Identification of the metabolites of simple phthalate diesters in rat urine

Albro, Phillip W.; Moore, Bryant M.

doi:10.1016/s0021-9673(01)92368-4

Cited by 145 publications

(71 citation statements)

References 6 publications

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“…After orally administering DBP to rats, DBP, monobutyl phthalate (MBP), phthalic acid, MBP-glucuronide and various ω-and ω-1-oxidation products of MBP (more polar ketones and carboxylates) are detected in serum (Albro and Moore, 1974;Williams and Blanchfield, 1975;Tanaka et al, 1978;Foster et al, 1983). Furthermore, after administering 2.0 g DBP/kg orally to rats, MBP and MBP-glucuronide in urine accounted for 38% and 14% of the dose, respectively (Foster et al, 1983).…”

Section: Introductionmentioning

confidence: 99%

Retraction: In utero-exposed di(n-butyl) phthalate induce dose dependent, age-related changes of morphology and testosterone-biosynthesis enzymes/associated proteins of Leydig cell mitochondria in rats

Motohashi

Wempe

Mutou³

et al. 2016

J. Toxicol. Sci.

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-Female pregnant Sprague-Dawley rats were intragastrically (ig) administered di(n-butyl) phthalate (DBP) at four doses (0, 10, 50 and 100 mg/kg) during gestation days (GD) 12-21 (n = 5 per group). The age-related morphological changes of Leydig cell mitochondrion (LC-Mt) and testosterone biosynthesis enzymes/associated genes/proteins expression levels were investigated. As compared to the control (no DBP), the 10 mg, and 50 mg DBP dose groups, the 100 mg DBP dose group at weeks 5 and 7 showed a significant amount of small LC-Mt. Thereafter, from weeks 9 to 17, the LC-Mt size and quantity in the100 mg DBP dose group increased and became statistically similar to the other dose groups; hence, dose and time-dependent LC-Mt changes were observed. Throughout the study, the 100 mg DBP dose group had significantly lower testosterone levels. In addition, the 100 mg DBP dose group displayed lower StAR (StAR, steroidogenic acute regulatory protein) and P450scc (CYP11a1, cholesterol side-chain cleavage enzyme) levels at weeks 5 and 7, but they became statistically similar to all other dose groups at weeks 9 to 17; in contrast, the SR-B1 (Sarb1, scavenger receptor class B member 1) levels were similar for all DBP dose groups. The rats in utero 100 mg DBP /kg/day (GD 12-21) exposure results from this study indicate a dose-dependent, age-related morphological change in LC-Mt which are linked to reductions in testosterone biosynthesis genes / proteins expression, specifically StAR and P450scc.

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Section: Introductionmentioning

confidence: 99%

Retraction: In utero-exposed di(n-butyl) phthalate induce dose dependent, age-related changes of morphology and testosterone-biosynthesis enzymes/associated proteins of Leydig cell mitochondria in rats

Motohashi

Wempe

Mutou³

et al. 2016

J. Toxicol. Sci.

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“…F UE value of 0.0215 was used for MINP based on report of Koch et al [25]. For MnOP, 0.043 was used from the animal data of Albro and Moore [26]. MW d and MW m are the molecular weight of phthalate diesters and phthalate monoesters, respectively.…”

Section: Daily Intake Estimatesmentioning

confidence: 99%

Exposure assessment of phthalate esters in Japanese pregnant women by using urinary metabolite analysis

Suzuki

Niwa

Yoshinaga

et al. 2009

Environ Health Prev Med

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Objectives Our objectives were (1) to evaluate whether single spot urine is suitable media for longer-term phthalate esters exposure assessment, and (2) to estimate intake level of phthalate esters of Japanese pregnant women using urinary metabolites as an indicator of prenatal exposure level in their offspring. Methods We analyzed nine metabolites (MMP, MEP, MnBP, MBzP, MEHP, MEOHP, MEHHP, MINP, MnOP) of seven phthalate esters in spot urine samples from 50 pregnant women by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Using four urine samples collected from each of 12 subjects from 50 pregnant women within 5-12 weeks, we compared intra-and interindividual variation in urinary metabolites by calculation of intraclass correlation coefficient (ICC). We estimated daily intakes of 50 pregnant women from their urinary metabolite concentrations.Results ICCs for seven phthalate metabolite concentrations in single spot urine samples were: MMP (0.57), MEP (0.47), MnBP (0.69), MBzP (0.28), MEHP (0.51), MEHHP (0.43), and MEOHP (0.41) in 12 pregnant women. Phthalate ester metabolites had high detection rates in 50 subjects. The mean daily intake ranged from 0.01 to 2 lg/kg per day. The daily intake levels in all subjects were lower than corresponding tolerable daily intake (TDI) set by the European Food Safety Authority (EFSA), though maximum value for DnBP of 6.91 lg/kg per day accounted for 70% of TDI value. Conclusions Higher ICCs indicated that phthalate metabolite levels in single spot urine could reflect longer-term exposure to the corresponding diesters of subjects. Although the current exposure level was less than TDIs, further studies and exposure monitoring are needed to reveal the toxicity of phthalate esters to sensitive subpopulation.

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“…The side chain of each ester is excreted as the product of w-1 and w-oxidation. In the case of MnOP, 21% is excreted as the product of w-1 oxidation and 62% as the product of w-oxidation followed by two rounds of P-oxidation (67). In the case of MEHP, 35% is excreted as the product of w-1 oxidation and 30% as the product of w-oxidation, only 5% of which undergoes (-oxidation (68).…”

Section: Development Of Hepatic Changesmentioning

confidence: 99%

Effects of phthalic acid esters on the liver and thyroid.

Hinton¹,

Mitchell²,

Mann³

et al. 1986

Environ Health Perspect

127

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The effects, over periods from 3 days to 9 months of administration, of diets containing di-2-ethylhexyl phthalate are very similar to those observed in rats administered diets containing hypolipidemic drugs such as clofibrate. Changes occur in a characteristic order commencing with alterations in the distribution of lipid within the liver, quickly followed by proliferation of hepatic peroxisomes and induction of the specialized P450 isoenzyme(s) catalyzing w oxidation of fatty acids. There follows a phase of mild liver damage indicated by induction of glucose-6-phosphatase activity and a loss of glycogen, eventually leading to the formation of enlarged lysosomes through autophagy and the accumulation of lipofuscin. Associated changes are found in the kidney and thyroid. The renal changes are limited to the proximal convoluted tubules and are generally similar to changes found in the liver. The effects on the thyroid are more marked. Although the levels of thyroxine in plasma fall to about half normal values, serum triiodothyronine remains close to normal values while the appearance of the thyroid varies, very marked hyperactivity being noted 7 days after commencement of treatment, this is less marked at 14 days, but even after 9 months treatment there is clear cut evidence for hyperactivity with colloid changes which indicate this has persisted for some time. Straight chain analogs of di-2-ethylhexyl phthalate, di-n-hexyl phthalate and di-n-oxtyl phthalate differ entirely in their short-term effects on the liver and kidney but have similar effects on the thyroid.The short-term in vivo hepatic effects of the three phthalate esters can be reproduced in hepatocytes in tissue culture. All three phthalate esters, as well as clofibrate, have early marked effects on the metabolism of fatty acids in isolated hepatocytes. The nature of these changes is such as to increase storage of lipid in the liver. A hypothesis is presented to explain the progress from these initial metabolic effects to the final formation of liver tumors.

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Identification of the metabolites of simple phthalate diesters in rat urine

Cited by 145 publications

References 6 publications

Retraction: <i>In utero</i>-exposed di(<i>n</i>-butyl) phthalate induce dose dependent, age-related changes of morphology and testosterone-biosynthesis enzymes/associated proteins of Leydig cell mitochondria in rats

Retraction: <i>In utero</i>-exposed di(<i>n</i>-butyl) phthalate induce dose dependent, age-related changes of morphology and testosterone-biosynthesis enzymes/associated proteins of Leydig cell mitochondria in rats

Exposure assessment of phthalate esters in Japanese pregnant women by using urinary metabolite analysis

Effects of phthalic acid esters on the liver and thyroid.

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