Skip to main content
Log in

Phthalate esters

II. Effects of inhaled dibutylphthalate on cytochrome P-450 mediated metabolism in rat liver and lung

  • Original Investigations
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Male Sprague Dawley rats were exposed to dibutylphthalate (DBP) by inhalation with concentrations of 0.5, 2.5, and 7.0 ppm in the air for 5 days. The concentrations were considered relevant to human exposure. No quantitative changes were observed in liver microsomal cytochrome P-450 related enzymes, but significant increase was observed in the liver microsomal metabolism of benzo(a)pyrene and n-hexane, in the 2.5 ppm and 0.5 ppm groups, respectively. Inhaled DBF decreased in a dose-dependent way the lung microsomal concentration of cytochrome P-450 by as much as 63%, which was reflected in a significant reduction of the microsomal metabolism of n-hexane and benzo(a)pyrene in the 7.0 ppm group. It is concluded that DBP in doses relevant to human air exposure influences the cytochrome P-450 enzyme system in both liver and lung, with lung as the main target organ. The observed effects in lung microsomes were similar to those earlier reported after IP administration of high doses of DBP.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aitio A, Parkki M (1978) Effects of phthalate esters on drug metabolizing enzyme activities in rat liver. Arch Int Pharmacodyn 235: 187–195

    Google Scholar 

  • Ciornall AG, Bardawill CH, David MM (1949a) Determination of serum proteins by means of the biuret reaction. J Biol Chem 177: 715–766

    Google Scholar 

  • Hites RA (1973) Phthalates in the Charles and the Merrimack rivers. Environ Health Persp 1: 17–21

    Google Scholar 

  • Johannesen KAM, De Pierre JW (1978) Measurement of cytochrome P-450 in the presence of large amounts of contaminating hemoglobin and methemoglobin. Anal Biochem 86: 725–732

    Google Scholar 

  • Johannesen K, De Pierre JW, Bergstrand A, Dallner G, Eruster L (1977) Preparation and characterisation of total, rough and smooth microsomes from the lung of control and methylcholanthrene-treated rats. Biochim Biophys Acta 496: 115–135

    Google Scholar 

  • Lake BG, Gangolli SD, Grasso P, Lloyd AG (1975) Studies on the hepatic effects of orally administrated di-(2-ethylhexal)phthalate in the rat. Toxicol Appl Pharmacol 32: 355–367

    Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193: 265–275

    Google Scholar 

  • Mayer FL, Stalling DL, Johnson JL (1972) Phthalate esters as environmental contaminants. Nature 238: 411–413

    Google Scholar 

  • Milkov LE, Aldyreva MV, Popova TB, Lopukhova KA, Makarenko YL, Malyar LM, Shakhova TK (1973) Health status of workers exposed to phthalate plasticizers in the manufacture of artifical leather and films based on PVC resins. Environ Health Persp 3: 175–178

    Google Scholar 

  • Nilson OG, Toftgård R, Eng L, Gustafsson JA (1981) Regio-selectivity of purified forms of rabbit liver microsomal cytochrome P-450 in the metabolism of benzo(a)pyrene, n-hexane and 7-ethoxyresorufin. Acta Pharmacol Toxico 48: 369–376

    Google Scholar 

  • Omura T, Sato R (1964) The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J Biol Chem 239: 2370–2378

    Google Scholar 

  • Patel JM (1979) The destruction of pulmonary and hepatic cytochrome P-450 by phthalaldehyde. Toxicol Appl Pharmacol 48: 337–342

    Google Scholar 

  • Pinnel AE, Northam BE (1978) New automated dye-binding method for serum albumin determination with bromcresol purple. Clin Chem 24: 80–86

    Google Scholar 

  • Srivastava SP, Agarwal DK, Mushtaq M, Seth PK (1978) Effects of di-(2-ethylhexyl)phthalate (DEHP) on chemical constituents and enzymatic activity on rat liver. Toxicology 11: 271–275

    Google Scholar 

  • The Committee on Enzymes of the Scandinavian Society for Clinical Chemistry and Clinical Physiology (1974) Recommended methods for the determination of four enzymes in blood. Scand J Clin Lab Invest 33: 287–291

    Google Scholar 

  • Thomas GH (1973) Quantitative determination and confirmation of identity of trace amount of dialkyl phthalates in environmental samples. Environ Health Persp 1: 23–25

    Google Scholar 

  • Toftgård R, Nilsen OG, Ingelman-Sundberg M, Gustafsson J-Å (1980) Correlation between changes in enzymatic activities induction of different forms of rat liver microsomal cytochrome P-450 after phenobarbital-, 3-methylcholanthrene- and 16-cyanopregnenolone treatment. Acta Pharmacol Toxicol 46: 353–361

    Google Scholar 

  • Walseth F, Toftgård R, Nilsen OG (1982) Phthalate Esters I: Effects on cytochrome P-450 mediated metabolism in rat liver and lung, serum enzymatic activites and serum protein levels. Arch Toxicol 50: 1–10

    Google Scholar 

  • Williams DT (1973) Dibutyl- and di-(2-ethylhexyl)phthalate in fish. J Agr Food Chem 21: 1128–1129

    Google Scholar 

  • Williams Ch, Kamin H (1962) Microsomal triphosphopyridine nucleotide-cytochrome c reductase of liver. J Biol Chem 237: 587–595

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Walseth, F., Nilsen, O.G. Phthalate esters. Arch Toxicol 55, 132–136 (1984). https://doi.org/10.1007/BF00346052

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00346052

Key words

Navigation