Species and inter-individual differences in metabolic capacity of di(2-ethylhexyl)phthalate (DEHP) between human and mouse livers

Yuki Ito, Michihiro Kamijima, Chie Hasegawa, Masahiro Tagawa, Toshio Kawai, Mio Miyake, Yumi Hayashi, Hisao Naito, Tamie Nakajima

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Objectives: This study was conducted to assess inter-species and inter-individual differences in the metabolism of di(2-ethylhexyl)phthalate (DEHP) in humans and mice. Methods: The activities of four DEHP-metabolizing enzymes [lipase, UDP-glucuronocyltransferase (UGT), alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH)] were measured in the livers of 38 human subjects of various ages and in eight 129/Sv male mice. Results: Microsomal lipase activity was significantly lower in humans than in mice. The V max/Km value in humans was one-seventh of that in mice, microsomal UGT activity in humans was a sixth of that in mice, and cytosolic ALDH activity for 2-ethylhexanal in humans was one-half of that in mice. In contrast, ADH activity for 2-ethylhexanol was twofold higher in humans than in mice. The total amount of DEHP urinary metabolites and the concentration of mono(2-ethylhexyl)phthalate (MEHP) were much higher in intact mice than in the U.S. general population based on data reported elsewhere, regardless of the similar estimated DEHP intake between these mice and the human reference population. However, mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP) and mono(2-ethyl-5-carboxypentyl)phthalate (5cx-MEPP) levels were higher in the latter than in the former. Of note, inter-subject variability in the activities of all enzymes measured was 10-26-fold. Conclusion: The inter-individual variation in the metabolism of DEHP in humans may be greater than the difference between mice and humans (inter-species variation), and both may affects the risk assessment of DEHP.

Original languageEnglish
Pages (from-to)117-125
Number of pages9
JournalEnvironmental Health and Preventive Medicine
Volume19
Issue number2
DOIs
Publication statusPublished - 01-01-2014

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Individuality
Liver
Aldehyde Dehydrogenase
Uridine Diphosphate
Alcohol Dehydrogenase
Lipase
phthalic acid
Enzymes
Human Activities
Population

All Science Journal Classification (ASJC) codes

  • Public Health, Environmental and Occupational Health

Cite this

Ito, Yuki ; Kamijima, Michihiro ; Hasegawa, Chie ; Tagawa, Masahiro ; Kawai, Toshio ; Miyake, Mio ; Hayashi, Yumi ; Naito, Hisao ; Nakajima, Tamie. / Species and inter-individual differences in metabolic capacity of di(2-ethylhexyl)phthalate (DEHP) between human and mouse livers. In: Environmental Health and Preventive Medicine. 2014 ; Vol. 19, No. 2. pp. 117-125.
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abstract = "Objectives: This study was conducted to assess inter-species and inter-individual differences in the metabolism of di(2-ethylhexyl)phthalate (DEHP) in humans and mice. Methods: The activities of four DEHP-metabolizing enzymes [lipase, UDP-glucuronocyltransferase (UGT), alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH)] were measured in the livers of 38 human subjects of various ages and in eight 129/Sv male mice. Results: Microsomal lipase activity was significantly lower in humans than in mice. The V max/Km value in humans was one-seventh of that in mice, microsomal UGT activity in humans was a sixth of that in mice, and cytosolic ALDH activity for 2-ethylhexanal in humans was one-half of that in mice. In contrast, ADH activity for 2-ethylhexanol was twofold higher in humans than in mice. The total amount of DEHP urinary metabolites and the concentration of mono(2-ethylhexyl)phthalate (MEHP) were much higher in intact mice than in the U.S. general population based on data reported elsewhere, regardless of the similar estimated DEHP intake between these mice and the human reference population. However, mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP) and mono(2-ethyl-5-carboxypentyl)phthalate (5cx-MEPP) levels were higher in the latter than in the former. Of note, inter-subject variability in the activities of all enzymes measured was 10-26-fold. Conclusion: The inter-individual variation in the metabolism of DEHP in humans may be greater than the difference between mice and humans (inter-species variation), and both may affects the risk assessment of DEHP.",
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Species and inter-individual differences in metabolic capacity of di(2-ethylhexyl)phthalate (DEHP) between human and mouse livers. / Ito, Yuki; Kamijima, Michihiro; Hasegawa, Chie; Tagawa, Masahiro; Kawai, Toshio; Miyake, Mio; Hayashi, Yumi; Naito, Hisao; Nakajima, Tamie.

In: Environmental Health and Preventive Medicine, Vol. 19, No. 2, 01.01.2014, p. 117-125.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Species and inter-individual differences in metabolic capacity of di(2-ethylhexyl)phthalate (DEHP) between human and mouse livers

AU - Ito, Yuki

AU - Kamijima, Michihiro

AU - Hasegawa, Chie

AU - Tagawa, Masahiro

AU - Kawai, Toshio

AU - Miyake, Mio

AU - Hayashi, Yumi

AU - Naito, Hisao

AU - Nakajima, Tamie

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Objectives: This study was conducted to assess inter-species and inter-individual differences in the metabolism of di(2-ethylhexyl)phthalate (DEHP) in humans and mice. Methods: The activities of four DEHP-metabolizing enzymes [lipase, UDP-glucuronocyltransferase (UGT), alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH)] were measured in the livers of 38 human subjects of various ages and in eight 129/Sv male mice. Results: Microsomal lipase activity was significantly lower in humans than in mice. The V max/Km value in humans was one-seventh of that in mice, microsomal UGT activity in humans was a sixth of that in mice, and cytosolic ALDH activity for 2-ethylhexanal in humans was one-half of that in mice. In contrast, ADH activity for 2-ethylhexanol was twofold higher in humans than in mice. The total amount of DEHP urinary metabolites and the concentration of mono(2-ethylhexyl)phthalate (MEHP) were much higher in intact mice than in the U.S. general population based on data reported elsewhere, regardless of the similar estimated DEHP intake between these mice and the human reference population. However, mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP) and mono(2-ethyl-5-carboxypentyl)phthalate (5cx-MEPP) levels were higher in the latter than in the former. Of note, inter-subject variability in the activities of all enzymes measured was 10-26-fold. Conclusion: The inter-individual variation in the metabolism of DEHP in humans may be greater than the difference between mice and humans (inter-species variation), and both may affects the risk assessment of DEHP.

AB - Objectives: This study was conducted to assess inter-species and inter-individual differences in the metabolism of di(2-ethylhexyl)phthalate (DEHP) in humans and mice. Methods: The activities of four DEHP-metabolizing enzymes [lipase, UDP-glucuronocyltransferase (UGT), alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH)] were measured in the livers of 38 human subjects of various ages and in eight 129/Sv male mice. Results: Microsomal lipase activity was significantly lower in humans than in mice. The V max/Km value in humans was one-seventh of that in mice, microsomal UGT activity in humans was a sixth of that in mice, and cytosolic ALDH activity for 2-ethylhexanal in humans was one-half of that in mice. In contrast, ADH activity for 2-ethylhexanol was twofold higher in humans than in mice. The total amount of DEHP urinary metabolites and the concentration of mono(2-ethylhexyl)phthalate (MEHP) were much higher in intact mice than in the U.S. general population based on data reported elsewhere, regardless of the similar estimated DEHP intake between these mice and the human reference population. However, mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP) and mono(2-ethyl-5-carboxypentyl)phthalate (5cx-MEPP) levels were higher in the latter than in the former. Of note, inter-subject variability in the activities of all enzymes measured was 10-26-fold. Conclusion: The inter-individual variation in the metabolism of DEHP in humans may be greater than the difference between mice and humans (inter-species variation), and both may affects the risk assessment of DEHP.

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