Dangerous exposures to chemicals managed by Poison Centers all around the world during the COVID-19 pandemic: a systematic review and proportional meta-analysis.

INTRODUCTION: During COVID-19 pandemic, cleaning/disinfection activities were highly recommended. This study summarizes the state of art and estimates the prevalence of dangerous exposures to specific chemicals managed by Poison Centers (PCs) from all over the world during 2020 vs 2019, trying to overcome the critical aspects of the product categorization systems used by PCs. MATERIALS AND METHODS: A systematic research was conducted in 3 major databases and 2 websites of PCs associations. Proportional meta-analyses were performed to estimate the prevalence of exposures to disinfectants, household products and hand sanitizers in 2020 vs 2019. RESULTS: The pooled prevalence of exposures to disinfectants, household products and hand sanitizers were respectively 5.9% (95% CI 4.9-7.0) (2019: 4.4% vs 2020: 7.8%; p=0.22), 25.9% (95% CI 24.0-27.7) (2019: 25.0% vs 2020: 28.6%; p=0.71) and 1.6% (95% CI 1.3-1.9) (2019: 0.6% vs 2020: 2.8%; p<0.001). CONCLUSIONS: This study detected overall increases of exposures to specific chemicals in 2020, suggesting that the awareness on topics related to the safe use of these products should be improved, especially during health emergencies, highlighting the need to develop standardized systems to better compare data coming from PCs all over the world.

Biodegradable scaffolds based on plant stems for application in regenerative medicine.

Several synthetic and natural materials have been studied for the confection of temporary grafts for application in regenerative medicine, however, the development of a material with adequate properties remains a challenge, mainly because its degradation kinetics in biological systems. Nature provides materials with noble properties that can be used as such for many applications, thus, taking advantage of the available morphology and assembled structures of plants, we propose to study the vegetable stems for use as temporary graft. Since thein vivodegradation is maybe one of the most important features of the temporary grafts, here we have implanted the plant stems from pumpkin, papaya, and castor into the subepithelial tissue of animals and followed their biodegradation process and the local inflammatory response. Mechanical tests, FTIR and contact angle with water were also analysed. The results indicated the mechanical properties and the contact angle were adequate for use in regenerative medicine. The results of thein vivostudies indicated a beneficial inflammatory process and a gradual disintegration of the materials within 60 days, suggesting the plants stems as new and potential materials for development of grafts for use in the field of regenerative medicine.

Quantification of preservatives in tattoo and permanent make-up inks in the frame of the new requirements under the REACH Regulation.

BACKGROUND: According to the REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) restriction, tattoo and permanent make-up (PMU) inks placed on the European Union market after January 4, 2022, shall not contain methylisothiazolinone, benzisothiazolinone (BIT), octylisothiazolinone (OIT), or other skin sensitizers in concentrations of 10 mg/kg or higher and phenoxyethanol (PE) or other eye irritants or damaging substances in concentrations of 100 mg/kg or higher. In addition, preservatives and other substances enlisted in Annex II to Cosmetic Product Regulation shall not be present in concentrations of 0.5 mg/kg or higher. OBJECTIVES: This study aims to quantify 14 preservatives in 99 tattoo and 39 PMU inks from the Italian market and presents a comparison with concentration limits set by the REACH restriction. METHODS: Inks were analysed by applying validated analytical methods based on liquid chromatography techniques. RESULTS: About 24.0%, 15.2% and 1.5% of the overall samples contained BIT, PE and OIT, respectively, at concentrations exceeding REACH concentration limits. The number of noncompliant tattoo inks (49.5%) would be significantly greater than that of the PMU inks (17.9%). CONCLUSIONS: About 40.6% of the samples would be noncompliant with the restriction for the presence of preservatives above the permitted level. Additional concentration limits will apply to skin sensitizing preservatives for proper labelling of inks under CLP (Classification, Labelling and Packaging) Regulation.

Monitoring of alcohol-based hand rubs in SARS-CoV-2 prevention by HS-GC/MS and electrochemical biosensor: A survey of commercial samples.

Alcohol-based hand rubs (ABHRs) have found large diffusion during the Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV-2, thus becoming the most widespread means for hand hygiene. Whereby, it is fundamental to assess the alignment of commercial ABHRs to the indications provided by the principal health agencies regarding alcohol content and possible impurities. In this work, a novel improvement of previous existent methods for the determination of alcohol content in such products was reported. In particular, two alternative sensitive and reproducible methods, such as an electrochemical screen-printed based enzymatic (alcohol oxidase) biosensor and a Headspace Gas Chromatography coupled with Mass Spectrometry (HS-GC/MS) were proposed. The electrochemical device represents a rapid, low-cost and accurate fraud screening method for alcohol-based hand rubs. The second technique confirms, identifies and simultaneously determines ethyl alcohol, isopropyl alcohol, n-propyl alcohol and methyl alcohol, improving their extraction through acidification in the sample pre-treatment step. The developed specific HS-GC/MS method was in-house validated according to ISO/IEC 17025 requirements. Analytical parameters such as limit of detection (LoD 0.13%v/v - 0.17%v/v), limit of quantification (LoQ 0.44% v/v - 0.57% v/v), inter-day repeatability (RSDR 2.1-10.7%) and recovery (80-110%) were assessed. The relative expanded uncertainties range (between 0.1%v/v and 3.4%v/v) for all the analytes were evaluated. Results obtained using the different analytical approaches were compared and indicated that the two data sets were comparable (median; HS-GC/MS, 56%v/v; electrochemical biosensor, 62%v/v) and were not statistically different (one-way ANOVA test; p = 0.062). In addition, a good correlation (95%) was found. This study noticed that only 39% of the tested hand sanitiser products had the recommended average alcohol content, thus highlighting the need for analytical controls on this type of products.

Proof of nicotine transfer to rat pups through maternal breast feeding to evaluate the neurobehavioral consequences of nicotine exposure.

This study investigates the transfer of nicotine from lactating dams to their offspring through breast milk, in the frame of a research focused to ascertain toxicological and neuro-behavioural effects on pups as consequence of either unavoidable ("yoked & forced") or voluntary ("freely-chosen") maternal nicotine exposure. To this aim, plasmatic concentrations of nicotine and cotinine were determined by LC-MS/MS in Wistar rat pups whose mothers were orally administered with nicotine during lactation. Mothers were divided into a voluntary drinking group, an unavoidable consumption group, and controls. The limits of detection and quantification of the LC-MS/MS method were 0.20 and 0.65 ng/mL, respectively. Within-laboratory reproducibility (CV%) was <12%, with recovery of 86.2-118.8%. Results showed the presence of nicotine in 67% of samples from freely-chosen consumption group (1.30 ± 0.31 ng/mL) and in 60% of samples from yoked-consumption group (1.19 ± 0.62 ng/mL); cotinine was found in all the samples from freely-chosen (1.92 ± 0.77 ng/mL) and yoked-consumption groups (1.43 ± 0.30 ng/mL). Data provide an evidence-based support to maternal/offspring nicotine transfer as function of different ways of oral exposure.

Liquid chromatography with tandem mass spectrometry method for the determination of nicotine and minor tobacco alkaloids in electronic cigarette refill liquids and second-hand generated aerosol.

A liquid chromatography with tandem mass spectrometry method for the simultaneous quantification of nicotine and seven minor tobacco alkaloids in both refill liquids for electronic cigarettes and their generated aerosol was developed and validated. The limit of detection and limit of quantification values were 0.3-20.0 and 1.0-31.8 ng/mL, respectively. Within-laboratory reproducibility was 8.2-14.2% at limit of quantification values and 4.8-12.7% at other concentration levels. Interday recovery was 75.8-116.4%. The method was applied to evaluate the compliance of commercial liquids (n = 95) with their labels and to assess levels of minor alkaloids. Levels of nicotine and its corresponding compounds were also evaluated in generated aerosol. About 47% of samples showed differences above ±10 % of the stated nicotine concentration. About 78% of the "zero nicotine" liquids showed traces in the range of 1.3 ± 0.1-254.0 ± 14.6 µg/mL. Nicotine-N'-oxides, myosmine, and anatabine were the most common minor alkaloids in liquids containing nicotine. Nicotine and N'-oxides were detected in all air samples when aerosol was generated from liquids containing nicotine. Nicotine average emissions from electronic cigarette (2.7 ± 0.9 µg/m3 ) were significantly lower (p < 0.01, t-test) with respect to conventional cigarette (30.2 ± 1.5 µg/m3 ).

The chemical components of electronic cigarette cartridges and refill fluids: review of analytical methods.

INTRODUCTION: To date, several concerns have been raised on the purity of ingredients employed in the manufacturing processes of refill fluids and cartridges, the device functionality, and the quality control of electronic cigarettes. This article reviews analytical methods so far described for the analysis of liquids to detect their chemical components and to investigate the presence of toxicants and carcinogens that can potentially occur as impurities of ingredients or as a consequence of their degradation. RESULTS AND DISCUSSION: Based on the scientific literature, high-performance liquid chromatography with diode-array detection (HPLC/DAD) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) are most appropriate for determining nicotine and related compounds in fluids and cartridges, whereas LC-MS/MS has been successfully used to determine nitrosamines. Content analyses of glycols have been performed using gas chromatography equipped with flame ionization detector or gas chromatography/mass spectrometry (GC/MS), whereas carbonyl and other volatile organic compounds determinations have been performed by HPLC/DAD and GC/MS, respectively. Content analyses of heavy metals have been performed by inductively coupled plasma optical emission spectroscopy or inductively coupled plasma mass spectrometry. Since new potentially toxic substances may be created during heating, it is also necessary to investigate the chemical composition of generated aerosol. In this case, similar methods applied for tobacco smoke can be adopted. CONCLUSIONS: A broad range of analytical techniques are available for the detection of constituents and toxicants in e-liquids and cartridges. Analyses of liquids have been performed with pharmacopeia procedures and methods (International Organization for Standardization, Environmental Protection Agency, and American Public Health Association) developed for other matrices but applicable to e-liquids. Because new potentially harmful substances may be produced during heating process, analyses of aerosol are needed to correlate its composition to the chemical components of liquids.

Excretion profile of corticosteroids in bovine urine compared with tissue residues after therapeutic and growth-promoting administration of dexamethasone.

The illicit use of dexamethasone as growth-promoting agent in animal breeding is still practiced within the EU constituting a health risk for meat consumers. An experimental study was developed to assess dexamethasone urinary excretion and tissue distribution (liver, kidney, and muscle) in male calves after therapeutic and growth-promoting administration. Urine and tissue samples collected from treated and untreated bovines were also investigated for the presence of other natural and synthetic corticosteroids (prednisolone, prednisone, hydrocortisone, and cortisone), in order to study a possible correlation with dexamethasone administration and to clarify prednisolone origin. Analyses were performed by a multi-residue LC-MS/MS method developed and validated according to the Commission Decision 2002/657/EC. The results confirm the rapid rate of dexamethasone urinary excretion, irrespective of the dosage, the duration and the route of administration, and the disappearance of cortisone and hydrocortisone during the treatment. Dexamethasone was distributed to the tissues where the elimination rate proceeded relatively slower as suggested by the presence of residues one month after the withdrawal of the therapeutic treatment. An increase in the number of positive findings for prednisolone, in association with higher levels of cortisone and hydrocortisone, was observed in urine samples collected from slaughterhouse rather than those collected at the farm. Prednisone residues were found only in one urine sample that showed the highest levels of prednisolone, hydrocortisone, and cortisone. The occurrence of prednisolone residues in urine and even in tissue samples confirms the endogenous nature of this molecule.

Studies on the presence of natural and synthetic corticosteroids in bovine urine.

Natural and synthetic corticosteroids are widely used in veterinary medicine for their anti-inflammatory properties, but are also illegally used in animal breeding as growth-promoting agents: this latter application in livestock production has been banned within the European Union due to health concerns for the consumer. In this work urine samples collected from bovines experimentally treated with dexamethasone (0.4 mg of dexamethasone 21-disodium phosphate per capita/day for 20 consecutive days) and bovines bred under strictly controlled conditions were investigated for the presence of natural and synthetic corticosteroids, using a simple multi-residue liquid chromatography-tandem mass spectrometry method, developed and validated in accordance with the criteria of the Commission Decision 2002/657/EC. The aim of this work is to investigate the effect of a low dosage and long term dexamethasone treatment on the levels of endogenous corticosteroids in cattle and to evaluate the possible presence of prednisolone residues in bovines bred under strictly controlled conditions. Our findings confirm the high and rapid rate of dexamethasone urinary excretion. Dexamethasone treatment elicited an early reduction of hydrocortisone and cortisone, suggesting the disappearance of these two hormones as an indirect indicator of corticosteroid treatment in cattle. Prednisolone residues were found (concentration interval 0.4-1.4 ngmL(-1)) in urine samples collected from control bovines especially at the slaughterhouse, together with high levels of hydrocortisone and cortisone. Further studies are necessary to find out the reason of unexplained excretion of this hormone in urine samples of untreated bovines.

Simultaneous analysis of 17alpha-estradiol and 17beta-estradiol in bovine serum by liquid chromatography-tandem mass spectrometry.

A new LC-MS/MS method for the separation, identification and quantification of residues of 17alpha-estradiol (17alpha-E2) and 17beta-estradiol (17beta-E2) in bovine serum is reported. Deuterium-labelled 17beta-estradiol was used as internal standard. The method was in-house validated in accordance with European Union criteria and adopted in a proficiency study organised by the Community Reference Laboratory (CRL-RIVM, Bilthoven, The Netherlands). The analytes were extracted from serum using acetate buffer, purified by C18 solid-phase extraction (SPE) and chromatographed on a C18 LC column. They were then ionized in a heated nebulizer (HN) interface operating in negative ion mode, where only intact deprotonated molecules, [M-H](-), were generated at m/z 271 and 274 for 17alpha/17beta-E2 and 17beta-E2-d(3), respectively. The decision limits obtained (CCalpha, i.e., critical concentration alpha) were 0.06 ng/mL and 0.03 ng/mL, respectively for 17alpha-E2 and 17beta-E2. Detection capability (CCbeta, i.e., critical concentration beta) values were 0.08 ng/mL and 0.04 ng/mL, respectively, for 17alpha-E2 and 17beta-E2. Precision, accuracy and specificity were satisfactory, recovery ranged from 86.3% to 93.2% and the method resulted sensitive for the required purposes. This method is currently in use for Official Control purposes.

Integrated analytical approach in veal calves administered the anabolic androgenic steroids boldenone and boldione: urine and plasma kinetic profile and changes in plasma protein expression.

Surveillance of illegal use of steroids hormones in cattle breeding is a key issue to preserve human health. To this purpose, an integrated approach has been developed for the analysis of plasma and urine from calves treated orally with a single dose of a combination of the androgenic steroids boldenone and boldione. A quantitative estimation of steroid hormones was obtained by LC-APCI-Q-MS/MS analysis of plasma and urine samples obtained at various times up to 36 and 24 h after treatment, respectively. These experiments demonstrated that boldione was never found, while boldenone alpha- and beta-epimers were detected in plasma and urine only within 2 and 24 h after drug administration, respectively. Parallel proteomic analysis of plasma samples was obtained by combined 2-DE, MALDI-TOF-MS and muLC-ESI-IT-MS/MS procedures. A specific protein, poorly represented in normal plasma samples collected before treatment, was found upregulated even 36 h after hormone treatment. Extensive mass mapping experiments proved this component as an N-terminal truncated form of apolipoprotein A1 (ApoA1), a protein involved in cholesterol transport. The expression profile of ApoA1 analysed by Western blot analysis confirmed a significant and time dependent increase of this ApoA1 fragment. Then, provided that further experiments performed with a growth-promoting schedule will confirm these preliminary findings, truncated ApoA1 may be proposed as a candidate biomarker for steroid boldenone and possibly other anabolic androgens misuse in cattle veal calves, when no traces of hormones are detectable in plasma or urine.

Synthesis of hydroxystilbenes and their derivatives via Heck reaction.

A group of differently substituted acetoxy- and methoxystilbenes were synthesised via Heck reaction. A comparison between the use--as coupling reagents--of iodobenzene derivatives and diazonium salts was performed. A successful microwave-assisted demethylation by pyridine hydrochloride of some methoxystilbenes was carried out.

An improved synthesis of resveratrol.

In this article we report an improved total synthesis of resveratrol, increasing the overall yield from 22 to 71%. The synthesis reported in our previous publication was made up of two fundamental steps: a Wittig reaction and a Heck coupling. Here we studied these steps separately to increase the individual yields. The yield of the Wittig reaction was increased up to 98%; however, we could not find better reaction conditions for the Heck coupling than those reported in the previous article.