Expert Views :: Metals: An Old Problem with New Tricks
Rosslyn Grosely and Marlo Sellin
“For the first time in the history of the world, every human being is now subjected to contact with dangerous chemicals, from the moment of conception until death.”Rachel Carson, Silent Spring, 1962
Over the past decade, endocrine disruption research has primarily focused on organic compounds such as pesticides, plasticizers, drugs, and industrial mixtures including kraft pulp mill effluent. In contrast, relatively little research has been done on metals as endocrine disruptors. The need for more research in this area is warranted based upon the following: 1) metals are ubiquitous and persistent in the environment, 2) some metals are estrogenic, 3) the endocrine disrupting effects of a few metals have been established, and 4) metals have been shown to be maternally transferred from mother to offspring where they can cause organizational effects.
Heavy metals are ubiquitous and exposures are virtually unavoidable. Humans and wildlife are exposed to heavy metals on a daily basis through both natural and anthropogenic sources. For example, mercury is found in the fish we eat and in some paints; cadmium is a component of cigarette smoke and may be found in drinking water, air, or food; and manganese is added to gasoline and is utilized in several industrial processes (1). Due to the overwhelming presence of these metals, as well as a variety of others in the environment, it is essential that research be conducted to elucidate their effects.
Choe et. al. tested the estrogenicity of 20 different metal compounds (2). Both the relative binding efficiencies (RBE) and relative proliferative effects (RPE) were measured for each metal compound using an estrogen receptor dependent transcriptional expression assay and an E-screen assay respectively. The three compounds with the highest estrogenicity were bis(tri-n-butyltin), cadmium chloride, and antimony chloride. Correspondingly, the RBE for each was 93.5%, 73.8%, and 60.9%, while the RPEs were 80.9%, 59.7%, and 49.2%. Although several metal compounds scored in the mid to low range, the very fact that these compounds demonstrate estrogenicity gives rise to the necessity for further investigation.
While estrogenicity is a useful tool in determining potential endocrine disruptors, estrogenicity is not the only mechanism of endocrine disruption. For example, mercury is a potent endocrine disruptor, yet, neither dimethylmercury nor mercuric chloride is estrogenic (2). Fish exposed to mercury experience suppressed sex steroid levels, inhibited gonadal development, and reduced reproductive success (3). Cadmium, tributyltin, and lead are also identified as reproductive endocrine disruptors, and again, the mechanism may not necessarily be estrogenicity. Exposure to tributyltin leads to altered sex ratios in some fish species (4) and imposex in several gastropod species (5). In humans, there is evidence that lead alters testosterone levels in males, induces spontaneous abortions in females, and hinders neurological and behavioral development in children (1).
A large proportion of studies implicating metals as endocrine disruptors have examined the consequences of adult exposures. Studies designed to address the long-term consequences of fetal exposures to endocrine disrupting metals would also be valuable considering that these compounds maternally transfer from a female to her offspring (1,6). Adult exposures typically lead to activational effects that are transitory and reversible, while exposures during or shortly after embryonic development lead to organizational effects that are permanent and irreversible (7). For example, male rats exposed to manganese during fetal development suffer effects including reduced testosterone concentrations and retarded testicular growth (1).
Evidence suggests that metals are endocrine disruptors. While some metals have been identified and studied as endocrine disruptors, in general, research on metals and endocrine disruptors is lacking. As the list of endocrine disruptors grows, it is important that environmentally ubiquitous compounds such as metals not be overlooked.