Reproductive stimulation by low doses of xenoestrogens contrasts with the view of hormesis as an adaptive response.
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, resulting 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 diethylstilbestrol. Adverse low-dose effects include oviduct rupture, an enlarged prostate, feminization of males and reduced sperm quality. These adverse stimulatory effects divert energy needed for other processes, resulting in reduced fitness. In conclusion, while there are similarities (inverted-U dose-response), there are also differences, adaptive response for hormesis versus adverse stimulatory response for low doses of manmade xenoestrogens, that have been almost totally ignored in discussions of hormesis. We propose that the risk posed by low doses of manmade xenoestrogens that show inverted-U dose-response curves is underestimated by the current threshold model used in risk assessment, and this is likely to apply to other endocrine-disrupting chemicals.
Weltje
Lennart
L
Department of Ecology and Evolution-Ecotoxicology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany. weltje@zoology.uni-frankfurt.de
vom Saal
Frederick S
FS
Oehlmann
Jörg
J
D000818:Animals; D001559:Benzhydryl Compounds; D017173:Caenorhabditis elegans / Q000187:drug effects*; D004054:Diethylstilbestrol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000494:pharmacology* / Q000633:toxicity; D045166:Estradiol Congeners / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D019055:No-Observed-Adverse-Effect Level; D010636:Phenols / Q000494:pharmacology; D012098:Reproduction / Q000187:drug effects*; D018570:Risk Assessment; D012908:Snails / Q000187:drug effects*; D013268:Stimulation, Chemical; D015262:Xenobiotics / Q000494:pharmacology* / Q000633:toxicity; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004054:Diethylstilbestrol; D052244:Endocrine Disruptors; D045166:Estradiol Congeners; D010636:Phenols; D015262:Xenobiotics; C474055:octylphenol; C006780:bisphenol A; D000098826:Bisphenol A Compounds