Assessment of in vivo assays for endocrine disruption

Clode, Sally

doi:10.1016/j.beem.2005.09.011

Cited by 46 publications

(29 citation statements)

References 22 publications

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“…Among them, atrazine (ATZ), bisphenol A (BPA), methoxychlor (MXC), and vinclozolin (VCZ) have long been studied and have been described as estrogeno-mimetic (ATZ, BPA, and MXC) or anti-androgenic (VCZ) in vitro [4][5][6][7]. Despite the high importance of the androgen-to-estrogen balance in evaluating reproductive effects [8], the great majority of in vivo studies have dealt with the determination of estrogens in females and androgens in males [9]. Moreover, the biological processes that occur between administration of the dose and tissue response are often poorly investigated and thus poorly understood.…”

Section: Introductionmentioning

confidence: 98%

Quantification of steroids and endocrine disrupting chemicals in rat ovaries by LC-MS/MS for reproductive toxicology assessment

et al. 2012

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Reproductive function is controlled by a finely tuned balance of androgens and estrogens. Environmental toxicants, notably endocrine disrupting chemicals (EDCs), appear to be involved in the disruption of hormonal balance in several studies. To further describe the effects of selected EDCs on steroid secretion in female rats, we aim to simultaneously investigate the EDC concentration and the sex hormone balance in the ovaries. Therefore, an effective method has been developed for the quantification of the sex steroid hormones (testosterone, androstenedione, estradiol, and estrone) and four endocrine disrupting chemicals (bisphenol A, atrazine, and the active metabolites of methoxychlor and vinclozolin) in rat ovaries. The sample preparation procedure is based on the so-called "quick, easy, cheap, effective, rugged, and safe" approach, and an analytical method was developed to quantify these compounds with low detection limits by liquid chromatography coupled with a tandem mass spectrometer. This analytical method, applied to rat ovary samples following subacute EDC exposure, revealed some new findings for toxicological evaluation. In particular, we showed that EDCs with the same described in vitro mechanisms of action have different effects on the gonadal steroid balance. These results highlight the need to develop an integrative evaluation with the simultaneous measurement of EDCs and numerous steroids for good risk assessment.

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Section: Introductionmentioning

confidence: 98%

Quantification of steroids and endocrine disrupting chemicals in rat ovaries by LC-MS/MS for reproductive toxicology assessment

et al. 2012

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“…Strategies for determining whether a ligand possesses oestrogenic activity therefore begin with investigation of the ability to bind to ER and the ability to induce oestrogen-regulated gene expression, and then progress to the question of whether physiological responses can be induced in cells in culture or in whole animal models (Soto et al, 2006;Clode, 2006). Growth of oestrogendependent cells, especially of the MCF7 human breast cancer cell line, has provided a sensitive and reliable measure of cell growth response (Soto et al, 2006) and increase in uterine weight in the immature female rodent has provided a reliable indicator of oestrogenic activity in a whole animal model (Clode, 2006). The majority of studies shown in Table 2 report oestrogen agonist activity of parabens, a minority of studies (one out of 25 in vitro studies, and seven out of 30 in vivo studies in Table 2) reported negative ¼ndings in oestrogenicity assays.…”

Section: Oestrogenic Activity Of Parabens and Its Main Metabolite P-hmentioning

confidence: 99%

Paraben esters: review of recent studies of endocrine toxicity, absorption, esterase and human exposure, and discussion of potential human health risks

Darbre

Harvey

2008

J of Applied Toxicology

604

375

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This toxicology update reviews research over the past four years since publication in 2004 of the ¼rst measurement of intact esters of p-hydroxybenzoic acid (parabens) in human breast cancer tissues, and the suggestion that their presence in the human body might originate from topical application of bodycare cosmetics. The presence of intact paraben esters in human body tissues has now been con¼rmed by independent measurements in human urine, and the ability of parabens to penetrate human skin intact without breakdown by esterases and to be absorbed systemically has been demonstrated through studies not only in vitro but also in vivo using healthy human subjects. Using a wide variety of assay systems in vitro and in vivo, the oestrogen agonist properties of parabens together with their common metabolite ( p-hydroxybenzoic acid) have been extensively documented, and, in addition, the parabens have now also been shown to possess androgen antagonist activity, to act as inhibitors of sulfotransferase enzymes and to possess genotoxic activity. With the continued use of parabens in the majority of bodycare cosmetics, there is a need to carry out detailed evaluation of the potential for parabens, together with other oestrogenic and genotoxic co-formulants of bodycare cosmetics, to increase female breast cancer incidence, to interfere with male reproductive functions and to in½uence development of malignant melanoma which has also recently been shown to be in½uenced by oestrogenic stimulation.

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“…the standard test for disruption of normal estrogen function is the in vivo uterotrophic assay, i.e., a test with immature or ovariectomized rodents using uterus weight as the crucial read-out parameter (Clode, 2006;Owens and Ashby, 2002). With a view to the ReACH Regulation (eC, 2006) and the need to reduce, refine, and replace the use of experimental animals for safety testing (3Rs), modulation of eR activity is usually quantitatively analyzed by assaying eR binding, eR-controlled reporter genes, or other downstream events such as estrogen receptor-mediated cell proliferation (Bovee and Pikkemaat, 2009).…”

Section: Introductionmentioning

confidence: 99%

A 155-plex high-throughput in vitro coregulator binding assay for (anti-)estrogenicity testing evaluated with 23 reference compounds

Wang

Melchers

Aarts

et al. 2013

ALTEX

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Assessment of in vivo assays for endocrine disruption

Cited by 46 publications

References 22 publications

Quantification of steroids and endocrine disrupting chemicals in rat ovaries by LC-MS/MS for reproductive toxicology assessment

Quantification of steroids and endocrine disrupting chemicals in rat ovaries by LC-MS/MS for reproductive toxicology assessment

Paraben esters: review of recent studies of endocrine toxicity, absorption, esterase and human exposure, and discussion of potential human health risks

A 155-plex high-throughput in vitro coregulator binding assay for (anti-)estrogenicity testing evaluated with 23 reference compounds

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