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Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 2002 Apr;110(4):405–410. doi: 10.1289/ehp.02110405

The association between biomarker-based exposure estimates for phthalates and demographic factors in a human reference population.

Jung-Wan Koo 1, Frederick Parham 1, Michael C Kohn 1, Scott A Masten 1, John W Brock 1, Larry L Needham 1, Christopher J Portier 1
PMCID: PMC1240804  PMID: 11940459

Abstract

Population-based estimates of environmental exposures using biomarkers can be difficult to obtain for a variety of reasons, including problems with limits of detection, undersampling of key strata, time between exposure and sampling, variation across individuals, variation within individuals, and the ability to find and interpret a given biomarker. In this article, we apply statistical likelihoods, weighted sampling, and regression methods for censored data to the analysis of biomarker data. Urinary metabolites for seven phthalates, reported by Blount et al., are analyzed using these methods. In the case of the phthalates data, we assumed the underlying model to be a log-normal distribution with the mean of the distribution defined as a function of a number of demographic variables that might affect phthalate levels in individuals. Included as demographic variables were age, sex, ethnicity, residency, family income, and education level. We conducted two analyses: an unweighted analysis where phthalate distributions were estimated with changes in the means of these distributions as a function of demographic variables, and a weighted prediction for the general population in which weights were assigned for a subset of the population depending on the frequency of their demographic variables in the general U.S. population. We used statistical tests to determine whether any of the demographic variables affected mean phthalate levels. Individuals with only a high school education had higher levels of di-n-butyl phthalate than individuals with education beyond high school. Subjects who had family income less than $1,500 in the month before sampling and/or only high school education had higher levels of n-butyl benzyl phthalate levels than other groupings. Di(2-ethylhexyl) phthalate was higher in males and/or in urban populations and/or in people who had family income less than $1,500 per month. Our findings suggest that there may be significant demographic variations in exposure and/or metabolism of phthalates and that health-risk assessments for phthalate exposure in humans should consider different potential risk groups.

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Selected References

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  1. Aitio A., Parkki M. Effect of phthalate esters on drug metabolizing enzyme activities in rat liver. Arch Int Pharmacodyn Ther. 1978 Oct;235(2):187–195. [PubMed] [Google Scholar]
  2. Albro P. W., Moore B. Identification of the metabolites of simple phthalate diesters in rat urine. J Chromatogr. 1974 Jul 17;94(0):209–218. doi: 10.1016/s0021-9673(01)92368-4. [DOI] [PubMed] [Google Scholar]
  3. Autian J. Toxicity and health threats of phthalate esters: review of the literature. Environ Health Perspect. 1973 Jun;4:3–26. doi: 10.1289/ehp.73043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bell F. P., Patt C. S., Brundage B., Gillies P. J., Phillips W. A. Studies on lipid biosynthesis and cholesterol content of liver and serum lipoproteins in rats fed various phthalate esters. Lipids. 1978 Jan;13(1):66–74. doi: 10.1007/BF02533369. [DOI] [PubMed] [Google Scholar]
  5. Blount B. C., Silva M. J., Caudill S. P., Needham L. L., Pirkle J. L., Sampson E. J., Lucier G. W., Jackson R. J., Brock J. W. Levels of seven urinary phthalate metabolites in a human reference population. Environ Health Perspect. 2000 Oct;108(10):979–982. doi: 10.1289/ehp.00108979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Burmaster D. E., Wilson A. M. Fitting second-order finite mixture models to data with many censored values using maximum likelihood estimation. Risk Anal. 2000 Apr;20(2):261–271. doi: 10.1111/0272-4332.202025. [DOI] [PubMed] [Google Scholar]
  7. Creasy D. M., Foster J. R., Foster P. M. The morphological development of di-N-pentyl phthalate induced testicular atrophy in the rat. J Pathol. 1983 Mar;139(3):309–321. doi: 10.1002/path.1711390307. [DOI] [PubMed] [Google Scholar]
  8. Daniel J. W., Bratt H. The absorption, metabolism and tissue distribution of di(2-ethylhexyl)phthalate in rats. Toxicology. 1974 Mar;2(1):51–65. doi: 10.1016/0300-483x(74)90042-0. [DOI] [PubMed] [Google Scholar]
  9. Eigenberg D. A., Bozigian H. P., Carter D. E., Sipes I. G. Distribution, excretion, and metabolism of butylbenzyl phthalate in the rat. J Toxicol Environ Health. 1986;17(4):445–456. doi: 10.1080/15287398609530839. [DOI] [PubMed] [Google Scholar]
  10. Ema M., Harazono A., Miyawaki E., Ogawa Y. Developmental toxicity of mono-n-benzyl phthalate, one of the major metabolites of the plasticizer n-butyl benzyl phthalate, in rats. Toxicol Lett. 1996 Jul;86(1):19–25. doi: 10.1016/0378-4274(96)03665-x. [DOI] [PubMed] [Google Scholar]
  11. Ema M., Itami T., Kawasaki H. Teratogenic phase specificity of butyl benzyl phthalate in rats. Toxicology. 1993 Mar 30;79(1):11–19. doi: 10.1016/0300-483x(93)90202-4. [DOI] [PubMed] [Google Scholar]
  12. Foster P. M., Cook M. W., Thomas L. V., Walters D. G., Gangolli S. D. Differences in urinary metabolic profile from di-n-butyl phthalate-treated rats and hamsters. A possible explanation for species differences in susceptibility to testicular atrophy. Drug Metab Dispos. 1983 Jan-Feb;11(1):59–61. [PubMed] [Google Scholar]
  13. Foster P. M., Thomas L. V., Cook M. W., Gangolli S. D. Study of the testicular effects and changes in zinc excretion produced by some n-alkyl phthalates in the rat. Toxicol Appl Pharmacol. 1980 Jul;54(3):392–398. doi: 10.1016/0041-008x(80)90165-9. [DOI] [PubMed] [Google Scholar]
  14. Gray T. J., Beamand J. A. Effect of some phthalate esters and other testicular toxins on primary cultures of testicular cells. Food Chem Toxicol. 1984 Feb;22(2):123–131. doi: 10.1016/0278-6915(84)90092-9. [DOI] [PubMed] [Google Scholar]
  15. Harris C. A., Henttu P., Parker M. G., Sumpter J. P. The estrogenic activity of phthalate esters in vitro. Environ Health Perspect. 1997 Aug;105(8):802–811. doi: 10.1289/ehp.97105802. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Heindel J. J., Powell C. J. Phthalate ester effects on rat Sertoli cell function in vitro: effects of phthalate side chain and age of animal. Toxicol Appl Pharmacol. 1992 Jul;115(1):116–123. doi: 10.1016/0041-008x(92)90374-2. [DOI] [PubMed] [Google Scholar]
  17. Kluwe W. M., McConnell E. E., Huff J. E., Haseman J. K., Douglas J. F., Hartwell W. V. Carcinogenicity testing of phthalate esters and related compounds by the National Toxicology Program and the National Cancer Institute. Environ Health Perspect. 1982 Nov;45:129–133. doi: 10.1289/ehp.8245129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kluwe W. M. Overview of phthalate ester pharmacokinetics in mammalian species. Environ Health Perspect. 1982 Nov;45:3–9. doi: 10.1289/ehp.82453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kohn M. C., Parham F., Masten S. A., Portier C. J., Shelby M. D., Brock J. W., Needham L. L. Human exposure estimates for phthalates. Environ Health Perspect. 2000 Oct;108(10):A440–A442. doi: 10.1289/ehp.108-a440b. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Leyder F., Boulanger P. Ultraviolet absorption, aqueous solubility, and octanol-water partition for several phthalates. Bull Environ Contam Toxicol. 1983 Feb;30(2):152–157. doi: 10.1007/BF01610114. [DOI] [PubMed] [Google Scholar]
  21. Lindsey J. K., Byrom W. D., Wang J., Jarvis P., Jones B. Generalized nonlinear models for pharmacokinetic data. Biometrics. 2000 Mar;56(1):81–88. doi: 10.1111/j.0006-341x.2000.00081.x. [DOI] [PubMed] [Google Scholar]
  22. Matthews H. B., Anderson M. W. The distribution and excretion of 2,4,5,2',5'-pentachlorobiphenyl in the rat. Drug Metab Dispos. 1975 May-Jun;3(3):211–219. [PubMed] [Google Scholar]
  23. Moody D. E., Reddy J. K. Hepatic peroxisome (microbody) proliferation in rats fed plasticizers and related compounds. Toxicol Appl Pharmacol. 1978 Aug;45(2):497–504. doi: 10.1016/0041-008x(78)90111-4. [DOI] [PubMed] [Google Scholar]
  24. Nativelle C., Picard K., Valentin I., Lhuguenot J. C., Chagnon M. C. Metabolism of n-butyl benzyl phthalate in the female Wistar rat. Identification of new metabolites. Food Chem Toxicol. 1999 Aug;37(8):905–917. doi: 10.1016/s0278-6915(99)00071-x. [DOI] [PubMed] [Google Scholar]
  25. Oishi S., Hiraga K. Effects of monoesters of O-phthalic acid on serum lipid composition of rats. Toxicol Lett. 1982 Nov;14(1-2):79–84. doi: 10.1016/0378-4274(82)90012-1. [DOI] [PubMed] [Google Scholar]
  26. Oishi S., Hiraga K. Testicular atrophy induced by di-2-ethylhexyl phthalate: effect of zinc supplement. Toxicol Appl Pharmacol. 1983 Aug;70(1):43–48. doi: 10.1016/0041-008x(83)90177-1. [DOI] [PubMed] [Google Scholar]
  27. Peck C. C., Albro P. W. Toxic potential of the plasticizer Di(2-ethylhexyl) phthalate in the context of its disposition and metabolism in primates and man. Environ Health Perspect. 1982 Nov;45:11–17. doi: 10.1289/ehp.824511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pirkle J. L., Sampson E. J., Needham L. L., Patterson D. G., Ashley D. L. Using biological monitoring to assess human exposure to priority toxicants. Environ Health Perspect. 1995 Apr;103 (Suppl 3):45–48. doi: 10.1289/ehp.95103s345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Pittman K. A., Wiener M., Treble D. H. Mirex kinetics in the rhesus monkey. II. Pharmacokinetic model. Drug Metab Dispos. 1976 May-Jun;4(3):288–295. [PubMed] [Google Scholar]
  30. Reddy J. K., Azarnoff D. L., Hignite C. E. Hypolipidaemic hepatic peroxisome proliferators form a novel class of chemical carcinogens. Nature. 1980 Jan 24;283(5745):397–398. doi: 10.1038/283397a0. [DOI] [PubMed] [Google Scholar]
  31. Rozman T., Rozman K., Williams J., Greim H. Enhanced fecal excretion of mirex in rhesus monkeys by 5% mineral oil in the diet. Drug Chem Toxicol. 1981;4(3):251–262. doi: 10.3109/01480548109018132. [DOI] [PubMed] [Google Scholar]
  32. Shiota K., Chou M. J., Nishimura H. Embryotoxic effects of di-2-ethylhexyl phthalate (DEHP) and di-n-buty phthalate (DBP) in mice. Environ Res. 1980 Jun;22(1):245–253. doi: 10.1016/0013-9351(80)90136-x. [DOI] [PubMed] [Google Scholar]
  33. Tanaka A., Adachi T., Takahashi T., Yamaha T. Biochemical studies on phthalic esters I. Elimination, distribution and metabolism of di-(2-ethylhexyl)phthalate in rats. Toxicology. 1975 May;4(2):253–264. doi: 10.1016/0300-483x(75)90105-5. [DOI] [PubMed] [Google Scholar]
  34. Tanaka A., Matsumoto A., Yamaha T. Biochemical studies on phthalic esters. III. Metabolism of dibutyl phthalate (DBP) in animals. Toxicology. 1978 Feb;9(1-2):109–123. doi: 10.1016/0300-483x(78)90036-7. [DOI] [PubMed] [Google Scholar]
  35. Tsay J. Y., Chen I. W., Maxon H. R., Heminger L. A statistical method for determining normal ranges from laboratory data including values below the minimum detectable value. Clin Chem. 1979 Dec;25(12):2011–2014. [PubMed] [Google Scholar]
  36. Vlachonikolis I. G., Marriott F. H. Evaluation of censored contamination data. Food Addit Contam. 1995 Sep-Oct;12(5):637–644. doi: 10.1080/02652039509374352. [DOI] [PubMed] [Google Scholar]
  37. Walseth F., Toftgård R., Nilsen O. G. Phthalate esters I: Effects on cytochrome P-450 mediated metabolism in rat liver and lung, serum enzymatic activities and serum protein levels. Arch Toxicol. 1982 May;50(1):1–10. doi: 10.1007/BF00569231. [DOI] [PubMed] [Google Scholar]
  38. Williams D. T., Blanchfield B. J. Retention, excretion and metabolism of di-(2-ethylhexyl) phthalate administered orally to the rat. Bull Environ Contam Toxicol. 1974 Apr;11(4):371–378. doi: 10.1007/BF01684945. [DOI] [PubMed] [Google Scholar]
  39. Williams D. T., Blanchfield B. J. The retention, distribution, excretion, and metabolism of dibutyl phthalate-7-14 C in the rat. J Agric Food Chem. 1975 Sep-Oct;23(5):854–858. doi: 10.1021/jf60201a047. [DOI] [PubMed] [Google Scholar]
  40. Wolf C., Jr, Lambright C., Mann P., Price M., Cooper R. L., Ostby J., Gray L. E., Jr Administration of potentially antiandrogenic pesticides (procymidone, linuron, iprodione, chlozolinate, p,p'-DDE, and ketoconazole) and toxic substances (dibutyl- and diethylhexyl phthalate, PCB 169, and ethane dimethane sulphonate) during sexual differentiation produces diverse profiles of reproductive malformations in the male rat. Toxicol Ind Health. 1999 Jan-Mar;15(1-2):94–118. doi: 10.1177/074823379901500109. [DOI] [PubMed] [Google Scholar]

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