Retention, distribution, excretion, and metabolism of dibutyl phthalate-7-14C in the rat

Williams, David T.; Blanchfield, B.

doi:10.1021/jf60201a047

Cited by 77 publications

(25 citation statements)

References 9 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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“…Most of a phthalate dose is cleared in 24 hr and completely eliminated in 3-5 days (13,(19)(20)(21)(22). Because phthalates are lipophilic (23), it might be predicted that these compounds would accumulate in fat.…”

Section: Discussionmentioning

confidence: 99%

The association between biomarker-based exposure estimates for phthalates and demographic factors in a human reference population.

Koo

Parham

Kohn

et al. 2002

Environ Health Perspect

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Phthalates are important industrial chemicals used in the manufacture of a wide range of plastic and nonplastic products and can be divided into two basic groups: those used as plasticizers for synthetic polymers that are incorporated into food wrap, medical tubing, and molded toys, and those used primarily in consumers products such as varnishes, perfumes, nail polishes, and insect repellents. It is conceivable that the route of exposure of an organism to phthalates is an important parameter when considering metabolism of these chemicals in vivo. Phthalates are readily metabolized in the gut, such that oral exposure would not lead to accumulation of high concentrations of these chemicals (1). However, few data are available on the metabolism of this group of chemicals after inhalation or dermal exposure. The primary route of phthalate exposure to the general human population has been presumed to be ingestion. Lower molecular-weight phthalates such as diethyl phthalate (DEP) and di-nbutyl phthalate (DBP) can be absorbed percutaneously, and the more volatile congeners can be inhaled. Dermal absorption is important for products applied to skin. (3) applied a simple pharmacokinetic model to estimate the total daily intake of phthalates that would result in the reported urinary concentrations of monoester metabolites. These intake estimates were used as a measure of total exposure to diethyl phthalate (DEP), di-n-butyl phthalate (DBP), n-butyl benzyl phthalate (BBP), dicyclohexyl phtha-Blount et al. (2) reported a considerable number of observations in which the analyte levels in urine were below the limit of detection (LOD) for the procedure being used. This analysis excluded analytes for which more than 25% of the studied individuals were below the LOD and discarded individuals below the LOD for analytes they did analyze. This represents a substantial loss of information. Maximum likelihood methods for censored observations (4-7) have been used for many years to analyze survival data and data for which some observations cannot be seen, but it is known that the observation is beyond some critical point. For urinary metabolite data, an observation below the LOD can be assumed to have a metabolite concentration less than the LOD. Methods have been developed for analyzing biomarkers of exposure-including observations below the LOD-by using statistical likelihoods and regression methods for censored data (8). Using a likelihood for censored data, these fractional pieces of information contribute to the overall interpretation of the data and can be used in a natural framework to estimate parameters and test for population differences. To account for strata differences of demographic factors, we estimated population-based exposures to phthalates using a weighted analysis in which weights were assigned for each individual group depending on the frequency of their demographic variables in the general U.S. population.The aim of this study was to present methods for the analysis of exposure estimates based on urinary biomar...

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“…The following facts also favor this assumption. First, pharmacokinetic studies show that DEHP is metabolized and eliminated rapidly in mice (22,23), rats (18,24) and humans (1,25).…”

Section: Discussionmentioning

confidence: 99%

Teratogenicity of di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DBP) in mice.

Shiota¹,

Nishimura²

1982

Environ Health Perspect

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Di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DBP) were mixed with diet at graded levels of 0.05, 0.1, 0.2, 0.4 and 1.0 wt-% and given to pregnant ICR mice throughout gestation. Maternal weight gain was suppressed and fetal resorptions increased at 0.2, 0.4 and 1.0%o levels of DEHP and 1.0%o level of DBP. All the implanted ova died early in rats fed 0.4 and 1.0% levels of DEHP. External malformations increased significantly by 0.2% DEHP, and 1.0% DBP showed borderline significance. The major malformations in treated groups were neural tube defects (exencephaly and myeloschisis), suggesting that the phthalic acid esters (PAEs) affect neural tube closure in developing embryos. Treatment with the compounds caused intrauterine growth retardation and delayed ossification with an apparently dose-related response pattern. These results indicate that a high dose of DEHP and DBP might be embryotoxic and teratogenic in mice. The maximum nonembryotoxic doses of PAEs in mice were more than 2000 times the estimated level of human intake through the food chain. Thus it is assumed that the current "normal" exposure level of PAEs does not pose an imminent threat to human fetal development.

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Retention, distribution, excretion, and metabolism of dibutyl phthalate-7-14C in the rat

Cited by 77 publications

References 9 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

The association between biomarker-based exposure estimates for phthalates and demographic factors in a human reference population.

Teratogenicity of di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DBP) in mice.

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