Human body burdens of chemicals used in plastic manufacture

In the last decades, the availability of sophisticated analytical chemistry techniques has facilitated measuring trace levels of multiple environmental chemicals in human biological matrices (i.e. biomonitoring) with a high degree of accuracy and precision. As biomonitoring data have become readily available, interest in their interpretation has increased. We present an overview on the use of biomonitoring in exposure and risk assessment using phthalates and bisphenol A as examples of chemicals used in the manufacture of plastic goods. We present and review the most relevant research on biomarkers of exposure for phthalates and bisphenol A, including novel and most comprehensive biomonitoring data from Germany and the United States. We discuss several factors relevant for interpreting and understanding biomonitoring data, including selection of both biomarkers of exposure and human matrices, and toxicokinetic information.

[1]  F. H. Field,et al.  Gas chromatographic--mass spectrometric detection of circulating plasticizers in surgical patients. , 1981, Journal of chromatography.

[2]  D. Shen,et al.  Circulating concentrations of di(2-ethylhexyl) phthalate and its de-esterified phthalic acid products following plasticizer exposure in patients receiving hemodialysis. , 1985, Toxicology and applied pharmacology.

[3]  S. Gangolli,et al.  Aspects of the testicular toxicity of phthalate esters. , 1986, Environmental health perspectives.

[4]  P. Albro,et al.  Metabolism of di(2-ethylhexyl)phthalate. , 1989, Drug metabolism reviews.

[5]  H. Dirven,et al.  Metabolites of the plasticizer di (2-ethylhexyl) phthalate in urine samples of workers in polyvinylchloride processing industries , 1993, International archives of occupational and environmental health.

[6]  L L Needham,et al.  Improving exposure assessment by monitoring human tissues for toxic chemicals. , 1995, Journal of exposure analysis and environmental epidemiology.

[7]  Malcolm Williams,et al.  Toxicological profile for diethyl phthalate , 1995 .

[8]  J. Furr,et al.  Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat. , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[9]  R. M. David Exposure to phthalate esters. , 2000, Environmental health perspectives.

[10]  L L Needham,et al.  Human exposure estimates for phthalates. , 2000, Environmental health perspectives.

[11]  O. Rosario,et al.  Identification of phthalate esters in the serum of young Puerto Rican girls with premature breast development. , 2000, Environmental health perspectives.

[12]  L L Needham,et al.  Levels of seven urinary phthalate metabolites in a human reference population. , 2000, Environmental health perspectives.

[13]  KEN SEXTON,et al.  Introduction and overview: Assessing children's exposure to hazardous environmental chemicals: an overview of selected research challenges and complexities , 2000, Journal of Exposure Analysis and Environmental Epidemiology.

[14]  C Springall,et al.  A biomarker approach to measuring human dietary exposure to certain phthalate diesters , 2001, Food additives and contaminants.

[15]  D. Barr,et al.  Measurement of organophosphate metabolites in postpartum meconium as a potential biomarker of prenatal exposure: a validation study. , 2001, Environmental health perspectives.

[16]  W. Kessler,et al.  No background concentrations of di(2-ethylhexyl) phthalate and mono(2-ethylhexyl) phthalate in blood of rats , 2001, Archives of Toxicology.

[17]  R. H. Mckee,et al.  Esters of Aromatic Mono‐, Di‐, and Tricarboxylic Acids, Aromatic Diacids and Di‐, Tri‐, Or Polyalcohols , 2001 .

[18]  undefined Fda,et al.  Safety assessment of Di-(2-ethylhexyl) phthalate (DEHP) released from PVC medical devices , 2001 .

[19]  N. Samyn,et al.  Use of Alternative Specimens: Drugs of Abuse in Saliva and Doping Agents in Hair , 2002, Therapeutic drug monitoring.

[20]  T. Weiss,et al.  Biological monitoring : prospects in occupational and environmental medicine , 2002 .

[21]  Shaw Watanabe,et al.  Measurement of bisphenol A in human urine using liquid chromatography with multi-channel coulometric electrochemical detection. , 2002, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[22]  T. Remer,et al.  Anthropometry-based reference values for 24-h urinary creatinine excretion during growth and their use in endocrine and nutritional research. , 2002, The American journal of clinical nutrition.

[23]  I. Chahoud,et al.  Parent bisphenol A accumulation in the human maternal-fetal-placental unit. , 2002, Environmental health perspectives.

[24]  Wolfgang Völkel,et al.  Metabolism and kinetics of bisphenol a in humans at low doses following oral administration. , 2002, Chemical research in toxicology.

[25]  J. Brock,et al.  Phthalate Monoesters Levels in the Urine of Young Children , 2002, Bulletin of environmental contamination and toxicology.

[26]  Holger M Koch,et al.  Internal exposure of the general population to DEHP and other phthalates--determination of secondary and primary phthalate monoester metabolites in urine. , 2003, Environmental research.

[27]  Ian T. Cousins,et al.  Assessment of Critical Exposure Pathways , 2003 .

[28]  Masatoshi Morita,et al.  Bisphenol A levels in human urine. , 2002, Environmental health perspectives.

[29]  T. Kawamoto,et al.  Biological Monitoring of Bisphenol A in a Korean Population , 2003, Archives of environmental contamination and toxicology.

[30]  M. Pyo,et al.  Gender differences in the levels of bisphenol A metabolites in urine. , 2003, Biochemical and biophysical research communications.

[31]  Holger M Koch,et al.  An estimation of the daily intake of di(2-ethylhexyl)phthalate (DEHP) and other phthalates in the general population. , 2003, International journal of hygiene and environmental health.

[32]  S. Bloomfield Home hygiene: a risk approach. , 2003, International journal of hygiene and environmental health.

[33]  J. Brock,et al.  Quantitative detection of nine phthalate metabolites in human serum using reversed-phase high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. , 2003, Journal of analytical toxicology.

[34]  Holger M. Koch,et al.  Di(2-ethylhexyl)phthalate (DEHP) metabolites in human urine and serum after a single oral dose of deuterium-labelled DEHP , 2004, Archives of Toxicology.

[35]  M. Hirose,et al.  Diverse developmental toxicity of di-n-butyl phthalate in both sexes of rat offspring after maternal exposure during the period from late gestation through lactation. , 2004, Toxicology.

[36]  J. Angerer,et al.  DEHP metabolites in urine of children and DEHP in house dust. , 2004, International journal of hygiene and environmental health.

[37]  Holger M Koch,et al.  Internal exposure of nursery-school children and their parents and teachers to di(2-ethylhexyl)phthalate (DEHP). , 2004, International journal of hygiene and environmental health.

[38]  D Stewart Irvine,et al.  How strong is the evidence of a link between environmental chemicals and adverse effects on human reproductive health? , 2004, BMJ : British Medical Journal.

[39]  R. H. Mckee Phthalate Exposure and Early Thelarche , 2004, Environmental health perspectives.

[40]  A. Calafat,et al.  Exposure to di-(2-ethylhexyl) phthalate among premature neonates in a neonatal intensive care unit. , 2004, Pediatrics.

[41]  J. G. Vandenbergh,et al.  A Mixture of the “Antiandrogens” Linuron and Butyl Benzyl Phthalate Alters Sexual Differentiation of the Male Rat in a Cumulative Fashion1 , 2004, Biology of reproduction.

[42]  J. Yoshinaga,et al.  Daily urinary excretion of bisphenol A , 2004, Environmental health and preventive medicine.

[43]  A. Calafat,et al.  Automated solid phase extraction and quantitative analysis of human milk for 13 phthalate metabolites. , 2004, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[44]  R. Tyl,et al.  Reproductive toxicity evaluation of dietary butyl benzyl phthalate (BBP) in rats. , 2004, Reproductive toxicology.

[45]  R. Pacifici,et al.  Development and validation of a high-performance liquid chromatography-mass spectrometry assay for determination of amphetamine, methamphetamine, and methylenedioxy derivatives in meconium. , 2004, Analytical chemistry.

[46]  Russ Hauser,et al.  Medications as a source of human exposure to phthalates. , 2004, Environmental health perspectives.

[47]  Holger M. Koch,et al.  New metabolites of di(2-ethylhexyl)phthalate (DEHP) in human urine and serum after single oral doses of deuterium-labelled DEHP , 2005, Archives of Toxicology.

[48]  Joshua T. Cohen,et al.  Weight of the Evidence Evaluation of Low-Dose Reproductive and Developmental Effects of Bisphenol A , 2004 .

[49]  Dana B Barr,et al.  Urinary levels of seven phthalate metabolites in the U.S. population from the National Health and Nutrition Examination Survey (NHANES) 1999-2000. , 2003, Environmental health perspectives.

[50]  Ibrahim Chahoud,et al.  Blood burden of di(2-ethylhexyl) phthalate and its primary metabolite mono(2-ethylhexyl) phthalate in pregnant and nonpregnant rats and marmosets. , 2004, Toxicology and applied pharmacology.

[51]  Dana B Barr,et al.  Uses of speciation techniques in biomonitoring for assessing human exposure to organic environmental chemicals , 2005, Analytical and bioanalytical chemistry.

[52]  P. Foster,et al.  Critical window of male reproductive tract development in rats following gestational exposure to di-n-butyl phthalate. , 2005, Birth defects research. Part B, Developmental and reproductive toxicology.

[53]  J. Angerer,et al.  Biological monitoring of the five major metabolites of di-(2-ethylhexyl)phthalate (DEHP) in human urine using column-switching liquid chromatography-tandem mass spectrometry. , 2005, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[54]  Antonia M. Calafat,et al.  Personal Care Product Use Predicts Urinary Concentrations of Some Phthalate Monoesters , 2005, Environmental health perspectives.

[55]  R. Kruse,et al.  Decrease in Anogenital Distance among Male Infants with Prenatal Phthalate Exposure , 2005, Environmental health perspectives.

[56]  Dana B. Barr,et al.  Biologic Monitoring of Exposure to Environmental Chemicals throughout the Life Stages: Requirements and Issues for Consideration for the National Children’s Study , 2005, Environmental health perspectives.

[57]  J. Angerer,et al.  Di(2-ethylhexyl)phthalate (DEHP) exposure of voluntary plasma and platelet donors. , 2005, International journal of hygiene and environmental health.

[58]  C. Hughes,et al.  An Extensive New Literature Concerning Low-Dose Effects of Bisphenol A Shows the Need for a New Risk Assessment , 2005, Environmental health perspectives.

[59]  J. Moline,et al.  Analysis of environmental biomarkers in urine using an electrochemical detector. , 2005, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[60]  Samuel P. Caudill,et al.  Urinary Concentrations of Bisphenol A and 4-Nonylphenol in a Human Reference Population , 2004, Environmental health perspectives.

[61]  L. Hagmar,et al.  Urinary Phthalate Metabolites and Biomarkers of Reproductive Function in Young Men , 2005, Epidemiology.

[62]  A. Calafat,et al.  Urinary metabolites of di-n-octyl phthalate in rats. , 2005, Toxicology.

[63]  Holger M Koch,et al.  Exposure of nursery school children and their parents and teachers to di-n-butylphthalate and butylbenzylphthalate , 2005, International archives of occupational and environmental health.

[64]  A. Calafat,et al.  Quantification of urinary conjugates of bisphenol A, 2,5-dichlorophenol, and 2-hydroxy-4-methoxybenzophenone in humans by online solid phase extraction–high performance liquid chromatography–tandem mass spectrometry , 2005, Analytical and bioanalytical chemistry.

[65]  Wolfgang Völkel,et al.  QUANTITATION OF BISPHENOL A AND BISPHENOL A GLUCURONIDE IN BIOLOGICAL SAMPLES BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY , 2005, Drug Metabolism and Disposition.

[66]  Simon Watkins,et al.  Personalized Exposure Assessment: Promising Approaches for Human Environmental Health Research , 2005, Environmental health perspectives.

[67]  Frederick S vom Saal,et al.  Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure. , 2006, Endocrinology.

[68]  J. Furr,et al.  Adverse effects of environmental antiandrogens and androgens on reproductive development in mammals. , 2006, International journal of andrology.

[69]  K. Hungerbühler,et al.  What Are the Sources of Exposure to Eight Frequently Used Phthalic Acid Esters in Europeans? , 2006, Risk analysis : an official publication of the Society for Risk Analysis.

[70]  A. Calafat,et al.  Altered Semen Quality in Relation to Urinary Concentrations of Phthalate Monoester and Oxidative Metabolites , 2006, Epidemiology.

[71]  Nancy G Doerrer,et al.  Strategic biomonitoring initiatives: moving the science forward. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[72]  J. Weuve,et al.  Exposure to Phthalates in Neonatal Intensive Care Unit Infants: Urinary Concentrations of Monoesters and Oxidative Metabolites , 2006, Environmental health perspectives.

[73]  J. Angerer,et al.  Di(2-ethylhexyl)phthalate (DEHP): human metabolism and internal exposure-- an update and latest results. , 2006, International journal of andrology.

[74]  Yoshiki Katayama,et al.  Human exposure to bisphenol A. , 2006, Toxicology.

[75]  Paul M D Foster,et al.  Disruption of reproductive development in male rat offspring following in utero exposure to phthalate esters. , 2006, International journal of andrology.

[76]  Anogenital Distance and Phthalate Exposure: Swan et al. Respond , 2006, Environmental Health Perspectives.

[77]  T. Kawamoto,et al.  Urinary concentrations of bisphenol A in relation to biomarkers of sensitivity and effect and endocrine‐related health effects , 2006, Environmental and molecular mutagenesis.

[78]  M. Dalgaard,et al.  Diisobutyl phthalate has comparable anti-androgenic effects to di-n-butyl phthalate in fetal rat testis. , 2006, Toxicology letters.

[79]  A. Calafat,et al.  Measurement of eight urinary metabolites of di(2-ethylhexyl) phthalate as biomarkers for human exposure assessment , 2006, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[80]  A. Calafat,et al.  Quantifying phthalate metabolites in human meconium and semen using automated off-line solid-phase extraction coupled with on-line SPE and isotope-dilution high-performance liquid chromatography--tandem mass spectrometry. , 2006, Analytical chemistry.

[81]  Ken-ichi Miyamoto,et al.  Estimation of daily bisphenol a intake of Japanese individuals with emphasis on uncertainty and variability. , 2006, Environmental sciences : an international journal of environmental physiology and toxicology.

[82]  Julie E Goodman,et al.  An Updated Weight of the Evidence Evaluation of Reproductive and Developmental Effects of Low Doses of Bisphenol A , 2006, Critical reviews in toxicology.

[83]  A. Calafat,et al.  Urinary biomarkers of di-isononyl phthalate in rats. , 2006, Toxicology.

[84]  A. Calafat,et al.  Urinary oxidative metabolites of di(2-ethylhexyl) phthalate in humans. , 2006, Toxicology.

[85]  Tracey J. Woodruff,et al.  Estimated Daily Phthalate Exposures in a Population of Mothers of Male Infants Exhibiting Reduced Anogenital Distance , 2006, Environmental health perspectives.

[86]  Validity of Anogenital Distance as a Marker of in Utero Phthalate Exposure , 2006, Environmental health perspectives.

[87]  A. Calafat,et al.  Oxidative Metabolites of Diisononyl Phthalate as Biomarkers for Human Exposure Assessment , 2006, Environmental health perspectives.

[88]  A. Calafat,et al.  Mono-(3-Carboxypropyl) Phthalate, A Metabolite of Di-n-Octyl Phthalate , 2006, Journal of toxicology and environmental health. Part A.

[89]  Lisbeth E Knudsen,et al.  Phthalate monoesters in perfusate from a dual placenta perfusion system, the placenta tissue and umbilical cord blood. , 2007, Reproductive toxicology.

[90]  L Earl Gray,et al.  Cumulative effects of dibutyl phthalate and diethylhexyl phthalate on male rat reproductive tract development: altered fetal steroid hormones and genes. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[91]  Dana B Barr,et al.  Uses and issues of biomonitoring. , 2007, International journal of hygiene and environmental health.

[92]  A. Calafat,et al.  Assessment of human exposure to di-isodecyl phthalate using oxidative metabolites as biomarkers , 2007, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[93]  Bernhard Liebl,et al.  Intake of phthalates and di(2-ethylhexyl)adipate: results of the Integrated Exposure Assessment Survey based on duplicate diet samples and biomonitoring data. , 2007, Environment international.

[94]  J. Angerer,et al.  Human biomonitoring: state of the art. , 2007, International journal of hygiene and environmental health.

[95]  Laura N. Vandenberg,et al.  Human exposure to bisphenol A (BPA). , 2007, Reproductive toxicology.

[96]  J. Vílchez,et al.  Bisphenol-A and chlorinated derivatives in adipose tissue of women. , 2007, Reproductive toxicology.

[97]  J. Angerer,et al.  Di-iso-nonylphthalate (DINP) metabolites in human urine after a single oral dose of deuterium-labelled DINP. , 2007, International journal of hygiene and environmental health.

[98]  Marike Kolossa-Gehring,et al.  Daily intake of di(2-ethylhexyl)phthalate (DEHP) by German children -- A comparison of two estimation models based on urinary DEHP metabolite levels. , 2007, International journal of hygiene and environmental health.

[99]  A. Calafat,et al.  Pilot Study of Urinary Biomarkers of Phytoestrogens, Phthalates, and Phenols in Girls , 2006, Environmental health perspectives.

[100]  A. Calafat,et al.  Urinary metabolites of diisodecyl phthalate in rats. , 2007, Toxicology.

[101]  Shuk-Mei Ho,et al.  Chapel Hill bisphenol A expert panel consensus statement: integration of mechanisms, effects in animals and potential to impact human health at current levels of exposure. , 2007, Reproductive toxicology.

[102]  Marike Kolossa-Gehring,et al.  Di-n-butylphthalate and butylbenzylphthalate — urinary metabolite levels and estimated daily intakes: pilot study for the German Environmental Survey on children , 2007, Journal of Exposure Science and Environmental Epidemiology.

[103]  A. Calafat,et al.  Metabolite profiles of di-n-butyl phthalate in humans and rats. , 2007, Environmental science & technology.

[104]  Gerhard Andreas Wiesmüller,et al.  Internal phthalate exposure over the last two decades--a retrospective human biomonitoring study. , 2007, International journal of hygiene and environmental health.

[105]  D. Helm Correlation between production amounts of DEHP and daily intake. , 2007, The Science of the total environment.

[106]  Marika Berglund,et al.  Phthalate Diesters and Their Metabolites in Human Breast Milk, Blood or Serum, and Urine as Biomarkers of Exposure in Vulnerable Populations , 2007, Environmental health perspectives.

[107]  Antonia M. Calafat,et al.  Exposure of the U.S. Population to Bisphenol A and 4-tertiary-Octylphenol: 2003–2004 , 2007, Environmental health perspectives.

[108]  L Earl Gray,et al.  A mixture of seven antiandrogens induces reproductive malformations in rats. , 2008, International journal of andrology.

[109]  Hermann Fromme,et al.  Determination of free and total bisphenol A in human urine to assess daily uptake as a basis for a valid risk assessment. , 2008, Toxicology letters.

[110]  M. Wittassek,et al.  Phthalates: metabolism and exposure. , 2008, International journal of andrology.

[111]  Susan R Woskie,et al.  NTP-CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A. , 2008, Birth defects research. Part B, Developmental and reproductive toxicology.

[112]  Wolfgang Völkel,et al.  Human exposure to bisphenol A by biomonitoring: methods, results and assessment of environmental exposures. , 2008, Toxicology and applied pharmacology.

[113]  Carol Potera Air Pollution: Floral Scents Going Off the Air? , 2008, Environmental health perspectives.

[114]  Shanna H Swan,et al.  Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans. , 2008, Environmental research.

[115]  Frederica P. Perera,et al.  Characterization of Phthalate Exposure among Pregnant Women Assessed by Repeat Air and Urine Samples , 2008, Environmental health perspectives.

[116]  A. Calafat,et al.  Factors affecting the evaluation of biomonitoring data for human exposure assessment. , 2008, International journal of andrology.

[117]  Catherine J Karr,et al.  Baby Care Products: Possible Sources of Infant Phthalate Exposure , 2008, Pediatrics.

[118]  Frederick S vom Saal,et al.  Components of plastic: experimental studies in animals and relevance for human health , 2009, Philosophical Transactions of the Royal Society B: Biological Sciences.

[119]  Richard C. Thompson,et al.  Plastics, the environment and human health: current consensus and future trends , 2009, Philosophical Transactions of the Royal Society B: Biological Sciences.

[120]  S. Swan,et al.  Phthalates and other additives in plastics: human exposure and associated health outcomes , 2009, Philosophical Transactions of the Royal Society B: Biological Sciences.

[121]  A. Calafat,et al.  Urinary Phthalate Metabolites in Relation to Preterm Birth in Mexico City , 2009, Environmental health perspectives.

[122]  V. Preedy,et al.  National Health and Nutrition Examination Survey , 2010 .