Sewage analysis as an alternative tool for assessing drug of abuse and new psychoactive substances in Tunisia.

Many studies attest to the pollution of wastewaters by organic molecules including drug of abuse (DAs) residues and new psychoactive substances (NPS) at trace levels. The occurrence of these emerging micropollutants in influent wastewaters (IWW) from three Tunisian Wastewater Treatment Plants (WWTPs) was assessed. Influent wastewater composite samples (24 h) were collected over 7 consecutive days in November 2019. The determination and quantification of 11 drug of abuse or their metabolites was performed by the application of an optimized multi-residue method liquid chromatography tandem mass spectrometry (LC-MS/MS). MDMA, THC and the cocaine metabolite benzoyl ecgonine were the most detected substances across the three investigated sewage plants. A new wastewater-based epidemiology (WBE) approach was applied in this study to estimate illicit drug consumption. This innovative approach was used to calculate and to assess collective drug consumption of illicit drug at a community level, based on the concentration of selected illicit substances and their major metabolites in influent wastewater. The average MDMA consumption found in the selected cities ranged between 35,8-1531,1 mg day- 1/1000 inhabitants and increased during the weekends. Cocaine consumption varied from 24.5 to 179.8 mg day- 1/1000 inhabitants. Complementary qualitative investigation of new psychoactive substances was monitored for the first time for an African country, examining the occurrence of 33 NPS in wastewaters samples. Out of 33 totals screened NPS across all sampling sites, 16 were tentatively identified with this approach. The 16 detected NPS covered most of the representative and used molecules of different NPS classes; including synthetic opioids, synthetic cathinones, amphetamines derivatives and synthetic cannabinoids.

Illicit substances identified in the urine of 11.170 suspected drug users in North Tunisia.

INTRODUCTION: according to the latest World Drug Report, 271 million people worldwide (5.5% of the global population) aged 15-64 years are drug users. Drug addiction and trafficking became an urgent public health problem that affects human health and social life. A cross-sectional study was conducted from January 2016 to December 2018, to identify the socio-demographic profile of drug users captured by the anti-narcotics squad in North of Tunisia (North African country) and to type, through toxicological analysis, the nature of the substances consumed. METHODS: data were collected from expertise files of 11170 suspected drug users. Fresh urine samples were collected from suspected drugs users and submitted in the toxicology laboratory of the center for Urgent Medical Assistance (Tunis) for forensic urinalysis. Drugs screening was carried out by immunochemical methods. Positive samples were analyzed with gas chromatography coupled to mass selective detector (GC-MS) for confirmation. RESULTS: the investigation revealed that drug users were mainly males 97.4% (sex ratio 37), the median age was 29 ± 7.91 years, 91.3% were singles and 79% were daily workers. On a total of 11170 urine samples screened, 5 409 (48.4%) were positives for illicit drugs. The prevalence of positive samples was 55.4% in 2016; 50.45% in 2017 and 40.8% in 2018. Cannabis was the most widely consumed drug (95%), followed by Benzodiazepines (1.2%), Buprenorphine (1%), cocaine (0.95%), MDMA (0.24%) and opiates (0.13%). Polydrug abuse was observed in 79 specimens (1.5%). CONCLUSION: this study provides an overview of the illicit drug consumption in the north of Tunisia (knowing that nowadays epidemiological data are almost same since 2016) in order to set up an effective policy to fight against drugs and addictive behaviors and to provide health professionals with the epidemiological elements necessary for better medical care of drug users.

Effects of lead, cadmium, copper and zinc levels on the male reproductive function.

This study aimed to investigate the effects of heavy metals on measures of male fertility. One hundred and two infertile men with occupational exposure and thirty fertile men were included in this study. Blood and urinary levels of lead, cadmium, zinc and copper were measured by atomic absorption spectrophotometry. Semen parameters and a motile sperm organelle morphology examination were also performed. Measures of hormonal levels, oxidation-reduction potential, DNA fragmentation index and chromatin condensation were assessed for all participants. Heavy metals levels, oxidative stress and DNA quality were significantly higher in the infertile group compared to controls. FSH and testosterone levels were lower in the infertile group. A urinary cadmium level was positively associated with abnormal sperm morphology (r = .225, p < .05). Normal morphology was inversely correlated with the duration of the exposure (r = -.227, p = .022). The blood lead level was positively related to the level of testosterone (r = .223, p = .031). Cadmium and lead blood levels were positively correlated with the level of chromatin decondensation (r = .528, p < .001; r = .280, p = .017). Our study showed that occupational exposure to heavy metals is very harmful to reproductive health. DNA quality and oxidative stress investigations must be recommended for reprotoxic exposed patients prior to in vitro fertilisation treatment.

Biomonitoring chronic lead exposure among battery manufacturing workers in Tunisia.

The aim of the study was the biomonitoring of the chronic exposure to Pb by measuring its levels in blood, urine, and hair of battery workers. Blood lead (BPb), urinary lead (UPb), hair lead (HPb), and urinary δ-aminolevulinic acid (UALA) levels were determined for 52 workers in a battery plant and compared to those of 20 non-occupational exposed subjects (controls). BPb and UPb levels were determined by graphite furnace atomic absorption spectrometry (GFAAS). HPb levels were measured by triple quadrupole ICP-MS and UALA levels were determined using cation exchanger column. The measured levels were significantly higher compared to the controls exceeding the OSHA cutoff values (p < 0.01). The GM mean levels of BPb, UPb, UALA, and HPb of workers were 715 µg L-1, 331 µg L-1, 16.3 mg g-1, and 234 µg g-1, respectively. The GM mean levels of BPb, UPb, UALA, and HPb of controls were 93.6 µg L-1, 36.3 µg L-1, 1.9 mg g-1, and 1.8 µg g-1, respectively. Significant correlations were observed between BPb and UALA (r = 0.630, p = 0.000), UPb and UALA (r = 0.566, p = 0.000), and between BPb and HPb (r = 0.466, p = 0.004). The significant correlation between BPb and HPb suggests the usefulness of hair for assessing occupational exposure particularly when the study area presents medium to high levels of Pb pollution. The association between Pb biomarkers and potential confounding factors revealed significant influence of the occupational factor over smoking and alcohol consumption. The results of this study urge for the reinforcement of the implemented engineering controls and safety measures in order to reduce exposure and to address the health issues related to Pb poisoning.

Evaluation of the status and the relationship between essential and toxic elements in the hair of occupationally exposed workers.

Lead poisoning is a common disease in lead-acid battery manufacturing industries. Workers can be also exposed to various toxic elements present as contaminants or used as catalysts to enhance batteries' performances. In the present study, levels of essential and toxic elements and their relationship were assessed by analyzing scalp hair samples of 52 workers in a Pb battery manufacturing plant. The impact of some confounding factors on hair mineral contents was also investigated. For comparative purposes, nonoccupationally exposed subjects were selected as controls. All elements were determined by triple quadrupole ICP-MS. The results indicated significantly higher levels of Pb, Sb, As, and Cd in the hair of workers when compared to controls (p < 0.01). The Spearman correlation test revealed significant correlations between Pb/Cr, Pb/Mn, Pb/Ni, Pb/As, Pb/Se, Pb/Sb, Hg/As, Hg/Sn, Hg/Sb, Sb/Cr, Sb/As, Sb/Se, Sb/Cd, Sb/Sn, Sn/Cr, Sn/As, Sn/Cd, Cd/As, Se/Ni, As/Cr, Ni/Cr, Ni/Mn, and Mn/Cr in the hair of workers and Pb/Cr, Pb/Mn, Pb/Ni, Pb/Cd, Mn/Ni, Mn/Cd, Cd/Ni, As/Ni, Sn/Ni, Sb/Sn, and Hg/Sn in the hair of controls. Multiple linear regression analysis revealed linear dependence including Cr = f(Pb, Ni, Sb), Mn = f(Ni, Sb), Ni = f(Mn, Cr, -Cd) (Cd was negatively correlated, ß < 0), As = f(Sn, Sb, Hg), Se = f(Ni); Sn = f(As), Sb = f(As, Mn, -Hg, Sn, Se, -Ni) (Hg and Ni were negatively correlated), Hg = f(As, -Sb, Sn) (Sb was negatively correlated), and Pb = f(Cr). The result of this study can be very useful to explain the interactions between elements or for comparison studies when establishing reference ranges or monitoring elements in workplaces.

Health Risk Assessment of Heavy Metals in Traditional Cosmetics Sold in Tunisian Local Markets.

This study was undertaken in order to determine heavy metal contents in twelve (n = 12) henna brands and eleven (n = 11) kohl products. An analytical test was performed for Pb, Cd, Cu, and Zn in henna and kohl products using atomic absorption spectrophotometery. The overall mean concentrations of heavy metals in henna varied between 1.2 and 8.9 µg g(-1) for Pb; 0.8 and 18.6 µg g(-1) for Cd; 0.5 µg g(-1) and 3.3 µg g(-1) for Cu; and 3.7 µg g(-1) and 90.0 µg g(-1) for Zn. As for kohl products, Pb concentrations ranged between 51.1 µg g(-1) and 4839.5 µg g(-1), Cd concentrations ranged between 1.0 µg g(-1) and 158.6 µg g(-1), Cu concentrations ranged between 2.5 µg g(-1) and 162.5 µg g(-1), and Zn concentrations ranged between 0.7 µg g(-1) and 185.0 µg g(-1). The results of our study revealed that Pb, Cd, Cu, and Zn contents in investigated samples were high, making from the prolonged use of such products a potential threat to human health. Therefore, major quality controls are recommended in order to enforce acceptable limits of potential contaminants in cosmetics and good manufacturing practice.

[Acute poisoning with anticholinesterase carbamate pesticides: methomyl-lannate®]. / Intoxications aiguës aux pesticides anti-cholinestérasiques de type carbamate : méthomyl-lannate®.

The methomyl is increasingly involved in suicidal and autolytic attempts. Intoxication with carbamate (CM) compounds is still a frequent cause for admission in the Emergency department of the medical assistance center (MAC) in Tunis, Tunisia. The aim of this study was to describe the demographics, clinical features and hospital course of patients presenting with CM intoxication to the ED of MAC in Tunis, Tunisia. This was a retrospective study about 52 cases of acute poisoning by methomyl, compiled in the MAC from 1st January, 2009 to December 31, 2012. Intoxications were all oral, mostly intentional (33 cases: 65%) and in young patients (29 years old). Females outnumbered males by almost 2:1. The most frequent symptom was hypotension (41 cases: 80%), followed by miosis (39 cases: 75%), rhabdomyolysis (29 cases: 55%), vomiting (18 cases: 43%), bronchorrhea (14 cases: 27%), diarrhea (11 cases: 21%) and fasciculations (8 cases: 17%). Treatments included gastric lavage in 16 patients (32%), assisted ventilation in 8 cases (17%) and atropine in 44 patients (85%). Seven patients died during hospitalization. Pesticide poisoning is a significant public health problem and some preventive measures must be strictly enforced to limit this kind of intoxication.

Detection and disposition of JWH-018 and JWH-073 in mice after exposure to "Magic Gold" smoke.

The disposition in mice of the cannabimimetics JWH-018 and JWH-073 in blood and brain following inhalation of the smoke from the herbal incense product (HIP) "Magic Gold" containing 3.6% JWH-018, 5.7% JWH-073 and less than 0.1% JWH-398 (w/w) is presented. Specimens were analyzed by HPLC/MS/MS. The validation of the method is also presented. Five C57BL6 mice were sacrificed 20 min after exposure to the smoke of 200 mg of "Magic Gold" and a second set of five exposed mice were sacrificed after 20 h. Twenty minutes after exposure to "Magic Gold" smoke, blood concentrations of JWH-018 ranged from 42 to 160 ng/mL (mean: 88 ng/mL ± 42) and those of JWH-073 ranged from 67 to 244 ng/mL (mean: 134 ng/mL ± 62). Brain concentrations 20 min after exposure to "Magic Gold" smoke for JWH-018 ranged from 225 to 453 ng/g (mean: 317 ng/g ± 81) and those of JWH-073 ranged from 412 to 873 ng/g (mean: 584 ng/g ± 163). Twenty hours after exposure to "Magic Gold" smoke, JWH-018 was detected and quantified in only two of the five blood samples. Blood concentrations of JWH-018 were 3.4 ng/mL and 9.4 ng/mL. JWH-073 was detected in only one blood specimen 20 h after exposure at 4.3 ng/mL. Brain concentrations 20 h post exposure for JWH-018 ranged from 7 to 32 ng/g (mean: 19 ng/g ± 9). JWH-073 was not detected in 20 h post exposure brain specimens. JWH-398 was not detected in any of the blood or brain samples. The disposition data presented with the limited data available from human experience provide reasonable expectations for forensic toxicologists in JWH-018 or JWH-073 cases. As with THC after smoking marijuana, blood and brain concentrations of JWH-018 and JWH-073 after HIP smoking can be expected to rise initially to readily detected values, and then drop dramatically over the next few hours to several ng/mL or ng/g, and finally to be at extremely low or undetectable concentrations by 24h apparently due to extensive biotransformation, and redistribution to body fat.

Determination of naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018) in mouse blood and tissue after inhalation exposure to 'buzz' smoke by HPLC/MS/MS.

The disposition of the cannabimimetic naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018) in mice following inhalation of the smoke of the herbal incense product (HIP) 'Buzz' is presented. A high-pressure liquid chromatography with electrospray ionization triple quadrupole mass spectrometer (HPLC/MS/MS) method was validated for the analysis of JWH-018 in the specimens using deuterated Δ(9) -tetrahydrocannabinol (d(3) -THC) as the internal standard. JWH-018 was isolated by cold acetonitrile liquid-liquid extraction. Chromatographic separation was performed on a Zorbaz eclipse XDB-C(18) column. The assay was linear from 1 to 1000 ng/mL. Six C57BL6 mice were sacrificed 20 min after exposure to the smoke of 200 mg 'Buzz' containing 5.4% JWH-018. Specimen concentrations of JWH-018 were: blood, 54-166 ng/mL (mean 82 ± 42 ng/mL); brain, 316-708 ng/g (mean 510 ± 166 ng/g); and liver, 1370-3220 ng/mL (mean 1990 ± 752 ng/mL). The mean blood to brain ratio for JWH-018 was 6.8 and ranged from 4.2 to 10.9. After exposure, the responses of the mice were consistent with cannabinoid receptor type 1 activity: body temperatures dropped 7.3 ± 1.1 °C, and catalepsy, hyperreflexia, straub tail and ptosis were observed. The brain concentrations and physiological responses are consistent with the hypothesis that the behavioral effects of 'Buzz' are attributable to JWH-018.