Development of a Physiologically Based Pharmacokinetic Model Describing 2-Methoxyacetic Acid Disposition in the Pregnant Mouse

Terry, Ketti K.; Elswick, Barbara A.; Welsch, Frank; Conolly, Rory B.

doi:10.1006/taap.1995.1091

Cited by 41 publications

(11 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This teratoproteomics analysis revealed that HSP70 is overexpressed in the forelimb bud 4 hr after MAA treatment. The finding is in accord with an observation that the MAA concentration peaks 2 hr after MAA treatment when a single dose of 2‐ME is administered orally on GD 11 to mice (Terry et al, 1996). Moreover, a MAA dosimetry study indicated that the half‐elimination time of MAA in mouse is 6 hr (Welsch et al, 1996).…”

Section: Discussionsupporting

confidence: 89%

A teratoproteomics analysis: Heat shock protein 70 is upregulated in mouse forelimb bud by methoxyacetic acid treatment

Ruyani¹,

Sudarwati²,

Sutasurya³

et al. 2005

Birth Defects Research

View full text Add to dashboard Cite

BACKGROUND Methoxyacetic acid (MAA) causes fetal limb abnormalities when the substance is administrated on gestation day (GD) 11 in mice. Limb abnormalities are caused mainly by extensive cell death in the mesoderm of the limb plate. This investigation focused on identifying a protein that is linked with mouse limb teratogenicity. METHODS A single dose of MAA at 10 mmol/kg body weight was administered by gavage on GD 11; controls were administered vehicle only. Dams were killed by cervical dislocation 4 hr after treatment and forelimb buds were isolated from both the control and treated embryos. Proteins in forelimb buds GD 11 + 4 hr were precipitated out using 40–60% ammonium sulfate and were then analyzed by 2D SDS‐PAGE. Excised protein spots were identified by mass spectrometry and amino acid internal sequence analysis. Identified protein was further confirmed by Western blotting. RESULTS Two‐dimensional gel analysis indicated that 1 protein spot of 81.7 kDa/pI 7.3 was overexpressed, and the protein matched heat shock protein 70 (HSP70; accession no. P08109, SwissProt). CONCLUSIONS The results suggest that MAA, when administered to pregnant mice, upregulates HSP70 in the forelimb buds. Birth Defects Research (Part A), 2005. © 2005 Wiley‐Liss, Inc.

show abstract

Section: Discussionsupporting

confidence: 89%

A teratoproteomics analysis: Heat shock protein 70 is upregulated in mouse forelimb bud by methoxyacetic acid treatment

Ruyani¹,

Sudarwati²,

Sutasurya³

et al. 2005

Birth Defects Research

View full text Add to dashboard Cite

show abstract

“…Of the PBPK models in pregnant rats for volatile chemicals to date (Fisher et al, 1989;Gargas et al, 2000;Hays et al, 2000;Terry et al, 1995;Ward et al, 1997), the scaled ventilation for nonpregnant rats was used for the pregnant rats. However, as measured in the current study, the scaled ventilation in the pregnant rats at GD 21 is approximately 16% lower compared with nonpregnant rats.…”

Section: Discussionmentioning

confidence: 99%

“…Corley et al (2003) published a literature review of models for the disposition of xenobiotics during pregnancy. PBPK models for inhaled xenobiotics including trichloroethylene, methanol, and 2-methoxyethanol (Fisher et al, 1989;Gargas et al, 2000;Hays et al, 2000;Terry et al, 1995;Ward et al, 1997) have been developed for pregnant animals. In general, these models assumed that the alveolar ventilation scaled to body weight in pregnant and nonpregnant rats were equivalent.…”

mentioning

confidence: 99%

Respiration in Sprague-Dawley Rats During Pregnancy

Leavens

Parkinson

James

et al. 2006

Inhalation Toxicology

View full text Add to dashboard Cite

Minute ventilation and tidal volume increase in humans during pregnancy. Little data exists, however, on the respiration in pregnant rats, despite their widespread use as an animal model. Since respiration will affect the pharmacokinetics of volatile compounds and ultimately the dose to the fetus, we conducted a study to evaluate respiration in rats during pregnancy. Whole-body plethysmography was used to measure the breathing frequency and tidal volume approximately every other day from gestation day (GD) 1 to 21 in 16 timed pregnant and 16 nonpregnant, female, Sprague-Dawley rats. Minute ventilation was calculated as a product of the breathing frequency and tidal volume, and the body weight of each rat was used to determine the scaled ventilation. Multivariate analysis of variance methods for a repeated-measures design were used to analyze the respiratory data. Breathing frequency was not affected by pregnancy; however, tidal volume was somewhat greater in pregnant versus nonpregnant rats. The increase in tidal volume resulted in significantly increased minute ventilation in pregnant rats compared to nonpregnant rats during the latter period of gestation. Due to the increased body weight of the pregnant rats, the scaled ventilation at the end of gestation was significantly lower in pregnant rats compared to nonpregnant rats. This study provides important reference values that can be used in pharmacokinetic models during pregnancy.

show abstract

“…PBPK modeling of various chemicals in animals during pregnancy has been reported (95,(128)(129)(130)(131)(132). For example, O'Flaherty et al (95) developed a PBPK model in the pregnant rat and mouse for 5,5´-dimethyloxazolidine-2,4-dione (DMO) that accounted for physiologic changes that occur throughout gestation.…”

Section: Application Of Dosimetry Modeling To Developmental Neurotoximentioning

confidence: 99%

Methods to identify and characterize developmental neurotoxicity for human health risk assessment. III: pharmacokinetic and pharmacodynamic considerations.

DORMAN

Allen

Byczkowski

et al. 2001

Environ Health Perspect

View full text Add to dashboard Cite

We review pharmacokinetic and pharmacodynamic factors that should be considered in the design and interpretation of developmental neurotoxicity studies. Toxicologic effects on the developing nervous system depend on the delivered dose, exposure duration, and developmental stage at which exposure occurred. Several pharmacokinetic processes (absorption, distribution, metabolism, and excretion) govern chemical disposition within the dam and the nervous system of the offspring. In addition, unique physical features such as the presence or absence of a placental barrier and the gradual development of the blood--brain barrier influence chemical disposition and thus modulate developmental neurotoxicity. Neonatal exposure may depend on maternal pharmacokinetic processes and transfer of the xenobiotic through the milk, although direct exposure may occur through other routes (e.g., inhalation). Measurement of the xenobiotic in milk and evaluation of biomarkers of exposure or effect following exposure can confirm or characterize neonatal exposure. Physiologically based pharmacokinetic and pharmacodynamic models that incorporate these and other determinants can estimate tissue dose and biologic response following in utero or neonatal exposure. These models can characterize dose--response relationships and improve extrapolation of results from animal studies to humans. In addition, pharmacologic data allow an experimenter to determine whether exposure to the test chemical is adequate, whether exposure occurs during critical periods of nervous system development, whether route and duration of exposure are appropriate, and whether developmental neurotoxicity can be differentiated from direct actions of the xenobiotic.

show abstract

Development of a Physiologically Based Pharmacokinetic Model Describing 2-Methoxyacetic Acid Disposition in the Pregnant Mouse

Cited by 41 publications

References 0 publications

A teratoproteomics analysis: Heat shock protein 70 is upregulated in mouse forelimb bud by methoxyacetic acid treatment

A teratoproteomics analysis: Heat shock protein 70 is upregulated in mouse forelimb bud by methoxyacetic acid treatment

Respiration in Sprague-Dawley Rats During Pregnancy

Methods to identify and characterize developmental neurotoxicity for human health risk assessment. III: pharmacokinetic and pharmacodynamic considerations.

Contact Info

Product

Resources

About