Endocrine disruption

No data are available on endocrine-related effects of methyltins. 

Tributyltin is well established as an aromatase inhibitor (IPCS, 1990). Quantitative comparisons of potency cannot be defined for other organotins, because a full range of in vitro tests has not been performed. 

In recent in vitro studies, an aromatase inhibiting effect on human placental microsomal extracts has been demonstrated with both tributyltin chloride and dibutyltin dichloride (Heidrich et al, 2001 Cooke, 

Investigations of the aromatase inhibiting effects in in vitro assays gave no indicahon of an endocrine response after incubation with mono-, di-, or trioctyltin (Cooke, 2002). 

Humans have evolved rapidly as a dominant species because of three characteristics the desire to know, 

Endocrine disrupters are present in much of our environment, and the threats of these compounds seem to be worsening as more and more new biochanicals are being used. Many of these compounds are present in drinking water it has been found that wastewater treatment does not remove many of them, and low concentrations of medicines, pesticides, food preservatives, and industrial chemicals have been discovered in ground water and municipal water. 

All of the endocrine disrupting compounds have not been identified, and determining which compounds have this effect is a daunting task. There are nearly 90,000 chemicals that need to be tested, but common chemical structural characteristics have not been found to make the identification easier. To make matters worse, endocrine disrupters may have opposite effects at low and high doses, or may be most potent at low doses (Vandenbergh, 2003). 

These componnds can interfere with normal animal development or reproduction. They have been implicated in problems occnrring in marine snails, frogs, alligators, and people, among others. 

A common estrogen mimic called bisphenol A is found in the lining of food and beverage containers and in dental resins. It leaches into human food and into the surrounding environment. Female mice pnps whose mothers were fed bisphenol A during pregnancy were found to have accelerated puberty onset. The effects of this compound were modulated by their fetal exposure to uterine testosterone (Vandenbergh, 2003). 

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US Environmental Protection Agency, Special Report on Environmental Endocrine Disruption An Effects Assessment and Analysis, EPA, Washington, 1997, EPA Report No. EPA/630/R-96/012. 

Issues in Environmental Science and Technology No. 12 Endocrine Disrupting Chemicals The Royal Society of Chemistry, 1999... 

Known and suspected endocrine disrupting chemicals needed to be ranked in order of priority for possible regulatory action. 

In order to establish consensus on the scope of the endocrine disrupter issue, to facilitate the identification of active chemicals and, ultimately, to underpin any future regulatory control, it is essential to agree a precise definition of an endocrine disrupter (ED). Such a definition was proposed at a major European Workshop on EDs. ... 

An endocrine disrupter is an exogenous substance that causes adverse health ejfects in an intact organism, or its progeny, subseguent to changes in endocrine function. ... 

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 ... 

A potential endocrine disrupter is a substance that possesses properties that might be expected to lead to endocrine disruption in an intact organism. ... 

The US Environmental Protection Agency (EPA) Risk Assessment Foriim An endocrine disrupter is an exogenous agent that interferes with the synthesis, secretion, transport, binding, action, or elimination of natural... 

P.T. C. Harrison, P. Holmes and C. D.N. Humfrey, Sci. Total Environ., 1997, 205, 97. European Commission DGXll, Report EUR 17549 European Workshop on the Impact of Endocrine Disrupters on Hnman Health and Wildlife, Brussels, 1997. 

Effects in humans for which links with exposure to endocrine disrupters have been suggested include the following. 

It has also been suggested that endocrine disruption may play a part in an... 

Endocrine disruption has been postulated as the cause of a large number of adverse affects on the health of various species of animals in the wild. The majority of cases involve reproductive abnormalities that might be linked to population declines. Data supporting causative associations between the biological... 

The impact of chemical pollution on the reproductive success and population sizes of wildlife species is often difficult to assess. In many cases, environmental factors such as habitat restriction, stress due to human intrusion and changes in natural food supplies owing to hunting, fishing and restocking policies may have a significant, even predominant, effect on population size. This makes it difficult to determine to what extent, if any, environmental endocrine disrupters may be contributing to observed effects on reproduction or population size in wildlife species. 

In the initial phase of development of endocrine disruption research, attention... 

Table 2 Some known or suspected endocrine disrupting chemicals...

Of all the uncertainties surrounding the hypothesis that environmental chemicals with endocrine disrupting properties are responsible for the observed effects in humans and wildlife, one of the major unknowns relates to exposure. Humans and wildlife can be, and sometimes are, exposed to these substances in the environment but our knowledge of the levels, routes and timing of exposure is poor. 

Human exposure to environmental contaminants has been investigated through the analysis of adipose tissue, breast milk, blood and the monitoring of faecal and urinary excretion levels. However, while levels of persistent contaminants in human milk, for example, are extensively monitored, very little is known about foetal exposure to xenobiotics because the concentrations of persistent compounds in blood and trans-placental transmission are less well studied. Also, more information is needed in general about the behaviour of endocrine disruptive compounds (and their metabolites) in vivo, for example the way they bind to blood plasma proteins. 

The main conclusion of an expert workshop on endocrine modulators and wildlife in 1997 was that some existing test methods, as defined in guidelines published by the Organization for Economic Cooperation and Development (OECD), could be adapted to incorporate specific endocrine disrupting endpoints, but that there might also be the need to develop new tests, e.g. for fish. On behalf of the UK Government, the MRC Institute for Environment and Health (lEH)... 

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