Pharmacokinetic Considerations in the Maternal - Placental - Fetal Unit

Juchau, Mont R.; Faustman-Watts, Elaine M.

doi:10.1097/00003081-198306000-00020

Cited by 19 publications

(8 citation statements)

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“…The entire set of maternal toxicokinetic factors (e.g., absorption, distribution, serum binding, and elimination) also influences the concentration of active agent at the target site. Because of the physiologic changes that occur during pregnancy, the influence of these maternal factors on chemical delivery may also change during gestation (Bogaert and Thiery 1983;Cummings 1983;Juchau 1995;Juchau and Faustman-Watts 1983;Noschel et al 1980). These issues have been reviewed (Brock-Utne et al 1980;Juchau and Faustman-Watts 1983;Krauer et al 1980;Levy 1981;Slikker and Miller 1994).…”

Section: Phase Ii: Data Analysis and Development Of Risk Assessment Amentioning

confidence: 99%

“…As with most organ systems, the various chemicalmetabolizing systems undergo quantitative if not qualitative changes during development. Chemical biotransformation by the developing conceptus has been extensively reviewed (Dutton 1978;Dutton and Leakey 1981;Dvorchik 1981;Eltom et al 1993;Juchau and Faustman-Watts 1983;Leakey 1983;Nau and Neubert 1978;Neims et al 1976;Pelkonen 1977Pelkonen , 1980Rane and Tomson 1980;Slikker 1987Slikker , 1994Slikker and Miller 1994). Despite that data have been collected using a variety of techniques and some data gaps exist because of technical or ethical reasons, several general conclusions may be drawn from the literature.…”

Section: Phase Ii: Data Analysis and Development Of Risk Assessment Amentioning

confidence: 99%

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Incorporating children's toxicokinetics into a risk framework.

Ginsberg

Slikker

Bruckner

et al. 2004

Environ Health Perspect

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Children's responses to environmental toxicants will be affected by the way in which their systems absorb, distribute, metabolize, and excrete chemicals. These toxicokinetic factors vary during development, from in utero where maternal and placental processes play a large role, to the neonate in which emerging metabolism and clearance pathways are key determinants. Toxicokinetic differences between neonates and adults lead to the potential for internal dosimetry differences and increased or decreased risk, depending on the mechanisms for toxicity and clearance of a given chemical. This article raises a number of questions that need to be addressed when conducting a toxicokinetic analysis of in utero or childhood exposures. These questions are organized into a proposed framework for conducting the assessment that involves problem formulation (identification of early life stage toxicokinetic factors and chemical-specific factors that may raise questions/concerns for children); data analysis (development of analytic approach, construction of child/adult or child/animal dosimetry comparisons); and risk characterization (evaluation of how children's toxicokinetic analysis can be used to decrease uncertainties in the risk assessment). The proposed approach provides a range of analytical options, from qualitative to quantitative, for assessing children's dosimetry. Further, it provides background information on a variety of toxicokinetic factors that can vary as a function of developmental stage. For example, the ontology of metabolizing systems is described via reference to pediatric studies involving therapeutic drugs and evidence from in vitro enzyme studies. This type of resource information is intended to help the assessor begin to address the issues raised in this paper.

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Section: Phase Ii: Data Analysis and Development Of Risk Assessment Amentioning

confidence: 99%

Section: Phase Ii: Data Analysis and Development Of Risk Assessment Amentioning

confidence: 99%

Incorporating children's toxicokinetics into a risk framework.

Ginsberg

Slikker

Bruckner

et al. 2004

Environ Health Perspect

View full text Add to dashboard Cite

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“…During pregnancy, many physiologic changes occur, and these changes can impact the kinetic aspects of chemicals (90 Figure 6 taken from Cresteil (91) shows elegant work to evaluate the evolution of various isoforms of human liver cytochrome P450s in utero and throughout childhood. As is evident from this figure, each isoform has its own developmental profile.…”

Section: Toxicokinetic Considerationsmentioning

confidence: 99%

Mechanisms underlying Children's susceptibility to environmental toxicants.

Faustman

Silbernagel

Fenske

et al. 2000

Environ Health Perspect

245

163

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An important public health challenge has been the need to protect children's health. To accomplish this goal, the scientific community needs scientifically based child-specific risk assessment methods. Critical to their development is the need to understand mechanisms underlying children's sensitivity to environmental toxicants. Risk is defined as the probability of adverse outcome and when applied to environmental risk assessment is usually defined as a function of both toxicity and exposure. To adequately evaluate the potential for enhanced health risks during development, both child-specific factors affecting toxicity and exposure need to be considered. In the first section of this article, example mechanisms of susceptibility relevant for toxicity assessment are identified and discussed. In the second section, examples of exposure factors that help define children's susceptibility are presented. Examples of pesticide research from the newly funded Child Health Center at the University of Washington will be given for illustration. The final section discusses the importance of putting these considerations of children's susceptibility into an overall framework for ascertaining relevancy for human risk assessment. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 6

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“…These conditions may influence the distribution of xenobiotics between the mother and the conceptus. In addition to maternal physiology, the limited evidence available suggests that relative rates of drug metabolizing enzymes also change during pregnancy (Juchau, 1981;Juchau & Faustman-Watts, 1983). In experimental animals, the hepatic metabolism of xenobiotics is altered during pregnancy.…”

Section: Pregnancymentioning

confidence: 99%

Expressing urine from a gel disposable diaper for biomonitoring using phthalates as an example

Liu

Xia

Guo

et al. 2012

J Expo Sci Environ Epidemiol

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The urinary metabolites of phthalates are well-accepted exposure biomarkers for adults and children older than 6 years but are not commonly used for infants owing to non-convenient sampling. In the light of this situation, a novel sampling method based on monitoring the urine expressed from the gel diaper was developed. The urine was expressed from the gel absorbent after mixing the absorbent with CaCl2 and then collected by a laboratory-made device; the urinary phthalate metabolites were extracted and cleaned using a solid-phase extraction (SPE) column and analyzed with high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry / mass spectrometry. To evaluate the method's feasibility, the following factors were investigated: the proportion of CaCl2 to gel absorbent, the urination volume variation and the target compounds' deposition bias in the diaper, the matrix blank of the different diaper brands, the storage stabilities and the recoveries of creatinine and phthalate metabolites in the expressed urine. Mono-methyl phthalate, mono-ethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, mono-2-ethylhexyl phthalate and mono-2-ethyl-5-oxohexyl phthalate were involved. 70-80% of the urine can be expressed from the diaper, and the expressed spiking recoveries and the limit of detection of mono-phthalates ranged from 88.5-115% and 0.21-0.50 ng/ml. The method was applied to measure phthalate metabolites in 65 gel diaper samples from 15 infants, and the pilot data suggests the infants are commonly exposed to phthalates. In summary, the method for monitoring of infant exposure to phthalates is sound and validated, and the potential health effects from the vulnerable infants' exposure to phthalates should be concerned.39th Scientific Research Foundation for the Returned Overseas Chinese Scholars (SRF for ROCS); Hundred Talent Program of Chinese Academy of Sciences (CAS); CAS/SAFEA International Partnership Program for Creative Research Teams [KZCX2-YW-T08

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Pharmacokinetic Considerations in the Maternal - Placental - Fetal Unit

Cited by 19 publications

References 0 publications

Incorporating children's toxicokinetics into a risk framework.

Incorporating children's toxicokinetics into a risk framework.

Mechanisms underlying Children's susceptibility to environmental toxicants.

Expressing urine from a gel disposable diaper for biomonitoring using phthalates as an example

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