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...

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Hormones and endocrine-disrupting chemicals: Low-dose effects and nonmonotonic dose responses

Human exposure to bisphenol A (BPA).

Toxicity, metabolism, and impact of mycotoxins on humans and animals.

Exposure based waiving: The application of the toxicological threshold of concern (TTC) to inhalation exposure for aerosol ingredients in consumer products

BackgroundBisphenol A (BPA) is one of the highest-volume chemicals produced worldwide, and human exposure to BPA is thought to be ubiquitous. Thus, there are concerns that the amount of BPA to whic...

/pdf/urinary-circulating-and-tissue-biomonitoring-studies-3sv3m05feu.pdf

Urinary, circulating, and tissue biomonitoring studies indicate widespread exposure to bisphenol A.

Carcinogenicity categorization of chemicals-new aspects to be considered in a European perspective.

SCCP (Scientific Committee on Consumer Products) / SCHER (Scientific Committee on Health& Environment Risks) / SCENIHR (Scientific Committee on Emerging and Newly- Identified Health Risks) opinion on: Risk assessment methodologies and approaches for genotoxic and carcinogenic substances

Antioxidant activities of major thyme ingredients and lack of (oxidative) DNA damage in V79 Chinese hamster lung fibroblast cells at low levels of carvacrol and thymol.

Differences in aflatoxin B1-susceptibility of rat and mouse are correlated with the capability in vitro to inactivate aflatoxin B1- epoxide

Endocrine disruptors and their possible impact on human and animal health have become a topic of discussion and an area of active research in toxicology. A focus has been on xenoestrogens, i.e., environmental chemicals with estrogenic activity. In principle, there is agreement that such compounds, in high doses, may cause developmental, reproductive and tumorigenic effects (“hazard”). A matter of controversy is the question of risks associated with xenoestrogens under realistic (low) exposure scenarios; this is due to uncertainty on how to assess the interactions of exogenous compounds with the endocrine system and its complex regulation. Our overview will address topics including: consequences from previous clinical use of the potent estrogen diethyl- stilbestrol with particular emphasis on dose-response relationships, other observations in humans exposed to estrogenic chemicals in an occupational context, and available information on exposure levels of synthetic and naturally occurring estrogens in the diet. Together with a critical appraisal of methods to detect and quantitate the estrogenic activity of synthetic and naturally occurring chemicals, novel aspects in the risk assessment for endocrine active compounds are discussed.

Gisela H. Degen

Papers

Carcinogenicity categorization of chemicals-new aspects to be considered in a European perspective.

SCCP (Scientific Committee on Consumer Products) / SCHER (Scientific Committee on Health& Environment Risks) / SCENIHR (Scientific Committee on Emerging and Newly- Identified Health Risks) opinion on: Risk assessment methodologies and approaches for genotoxic and carcinogenic substances

Antioxidant activities of major thyme ingredients and lack of (oxidative) DNA damage in V79 Chinese hamster lung fibroblast cells at low levels of carvacrol and thymol.

Differences in aflatoxin B1-susceptibility of rat and mouse are correlated with the capability in vitro to inactivate aflatoxin B1- epoxide

Endocrine Disruptors : Update on Xenoestrogens