Phthalate esters in normal and pathological human kidneys

Overturf, M. L.; Druilhet, Robert E.; Liehr, Joachim G.; Kirkendall, Walter M.; Caprioli, Richard M.

doi:10.1007/bf02026983

Cited by 25 publications

(7 citation statements)

References 36 publications

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“…1975;Ching et al 1981). Furthermore, the presence of DBP in human kidneys and plasma obtained from individuals without a recent history of medical exposure to phthalate have also been reported (Overturf et al 1979;Shintani 1985). However, so far there is no evidence of DBP toxicity in humans.…”

Section: Introductionmentioning

confidence: 86%

Testicular effects of di-n-butyl phthalate (DBP): Biochemical and histopathological alterations

et al. 1990

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Di-n-butyl phthalate (DBP) was administered to young male rats by gavage at the doses of 250, 500 and 1,000 mg/kg body weight/day for 15 days. A significant decrease in testes weight was observed at 500 and 1,000 mg/kg doses of DBP. Histopathological examination revealed marked degeneration of seminiferous tubules. The activities of testicular enzymes associated with postmeiotic spermatogenic cells, such as sorbitol dehydrogenase and acid phosphatase, were decreased significantly, while that of lactate dehydrogenase was significantly increased, coincident with degeneration of spermatogenic cells. The activities of enzymes associated with premeiotic spermatogenic cells, Sertoli cells or interstitial cells, beta-glucuronidase, gamma-glutamyl transpeptidase and glucose-6-phosphate dehydrogenase were significantly increased. Thus the alterations in activity of these testicular cell specific enzymes suggest that DBP exposure during early life could affect the testicular functions.

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Section: Introductionmentioning

confidence: 86%

Testicular effects of di-n-butyl phthalate (DBP): Biochemical and histopathological alterations

et al. 1990

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“…The widespread use of phthalates and phthalate-containing products in all segments of society has, within the span of a few decades, resulted in global contamination by this class of compounds. The presence of phthalate esters in virtually all ecosystems (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) and in the tissues of man (18)(19)(20)(21)(22), animals (6,7,9,11,16,23,24), and in the food supply of man (24)(25)(26)) is a shocking revelation.…”

Section: Introductionmentioning

confidence: 99%

Effects of phthalate esters on lipid metabolism in various tissues, cells and organelles in mammals.

Bell¹

1982

Environ Health Perspect

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The effect of phthalate ester plasticizers on a variety of enzyme systems was studied in rats, rabbits and pigs. The feeding of di(2-ethylhexyl) phthalate (DEHP) to animals at levels from 0.1% to 1.0% in the diet resulted in diverse biochemical effects, such as inhibition of cholesterologenesis in liver, testes, and adrenal gland; inhibition of cholesterologenesis in brain and liver of fetal rats from DEHP-fed dams; decreased plasma cholesterol levels; decreased synthesis of hepatic phospholipid and triglyceride; increased fatty acid oxidation in isolated liver mitochondria; and a transient decrease in fatty acid oxidation in isolated heart mitochondria. The addition of DEHP to preparations of rat liver in vitro resulted in inhibition of cholesterologenesis, and its addition to isolated mitochondria from rat heart produced an inhibition of adenine nucleotide translocase. DEHP-feeding to rats and rabbits, however, did not affect platelet function as judged by collagen-and ADP-induced aggregation. The studies presented here indicate that the exposure of animals to phthalate esters can result in a significant perturbation of normal metabolism in liver, heart, testes, adrenal gland and brain and can affect blood lipid levels.

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“…Tissue concentrations of DEHP from accident victims ranged from 0.3 to 1.0 ppm in adipose tissue (Mes et al, 1974). DEHP has also been isolated in the kidneys of autopsied patients (Overturf et al, 1979). However, since DEHP can easily contaminate biological samples during laboratory processing operations, the presence of DEHP in tissues may be an artifact.…”

Section: Absorptionmentioning

confidence: 99%

Challenges in the application of quantitative approaches in risk assessment: a case study with di-(2-ethylhexyl)phthalate

Gentry

Clewell

et al. 2011

Critical Reviews in Toxicology

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The constantly evolving science of risk assessment is currently faced with many challenges, not only from the interpretation of the volume of data being generated with new innovative technologies, but also in attempting to quantitatively incorporate this information into understanding potential risk of adverse events in human populations. The objective of the case study described was to use the more recent data for di-(2-ethylhexyl)phthalate (DEHP) to investigate the impact of innovative quantitative approaches on the risk assessment of a compound, specifically as it can be used to move towards the new vision of risk assessment involving the integration of the available toxicological data to understand underlying biological processes. What emerged were several outcomes that demonstrated clearly the importance of the integration of the toxicological data, specifically to understand the biological processes being impacted, because standard statistical modeling approaches may not be adequate to describe the dose-response relationships observed. Alternative approaches demonstrate that a definitive mode of action is not needed to justify the shape of the low-dose region or a threshold, when the integration of the available data assist risk assessors in understanding the shape of the dose-response curve for both noncancer and cancer endpoints. Many of the challenges described as part of this case study would likely be encountered with compounds other than DEHP, especially other receptor-mediated compounds or compounds that "perturb" biological pathways, such as endocrine disruptors. This case study also highlights the importance of communication between risk assessors and the research community to focus on the generation of data most relevant for assessing the potential for chemicals to impact biological systems in the human.

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Phthalate esters in normal and pathological human kidneys

Cited by 25 publications

References 36 publications

Testicular effects of di-n-butyl phthalate (DBP): Biochemical and histopathological alterations

Testicular effects of di-n-butyl phthalate (DBP): Biochemical and histopathological alterations

Effects of phthalate esters on lipid metabolism in various tissues, cells and organelles in mammals.

Challenges in the application of quantitative approaches in risk assessment: a case study with di-(2-ethylhexyl)phthalate

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