Skip to main content
PMC home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 2004 May;112(6):751–753. doi: 10.1289/ehp.6804

Medications as a source of human exposure to phthalates.

Russ Hauser 1, Susan Duty 1, Linda Godfrey-Bailey 1, Antonia M Calafat 1
PMCID: PMC1241971  PMID: 15121520

Abstract

Phthalates are a group of multifunctional chemicals used in consumer and personal care products, plastics, and medical devices. Laboratory studies show that some phthalates are reproductive and developmental toxicants. Recently, human studies have shown measurable levels of several phthalates in most of the U.S. general population. Despite their widespread use and the consistent toxicologic data on phthalates, information is limited on sources and pathways of human exposure to phthalates. One potential source of exposure is medications. The need for site-specific dosage medications has led to the use of enteric coatings that allow the release of the active ingredients into the small intestine or in the colon. The enteric coatings generally consist of various polymers that contain plasticizers, including triethyl citrate, dibutyl sebacate, and phthalates such as diethyl phthalate (DEP) and dibutyl phthalate (DBP). In this article we report on medications as a potential source of exposure to DBP in a man who took Asacol [active ingredient mesalamine (mesalazine)] for the treatment of ulcerative colitis. In a spot urine sample from this man collected 3 months after he started taking Asacol, the concentration of monobutyl phthalate, a DBP metabolite, was 16,868 ng/mL (6,180 micro g/g creatinine). This concentration was more than two orders of magnitude higher than the 95th percentile for males reported in the 1999-2000 National Health and Nutrition Examination Survey (NHANES). The patient's urinary concentrations of monoethyl phthalate (443.7 ng/mL, 162.6 micro g/g creatinine), mono-2-ethylhexyl phthalate (3.0 ng/mL, 1.1 micro g/g creatinine), and monobenzyl phthalate (9.3 ng/mL, 3.4 micro g/g creatinine) were unremarkable compared with the NHANES 1999-2000 values. Before this report, the highest estimated human exposure to DBP was more than two orders of magnitude lower than the no observable adverse effect level from animal studies. Further research is necessary to determine the proportional contribution of medications, as well as personal care and consumer products, to a person's total phthalate burden.

Full Text

The Full Text of this article is available as a PDF (113.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Agarwal D. K., Maronpot R. R., Lamb J. C., 4th, Kluwe W. M. Adverse effects of butyl benzyl phthalate on the reproductive and hematopoietic systems of male rats. Toxicology. 1985 Jun 14;35(3):189–206. doi: 10.1016/0300-483x(85)90015-0. [DOI] [PubMed] [Google Scholar]
  2. Ashford M., Fell J. T. Targeting drugs to the colon: delivery systems for oral administration. J Drug Target. 1994;2(3):241–257. doi: 10.3109/10611869408996806. [DOI] [PubMed] [Google Scholar]
  3. Blount B. C., Milgram K. E., Silva M. J., Malek N. A., Reidy J. A., Needham L. L., Brock J. W. Quantitative detection of eight phthalate metabolites in human urine using HPLC-APCI-MS/MS. Anal Chem. 2000 Sep 1;72(17):4127–4134. doi: 10.1021/ac000422r. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Castle L., Jickells S. M., Gilbert J., Harrison N. Migration testing of plastics and microwave-active materials for high-temperature food-use applications. Food Addit Contam. 1990 Nov-Dec;7(6):779–796. doi: 10.1080/02652039009373940. [DOI] [PubMed] [Google Scholar]
  6. Cater B. R., Cook M. W., Gangolli S. D., Grasso P. Studies on dibutyl phthalate-induced testicular atrophy in the rat: effect on zinc metabolism. Toxicol Appl Pharmacol. 1977 Sep;41(3):609–618. doi: 10.1016/s0041-008x(77)80014-8. [DOI] [PubMed] [Google Scholar]
  7. Duty Susan M., Silva Manori J., Barr Dana B., Brock John W., Ryan Louise, Chen Zuying, Herrick Robert F., Christiani David C., Hauser Russ. Phthalate exposure and human semen parameters. Epidemiology. 2003 May;14(3):269–277. [PubMed] [Google Scholar]
  8. Duty Susan M., Singh Narendra P., Silva Manori J., Barr Dana B., Brock John W., Ryan Louise, Herrick Robert F., Christiani David C., Hauser Russ. The relationship between environmental exposures to phthalates and DNA damage in human sperm using the neutral comet assay. Environ Health Perspect. 2003 Jul;111(9):1164–1169. doi: 10.1289/ehp.5756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Frohoff-Hülsmann M. A., Schmitz A., Lippold B. C. Aqueous ethyl cellulose dispersions containing plasticizers of different water solubility and hydroxypropyl methylcellulose as coating material for diffusion pellets. I. Drug release rates from coated pellets. Int J Pharm. 1999 Jan 15;177(1):69–82. doi: 10.1016/s0378-5173(98)00327-5. [DOI] [PubMed] [Google Scholar]
  11. Li L. H., Jester W. F., Jr, Orth J. M. Effects of relatively low levels of mono-(2-ethylhexyl) phthalate on cocultured Sertoli cells and gonocytes from neonatal rats. Toxicol Appl Pharmacol. 1998 Dec;153(2):258–265. doi: 10.1006/taap.1998.8550. [DOI] [PubMed] [Google Scholar]
  12. Marvola M., Nykänen P., Rautio S., Isonen N., Autere A. Enteric polymers as binders and coating materials in multiple-unit site-specific drug delivery systems. Eur J Pharm Sci. 1999 Feb;7(3):259–267. doi: 10.1016/s0928-0987(98)00032-3. [DOI] [PubMed] [Google Scholar]
  13. Mylchreest E., Sar M., Cattley R. C., Foster P. M. Disruption of androgen-regulated male reproductive development by di(n-butyl) phthalate during late gestation in rats is different from flutamide. Toxicol Appl Pharmacol. 1999 Apr 15;156(2):81–95. doi: 10.1006/taap.1999.8643. [DOI] [PubMed] [Google Scholar]
  14. Mylchreest E., Wallace D. G., Cattley R. C., Foster P. M. Dose-dependent alterations in androgen-regulated male reproductive development in rats exposed to Di(n-butyl) phthalate during late gestation. Toxicol Sci. 2000 May;55(1):143–151. doi: 10.1093/toxsci/55.1.143. [DOI] [PubMed] [Google Scholar]
  15. Mylchreest Eve, Sar Madhabananda, Wallace Duncan G., Foster Paul M. D. Fetal testosterone insufficiency and abnormal proliferation of Leydig cells and gonocytes in rats exposed to di(n-butyl) phthalate. Reprod Toxicol. 2002 Jan-Feb;16(1):19–28. doi: 10.1016/s0890-6238(01)00201-5. [DOI] [PubMed] [Google Scholar]
  16. Nässberger L., Arbin A., Ostelius J. Exposure of patients to phthalates from polyvinyl chloride tubes and bags during dialysis. Nephron. 1987;45(4):286–290. doi: 10.1159/000184165. [DOI] [PubMed] [Google Scholar]
  17. Page B. D., Lacroix G. M. The occurrence of phthalate ester and di-2-ethylhexyl adipate plasticizers in Canadian packaging and food sampled in 1985-1989: a survey. Food Addit Contam. 1995 Jan-Feb;12(1):129–151. doi: 10.1080/02652039509374287. [DOI] [PubMed] [Google Scholar]
  18. Park Jung D., Habeebu Sultan S. M., Klaassen Curtis D. Testicular toxicity of di-(2-ethylhexyl)phthalate in young Sprague-Dawley rats. Toxicology. 2002 Feb 28;171(2-3):105–115. doi: 10.1016/s0300-483x(01)00567-4. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Rao P. R., Diwan P. V. Permeability studies of cellulose acetate free films for transdermal use: influence of plasticizers. Pharm Acta Helv. 1997 Feb;72(1):47–51. doi: 10.1016/s0031-6865(96)00060-x. [DOI] [PubMed] [Google Scholar]
  21. Rudel Ruthann A., Camann David E., Spengler John D., Korn Leo R., Brody Julia G. Phthalates, alkylphenols, pesticides, polybrominated diphenyl ethers, and other endocrine-disrupting compounds in indoor air and dust. Environ Sci Technol. 2003 Oct 15;37(20):4543–4553. doi: 10.1021/es0264596. [DOI] [PubMed] [Google Scholar]
  22. Schroeder K. W. Role of mesalazine in acute and long-term treatment of ulcerative colitis and its complications. Scand J Gastroenterol Suppl. 2002;(236):42–47. doi: 10.1080/003655202320621445. [DOI] [PubMed] [Google Scholar]
  23. Silva Manori J., Malek Nicole A., Hodge Carolyn C., Reidy John A., Kato Kayoko, Barr Dana B., Needham Larry L., Brock John W. Improved quantitative detection of 11 urinary phthalate metabolites in humans using liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Jun 15;789(2):393–404. doi: 10.1016/s1570-0232(03)00164-8. [DOI] [PubMed] [Google Scholar]
  24. Sjöberg P., Lindqvist N. G., Plöen L. Age-dependent response of the rat testes to di(2-ethylhexyl) phthalate. Environ Health Perspect. 1986 Mar;65:237–242. doi: 10.1289/ehp.65-1474698. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES