Showing papers in "Pure and Applied Chemistry in 2003"

Endocrine disruptors in the environment (IUPAC Technical Report)

Abstract: Many chemical substances of natural or anthropogenic origin are suspected or known to be endocrine disruptors, which can influence the endocrine system of life. This observation has led to increased interest on the part of the public and the media, as well as to a steep rise of research activities in the scientific community. New papers and results are presented so fast that it is impossible to give a complete review of this emerging research field. Therefore, this paper tries to give insight into some topics of the great scope of endocrine disruptors in the environment. To get a general idea of the biochemical and biological background, some parts of the endocrine systems of mammalians and nonmammalians are explained. The sections that follow describe important mechanisms of endocrine disruption such as interactions with hormone receptors. Test strategies for anthropogenic chemicals on various organisms are critically reviewed with respect to their problems and gaps concerning endocrine disruptors. The main emphasis of the paper is on the chemical substances suspected or known to be endocrine disruptors. To get a better comprehension of their behavior in the environment, physicochemical data such as water solubility or K o w , as well as information about their use and/or function are reviewed and compared. The main routes of exposure for most chemicals are shortly described, and data about concentrations in the environment (soil/sediment, water) are detailed.

Glossary of Terms used in Photochemistry

Abstract: This chapter presents a Glossary that was prepared by the Photochemistry Commission of the Organic Chemistry Division of the International Union of Pure and Applied Chemistry during the period 1978–1985 The purpose of the glossary is to provide definitions of terms and symbols commonly used in the field in order to achieve consensus on the adoption of some definitions and on the abandonment of inadequate terms

Regulatory limits for pesticide residues in water (IUPAC Technical Report)

Abstract: National governments introduced residue limits and guideline levels for pesticide residues in water when policies were implemented to minimize the contamination of ground and surface waters. Initially, the main attention was given to drinking water. Regulatory limits for pesticide residues in waters should have the following characteristics: definition of the type of water, definition of the residue, a suitable analytical method for the residues, and explanation for the basis for each limit. Limits may be derived by applying a safety factor to a no-effect-level, or from levels occurring when good practices are followed and also passing a safety assessment, or from the detection limit of an analytical method, or directly by legislative decision. The basis for limits and guideline values issued by WHO, Australia, the United States, New Zealand, Japan, Canada, European Union, and Taiwan is described, and examples of the limits are provided. Limits have been most commonly developed for drinking water, but values have also been proposed for environmental waters, effluent waters, irrigation waters, and livestock drinking waters. The contamination of ground water is of concern because it may be used as drinking water and act as a source of contamination for surface waters. Most commonly, drinking water standards have been applied to ground water. The same terminology may have different meanings in different systems. For example, guideline value (GV) in WHO means a value calculated from a toxicology parameter, whereas in Australia, a GV is at or about the analytical limit of determination or a maximum level that might occur if good practices are followed. In New Zealand, the GV is the concentration where aesthetic significance is influenced.The Australian health value (HV) is conceptually the same as the WHO GV. The New Zealand maximum acceptable value (MAV) and the Canadian maximum acceptable concentration (MAC) are also conceptually the same as the WHO GV. Each of the possible ways of defining the residues has its merits. A residue limit in water expressed as the sum of parent and toxicologically relevant transformation products makes sense where it is derived from the acceptable daily intake (ADI). For monitoring purposes, where it is best to keep the residue definition as simple as possible for the sake of practical enforcement and economy, theparent or a marker residue is preferable. It is also possible for parent and degradation products (hydrolysis and photolysis products and metabolites) to become physically separated as the water moves through soil strata, which suggests that separate limits should be set for parent and important degradation products. The Commission has made 12 recommendations for regulatory limits for pesticide residues in water. The recommendations will act as a checklist for authorities introducing or revising limits or guidelines for pesticide residues in water.

Endocrine disruption in wild freshwater fish

Abstract: Endocrine disruption has been reported in freshwater fish populations around the world. This phenomenon ranges from subtle changes in the physiology and sexual behavior of fish to permanently altered sexual differentiation and impairment of fertility. Despite wide- spread reports of endocrine disruption in fish (and this is well characterized at the individual level), few studies have demonstrated population-level consequences as a result of exposure to endocrine-disrupting chemicals (EDCs). An exception to this is in Lake Ontario Lake trout where precipitous declines in the population have been linked with periods of high exposure to organochlorine chemicals (known EDCs). Recently, it has been established that roach (Rutilus rutilus) exposed to treated sewage effluent (that contains complex mixtures of EDCs) in UK rivers, have a reduced reproductive capacity. This, in turn, may have popula- tion-level consequences. Evidence for a link between exposure to effluents from kraft mill (BKME) and sewage treatment works (STW) and altered reproductive function in freshwater fish is compelling. In most cases, however, a causal link between a specific chemical and a physiological effect has not been established. Indeed, identifying specific chemical(s) responsible for adverse effects observed in the wild is difficult, given that tens of thousands of man-made chemicals enter the aquatic environment and that mixtures of chemicals can have combination (e.g., additive) effects. Some EDCs are known to act at a number of different body targets to affect a variety of physiological processes, further complicating the identification of the causative agent(s). Endocrine disruption appears to be particularly widespread in freshwater fish popula- tions. There is little evidence, however, to suggest fish are more susceptible to EDCs relative to other wildlife. Notwithstanding this, there are some features of the endocrine physiology of fish that may be particularly susceptible to the effects of EDCs, including the processes of sex-determination and smoltification (in salmonids). Furthermore, their aquatic existence means that fish can be bathed constantly in a solution containing pollutants. In addition, up- take of chemicals readily occurs via the gills and skin, as well as via the diet (the major ex- posure route for most EDCs in terrestrial animals). The exposure of fish early life stages to the cocktail of EDCs present in some aquatic environments may be of particular concern, given that this is an especially vulnerable period in their development. The challenge, from the point of view of ecological risk assessment, is to determine ef- fects of EDCs on freshwater fish populations and freshwater ecosystems. In order to meet this challenge, high-quality data are required on the population biology of freshwater fish, on the effects of EDCs on their various life history characteristics, and comprehensive and ap-

Naturally produced steroid hormones and their release into the environment

Abstract: Steroidal hormones produced by humans and animals are constantly excreted into the environment in their active forms The primary steroid hormones are progesterone, es- trone, estradiol, testosterone, and cortisol, all of which are lipophilic and poorly soluble in water The steroids of major concern are estrone and estradiol-17β, since they exert their physiological effects at a lower concentration than other steroids and can be found in the en- vironment in concentrations above their lowest observable effect level for fish and plants (10 ng/l) The steroid hormones can be readily measured in run-off, soil, and groundwater, but each steroid has its distinct pathway of transport Since the major source of steroids in the environment appears to be cattle and chickens, the hormonal steroid input into the envi- ronment could be drastically reduced by well-established techniques such as buffer strips and composting

Applications of tert -butanesulfinamide in the asymmetric synthesis of amines

Abstract: tert-Butanesulfinamide is prepared using catalytic enantioselective methods in two steps from the extremely inexpensive oil waste by-product, tert-butyl disulfide. Direct con- densation of tert-butanesulfinamide with aldehydes and ketones provides tert-butanesulfinyl imines in uniformly high yields. The tert-butanesulfinyl group activates the imines for the addition of many different classes of nucleophiles, serves as a powerful chiral directing group, and after nucleophilic addition is readily cleaved by treatment with acid. A wide range of highly enantioenriched amines, including α-branched and α,α-dibranched amines, α- and β-amino acids, 1,2- and 1,3-amino alcohols and α-trifluoromethyl amines are efficiently syn- thesized using this methodology.

Mevalonate-independent methylerythritol phosphate pathway for isoprenoid biosynthesis. Elucidation and distribution*

Abstract: A long-overlooked metabolic pathway for isoprenoid biosynthesis, the mevalonate- independent methylerythritol phosphate (MEP) pathway, is present in many bacteria and in the chloroplasts of all phototrophic organisms. It represents an alternative to the well-known mevalonate pathway, which is present in animals, fungi, plant cytoplasm, archaebacteria, and some eubacteria. This contribution summarizes key steps of its elucidation and the state-of- the-art knowledge of this biosynthetic pathway, which represents a novel target for antibac- terial and antiparasitic drugs.

Millimeter-scale self-assembly and its applications

Abstract: Self-assembly is a concept familiar to chemists. In the molecular and nanoscale regimes, it is often used as a strategy in fabricating regular 3D structures—that is, crystals. Self-assembly of components with sizes in the µm-to-mm range is less familiar to chemists; this type of self-assembly may, however, become technologically important in the future. In this size range, self-assembly offers methods to form regular 3D structures from components too small or too numerous to be manipulated by other means, and methods to incorporate function into these structures; it also offers simplicity and economy. This paper focuses on the use of self-assembly to build functional systems of compo- nents with sizes in the range from microns to millimeters. It compares the principles of self- assembly at the molecular and millimeter scales, reviews the possible applications of meso- scale, self-assembled systems, and outlines some of the most important issues in the use of self-assembly to build functional systems.

Endocrine disruption in invertebrates

Abstract: Recent reports have shown that a number of xenobiotics in the environment are capable of interfering with the normal endocrine function in a variety of animals. The over- whelming majority of the studies on the effects of hormone-mimetic industrial chemicals were focused on findings in vertebrates. More detailed information about the effects on and mechanisms of action in invertebrates has only been obtained from a few cases, although in- vertebrates represent more than 95 % of the known species in the animal kingdom and are extremely important with regard to ecosystem structure and function. The limited number of examples for endocrine disruption (ED) in invertebrates is partially due to the fact that their hormonal systems are rather poorly understood in comparison with vertebrates. Deleterious endocrine changes following an exposure to certain compounds may easily be missed or simply be unmeasurable at present, even though a number of studies show that endocrine disruption has probably occurred. The well-documented case studies of tri- butyltin effects in mollusks and of insect growth regulators, the latter as purposely synthe- sized endocrine disruptors, are explained to support this view. According to our present knowledge, there is no reason to suppose that such far-reaching changes are in any sense unique. The additional existing evidence for ED in invertebrates from laboratory and field studies are summarized as an update and amendment of the EDIETA report from 1998. Finally, conclusions about the scale and implications of the observed effects are drawn and further research needs are defined.

Critical review of analytical applications of Mössbauer spectroscopy illustrated by mineralogical and geological examples (IUPAC Technical Report)

Abstract: We have developed a new terminology for Mossbauer pattern analysis in order to enhance the performance of qualitative analysis by Mossbauer spectroscopy. In this approach, Mossbauer parameters are considered as a functionof a number of externally adjusted experimental parameters at which the spectrum has been recorded. The basis of analytical classification is the microenvironment, which is determined by an assembly of atoms causing the same hyperfine interactions at one particular class of the Mossbauer probe atoms. Since Mossbauer spectroscopy measures hyperfine interactions very sensitively, the microenvironment presents itself as a fundamental concept for analytical purposes. Our approach can also help to systematize the Mossbauer data for the identification of individual physicochemical species from the corresponding patterns present in the spectrum.

Boron clusters: Do they receive the deserved interest?

Abstract: New applications in which the carborane and metallacarborane species play a cru- cial role have been recently developed. In these applications, clusters display many particu- lar characteristics that do not find parallel in their organic counterparts. The o-carborane can modulate the C⋅⋅⋅C distances depending on the substituents bonded to the cluster carbon atom and can lead to the formation of uncommon halogenophosphane charge-transfer "spoke" complexes with iodine due to their electron-withdrawing capacity. Besides, metallacar- boranes have been used as doping agents in organic conducting polymers and as catalysts in Kharasch reactions.

Molecular porphyrin­fullerene architectures

Abstract: This article describes the utilization of porphyrin and fullerene architectures— yielding artificial light-harvesting antenna and reaction center mimics—to tune the electronic coupling element between electron donor and electron acceptor and ultimately to affect the total reorganization energy. Most importantly, the effects that these parameters have on the rate, yield, and lifetime of the energetic charge-separated states are discussed.

Critical evaluation of stability constants and thermodynamic functions of metal complexes of crown ethers (IUPAC Technical Report)

Abstract: Stability constants and thermodynamic functions of metal complexes of crown ethers in various solvents published between 1971 and the beginning of 2000 have been critically evaluated. The most studied crown ethers have been selected: 1,4,7,10-tetraoxacyclododecane (12C4), 1,4,7,10,13-pentaoxacyclopentadecane (15C5), and 1,4,7,10,13,16-hexaoxacyclooctadecane (18C6). The metal ions chosen are: alkali and alkaline earth metal ions, Ag + , Tl + , Cd 2 + , and Pb 2 + . The solvents considered are: water, methanol, ethanol, and their mixtures, as well as acetonitrile, N,N'-dimethylformamide, dimethylsulfoxide, and propylene carbonate. The published data have been examined and grouped into two categories, "accepted" and "rejected". The "accepted" values were considered as: (i) recommended (R), when the standard deviations (s.d.) on the constant K or on Δ r H were ≤0.05 lg unit or ≤1 kJ mol - 1 , respectively; (ii) provisional (P), when 0.05 < s.d. ≤ 0.2 for lg K or 1 < s.d. ≤ 2 kJ mol - 1 for Δ r H; (iii) recommended 1 (R1), if the values were obtained by a single research group, but were considered reliable in comparison with related systems, and considering that the research team usually presents R-level values for other similar systems.

Atomic weights of the elements 2001 (IUPAC Technical Report)

Abstract: The biennial review of atomic-weight, Ar(E), determinations and other cognate data have resulted in changes for the standard atomic weights of the following elements: From To Zinc 65.39 ± 0.02 65.409 ± 0.004 Krypton 83.80 ± 0.01 83.798 ± 0.002 Molybdenum 95.94 ± 0.01 95.94 ± 0.02 Dysprosium 162.50 ± 0.03 162.500 ± 0.001 Presented are updated tables of the standard atomic weights and their uncertainties estimated by combining experimental uncertainties and terrestrial variabilities. In addition, this report again contains an updated table of relative atomicmass values and half-lives of selected radioisotopes. Changes in the evaluated isotope abundance values from those published in 1997 are relatively minor and will be published in a major review of each element in 2003. Many elements have a different isotopic composition in some nonterrestrial materials. Some recent data on parent nuclides that might affect isotope abundances or atomic-weight values are included in this report for the information of the interested scientific community.

Rotaxanes and catenanes as prototypes of molecular machines and motors

Abstract: In the course of the last 20 years, our view on rotaxanes and catenanes has com- pletely changed. Copper(I)-templated strategies, in particular, have allowed us to prepare catenanes on a real preparative scale, in a few chemical steps from commercially available compounds. A particularly significant improvement was the introduction of the recently de- veloped ring-closing metathesis reaction, using Grubbs catalyst. The dynamic properties of rotaxanes and catenanes has been exploited to construct molecular systems for which one component can be set in motion under the action of an external signal, while the other com- ponents can be considered as motionless (artificial molecular "machines" and "motors"). A particularly representative example is that of a rotaxane dimer, whose overall length can be controlled chemically: A metal exchange reaction (Cu I /Zn II ) triggers a reversible contrac- tion/stretching process of the same molecular assembly, in a way reminiscent of the func- tioning of biological muscles.

Endocrine disruption in marine fish

Abstract: This topic reviews the whole field of endocrine disruption (ED) in marine fish and compares this with our knowledge of the situation in freshwater species. In broad terms, sim- ilar types of ED have been observed in the two groups, although effects in the marine envi- ronment tend to be less marked, presumably due to dispersion and dilution. There are, how- ever, some data which suggest that marine fish that are top-predators can experience ED due to biomagnification of organochlorines. Processes such as smoltification, metamorphosis, and hermaphroditism, which are common in some marine species, may be particularly sus- ceptible to ED, but have as yet been scarcely studied. As with freshwater fish, firm links to population-level effects have not yet been demonstrated, although it is not unreasonable to suppose that they are occurring in some locations. The topic concludes with some recom- mendations for future research.

Male reproductive disorders and the role of endocrine disruption: Advances in understanding and identification of areas for future research

Abstract: This review addresses whether there is a secular increasing trend in male repro- ductive developmental disorders (cryptorchidism, hypospadias, testis cancer, low sperm counts), and highlights the limitations of available data and how these issues are being ad- dressed. These disorders are considered to represent a syndrome of disorders (testicular dys- genesis syndrome (TDS)) with a common origin in fetal life, and in which "endocrine dis- ruption" plays a central role. The potential involvement of environmental estrogens in the etiology of these disorders is reviewed in light of new understanding about the pathways and dose-effect relationships of estrogen action on male reproductive development. Several new pathways of estrogen action have been identified, including suppression of the production of testosterone and insulin-like factor-3 by fetal/neonatal Leydig cells and suppression of an- drogen receptor expression in androgen target tissues. It is tentatively concluded that identi- fied environmental chemicals are unlikely to activate these pathways because of their intrin- sically weak estrogenicity. However, chemicals that may alter endogenous estrogen production, bioavailability, or inactivation represent a new focus of concern. Additionally, environmental chemicals that alter endogenous levels of androgens in the rat fetus (certain phthalates) induce a similar collection of disorders to TDS. Whether human exposure to such compounds might contribute to TDS remains to be shown, but studies in animals should help to define susceptible pathways for induction of TDS.

Review of the effects of endocrine-disrupting chemicals in birds*

Abstract: There have been several case studies of the impact of chemical contaminants on birds at the level of individuals or populations. While many of the chemicals involved in these incidents have been classified as endocrine-disrupting chemicals or endocrine active sub- stances (EASs) the mechanisms by which these chemicals affect birds are not clearly or fully understood.

Synthetic studies on the marine natural product halichondrins

Abstract: In connection with the development of a practical synthesis of the right half, and its analog E7389, of halichondrin B, an efficient and scalable synthesis of the two major building blocks is reported. In addition, a new synthesis of the C20-C26 segment via a regiospecific and stereoselective S N 2' process is presented. A sulfonamide class of ligands is shown to be effective for asymmetric Ni/Cr-mediated reactions under both stoichiometric and catalytic conditions, and the X-ray structure reveals this class of ligands to be tridentate. On the basis of three X-ray structures, a possible mechanism is suggested for this process. Stable and crystalline Cr(III)/sulfonamide complexes are shown to be effective for catalytic Cr-mediated coupling reactions of allyl, alkenyl, and alkyl halides with aldehydes, and some examples for application of the stoichiometric and catalytic asymmetric processes are pre- sented.

Critical evaluation of observed adverse effects of endocrine active substances on reproduction and development, the immune system, and the nervous system

Abstract: The last 40 years have seen many reports that man-made chemicals and environmental pollutants cause adverse effects in humans and wildlife; however, actually linking an exposure with a mechanism and an effect has yet to be done for endocrine disruption. Certainly, studies in experimental animals have shown that sufficient doses of select compounds can disrupt the endocrine system and produce the attendant adverse outcomes. The purpose of this contribution is to evaluate some of the recent reports of the adverse effects on reproduction and development, the immune system, and the nervous system that have been observed in experimental animals after treatment with man-made chemicals and environmental pollutants. Space limitations prevent us from presenting a comprehensive review of all reported endocrine active chemicals and their effects. Instead, we have focused on drawing conclusions as to the scope and etiology of the adverse effects in experimental animals using examples from the scientific literature, and on suggesting a path forward for further work.

Semisynthesis and degradation of the tubulin inhibitors epothilone and tubulysin

Abstract: The structure-activity relationships of epothilones indicate that major modifica- tions are only tolerated in the western ring segment. In particular, C2 methyl of the thiazole ring appears to be most flexible. Its broad modification started from epothilone F, which was obtained from natural epothilone B by hydroxylation via the N-oxide. Some of the prepared derivatives exhibit improved esterase stability in addition to high cytotoxic activity. For these and other favorable properties, amine (BMS-310705) was recently introduced in clinical trials. In an alternative approach, modified side chains were introduced by replacement of the C12,C15 ring segment via ring-opening olefin metathesis (ROM) of epothilone C in the pres- ence of ethylene to 12,13-seco-epothilone C, introduction of a synthetic building block fol- lowed by ring-closing olefin metathesis (RCM), and epoxidation to the 16-alkyne analog of epothilone A. The structure of the tetrapeptide tubulysin D was confirmed by total hydrolysis to N-methyl D-pipecolic acid, L-isoleucine, tubuvaline (Tuv), tubuphenylalanine (Tup), formaldehyde, and 3-methylbutyric acid. Mild acidic hydrolysis to cyclo-tubulysin and oxidative degradation to L-valine allowed the assignment of the stereocenters of Tuv, hydrazi- nolysis, and comparison with synthetic reference samples to that of Tup. The absolute con- figuration of tubulysin D is: (R)-Mep, (2S,3S)-Ile, (1'R,3'R)-Tuv, and (2S,4R)-Tup.

Chemoenzymatic methods for the enantioselective preparation of sesquiterpenoid natural products from aromatic precursors

Abstract: The enantiomerically pure cis-1,2-dihydrocatechols 2, which are generated by en- zymatic dihydroxylation of the corresponding aromatic, engage in regio- and stereo-controlled Diels-Alder cycloaddition reactions to give a range of synthetically useful bicyclo(2.2.2)octenes. Certain examples of the latter type of compound have been used as starting materials in the synthesis of the sesquiterpenoids (-)-patchoulenone and (-)-hirsutene.

Brominated flame retardants and endocrine disruption

Abstract: From an environmental point of view, an increasing important group of organo- halogen compounds are the brominated flame retardants (BFRs), which are widely used in polymers and textiles and applied in construction materials, furniture, and electronic equip- ment. BFRs with the highest production volume are the polybrominated diphenyl ethers (PBDEs), tetrabromobisphenol A (TBBP-A), and hexabromocyclododecane (HBCD). Because of their persistence and low biodegradation profile, several of the PBDE congeners accumulate in biota and are widely found in the aquatic food chain. Their levels in the envi- ronment and in humans have increased during the last decades, in contrast to compounds such as polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT), for example. Humans may be exposed to PBDEs mainly through consumption of fatty food of animal origin (e.g., fish), but exposure through skin contact with textiles protected with flame retardants or through inhalation of BFRs volatilized from electronic and electric equipment may also occur. The levels of PBDEs in Swedish human milk showed a doubling in concen- tration every five years over the period 1972 to 1997 (2,2',4,4'-tetraBDE being the predomi- nant congener). The levels of penta- and hexa-BDEs increased at the same rate in ringed seals collected in the Canadian Arctic from 1981 to 2000. PBDEs exhibit a great variety of bio- logical effects, depending on the bromine substitution pattern. PBDEs are potential endocrine disrupters, based on shared toxicity with the structurally related PCBs, polychlorinated dibenzofurans (PCDFs), and polychlorinated dibenzo-p-dioxins (PCDDs) (partial aryl hydro- carbon- (Ah-) receptor agonist and antagonist activity in vitro, thyroid toxicity, and immune effects), including developmental toxicity. The potency of TBBP-A to interact with thyroid hormone homeostasis is indicated from in vitro studies in which the compound competes with thyroxin (T4) for binding to transthyretin (TTR). So far, the toxicological profile of many BFRs is too incomplete and insufficient to perform an adequate risk assessment, and further information is required regarding the potential for endocrine disruption of these com- pounds that are of increasing environmental concern.

Effects of endocrine disruptors in aquatic mammals

Abstract: In the last few decades, various studies have shown that aquatic mammals are sen- sitive to the toxicological effects of certain xenobiotic compounds, including the large class of endocrine-disrupting chemicals (EDCs). Since some EDCs, particularly organochlorines, tend to bioaccumulate and biomagnify in the aquatic food chain, various aquatic mammals, particularly those high in the food chain, such as pinnipeds, odontocete cetaceans, and polar bears, are potentially "at risk". The main aim of this chapter is to define the state of the art on effects of endocrine disruptors in aquatic mammals, both freshwater and marine. Another aim is to formulate recommendations for future research in this field and finally to define what can be done internationally for hazard/risk assessment and communication of the find- ings.

Critical evaluation of stability constants for alpha-hydroxycarboxylic acid complexes with protons and metal ions and the accompanying enthalpy changes. Part II. Aliphatic 2-hydroxycarboxylic acids (IUPAC Technical Report)

Abstract: Stability constants for different aliphatic 2-hydroxycarboxylic acid complexes in aqueous solutions with protons and metal ions published between 1960 and the end of 1994 have been critically evaluated.

Pharmaceuticals and personal care products: A source of endocrine disruption in the environment?

Abstract: A wide variety of chemicals are used in pharmaceuticals. Most of these are already under thorough control for endocrine activity. The main causal agents recognized for en- docrine disruption from sewage are substances used in medicine (sex hormones, glucocorti- coids, and others), natural substances (estrone and 17β-estradiol), and synthetic estrogens (e.g., 17α-ethinylestradiol). Similar substances are used in anabolic agents (growth hor- mones) in livestock production in some countries. Although the estimated use of anabolic agents in livestock production is approximately one order of magnitude below the natural re- lease of estrogens from farm animals, their possible significance remains unanswered. At present, no other medical substances are recognized as endocrine disruptors in the environment. However, candidates may be identified on the basis of simple assumptions re- garding their use and activity: (1) Nonestrogenic steroids may react with environmental en- docrine receptors or metabolize on their way to the environment and thus form endocrine dis- ruptors. (2) Many high-volume drugs released to the environment have not yet been tested for their endocrine properties, and some of these are known to interact with the human en- docrine system. (3) Compared to medicinal substances, personal care products and additives in drugs are used in high amounts; from this group, parabens, siloxanes, and other substances are suspected of causing endocrine disruption in the environment.

Interactions of xenobiotics with the steroid hormone biosynthesis pathway

Abstract: Environmental contaminants can potentially disrupt endocrine processes by inter- fering with the function of enzymes involved in steroid synthesis and metabolism. Such in- terferences may result in reproductive problems, cancers, and toxicities related to (sexual) differentiation, growth, and development. Various known or suspected endocrine disruptors interfere with steroidogenic enzymes. Particular attention has been given to aromatase, the enzyme responsible for the conversion of androgens to estrogens. Studies of the potential for xenobiotics to interfere with steroidogenic enzymes have often involved microsomal frac- tions of steroidogenic tissues from animals exposed in vivo, or in vitro exposures of steroid- ogenic cells in primary culture. Increasingly, immortalized cell lines, such as the H295R human adrenocortical carcinoma cell line are used in the screening of effects of chemicals on steroid synthesis and metabolism. Such bioassay systems are expected to play an increasingly important role in the screening of complex environmental mixtures and individual contami- nants for potential interference with steroidogenic enzymes. However, given the complexities in the steroid synthesis pathways and the biological activities of the hormones, together with the unknown biokinetic properties of these complex mixtures, extrapolation of in vitro effects to in vivo toxicities will not be straightforward and will require further, often in vivo, inves- tigations.

Evolving patterns in boron cluster chemistry

Abstract: This paper outlines the development of our knowledge and understanding of the structures and bonding of boron cluster compounds, with particular reference to the evolving complementary roles localized bonding and molecular orbital treatments have played in providing simple rationalizations of their polyhedral molecules. INTRODUCTION: EARLY DEVEL OPMENTS The polyhedral patterns that characterize boron cluster chemistry have provided rich pickings for the structural and bonding enthusiast since they first become apparent, too rich to do justice to in a short paper. Here, we outline how those patterns and our attempts to understand them have evolved. Life itself, at least as we know it, evolved in an electron-rich world, one in which there was such an abundance of electrons that our early ideas about valency assumed that at least two electrons, shared between a pair of atoms, were needed to form a covalent chemical bond between them (1). Early boranes provided a challenge to this by existing despite their apparent electron deficiency. Compounds B n H n+4 (n = 2, 5, 6, or 10) and B n H n+6 (n = 4 or 5), prepared in A. Stock's pioneering researches (2), in which he invented vacuum line technology to deal with these highly reactive substances, were labeled "electron-deficient" because they contained too few electrons to provide a pair for every 2-center link in their molecules, evident even before their molecular structures were determined. Containing (2n + 4) or (2n + 6) atoms respectively these borane molecules have only (2n + 2) or (2n + 3) valence shell electron pairs, fewer than the minimum number, (2n + 3) or (2n + 5), of 2-center links required. A real structural breakthrough was provided by R. P. Bell and H. C. Longuet-Higgins. They deduced the structure of diborane, B 2 H 6 , from its vibrational spectrum (3). The value of the 3c2e bond concept, to explain its BHB links, soon followed. Subsequently, W. N. Lipscomb put borane structural chemistry on a sound basis by his classic low-temperature X-ray crystallographic studies of key boranes B n H n+m and perceptive analysis of the bonding implications of their intricate structures (4). He noted that the n boron atoms and m (endo) hydrogen atoms lay on an inner, near-spherical surface; the remaining n (exo) hydrogen atoms lay on an outer sphere, attached to the boron atoms by 2c2e BH bonds pointing radially outwards from the cluster center. Bonding between the boron and endo-hydrogen atoms on the inner sphere involved (2n + m) electrons (two from each BH unit, one from each endo-hydrogen) which Lipscomb allocated to four types of localized electron pair bonds, s BHB and t BBB 3c2e bonds and y BB and x BH 2c2e bonds. Electron, orbital, and boron atom counts led to three equations linking the values of s, t, y, and x to n and m: s = m - x = n - t = 2y + x

Historical perspective on endocrine disruption in wildlife

Abstract: Endocrine disruption (ED) as a named field of research has been very active for over 10 years, but effects in wildlife that would now be labeled as ED have been studied since the 1940s. This paper briefly surveys the progress in wildlife studies that has been made to date and draws out the major themes and issues that have been identified. In particular, it dis- cusses information concerning causative substances, modes of action, ubiquity of effects across taxa, individual- and population-level impacts, and the importance of low-dose and mixture effects. The main conclusion is that while most wildlife taxa are showing some ED effects at some locations, good evidence for population-level impacts is still limited to a few groups. In order to improve both the interpretation of field observations and the way in which environmental risk assessments are conducted, we need to develop an enhanced ability to predict effects on populations and communities from a knowledge of effects on individuals.

Carbenes. Pincers, chelates, and abnormal binding modes

Abstract: Routes to pincer and chelate carbene complexes of Pd, Rh, and Ir include double geminal CH activation, metallation, and CH activation. Abnormal binding via imidazole C5 can occur, and ion pairing can strongly influence C2 vs. C5 binding. Prior ligand binding via pyridine N before metallation is not essential. Computational methods are used extensively, for example, to compare N vs. C binding in imidazole. The possibility of C binding by his- tidine in metalloenzymes is discussed.