Simultaneous determination of phthalate diesters and monoesters in soil using accelerated solvent extraction and ultra-performance liquid chromatography coupled with tandem mass spectrometry.

Phthalate diesters are a group of plasticizers extensively used in the manufacturing and processing of plastics. Phthalate monoesters are the primary degradation products of the diesters. Accumulation of endocrine disruptive diesters and monoesters in soil is of great concern because of the extensive use of plastic mulching and misdisposal of plastics. Accurate determination of their levels in soil is critical to assess the occurrence, exposure, and risks of phthalate diesters and monoesters. In this study, we aimed to develop a robust and environmentally friendly method for the simultaneous determination of phthalate diesters and monoesters in soil. Ultra-performance liquid chromatography coupled with electrospray tandem mass spectrometry was used for quantification, combined with accelerated solvent extraction and in-line cleanup for sample preparation. The method detection limits for the 14 diesters and 11 monoesters were in the range of 0.59 to 10.08 ng g-1 d.w. Acceptable recoveries (69%-131%) for these analytes were obtained when four deuterated analogs were used for internal calibration, and intra- and inter-day variations were less than 15%. This method was later successfully applied to five soil samples, and 8 diesters and 7 monoesters were detected with the maximum concentration up to 1142.2 ng g-1 d.w. The method developed in this study can be used for screening and accurate quantification of phthalate diesters and monoesters in soil and possibly in other environmental matrices.

Identification of intentionally and non-intentionally added substances in plastic packaging materials and their migration into food products.

Plastic materials are widely used in food packaging applications; however, there is increased concern because of the possible release of undesirable components into foodstuffs. Migration of plastic constituents not only has the potential to affect product quality but also constitutes a risk to consumer health. In order to check the safety of food contact materials, analytical methodologies to identify potential migrants are required. In the first part of this work, a GC/MS screening method was developed for the identification of components from plastic packaging materials including intentionally and "non-intentionally added substances" (NIAS) as potential migrants. In the second part of this study, the presence of seven compounds (bis (2-ethylhexyl) phthalate (DEHP), diethyl phthalate (DEP), diisobutyl phthalate (DIBP), dibutyl phthalate (DBP), butylated hydroxytoluene (BHT), acetyl tributyl citrate (ATBC), benzophenone (BP)) previously identified in packaging materials were investigated in food products (corn and potatoes snacks, cookies, and cakes). For this purpose, a suitable extraction method was developed and quantification was performed using GC-MS. The developed method was validated in terms of linearity, recovery, repeatability, and limits of detection and quantification. The spiked recoveries varied between 82.7 and 116.1%, and relative standard deviation (RSD) was in the range of 2.22-15.9%. The plasticizer ATBC was the most detected compound (94% samples), followed by DEP (65%), DEHP (47%), BP (44%), DBP (35%), DIBP (21%), and BHT (12%). Regarding phthalates, DEP and DEHP were the most frequently detected compounds in concentrations up to 1.44 µg g-1. In some samples, only DBP exceeded the European SML of 0.3 mg kg-1 established in Regulation 10/2011. Graphical abstract Chemical migration from plastic packaging into food.

Review: UK medicines likely to be affected by the proposed European Medicines Agency's guidelines on phthalates.

BACKGROUND: Phthalates are excipients in drug formulations. However, concerns have been raised about the effects of particular phthalates on reproduction and development. As a result the EMA has introduced guidelines for permitted daily exposure (PDE) limits for certain phthalates. Therefore, the objective of this study was to identify UK licensed medicines that contain the relevant phthalates and determine if they fall within the recommended PDE. METHODS: The eMC was used to identify which UK licensed medicines contain the phthalates in question. Companies were then contacted for information on the phthalate levels in their products, which was compared with the PDE recommended by the EMA. RESULTS: The eMC search revealed that 54 medicines contained at least one of the phthalates in question. However, only six medicines, namely Asacol 800 mg MR (Warner Chilcott UK), Epilim 200 Gastro-resistant tablets (Sanofi), Prednisolone 2.5 mg and 5 mg Gastro-resistant tablets (Actavis UK), Vivotif (Crucell Italy S.r.l), and Zentiva 200 mg Gastro-resistant tablets (Winthrop Pharmaceuticals UK), were identified as containing levels that exceeded the recommended PDE. CONCLUSIONS: These findings indicate that very few UK licensed medicines will be affected by the proposed EMA guidelines. For those medicines identified as exceeding recommendations, these findings highlight the need to instigate a risk-benefit review.

Development of a multi-VOC reference material for quality assurance in materials emission testing.

Emission test chamber measurement is necessary to proof building materials as sources of volatile organic compounds (VOCs). The results of such measurements are used to evaluate materials and label them according to their potential to emit harmful substances, polluting indoor air. If only labelled materials were installed indoors, this would improve indoor air quality and prevent negative impacts on human health. Because of the complex testing procedure, reference materials for the quality assurance are mandatory. Currently, there is a lack of such materials because most building products show a broad variation of emissions even within one batch. A previous study indicates lacquers, mixed with volatile organic pollutants, as reproducible emission source for a wide range of substances. In the present study, the curing of the lacquer-VOC mixture inside micro-chambers was optimised. Therefore, the humidity and the chamber flow were varied. Typical indoor air pollutants with a wide range of volatilities, for example, styrene, n-hexadecane, dimethyl and dibutyl phthalate were selected. It turned out that, under optimised curing parameters inside the micro-chamber, their emission can be reproduced with variations of less than 10 %. With this, a next important step towards a reference material for emission testing was achieved.

Occurrence of phthalate esters in sediments in Qiantang River, China and inference with urbanization and river flow regime.

Phthalate esters (PAEs), a group of emerging organic contaminants, have become a serious issue arousing much attention for their ubiquitous presence and hazardous impact on the environment. This study provides the first data on distribution of PAEs in the sediments in the Qiantang River, Zhejiang Province, China, and the inference with urbanization and river flow regime. PAEs were detected in all 23 sediment samples analyzed, and the total concentrations of their 16 congeners in sediments ranged from 0.59 to 6.74µg/g dry weight (dw), with the geometric mean value of 2.03µg/g dw. Of the 16 PAE congeners, di-n-butyl phthalate (DnBP), diisobutyl phthalate (DiBP), and di(2-ethylhexyl) phthalate (DEHP) were present in all sediment samples. The PAEs concentrations in urban regions were higher than those in rural regions because of higher discharge of PAEs from plastic materials in urbanized areas. Concentrations of PAEs were positively correlated with sediment organic matter (fOM) and negatively correlated with logistic value of annual average flow volume at sample sites. River flow regime modified by man-made dams significantly affected the distribution of PAEs. Analysis of congener composition of PAEs indicated that the DEHP was predominant congener in the Qiantang River. The normalized concentration of DEHP exceeded recommended environmental risk limit (ERL).

Selecting adequate exposure biomarkers of diisononyl and diisodecyl phthalates: data from the 2005-2006 National Health and Nutrition Examination Survey.

BACKGROUND: High-molecular-weight phthalates, such as diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP), are used primarily as polyvinyl chloride plasticizers. OBJECTIVES: We assessed exposure to DINP and DIDP in a representative sample of persons ≥ 6 years of age in the U.S. general population from the 2005-2006 National Health and Nutrition Examination Survey (NHANES). METHODS: We analyzed 2,548 urine samples by using online solid-phase extraction coupled to isotope dilution high-performance liquid chromatography-tandem mass spectrometry. RESULTS: We detected monocarboxyisooctyl phthalate (MCOP), a metabolite of DINP, and monocarboxyisononyl phthalate (MCNP), a metabolite of DIDP, in 95.2% and 89.9% of the samples, respectively. We detected monoisononyl phthalate (MNP), a minor metabolite of DINP, much less frequently (12.9%) and at concentration ranges (> 0.8 µg/L-148.1 µg/L) much lower than MCOP (> 0.7 µg/L- 4,961 µg/L). Adjusted geometric mean concentrations of MCOP and MCNP were significantly higher (p < 0.01) among children than among adolescents and adults. CONCLUSIONS: The general U.S. population, including children, was exposed to DINP and DIDP. In previous NHANES cycles, the occurrence of human exposure to DINP by using MNP as the sole urinary biomarker has been underestimated, thus illustrating the importance of selecting the most adequate biomarkers for exposure assessment.

Human monitoring of phthalates and risk assessment.

Some phthalates, such as di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP), and their metabolites are suspected of producing teratogenic and endocrino-disrupting effects. In this study, urinary levels of phthalates (DEHP, DBP, diethyl phthalate (DEP), butylbenzyl phthalate BBP), and monoethylhexyl phthalate (MEHP, a major metabolite of DEHP) were measured by high performance liquid chromatography (HPLC) in human populations (women [hospital visitors], n = 150, and children, n = 150). Daily exposure level of DEHP in children was estimated to be 12.4 microg/kg body weight/d (male 9.9 microg/kg body weight/d, female 17.8 microg/kg body weight/d), but, in women was estimated to be 41.7 microg/kg body weight/d, which exceeded the tolerable daily intake (TDI, 37 microg/kg body weight/day) level established by the European Union (EU) Scientific Committee for Toxicity, Ecotoxicity, and the Environment (SCTEE) based on reproductive toxicity. Based on these data, hazard indices (HIs) were calculated to be 1.12 (41.7/37 TDI) for women and 0.33 (12.4/37 TDI) for children, respectively. These data suggest that Koreans (women and children) were exposed to significant levels of phthalates, which should be reduced to as low a level as technologically feasible to protect Koreans from the exposure to toxic phthalates.

Determination of phthalate monoesters in human milk, consumer milk, and infant formula by tandem mass spectrometry (LC-MS-MS).

Daily exposure of humans to phthalates may be a health risk because animal experiments have shown these compounds can affect the differentiation and function of the reproductive system. Because milk is the main source of nutrition for infants, knowledge of phthalate levels is important for exposure and risk assessment. Here we describe the development and validation of a quantitative analytical procedure for determination of phthalate metabolites in human milk. The phthalate monoesters investigated were: monomethyl phthalate (mMP), monoethyl phthalate (mEP), mono-n-butyl phthalate (mBP), monobenzyl phthalate (mBzP), mono-(2-ethylhexyl) phthalate (mEHP), and monoisononyl phthalate (mNP). The method is based on liquid extraction with a mixture of ethyl acetate and cyclohexane (95:5) followed by two-step solid-phase extraction (SPE). Detection and quantification of the phthalate monoesters were accomplished by high-pressure liquid chromatography using a Betasil phenyl column (100 mmx2.1 mmx3 microm) and triple tandem mass spectrometry (LC-MS-MS). Detection limits were in the range 0.01 to 0.5 microg L(-1) and method variation was from 5 to 15%. Analysis of 36 milk samples showed that all these phthalates were present, albeit at different concentrations. Median values (microg L(-1)) obtained were 0.11 (mMP), 0.95 (mEP), 3.5 (mBP), 0.8 (mBzP), 9.5 (mEHP), and 101 (mNP). We also analysed seven samples of consumer milk and ten samples of infant formula. Only mBP and mEHP were detected in these samples, in the ranges 0.6-3.9 microg L(-1) (mBP) and 5.6-9.9 microg L(-1) (mEHP).

[Polyethylene terephthalate (PET)--health aspects and food packaging application]. / Politereftalan etylenu (PET)--aspekty zdrowotne i zastosowanie do pakowania zywnosci.

Polyethylene terephthalate (PET) due to its physicochemical properties, especially regidity and glass-like transparency is widely used as food packaging material. The relevant legislation states that substances may not migrate from food contacting materials in quantities that may cause undesirable changes in organoleptic properties of food coming into contact with such material. The lists of substances authorized for food contact plastic materials and requirements for the final product were established. The requirements concern global migration limits (60 mg/kg or 10 mg/dm2) and specific migration limits (SML) set for substances which, when migrate into food in grater quantities may cause risk for human health. For the products manufactured from PET the specific migration limits were set for terephthalic acid (7.5 mg/kg), for isophthalic acid (5 mg/kg), for isophthalic acid dimethyl ester (0.05 mg/kg) and for ethylene and diethylene glycol (30 mg/kg). PET may undergo thermal degradation resulting in formation of acetaldehyde, which may influence organoleptic characteristics of packaged foods changing taste and smell.

[Cytogenetic effect of pesticides in relation to their hygienic standardization]. / Tsitogeneticheskaia aktivnost' pestitsidov pri ikh gigienicheskom reglamentirovanii.

Cytogenetic activity of 7 pesticides from various chemical classes was studied on mice bone marrow cells. 6 substances produced a mutagenic effect of different degrees of severity. The dependence of cytogenetic activity on the path, duration of administration into the organism and terms of cell fixation was stated. Hygienic standards and regulations for the production and use of the studied pesticides were developed with regard for the data obtained. The mutagenic effect appeared to be a limiting criterion of harmfulness for 2 substances in the substantiation of their MACs in the air of occupational area.

Properties of reference Escherichia coli endotoxin and its phthalylated derivative in humans.

The properties of a reference bacterial endotoxin prepared from Escherichia coli and its phthalylated derivative were studied in normal human volunteers infected intravenously with the compounds. The minimal pyrogenic dose of the reference endotoxin is about 0.1-0.5 ng/kg. The increase in white blood cell count, absolute granulocyte count, absolute immature granulocyte count, and concentrations of serum amyloid A, cortisol, and growth hormone was directly related to the concentration of reference endotoxin administered. Phthalylated reference endotoxin up to 1,000 ng/kg (at least 500 ng of the patent compound/kg) was administered to normal human volunteers without significant changes in temperature, white blood cell count, absolute granulocyte count, and concentrations of serum amyloid A, cortisol, and growth hormone. Thus, this study defines biologic properties of the new reference bacterial endotoxin in humans and demonstrates effective detoxification by phthalylation of the present compound.