Endocrine effects of polycyclic musks: do we smell a rat?

Synthetic polycyclic musks are used extensively as fragrances and are released ubiquitously in our environment, particularly water. We have demonstrated that these compounds display very weak oestrogenic activity in vitro, although no obvious oestrogenic activity was found in young rats or zebrafish. We demonstrated, however, that the oestrogenic effect of these compounds is cell- and oestrogen receptor-type specific, raising the possibility that the in vivo models may have underestimated some effects. In addition, polycyclic musks were found to possess antioestrogenic (ERbeta-selective), antiandrogenic and antiprogestagenic activity. As recent research clearly demonstrates the possibility of endocrine disrupting environmental compounds to act in concert, more research to these combined effects is important. We have developed efficient methods to measure such combined bioactivities in a range of matrices using human cell-based reporter gene assays. So far, we found agonistic, rather than antagonistic, effects in water samples, suggesting a predominance of agonistic compounds in such samples.

[1]  P. Schmid,et al.  Persistent organic pollutants, brominated flame retardants and synthetic musks in fish from remote alpine lakes in Switzerland. , 2007, Chemosphere.

[2]  Juliette Legler,et al.  Estrogenic and dioxin-like compounds in sediment from Zierikzee harbour identified with CALUX assay-directed fractionation combined with one and two dimensional gas chromatography analyses. , 2006, Chemosphere.

[3]  Young In Park,et al.  Comparison of prostate cancer cell lines for androgen receptor-mediated reporter gene assays. , 2006, Toxicology in vitro : an international journal published in association with BIBRA.

[4]  A. Murk,et al.  Selected Titles , 2006 .

[5]  C. Sonnenschein,et al.  Strengths and weaknesses of in vitro assays for estrogenic and androgenic activity. , 2006, Best practice & research. Clinical endocrinology & metabolism.

[6]  M. Lamoree,et al.  Biological validation of a sample preparation method for ER-CALUX bioanalysis of estrogenic activity in sediment using mixtures of xeno-estrogens. , 2006, Environmental science & technology.

[7]  Kurunthachalam Kannan,et al.  A survey of polycyclic musks in selected household commodities from the United States. , 2006, Chemosphere.

[8]  K. Kannan,et al.  Polycyclic musk compounds in higher trophic level aquatic organisms and humans from the United States. , 2005, Chemosphere.

[9]  L. Duedahl-Olesen,et al.  Synthetic musk fragrances in trout from Danish fish farms and human milk. , 2005, Chemosphere.

[10]  B. van der Burg,et al.  Examination of the in vitro (anti)estrogenic, (anti)androgenic and (anti)dioxin-like activities of tetralin, indane and isochroman derivatives using receptor-specific bioassays. , 2005, Toxicology letters.

[11]  Bart van der Burg,et al.  Interaction of polycyclic musks and UV filters with the estrogen receptor (ER), androgen receptor (AR), and progesterone receptor (PR) in reporter gene bioassays. , 2004, Toxicological sciences : an official journal of the Society of Toxicology.

[12]  Abraham Brouwer,et al.  Development of androgen- and estrogen-responsive bioassays, members of a panel of human cell line-based highly selective steroid-responsive bioassays. , 2004, Toxicological sciences : an official journal of the Society of Toxicology.

[13]  Juliette Legler,et al.  Identification of estrogenic compounds in fish bile using bioassay-directed fractionation. , 2004, Environmental science & technology.

[14]  David J. Waxman,et al.  trans-Activation of PPARα and Induction of PPARα Target Genes by Perfluorooctane-Based Chemicals , 2004 .

[15]  B. van der Burg,et al.  In vitro and in vivo antiestrogenic effects of polycyclic musks in zebrafish. , 2004, Environmental science & technology.

[16]  B. van der Burg,et al.  A novel specific bioassay for the determination of glucocorticoid bioavailability in human serum , 2003, Clinical endocrinology.

[17]  Juliette Legler,et al.  Detection of estrogenic activity in sediment-associated compounds using in vitro reporter gene assays. , 2002, The Science of the total environment.

[18]  A. Kortenkamp,et al.  Something from "nothing"--eight weak estrogenic chemicals combined at concentrations below NOECs produce significant mixture effects. , 2002, Environmental science & technology.

[19]  J. McLachlan,et al.  Environmental signaling: what embryos and evolution teach us about endocrine disrupting chemicals. , 2001, Endocrine reviews.

[20]  B. van der Burg,et al.  4-Hydroxytamoxifen Trans-Represses Nuclear Factor-κB Activity in Human Osteoblastic U2-OS Cells through Estrogen Receptor (ER)α, and Not through ERβ. , 2001, Endocrinology.

[21]  P. Schepens,et al.  Comparison of chemical-activated luciferase gene expression bioassay and gas chromatography for PCB determination in human serum and follicular fluid. , 2000, Environmental health perspectives.

[22]  G G Rimkus,et al.  Polycyclic musk fragrances in the aquatic environment. , 1999, Toxicology letters.

[23]  R. Pieters,et al.  AHTN and HHCB show weak estrogenic--but no uterotrophic activity. , 1999, Toxicology Letters.

[24]  S. Safe,et al.  Differential Interaction of the Methoxychlor Metabolite 2,2-Bis-(p-Hydroxyphenyl)-1,1,1-Trichloroethane with Estrogen Receptors α and β1. , 1999, Endocrinology.

[25]  A D Vethaak,et al.  Development of a stably transfected estrogen receptor-mediated luciferase reporter gene assay in the human T47D breast cancer cell line. , 1999, Toxicological sciences : an official journal of the Society of Toxicology.

[26]  K. Gaido,et al.  Inhibition of androgen receptor-dependent transcriptional activity by DDT isomers and methoxychlor in HepG2 human hepatoma cells. , 1998, Toxicology and applied pharmacology.

[27]  E. Wilson,et al.  Environmental antiandrogens: developmental effects, molecular mechanisms, and clinical implications , 1997, Journal of Molecular Medicine.

[28]  Willem G Schoonen,et al.  Comparison of in vitro and in vivo screening models for androgenic and estrogenic activities. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.