High concentrations of heavy metals in neighborhoods near ore smelters in northern Mexico.
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In developing countries, rapid industrialization without environmental controls has resulted in heavy metal contamination of communities. We hypothesized that residential neighborhoods located near ore industries in three northern Mexican cities would be heavily polluted with multiple contaminants (arsenic, cadmium, and lead) and that these sites would be point sources for the heavy metals. To evaluate these hypotheses, we obtained samples of roadside surface dust from residential neighborhoods within 2 m of metal smelters [Torreon (n = 19)] and Chihuahua (n = 19)] and a metal refinery [Monterrey (n = 23)]. Heavy metal concentrations in dust were mapped with respect to distance from the industrial sites. Correlation between dust metal concentration and distance was estimated with least-squares regression using log-transformed data. Median dust arsenic, cadmium, and lead concentrations were 32, 10, and 277 microg/g, respectively, in Chihuahua; 42, 2, and 467 microg/g, respectively, in Monterrey, and 113, 112, and 2,448 microg/g, respectively, in Torreon. Dust concentrations of all heavy metals were significantly higher around the active smelter in Torreon, where more than 90% of samples exceeded Superfund cleanup goals. At all sites, dust concentrations were inversely related to distance from the industrial source, implicating these industries as the likely source of the contamination. We concluded that residential neighborhoods around metal smelting and refining sites in these three cities are contaminated by heavy metals at concentrations likely to pose a health threat to people living nearby. Evaluations of human exposure near these sites should be conducted. Because multiple heavy metal pollutants may exist near smelter sites, researchers should avoid attributing toxicity to one heavy metal unless others have been measured and shown not to coexist. (+info)
Effects of endocrine-disrupting contaminants on amphibian oogenesis: methoxychlor inhibits progesterone-induced maturation of Xenopus laevis oocytes in vitro.
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There is currently little evidence of pollution-induced endocrine dysfunction in amphibia, in spite of widespread concern over global declines in this ecologically diverse group. Data regarding the potential effects of endocrine-disrupting contaminants (EDCs) on reproductive function in amphibia are particularly lacking. We hypothesized that estrogenic EDCs may disrupt progesterone-induced oocyte maturation in the adult amphibian ovary, and tested this with an in vitro germinal vesicle breakdown assay using defolliculated oocytes from the African clawed frog, Xenopus laevis. While a variety of natural and synthetic estrogens and xenoestrogens were inactive in this system, the proestrogenic pesticide methoxychlor was a surprisingly potent inhibitor of progesterone-induced oocyte maturation (median inhibitive concentration, 72 nM). This inhibitory activity was specific to methoxychlor, rather than to its estrogenic contaminants or metabolites, and was not antagonized by the estrogen receptor antagonist ICI 182,780, suggesting that this activity is not estrogenic per se. The inhibitory activity of methoxychlor was dose dependent, reversible, and early acting. However, washout was unable to reverse the effect of short methoxychlor exposure, and methoxychlor did not competitively displace [3H]progesterone from a specific binding site in the oocyte plasma membrane. Therefore, methoxychlor may exert its action not directly at the site of progesterone action, but downstream on early events in maturational signaling, although the precise mechanism of action is unclear. The activity of methoxychlor in this system indicates that xenobiotics may exert endocrine-disrupting effects through interference with progestin-regulated processes and through mechanisms other than receptor antagonism. (+info)
Animals as sentinels of human health hazards of environmental chemicals.
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A workshop titled "Using Sentinel Species Data to Address the Potential Human Health Effects of Chemicals in the Environment," sponsored by the U.S. Army Center for Environmental Health Research, the National Center for Environmental Assessment of the EPA, and the Agency for Toxic Substances and Disease Registry, was held to consider the use of sentinel and surrogate animal species data for evaluating the potential human health effects of chemicals in the environment. The workshop took a broad view of the sentinel species concept, and included mammalian and nonmammalian species, companion animals, food animals, fish, amphibians, and other wildlife. Sentinel species data included observations of wild animals in field situations as well as experimental animal data. Workshop participants identified potential applications for sentinel species data derived from monitoring programs or serendipitous observations and explored the potential use of such information in human health hazard and risk assessments and for evaluating causes or mechanisms of effect. Although it is unlikely that sentinel species data will be used as the sole determinative factor in evaluating human health concerns, such data can be useful as for additional weight of evidence in a risk assessment, for providing early warning of situations requiring further study, or for monitoring the course of remedial activities. Attention was given to the factors impeding the application of sentinel species approaches and their acceptance in the scientific and regulatory communities. Workshop participants identified a number of critical research needs and opportunities for interagency collaboration that could help advance the use of sentinel species approaches. (+info)
Polycyclic aromatic hydrocarbons in carcinogenesis.
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A symposium on "Polycyclic Aromatic Hydrocarbons (PAHs) in Carcinogenesis" was presented at the third International Congress of Pathophysiology held in Lathi, Finland, 28 June-3 July 1998. The congress was also sponsored by the International Union of Biological Sciences and the International Society of Free Radical Research. Institutional support for the symposium included the Electric Power Research Institute, National Center for Toxicological Research, and EPA/National Health and Environmental Effects Research Laboratory and the Office of Solid Waste and Emergency Response. The symposium focused on the sources, carcinogenicity, genotoxicity, and risk assessment of individual and mixtures of PAHs that are found in solid wastes, Superfund sites, and other hazardous waste sites. Based on the occurrence of PAHs at numerous Superfund sites and the significant data gaps on the toxic potential of certain PAHs, the information developed during this symposium would be of value in assessing health risks of these chemicals at Superfund and other hazardous waste sites. (+info)
Serum dioxin and cancer in veterans of Operation Ranch Hand.
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We studied cancer prevalence and exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) in veterans of Operation Ranch Hand, the Air Force unit responsible for the aerial spraying of herbicides in Vietnam from 1962 to 1971. A comparison group of Air Force veterans who served in Southeast Asia during the same period and who were not involved with spraying herbicides was included. Comparison veterans were matched to Ranch Hand veterans on age, race, and military occupation. We measured dioxin in 1987 or 1992, extrapolated the result to the time of service in Southeast Asia, and assigned each Ranch Hand veteran to Background, Low, or High exposure categories. This study had low power to detect an effect for specific or rare cancers. The risk of cancer at sites other than the skin within 20 years of service was increased in the Low (odds ratio (OR) = 3.4, 95% confidence interval (CI) 1.5-8.0) and High (OR = 2.7, 95% CI 0.9-8.0) categories, but the pattern was inconsistent with another study, suggesting that the excess risk may not have been caused by dioxin exposure. Overall, we found no consistent evidence of a dose-response gradient and no significant increase in cancer risk in the High dioxin exposure category, the subgroup of greatest a priori interest. (+info)
Environmental pathology: new directions and opportunities.
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The National Institute of Environmental Health Sciences (NIEHS) supports a number of training programs for predoctoral and postdoctoral (D.V.M., M.D., Ph.D.) fellows in toxicology, epidemiology and biostatistics, and environmental pathology. At the Experimental Biology meeting in April 1997, the American Society of Investigative Pathology (ASIP) sponsored a workshop including directors, trainees, and other interested scientists from several environmental pathology programs in medical and veterinary colleges. This workshop and a related session on "Novel Cell Imaging Techniques for Detection of Cell Injury" revealed advances in molecular and cell imaging approaches as reviewed below that have a wide applicability to toxicologic pathology. (+info)
Stimulation of pregnant rat uterine contraction by the polychlorinated biphenyl (PCB) mixture aroclor 1242 may be mediated by arachidonic acid release through activation of phospholipase A2 enzymes.
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The polychlorinated biphenyl (PCB) mixture Aroclor 1242 (A1242) increases frequency of contractions of pregnant rat uteri, suggesting a possible mechanism for decreased gestational age and increased spontaneous abortion in women and animals exposed to PCBs. In the present study, we hypothesized that A1242-induced stimulation of uterine contraction is mediated by arachidonic acid released by phospholipase A2 (PLA2) enzymes. Isometric uterine contraction was measured in longitudinal uterine strips isolated from gestation day 10 rat. Pretreatment of uterine strips with the PLA2 inhibitor (E)-6-(bromomethylene)tetrahydro-3-(1-naphthalenyl)-2H-pyran-2-one (HELSS) or manoalide, or an inhibitor of the G protein of PLA2, isotetrandrine, completely prevented the increase of contractile frequency induced by 50 microM A1242. However, the phospholipase C inhibitors 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (NCDC) and neomycin were unable to block stimulation of uterine contraction by A1242. In accordance, A1242 (100 microM) did not release inositol phosphates from myo-[3H]inositol-labeled myometrial cells, whereas myometrial cells prelabeled with [3H]arachidonic acid released arachidonic acid in a concentration- and time-dependent manner after exposure to A1242 (10-100 microM). A1242 significantly stimulated arachidonic acid release in the absence of extracellular calcium, although the release was attenuated. Analysis of the eicosanoids released by A1242 indicated that only 0.83% of released [3H]arachidonic acid was metabolized to eicosanoids and 99.07% remained as free arachidonate. Uterine contraction increased in strips exposed to exogenous arachidonic acid (1-100 microM). This study suggests that A1242 stimulates contraction in pregnant rat uterus by a mechanism involving PLA2-mediated arachidonic acid release, and that arachidonic acid, rather than eicosanoids, may mediate A1242 uterotonic action in the uterus. (+info)
Induction of human UDP glucuronosyltransferases (UGT1A6, UGT1A9, and UGT2B7) by t-butylhydroquinone and 2,3,7,8-tetrachlorodibenzo-p-dioxin in Caco-2 cells.
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Human colon carcinoma Caco-2 cells were used to study the induction of UDP glucuronosyltransferase (UGT) isoforms UGT1A6, UGT1A9, and UGT2B7 by aryl hydrocarbon receptor agonists and by antioxidant-type inducers with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and t-butylhydroquinone (TBHQ), respectively. Early- (PF11) and late-passage clones (TC7) of Caco-2 cells, which show low and high constitutive UGT1A6 expression, respectively, were selected. The following results were obtained: 1) In Caco-2 cells UGT activity (4-methylumbelliferone as substrate) was significantly enhanced by 10 nM TCDD or 40 to 80 microM TBHQ and 2) duplex reverse-transcription-polymerase chain reaction analysis showed for the first time that the expression of human UGT1A6, UGT1A9, and UGT2B7 was enhanced by 40 to 80 microM TBHQ; both UGT1A6 and UGT1A9 were induced by 10 nM TCDD, whereas UGT2B7 was not induced by TCDD. The results suggest that at least two human UGTs (UGT1A6 and UGT1A9) are inducible by aryl hydrocarbon receptor agonists and even more isoforms (UGT1A6, UGT1A9, and UGT2B7) are inducible by antioxidant-type inducers in Caco-2 cells. (+info)