Endocrine disruption in vitro

In vivo studies in animals suggest that endosulfan may disrupt normal reproductive hormone levels in male animals, but that it is not an endocrine disrupter in females. Persistent depressed testicular testosterone was seen in male rats after intermediate duration oral exposures to endosulfan. In ovariectomized female rats, orally administered endosulfan did not induce normal development of female reproductive tissues, and in female mice and immature female rats, acute parenteral exposure to endosulfan did not affect several endocrine-related end points. In vitro studies have evaluated endosulfan for estrogen receptor (ER) and cytosolic protein binding affinity, ER-mediated reporter gene expression, estrogenic induction of cell proliferation, and alteration of relative abundance of active estradiol metabolites. Overall, in vitro evidence in favor of endosulfan estrogenicity indicates relatively weak potency compared to 17[3-estradiol. Apparently contradictory results were reported in different... 

Hutchinson TH. 2002. Reproductive and developmental effects of endocrine disrupters in invertebrates in vitro and in vivo approaches. Toxicol Lett 131 75-81. 

It was agreed at the workshop that endocrine disrupting activity could only be adequately defined in terms of effects in intact animals, be they juvenile or adult, or in the offspring of exposed parents. For many chemicals, evidence of endocrine disrupting activity has been obtained only by the use of in vitro models, such as hormone binding assays. It was accepted, therefore, that chemicals active in such models should be considered only as potential EDs and should be distinguished from those established as active in vivo. For such chemicals, an alternative definition was recommended ... 

It is also clear that it is difficult to relate cause and effect to any specific chemical since, with the exception of point source effluents, many waterways contain a multitude of chemicals, of which the active endocrine disruptor may not be that which has been measured in the water or tissue. For such reasons, many studies have used in vitro experiments in which isolated tissue, either from a control animal or one captured in a polluted water system, is exposed to a single pollutant in the laboratory. Such experiments have shown significant disruption to testicular activity by a wide range of xenobiotics, including cadmium, lindane, DDT, cythion, hexadrin and PCBs. ... 

Tributyltin is well established as an aromatase inhibitor, and dibutyltin appears to have some potency also (exact characterization of the endocrine disrupting capacity of dibutyltin alone is difficult because of the presence of tributyltin as an impurity). Monobutyltin and mono- and dioctyltins have no aromatase inhibiting capacity in in vitro tests. No data are available for this end-point for the methyltins. 

The designation potential endocrine disrupter has been proposed for chemical products with an endocrine-disruption ability that is demonstrated in an in vitro assay but not confirmed in an in vivo animal model. To date, most of the available information on chemical products with endocrine disrupter activity has been generated by in vitro experiments [10]. Various existing tests and bioassays of very different types have been proposed by distinct international bodies to identify hormonal... 

Houtman, C.J., Cenijn, P.H., Hamers, T., Lamoree, M.H., Legler, J., Murk, A.J., Brouwer, A. (2004). Toxicological profiling of sediments using in vitro bioassays with emphasis on endocrine disruption. Environmental Toxicology... 

Polybrominated Diphenyl Ethers. Results of in vitro estrogen receptor and thyroid hormone transport protein binding assays and in vivo studies of thyroid hormone homeostasis indicate that PBDEs have the potential to disrupt normal endocrine function. 

Substances that are carcinogenic, mutagenic, or reproductively toxic (i.e., CMRs), for example, some endocrine disrupters, may pose special problems for derivation of aquatic EQSs (e.g., lack of internationally agreed tests in some cases difficulties with prediction of safe concentrations), but use of special tests for these properties is only justified for a small subset of chemicals that meet clear criteria. Furthermore, EQSs for these substances should not be derived directly from in vitro data or from biomarkers of exposure but from in vivo tests alone. 

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