Prevalence and clinical implications of heightened plastic chemical exposure in pediatric patients undergoing cardiopulmonary bypass.

BACKGROUND: Phthalate chemicals are used to manufacture plastic medical products, including many components of cardiopulmonary bypass (CPB) circuits. We aimed to quantify iatrogenic phthalate exposure in pediatric patients undergoing cardiac surgery and examine the link between phthalate exposure and postoperative outcomes. STUDY DESIGN AND METHODS: The study included pediatric patients undergoing (n=122) unique cardiac surgeries at Children's National Hospital. For each patient, a single plasma sample was collected preoperatively and two additional samples were collected postoperatively upon return from the operating room and the morning after surgery. Concentrations of di(2-ethylhexyl) phthalate (DEHP) and its metabolites were quantified using ultra high-pressure liquid chromatography coupled to mass spectrometry. RESULTS: Patients were subdivided into three groups, according to surgical procedure: (1) cardiac surgery not requiring CPB support, (2) cardiac surgery requiring CPB with a crystalloid prime, and (3) cardiac surgery requiring CPB with red blood cells (RBCs) to prime the circuit. Phthalate metabolites were detected in all patients, and postoperative phthalate levels were highest in patients undergoing CPB with an RBC-based prime. Age-matched (<1 year) CPB patients with elevated phthalate exposure were more likely to experience postoperative complications. RBC washing was an effective strategy to reduce phthalate levels in CPB prime. DISCUSSION: Pediatric cardiac surgery patients are exposed to phthalate chemicals from plastic medical products, and the degree of exposure increases in the context of CPB with an RBC-based prime. Additional studies are warranted to measure the direct effect of phthalates on patient health outcomes and investigate mitigation strategies to reduce exposure.

[The decade hemogram of workers of phthalate industry].

The article presents decade dynamics of hemogram of workers started their labor activity in factories of terephthalic acid, purifed terephthalic acid and polyethylene terephthalate. The study established a hemodynamics depended on career pattern, characterizing hematologic shifts i.e. decreasing of content of red blood elements, adaptative compensatory reactions of white blood, increasing of sensitization and allergizing.

Serum concentrations of phthalate metabolites are related to abdominal fat distribution two years later in elderly women.

BACKGROUND: Phthalates, commonly used to soften plastic goods, are known PPAR-agonists affecting lipid metabolism and adipocytes in the experimental setting. We evaluated if circulating concentrations of phthalates were related to different indices of obesity using data from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Data from both dual-energy X-ray absorptiometry (DXA) and abdominal magnetic resonance imaging (MRI) were used. METHODS: 1,016 subjects aged 70 years were investigated in the PIVUS study. Four phthalate metabolites were detected in the serum of almost all subjects (> 96%) by an API 4000 liquid chromatograph/tandem mass spectrometer. Abdominal MRI was performed in a representative subsample of 287 subjects (28%), and a dual-energy X-ray absorptiometry (DXA)-scan was obtained in 890 (88%) of the subjects two year following the phthalate measurements. RESULTS: In women, circulating concentrations of mono-isobutyl phthalate (MiBP) were positively related to waist circumference, total fat mass and trunk fat mass by DXA, as well as to subcutaneous adipose tissue by MRI following adjustment for serum cholesterol and triglycerides, education, smoking and exercise habits (all p < 0.008). Mono-methyl phthalate (MMP) concentrations were related to trunk fat mass and the trunk/leg-ratio by DXA, but less powerful than MiBP. However, no such statistically significant relationships were seen in men. CONCLUSIONS: The present evaluation shows that especially the phthalate metabolite MiBP was related to increased fat amount in the subcutaneous abdominal region in women measured by DXA and MRI two years later.

Concentrations of phthalate metabolites in milk, urine, saliva, and Serum of lactating North Carolina women.

BACKGROUND: Phthalates are ubiquitous in the environment, but concentrations in multiple media from breast-feeding U.S. women have not been evaluated. OBJECTIVES: The objective of this study was to accurately measure and compare the concentrations of oxidative monoester phthalate metabolites in milk and surrogate fluids (serum, saliva, and urine) of 33 lactating North Carolina women. METHODS: We analyzed serum, saliva, urine, and milk for the oxidative phthalate metabolites mono(3-carboxypropyl) phthalate, mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(2-ethyl-5-hydroxyhexyl) phthalate, and mono(2-ethyl-5-oxohexyl) phthalate using isotope-dilution high-performance liquid chromatography tandem mass spectroscopy. Because only urine lacks esterases, we analyzed it for the hydrolytic phthalate monoesters. RESULTS: We detected phthalate metabolites in few milk (< 10%) and saliva samples. MECPP was detected in > 80% of serum samples, but other metabolites were less common (3-22%). Seven of the 10 urinary metabolites were detectable in > or = 85% of samples. Monoethyl phthalate had the highest mean concentration in urine. Metabolite concentrations differed by body fluid (urine > serum > milk and saliva). Questionnaire data suggest that frequent nail polish use, immunoglobulin A, and fasting serum glucose and triglyceride levels were increased among women with higher concentrations of urinary and/or serum phthalate metabolites; motor vehicle age was inversely correlated with certain urinary phthalate concentrations. CONCLUSIONS: Our data suggest that phthalate metabolites are most frequently detected in urine of lactating women and are less often detected in serum, milk, or saliva. Urinary phthalate concentrations reflect maternal exposure and do not represent the concentrations of oxidative metabolites in other body fluids, especially milk.

Plasticizers from plastic devices extraction, metabolism, and accumulation by biological systems.

Phthalate ester plasticizers were found to be extracted by blood from plastic tubing and from plastic bags used for blood storage. One such plasticizer was metabolized by the isolated perfused rat liver while another was found to be accumulated in the liver unchanged. In addition, this latter plasticizer was identified in samples of human tissue taken from patients who had received transfusions of blood stored in plastic bags. The biological implications of these observations are considered.

[Clinical aspects of the quality control of synthetic polymers used in hematology]. / Kliniczne aspekty kontroli jakosci polimerów syntetycznych uzytkowanych w sluzbie krwi.

Polyvinyl chloride (PCW) is the most often used synthetic polymer in production of so widely employed in blood service instruments as containers for blood and its preparations, apparatuses for blood transfusions, etc. Di(2-ethylhexyl) phthalate DEHP is an often employed plasticider in production of PCW for medical purposes. Since 1967 is has been known that DEHP from the walla of a PCW container penetrates the preservative liquid, blood, or any preparation. The paper, based on results from literature and on the authors own studies, discusses the abilities of DEHP to penetrate blood, and its unequal contents in particular blood preparations. Also multiple blood transfusions are capable of introducing large quantities of phthalates into the patient's organism. Although till now it has not been shown that there is any clear risk related to usage containers with PCW containing DEHP, yet its presence in blood, or in its preparations, should be taken into account, as well as possible influence of this compound (besides other factors) on the patient's state. That is why recently PCW without DEHP, or with other synthetic polymers (polyolefins, etc.), has been used in production of objects used in blood service, esp. in containers for thrombocyte concentrates. The containers seem to be free from the additional factors threatening the patient.

Detection of phthalate metabolites in human saliva.

In assessment of exposure to environmental contaminants, the use of unconventional matrices is becoming an increasingly important area of research. Saliva is one of the most promising alternative matrices because its collection is easy, noninvasive, and inexpensive. In this study, we measured the salivary concentrations of 14 phthalate metabolites in 39 anonymous adult volunteers using isotope-dilution, automated solid phase extraction-high performance liquid chromatography-tandem mass spectrometry. Seven phthalate metabolites were detected at the concentrations ranging from below the limit of detection (<1 ng/mL) to 10.6 ng/mL for phthalic acid, 3.1 ng/mL for monomethyl phthalate (MMP), 91.4 ng/mL for monoethyl phthalate (MEP), 65.8 ng/mL for mono-n-butyl phthalate (MBP), 17.9 ng/mL for mono-iso-butyl phthalate, 353.6 ng/mL for monobenzyl phthalate, and 6.8 ng/mL for mono-2-ethylhexyl phthalate (MEHP). The frequency of detection was highest for MBP (85%) and lowest for MMP (8%). The median salivary MBP level in this group of adults was higher than the median serum MBP level in another non-occupationally exposed human adult population in the United States, whereas, the median salivary levels of MEP and MEHP were lower than the corresponding median serum levels. The frequency of detection and the salivary levels of each phthalate monoester in this study population were lower than the frequency of detection and urinary level of the same monoester in the general US population. Although urine is preferred for exposure assessment to non-persistent chemicals such as phthalates, the similar levels in serum and saliva suggest that saliva could be used as a surrogate matrix for measuring the bioavailable dose of phthalates in biomonitoring studies.

Migration of plasticiser from haemodialysis blood tubing.

Di-2-ethylhexyl phthalate (DEHP) was found to migrate from polyvinyl chloride (PVC) blood tubing into human blood during both in vivo and in vitro haemodialysis. DEHP blood level increased during in vivo dialysis but decreased again toward the end of a six hour dialysis period. During in vitro haemodialysis of outdated human blood DEHP accumulated up to 5580 ppb. Although toxic effects have not yet been observed, we believe plastic tubing that does not contain extractable materials should be developed.

The accumulation of mono-2-ethylhexylphthalate (MEHP) during storage of whole blood and plasma.

The accumulation of the plasticizer di-2-ethylhexylphthalate (DEHP) in blood and blood components has been of considerable concern for some time. We have followed the accumulation of DEHP and one of its major metabolities, mono-2-ethylhexylphthalate (MEHP) during storage of whole blood, platelet-rich plasma, platelet concentrates, and platelet-poor plasma for periods ranging from 72 hours to four weeks. Both phthalates showed a progressive increase in concentration with time. While the levels of DEHP were much greater than those of MEHP, there was nonetheless a significant and continual increase in MEHP in all preparations. The highest concentrations of both DEHP and MEHP were found in the platelet-poor plasma, indicating that platelets do not have a major role in the accumulation of the phthalates in blood. The accumulation of MEHP was shown to be a direct result of the metabolism of DEHP by plasma protein(s) rather than leaching from the blood bag.

Quantification of protein adducts of hexahydrophthalic anhydride and methylhexahydrophthalic anhydride in human plasma.

Hexahydrophthalic anhydride (HHPA) and methylhexahydrophthalic anhydride (MHHPA) are two highly allergenic compounds used in the chemical industry. A method was developed for quantification of protein adducts of HHPA and MHHPA in human plasma. The plasma was dialysed and the anhydrides were hydrolysed from the proteins at mild acidic conditions. The released hexahydrophthalic acid (HHP acid) and methylhexahydrophthalic acid (MHHP acid) were purified by reversed solid phase extraction followed by derivatisation with pentafluorobenzyl bromide. The derivatives were analysed using GC-MS in negative ion chemical ionisation mode with ammonia as moderating gas. As internal standards, deuterium labelled HHP and MHHP acids were used. The detection limits were 0.06 pmol mL(-1) plasma for HHP acid and 0.03 pmol mL(-1) plasma for MHHP acid. The between-day precisions for HHP acid were 18% at 0.3 pmol mL(-1) and 8% at 4 pmol mL(-1). For MHHP acid, the precisions were 13% at 0.3 pmol mL(-1) and 9% at 4 pmol mL(-1). There were strong correlations (r=0.94 for HHPA and 0.99 for MHHPA) between total plasma protein adduct concentrations and serum albumin adduct levels. Workers exposed to time-weighted average air levels of HHPA between < 1 and 340 microg m(-3) and between 2 and 160 microg m(-3) for MHHPA had plasma adduct levels between the detection limits of the methods and 8.40 and 19.0 pmol mL(-1), respectively.

Decreased accumulation of phthalate plasticizer during storage of blood as packed cells.

Accumulation of phthalate plasticizer (di-(2-ethylhexyl) phthalate, DEHP) was markedly reduced in blood stored as packed cells rather than as whole blood. After the first week, the accumulation rate in whole blood was essentially linear, but in packed cells DEHP accumulation was lower, and reached a plateau. At three weeks whole blood contained about three times more DEHP than did packed cells. Smaller amounts of plasma and restricted diffusion probably limited DEHP accumulation in packed cell preparations.