Urinary levels of seven phthalate metabolites in the U.S. population from the National Health and Nutrition Examination Survey (NHANES) 1999-2000.

We measured the urinary monoester metabolites of seven commonly used phthalates in approximately 2,540 samples collected from participants of the National Health and Nutrition Examination Survey (NHANES), 1999-2000, who were greater than or equal to 6 years of age. We found detectable levels of metabolites monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), and mono-(2-ethylhexyl) phthalate (MEHP) in > 75% of the samples, suggesting widespread exposure in the United States to diethyl phthalate, dibutyl phthalate or diisobutylphthalate, benzylbutyl phthalate, and di-(2-ethylhexyl) phthalate, respectively. We infrequently detected monoisononyl phthalate, mono-cyclohexyl phthalate, and mono-n-octyl phthalate, suggesting that human exposures to di-isononyl phthalate, dioctylphthalate, and dicyclohexyl phthalate, respectively, are lower than those listed above, or the pathways, routes of exposure, or pharmacokinetic factors such as absorption, distribution, metabolism, and elimination are different. Non-Hispanic blacks had significantly higher concentrations of MEP than did Mexican Americans and non-Hispanic whites. Compared with adolescents and adults, children had significantly higher levels of MBP, MBzP, and MEHP but had significantly lower concentrations of MEP. Females had significantly higher concentrations of MEP and MBzP than did males, but similar MEHP levels. Of particular interest, females of all ages had significantly higher concentrations of the reproductive toxicant MBP than did males of all ages; however, women of reproductive age (i.e., 20-39 years of age) had concentrations similar to adolescent girls and women 40 years of age. These population data on exposure to phthalates will serve an important role in public health by helping to set research priorities and by establishing a nationally representative baseline of exposure with which population levels can be compared.

[1]  L. Gray,et al.  The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat. , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[2]  J. Brock,et al.  Quantitative detection of eight phthalate metabolites in human urine using HPLC-APCI-MS/MS. , 2000, Analytical chemistry.

[3]  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.

[4]  GA. Agency for Toxic Substances and Disease Registry. , 2022 .

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

[6]  R. H. Mckee,et al.  Absorption, disposition and metabolism of di‐isononyl phthalate (DINP) in F‐344 rats , 2002, Journal of applied toxicology : JAT.

[7]  Jessilynn Taylor,et al.  Toxicological profile for di-n-butyl phthalate , 1997 .

[8]  J. Brock,et al.  Improved quantitative detection of 11 urinary phthalate metabolites in humans using liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry. , 2003, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[9]  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.

[10]  P. Foster,et al.  Male reproductive tract malformations in rats following gestational and lactational exposure to Di(n-butyl) phthalate: an antiandrogenic mechanism? , 1998, Toxicological sciences : an official journal of the Society of Toxicology.

[11]  J. Angerer,et al.  On-line clean-up by multidimensional liquid chromatography-electrospray ionization tandem mass spectrometry for high throughput quantification of primary and secondary phthalate metabolites in human urine. , 2003, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[12]  R. Schulte‐Hermann,et al.  Hepatocarcinogenic potential of di(2-ethylhexyl)phthalate in rodents and its implications on human risk. , 1996, Critical reviews in toxicology.

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

[14]  E Mylchreest,et al.  Effects of phthalate esters on the developing reproductive tract of male rats , 2001, Human reproduction update.

[15]  M. Luyckx,et al.  Exposure of hemodialysis patients to di-2-ethylhexyl phthalate. , 1999, International journal of pharmaceutics.

[16]  R. Hornung,et al.  Estimation of Average Concentration in the Presence of Nondetectable Values , 1990 .

[17]  Robin M Whyatt,et al.  Prenatal exposures to phthalates among women in New York City and Krakow, Poland. , 2003, Environmental health perspectives.

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

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

[20]  David C Christiani,et al.  The relationship between environmental exposures to phthalates and DNA damage in human sperm using the neutral comet assay. , 2002, Environmental health perspectives.

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

[22]  M. Ema,et al.  Adverse effects on development of the reproductive system in male offspring of rats given monobutyl phthalate, a metabolite of dibutyl phthalate, during late pregnancy. , 2001, Reproductive toxicology.

[23]  J. Spengler,et al.  Phthalates, alkylphenols, pesticides, polybrominated diphenyl ethers, and other endocrine-disrupting compounds in indoor air and dust. , 2003, Environmental science & technology.

[24]  G. Foster,et al.  National Health and Nutrition Examination Survey , 2005 .

[25]  T. Mettang,et al.  Uraemic pruritus and exposure to di(2-ethylhexyl) phthalate (DEHP) in haemodialysis patients. , 1996, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[26]  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.

[27]  Michigan.,et al.  Toxicological profile for dichloropropenes , 2008 .

[28]  C. C. Hodge,et al.  Glucuronidation patterns of common urinary and serum monoester phthalate metabolites , 2005, Archives of Toxicology.

[29]  D. Baird,et al.  Reproducibility of urinary phthalate metabolites in first morning urine samples. , 2002, Environmental health perspectives.

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

[31]  S. Jackson.  Creatinine in urine as an index of urinary excretion rate. , 1966, Health physics.

[32]  G. Jham,et al.  Gas chromatographic quantitation of two plasticizers contaminating intravenous fluids stored in plastic containers. , 1981, Journal of chromatography.

[33]  A. Calafat,et al.  Assessing human exposure to phthalates using monoesters and their oxidized metabolites as biomarkers. , 2003, Environmental health perspectives.

[34]  M. Ema,et al.  Effects of monobutyl phthalate on reproductive function in pregnant and pseudopregnant rats. , 2001, Reproductive toxicology.