Induction of the Estrogenic Marker Calbindn-D9k by Octamethylcyclotetrasiloxane

Lee, Dong‐Oh; Ahn, Changhwan; An, Beum‐Soo; Jeung, Eui‐Bae

doi:10.3390/ijerph121114610

Cited by 15 publications

(6 citation statements)

References 53 publications

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“…At its maximum achievable vapor concentration (700 ppm; Quinn et al 2007 ) and oral doses (1000 mg/kg/day; McKim et al 2001 ; He et al 2003 ), D4 only partially displaces 17β-estradiol binding from ERα (He et al 2003 ) but not from ERβ (Quinn et al 2007 ). Its weak uterotrophic activity and weak partial antagonism of full uterotrophism by 17β-estradiol or 17α-ethinyl estradiol occurs at high air concentrations (700 ppm; Quinn et al 2007 ) and oral doses (1000 mg/kg/day; McKim et al 2001 ; He et al 2003 ), but is absent by the oral route of exposure in ERα-knockout mice (He et al 2003 ) and in some rat studies (Lee et al 2015 ).…”

Section: Proposed Hrpt For the Erα Agonist Moamentioning

confidence: 99%

Human-relevant potency threshold (HRPT) for ERα agonism

Borgert¹,

Matthews

Baker

2018

Arch Toxicol

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The European Commission has recently proposed draft criteria for the identification of endocrine disrupting chemicals (EDCs) that pose a significant hazard to humans or the environment. Identifying and characterizing toxic hazards based on the manner by which adverse effects are produced rather than on the nature of those adverse effects departs from traditional practice and requires a proper interpretation of the evidence regarding the chemical’s ability to produce physiological effect(s) via a specific mode of action (MoA). The ability of any chemical to produce a physiological effect depends on its pharmacokinetics and the potency by which it acts via the various MoAs that can lead to the particular effect. A chemical’s potency for a specific MoA—its mechanistic potency—is determined by two properties: (1) its affinity for the functional components that comprise the MoA, i.e., its specific receptors, enzymes, transporters, transcriptional elements, etc., and (2) its ability to alter the functional state of those components (activity). Using the agonist MoA via estrogen receptor alpha, we illustrate an empirical method for determining a human-relevant potency threshold (HRPT), defined as the minimum level of mechanistic potency necessary for a chemical to be able to act via a particular MoA in humans. One important use for an HRPT is to distinguish between chemicals that may be capable of, versus those likely to be incapable of, producing adverse effects in humans via the specified MoA. The method involves comparing chemicals that have different ERα agonist potencies with the ability of those chemicals to produce ERα-mediated agonist responses in human clinical trials. Based on this approach, we propose an HRPT for ERα agonism of 1E-04 relative to the potency of the endogenous estrogenic hormone 17β-estradiol or the pharmaceutical estrogen, 17α-ethinylestradiol. This approach provides a practical way to address Hazard Identification according to the draft criteria for identification of EDCs recently proposed by the European Commission.Electronic supplementary materialThe online version of this article (10.1007/s00204-018-2186-z) contains supplementary material, which is available to authorized users.

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Section: Proposed Hrpt For the Erα Agonist Moamentioning

confidence: 99%

Human-relevant potency threshold (HRPT) for ERα agonism

Borgert¹,

Matthews

Baker

2018

Arch Toxicol

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“…Current studies show that EDCs such as bisphenol A are suggested to cause and worsen autism spectrum disorder [13,14]. The correlation between EDCs and neurodevelopmental disorders such as autism spectrum disorder, schizophrenia, and attention deficit-hyperactivity disorder (ADHD) has been studied, and several chemicals with neurodevelopment toxicity have been prohibited owing to their serious side effects [7,14,15].…”

Section: Introductionmentioning

confidence: 99%

Effects of Maternal Exposure to Decamethylcyclopentasiloxane on the Alternations in Offspring Behaviors in Mice

Kim

Lee

et al. 2022

Biomedicines

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D5, a member of the cyclic siloxane family, is widely used in personal care products such as shampoo, cosmetics, and deodorant and as an industrial intermediate. D5 can mainly be absorbed orally or through inhalation. Through these routes, people are exposed to D5 daily. However, the risk of prenatal exposure to D5 has not been fully elucidated. In this study, the effect of D5 on neural development was established through behavioral tests on offspring mice. The result confirmed that the maternal administration of 12 mg/kg of D5 showed depression in tail suspension and decreased performance in the forced swimming test as well as an increase in repetitive activity in both the marble-burying test and grooming test compared to the vehicle group. Furthermore, the 12 mg/kg group showed a decrease in cognitive ability and social behavior in the three-chamber test. In the novel object recognition test, memory impairment and a lack of exploring ability were found in the 12 mg/kg group. In conclusion, it is suggested that maternal D5 exposure has developmental neurotoxicity and can cause behavioral disorders in the offspring of mice. Thus, the usage of D5 needs to be considered carefully.

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“…Therefore, there is increasing concern about the fate and effects of D4 [ 13 ]. D4 is an endocrine-disrupting chemical (EDC) with estrogenic potential [ 14 ]. Chronic exposure to D4 increased the liver, kidney, testes, and uterine weight with correlating morphological changes in rats [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Prenatal Octamethylcyclotetrasiloxane Exposure Impaired Proliferation of Neuronal Progenitor, Leading to Motor, Cognition, Social and Behavioral Functions

Tran

Park

Jung

et al. 2021

IJMS

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Cyclic siloxane octamethylcyclotetrasiloxane (D4) has raised concerns as an endocrine-disrupting chemical (EDC). D4 is widely used in detergent products, cosmetics, and personal care products. Recently, robust toxicological data for D4 has been reported, but the adverse effects of D4 on brain development are unknown. Here, pregnant mice on gestational day 9.5 were treated daily with D4 to postnatal day 28, and the offspring mice were studied. The prenatal D4-treated mice exhibited cognitive dysfunction, limited memory, and motor learning defect. Moreover, prenatal D4 exposure reduced the proliferation of neuronal progenitors in the offspring mouse brain. Next, the mechanisms through which D4 regulated the cell cycle were investigated. Aberrant gene expression, such as cyclin-dependent kinases CDK6 and cyclin-dependent kinase inhibitor p27, were found in the prenatal D4-treated mice. Furthermore, the estrogen receptors ERa and ERb were increased in the brain of prenatal D4-treated mice. Overall, these findings suggest that D4 exerts estrogen activity that affects the cell cycle progression of neuronal progenitor cells during neurodevelopment, which may be associated with cognitive deficits in offspring.

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Induction of the Estrogenic Marker Calbindn-D9k by Octamethylcyclotetrasiloxane

Cited by 15 publications

References 53 publications

Human-relevant potency threshold (HRPT) for ERα agonism

Human-relevant potency threshold (HRPT) for ERα agonism

Effects of Maternal Exposure to Decamethylcyclopentasiloxane on the Alternations in Offspring Behaviors in Mice

Prenatal Octamethylcyclotetrasiloxane Exposure Impaired Proliferation of Neuronal Progenitor, Leading to Motor, Cognition, Social and Behavioral Functions

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