of illicit tobacco report significantly worse health than other smokers. Nicotine & Tobacco Research 11(8): 996-1001, 2009. (34 refs.)

Introduction: The aim of this study was to ascertain whether the health of past and current smokers of illicit tobacco (chop-chop) differs from that of smokers of licit tobacco. Methods: The design was a telephone survey, stratified by state, using computer aided telephone interviewing, with households selected by random digit dialing from the telephone white pages. Setting was all Australian states and territories, 1,621 regular tobacco smokers aged 18+ years. Measures were social and personal characteristics of tobacco smokers, smoking histories and patterns, and health status (SF-8 and disability weights). Binary logistic regression was used to identify variables associated with current and lifetime chop-chop use. Results: Compared with licit-only tobacco smokers, current users of chop-chop had significantly greater odds of beginning smoking aged <16 years (odds ratio [OR] 1.65, 95% CI = 1.09-2.50), of reporting below-average social functioning (OR 1.61, 95% CI = 1.06-2.44), and of a measurable disability (OR 1.95, 95% CI = 1.08-3.51). Lifetime chop-chop users were relatively likely to be less than 45 years of age (OR 1.82, 95% CI = 1.38 2.39), report below-average mental health (OR 1.61, 95% CI = 1.22-2.13) and above-average bodily pain (OR 1.40, 95% CI = 1.06-1.85), smoke more than 120 cigarettes/week (OR 1.39, 95% CI = 1.06-1.83), and to have begun smoking aged < 16 years (OR 1.33, 95% CI = 1.01-1.75). Discussion: Current and lifetime users of chop-chop report significantly worse health than smokers of licit tobacco. Investigation of how to communicate this finding to current and potential chop-chop smokers is warranted.

Beaumont G. Anthrax in a Scottish intravenous drug user. Journal of Forensic and Legal Medicine 17(8): 443-445, 2010. (12 refs.)

Anthrax, caused by Bacillus anthracis, is an uncommon disease in the United Kingdom. In December 2009, the first recorded case of injectable anthrax in the UK was diagnosed in Glasgow, Scotland. This case report describes the disease presentation in a detained person in police custody in Dumfries, South West Scotland. The case highlights to forensic physicians the clinical features of anthrax, particularly in relation to intravenous drug misuse and the importance of early recognition. Anthrax and its presence in the UK is discussed.

Been F; Roggo Y; Degardin K; Esseiva P; Margot P. Profiling of counterfeit medicines by vibrational spectroscopy. Forensic Science International 211(1-3): 83-100, 2011. (35 refs.)

Counterfeit pharmaceutical products have become a widespread problem in the last decade. Various analytical techniques have been applied to discriminate between genuine and counterfeit products. Among these, near-infrared (NIR) and Raman spectroscopy provided promising results. The present study offers a methodology allowing to provide more valuable information for organisations engaged in the fight against counterfeiting of medicines. A database was established by analyzing counterfeits of a particular pharmaceutical product using Near-infrared (NIR) and Raman spectroscopy. Unsupervised chemometric techniques (i.e. principal component analysis - PCA and hierarchical cluster analysis - HCA) were implemented to identify the classes within the datasets. Gas Chromatography coupled to Mass Spectrometry (GC-MS) and Fourier Transform Infrared Spectroscopy (FT-IR) were used to determine the number of different chemical profiles within the counterfeits. A comparison with the classes established by NIR and Raman spectroscopy allowed to evaluate the discriminating power provided by these techniques. Supervised classifiers (i.e. k-Nearest Neighbors, Partial Least Squares Discriminant Analysis, Probabilistic Neural Networks and Counterpropagation Artificial Neural Networks) were applied on the acquired NIR and Raman spectra and the results were compared to the ones provided by the unsupervised classifiers. The retained strategy for routine applications, founded on the classes identified by NIR and Raman spectroscopy, uses a classification algorithm based on distance measures and Receiver Operating Characteristics (ROC) curves. The model is able to compare the spectrum of a new counterfeit with that of previously analyzed products and to determine if a new specimen belongs to one of the existing classes, consequently allowing to establish a link with other counterfeits of the database.

Brunt TM; Rigter S; Hoek J; Vogels N; van Dijk P; Niesink RJM. An analysis of cocaine powder in the Netherlands: Content and health hazards due to adulterants. Addiction 104(5): 798-805, 2009. (38 refs.)

Aims: To report on trends in the content and adulterants present in street cocaine ( powder) in the Netherlands and to describe the associated health hazards. Design and participants Drug consumers handed in samples of cocaine powder from 1999 to 2007 for analysis. Reports were compiled of users' experiences with the samples received. Measurements and analysis Linear regression analysis was used to assess the trend in adulterated cocaine powder across the study period, and comparison of reported adverse effects of adulterated with those of unadulterated cocaine by Fisher's exact test. Findings There has been a statistically significant upward trend in the occurrence of adulterated cocaine powder over the years. Adulterated cocaine was associated more frequently with reported adverse effects than unadulterated cocaine. Phenacetin, hydroxyzine and diltiazem appeared to be three adulterants contributing to these adverse effects. Conclusions An increase in adulterants was detected in the analysed cocaine powder between 1999 and 2007. This increase is associated with relatively more adverse effects with cocaine use. The cardiac and hallucinatory effects that were reported more frequently are not understood clearly. Adverse effects are likely to be due to several factors, including interactions of adulterants with cocaine and the route of administration.

Buchanan JA; Lavonas EJ. Agranulocytosis and other consequences due to use of illicit cocaine contaminated with levamisole. (review). Current Opinion in Hematology 19(1): 27-31, 2012. (44 refs.)

Purpose of review: Most of the illicit cocaine consumed in the United States and elsewhere is contaminated with levamisole, a veterinary medication. Agranulocytosis caused by levamisole exposure through cocaine abuse was first described in 2009. Since then, levamisole has also been shown and is known to cause vascular and neurologic complications. In this review, we provide an overview of the medical consequences of exposure to levamisole from adulterated cocaine. Recent findings: Within the past year, several new case series have deepened our understanding of the levamisole-agranulocytosis vasculopathy syndrome. The common nature of this exposure has been delineated, cocaine contaminated with levamisole. Significant controversy surrounds the role of granulocyte colony stimulating factor (GCSF) in levamisole-associated agranulocytosis. Summary: More than three fourths of cocaine users in the United States are exposed to levamisole; a significant minority of these individuals will develop autoimmune-mediated neutropenia, cutaneous vascular complications, and/or leukoencephalopathy. Levamisole exposure should be considered in the differential diagnosis of patients who present with these conditions in the setting of cocaine abuse. Neutropenia appears to resolve rapidly with cessation of exposure, so that GCSF therapy and a work-up for other causes may not be needed in all patients.

Buxton JA; Sebastian R; Clearsky L; Angus N; Shah L; Lem M et al. Chasing the dragon: Characterizing cases of leukoencephalopathy associated with heroin inhalation in British Columbia. Harm Reduction Journal 8: article 3, 2011. (34 refs.)

An association between leukoencephalopathy, a disease of the white matter of the brain, and smoking heroin is well recognized. This paper describes 27 cases of leukoencephalopathy identified in two cities in British Columbia, Canada 2001-2006; the largest number of geographically and temporally defined reported cases in North America. Twenty cases of leukoencephalopathy were identified in and around Vancouver with onset dates December 2001 to July 2003; seven further cases were identified in Victoria September 2005-August 2006. Twenty (74%) of all cases were male, two couples were reported and eleven cases (55%) had Asian ethnicity. One case reported smoking heroin on a single occasion and developed mild symptoms; all other cases were hospitalized. Thirteen (48%) cases died; all had smoked heroin for a minimum of 3 years. Testing of one available heroin sample identified no substance other than common cutting agents. Although a specific etiology was not identified our study supports the theory of an intermittent exposure to a toxic agent added to the heroin or a combustion by-product. It also suggests a dose response effect rather than genetic predisposition. Collaboration with public health, health professionals, law enforcement and persons who use illegal drugs, will facilitate the early identification of cases to enable timely and complete follow-up including obtaining samples. Testing of implicated heroin samples may allow identification of the contaminant and therefore prevent further cases. It is therefore important to ensure key stakeholders are aware of our findings.

Cox LA. Could removing arsenic from tobacco smoke significantly reduce smoker risks of lung cancer? Risk Analysis 29(1): 3-17, 2009. (61 refs.)

If a specific biological mechanism could be determined by which a carcinogen increases lung cancer risk, how might this knowledge be used to improve risk assessment ? To explore this issue, we assume (perhaps incorrectly) that arsenic in cigarette smoke increases lung cancer risk by hypermethylating the promoter region of gene p16INK4a, leading to a more rapid entry of altered (initiated) cells into a clonal expansion phase. The potential impact on lung cancer of removing arsenic is then quantified using a three-stage version of a multistage clonal expansion (MSCE) model. This refines the usual two-stage clonal expansion (TSCE) model of carcinogenesis by resolving its intermediate or "initiated" cell compartment into two subcompartments, representing experimentally observed "patch" and "field" cells. This refinement allows p16 methylation effects to be represented as speeding transitions of cells from the patch state to the clonally expanding field state. Given these assumptions, removing arsenic might greatly reduce the number of nonsmall cell lung cancer cells (NSCLCs) produced in smokers, by up to two-thirds, depending on the fraction (between 0 and 1) of the smoking-induced increase in the patch-to-field transition rate prevented if arsenic were removed. At present, this fraction is unknown (and could be as low as zero), but the possibility that it could be high (close to 1) cannot be ruled out without further data.

Cunningham JK; Liu LM; Callaghan R. Impact of US and Canadian precursor regulation on methamphetamine purity in the United States. Addiction 104(3): 441-453, 2009. (62 refs.)

Reducing drug purity is a major, but largely unstudied, goal of drug suppression. This study examines whether US methamphetamine purity was impacted by the suppression policy of US and Canadian precursor chemical regulation. Autoregressive integrated moving average (ARIMA)-intervention time-series analysis. Continental United States and Hawaii (1985-May 2005). US federal regulations targeting precursors, ephedrine and pseudoephedrine, in forms used by large-scale producers were implemented in November 1989, August 1995 and October 1997. US regulations targeting precursors in forms used by small-scale producers (e.g. over-the-counter medications) were implemented in October 1996 and October 2001. Canada implemented federal precursor regulations in January 2003 and July 2003 and an essential chemical (e.g. acetone) regulation in January 2004. Monthly median methamphetamine purity series. US regulations targeting large-scale producers were associated with purity declines of 16-67 points; those targeting small-scale producers had little or no impact. Canada's precursor regulations were associated with purity increases of 13-15 points, while its essential chemical regulation was associated with a 13-point decrease. Hawaii's purity was consistently high, and appeared to vary little with the 1990s/2000s regulations. US precursor regulations targeting large-scale producers were associated with substantial decreases in continental US methamphetamine purity, while regulations targeting over-the-counter medications had little or no impact. Canada's essential chemical regulation was also associated with a decrease in continental US purity. However, Canada's precursor regulations were associated with purity increases: these regulations may have impacted primarily producers of lower-quality methamphetamine, leaving higher-purity methamphetamine on the market by default. Hawaii's well-known preference for 'ice' (high-purity methamphetamine) may have helped to constrain purity there to a high, attenuated range, possibly limiting its sensitivity to precursor regulation.

Davies S; Wood DM; Smith G; Button J; Ramsey J; Archer R et al. Purchasing 'legal highs' on the Internet-is there consistency in what you get? QJM-An International Journal of Medicine 103(7): 489-493, 2010. (15 refs.)

Background: The supply of recreational drugs has changed and users increasingly buy 'legal highs' over the Internet. Use of these is common and there is a potential for significant toxicity associated with their use. Aim: To determine the content of legal highs available for purchase in the UK and whether the content of these remains consistent. Methods: Twenty-six legal highs were purchased monthly from five different Internet sites over 6 months. These were analysed to determine the drugs in the products and whether there were any changes in their content over this time period. Results: All products were supplied initially, but there was a decline in supply of products month by month. The following drug classes were detected: piperazines, cathinones, caffeine/ephedrine or products in which no psychoactive drugs were detected. Of the products supplied on more than one occasion, 15 (75%) contained the same compounds on each occasion. In three products there was a change in the piperazine detected, with 1-benzylpiperazine being substituted for 1-methyl-4-benzylpiperazine or vice versa. In two other products there was a cathinone [4-fluorophenylpiperazine (pFPP) or 3-fluromethcathinone (3FMC)] detected in products purchased in Month 1 that was not present in the products purchased in subsequent months. Conclusions: Whilst there was no variation in the composition of most legal highs supplied over 6 month, there was significant variation in the piperazine or cathinone content of one quarter of the products. This variation could be of clinical significance as the cathinone and piperazine products can be associated with significant toxicity.

de la Hera I; Sanz V; Cullen D; Chico R; Petiti G; Villar M et al. Necrosis of ears after use of cocaine probably adulterated with levamisole. Dermatology 223(1): 25-28, 2011. (19 refs.)

Background/Aims: Levamisole is an anthelminthic drug with immunomodulatory properties that has been found to be an adulterant of cocaine in the last 2 years. It was present at least in 70% of tainted cocaine in the USA in 2009. Methods: We present the case of a 40-year-old patient with a history of weekend cocaine use who consulted for bilateral necrotic lesions in the ears that had appeared 3 days after the last use. Results: Levamisole causes a typical clinical picture characterized by bilateral necrosis of the ears, positive perinuclear antineutrophil cytoplasmic antibodies and laboratory findings of antiphospholipid syndrome, such as anticardiolipin antibodies and/or lupus anticoagulant. Conclusion: Dermatologists should be aware of this new entity, which is likely to be more and more frequent due to the increasing use of cocaine. Here we describe a clinical case that is likely to be secondary to levamisole-tainted cocaine and review the literature.

Dettmeyer RB; Verhoff MA; Bruckel B; Walter D. Widespread pulmonary granulomatosis following long time intravenous drug abuse-A case report. Forensic Science International 19(1-3): E27-E30, 2010. (22 refs.)

Foreign body granulomas in the lungs following acute singular or long time intravenous drug abuse are frequent findings during microscopic investigation of the lungs. Most cases present single granulomas. Cases with multiple foreign body granulomas, already palpable during autopsy and leading to pulmonary granulomatosis with multiple granulomas are less frequent. We report the case of a 32-year old man, dying suddenly and unexpectedly after a well-known history of drug abuse for more than a decade. The granulomas are caused by foreign particle embolization immediately after intravenous injection of not only the drug itself but also of adulterants, e. g. cotton fibers, potato starch or microcrystalline cellulose. At the end, a reduction in the size of the pulmonary bed had occurred followed by pulmonary hypertension. For the first time, lung dust in such a case was characterised by energy dispersive X-ray (EDX).

Diep F. Cocaine's newest risks. (editorial). Scientific American 305(3): 30, 2011. (0 refs.)

A new drug contaminant is causing frightening outbreaks of blackened skin and low white blood cell counts. To the list of cocaine's many dangers, health officials have added at least one more: purpura, a rash caused by internal bleeding from small blood vessels. Two recent papers in major medical journals have documented cases of cocaine users showing up in emergency rooms with patches of blackened, dying skin on the ears, face, trunk or extremities. The condition causes scarring and sometimes requires reconstructive surgery. Noah Craft, a dermatologist at the HarborUCLA Medical Center who coauthored a paper on the condition published online by the Journal of the American Academy of Dermatology in June, says he now sees about one case per month: "It's become almost routine." The cause of the outbreak is a veterinary deworming medication that has become the most common ingredient used to dilute, or cut, cocaine coming into the U.S. from South America. The drug, called levamisole, was once approved for cancer treatment but was later pulled because of its side effects. Three quarters of the cocaine bricks seized by the U.S. Drug Enforcement Administration now contain levamisole. Equally worrying is another of its side effects: a sometimes fatal lowered count of white blood cells that are called neutrophils. Doctors suspect that both conditions are allergic reactions to the drug. In one disease, the body's immune system attacks the skin; in the other, it attacks the bone marrow.

Donike M. The detection of doping by means of chromatographic methods. Drug Testing and Analysis 3(1): 15-17, 2011. (14 refs.)

This article was first published in German in Der Sportarzt, 1966, 2, 81-84 as Der Dopingnachweis mit Hilfe chromatographischer Methoden. Translated and republished with permission. Doping has become an issue in elite sport and necessitates sensitive detection assays that enable the identification of organic compounds on a microscale level in urine. In agreement with modern toxicological methods, sports drug testing approaches can utilize paper, thin layer or gas chromatographic methods to reveal the presence of prohibited substances such as strychnine, pervitine, captagone, benzedrine etc. in doping control specimens. Basic principles of these strategies are summarized and considerations for future applications discussed.

Duterte M; Jacinto C; Sales P; Murphy S. What's in a label? Ecstasy sellers' perceptions of pill brands. Journal of Psychoactive Drugs 41(1): 27-37, 2009. (45 refs.)

This article presents selected findings from a qualitative study of Ecstasy sellers and their sales practices, knowledge of distribution networks, buyer-seller relationships, and self-reported drug use. In-depth interviews were conducted with 80 men and women who had sold five or more hits of Ecstasy five or more times in the six months prior to the interview. Study participants described their perceptions of the various types of Ecstasy they had distributed or used themselves. The participants had experience with a variety of Ecstasy labels, from the popular "Blue Dolphin" tablets to the powdered form called "Molly." We tracked pill brand mentions on Ecstasy-related websites to compare with interviewees' descriptions of Ecstasy brands. This study examines Ecstasy sellers' ideas about the role of brand names in Ecstasy markets and their relationship to their beliefs about different types of Ecstasy's purity and quality. We demonstrate that considering Ecstasy branding increases our understanding of buyer and seller relationships.

Elsayed RK; Glisson JK; Minor DS. Rhabdomyolysis associated with the use of a mislabeled "acai berry" dietary supplement. American Journal of the Medical Sciences 342(6): 535-538, 2011. (25 refs.)

Introduction: This case report describes a patient who developed rhabdomyolysis temporally associated with the use of a mislabeled acai berry dietary supplement. Methods and Results. The authors describe a 22-year-old man presenting with rhabdomyolysis approximately 2 weeks after starting a weight-loss dietary supplement. His medical history was significant only for hypertension treated with amlodipine. The diagnosis of rhabdomyolysis was confirmed (creatine kinase, 84,000 IU/L, positive urine myoglobin) with other potential causes ruled out. The signs and symptoms of the patient gradually resolved and he was discharged on hospital day 5. Assessment using the Naranjo Adverse Drug Reaction Probability Scale yielded a score of 3, indicating a possible relationship between the supplement and rhabdomyolysis. Although the product was labeled and promoted as containing acai berry and additional ingredients, there was no acai berry found on analysis. Conclusion: Clinicians should be aware that all dietary supplements may vary in uniformity and contain unknown contaminants.

Evrard I; Legleye S; Cadet-Tairou A. Composition, purity and perceived quality of street cocaine in France. International Journal of Drug Policy 21(5): 399-406, 2010. (52 refs.)

Background: There is little knowledge about the composition and cocaine content of street cocaine, nor about what users know about it. Method: 373 cocaine users were face to face interviewed between May and December 2006 about the last sample of cocaine they had consumed and residual amounts of the substances actually used were analysed using gas phase chromatography coupled to mass spectrometry (GC-MS). Users rated the perceived quality of their product ("good", "average", "poor"), its "estimated percentage of cocaine" and any cutting agents it contained. Price, quantity, place of purchase (street, dealer's premise, appointment), mode of administration (sniffing, injection, smoking) and the supposed nature of the sample (natural, synthetic, no distinction ever made) were also reported. Perceived quality was modelled using multivariate multinomial regression. Results: The median cocaine content was 22%. Altogether, 343 samples contained cocaine, among which 75% contained at least one adulterant. The most frequently occurring were phenacetin (54% of the samples), caffeine (17%), paracetamol (14%), diltiazem and lidocaine (11%). Users showed relatively poor discrimination concerning cocaine purity, and only 12% reported at least one of the detected adulterants. The major determinants of their perception of cocaine quality were: place of purchase, natural origin, price per gram, actual cocaine content and mode of administration. Conclusion: The composition of street cocaine is largely unknown to users. Users' perceptions of cocaine quality are based partly on false beliefs and certain administration modes. This may contribute to favouring very risky practices. The effects of adulterants on users' health should be investigated.

Friedman LS. Real-time surveillance of illicit drug overdoses using poison center data. Clinical Toxicology 47(6): 573-579, 2009. (29 refs.)

Background. In early 2006, government and media sources reported that crime syndicates were mixing fentanyl with heroin. This was followed by an increase in heroin overdoses and opiate-related deaths. The most recent fentanyl outbreak illustrated the need for identifying and establishing effective and responsive real-time surveillance tools to monitor drug overdoses in the United States. Objective. In this study, poison call center data from Illinois were evaluated to determine whether the data could have detected the outbreak that occurred in Illinois in early 2006 and whether it could be used for real-time surveillance. Methods. For this analysis, a two-step approach was used to analyze potential heroin-related calls. First, the data were analyzed retrospectively to identify whether any significant temporal shifts occurred, then a prospective analysis was conducted to simulate real-time surveillance. Results. Between 2002 and 2007, there were a total of 1,565 potential heroin-related calls, and the calls increased by 63.6% in 2006 compared to 2005. In the prospective analysis, the principal model would have identified the outbreak in March 2006. Conclusions. If there had been a real-time surveillance program using poison center data, the outbreak would have been identified I month before the initial postmortem reports to the Centers for Disease Control and Prevention at the end of April 2006. Poison center data provide the potential for an earlier warning system than postmortem data sources, because the reports are usually made within hours of the exposure. Poison center data can be effectively used to monitor heroin-related exposures.

Fucci N. Maybe a new killer in illicit cocaine. Forensic Science International 209(1-3): E23-E25, 2011. (10 refs.)

This is the study of the author that refers about a case of a 46 years old man found dead inside his house, the death was related to cocaine intake. The police found the corpse laying in his bed with a sheet of newspaper rolled up and a few plastic coverings containing trace of cocaine on the desk. Toxicologyogical analysis was performed and drug levels measured by means of gas chromatography/mass spectrometry technology. Based on the autopsy findings and toxicological results the cause of death was related to an acute intoxication due to cocaine "overdose". In addition to the presence of cocaine and smaller alkaloids, in the sheet made of newspaper rolled up and eluted of the nasal mucosas has been highlighted the presence of 2,6-disopropylnaphtalene (2,6-DIPN), a fungicidal pesticide very health hazard for human. A very easy, simple and selective gas chromatography mass spectrometry method was employed for the detection of 2,6-DIPN in the cocaine powder.

Godwin WS; Subha VR; Feroz KM. Po-210 radiation dose due to cigarette smoking. Current Science 98(5): 681-686, 2010. (34 refs.)

The level of Po-210 in eight brands of cigarettes and four brands of bidis popular in and around Nagercoil town was determined to evaluate the annual effective dose. The Po-210 activity in a full cigarette ranged from 32.8 +/- 3.6 to 68.4 +/- 5.9 mBq and from 34.3 +/- 3.5 to 62.9 +/- 5.8 mBq in a bidi. In tobacco, the highest Po-210 content was recorded in the brand C4 (23.0 +/- 1.2 mBq) whereas for bidis it was the highest in the brand B2 (21.1 +/- 1.1 mBq). The activity in mainstream varied from 15.2 +/- 0.75 to 36.8 +/- 2.1 mBq in a cigarette and from 20.7 +/- 3.1 to 39.8 +/- 4.0 mBq in a bidi. With regard to Po-210 activity concentration, not much specificity was noted with respect to the tobacco brand. The data showed a relatively wide range of activity concentration of Po-210 in the different cigarette/bidi brands and even within the same brand. The bidis showed a higher activity when compared to cigarettes. The popular brands concentrated more activity than the fine brands. Smokers who smoke one pack (10 cigarettes/bidis) per day may inhale about 100-300 mBq d(-1) (0.1-0.3 Bq d(-1)) of Po-210. In this study, radiation dose values in the range of 153.5-372.9 mu Sv Y-1 from cigarettes and from 209.2 to 402.7 mu Sv Y-1 from bidis was estimated for the whole body.

Graf J; Lynch K; Yeh CL; Tarter L; Richman N; Nguyen T et al. Purpura, cutaneous necrosis, and antineutrophil cytoplasmic antibodies associated with levamisole-adulterated cocaine. Arthritis and Rheumatism 63(12): 3998-4001, 2011. (17 refs.)

Objective: To describe the clinical and serologic abnormalities in 6 patients who presented with retiform purpura and extensive cutaneous necrosis after exposure to levamisole-adulterated cocaine. Methods. All patients were evaluated at San Francisco General Hospital or the University of California San Francisco Medical Center. Each underwent standard screening for substances of abuse and had urine tested for the presence of levamisole by liquid chromatography tandem mass spectrometry. Routine laboratory, autoantibody, and antiphospholipid antibody testing was performed in the hospitals' clinical or reference laboratories. Testing for atypical antineutrophil cytoplasmic antibodies (ANCAs) was performed separately using commercially available enzyme-linked immunosorbent assay kits. Results: The patients were women ages 39-50 years who presented with retiform purpura and cutaneous necrosis. Skin biopsies revealed a predominantly small-vessel thrombotic vasculopathy with varying degrees of vasculitis. Four patients were neutropenic. All tested positive for lupus anticoagulant, had IgM antibodies to cardiolipin, and tested strongly positive for ANCAs in a perinuclear pattern by immunofluorescence. Each patient had antibodies to multiple components of neutrophil granules, including neutrophil elastase, lactoferrin, cathepsin G, proteinase 3, and myeloperoxidase. Conclusion:. Rheumatologists should be aware of this distinctive form of necrotic purpura, its associated autoantibodies, and its link to levamisole-adulterated cocaine.

Gross RL; Brucker J; Bahce-Altuntas A; Abadi MA; Lipoff J; Kotlyar D et al. A novel cutaneous vasculitis syndrome induced by levamisole-contaminated cocaine. (review). Clinical Rheumatology 30(10): 1385-1392, 2011. (41 refs.)

In order to describe the clinical and serologic features of a cutaneous vasculitis due to cocaine contaminated with the adulterant levamisole, we report four new cases of this syndrome along with 12 previously reported cases identified through a PubMed Literature search (1964 to March 2011). Of the 16 patients described, the average age was 43, with a female predominance (81% of patients). Over half of patients had involvement of the earlobes, and the rash frequently affected the extremities in a "retiform" pattern. Leukopenia or neutropenia was reported in 56% of patients. Ninety-three percent were anti-neutrophil cytoplasmic antibody positive, and 63% tested positive for anti-phospholipid antibodies. The predominant pattern seen on histopathological examination of the skin was small vessel vasculitis and/or a thrombotic vasculopathy. Treatment in these patients varied widely, with several patients showing improvement or resolution of the rash without specific therapy following cessation of illicit drug use. This new cutaneous vasculitis syndrome can be recognized by its characteristic rash and skin pathology, together with leukopenia and autoantibody production. Certain clinical features can be attributed to the adulterant levamisole, though cocaine as well may play a role in its pathogenesis.

Hina B; Rizwani GH; Naseem S. Determination of toxic metals in some herbal drugs through atomic absorption spectroscopy. Pakistan Journal of Pharmaceutical Sciences 24(3): 353-358, 2011. (27 refs.)

This study presents a picture of occurrence of heavy metals (Pb, Cd, Cu, Cr, Co, Fe, Ni, Zn) in some selected valuable herbal drugs (G. glabra, O. bracteatum, V. odorata, F. vulgare, C. cyminum, C. sativum, and Z. officinalis) purchased from three different zones (southern, eastern, and western) of Karachi city using atomic absorption spectrophotometer. Heavy metal concentrations in these drugs were found in the range of: 3.26-30.46 for Pb, 1.6-4.91 for Cd, 0.65-120.21 for Cu, 83.74-433.76 for Zn, 1.61-186.75 for Cr, 0.48-76.97 for Ni, 5.54-77.97 for Co and 65.68-1652.89 mu g/g for Fe. Percentage of heavy metals that were found beyond the permissible limits were: 71.4% for Pb, 28.51% for Cd, 14.2% for Cu, and 9.5 % for Cr. Significant difference was noticed for each heavy metal among herbal drugs as well as their zones of collection using two way ANOVA followed by least significant (LSD) test at p < 0.05.Purpose of this research is to detect each type of heavy metal contaminant of herbal drugs by environmental pollution, as well as to highlight the health risks associated with the use of such herbal drugs that contain high levels of toxic heavy metals.

Hunter L; Gordge L; Dargan PI; Wood DM. Methaemoglobinaemia associated with the use of cocaine and volatile nitrites as recreational drugs: A review. (review). British Journal of Clinical Pharmacology 72(1): 18-26, 2011. (54 refs.)

Methaemoglobinaemia can cause significant tissue hypoxia, leading to severe, potentially life-threatening clinical features and/or death. Over recent years there have been increasing reports of methaemoglobinaemia related to recreational drug use. There have been 25 articles describing methaemoglobinaemia related to recreational use of volatile nitrites (poppers) and more recently, four reports of methaemoglobinaemia in association with recreational cocaine use. In this article we discuss the mechanisms by which methaemoglobinaemia occurs in relation to the use of both volatile nitrites and cocaine, and summarize the published cases of recreational drug-related methaemoglobinaemia. The volatile nitrites can cause methaemoglobinaemia directly through their activity as oxidizing agents. However, with cocaine, methaemoglobinaemia is related to adulterants such as local anaesthetics or phenacetin, rather than to the cocaine itself. Clinicians managing patients with acute recreational drug toxicity should be aware of the potential for methaemoglobinaemia in these patients, particularly in patients with cyanosis or unexplained low oxygen saturations on pulse oximetry, and ensure that appropriate and timely management is provided, including, where appropriate, the use of methylthioninium chloride (methylene blue).

John S; Manda S; Hamrock D. Cocaine-induced thrombotic vasculopathy. American Journal of the Medical Sciences 342(6): 524-526, 2011. (22 refs.)

Cocaine has been associated with a number of cutaneous manifestations, and most reports in the literature have described cocaine-induced vasculitis. However, not all reactive patterns secondary to cocaine use are vasculitic in nature. Recently, there has been a disturbing trend of "cutting" cocaine with pharmacologically active substances, the most common being levamisole. This agent is known to cause serious adverse effects including agranulocytosis and cutaneous eruptions. The authors describe a 52-year-old woman who acutely developed an extensive bullous rash in the lower extremities after she snorted cocaine. The clinical, hematological and serological findings were suggestive of levamisole-induced vasculitis, but histopathology of the skin showed thrombogenic vasculopathy with no inflammatory infiltrate. A skin biopsy is an essential component in the diagnosis of cocaine-related syndromes and can aid in the distinction from true autoimmune vasculitis.

Judkins CMG; Teale P; Hall DJ. The role of banned substance residue analysis in the control of dietary supplement contamination. Drug Testing and Analysis 2(9-10): 417-420, 2010. (19 refs.)

The potential for contaminated dietary supplements to result in a failed doping test remains a concern for athletes, trainers, and sporting authorities despite improvements to regulatory guidelines. Previous surveys of readily available supplements confirm that many are contaminated with steroids and stimulants prohibited for use in elite sport. Suggested responses to this issue include the complete avoidance of all supplements. Many athletes, however, use nutritional supplements to achieve effective training and also to ensure that daily nutritional requirements are met (e.g. recommended levels of vitamins and minerals). This ensures that the use of supplements is and will remain the norm for a range of sports. As a result, an alternative approach of rigorous testing of materials destined for use by elite athletes has been introduced in several countries. While the testing of final product for banned substances may help mitigate the problem, it will not help to remove the underlying issue of contamination. In this article we describe an alternative approach that uses appropriate quality assurance procedures backed up by testing to remove sources of contamination. The decrease in the incidence of contamination amongst supplement companies adopting such a system is explained, and contrasted with the relatively high incidences of contamination found in products that are not part of a quality system. These findings are of key importance to both supplement manufacturers and those involved in advising athletes about supplement use.

Kanteres F; Lachenmeier DW; Rehm J. Alcohol in Mayan Guatemala: Consumption, distribution, production and composition of cuxa. Addiction 104(5): 752-759, 2009. (10 refs.)

ims: To describe the consumption, distribution, production and chemical composition of alcohol, including cuxa (pronounced 'coo sha'), in Nahuala, a highland Mayan municipality in Guatemala. Cuxa is a sugarcane-derived spirit, in part produced clandestinely, that has been distributed in the community for several decades. Methods: Key informant interviews with alcohol distributors and consumers, cuxa producers and health professionals, as well as analyses of questionnaires from a sample of 47 spouses who came to the local health centre for problems related to their husband's drinking. Sampling and chemical analysis of cuxa from 12 of 13 identified sales points in the head-town of Nahuala and its nearby settlements ( 10 km radius). Fieldwork was conducted between November 2007 and March 2008. Results: Alcohol consumption was found to be integrated culturally in this community. The overall drinking culture was marked by irregular heavy drinking occasions, especially around market days, with substantial inebriation and health problems, especially among street inhabiting drinkers. Cuxa contributed to these problems, and cuxa drinking was socially stigmatized. Cuxa was produced both clandestinely and industrially, and sold legally by taverns and illegally by clandestine distributors. The alcoholic strength of the samples was typically between 17 and 19% vol.; clandestinely produced cuxa samples showed acetaldehyde contamination. Conclusions: Measures should be taken to reduce the harm associated with alcohol in this community, including efforts to reduce acetaldehyde levels in cuxa.

Khajeamiri AR; Kobarfard F; Ahmadkhaniha R; Mostashari G. Profiling of ecstasy tablets seized in Iran. Iranian Journal of Pharmaceutical Research 10(2): 211-220, 2011. (9 refs.)

In this study 50 samples of ecstasy tablets seized in Iran during the period of 2007 through 2008 were examined and their physical characteristics (appearance, marking, scored/not scored, color, weight, diameter, thickness) were determined. In order to determine the chemical characteristics of these tablets, color tests (Marquis test, Simon's test, Chen's test and Gallic acid test), Thin Layer Chromatography (TLC), anion test, residual solvents, Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS) were carried out on the tablets. The range of tablets weight was 96-308 mg and the range of 3,4-methylenedioxymethamphetamine (MDMA) hydrochloride content in these tablets was 60180 mg. No good correlation was found between the tablets weight and their MDMA contents. All of the tablets containing MDMA had this compound in hydrochloride form. Ketamine, phenmetrazine and ephedrine (or pseudoephedrine) were found in some of the tablets along with MDMA. No MDMA was found in 10% of the tablets. Some of these tablets contained compounds such as caffeine or tramadol as their active ingredient.

Khan TA; Cuchacovich R; Espinoza LR; Lata S; Patel NJ; Garcia-Valladares I et al. Vasculopathy, hematological, and immune abnormalities associated with levamisole-contaminated cocaine use. (review). Seminars in Arthritis and Rheumatism 41(3): 445-454, 2011. (53 refs.)

Objectives: To report 4 cases of cocaine-related purpura and to review previously reported cases of levamisole, levamisole-contaminated cocaine, and cocaine-induced vasculopathy. Methods: We describe 4 patients suspected of vasculopathy associated with levamisole-tainted cocaine use. A retrospective review of the literature was performed using the PubMed, PubJet, MD consult, and Cochrane review databases. Results: Four cases (2 females and 2 males), 46 to 55 years of age, presented with cocaine-related purpura, mainly affecting the ears, neutropenia, and autoantibodies. Skin biopsies revealed a mixed pattern of leukocytoclastic vasculitis and microvascular thrombosis in 2 cases, and pure thrombosis in the third case. The mixed vasculopathic pattern in association with neutropenia, both known adverse effects of levamisole, and levamisole positivity in 2 cases point to this compound as the true etiologic agent in our patients. Eleven cases of levamisole-contaminated cocaine-induced vasculopathy have been described in the English literature. Among these, 10 were females. Age range was 22 to 57 years. Urine levamisole positivity was tested and confirmed in 3 of the 11 cases. The clinical characteristics, laboratory features, histology, treatment, and recovery rates were compared for the published cases of levamisole, levamisole-contaminated cocaine, and cocaine-induced vasculopathy. Conclusions: Adulterated cocaine abuse is an increasingly recognized phenomenon in North America. Levamisole is among the many contaminants that have been detected in seized cocaine throughout North America and Europe. Recent reports described an association between levamisole-tainted cocaine and purpuric skin rash, neutropenia, and the presence of autoantibodies.

Khlifi R; Hamza-Chaffai A. Head and neck cancer due to heavy metal exposure via tobacco smoking and professional exposure: A review. Toxicology and Applied Pharmacology 248(2): 71-88, 2010. (338 refs.)

Chronic exposures to heavy metals via tobacco smoking and professional exposure may increase the risk of head and neck cancer, although the epidemiologic evidence is limited by problems of low study power and inadequate adjustment for tobacco and professional exposure use. Numerous scientific reviews have examined the association of various heavy metals exposure with respiratory cancer as well as other cancer types, but few have been published on head and neck cancer. The purpose of this paper, therefore, is to review the head and neck tract cancer-related data on exposure to heavy metals via smoking and working exposure and to study the major mechanisms underlying some toxic metals carcinogenesis.

Knowles L; Buxton JA; Skuridina N; Achebe I; LeGatt D; Fan S et al. Levamisole tainted cocaine causing severe neutropenia in Alberta and British Columbia. (case report). Harm Reduction Journal 6(1): article 30, 2009. (26 refs.)

Background: Five cases of severe neutropenia (neutrophil counts < 0.5 per 109 cells/L) associated with exposure to cocaine and levamisole, an antihelimithic agent no longer available in Canada, were identified in Alberta in 2008. Alberta and British Columbia (BC) public health officials issued an advisory and urged health care professionals to report cases to public health. This paper presents the findings of the public health investigations. Methods: Cases were identified prospectively through reporting by clinicians and a retrospective review of laboratory and medical examiners data from January 1, 2006 to March 31, 2009. Cases were categorized as confirmed, probable or suspect. Only the confirmed and probable cases are included in this paper. Results: We compare cases of severe neutropenia associated with tainted cocaine (NATC) identified in Alberta and BC between January 1, 2008 to March 31, 2009. Of the 42 NATC cases: 23(55%) were from Alberta; 19(45%) were from British Columbia; 57% of these cases reported crack cocaine use (93% of those who identified type of cocaine used); 7% reported using cocaine powder; and the main route of cocaine administration was from smoking (72%). Fifty percent of the NATC cases had multiple episodes of neutropenia associated with cocaine use. Cases typically presented with bacterial/fungal infections and fever. One Alberta NATC case produced anti-neutrophil antibodies, and four were positive for anti-neutrophil cytoplasmic antibody (ANCA). Analysis of two crack pipes and one drug sample obtained from NATC cases confirmed the presence of both cocaine and levamisole. A further 18 cases were identified through the retrospective review of laboratory and medical examiner data in Alberta. Interpretation: Our findings support a link between neutropenia and levamisole tainted cocaine; particularly from smoking the crack form of cocaine. Some patients may be genetically predisposed to develop levamisole-related neutropenia. Awareness of the differential diagnosis will assist clinicians with case timely detection and appropriate management.

Knox D; Murray G; Millar M; Hamilton D; Connor M; Ferdinand RD et al. Subcutaneous anthrax in three intravenous drug users: A new clinical diagnosis. Journal of Bone and Joint Surgery-British Volume 93B(3): 414-417, 2011. (11 refs.)

Anthrax is extremely rare in the western world but is endemic to areas of south and central Asia. In early 2010 an outbreak was identified in heroin-injecting intravenous drug users in the United Kingdom and Europe. Afghanistan is currently the principal source of heroin which reaches the United Kingdom. When anthrax occurs, cutaneous disease accounts for over 95% of cases. At least 47 cases with 13 deaths have been confirmed so far. We present three cases presenting during this time with marked swelling, one resulting in compartment syndrome but all with an absence of the expected cutaneous appearances. We suggest that rather than cutaneous anthrax, these patients represent a new subcutaneous presentation of anthrax.

Koushesh HR; Afshari R. A new illicit opioid dependence outbreak, evidence for a combination of opioids and steroids. Drug and Chemical Toxicology 32(2): 114-119, 2009. (23 refs.)

Opioid abuse is common in Iran. In 2005, a new version of locally produced illicit opioid vials, so called Norgesic, appeared in the illicit market, which gained popularity rapidly and led to an improvement of stigmatizing the general appearance of dependent cases. Later, some cases suffered Cushing's-like problems. A prospective case series was designed to evaluate 18 Norgesic-dependent subjects who volunteered for abstinence therapy in a rehabilitation clinic from November 1, 2005, to December 30, 2005. In this study, we aimed to describe the clinical and paraclinical findings in detail and define the potential determinants of this Cushing's syndrome outbreak. History, physical examination, plasma cortisol level, and urine screen tests were used to describe the patients. All subjects were male with a mean (SEM) age of 29.8 +/- 1.6 years. The opioid-dependence period was 8.4 +/- 0.9 years. In an average of 4.7 +/- 0.3 months, subjects increased their usage to 5.5 +/- 0.5 vials a day. Patients claimed to gain weight. Striae were seen in 38.9%, previously documented psychological problems in 33.3%, weakness in 27.8%, high systolic blood pressure in 22.2%, moon face in 16.7%, hirsutism in 11.1%, extensive dermal infection in 11.1%, gynecomastia in 5.6%, back pain in 5.6%, insomnia in 5.6%, and lack of potency in 5.6%. Their cortisol level, on average, was 4.8 +/- 1.1 mu g/dL. Hepatitis C virus was positive in 22.2%. Urine-screening tests were positive for morphine and negative for buprenorphine. In conclusion, these new vials contain steroids as well as opioids. This combination could be more dangerous than opioids themselves.

Kowalski R; Wiercinski J. Mercury content in smoke and tobacco from selected cigarette brands. Ecological Chemistry and Engineering 16(2): 155-162, 2009. (13 refs.)

The study aimed at evaluating the total mercury content in tobacco and smoke released from selected cigarette brands. "Mechanical lips" were applied for determining the mercury concentration in cigarette smoke, and its level was calculated by balancing it in tobacco, ash, and cigarette filter. Analyses were made using mercury analyser AMA-254. The study material consisted of selected-brands cigarettes grouped according to tar and nicotine substances contents declared by a producer: 3 brands (L1, L2, and L3) filled with low-tar and low-nicotine tobacco (4 and 0.3 mg/cigarette); 5 brands (M1, M2, M3, M4, and M5) characterized by medium tar and medium nicotine contents (6 divided by 8 and 0.5 divided by 0.6 mg/cigarette), and two remaining brands (S1, S2) with high-tar and high-nicotine levels (12 and 1.0 mg/cigarette). Mercury contents in tobacco from tested cigarette brands ranged from 2.95 to 10.2 ng Hg per a single cigarette. Almost all mercury contained was released to the smoke (from 86.7 to 100%). Cigarette filters made of cellulose acetate appeared to be insufficient barrier for volatile mercury. In some cases, release of mercury from the filter into the smoke was observed. The element content in the filter was higher after than before smoking the cigarette for most brands; however, these were similar values to the metal content before smoking out. Applied filter filled with activated charcoal (single cigarette brand) contained the same amount of mercury before and after smoking the cigarette. Considering 20 smoked cigarettes as daily mean value for an individual person, it can be stated that it is a serious mercury source which supplies the smoker with a dose of 60 divided by 200 ng of the toxic element into his/her lungs every day.

Lachenmeier DW; Kanteres F; Kuballa T; Lopez MG; Rehm J. Ethyl carbamate in alcoholic beverages from Mexico (tequila, mezcal, bacanora, sotol) and cuatemala (Cuxa): Market survey and risk assessment. International Journal of Environmental Research and Public Health 6(1): 349-360, 2009. (40 refs.)

Ethyl carbamate (EC) is a recognized genotoxic carcinogen, with widespread occurrence in fermented foods and beverages. No data on its occurrence in alcoholic beverages from Mexico or Central America is available. Samples of agave spirits including tequila, mezcal, bacanora and sotol (n=110), and of the sugarcane spirit cuxa (n=16) were purchased in Mexico and Guatemala, respectively, and analyzed for EC. The incidence of EC contamination was higher in Mexico than in Guatemala, however, concentrations were below international guideline levels (< 0.15 mg/L). Risk assessment found the Margin of Exposure (MOE) in line with that of European spirits. It is therefore unlikely that EC plays a role in high rates of liver cirrhosis reported in Mexico.

Lachenmeier DW; Leitz J; Schoeberl K; Kuballa T; Straub I; Rehm J. Quality of illegally and informally produced alcohol in Europe: Results from the AMPHORA project. Adicciones 23(2): 133-140, 2011. (40 refs.)

Background. In the WHO region Europe, the average unrecorded adult per capita alcohol consumption was 2.67 L pure ethanol in 2005, which is 22% of the total consumption of 12.20 L. Despite concerns about potential health harms from the chemical composition of unrecorded alcohol, there are surprisingly few data on the problem in the European Region. This study reports the results from the Alcohol Measures for Public Health Research Alliance (AMPHORA) project, which assessed the quality of unrecorded alcohol in a Europe-wide study. Methods. Samples of unrecorded alcohol were collected in 16 European countries and chemically analyzed for potentially health-relevant parameters. Thresholds for parameters were defined based on potential health hazards of daily drinking. Results. The average alcoholic strength of unrecorded wine products was 14.9% vol, and 47.8% vol in unrecorded spirits. One half of the samples (n=57) showed acceptable alcohol quality. The other half (n=58) showed one or several deficits with the most prevalent problem being ethyl carbamate contamination (n=29). Other problems included copper (n=20), manganese (n=16) and acetaldehyde (n=12). All other parameters (including methanol, higher alcohols, phthalates) were only seldom problematic (limit exceedance in less than 10 samples). The price of unrecorded alcohol was approximately 45% of the price of recorded alcohol. Conclusions. The major problem regarding unrecorded alcohol appears to be ethanol itself, as it is often higher in strength and its lower price may further contribute to higher drinking amounts. Compared to the health effects of ethanol, the contamination problems detected may be of minor importance as exposure will only in worst-case scenarios reach tolerable daily intakes of these substances.

Lachenmeier DW; Samokhvalov AV; Leitz J; Schoeberl K; Kuballa T; Linskiy IV et al. The composition of unrecorded alcohol from eastern Ukraine: Is there a toxicological concern beyond ethanol alone? Food and Chemical Toxicology 48(10): 2842-2847, 2010. (51 refs.)

In 2005, approximately half of all alcohol consumption in Ukraine was unrecorded. This paper investigates the chemical composition of unrecorded and low-cost alcohol, including a toxicological evaluation. A sample of alcohol products (n = 78) from both recorded and unrecorded sources was obtained mainly from eastern Ukraine, and chemically analyzed. entailed alcoholic strength, levels of volatile compounds (methanol, acetaldehyde, higher alcohols), ethyl carbamate, anions, and inorganic elements. The majority of unrecorded alcohol was homemade samohon with alcoholic strength averaging close to 40% vol. A limited number of samples, advertised for medicinal purposes, were identified with high alcoholic strengths (above 60% vol.). Single samples showed contamination with acetaldehyde and ethyl carbamate above the levels of toxicological concern. Metal contamination was frequent, with copper levels above 2 mg/l in 33 samples, and zinc above 5 mg/l in 10 samples. Overall, however, the composition of unrecorded samples did not raise major public health concerns other those for ethanol. The priority of alcohol policy in Ukraine should be the general reduction of alcohol consumption with a specific focus on that from small-scale home production. Further research is needed on potential mitigative measures and the origin of the metal contamination in particular alcoholic beverages.

Lachenmeier DW; Sarsh B; Rehm J. The composition of alcohol products from markets in Lithuania and Hungary, and potential health consequences: A pilot study. Alcohol and Alcoholism 44(1): 93-102, 2009. (42 refs.)

Aims: The rates of alcohol-attributable mortality in Lithuania and Hungary have been shown to be higher than those in most other European countries. Quality of alcohol products is investigated as a possible explanation. Methods: In a descriptive pilot study, a convenience sample of alcohol products was collected from local city markets in both countries (Lithuania n = 10, Hungary n = 15) and chemical analyses, including some that have not been done in prior studies, were conducted. The parameters studied were alcoholic strength, volatiles (methanol, acetaldehyde, higher alcohols), ethyl carbamate, anions (including nitrate) and inorganic elements (including lead). Additionally, a multi-target screening analysis for toxicologically relevant substances was conducted. Results: The majority of samples (64%) had an alcohol content between 35% vol. and 40% vol., being in accordance with the typical strength of legal spirits in Europe. Three samples containing significantly higher concentrations of alcohol above 60% vol. were found to be unrecorded alcohol products, defined as any alcohol that is outside of legal and taxed production. Screening analysis showed that those samples contained various flavourings, including the hepatotoxic substance coumarin, at concentrations above the legal limit for foods. All other substance classes under study were found to be at levels of no toxicological concern. Conclusions: Although some problems with the quality of the alcohol samples were found, there is insufficient evidence from this pilot study to conclude that alcohol quality has an influence on health as reflected in alcohol-attributable mortality rates. Given the extent of alcohol-attributable disease burden in central and eastern European countries, future research should focus on collection of large, representative samples, particularly of unrecorded sources, which was the most problematic product group in our study.

Lachenmeier DW; Schoeberl K; Kanteres F; Kuballa T; Sohnius EM; Rehm J. Is contaminated unrecorded alcohol a health problem in the European Union? A review of existing and methodological outline for future studies. Addiction 106(Supplement 1): 20-30, 2011. (66 refs.)

Aims: Some European countries with high levels of unrecorded alcohol consumption have anomalously high rates of death attributable to liver cirrhosis. Hepatotoxic compounds in illegally produced spirits may be partly responsible. Based on a review of the evidence on the chemical composition and potential harm from unrecorded alcohol, the Alcohol Measures for Public Health Research Alliance (AMPHORA) project's methodology for identifying, analysing and toxicologically evaluating such alcohols is provided. Methods: A computer-assisted literature review concentrated on unrecorded alcohol. Additionally, we refer to our work in the capacity of governmental alcohol control authority and a number of pilot studies. Results: The risk-oriented identification of substances resulted in the following compounds probably posing a public health risk in unrecorded alcohol: ethanol, methanol, acetaldehyde, higher alcohols, heavy metals, ethyl carbamate, biologically active flavourings (e.g. coumarin) and diethyl phthalate. Suggestions on a sampling strategy for identifying unrecorded alcohol that may be most prone to contamination include using probable distribution points such as local farmers and flea markets for selling surrogate alcohol (including denatured alcohol) to focusing on lower socio-economic status or alcohol-dependent individuals, and selecting home-produced fruit spirits prone to ethyl carbamate contamination. Conclusions: Standardized guidelines for the chemical and toxicological evaluation of unrecorded alcohol that will be used in a European-wide sampling and are applicable globally are provided. These toxicological guidelines may also be used by alcohol control laboratories for recorded alcohol products, and form a scientific foundation for establishing legislative limits.

Laugesen M; Epton M; Frampton CMA; Glover M; Lea RA. Hand-rolled cigarette smoking patterns compared with factory-made cigarette smoking in New Zealand men. BMC Public Health 9: article 194, 2009. (18 refs.)

Background: Roll-your-own (RYO) cigarettes have increased in popularity, yet their comparative potential toxicity is uncertain. This study compares smoking of RYO and factory-made (FM) cigarettes on smoking pattern and immediate potential toxicity. Methods: At a research clinic, 26 RYO and 22 FM volunteer male cigarette smokers, (addicted and overnight-tobacco-abstinent) each smoked 4 filter cigarettes, one half-hourly over 2 hours, either RYO or FM according to usual habit, using the CReSSMicro flowmeter. First cigarette smoked was their own brand. Subsequent cigarettes, all Holiday regular brand, were RYOs (0.5 g tobacco with filter), or FM with filter. Cravings on 100 mm visual analogue scale, and exhaled carbon monoxide (CO) were measured before and after each cigarette smoked. Results: Smokers reported similar daily cigarette consumption (RYO 19.0, FM 17.4, p = 0.45), and similar time after waking to first cigarette. (RYO 6.1 minutes, FM 8.6 minutes, p = 0.113). First cigarette's RYO tobacco (0.45 g) weighed less than for FM (0.7 g, p < 0.001); less tobacco was burnt (0.36 g, FM 0.55 g, p < 0.001) but smoking patterns were no different. RYO smokers smoked subsequent cigarettes more intensively; inhaled 28% more smoke per cigarette (RYO 952 mL, FM 743 mL, p = 0.025); took 25% more puffs (RYO 16.9, FM 13.6, p = 0.035); puffed longer (RYO 28 seconds, FM 22 seconds, p = 0.012), taking similar puffs (RYO 57 mL, FM 59 mL). Over four cigarettes, RYOs boosted alveolar CO (RYO 13.8 ppm, FM 13.8 ppm), and reduced cravings (RYO 53%, FM 52%) no differently from FM cigarettes. Conclusion: In these smokers, RYO smoking was associated with increased smoke exposure per cigarette, and similar CO breath levels, and even with filters is apparently no less and possibly more dangerous than FM smoking. Specific package warnings should warn of RYO smoking's true risk. RYOs are currently taxed much less than FM cigarettes in most countries; similar harm merits similar excise per cigarette.

Lee BL; Stone JH; Gimbel D; Khosroshahi A. A 44-year-old woman with cutaneous bullae and extensive skin necrosis. Arthritis Care and Research 62(12): 1805-1811, 2010. (41 refs.)

This is a case presentation of a 44-year old woman with a history of cocaine and heroin abuse who presented with a painful, necrotic rash. The couse of her illness is described. Five weeks prior to her presentation, she was diagnosed with pneumonia and compleed a 7-day course of ciprogloxacin and doxycline. Three weeks before presentation she reported fever, cills, athralgia and myalgias and a small erythemotous lesion, and sfuther lesion develped on her chest, abdomen, arms and back. She was hospitalized and cocaine-induced fasculitis. The rash continued to progress, and she reported the continued use of cocaine and intranasal heroin. Of noteshe reported acquiring cocaine from a new supplier 2 weeks before the rash appeared. The author provides a systems review, findings of the physical examination, laboratory findings and the differential diagnosis. In the discussion it is pointed out that about 70% of seized cocaine entering the US contains levamisol, which has been associated with vasculitis and vasculopathy, the latter the final diagnosis.

Lee S; Han E; In S; Choi H; Chung H; Chung KH. Analysis of pubic hair as an alternative specimen to scalp hair: A contamination issue. Forensic Science International 206(1-3): 19-21, 2011. (8 refs.)

Pubic hair is often analyzed as an alternative to scalp hair to prove previous drug use. However, urine is a potential source of external contamination. In the present study, the concentrations of methamphetamine (MA) and amphetamine (AP) in both scalp and pubic hair from illegal MA users were compared. Furthermore, in order to investigate the external contamination of pubic hair by urine, MA and AP absorbed into pubic hair that had been contaminated with authentic urine from a MA user were measured using a previously validated method. The effect of shampoo-wash on the contaminated pubic hair was also examined. However, no correlation was found in the MA and AP concentrations between scalp and pubic hair from illegal MA users. As the number of contamination events by authentic urine increased, the concentrations of MA and AP in pubic hair increased. Both MA and AP were detected in the first methanol washes of the contaminated hair samples but were not detected in the second methanol washes. As the number of shampoo-washes of the contaminated pubic hair increased, the concentrations of MA and AP gradually decreased. Even though pubic hair can be used as an alternative to scalp hair to prove previous drug use, it should be avoided when estimating drug use history. It should be also noted that higher quantitative results in pubic hair do not necessarily represent heavier drug use.

Lee S; Kim J; In S; Choi H; Chung H; Chung KH. Detection of phentermine in hair samples from drug suspects. Forensic Science International 207(1-3): E5-E7, 2011. (13 refs.)

Phentermine (PT) has been widely used as an anti-obesity drug. This drug has to be used with caution due to its close resemblance with amphetamines in its structure and toxicity profile. Recently, PT is in distribution by illegal modes and is found to be available through sources such as the internet, thus their misuse and/or abuse is threatening to be a serious social issue. In the present study, 32 cases of drug suspects were observed for PT abuse, detected using hair samples for drug analysis. PT and other amphetamines, such as methamphetamine (MA), amphetamine (AP), 3,4-methylenedioxyamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA), were extracted using 1% HCl in methanol for 20 h at 38 degrees C. The extracts were derivatized with trifluoroacetic anhydride (TFAA) and analyzed using gas chromatography/mass spectrometry (GC/MS). Among the 32 cases of PT abuse, MA and its main metabolite, AP were identified in seven cases and MDMA and its main metabolite, MDA were detected in two other cases.

Leitz J; Kuballa T; Rehm J; Lachenmeier DW. Chemical analysis and risk assessment of diethyl phthalate in alcoholic beverages with special regard to unrecorded alcohol. PLoS one 4(12): e-8127, 2009. (38 refs.)

Background: Phthalates are synthetic compounds with a widespread field of applications. For example, they are used as plasticizers in PVC plastics and food packaging, or are added to personal care products. Diethyl phthalate (DEP) may be used to denature alcohol, e.g., for cosmetic purposes. Public health concerns of phthalates include carcinogenic, teratogenic, hepatotoxic and endocrine effects. The aim of this study was to develop and validate a method for determining phthalates in alcohol samples and to provide a risk assessment for consumers of such products. Methodology/Principal Findings: A liquid-liquid extraction procedure was optimized by varying the following parameters: type of extraction solvent (cyclohexane, n-hexane, 1,1,2-trichlorotrifluoroethane), the ratio extraction solvent/sample volume (1:1 to 50:1) and the number of extraction repetitions (1-10). The best extraction yield (99.9%) was achieved with the solvent 1,1,2-trichlorotrifluoroethane, an extraction solvent volume/sample volume ratio of 10: 1 and a double extraction. For quantification, gas chromatography/mass spectrometry with deuterated internal standards was used. The investigated samples were alcoholic beverages and unrecorded alcohol products from different countries (n = 257). Two unrecorded alcohol samples from Lithuania contained diethyl phthalate in concentrations of 608 mg/L and 210 mg/L. Conclusions/Significance: The consumption of the phthalate-positive unrecorded alcohols would exceed tolerable daily intakes as derived from animal experiments. Both positive samples were labelled as cosmetic alcohol, but had clearly been offered for human consumption. DEP seems to be unsuitable as a denaturing agent as it has no effect on the organoleptic properties of ethanol. In light of our results that DEP might be consumed by humans in unrecorded alcohols, the prohibition of its use as a denaturing agent should be considered.

MacKenzie R; Chapman S. Pig's blood in cigarette filters: How a single news release highlighted tobacco industry concealment of cigarette ingredients. Tobacco Control 20(2): 169-172, 2011. (37 refs.)

The tobacco industry is not obligated to disclose ingredients and additives used in manufactured tobacco production. This paper describes global reaction to a press release highlighting evidence that porcine haemoglobin ("pig's blood") was sometimes used in cigarette manufacturing while never being disclosed to smokers. The case study illustrates the power of press releases to ignite major interest in tobacco control issues.

McGrath MM; Isakova T; Rennke HG; Mottoa AM; Laliberte KA; Niles JL. Contaminated cocaine and antineutrophil cytoplasmic antibody-associated disease. Clinical Journal of the American Society of Nephrology 6(12): 2799-2805, 2011. (47 refs.)

Background and objectives: Approximately 70% of illicit cocaine consumed in the United States is contaminated with levamisole. Most commonly used as a veterinary antihelminthic agent, levamisole is a known immunomodulating agent. Prolonged use in humans has been associated with cutaneous vasculitis and agranulocytosis. We describe the development of a systemic autoimmune disease associated with antineutrophil cytoplasmic antibodies (ANCA) in cocaine users. This complication appears to be linked to combined cocaine and levamisole exposure. Design, setting, participants, & measurements Cases were identified between March 2009 and November 2010 at Massachusetts General Hospital's ANCA laboratory. Cocaine exposure was identified from patient history in all cases. Medical records were reviewed for clinical presentation and for laboratory and diagnostic evaluation. Results: Thirty cases of ANCA positivity associated with cocaine ingestion were identified. All had antimyeloperoxidase antibodies and 50% also had antiproteinase 3 antibodies. Complete clinical and laboratory data were available for 18 patients. Arthralgia (83%) and skin lesions (61%) were the most frequent complaints at presentation. Seventy-two percent of patients reported constitutional symptoms, including fever, night sweats, weight loss, or malaise. Four patients had biopsy-proven vasculitis. Two cases of acute kidney injury and three cases of pulmonary hemorrhage occurred. From the entire cohort of 30, two cases were identified during the first 3 months of our study period and nine cases presented during the last 3 months. Conclusions: We describe an association between the ingestion of levamisole-contaminated cocaine and ANCA-associated systemic autoimmune disease. Our data suggest that this is a potentially life-threatening complication of cocaine use.

Mirza SS; Shafique K; Vart P; Arain MI. Areca nut chewing and dependency syndrome: Is the dependence comparable to smoking? a cross sectional study. Substance Abuse Treatment, Prevention and Policy 6: article 23, 2011. (14 refs.)

Background: Areca nut is the seed of fruit oriental palm known as Areca catechu. Many adverse effects of nut chewing have been well documented in the medical literature. As these nuts are mixed with some other substances like tobacco and flavouring agents, it has been hypothesized that it might also cause some dependency symptoms among its users. Therefore, the objective of this study was to investigate dependency syndrome among areca nut users with and without tobacco additives and compare it with dependency associated with cigarette smoking among the male Pakistani population. Methods: This was an observational cross sectional study carried out on healthy individuals, who were users of any one of the three products (areca nut only, areca nut with tobacco additives, cigarette smokers). Participants were selected by convenience sampling of people coming to hospital to seek a free oral check up. Information was collected about the socio-demographic profile, pattern of use and symptoms of dependency using the DSM-IV criteria for substance dependence. We carried out multiple logistic regressions to investigate association between socio-demographic profile, pattern of substance use and dependency syndrome. Results: We carried out final analysis on 851 individuals, of which 36.8% (n = 314) were areca nut users, 28.4% (n = 242) were the chewers of areca with tobacco additives and 34.7% (n = 295) were regular cigarette smokers. Multivariate analyses showed that individuals using areca nut with tobacco additives were significantly more likely to have dependency syndrome (OR = 2.17, 95% CI 1.39-3.40) while cigarette smokers were eight times more likely to have dependency syndrome as compared to areca nut only users. Conclusions: Areca nut use with and without tobacco additives was significantly associated with dependency syndrome. In comparison to exclusive areca nut users, the smokers were eight times more likely to develop dependence while areca nut users with tobacco additives were also significantly more likely to suffer from the dependence.

Morefield KM; Keane M; Felgate P; White JM; Irvine RJ. Pill content, dose and resulting plasma concentrations of 3,4-methylendioxymethamphetamine (MDMA) in recreational 'ecstasy' users. Addiction 106(7): 1293-1300, 2011. (50 refs.)

Aims: To improve our understanding of the pharmacology of 'ecstasy' in recreational environments; in particular, to describe the composition of ecstasy pills, patterns of ecstasy use and the relationship between dose of 3,4-methylendioxymethamphetamine (MDMA) and resulting plasma concentrations. Design, setting and participants: A naturalistic observational study of 56 experienced 'ecstasy' users in recreational settings in Australia. Measurements: Drug use patterns (number of pills consumed, other drugs consumed). drug content of pills and resultant plasma concentrations of MDMA and related drugs were assessed by gas chromatography/mass spectrometry (GC/MS). Findings: Ecstasy pills generally contained MDMA, but this was often combined with other drugs such as 3,4-methylendioxyethylamphetamine (MDEA) and methamphetamine. The dose of MDMA per pill ranged from 0 to 245 mg and users consumed from one-half to five pills, with the total dose consumed ranging up to 280 mg. Plasma concentrations of MDMA increased with number of pills consumed and cumulative MDMA dose. Use of larger numbers of pills was associated with extended exposure to the drug. Conclusions: MDMA is the major active drug in ecstasy pills, but there is a high degree of variation in doses. Use of multiple pills over the course of one session is common and results in a sustained increase in MDMA plasma concentrations over a number of hours. This is likely to lead to a much greater exposure of the brain to MDMA than would be predicted from controlled single-dose pharmacokinetic studies.

Mouzakis J; Somboonwit C; Lakshmi S; Rumbak M; Sinnott J; Cherpelis B et al. Levamisole induced necrosis of the skin and neutropenia following intranasal cocaine use: A newly recognized syndrome. Journal of Drugs In Dermatology 10(10): 1204-1207, 2011. (10 refs.)

Levamisole is a veterinary anti-helminthic used to treat several autoimmune conditions but also commonly utilized as an additive in cocaine distribution. Toxicity resulting in agranulocytosis and cutaneous necrosis in association with cocaine use is an infrequently described phenomenon of an emerging problem. Although levamisole is found extensively in the cocaine supply of the United States, relatively few cases of necrotic skin lesions associated with intranasal use have been reported. The skin necrosis secondary to levamisole toxicity is characterized by variable findings on biopsy, ranging from leukocytoclastic vasculitis to occlusive vasculopathy. The following case describes a 54-year-old male who developed fever, agranulocytosis, p-ANCA autoantibodies and extensive skin necrosis following heavy intranasal cocaine use. Necrosis of greater than 50% of the patient's total body surface area resulted and was followed by thorough wound debridement.

O'Connor RJ; Li QA; Stephens WE; Hammond D; Elton-Marshall T; Cummings KM et al. Cigarettes sold in China: Design, emissions and metals. Tobacco Control 19(Supplement 2): i47, 2010. (33 refs.)

Background: China is the home to the world's largest cigarette maker, China National Tobacco Company (CNTC), yet little is known publicly about the design and emissions of Chinese cigarettes. CNTC is currently in the process of consolidating its brands and has ambitions to export its cigarettes. Machine-measured tar yields of many of its cigarette brands have also been reduced, similar to what occurred in Western countries from the 1970s through the 1990s with so-called 'low-tar' cigarettes introduced to address consumer concerns about health risks from smoking. Method: The current study examines the design and physical characteristics, labelled smoke emissions and tobacco metals content of leading brands of Chinese cigarettes from seven cities purchased in 2005-6 and in 2007. Results: Findings suggest that similar to most countries, tar levels of Chinese cigarettes are predicted primarily by tobacco weight and filter ventilation. Ventilation explained approximately 50% of variation observed in tar and 60% variation in carbon monoxide yields. We found little significant change in key design features of cigarettes purchased in both rounds. We observed significant levels of various metals, averaging 0.82 mu g/g arsenic (range 0.3-3.3), 3.21 mu g/g cadmium (range 2.0-5.4) and 2.65 mu g/g lead (range 1.2-6.5) in a subsample of 13 brands in 2005-6, substantially higher than contemporary Canadian products. Conclusion: Results suggest that cigarettes in China increasingly resemble those sold in Western countries, but with tobacco containing higher levels of heavy metals. As CNTC looks to export its product around the world, independent surveillance of tobacco product characteristics, including tobacco blend characteristics, will become increasingly important.

Papastefanou C. Radioactivity of tobacco leaves and radiation dose induced from smoking. International Journal of Environmental Research and Public Health 6(2): 558-567, 2009. (30 refs.)

The radioactivity in tobacco leaves collected from 15 different regions of Greece and before cigarette production was studied in order to find out any association between the root uptake of radionuclides from soil ground by the tobacco plants and the effective dose induced to smokers from cigarette tobacco due to the naturally occurring primordial radionuclides, such as Ra-226 and Pb-210 of the uranium series and Ra-228 of the thorium series and/or man-made radionuclides, such as Cs-137 of Chernobyl origin. Gammaray spectrometry was applied using Ge planar and coaxial type detectors of high resolution and high efficiency. It was concluded that the activities of the radioisotopes of radium, Ra-226 and Ra-228 in the tobacco leaves reflected their origin from the soil by root uptake rather than fertilizers used in the cultivation of tobacco plants. Lead-210 originated from the air and was deposited onto the tobacco leaves and trapped by the trichomes. Potassium-40 in the tobacco leaves was due to root uptake either from soil or from fertilizer. The cesium radioisotopes Cs-137 and Cs-134 in tobacco leaves were due to root uptake and not due to deposition onto the leaf foliage as they still remained in soil four years after the Chernobyl reactor accident, but were absent from the atmosphere because of the rain washout (precipitation) and gravitational settling. The annual effective dose due to inhalation for adults (smokers) for Ra-226 varied from 42.5 to 178.6 mu Sv/y (average 79.7 mu Sv/y), while for Ra-228 from 19.3 to 116.0 mu Sv/y (average 67.1 mu Sv/y) and for Pb-210 from 47.0 to 134.9 mu Sv/y (average 104.7 mu Sv/y), that is the same order of magnitude for each radionuclide. The sum of the effective doses of the three radionuclides varied from 151.9 to 401.3 mu Sv/y (average 251.5 mu Sv/y). The annual effective dose from Cs-137 of Chernobyl origin was three orders of magnitude lower as it varied from 70.4 to 410.4 nSv/y (average 199.3 nSv/y).

Park SR; Ha SD; Yoon JH; Lee SY; Hong KP; Lee EH et al. Exposure to ethyl carbamate in alcohol-drinking and nondrinking adults and its reduction by simple charcoal filtration. Food Control 20(10): 946-952, 2009. (34 refs.)

The risk of exposure to ethyl carbamate from the consumption of kimchi, soy sauce, and alcoholic beverages was assessed in alcohol-drinking and nondrinking adults. An alcohol-drinking adult obtains 5.6-9.2 ng/kg bw/day of ethyl carbamate through the addition of kimchi and soy sauce, while a nondrinking adult receives 3.3-4.0 ng/kg bw/day via kimchi and soy sauce alone. The average excess cancer risk of an alcohol-drinking adult (3.9 x 10(-7)) was also twice higher than that of an adult who does not drink (1.9 X 10(-7)). We achieved a maximum of 47% and 45% removal of the ethyl carbamate present in diluted spirits and soy sauce, respectively, through a simple charcoal filtration process. This resulted in a reduction of the average daily intakes of ethyl carbamate through diluted spirits and soy sauce from 1.7 and 2.2 ng/kg bw/day to 0.9 and 1.2 ng/kg bw/day, respectively.

Perkisas S; Vrelust I; Martin M; Gadisseur A; Schroyens W. A warning about agranulocytosis with the use of cocaine adulterated with levamisole. Acta Clinica Belgica 66(3): 226-227, 2011. (5 refs.)

Since 2004, the US Food And Drug Administration and the European Medicine Agency are giving warnings about cocaine adulterated with levamisole. Levamisole is primarily used as an anti-helminthic. One of the side-effects of levamisole is a decreased bone marrow function. Herein we describe the first case of agranulocytosis and neutropenic fever due to cocaine adulterated with levamisole reported in Europe.

Poon SH; Baliog CR; Sams RN; Robinson-Bostom L; Telang GH; Reginato AM. Syndrome of cocaine-levamisole-induced cutaneous vasculitis and immune-mediated leucopenia. (review). Seminars in Arthritis and Rheumatism 41(3): 434-444, 2011. (37 refs.)

Objective: We describe 4 patients who presented with palpable purpura, arthralgia or arthritis, leukopenia, and antineutrophil cytoplasmic antigen (ANCA) positivity most likely as a result of a hypersensitivity reaction to cocaine-levamisole induced vasculopathy. Methods: Cases were seen and reviewed in both the inpatient consult service and the outpatient clinics at Rhode Island Hospital from August 2009 to August 2010. Clinical characteristics as well as pertinent laboratory parameters were also reviewed and corroborated with a review of the present literature. Results: We describe 3 cases of cocaine-levamisole-related cutaneous vasculitis with or without associated neutropenia, and 1 case of severe neutropenia with oral mucosal ulceration. Further serologic studies revealed maximum titers of ANCA mostly in a perinuclear pattern. Antimyeloperoxidase tested negative or mildly elevated in our cohort. Three patients with neutropenia had positive antigranulocyte IgM antibody. Nonsteroidal anti-inflammatory drugs were effective as first-line treatment for joint pain. The use of colchicine and systemic corticosteroid was employed to manage severe and persistent skin lesions. Conclusions: Cocaine-levamisole-related cutaneous vasculitis with leukopenia is a diagnosis of exclusion, but this diagnosis should be strongly considered in patients with a history of cocaine abuse who present with a tetrad of cutaneous manifestations consisting of palpable purpura or bullae with ear involvement, arthralgias, leukopenia, and positive ANCA in high titers and negative Antimyeloperoxidase, when other infectious or idiopathic vasculitic entities have been excluded.

Rehm J; Kanteres F; Lachenmeier D. Unrecorded consumption, quality of alcohol and health consequences. (review). Drug and Alcohol Review 29(4): 426-436, 2010. (129 refs.)

Issues. This contribution aims to examine systematically the evidence on the impact of the quality of unrecorded alcohol products on health consequences. Approach. Systematic computer assisted review of the literature. Key Findings. There are a number of pathways related to alcohol quality that may lead to acute or chronic health problems. The following constituents and contaminants of alcoholic beverages were identified as likely contributors to these problems: (i) toxic metals (e.g. lead) from contaminated water sources or unsuitable distillation equipment; (ii) volatile constituents, such as acetaldehyde or higher alcohols, which may be produced in significant amounts due to faults in production technology or microbiological spoilage; (iii) ethyl carbamate (urethane), a carcinogenic contaminant with major occurrence in certain fruit and sugarcane spirits; (iv) biologically active flavour compounds (e.g. coumarin in cosmetics used as non-beverage alcohol); (v) toxic compounds used to denature alcohol (e.g. methanol or diethyl phthalate). In addition, the often higher ethanol content may have detrimental health effects. These pathways should not be assumed as present for all subcategories of unrecorded alcohol, but are more relevant to certain types and geographic regions. Implications. A health impact of unrecorded alcohol over and above the effect of ethanol cannot be excluded. More research is urgently needed, especially with respect to liver disease and alcohol poisoning as endpoints. Conclusion. A feasible approach for new research on the effects of unrecorded alcohol could be based on a representative sample from low socioeconomic regions with high prevalence of unrecorded consumption.

Schayer S; Nowak B; Wang YL; Qu QS; Cohen B. Po-210 and Pb-210 activity in Chinese cigarettes. Health Physics 96(5): 543-549, 2009. (36 refs.)

The radon decay products lead-210 (Pb-210) and polonium-210 (Po-210) are known components of tobacco. China is the world's largest producer and consumer of cigarettes, yet no comprehensive published reports of the Pb-210 and Po-210 activity concentrations in Chinese cigarettes are available. Twelve brands of cigarettes that were commonly smoked within a group of 184 Chinese smokers were selected for Ph-210 and Po-210 activity analysis. For each brand, the tobacco from two cigarettes was isolated, dried, weighed, spiked with a (209)po tracer for yield, and digested with concentrated HNO3, followed by HCl. The polonium in each digested solution was spontaneously deposited onto a nickel disc. The polonium activity was then counted rising alpha spectroscopy. The mean (range) Po-210 activity for all brands was 23 (18-29) mBq cig(-1). The state of radioactive equilibrium between (210)To and Pb-210 in each cigarette was verified in three brands of cigarettes. Cigarettes from two brands were smoked on a machine in order to estimate the fraction of Pb-210 and Po-210 inhaled. An average of 8% of the Pb-210 and 13% of the Po-210 in the tobacco of the cigarettes was transferred to the mainstream smoke. It is thus estimated that a person smoking 20 of these cigarettes per day in China would inhale a mean (range) of 37 (29-46) mBq d(-1) of Pb-210 and 60 (47-75) mBq d(-1) of Po-210. Cigarette smoking in China may therefore be a large source of a person's daily intake of Pb-210 and Po-210.

Schneider S; Meys F. Analysis of illicit cocaine and heroin samples seized in Luxembourg from 2005-2010. Forensic Science International 212(1-3): 242-246, 2011. (21 refs.)

This article discusses drug purity, frequency of appearance and concentration ranges of adulterants of 471 illicit cocaine and 962 illicit heroin samples seized in Luxembourg from January 2005 to December 2010. For cocaine samples the mean concentration was lowest in 2009 (43.2%) and highest in 2005 (54.7%) but no clear trend could be observed during the last 6 years. 14 different adulterants have been detected in cocaine samples, from which phenacetin has been the most abundant in terms of frequency of appearance and concentration until 2009. In 2010 the veterinary antihelminthic drug levamisole has become the most abundant adulterant detected in cocaine samples, its concentrations however remained low (1.5-4.1%). The mean heroin concentration was 26.6% in 2005, a decline has been observed in 2006 and the concentrations have been relatively stable since then (15.8-17.4%). Paracetamol and caffeine were by far the most abundant adulterants detected in heroin samples.

Schroeter M; Alpers K; Van Treeck U; Frank C; Rosenkoetter N; Schaumann R. Outbreak of wound botulism in injecting drug users. Epidemiology and Infection 137(11): 1602-1608, 2009. (32 refs.)

Between October and December 2005, 16 cases of wound botulism were notified to the health authorities of North Rhine-Westphalia, Germany. All patients were injecting drug users (IDU) and the epidemiological investigations suggested contaminated injection drugs as the most probable source of infection. Clostridium botulinum was cultivated from clinical samples of six patients and molecular typing revealed that the different isolates were clonally identical. Two samples of heroin, one of them provided by a patient, were examined but C. botulinum could not be isolated. This outbreak demonstrates that IDU are at risk for acquiring wound botulism by injecting contaminated drugs. A greater awareness of this disease is needed by physicians and a close cooperation between public health authorities, street workers, operators of sheltered injecting facilities, and medical centres focusing on IDU is essential to prevent and manage outbreaks in IDU in a timely manner.

Sepetdjian E; Saliba N; Shihadeh A. Carcinogenic PAH in waterpipe charcoal products. Food and Chemical Toxicology 48(11): 3242-3245, 2010. (23 refs.)

Because narghile waterpipe (shisha, hooka) smoking normally involves the use of burning charcoal, smoke inhaled by the user contains constituents originating from the charcoal in addition to those from the tobacco. We have previously found that charcoal accounts for most of the polyaromatic hydrocarbons (PAH) and carbon monoxide in the smoke of the waterpipe, both of which are present in alarming quantities. Because charcoal manufacturing conditions favor formation of PAH, it is reasonable to assume that charcoal sold off the shelf may be contaminated by PAH residues. These residues may constitute a significant fraction of the PAH inhaled by the waterpipe user and those in her/his vicinity. We measured PAH residues on three kinds of raw waterpipe charcoal sampled from Beirut stores and cafes. We found that PAH residues in raw charcoal can account for more than half of the total PAH emitted in the mainstream and sidestream smoke, and about one sixth of the carcinogenic 5- and 6-ring PAH compounds. Total PAH content of the three charcoal types varied systematically by a factor of six from the charcoal with the least to the greatest PAH residue. These findings indicate the possibility of regulating charcoal carcinogen content.

Shahab L; West R; McNeill A. A comparison of exposure to carcinogens among roll-your-own and factory-made cigarette smokers. Addiction Biology 14(3): 315-320, 2009. (34 refs.)

Consumption of roll-your-own (RYO) tobacco is rising, but little is known about: its in vivo delivery of toxins relative to factory-made (FM) cigarettes. To start to address this issue, this study compared the concentrations of metabolites of recognized human carcinogens in smokers of RYO tobacco and FM cigarettes. We opportunistically recruited 1.27 FM and 28 RYO cigarette smokers in central London and collected saliva and Urine samples. Saliva samples were assayed for cotinine while urinary samples were assayed for I.-hydroxypyrene (1-HOP) and total 4-(methylnitrosamino)-1(3-pyridyl)-1-butanol (NNAL), metabolic markers of polycyclic aromatic hydrocarbons and tobacco-specific N-nitrosamines, respectively. Data on socio-demographic, anthropometric and puffing characteristics were also obtained. Both unadjusted and adjusted analyses (controlling for age, sex, body mass index, puff flow, puff duration and cotinine) showed no difference in metabolic markers between RYO and FM cigarette smokers. However, significant main effects for cotinine levels and sex were observed in adjusted analyses. Greater levels of cotinine were associated with a greater concentration of both I-HOP (B = 0.002, P = 0.037) and NNAL (B = 0.002, P < 0.001). In addition, women had significantly greater concentrations of urinary I.-HOP (B = 0.679, P = 0.004) and total NNAL metabolites (B = 0.117, P = 0.024) than men, irrespective of the type of cigarettes smoked. More research is now needed to confirm these findings and gender-specific effects in a larger representative sample. However, results do not support the common belief that RYO cigarettes are less harmful than manufactured cigarettes.

Sim WJ; Lee JW; Lee ES; Shin SK; Hwang SR; Oh JE. Occurrence and distribution of pharmaceuticals in wastewater from households, livestock farms, hospitals and pharmaceutical manufactures. Chemosphere 82(2): 179-186, 2011. (35 refs.)

Twenty-four pharmaceuticals were measured in wastewater from 12 municipal wastewater treatment plants (M-WWTPs), four livestock WWTPs (L-WWTPs), four hospital WWTPs (H-WWTPs) and four pharmaceutical manufacture WWTPs (P-WWTPs). The total concentration of pharmaceuticals in the influent samples was highest in the L-WWTPs followed by the P-WWTPs, H-WWTPs and M-WWTPs. The effluents had different patterns of pharmaceuticals than their corresponding influents because of the different fate of each compound in the WWTPs. Non-steroidal anti-inflammatory drugs (NSAIDs) were the most dominant in the influents from the M-WWTPs and P-WWTPs, while antibiotics were dominantly detected in the L-WWTP. In the H-WWTP influents, NSAIDs, caffeine and carbamazepine were dominant. In the P-WWTPs, the distribution of pharmaceuticals in the effluents varied with sampling sites and periods. The M-WWTP influents had the highest daily loads, while the effluents showed somewhat similar levels in all source types.

Soltaninejad K; Fluckiger A; Shadnia S. Opium addiction and lead poisoning. Journal of Substance Use 16(3): 208- 212, 2011. (21 refs.)

Patients and Method: In this study, we evaluated 25 patients seen from 2002 to 2007 with lead poisoning in the Loghman Hakim Hospital Poison Center, Tehran, Iran. Data such as age, sex, causes of intoxication, route of poisoning, clinical manifestations on admission, duration of hospitalization, blood lead level and history of addiction were extracted from the patients' files. Results: Seven of the patients had a history of opium addiction as the only probable source of lead poisoning, and none of them had occupations known to involve exposure to lead. The average age of these patients was 38.7 +/-+/- 9.3 years. The average blood lead level in these patients was 109 +/-+/- 37.6 mu mu gdL. Conclusion: Lead poisoning should be considered in patients with a history of opium abuse who present with non-specific clinical manifestations.

Tahir SNA. Results of survey for assessing awareness level regarding radiological hazards of tobacco smoking. Radiation Protection Dosimetry 133(2): 111-114, 2009. (10 refs.)

Human consumption of tobacco is as old as human history. However, injurious health effects due to tobacco smoking may not be evident to the public at large. This article presents results of a questionnaire based on a survey carried out in the metropolitan city of Lahore of Pakistan with an aim to understand the awareness level of the general population about the radiological hazards associated with tobacco smoking. Some 3600 participants from different educational backgrounds from all segments of the society participated in this survey. Analysis of the data collected concluded that the awareness level of the representative participants regarding the radiological hazards associated with tobacco smoking was alarmingly poor. These results suggest that a nationwide mass media campaign may be launched by the government authorities in Health and Environment departments to enlighten the general public in this respect to avoid tobacco-smoking-associated health risks.

Talio MC; Luconi MO; Masi AN; Fernandez LP. Cadmium monitoring in saliva and urine as indicator of smoking addiction. Science of the Total Environment 408(16): 3125-3132, 2010. (24 refs.)

Cadmium is one of the many substances that may be acquired through active and passive smoking of tobacco. Saliva and urine are proposed for cadmium monitoring of non-smokers, second hand smokers, smokers and tobacco chewing appertaining to San Luis citizens without occupational exposition. Biological samples were collected by the same subjects, under strict proceeding instructions of sampling. Physical characteristics of samples were observed and checked with commercial test. Samples were analyzed using an adapted molecular fluorescence methodology with a previous extraction step. Stability of biological samples was daily studied for a period of one month. The method was successfully validated for accuracy, precision, linearity, specificity, and sensitivity. The simplicity and low coefficient of variance confirm the suitability of the method for urinary and salivary cadmium analyses. On the other side, the obtained results are in concordance with previous national epidemiological dates.

Vallersnes OM; Lund C; Duns AK; Netland H; Rasmussen IA. Epidemic of poisoning caused by scopolamine disguised as Rohypnol (TM) tablets. Clinical Toxicology 47(9): 889-893, 2009. (13 refs.)

Objective. An epidemic of scopolamine poisonings occurred in Oslo in 2008 among users of illicit drugs, caused by fake Rohypnol (TM) pills. The clinical features, diagnostic process, and handling of the epidemic are presented. Methods. Suspected cases of scopolamine poisoning were extracted by reviewing registration forms from an ongoing prospective clinical study of acute poisonings in Oslo. Medical records of extracted contacts were examined and cases included according to specified clinical criteria. Results. Forty-four cases of probable scopolamine poisoning were registered. Main clinical features were mydriasis, visual hallucinations, plucking behavior, agitation, and coma. No clinical diagnosis of anticholinergic syndrome was made prior to forensic analysis of the tablets, the most frequent diagnosis up to this point being unspecified drug-induced psychosis. Later in the epidemic, scopolamine poisoning became the dominating diagnosis. Ten patients were admitted to psychiatric hospitals, the rest recovered in medical units, or left health care against medical advice. Discussion. Scopolamine poisonings are rare, but the resulting anticholinergic syndrome is well described. The syndrome was not recognized until the forensic analysis result strikingly changed how the patients were diagnosed and handled. A unique aspect of this epidemic was the intoxicating agent being scopolamine-containing tablets looking like Rohypnol (TM), sold and used under the impression of being the latter. Conclusion. Recognizing the anticholinergic syndrome is important to provide proper treatment. Forensic analysis was the key to correct diagnosis in this outbreak, demonstrating its importance in verifying an epidemic of poisoning by fake drugs.

Vardavas CI; Patelarou E; Grander M; Chatzi L; Palm B; Fthenou E et al. The association between active/passive smoking and toxic metals among pregnant women in Greece. Xenobiotica 41(6): 456- 463, 2011. (45 refs.)

1. Exposure to toxic metals during pregnancy may have detrimental effects on foetal development. We assessed the role of sociodemographic characteristics and active and passive smoking on blood concentrations of metals (As, Cd, Pb, Hg, Sb, U, Mn and Mo). 2. Venous blood drawn from 50 pregnant women, randomly selected from the mother-child birth cohort 'Rhea'. Extensive questionnaire data on active and passive smoking were collected. Urinary cotinine was measured to validate self-reported exposure and non-smoking status. 3. Smokers had higher concentrations of Cd (1.0 mu g/L) as compared with non-smokers (0.29 mu g/L, P < 0.001) and a tendency for higher As and Hg. Among non-smokers, blood As and Hg concentrations were also associated with exposure to passive smoking in public venues and the family home and to overall greater secondhand smoke (SHS) exposure (As: 0.97 mu g/L among heavy-exposed compared with 0.20 mu g/L among the low-exposed, P < 0.05; Hg: 2.1 mu g/L vs. 0.9 mu g/L respectively, P < 0.05). Controlling for fish and seafood intake altered the statistical significance but not the direction of the above associations. 4. Smoking was associated with higher Cd concentrations in pregnant women, although the association between passive smoking and elevated As and Hg concentrations was indicative, however inconclusive.

Verheij J; Voortman J; van Nieuwkerk CMJ; Jarbandhan SVA; Mulder CJJ; Bloemena E. Hepatic morphopathologic findings of lead poisoning in a drug addict: A case report. Journal of Gastrointestinal and Liver Diseases 18(2): 225-227, 2009. (10 refs.)

We describe the case of a 40-year old Iranian man who was admitted to our hospital with severe abdominal pain, abnormal liver function tests and normocytic anemia. Suffering from multiple sclerosis, he was a regular user of opium for pain relief. Basophilic stippling of erythrocytes pointed towards the diagnosis of lead intoxication, the most likely source being contaminated Iranian opium. Serum lead and zinc protoporphyrin levels were strongly elevated. To assess the hepatotoxic effects of lead poisoning a liver biopsy was performed. Pathomorphologic findings of hepatotoxicity, rarely reported in humans, included active hepatitis together with extensive microvesicular and macrovesicular steatosis, hemosiderosis and cholestasis, and a lymphocytic cholangitis. Whilst treated with chelating therapy, liver enzymes returned to normal, suggesting reversibility of the histological findings.

Wilcox JA; Wilcox AH. Movement disorders and MDMA abuse. Journal of Psychoactive Drugs 41(2): 203-204, 2009. (12 refs.)

This article present the cases of two young men with chronic MDMA abuse who later developed movement disorders typical of the Parkinson's syndrome. It is worth noting that both men bought the presumed MDMA from the same illicit source. Potential risks of MDMA use and movement disorders are discussed. The risks inherent from contaminants and similar factors associated with illegal drug manufacture are discussed. The authors conclude that as long as nonpharmaceutical-grade MDMA is illicitly produced, health risks will be associated with its use.

Wood DM; Stribley V; Dargan PI; Davies S; Holt DW; Ramsey J. Variability in the 3,4-methylenedioxymethamphetamine content of 'ecstasy' tablets in the UK. Emergency Medicine Journal 28(9): 764-765, 2011. (9 refs.)

Background Toxicity, such as hyperpyrexia, associated with the use of 3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy') appears to be related to serum MDMA concentrations. However, there does not appear to be a similar association with the number of tablets ingested, suggesting variation in the tablet content of MDMA. Although work has shown this variation in other areas of the world, no studies have reported on the variation of MDMA content in UK ecstasy tablets. Methods Ecstasy tablets seized from individuals attending nightclubs were analysed qualitatively to determine if they contained MDMA and quantitatively to determine the MDMA content per tablet. Results: The mean amount of MDMA hydrochloride in 101 seized ecstasy tablets was 58.7 +/- 22.9 mg per tablet, with a range of 20 mg to 131 mg per tablet. The majority (96.0%) of tablets contained less than 100 mg MDMA per tablet. There appeared to be a bimodal distribution of MDMA content at approximately 20-40 mg per tablet and 60-80 mg per tablet. Conclusion: There is variability in the MDMA content of ecstasy tablets in the UK. This variability could potentially put users at increased risk of acute harm due to inadvertent excess ingestion of MDMA, as they are unaware of the differences in the MDMA content. Repeat sampling and quantification of MDMA content of ecstasy tablets in the UK will allow better education of users about the potential harms associated with the variability in the MDMA content. In addition, it will provide information to allow the monitoring of changes in not only the MDMA content, but also other adulterants, in ecstasy tablets.