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Related Concept Videos

Teratogenicity01:07

Teratogenicity

The ability of a drug to produce structural deformations and functional abnormalities in the developing embryo or the fetus is called teratogenicity, and the drug producing this effect is known as a teratogen. Teratogenic effects include stillbirth, miscarriage, intrauterine growth restriction, and neurocognitive delay. A teratogen may affect the embryo at different stages of development, which is important in determining the type and extent of the damage. During blastocyst formation, the early...
Pharmacokinetics in Pediatric Patients: Drug Metabolism01:24

Pharmacokinetics in Pediatric Patients: Drug Metabolism

In pediatric care, understanding the nuances of hepatic drug metabolism is crucial, as it significantly differs from that of adults. This divergence is primarily due to the developmental stage of drug-metabolizing enzymes, which affects how medications are processed in the body. In neonates, for instance, the activity of Phase I enzymes—critical for the initial breakdown of drugs—is markedly reduced, functioning at just 20–40% of the levels seen in adults. This reduction poses a challenge in...
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Pharmacokinetics in Pediatric Patients: Overview and Drug Absorption

Understanding the physiological differences in the pediatric population is crucial for effective pharmacotherapy. Neonates, infants, and children exhibit significant variations in gastric pH, gastric emptying time, intestinal transit time, and biliary function. These variations profoundly affect oral drug absorption, necessitating a nuanced approach to pediatric dosing.Neonates present with a unique physiological profile, having a gastric pH greater than 4 and faster and more irregular gastric...
Drug Toxicity: Dose-Dependent Reactions01:24

Drug Toxicity: Dose-Dependent Reactions

Drug toxicities can be stratified into pharmacological, pathological, or genotoxic based on their mechanisms. The incidence and severity of these toxicities generally increase with the drug's concentration in the body and exposure time.Pharmacological toxicity is evident when the therapeutic effects of drugs overshoot into adverse reactions in a predictable, dose-dependent manner. Central nervous system (CNS) depression from barbiturates is a classic example, with effects escalating from...
Toxicity Testing in Animals01:23

Toxicity Testing in Animals

Toxicity tests in animals are grounded on two main assumptions: first, the effects observed in laboratory animals can be extrapolated to humans, especially when adjusted for body surface area; second, high-dose exposure in animals is essential to identify potential human hazards from lower doses. This is based on the quantal dose-response concept, which faces the challenge of extrapolating results from relatively few test animals to much larger human populations. For example, a 0.01% incidence...
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Preclinical Development: Overview

Preclinical development consists of a series of tests that ensure the safety and efficacy of a new therapeutic compound before it is tested in humans. There are four main phases to this process. First, safety pharmacology tests are conducted to ensure the drug does not produce any acutely harmful effects. These tests examine parameters such as bronchoconstriction, cardiac dysrhythmias, blood pressure changes, and ataxia. Next, preliminary toxicological testing is performed to determine the...

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Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
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Bisphenol A: developmental toxicity from early prenatal exposure.

Mari S Golub1, Katherine Lily Wu, Farla L Kaufman

  • 1Office of Environmental Health Hazard Assessment, Reproductive and Cancer Hazard Assessment Branch, Sacramento, California, USA. mgolub@oehha.ca.gov

Birth Defects Research. Part B, Developmental and Reproductive Toxicology
|December 8, 2010
PubMed
Summary

Prenatal exposure to Bisphenol A (BPA) can impact offspring development, affecting growth, sex differentiation, and immune responses. Research highlights effects even at low doses, emphasizing the need for further human health risk assessment.

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Area of Science:

  • Developmental Biology
  • Toxicology
  • Endocrinology

Background:

  • Bisphenol A (BPA) exposure is common in pregnant women, yet its developmental consequences for offspring are understudied in humans.
  • Extensive research in animal models has explored BPA's impact on embryonic development, sex differentiation, and immune function.

Purpose of the Study:

  • To review existing research on the developmental consequences for offspring following maternal Bisphenol A (BPA) exposure during pregnancy.
  • To synthesize findings from laboratory rodent studies regarding BPA's effects on various developmental parameters.

Main Methods:

  • Review of extensive laboratory rodent studies evaluating BPA's impact on conceptus survival, growth, and embryonic development.
  • Analysis of research examining morphological and behavioral sex differentiation, immune responsiveness, and mechanisms of action.
  • Inclusion of studies utilizing sensitive measures such as gene expression (RAR, aryl hydrocarbon receptor, Hox A10), anogenital distance, and behavioral assessments.

Main Results:

  • BPA exposure can interfere with embryonic development, alter sex differentiation (morphological and behavioral), and affect immune responsiveness in offspring.
  • Many adverse effects are observed at low oral doses (10-50 µg/kg/d), while high doses (>500,000 µg/kg/d) compromise fetal viability.
  • Research indicates both estrogenic actions and potential thyroid-related mechanisms of action for BPA.

Conclusions:

  • Maternal BPA exposure during pregnancy poses risks to offspring development, impacting multiple biological systems.
  • Findings from animal models, particularly concerning low-dose effects and mechanisms of action, are crucial for human health risk assessment.
  • Integrating developmental biology, endocrine disruption concepts, and toxicology is essential for understanding BPA's impact.