Reproductive stimulation by low doses of xenoestrogens contrasts with the view of hormesis as an adaptive response

2005 ◽  
Vol 24 (9) ◽  
pp. 431-437 ◽  
Author(s):  
Lennart Weltje ◽  
Frederick S vom Saal ◽  
Jörg Oehlmann

We discuss the similarities and differences of two types of effects that occur at low but not high doses of chemicals: hormesis and stimulation by oestrogenic endocrine-disrupting chemicals or xenoestrogens. While hormesis is a general phenomenon evoked by many compounds, oestrogenic stimulation occurs for specific chemicals that disrupt actions of endogenous oestrogen. Both types of phenomena can induce an inverted-U dose-response curve, from low-dose stimulation of response, and thus challenge current methods of risk assessment. Hormesis is generally thought to be caused by an over-reaction of detoxification mechanisms, which is considered an adaptive response that should protect an organism from subsequent stress. One view of the hormetic low-dose stimulatory response, i.e., increased performance, is that it is beneficial. In contrast, we propose that for manmade xenoestrogens this is never the case. This is demonstrated with examples for low doses of the oestrogenic environmental chemicals bisphenol A and octylphenol, and the oestrogenic drug-response curves is underestimated by the current threshold model used in risk assessment, and this is likely to apply to other endocrine-disrupting chemicals.

2012 ◽  
Vol 33 (3) ◽  
pp. 378-455 ◽  
Author(s):  
Laura N. Vandenberg ◽  
Theo Colborn ◽  
Tyrone B. Hayes ◽  
Jerrold J. Heindel ◽  
David R. Jacobs ◽  
...  

For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of “the dose makes the poison,” because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from the cell culture, animal, and epidemiology literature. We illustrate that nonmonotonic responses and low-dose effects are remarkably common in studies of natural hormones and EDCs. Whether low doses of EDCs influence certain human disorders is no longer conjecture, because epidemiological studies show that environmental exposures to EDCs are associated with human diseases and disabilities. We conclude that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health.


The phenomenon of adaptive response is expressed in the increase of resistance of a biological object to high doses of mutagens under the conditions of previous exposure to these (or other) mutagens in low doses. Low doses of mutagen activate a number of protective mechanisms in a living object, which are called hormetic. Thus, the adaptive response and hormesis are links in the same chain. Radiation hormesis refers to the generally positive effect of low doses of low LET radiation on biological objects. The phenomenology of radiation-induced adaptive response and radiation hormesis for biological objects of different levels of organization is considered; the review of existing theories describing the dose-effect relationship has been reviewed. The hypothesis proposing one of the mechanisms of formation of radiation adaptive response of cells taking into account the conformational structure of chromatin has been submitted. The analysis of modern concepts of the phenomenon of hormesis on the basis of modeling of molecular mechanisms of formation of hormetic reactions to low-dose low LET radiation has been carried out. The parameters that can be used for quantitative and graphical evaluation of the phenomenon of hormesis was considered, and a formula for calculating the coefficient of radiation-induced adaptive response has been proposed. A review of mathematical models describing the radiation relative risk of gene mutations and neoplastic transformations at low-dose irradiation of cohorts has been performed. The following conclusions have been made: radiation hormesis and adaptive response are generally recognized as real and reproducible biological phenomena, which should be considered as very important phenomena of evolutionarily formed biological protection of living organisms from ionizing radiation. The hormesis model of dose-response relationship makes much more accurate predictions of a living object's response to radiation (or other stressors) in the low-dose range than the linear threshold (LNT) model does. The LNT model can adequately describe reactions only in the region of high doses of radiation, and, therefore, extrapolation modeling of biological object’s reactions from the zone of high doses to low doses is not correct.


2011 ◽  
Vol 30 (12) ◽  
pp. 2027-2030 ◽  
Author(s):  
Salvatore Chirumbolo

Hormesis is a dose–response phenomenon, usually present in plants and animals, characterized by a low-dose stimulation and high-dose inhibition, often resulting in typical U-shaped or J-shaped curves. Hormesis has become an interesting model for toxicology and risk assessment, as it has been described for several nature-derived phytochemicals but also because this adaptive response to stressors might hide an underlying more general behaviour of cell towards low doses.


Bioanalysis ◽  
2021 ◽  
Author(s):  
Rajesh Pradhan ◽  
Siddhanth Hejmady ◽  
Rajeev Taliyan ◽  
Gautam Singhvi ◽  
Rajesh Khadgawat ◽  
...  

Endocrine-disrupting chemicals (EDCs) are xenobiotics that disrupt the endocrine system in humans at ecologically significant concentrations. Various substances are exposed to human health via routes including food, water, air and skin that result in disastrous maladies at low doses as well. Therefore EDCs need a meticulous strategy of analysis for dependable and consistent monitoring in humans. The management and risk assessment necessitate advancements in the detection methodologies of EDCs. Hyphenated MS-based chromatograph and other validated laboratory analysis methods are widely available and employed. Besides, in vitro bioassay techniques and biosensors are also used to conduct accurate toxicological tests. This article provides a revision of various bioanalytical detection methods and technologies for the clinical estimation of EDCs.


Author(s):  
Adrienne Sprouse

This chapter describes the categories of 300+ environmental chemicals measured in the blood and urine of Americans by the US Centers for Disease Control and Prevention. Some are endocrine-disrupting chemicals (EDCs) and substitute for endogenous hormones in a variety of metabolic processes affecting sexual health, obesity, diabetes, and behavior. The Monotonic Dose-Response (linear dose-response) is inappropriate when evaluating the health consequences of EDCs. Nonmonotonic Dose-Response Curves are better for considering the affinity of the ligand for the receptor, receptor saturation, ligand specificity, and tissue specificity of the receptor distribution. These factors combine to explain why ambient levels of many environmental chemicals cause damage to tissues or development and why low-level exposures can create disease different from higher level exposures. Exposure during critical stages of fetal development may cause permanent changes not apparent until adulthood. Environmental chemicals that are not EDCs may harm by altering genetic material and causing apoptosis.


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Diksha Sirohi ◽  
Ruqaiya Al Ramadhani ◽  
Luke D. Knibbs

AbstractPurposeEndocrine-related diseases and disorders are on the rise globally. Synthetically produced environmental chemicals (endocrine-disrupting chemicals (EDCs)) mimic hormones like oestrogen and alter signalling pathways. Endometriosis is an oestrogen-dependent condition, affecting 10–15% of women of the reproductive age, and has substantial impacts on the quality of life. The aetiology of endometriosis is believed to be multifactorial, ranging from genetic causes to immunologic dysfunction due to environmental exposure to EDCs. Hence, we undertook a systematic review and investigated the epidemiological evidence for an association between EDCs and the development of endometriosis. We also aimed to assess studies on the relationship between body concentration of EDCs and the severity of endometriosis.MethodFollowing PRISMA guidelines, a structured search of PubMed, Embase and Scopus was conducted (to July 2018). The included studies analysed the association between one or more EDCs and the prevalence of endometriosis. The types of EDCs, association and outcome, participant characteristics and confounding variables were extracted and analysed. Quality assessment was performed using standard criteria.ResultsIn total, 29 studies were included. Phthalate esters were positively associated with the prevalence of endometriosis. The majority (71%) of studies revealed a significant association between bisphenol A, organochlorinated environmental pollutants (dioxins, dioxin-like compounds, organochlorinated pesticides, polychlorinated biphenyls) and the prevalence of endometriosis. A positive association between copper, chromium and prevalence of endometriosis was demonstrated in one study only. Cadmium, lead and mercury were not associated with the prevalence of endometriosis. There were conflicting results for the association between nickel and endometriosis. The relationship of EDCs and severity of endometriosis was not established in the studies.ConclusionWe found some evidence to suggest an association between phthalate esters, bisphenol A, organochlorinated environmental pollutants and the prevalence of endometriosis. Disentangling these exposures from various other factors that affect endometriosis is complex, but an important topic for further research.


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