Fernando Díaz-Barriga

Overview of human health and chemical mixtures: problems facing developing countries.

In developing countries, chemical mixtures within the vicinity of small-scale enterprises, smelters, mines, agricultural areas, toxic waste disposal sites, etc., often present a health hazard to the populations within those vicinities. Therefore, in these countries, there is a need to study the toxicological effects of mixtures of metals, pesticides, and organic compounds. However, the study of mixtures containing substances such as DDT (dichlorodiphenyltrichloroethane, an insecticide banned in developed nations), and mixtures containing contaminants such as fluoride (of concern only in developing countries) merit special attention. Although the studies may have to take into account simultaneous exposures to metals and organic compounds, there is also a need to consider the interaction between chemicals and other specific factors such as nutritional conditions, alcoholism, smoking, infectious diseases, and ethnicity.

Effects of Lead–Arsenic Combined Exposure on Central Monoaminergic Systems

Lead acetate (116 mg/kg/day), arsenic (11 or 13.8 mg/kg/day as sodium arsenite), a lead-arsenic mixture or vehicle were administered to adult mice through gastric intubation during 14 days. Then, the regional content of norepinephrine (NE), dopamine (DA), serotonin (5-HT), 3,4 dihydroxyphenyl-acetic acid (DOPAC), 5-hydroxyindole-3-acetic acid (5-HIAA), arsenic, and lead were quantified. Compared with the accumulation after single element exposures, the mixture elicited a higher accumulation of lead and a lower arsenic accumulation in the brain. Compared to controls, lead induced only an augmentation of DOPAC (200%) in the hypothalamus. By contrast, the mixture provoked increases of DOPAC in the hypothalamus (250%), DA and 5-HIAA in the striatum (67 and 187%, respectively) and NE decreased in the hypothalamus (45%). Although these alterations were similar to those produced by arsenic alone, the mixture provoked a 38% decrease of NE in the hippocampus and increases of 5-HT in midbrain and frontal cortex (100 and 90%, respectively) over control values, alterations that were not elicited by either metal alone. These results demonstrate an interaction arsenic/lead on the central monoaminergic systems of the adult mouse.

Effect of arsenic, cadmium and lead on the induction of apoptosis of normal human mononuclear cells

The aim of this work was to investigate the effect of cadmium, lead and arsenic on the apoptosis of human immune cells. Peripheral blood mononuclear cells (MNC) were incubated with increasing concentrations of these metals and then cellular apoptosis was determined by flow cytometry and by DNA electrophoresis. We found that arsenic induced a significant level of apoptosis at 15 μM after 48h of incubation. Cadmium had a similar effect, but at higher concentrations (65 μM). In addition, cadmium exerted a cytotoxic effect on MNC that seemed to be independent of the induction of apoptosis. In contrast, concentrations of lead as high as 500 μM were nontoxic and did not induce a significant degree of apoptosis. Additional experiments showed that arsenic at concentrations as low as 1·0 μM had a significant pro‐apoptotic effect when cells were cultured in the presence of this pollutant for more than 72 . Non‐T cells were more susceptible than T lymphocytes to the effect of arsenic and cadmium. Interestingly, MNC from children chronically exposed to arsenic showed a high basal rate of apoptosis and a diminished in vitro sensibility to this metalloid. Our results indicate that both arsenic and cadmium are able to induce apoptosis of lymphoid cells, and suggest that this phenomenon may contribute to their immunotoxic effect in vivo.

Fluoride-induced disruption of reproductive hormones in men

Fluoride-induced reproductive effects have been reported in experimental models and in humans. However, these effects were found in heavily exposed scenarios. Therefore, in this work our objective was to study reproductive parameters in a population exposed to fluoride at doses of 3-27 mg/day (high-fluoride-exposed group-HFEG). Urinary fluoride levels, semen parameters, and reproductive hormones in serum (LH, FSH, estradiol, prolactin, inhibin-B, free and total testosterone) were measured. Results were compared with a group of individuals exposed to fluoride at lower doses: 2-13 mg/day (low-fluoride-exposed group-LFEG). A significant increase in FSH (P<0.05) and a reduction of inhibin-B, free testosterone, and prolactin in serum (P<0.05) were noticed in the HFEG. When HFEG was compared to LFEG, a decreased sensitivity was found in the FSH response to inhibin-B (P<0.05). A significant negative partial correlation was observed between urinary fluoride and serum levels of inhibin-B (r=-0.333, P=0.028) in LFEG. Furthermore, a significant partial correlation was observed between a chronic exposure index for fluoride and the serum concentrations of inhibin-B (r=-0.163, P=0.037) in HFEG. No abnormalities were found in the semen parameters studied in the present work, neither in the HFEG, nor in the LFEG. The results obtained indicate that a fluoride exposure of 3-27 mg/day induces a subclinical reproductive effect that can be explained by a fluoride-induced toxic effect in both Sertoli cells and gonadotrophs.

E-Waste and Harm to Vulnerable Populations: A Growing Global Problem.

Background: Electronic waste (e-waste) is produced in staggering quantities, estimated globally to be 41.8 million tonnes in 2014. Informal e-waste recycling is a source of much-needed income in many low- to middle-income countries. However, its handling and disposal in underdeveloped countries is often unsafe and leads to contaminated environments. Rudimentary and uncontrolled processing methods often result in substantial harmful chemical exposures among vulnerable populations, including women and children. E-waste hazards have not yet received the attention they deserve in research and public health agendas. Objectives: We provide an overview of the scale and health risks. We review international efforts concerned with environmental hazards, especially affecting children, as a preface to presenting next steps in addressing health issues stemming from the global e-waste problem. Discussion: The e-waste problem has been building for decades. Increased observation of adverse health effects from e-waste sites calls for protecting human health and the environment from e-waste contamination. Even if e-waste exposure intervention and prevention efforts are implemented, legacy contamination will remain, necessitating increased awareness of e-waste as a major environmental health threat. Conclusion: Global, national, and local levels efforts must aim to create safe recycling operations that consider broad security issues for people who rely on e-waste processing for survival. Paramount to these efforts is reducing pregnant women and children’s e-waste exposures to mitigate harmful health effects. With human environmental health in mind, novel dismantling methods and remediation technologies and intervention practices are needed to protect communities. Citation: Heacock M, Kelly CB, Asante KA, Birnbaum LS, Bergman AL, Bruné MN, Buka I, Carpenter DO, Chen A, Huo X, Kamel M, Landrigan PJ, Magalini F, Diaz-Barriga F, Neira M, Omar M, Pascale A, Ruchirawat M, Sly L, Sly PD, Van den Berg M, Suk WA. 2016. E-waste and harm to vulnerable populations: a growing global problem. Environ Health Perspect 124:550–555; http://dx.doi.org/10.1289/ehp.1509699

Effects of oral exposure to mining waste on in vivo dopamine release from rat striatum.

Several single components of mining waste (arsenic, manganese, lead, cadmium) to which humans are exposed at the mining area of Villa de la Paz, Mexico, are known to provoke alterations of striatal dopaminergic parameters. In this study we used an animal model to examine neurochemical changes resulting from exposure to a metal mixture. We used microdialysis to compare in vivo dopamine release from adult rats subchronically exposed to a mining waste by oral route with those from a control group and from a sodium arsenite group (25 mg/kg/day). We found that arsenic and manganese do accumulate in rat brain after 2 weeks of oral exposure. The mining waste group showed significantly decreased basal levels of dihydroxyphenylacetic acid (DOPAC; 66.7 +/- 7.53 pg/ microl) when compared to a control group (113.7 +/- 14.3 pg/ microl). Although basal dopamine release rates were comparable among groups, when the system was challenged with a long-standing depolarization through high-potassium perfusion, animals exposed to mining waste were not able to sustain an increased dopamine release in response to depolarization (mining waste group 5.5 +/- 0.5 pg/ microl versus control group 21.7 +/- 5.8 pg/ microl). Also, DOPAC and homovanillic acid levels were significantly lower in exposed animals than in controls during stimulation with high potassium. The arsenite group showed a similar tendency to that from the mining waste group. In vivo microdialysis provides relevant data about the effects of a chemical mixture. Our results indicate that this mining waste may represent a health risk for the exposed population. ImagesFigure 1Figure 2Figure 3

Arsenite-induced formation of hydroxyl radical in the striatum of awake rats

Recent studies on the mechanisms of arsenite toxicity report that some of its effects have been traced to the generation of reactive oxygen species during oxidative stress. In this study we analyze the formation of hydroxyl radicals in the brain of awake, freely moving rats, in order to obtain direct evidence of arsenic-induced oxidative stress in this tissue. We examined the time-course of hydroxyl radical formation in the striatum of both female and male rats who underwent a direct infusion during 60 min of different concentrations of arsenite in that structure through a microdialysis probe. We report here that basal levels of hydroxyl radical production in female rats are significantly higher than those in male rats (91.9+/-16.1 vs. 59.2+/-18.1 pmol/ml, P<0.001) and that the treatment with arsenite induced significant increases of hydroxyl radical formation over basal levels at 50, 100, 200 and 400 microM (95, 98, 98 and 99% increases, respectively, P<0.05 in all cases). The maximal response to 100 microM arsenite is significantly higher in female than in male rats (194.6+/-50.1 female rats and 88.1+/-11.6 pmol/ml male rats, P=0.036). These results support the participation of hydroxyl radicals in arsenic-induced disturbances in the central nervous system.

Assessment of DDT levels in selected environmental media and biological samples from Mexico and Central America.

Taking into account the environmental persistence and the toxicity of DDT, the Pan American Health Organization (PAHO) organized a surveillance program in Mesoamerica which included the detection of residual DDT in environmental (soil) and biological samples (fish tissue and childrens blood). This program was carried out in communities from Mexico, Guatemala, El Salvador, Honduras, Nicaragua, Costa Rica and Panama. This paper presents the first report of that program. As expected, the results show that the levels for [summation operator] DDT in soil (outdoor or indoor) and fish samples in the majority of the locations studied are below guidelines. However, in some locations, we found children with high concentrations of DDT as in Mexico (mean level 50.2 ng/mL). Furthermore, in some communities and for some matrices, the DDT/DDE quotient is higher than one and this may reflect a recent DDT exposure. Therefore, more efforts are needed to avoid exposure and to prevent the reintroduction of DDT into the region. In this regard it is important to know that under the surveillance of PAHO and with the support of UNEP, a regional program in Mesoamerica for the collection and disposal of DDT and other POPs stockpiles is in progress.

Exposure assessment of polybrominated diphenyl ethers (PBDEs) in Mexican children.

Flame retardants (FRs) constitute a group of compounds that are added to materials in order to suppress, reduce, or delay fire. At present the most used FRs are the polybrominated diphenyl ethers (PBDEs), and diverse studies have found individuals exposed to them. However, few studies have reported data in children. The objective of this report was to assess PBDEs levels in children of six communities in México. During the year 2006 we analyzed a total of 173 healthy children (aged 6-13 years old). Plasma samples were taken and quantified (gas chromatography/mass spectrometer) for PBDEs. Six PBDEs congeners (BDE-47, BDE-99, BDE-100, BDE-153, BDE-154, and BDE-209) were quantified in blood serum. We detected exposure to PBDEs in all the communities. The total PBDEs levels ranged from no detectable (nd) to 43.4 ng g(-1) lipid, the dominant PBDE congener was BDE-47, followed by BDE-100, BDE-99 and BDE-153, whereas the levels of BDE-209 were below LOD. Children living in an industrial and urban area (Cd. Juarez, Chih) had the highest levels of PBDEs, approximately two times that of children living in El Refugio, S.L.P. (a rural area) or in Milpillas, S.L.P. (municipal landfill) and 4-5 times higher than levels found in children living in San Luis Potosi, S.L.P. (urban area), in Chihuahua, Chih. (urban area), and San Juan Tilapa, Edo. Mex. (municipal landfills). Results cannot be generalized since the communities selected are not representative of the Mexican population. However, they do indicate that Mexican children are exposed to PBDEs.

Methodologies to examine the importance of host factors in bioavailability of metals

Bioavailability provides a link between intrinsic toxicity and the ability to produce that toxic effect in an organism. Biomonitoring tools are essential to assess the health of ecosystems and their component parts, including humans. While field and laboratory data are available, two critical issues to our understanding of bioavailability are often missing: 1) knowing the relationship between dose and tissue concentrations, and 2) species extrapolations. Understanding of high to low dose extrapolation is also critical. Methods to understand the importance of host factors in bioavailability of metals must assess gender, age, nutritional status, individual variability, temporal changes, and critical habitat effects. Methods to examine these variables include correlational, observational, experimental, epidemiological, and modeling studies, or a combination of these. Data gaps include developing more representative studies of human and animal populations, better analytical tools for rapid determination of metal content in the field, improved analytical characterization of metal bioavailability, and concurrent studies of different metals.