Hydrolysis of di-n-butyl phthalate, butylbenzyl phthalate and di(2-ethylhexyl) phthalate in human liver microsomes

Nobumitsu Hanioka, Yuusuke Takahara, Yuka Takahara, Toshiko Tanaka-Kagawa, Hideto Jinno, Shizuo Narimatsu

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Diester phthalates are industrial chemicals used primarily as plasticizers to import flexibility to polyvinylchloride plastics. In this study, we examined the hydrolysis of di-n-butyl phthalate (DBP), butylbenzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP) in human liver microsomes. These diester phthalates were hydrolyzed to monoester phthalates (mono-n-butyl phthalate (MBP) from DBP, mono-n-butyl phthalate (MBP) and monobenzyl phthalate (MBzP) from BBzP, and mono(2-ethylhexyl) phthalate (MEHP)) by human liver microsomes. DBP, BBzP and DEHP hydrolysis showed sigmoidal kinetics in V-[S] plots, and the Hill coefficient (n) ranged 1.37-1.96. The S50, Vmax and CLmax values for DBP hydrolysis to MBP were 99.7μM, 17.2nmolmin-1mg-1 protein and 85.6μLmin-1mg-1 protein, respectively. In BBzP hydrolysis, the values of S50 (71.7μM), Vmax (13.0nmolmin-1mg-1 protein) and CLmax (91.3μLmin-1mg-1 protein) for MBzP formation were comparable to those of DBP hydrolysis. Although the S50 value for MBP formation was comparable to that of MBzP formation, the Vmax and CLmax values were markedly lower (50, Vmax and CLmax values for DEHP hydrolysis were 8.40μM, 0.43nmolmin-1mg-1 protein and 27.5μLmin-1mg-1 protein, respectively. The S50 value was about 10% of DBP and BBzP hydrolysis, and the Vmax value was also markedly lower (max values for monoester phthalate formation in DBP, BBzP and DEHP hydrolysis was BBzP to MBzP≥DBP to MBP>DEHP to MEHP>BBzP to MBP. These findings suggest that the hydrolysis activities of diester phthalates by human liver microsomes depend on the chemical structure, and that the metabolism profile may relate to diester phthalate toxicities, such as hormone disruption and reproductive effects.

Original languageEnglish
Pages (from-to)1112-1117
Number of pages6
JournalChemosphere
Volume89
Issue number9
DOIs
Publication statusPublished - Nov 2012

Fingerprint

Dibutyl Phthalate
phthalate
Liver Microsomes
Liver
hydrolysis
Hydrolysis
Proteins
Industrial chemicals
phthalic acid
butylbenzyl phthalate
Hormones
Plasticizers
Metabolism
Toxicity
protein
Plastics
monobutyl phthalate

Keywords

  • Butylbenzyl phthalate (BBzP)
  • Di(2-ethylhexyl) phthalate (DEHP)
  • Di-n-butyl phthalate (DBP)
  • Human liver microsomes
  • Hydrolysis

ASJC Scopus subject areas

  • Environmental Chemistry
  • Chemistry(all)

Cite this

Hanioka, N., Takahara, Y., Takahara, Y., Tanaka-Kagawa, T., Jinno, H., & Narimatsu, S. (2012). Hydrolysis of di-n-butyl phthalate, butylbenzyl phthalate and di(2-ethylhexyl) phthalate in human liver microsomes. Chemosphere, 89(9), 1112-1117. https://doi.org/10.1016/j.chemosphere.2012.05.095

Hydrolysis of di-n-butyl phthalate, butylbenzyl phthalate and di(2-ethylhexyl) phthalate in human liver microsomes. / Hanioka, Nobumitsu; Takahara, Yuusuke; Takahara, Yuka; Tanaka-Kagawa, Toshiko; Jinno, Hideto; Narimatsu, Shizuo.

In: Chemosphere, Vol. 89, No. 9, 11.2012, p. 1112-1117.

Research output: Contribution to journalArticle

Hanioka, N, Takahara, Y, Takahara, Y, Tanaka-Kagawa, T, Jinno, H & Narimatsu, S 2012, 'Hydrolysis of di-n-butyl phthalate, butylbenzyl phthalate and di(2-ethylhexyl) phthalate in human liver microsomes', Chemosphere, vol. 89, no. 9, pp. 1112-1117. https://doi.org/10.1016/j.chemosphere.2012.05.095
Hanioka, Nobumitsu ; Takahara, Yuusuke ; Takahara, Yuka ; Tanaka-Kagawa, Toshiko ; Jinno, Hideto ; Narimatsu, Shizuo. / Hydrolysis of di-n-butyl phthalate, butylbenzyl phthalate and di(2-ethylhexyl) phthalate in human liver microsomes. In: Chemosphere. 2012 ; Vol. 89, No. 9. pp. 1112-1117.
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N2 - Diester phthalates are industrial chemicals used primarily as plasticizers to import flexibility to polyvinylchloride plastics. In this study, we examined the hydrolysis of di-n-butyl phthalate (DBP), butylbenzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP) in human liver microsomes. These diester phthalates were hydrolyzed to monoester phthalates (mono-n-butyl phthalate (MBP) from DBP, mono-n-butyl phthalate (MBP) and monobenzyl phthalate (MBzP) from BBzP, and mono(2-ethylhexyl) phthalate (MEHP)) by human liver microsomes. DBP, BBzP and DEHP hydrolysis showed sigmoidal kinetics in V-[S] plots, and the Hill coefficient (n) ranged 1.37-1.96. The S50, Vmax and CLmax values for DBP hydrolysis to MBP were 99.7μM, 17.2nmolmin-1mg-1 protein and 85.6μLmin-1mg-1 protein, respectively. In BBzP hydrolysis, the values of S50 (71.7μM), Vmax (13.0nmolmin-1mg-1 protein) and CLmax (91.3μLmin-1mg-1 protein) for MBzP formation were comparable to those of DBP hydrolysis. Although the S50 value for MBP formation was comparable to that of MBzP formation, the Vmax and CLmax values were markedly lower (50, Vmax and CLmax values for DEHP hydrolysis were 8.40μM, 0.43nmolmin-1mg-1 protein and 27.5μLmin-1mg-1 protein, respectively. The S50 value was about 10% of DBP and BBzP hydrolysis, and the Vmax value was also markedly lower (max values for monoester phthalate formation in DBP, BBzP and DEHP hydrolysis was BBzP to MBzP≥DBP to MBP>DEHP to MEHP>BBzP to MBP. These findings suggest that the hydrolysis activities of diester phthalates by human liver microsomes depend on the chemical structure, and that the metabolism profile may relate to diester phthalate toxicities, such as hormone disruption and reproductive effects.

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