Adverse Effects Of Environmental Chemicals Research Articles

Association between exposure to chemical mixtures and epigenetic ageing biomarkers: Modifying effects of thyroid hormones and physical activity

Evidence on the effects of internal chemical mixture exposures on biological age is limited. It also remains unclear whether hormone homeostasis and lifestyle factors can modify such a relationship. Based on the Biomarkers for Air Pollutants Exposure (BAPE) study, which involved healthy older adults aged 60–69 years in China, we found that chemical mixture exposures, including metals, polycyclic aromatic hydrocarbons (PAHs), per- and polyfluoroalkyl substances (PFASs), phthalates (PAEs), and organophosphate esters (OPEs), were significantly associated with shortened DNAmTL and accelerated SkinBloodClock, in which PFASs and OPEs in blood were the primary contributors to DNAmTL, while metals and PAEs had relatively higher contributions in urine. Furthermore, lower levels of thyroxin appeared to exacerbate the adverse effects of environmental chemicals on epigenetic ageing but relatively higher levels of physical activity had the beneficial impact. These findings may have important implications for the development of healthy ageing strategy and aged care policy, particularly in light of the global acceleration of population ageing.

The Promises and Challenges of Toxico-Epigenomics: Environmental Chemicals and Their Impacts on the Epigenome.

Background:It has been estimated that a substantial portion of chronic and noncommunicable diseases can be caused or exacerbated by exposure to environmental chemicals. Multiple lines of evidence indicate that early life exposure to environmental chemicals at relatively low concentrations could have lasting effects on individual and population health. Although the potential adverse effects of environmental chemicals are known to the scientific community, regulatory agencies, and the public, little is known about the mechanistic basis by which these chemicals can induce long-term or transgenerational effects. To address this question, epigenetic mechanisms have emerged as the potential link between genetic and environmental factors of health and disease.Objectives:We present an overview of epigenetic regulation and a summary of reported evidence of environmental toxicants as epigenetic disruptors. We also discuss the advantages and challenges of using epigenetic biomarkers as an indicator of toxicant exposure, using measures that can be taken to improve risk assessment, and our perspectives on the future role of epigenetics in toxicology.Discussion:Until recently, efforts to apply epigenomic data in toxicology and risk assessment were restricted by an incomplete understanding of epigenomic variability across tissue types and populations. This is poised to change with the development of new tools and concerted efforts by researchers across disciplines that have led to a better understanding of epigenetic mechanisms and comprehensive maps of epigenomic variation. With the foundations now in place, we foresee that unprecedented advancements will take place in the field in the coming years. https://doi.org/10.1289/EHP6104

Revisiting the Trivers-Willard theory on birth sex ratio bias: Role of paternal condition in a Malagasy primate.

Within current theories on potential adaptive manipulation of offspring sex ratio, giving birth to a male or to a female is assumed to depend on the capacity of the mother to invest in offspring to maximize her fitness. The active role of the father in sex ratio bias at birth has been neglected until recently. The human sex ratio at birth is biased towards sons, although in occidental populations, the ratio has decreased regularly for 30 years and could be the consequence of the adverse effects of environmental chemicals on male hormones. In a Malagasy primate, the lesser mouse lemur, the potential effect of paternal testosterone levels on sex ratio bias at birth was tested on 130 litters (278 babies) produced in 52 mixed-sex groups. For each group, social dominance among males was characterized based on aggressive interactions and sexual behaviours. Using a multi correspondence analysis, high testosterone levels in grouped males, particularly those of the dominant male, were significantly correlated with more infants produced in male-biased litters, independent of the female condition. According to these results, predictions for sex ratio bias towards one sex or the other in mouse lemurs were discussed considering the influence of both parents.

Personal computers - risk factors for renal failure.

   Kidneys perform various biological functions in the human body, and hence, they are called multi-talented powerhouses in our physiological system. Increased blood flow, occurrence of metabolizing enzymes, and transport proteins are important factors enhancing the sensitivity of the kidney. In this context, the kidney is an important candidate organ for the evaluation of the adverse effects of environmental chemicals. Although kidneys reside in the abdominal cavity and are protected by other tissues, they still behave like security forces working at the border of a country facing the onslaughts of external agents.      With reference to its structure, the kidney is a complicated organ, comprising various cell types and having a neatly designed three-dimensional organization. Due to this complexity, the intact kidney is difficult to use for an adequate study of many biochemical, pharmacological and physiological processes. Renal proximal tubule cells derived from primary cultures have been considered an appropriate model for the study of either proximal tubule cell function or renal intact function. Culturing of renal proximal tubule cells derived from primary culture is a critical issue in renal research. The newly designed protocol of Gowder and McMartin will provide an appropriate method to grow good quality renal proximal tubule cells to evaluate toxicity and transport properties of drugs/chemicals. (1)  Since reductionism (Einsteinian theory) dominates over the holism (Newtonian theory) in personal medicine, investigation of cells will provide more compromising results than that of whole individuals. (2)   Kidney damage has been considered to be a major public health hazard in recent years.  Common lifestyle diseases, such as diabetes, hypertension, and infectious diseases, are significant causes of renal failure. Sugar-sweetened beverages, food additives, sodium, drugs, toxins, and smoking cause renal failure. (3-7)     In this modern age (computer age), computers are essential to our routine life. On the other hand, the waste products of computers will accumulate in our environment. Electronic waste products have become a severe threat to society in terms of various adverse effects on our physiological system. The development of new devices due to the advancement of science and technology also leads to the disposal of existing products in large quantities.     Many of the hazards associated with computers arise when the equipment is disassembled, recycled, incinerated, or deposited in a landfill. The computer products contain cadmium, mercury, chromium, lead, beryllium, etc. - compounds known to be hazardous to humans and the environment. Cadmium is used in chip resistors, semi-conductors, infrared detectors, stabilizers, cables, and wires. Circuit boards, switches, and relays contain mercury and chromium; circuit boards also contain lead and motherboards, and connectors contain beryllium. (8)     Cadmium accumulates in the human body through environmental exposures, mainly through diet. When inorganic mercury spreads out in the water, it is transformed to methylated mercury in the bottom sediments. Methylated mercury accumulates in living organisms and concentrates through the food chain, particularly via fish. Chromium enters our body system through water, and lead comes from dusts and fumes. People may be exposed to beryllium at the time of manufacturing or shredding of computer parts. These compounds (cadmium, mercury, chromium, lead, and beryllium) exhibit nephrotoxicity. (9) Bisphenol-A (BPA) is the primary compound in the production of polycarbonate plastics and epoxy resins. Computer parts also contain polycarbonate plastics. BPA is used as a softening agent for all electronic devices, including computers. BPA also exhibits nephrotoxic effect. (10)  From various available reports, we can conclude that these chemicals may induce oxidative stress and thereby result in renal damage or failure.     Proper waste disposal methods, appropriate handling methods for computer devices, safety methods, etc. are ways to prevent health hazards. Â

Environmental/lifestyle effects on spermatogenesis

The high incidence of low sperm counts in young (European) men and evidence for declining sperm counts in recent decades mean that the environmental/lifestyle impact on spermatogenesis is an important health issue. This review assesses potential causes involving adverse effects on testis development in perinatal life (primarily effects on Sertoli cell number), which are probably irreversible, or effects on the process of spermatogenesis in adulthood, which are probably mainly reversible. Several lifestyle-related (obesity, smoking) and environmental (exposure to traffic exhaust fumes, dioxins, combustion products) factors appear to negatively affect both the perinatal and adult testes, emphasizing the importance of environmental/lifestyle impacts throughout the life course. Apart from this, public concern about adverse effects of environmental chemicals (ECs) (pesticides, food additives, persistent pollutants such as DDT, polychlorinated biphenyls) on spermatogenesis in adult men are, in general, not supported by the available data for humans. Where adverse effects of ECs have been shown, they are usually in an occupational setting rather than applying to the general population. In contrast, a modern Western lifestyle (sedentary work/lifestyle, obesity) is potentially damaging to sperm production. Spermatogenesis in normal men is poorly organized and inefficient so that men are poorly placed to cope with environmental/lifestyle insults.

Histopathology of the Testis as a Sensitive Tool to Detect Potentially Adverse effects of Environmental Chemicals on Male Fertility in Japanese Quail

Histopathology proved a sensitive tool to detect adverse effects of environmental chemicals on testis morphology and function in Japanese quail even if there was no evidence of reduced fertility. This became apparent in one-generation studies with the fungicides vinclozolin and epoxiconazole in which microscopic findings, such as atrophy or epithelial degeneration, paralleled a reduction in spermatid count whereas testis weight was not altered and reproductive success not compromised at the same dose levels. In a study with methyl testosterone in which fertility was in fact reduced, lower spermatid count was accompanied by a strong decrease in testis weight. Histological examination of the testis and counting of spermatids might be suitable and sensitive methods to elucidate the mechanism if a male-mediated decline in reproductive success is suspected.

Anogenital Distance: Defining “Normal”

In their letter to EHP, McEwen and Renner (2006) dismissed the findings of Swan et al. (2005), who reported a significant relationship between a measure of anogenital distance (AGD) in boys and levels of phthalate metabolites in their mothers’ urine during pregnancy. AGD is a sexually dimorphic index that, on average, is twice as great in males as in females, so it serves as a marker of proper male development. McEwen and Renner based their argument on an idiosyncratic form of logic. They asserted that All male infants evaluated in the study appeared normal … there is no evidence for potential adverse effect in the test population. … no conclusion can be drawn whether the reported values are normal or abnormal. The range of AGD values … likely represents typical biologic variation that would be expected to occur among normal study subjects. McEwen and Renner seem to be wholly unfamiliar with the meaning of a modest or even a slight shift in the mean of an index that reflects the distribution of susceptibility in a population. I have pointed out (Weiss 1988) that even a 5-point (5%) reduction in mean intelligence quotient in a population of 100 million increases the number of individuals classified as retarded from 6 million to 9.4 million. It is this kind of relationship that eventually prompted the Centers for Disease Control and Prevention (CDC) to lower its definition of elevated lead risk levels in blood, set at 40 μg/dL in 1970, to 10 μg/dL in 1991 (CDC 1991). Bellinger (2006) put it this way: A small change in the mean signals predictable accompanying changes in the proportions of individuals in the source population who fall into the tails of the distribution, where individuals who meet diagnostic criteria are found. Thus, the importance of a shift in group mean lies not in what it indicates about the average change among members of the study sample, but what it implies about the changes in the tails of the distribution in the population from which the study sample was drawn. He noted, based on Rose (1981), that in a population with a prevalence of clinically defined hypertension of 15%, a 5-mm reduction in mean systolic blood pressure would result in a 33% decrease in prevalence (Bellinger 2006). Epidemiologists recognize that a slight decrease in mean blood pressure in a population is translated into a major decrease in the incidence of serious cardiovascular events such as heart attacks. We already know that shortened AGD at birth is one element, the leading edge, as it were, of the “phthalate syndrome” in rats, which is marked by testicular pathology, reduced spermatogenesis, hypospadias, and cryptorchidism, a compilation of signs indicating disordered male development that Sharpe (2001) and others have noted to be on the increase in industrialized nations. An almost imperceptible shift to a lower mean AGD in the human male would foreshadow a heightened prevalence of reproductive system dysfunction. Is that the connection now emerging in the clinic? If McEwen and Renner’s (2006) criteria for “normal” were to govern the way in which we define the health risks of lead exposure, we would be basing our criteria on the number of children brought into hospital emergency rooms with lead poisoning rather than on the threats it poses to their neurobehavioral development. No parent, and no community, would tolerate such a definition these days.

Hormones and testis development and the possible adverse effects of environmental chemicals

Development of a fetus into a phenotypic male depends, first, on testis formation and second, on hormone production by the fetal testis. Disorders of testicular hormone production or action can lead in severe cases to phenotypic abnormalities or can predispose towards impaired reproductive health. Evidence for deteriorating human male reproductive health, especially an increase in testicular cancer, points to disturbed (hormonal) development of the fetal testis. By comparison of testicular dysgenesis in humans and exposure to certain phthalates in fetal rats, the similarities in outcomes and testicular cell–cell disruption are highlighted as are the pathways via which oestrogenic and (especially) anti-androgenic environmental chemicals might act to induce such changes. The susceptibility of sperm production in adulthood to ‘hormonal’ disruption in fetal and neonatal life is also discussed. Though it is concluded that no direct evidence links human exposure to environmental chemicals and male reproductive disorders that stem from disturbed testis development, this is based mainly on lack of information. Using the example of phthalates, for which new data have emerged, it is argued that until the appropriate in vivo studies are undertaken, the safety of hormonally active environmental chemicals, especially in mixtures, will continue to give cause for concern as far as testicular development is concerned.