Synthetic chemicals currently used in a variety of industrial and agricultural applications are leading to widespread contamination of the environment. Even though the intended uses of pesticides, plasticizers, antimicrobials, and flame retardants are beneficial, effects on human health are a global concern. These so-called endocrine-disrupting chemicals (EDCs) can disrupt hormonal balance and result in developmental and reproductive abnormalities. New in vitro, in vivo, and epidemiological studies link human EDC exposure with obesity, metabolic syndrome, and type 2 diabetes. Here we review the main chemical compounds that may contribute to metabolic disruption. We then present their demonstrated or suggested mechanisms of action with respect to nuclear receptor signaling. Finally, we discuss the difficulties of fairly assessing the risks linked to EDC exposure, including developmental exposure, problems of high- and low-dose exposure, and the complexity of current chemical environments.

/pdf/endocrine-disruptors-from-endocrine-to-metabolic-disruption-212fm2fkju.pdf

Endocrine Disruptors: From Endocrine to Metabolic Disruption

Over the last two decades, the incidence of obesity and associated metabolic syndrome diseases has risen dramatically, becoming a global health crisis Increased caloric intake and decreased physical activity are believed to represent the root causes of this dramatic rise However, recent findings highlight the possible involvement of environmental obesogens, xenobiotic chemicals that can disrupt the normal developmental and homeostatic controls over adipogenesis and energy balance Environmental estrogens, ie chemicals with estrogenic potential, have been reported to perturb adipogenic mechanisms using in vitro model systems, but other classes of endocrine-disrupting chemicals are now coming under scrutiny as well Organotins represent one class of widespread persistent organic pollutants with potent endocrine-disrupting properties in both invertebrates and vertebrates New data identify tributyltin chloride and triphenyltin chloride as nanomolar agonist ligands for retinoid X receptor (RXR alpha, RXR beta, and RXR gamma) and peroxisome proliferator-activated receptor gamma, nuclear receptors that play pivotal roles in lipid homeostasis and adipogenesis The environmental obesogen hypothesis predicts that inappropriate receptor activation by organotins will lead directly to adipocyte differentiation and a predisposition to obesity and/or will sensitize exposed individuals to obesity and related metabolic disorders under the influence of the typical high-calorie, high-fat Western diet The linking of organotin exposure to adipocyte differentiation and obesity opens an important new area of research into potential environmental influences on human health and disease

/pdf/environmental-obesogens-organotins-and-endocrine-disruption-2qsa7jvx1r.pdf

Environmental Obesogens: Organotins and Endocrine Disruption via Nuclear Receptor Signaling

Nanoparticles for bioimaging.

http://www.medecine-maritime.fr/pdf/biblio/toxico/Environmental%20levels,%20toxicity%20and%20human%20exposure%20to%20tributyltin.pdf

Environmental levels, toxicity and human exposure to tributyltin (TBT)-contaminated marine environment. A review

Children's exposure to air pollution is a special concern because their immune system and lungs are not fully developed when exposure begins, raising the possibility of different responses than seen in adults. In addition, children spend more time outside, where the concentrations of pollution from traffic, powerplants, and other combustion sources are generally higher. Although air pollution has long been thought to exacerbate minor acute illnesses, recent studies have suggested that air pollution, particularly traffic-related pollution, is associated with infant mortality and the development of asthma and atopy. Other studies have associated particulate air pollution with acute bronchitis in children and demonstrated that rates of bronchitis and chronic cough declined in areas where particle concentrations have fallen. More mixed results have been reported for lung function. Overall, evidence for effects of air pollution on children have been growing, and effects are seen at concentrations that are common today. Although many of these associations seem likely to be causal, others require and warrant additional investigation.

http://coep.pharmacy.arizona.edu/HOPE/andrea/Air%20pollution%20and%20children%27s%20health.pdf

Air Pollution and Children's Health

Two-generation reproductive toxicity study of tributyltin chloride in male rats.

Four cases of toxic polyneuropathy due to glue-sniffing were reported. Neurological examination revealed motor predominant mixed type polyneuropathy. The cause of polyneuropathies in these cases was considered to be due to the inhalation of the vaporized elements of the adhesive agent, which contain mainly n-hexane and toluene. N-hexane is considered to be chiefly responsible for the polyneuropathy, though toluene also could have some influence on the illness.

https://jnnp.bmj.com/content/jnnp/37/7/848.full.pdf

Toxic polyneuropathy due to glue sniffing

A two-generation reproductive toxicity study of the effects of tributyltin chloride (TBTCl) was conducted in female rats using dietary concentrations of 5, 25, and 125 ppm TBTCl. Reproductive outcomes of dams (number and body weight of pups and the percentage of live pups) and the growth of female pups (the day of eye opening and body weight gain) were significantly decreased in the 125 ppm TBTCl group. A delay in vaginal opening and impaired estrous cyclicity were also observed in the 125 ppm TBTCl group. However, an increase in anogenital distance was found in all TBTCl groups on postnatal d 1. A dose-effect relationship was observed in TBTCl-induced changes in anogenital distance. These results indicate that the whole-life exposure to TBTCl affects the sexual development and reproductive function of female rats. In addition, the TBTCl-induced increase in anogenital distance seems to suggest it may exert a masculinizing effect on female neonates. However, the concentrations of TBTCl used in this study a...

Naohide Inoue

Papers

Two-generation reproductive toxicity study of tributyltin chloride in male rats.

Toxic polyneuropathy due to glue sniffing

Two-generation reproductive toxicity study of tributyltin chloride in female rats

Testicular toxicity of gallium arsenide, indium arsenide, and arsenic oxide in rats by repetitive intratracheal instillation.

Testicular toxicity evaluation of arsenic-containing binary compound semiconductors, gallium arsenide and indium arsenide, in hamsters