Courage for simplification and imperfection in the 21st century assessment of “Endocrine disruption”

Dietrich, Daniel R.

doi:10.14573/altex.2010.4.264

Cited by 18 publications

(8 citation statements)

References 122 publications

(138 reference statements)

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“…the state of the art was recently summarized on behalf of the european Commission (Kortenkamp et al, 2011). the report has received quite some criticism (Rhomberg et al, 2012), which we won't discuss, as our concern is the overall relevance of the hazard (Dietrich, 2010). The case shows, however, that specific concerns can be translated to specific assays, i.e., when a mechanism is known, mechanism-based tests can be put forward.…”

Section: Cell-based Assays For Toxicity Testingmentioning

confidence: 94%

Towards tailored assays for cell-based approaches to toxicity testing

Rossini

2012

ALTEX

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Section: Cell-based Assays For Toxicity Testingmentioning

confidence: 94%

Towards tailored assays for cell-based approaches to toxicity testing

Rossini

2012

ALTEX

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“…For example, literature surveys showed that 38 out of 48 endocrine-disrupting chemicals (79%) studied were positive in at least one cancer bioassay (Choi et al, 2004;Dietrich, 2010). A number of endocrine disruptor assays have been developed for the respective screening programs, and some of them have even been validated and accepted at OECD level.…”

Section: Specific Considerations For Non-genotoxic Carcinogensmentioning

confidence: 99%

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing

Basketter

Clewell

Kimber

et al. 2012

ALTEX

202

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“…Thus, if synthetic chemicals are to interfere with natural endocrine signals, their doses/concentrations and potencies need to be similar to or higher than those of natural hormones (Golden et al 1998 ; Dietrich 2010 ; Marty et al 2011 ). Otherwise, they cannot displace the numerous natural endogenous ligands present.…”

Section: Biochemical Principles Of Interaction At Receptors or Enzymementioning

confidence: 99%

Human exposure to synthetic endocrine disrupting chemicals (S-EDCs) is generally negligible as compared to natural compounds with higher or comparable endocrine activity: how to evaluate the risk of the S-EDCs?

et al. 2020

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Theoretically, both synthetic endocrine disrupting chemicals (S-EDCs) and natural (exogenous and endogenous) endocrine disrupting chemicals (N-EDCs) can interact with endocrine receptors and disturb hormonal balance. However, compared to endogenous hormones, S-EDCs are only weak partial agonists with receptor affinities several orders of magnitude lower. Thus, to elicit observable effects, S-EDCs require considerably higher concentrations to attain sufficient receptor occupancy or to displace natural hormones and other endogenous ligands. Significant exposures to exogenous N-EDCs may result from ingestion of foods such as soy-based diets, green tea and sweet mustard. While their potencies are lower as compared to natural endogenous hormones, they usually are considerably more potent than S-EDCs. Effects of exogenous N-EDCs on the endocrine system were observed at high dietary intakes. A causal relation between their mechanism of action and these effects is established and biologically plausible. In contrast, the assumption that the much lower human exposures to S-EDCs may induce observable endocrine effects is not plausible. Hence, it is not surprising that epidemiological studies searching for an association between S-EDC exposure and health effects have failed. Regarding testing for potential endocrine effects, a scientifically justified screen should use in vitro tests to compare potencies of S-EDCs with those of reference N-EDCs. When the potency of the S-EDC is similar or smaller than that of the N-EDC, further testing in laboratory animals and regulatory consequences are not warranted.

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Courage for simplification and imperfection in the 21st century assessment of “Endocrine disruption”

Cited by 18 publications

References 122 publications

Towards tailored assays for cell-based approaches to toxicity testing

Towards tailored assays for cell-based approaches to toxicity testing

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing

Human exposure to synthetic endocrine disrupting chemicals (S-EDCs) is generally negligible as compared to natural compounds with higher or comparable endocrine activity: how to evaluate the risk of the S-EDCs?

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