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Determination of four metabolites of the plasticizer di (2-ethylhexyl) phthalate in human urine samples

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Summary

A method for biological monitoring of exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) is described. In this method the four main metabolites of DEHP [i.e., mono (2-ethylhexyl) phthalate (MEHP), mono (5-carboxy-2-ethylpentyl)phthalate, mono(2-ethyl-5-oxohexyl)phthalate, and mono(2-ethyl-5-hydroxyhexyl)-phthalate] are determined in urine samples. The procedure includes enzymatic hydrolysis, ether extraction, and derivatization with triethyloxonium tetrafluoroborate. Analysis is performed by gas chromatography electron impact mass spectrometry. The detection limit for all four metabolites is less than 25 μg/l urine. The coefficient of variation based on duplicate determinations of urine samples of workers occupationally exposed to DEHP was 16% for MEHP (mean concentration 0.157 mg/l) and 6% -9% for the other three metabolites (mean concentrations 0.130-0.175 mg/1). The method described here was used to study DEHP metabolism in man. Most persons excrete mono(2-ethyl-5-oxohexyl)-phthalate and mono (2-ethyl-5-hydroxyhexyl)phthalate as a (glucuronide) conjugate. Mono (5-carboxy-2-ethyl-pentyl)phthalate is mainly excreted in free form, while for MEHP a large interindividual variation in conjugation status was observed. Of the four metabolites quantified, 52% are products of a ((ω-l)-hydroxylation reaction of MEHP [i.e., mono (2-ethyl-5-oxohexyl)phthalate and mono (2-ethyl-5-hydroxyhexyl)phthalate], 22% is the product of a ω-hydroxylation reaction of MEHP [i.e., mono (5-carboxy-2-ethylpentyl)phthalate], and 26% is not oxidized further (i.e., MEHP). A good correlation is obtained when the amount of MEHP ω-hydroxylation products is compared with the amount of MEHP (ω-1)hydroxylation products in urine samples. When the internal dose of DEHP has to be established we recommend that the levels of all four metabolites of DEHP be studied in urine samples.

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References

  • Albro PW (1986) The biochemical toxicology of di-(2-ethylhexyl) and related phthalates: testicular atrophy and hepatocarcinogenesis. Rev Biochem Tox 8:73–119

    Google Scholar 

  • Albro PW, Corbett JT, Schroeder JL, Jordan S, Matthews HB (1982) Pharmacokinetics, interactions with macromolecules and species differences in metabolism of DEHP. Environ Health Perspect 45:19–25

    Google Scholar 

  • Albro PW, Chae K, Philpot R, Corbett JT, Schroeder J, Jordan S (1984) In vitro metabolism of mono-(2-ethylhexyl)phthalate by microsomal enzymes. Similarity to w- and (c)-1)oxidation of fatty acids. Drug Metab Dispos 12:742–748

    Google Scholar 

  • Barry YA, Labow RS, Keon WJ, Tocchi M, Rock GM (1989) Perioperative exposure to plasticizers in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg 97:900–905

    Google Scholar 

  • Conway JG, Cattley RC, Popp JA, Butterworth BE (1989) Possible mechanisms in hepatocarcinogenesis by the peroxisome proliferator di(2-ethylhexyl)-phthalate. Drug Metab Rev 21:65–102

    Google Scholar 

  • Dirven HAAM, Theuws JLG, Jongeneelen FJ, Bos RP (1991) Non-mutagenicity of 4 metabolites of di(2-ethylhexyl)phthalate (DEHP) and 3 structurally related derivatives of di(2-ethylhexyl)adipate (DEHA) in the salmonella mutagenicity assay. Mutat Res 260:121–130

    Google Scholar 

  • Dirven HAAM, van den Broek PHH, Peters JGP, Noordhoek J, Jongeneelen FJ (1992) Microsomal lauric acid hydroxylase activities after treatment of rats with three classical cytochrome P450 inducers and peroxisome proliferating compounds. Biochem Pharmacol 43:2621–2629

    Google Scholar 

  • Elcombe CR, Mitchell AM (1986) Peroxisome proliferation due to di(2-ethylhexyl)phthalate: species differences and possible mechanisms. Environ Health Perspect 70:211–219

    Google Scholar 

  • Flaminio LM, Bergia R, De Angelis L, Ferazza M, Marinovich M, Galli G, Galli CL (1988) The fate of leached di-(2-ethylhexyl)phthalate in patients on chronic hemodialysis. Int J Artif Organs 11:428–435

    Google Scholar 

  • International Agency for Research on Cancer (1987) IARC monographs on the evaluation of carcinogenic risks to humans. Supplement 7. Lyon

  • Lhuguenot J-C, Mitchell AM, Milner G, Lock EA, Elcombe CR (1985) The metabolism of di(2-ethylhexyl)phthalate (DEHP) and mono- (2-ethylhexyl)-phthalate (MEHP) in rats: in vivo and in vitro dose and time dependency of metabolism. Toxicol Appl Pharmacol 80:11–22

    Google Scholar 

  • Liss GM, Albro PW, Hartle RW, Stringer WT (1985) Urinary phthalate determinations as an index of occupational exposure to phthalic anhydride and di(2-ethylhexyl)phthalate. Scand J Work Environ Health 11:381–387

    Google Scholar 

  • Nässberger L, Arbin A, Ostelius J (1987) Exposure of patients to phthalates from polyvinyl chloride tubes and bags during dialysis. Nephron 45:286–290

    Google Scholar 

  • National Toxicology Program (1982) NTP technical report on carcinogenesis bioassay of di(2-ethylhexyl)phthalate in F344 rats and B6C3F1 mice (feed study). NTP, NIH pub. No. 82-1773

  • Nielsen J, Åkesson B, Skerfving S (1985) Phthalate ester exposure - air levels and health of workers processing polyvinylchloride. Am Ind Hyg Assoc J 46:643–647

    Google Scholar 

  • Rock G, Secours VE, Franklin CA, Chu I, Villeneuve DC (1978) The accumulation of mono- (2-ethylhexyl) phthalate during storage of whole blood and plasma. Transfusion 18:553–558

    Google Scholar 

  • Schmid P, Schlatter C (1985) Excretion and metabolism of di(2- ethylhexyl)phthalate in man. Xenobiotica 15:251–256

    Google Scholar 

  • Sharma R, Lake BG, Foster J, Gibson GG (1988) Microsomal cytochrome P-452 induction and peroxisome proliferation by hypolipidaemic agents in rat liver. Biochem Pharmacol 37: 1193–1201

    Google Scholar 

  • Sjöberg POJ, Bondesson UG, Sedin EG, Gustafsson JP (1985) Exposure of newborn infants to plasticizers - plasma levels of di-(2-ethylhexyl)phthalated and mono-(2-ethylhexyl)phthalate during exchange transfusion. Transfusion 25:424–428

    Google Scholar 

  • Turnbull D, Rodricks JV (1985) Assessment of possible carcinogenic risk to humans resulting from exposure to di(2-ethylhexyl)phthalate (DEHP). J Am Coll Toxicol 4:111–145

    Google Scholar 

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Dirven, H.A.A.M., van den Broek, P.H.H. & Jongeneelen, F.J. Determination of four metabolites of the plasticizer di (2-ethylhexyl) phthalate in human urine samples. Int. Arch Occup Environ Heath 64, 555–560 (1993). https://doi.org/10.1007/BF00517700

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