Exposure of children to brominated flame retardants and heavy metals in Morocco: Urine and blood levels in association with global cytosine and adenine methylation.

Persistent pollutants, namely brominated flame retardants (BFRs) and heavy metals, are compounds that are added to a wide range of products and materials for preventing ignition, increasing the functionality of materials or improving their performance, e.g. electric conductivity. The exposure of children might consequently be inferred, through indoor dust and hand-to-mouth or toy-chewing behaviors. The current study is aimed at assessing the exposure of Moroccan children to BFRs and heavy metal elements, and evaluating their associations with global DNA methylation. First, parents responded to a questionnaire pertaining to children's lifestyle, then blood and urine samples were collected from (n = 93) children aged between 5 and 11 years for biomonitoring and DNA methylation analysis. BFRs were detected in 54.84% of samples with a median concentration of 0.01 nmol/mL (range: 0.004-0.051 nmol/mL) while metal elements were detected in more than 90% of samples. BFRs showed no variations with global DNA methylation, unlike metal elements, which revealed significant associations with global DNA methylation markers, namely 5-mC, 5-hmC and N6-mA levels. Moroccan children may be exposed to flame retardants and heavy metals through several routes. Further research is required to assess the exposure and the health impacts of environmental pollutants and ultimately protect the Moroccan population by the prevention of adverse health effects.

Bombé, an undetermined substance that caused an outbreak of illicit drug use in Kinshasa, Democratic Republic of the Congo.

BACKGROUND: Illegal drugs are becoming a public health problem in African cities. In 2021, Bombé, a new drug of unknown composition, caused an outbreak of neuro-psychiatric symptoms in Kinshasa. Bombé was rumored to be based on ground catalytic exhausts stolen from cars. METHODS: The chemical composition of six samples of Bombé obtained from different neighborhoods in Kinshasa was determined by triple quad liquid chromatography-mass spectrometry/mass spectrometry with confirmation by quadrupole time-of-flight mass spectrometry. Metals were determined by inductively coupled plasma-mass spectrometry, and polycyclic aromatic hydrocarbons were measured by gas chromatography-mass spectrometry. RESULTS: Analysis of the Bombé samples revealed that it contained heroin (2-12% of the total area under the curve of the samples) and opioid derivatives, plus paracetamol (33-72%), caffeine (17-26%), and also benzodiazepines (5/6 samples) and cyproheptadine (2/6 samples). The concentrations of neurotoxic metals were unremarkable. The median (range) concentrations of manganese and lead were 9.4 µg/g (range 3-334 µg/g) and 0.36 µg/g (range 0.1-3.12 µg/g ), respectively. All polycyclic aromatic hydrocarbons were below the level of detection (<0.10 µg/g). CONCLUSION: Thanks to international collaboration, Bombé was documented to be a heroin-based drug and its alleged origin from catalytic exhausts was not substantiated. The local human expertise and technical capacity for undertaking toxicological analyses should be increased in Africa.

Exposure of children to glyphosate in Morocco: Urinary levels and predictors of exposure.

Glyphosate is one of the most frequently used organophosphorus plant protection products worldwide, and has recently been classified as probably carcinogenic to humans by the International Agency for Research and Cancer (IARC). We aimed to evaluate the urinary levels of glyphosate and its metabolite aminomethylphosphonic acid (AMPA) in Moroccan children, to identify the main predictors and to perform a risk assessment. Data was collected during a cross sectional study of 48 children from an intensive agricultural area. Measurements included a questionnaire on life-style, socio-demographic and herbicide exposures. Urinary glyphosate and AMPA were extracted using solid phase extraction (SPE) and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Overall, glyphosate and AMPA were detected in 73% and 75% of urine samples, respectively. The mean concentrations were 0.97 µg L-1 (2.06 µg/gcreatinine) for glyphosate and 0.79 µg L-1 (1.52 µg/gcreatinine) for AMPA. Children younger than 5 years had a higher AMPA and glyphosate urine concentration (mean = 2.24 µg L-1; estimation coefficient (EC) = 1.39; 95% CI: 0.54-2.24) (mean = 4.05 µg L-1; EC = 2.92; 95% CI: 1.68-4.15), respectively, than children aged 6-12. Children living near the pesticide spraying fields (<50 m) had 14.91 µg L-1 and 2.35 µg L-1 more glyphosate and AMPA, respectively, than children living in urban counties (95% CI: 8.14-20.91 for glyphosate and 95% CI: 0.55-4.14 for AMPA). AMPA concentration varied significantly with the source of drinking water, AMPA was higher among children that used water from open water sources (mean = 1.49 µg L-1; EC = 2.98; 95% CI/0.67-5.78) compared to those using water from closed water sources. There were also non-significant associations found, such as total household net income, current parental job description, and dietary intake. With the regard to the health risk assessment, estimated daily intake (EDIs), hazard quotient (HQs), and a hazard index (HI) were calculated. The GMs of EDI were 4.38 and 2.26 µg/kg of body weight BW/day for glyphosate and AMPA, respectively. The HQs were calculated considering 0.5 mg/kg BW/day as an acceptable daily intake (ADI), which EFSA has established as a health-based reference value for both analytes. The value obtained were lower than 1, and therefore, low health risk due to glyphosate and AMPA was expected for the target population under the study. This study provides further evidence on factors associated with glyphosate exposure, especially in developing countries.

Quantification of three antineoplastic agents in urine using the UniSpray ionisation source.

BACKGROUND: Many guidelines and safety measures led to a decrease in exposure to antineoplastic agents. Since healthcare workers are often exposed to lower concentrations than patients, a sensitive method is needed to quantify occupational exposure. OBJECTIVE: The aim of this study was to develop and validate a sensitive method for simultaneous detection and quantification of cyclophosphamide, ifosfamide and paclitaxel in urine by use of UPLC-MS/MS with a UniSpray ionisation source. METHODS: Compounds were extracted from urine using Novum simplified liquid extraction cartridges, separated on a C18 column, ionised by a UniSpray ionisation source and detected with MS/MS. In the second part of the study, a field study was performed to assess occupational exposure to antineoplastic agents. RESULTS: Eighty-three samples from healthcare workers were analysed and resulted in seventeen samples containing quantifiable concentrations of at least one compound. In conclusion, a sensitive method for simultaneous detection and quantification of cyclophosphamide (LLOQ 0.05 ng/mL), ifosfamide (LLOQ 0.3 ng/mL) and paclitaxel (LLOQ 0.7 ng/mL) was developed and validated.

Surveillance of Indoor Air Concentration of Volatile Organic Compounds in Luxembourgish Households.

Exposure to air pollution is a well-known health risk. For instance, volatile and very volatile organic compounds (VOCs and VVOCs) are known to cause respiratory, haematologic or immune diseases, and even cancer. Based on the Luxembourgish indoor pollution surveillance program, we performed an exploratory analysis for the period 2014-2019, in order (1) to evaluate the prevalence of VOCs and VVOCs in households, and (2) to estimate the risks of lifelong exposure to selected VOCs on the health of the adult population. The database included 715 indoor air samples from 159 different households. Observed VOC and VVOC levels were similar to those in neighbouring countries. Our health impact assessment identified some health risks associated with the observed concentrations in Luxembourg. Furthermore, this study shows the major public health importance of having a national indoor pollution surveillance system in place. Highlights: (1) This study provides an overview of the domestic indoor pollution in Luxembourg. (2) (V)VOCs levels in Luxembourg were similar to those in neighbouring countries. (3) The results clearly show the importance of having a surveillance system in place.

The Parental Pesticide and Offspring's Epigenome Study: Towards an Integrated Use of Human Biomonitoring of Exposure and Effect Biomarkers.

In Morocco, due to the lack of education and the presence of a counterfeit market, pesticides constitute a major problem to be addressed by occupational and environmental health agencies. This paper aims to introduce the PaPOE (Parental Pesticides and Offspring Epigenome) prospective study and its goals, to motivate the study rationale and design, and to examine comprehensively whether multi-residue exposure to commonly used pesticides could induce epigenetic alterations through the oxidative stress pathway. The PaPOE project includes a cross-sectional study assessing the occupational exposure among 300 farmworkers in Meknes, and initiates a birth cohort of 1000 pregnant women. Data and biological samples are collected among farmworkers, and throughout pregnancy, and at birth. Oxidative stress biomarkers include Glutathione, Malondialdehyde, and 8-OHdG. Global and gene-specific DNA methylation is assessed. The study began enrollment in 2019 and is ongoing. As of 30 June 2021, 300 farmworkers and 125 pregnant women have enrolled. The results are expected to showcase the importance of biomonitoring for understanding individual risks, and to identify a number of regions where DNA methylation status is altered in the pesticides-exposed population, paving the way for an integrated biomonitoring system in Morocco and Africa to assess environmental exposures and their long-term health consequences.

An alternative method to assess permeation through disposable gloves.

Previously, we have demonstrated the capability of activated charcoal cloth (ACC) to assess dermal exposure to VOCs. Here we investigated whether ACC patches can be used as an under-glove indicator to evaluate the ingress of toluene through disposable gloves in a controlled environment, and compared these results to the amount of toluene ingress determined from the standardized test methods for determining chemical permeation through PPE. In a test chamber, with plugs for air sampling, five to six ACC patches were placed on a mannequin hand underneath disposable gloves (latex, nitrile, neoprene, polymer laminate). Three work-exposure scenarios were simulated to assess toluene ingress through the different gloves: vapor exposure; spray exposure, and immersion. The standard permeation test, using a diffusion cell, was carried with glove material of the palm, with continuous contact conditions. In all of ACC test, the order of toluene ingress was latex > neoprene > nitrile > Barrier, but for the standardized testing, the order of the neoprene and nitrile was reversed, and nitrile had higher levels of toluene ingress. These results show the need to think beyond standard testing techniques for occupational exposure to hazardous substances, and the added value of "application style" testing.

Environmental Contamination and Occupational Exposure of Algerian Hospital Workers.

Guidelines are in place to assure limited occupational exposure to cytostatic drugs. Even though this has led to a reduction in exposure, several studies reported quantifiable concentrations of these compounds in healthcare workers. In this study, we evaluated occupational exposure to cytostatic drugs in hospital workers from the University Hospital in Tlemcen, Algeria. Monitoring was performed by collecting wipe samples from surfaces, objects, personal protective equipment (gloves and masks) and from the skin of employees at an Algerian university hospital. Wipe samples were analyzed with ultra-performance liquid chromatography coupled to a mass spectrometer. Concentrations ranged from below the limit of quantification up to 208.85, 23.45, 10.49, and 22.22 ng/cm2 for cyclophosphamide, ifosfamide, methotrexate and 5-fluorouracil, respectively. The highest values were observed in the oncology department. Nowadays, there are still no safe threshold limit values for occupational exposure to cytostatic agents. Therefore, contamination levels should be kept as low as reasonably achievable. Yet, healthcare workers in this hospital are still exposed to cytostatic agents, despite the numerous guidelines, and recommendations. Consequently, actions should be taken to reduce the presence of harmful agents in the work environment.

Biomonitoring for Occupational Exposure to Diisocyanates: A Systematic Review.

Diisocyanates are a group of chemicals that are widely used in occupational settings. They are known to induce various health effects, including skin- and respiratory tract sensitization resulting in allergic dermatitis and asthma. Exposure to diisocyanates has been studied in the past decades by using different types of biomonitoring markers and matrices. The aim of this review as part of the HBM4EU project was to assess: (i) which biomarkers and matrices have been used for biomonitoring diisocyanates and what are their strengths and limitations; (ii) what are (current) biomonitoring levels of the major diisocyanates (and metabolites) in workers; and (iii) to characterize potential research gaps. For this purpose we conducted a systematic literature search for the time period 2000-end 2018, thereby focussing on three types of diisocyanates which account for the vast majority of the total isocyanate market volume: hexamethylene diisocyanate (HDI), toluene diisocyanate (TDI), and 4,4'-methylenediphenyl diisocyanate (MDI). A total of 28 publications were identified which fulfilled the review inclusion criteria. The majority of these studies (93%) investigated the corresponding diamines in either urine or plasma, but adducts have also been investigated by several research groups. Studies on HDI were mostly in the motor vehicle repair industry [with urinary hexamethylene diamine result ranging from 0.03 to 146.5 µmol mol-1 creatinine]. For TDI, there is mostly data on foam production [results for urinary toluene diamine ranging from ~0.01 to 97 µmol mol-1 creatinine] whereas the available MDI data are mainly from the polyurethane industry (results for methylenediphenyl diamine range from 0.01 to 32.7 µmol mol-1 creatinine). About half of the studies published were prior to 2010 hence might not reflect current workplace exposure. There is large variability within and between studies and across sectors which could be potentially explained by several factors including worker or workplace variability, short half-lives of biomarkers, and differences in sampling strategies and analytical techniques. We identified several research gaps which could further be taken into account when studying diisocyanates biomonitoring levels: (i) the development of specific biomarkers is promising (e.g. to study oligomers of HDI which have been largely neglected to date) but needs more research before they can be widely applied, (ii) since analytical methods differ between studies a more uniform approach would make comparisons between studies easier, and (iii) dermal absorption seems a possible exposure route and needs to be further investigated. The use of MDI, TDI, and HDI has been recently proposed to be restricted in the European Union unless specific conditions for workers' training and risk management measures apply. This review has highlighted the need for a harmonized approach to establishing a baseline against which the success of the restriction can be evaluated.

Assessment of the absorbed dose after exposure to surgical smoke in an operating room.

Surgical smoke produced by electrosurgery contains various chemical substances such as volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs). The aim of this study is to investigate airborne concentrations of VOCs and PAHs during electrosurgery in an operating room, in relation to metabolites in urine in order to assess the absorbed dose. A 5-day exposure study was set up in a general surgery operation room including surgeons, scrub assistants and circulation nurses (n = 15). Stationary and personal air sampling for VOCs and PAHs were carried out. Pre-, mid- and end-shift analysis of urinary S-phenylmercapturic acid (SPMA), o-cresol, mandelic acid and 1-hydroxypyrene was performed to assess the internal exposure to respectively benzene, toluene, styrene and PAHs. Several VOCs (styrene, ethyl benzene, benzene and toluene), ranging from 0.7 to 3.27 µg/m3 were detected in the air samples, along with one PAH (naphthalene, ranging from 0.012 to 0.39 µg/m3). There was no significant correlation between air monitoring and urinary biomonitoring. O-cresol levels were increased, especially among assistants and nurses at mid- and end-shift, exceeding current biological exposure indices several times. External and internal exposure for assistants and nurses was substantially more, compared to surgeons. This study confirms the presence of VOCs and PAHs in surgical smoke and shows the presence of their metabolites in urine, but the association is unclear. Urinary biomonitoring shows especially high concentrations of o-cresol.

Systematic review of comparative studies assessing the toxicity of pesticide active ingredients and their product formulations.

Humans are exposed to complex chemical mixtures, such as pesticides. Although the need for the assessment of health and environmental hazards deriving from the interactions between various substances found in commercial pesticide formulations is becoming increasingly recognized, the approval of pesticide products is still mostly limited to determining the toxicity of the individual ingredients ignoring the possible combined effects in mixtures. The objective of this study was to systematically review the literature of in vitro and in vivo studies that simultaneously examine the toxicity of pesticide product formulations and their declared active ingredients to compare their toxicity to human health and to the environment. Two electronic databases were searched for studies that assessed the health effects of active pesticide ingredients and their product formulations. The literature search was performed with a combination of the following terms: "pesticide", "formulation", "commercial product", "commercial pesticide" and "health". After screening by predefined inclusion and exclusion criteria, quality and reliability assessment of eligible publications was conducted by use of the ToxRTool. Two investigators independently screened the identified publications and extracted results from eligible studies. Our search yielded 36 toxicity studies; 23 studies investigated herbicides, 15 examined insecticides and 4 focused on fungicides. Twenty-four studies reported increased toxicity of the product formulations versus their active ingredients, which, in most cases, were attributed to the presence of adjuvants in the formulations. A significant number (n = 10) of studies focused on the comparative testing of glyphosate and glyphosate-based herbicides, and six of them concluded that Roundup, the dominant product formulation of glyphosate, is more toxic than the active ingredient alone. We identified only 8 studies demonstrating reduced toxicity of product formulations in relation to the active ingredient that might be due to a potential antagonistic effect between the constituents. The results of this review demonstrate the inadequacy of current EU testing requirements for assessing the health hazards of pesticide product formulations based mainly on the evaluation of the individual ingredients and of at least one representative use and formulation. Ignoring the possible risks deriving from the interaction between the active and other ingredients of various commercial pesticide product formulations might result in the misinterpretation of its toxicological profile. At EU level efforts are currently made to address this issue. In this context, we recommend that all product formulations should be fully assessed during the authorization process.

Study of temporal variability of salivary cortisol and cortisone by LC-MS/MS using a new atmospheric pressure ionization source.

There is a growing interest concerning the relevance of salivary cortisone levels in stress-related research. However, studies investigating morning patterns and day-to-day variability of cortisone versus cortisol levels are lacking. Cortisol and cortisone analysis by liquid chromatography-tandem mass spectroscopy (LC-MS/MS) has been widely used for routine laboratory measurements in the last years. The aim of this study was to develop an ultra-performance LC-MS/MS method for the simultaneous quantification of salivary cortisol and cortisone levels for assessing the temporal variability of these hormones. Saliva samples were collected from 18 healthy volunteers at 0, 15, and 30 min after awakening on each day for 1 week and analysed with the newly developed method. We used a novel atmospheric pressure ionization source, which resulted in high sensitivity and specificity for both cortisol and cortisone as well as higher peak values and signal-to-noise ratio as compared with the electrospray ionization source. Cortisone showed similar morning patterns as cortisol: a 25% and 49% increase in levels at 15 and 30 min after awakening, respectively. Most cortisone indices showed somewhat lower day-to-day variability and were less affected by state-related covariates. We recommend further exploration of the potential of salivary cortisone as a biomarker in stress-related research.

Assessment of exposure of gas station attendants in Sri Lanka to benzene, toluene and xylenes.

Exposure to benzene, toluene and p-, m-, o-xylene (BTX) was studied in 29 gas station attendants and 16 office workers in Sri Lanka. The aim of this study was to assess the exposure level and identify potential exposure mitigating measures. Pre- and post-shift samples of end-exhaled air were collected and analysed for BTX on a thermal desorption gas chromatography mass spectrometry system (TD-GC-MS). Urine was collected at the same timepoints and analysed for a metabolite of benzene, S-phenyl mercapturic acid (SPMA), using liquid chromatography-mass spectrometry (LC-MS). Environmental exposure was measured by personal air sampling and analysed by gas chromatography flame ionization detection (GC-FID). Median (range) breathing zone air concentrations were 609 (65.1-1960) µg/m3 for benzene and 746 (<5.0-2770) µg/m3 for toluene. Taking into account long working hours, 28% of the measured exposures exceeded the ACGIH threshold limit value (TLV) for an 8-h time-weighted average of 1.6 mg/m3 for benzene. Xylene isomers were not detected. End-exhaled air concentrations were significantly increased for gas station attendants compared to office workers (p < 0.005). The difference was 1-3-fold in pre-shift and 2-5-fold in post-shift samples. The increase from pre-to post-shift amounted to 5-15-fold (p < 0.005). Pre-shift BTX concentrations in end-exhaled air were higher in smokers compared to non-smokers (p < 0.01). Exposure due to self-reported fuel spills was related to enhanced exhaled BTX (p < 0.05). The same was found for sleeping at the location of the gas station between two work-shifts. Benzene in end-exhaled air was moderately associated with benzene in the breathing zone (r = 0.422; p < 0.001). Median creatinine-corrected S-phenyl mercapturic acid (SPMA) was similar in pre- and post-shift (2.40 and 3.02 µg/g) in gas station attendants but increased in office workers (from 0.55 to 1.07 µg/g). In conclusion, working as a gas station attendant leads to inhalation exposure and occasional skin exposure to BTX. Smoking was identified as the most important co-exposure. Besides taking preventive measure to reduce exposure, the reduction of working hours to 40 h per week is expected to decrease benzene levels below the current TLV.

Integrated evaluation of solvent exposure in an occupational setting: air, dermal and bio-monitoring.

The assessment of dermal exposure to volatile organic compounds (VOCs) is becoming increasingly important in industrial settings. The study aimed to evaluate the overall exposure (inhalation and dermal) of workers to VOCs, and to assess the suitability of activated charcoal cloth (ACC) patches for the evaluation of the contribution of dermal exposure (vs. inhalation exposure) to the whole body burden, as reflected by human biomonitoring. Inhalation exposure to toluene, acetone and styrene (passive 3 M organic vapour monitors, OVMs) and dermal exposure (ACC patches on the index finger, thumb and neck) were measured simultaneously in 37 subjects performing different tasks in a factory of thermoplastic panels. Systemic exposure was assessed in urine by quantification of mandelic acid (MA) and phenyl glyoxylic acid (PGA), as biomarkers for styrene, as well as acetone and hippuric acid (HA) as biomarkers for acetone and toluene, respectively. High styrene (range 30.66-302 mg/m3) and acetone (range 11-644 mg/m3) concentrations were found in the air of the workplace, while toluene was less abundantly present (range 0.05-2.6 mg/m3). On the ACC patches, considerable amounts of these VOCs were found. For employees manually handling styrene, dermal exposure on the index finger and thumb were substantially higher compared to the neck ACC patch. A good correlation between air and urinary levels of acetone exposure was found. MA and PGA levels in urine, markers for styrene exposure, were correlated with both air and dermal exposure. These data suggest that there is a substantial benefit from assessing dermal exposure in the work place in addition to the more conventional air monitoring and urinary biomonitoring.

A Method to Quantitatively Assess Dermal Exposure to Volatile Organic Compounds.

Assessing dermal exposure of workers to noxious chemicals becomes increasingly important in industrial settings. Among various chemicals, volatile organic compounds (VOCs) are widely used in industrialized countries, but still there are no validated methodologies able to accurately quantify skin exposure. In this study, we developed a sensitive methodology based on activated charcoal cloth (ACC) to quantitatively assess skin exposure to 181 VOCs. The majority of the VOCs (156) showed a constant desorption efficiency (DE) of ~100% over the studied concentration range. Seven VOCs showed a concentration dependency for the DEs, which we described by a Dubinin-Raduskevich desorption isotherm. For 18 compounds, the DEs were situated below 80% but showed to be constant over the concentration range. All tested VOCs showed a good storage stability on ACC, especially at -80°C storage. Only for n-pentane there was a decrease of ~40% when it was stored for a month. In a controlled environment test, ACC has shown to reflect well the increasing concentrations of VOCs in the air with a high linearity (R2 ≥ 0.812, except for gamma-butyrolactone where R2 = 0.570). In this study, we show that ACC is a suitable sampling material for quantitatively assessing dermal exposure to 181 VOCs in terms of sensitivity and DE. This method will allow more studies that are detailed on dermal exposure, which will lead to a better assessment of skin exposure in occupational settings.