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PubMed1990

Aplastic anaemia associated with organochlorine pesticide: case reports and review of evidence.

Three patients with aplastic anaemia had a history of substantial previous exposure to organochlorine pesticides. The temporal association between chemical exposure and the onset of first symptoms of anaemia was strongly supportive. Organochlorines have the property of lipid affinity and accumulation in adipose tissue. Objective evidence of clinically important concentrations of tissue pesticide residues may be a useful confirmation of previous exposure. In the patients studied the presence of Lindane (gamma hexachlorocyclohexane) was shown using gas chromatography/mass spectrometry with selective ion monitoring of fragments obtained from one heavily exposed patient, with concentrations about five times greater than a matched control. The presence of clinically important tissue concentrations of pentachlorophenol was also confirmed in a second patient exposed to this agent. The long term safety of organochlorine pesticides remains doubtful as they were introduced before adequate toxicological screening tests had been developed. The central registration of possible haematological adverse reactions, however, forms an important epidemiological method in the study of environmental chemical hazards and should be complied with whenever possible.

Adipose Tissue↗
PubMed1995

Effect of glucose on the superoxide dismutase production in fungal strain Humicola lutea.

The effect of glucose on superoxide dismutase (SOD) activity produced in Humicola lutea 110 was determined. The relatively high glucose concentration in the medium did not repress SOD levels in the cells. Glycerol, a nonfermentable carbon source, caused a slight stimulation of SOD synthesis. Furthermore, the specific rates of enzyme production in the medium with different glucose concentration showed an insignificant difference. Cyclic AMP had no effect on SOD levels. The shift in metabolism as glucose was depleted resulted in an increase in the rate of synthesis of both isocitric dehydrogenase and SOD. Pentachlorophenol and paraquat, which cause the production of superoxide radicals, caused an increase in SOD activity. These results led us to conclude that it is superoxide ion rather than glucose that is controlling SOD levels.

Citric Acid Cycle↗
PubMed1997

Sulfur tuft and turkey tail: biosynthesis and biodegradation of organohalogens by Basidiomycetes.

Chlorinated aliphatic and aromatic compounds are generally considered to be undesirable xenobiotic pollutants. However, the higher fungi, Basidiomycetes, have a widespread capacity for organohalogen biosynthesis. Adsorbable organic halogens (AOX) and/or low-molecular-weight halogenated compounds are produced by Basidiomycetes of 68 genera from 20 different families. Most of the 81 halogenated metabolites identified from Basidiomycetes to date are chlorinated, although brominated and iodated metabolites have also been described. Two broad categories of Basidiomycete organohalogen metabolites are the halogenated aromatic compounds and the haloaliphatic compounds. Some of these organohalogen metabolites have demonstrable physiological roles as antibiotics and as metabolites involved in lignin degradation. Basidiomycetes produce large amounts of low-molecular-weight organohalogens or adsorbable organic halogens (AOX) when grown on lignocellulosic substrates. In our view, Basidiomycetes, as decomposers of forest litter, are a major source of natural organohalogens in terrestrial environments. Basidiomycetes are also potent degraders of a wide range of chlorinated pollutants, such as bleachery effluent from kraft mills and pentachlorophenol, polychlorinated dioxins, and polychlorinated biphenyls. The extracellular, lignin-degrading enzymes of the Basidiomycetes are involved in the oxidative degradation of chlorophenols and dioxin and can cause reductive dechlorination of halomethanes. There is no clear-cut separation between "polluters" and "clean-uppers" within the Basidiomycetes. Several genera, e.g. Bjerkandera, Hericium, Phlebia, and Trametes, produce significant amounts of chlorinated compounds but are also highly effective in metabolizing or biotransforming chlorinated pollutants.

Anti-Bacterial Agents↗
PubMedDate not supplied

Dermatotoxicity of agricultural chemicals in the dorsal skin of hairless dogs.

Dermatotoxicity of agricultural chemicals (ACs) with or without ultraviolet (UV) irradiation was histologically examined using hairless descendants of Mexican hairless dogs. ACs examined were pentachlorophenol sodium salt, 2,4-dichlorophenoxyacetic acid (DCPAA), Maneb, and Zineb. One day after cessation of the 7-day AC treatment, the skin treated with DCPPA and Maneb indicated only slight histological changes. The UV + AC-treated sites had as much pigmentation as the control sites. Fourteen days after cessation of treatment, dogs treated with Maneb showed marked reactions such as epidermal degeneration, vasodilation, and intradermal infiltration of inflammatory cells. These histological changes were more severe in the UV + AC-treated sites. Zineb induced comedones with well-developed pilosebaceous glands. These results suggest that hairless dogs may be useful laboratory animals for the investigation of dermatotoxicity of ACs in conjunction with UV irradiation.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1989

Effects of halogenated hydrocarbons on rumen microorganisms.

Halogenated hydrocarbons such as polychlorinated biphenyls (PCB's), heptachlor (HEP), 1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane (DDT), and pentachlorophenol (PCP) are environmental contaminants and, at times, can bioaccumulate in the food chain. Cattle have been contaminated in a variety of ways, but generally it is believed that they are only affected by high concentrations of the chemicals. Rumen microorganisms, however, may be affected at lower doses, thus possibly affecting the cow's growth and milk production. Polychlorinated biphenyls, HEP, DDT, and PCP were tested by a 1-stage in vitro fermentation procedure. Substrate utilization was determined by measuring percent dry matter disappearance. Four concentrations (0, 10, 50, and 100 ppm) were studied, and in vitro incubations were conducted for 24 and 48 hr. Samples were removed from 48-hr incubations to determine if the chlorinated hydrocarbons were metabolized during fermentation. Dry matter disappearance proved to be a reliable method to determine microbial activity in the presence of chemicals. Substrate dry matter disappearance for controls and all concentrations of PCB's, HEP, and DDT was approximately 50 and 80% at 24 and 48 hr, respectively. The PCP significantly (P less than 0.05) depressed the percent dry matter disappearance in 50- and 100-ppm cultures to 45 and 30% at 24 hr and 70 and 50% at 48 hr, respectively. Metabolic changes in the test chemicals were not detected by gas chromatographic analysis.

Animals↗
PubMed2005

Induction and inhibition of oocyte maturation by EDCs in zebrafish.

BACKGROUND: Oocyte maturation in lower vertebrates is triggered by maturation-inducing hormone (MIH), which acts on unidentified receptors on the oocyte surface and induces the activation of maturation-promoting factor (MPF) in the oocyte cytoplasm. We previously described the induction of oocyte maturation in fish by an endocrine-disrupting chemical (EDC), diethylstilbestrol (DES), a nonsteroidal estrogen. METHODS: In this study, stimulatory and inhibitory effects of EDCs and natural steroids on oocyte maturation were examined in zebrafish. For effective agents, some details about the mechanism in induction or inhibition of maturation were examined. Possible groups of DES interacting with the MIH receptor are discussed based on relative potency of steroids to induce maturation. RESULTS: Among agents tested, tamoxifen (TAM) and its metabolite 4-hydroxytamoxifen (4-OHT) showed stimulatory activity similar to DES. The time courses of the change in germinal vesicle breakdown and an intracellular molecular event (the synthesis of cyclin B) induced by TAM were indistinguishable from those induced by MIH. In contrast, pentachlorophenol (PCP) had a potent inhibitory effect on MIH-induced oocyte maturation. PCP inhibited not only MIH-induced maturation but also DES- and TAM-induced maturation. Methoxychlor also inhibited maturation when oocytes were pre-treated with this agent. CONCLUSION: These results suggest that EDCs act as agonists or antagonists in the induction of oocyte maturation in fish.

Animals↗
PubMed2004

Immunomodulation of human natural killer cell cytotoxic function by organochlorine pesticides.

Organochlorine pesticides are used worldwide. To our knowledge there have been no studies dealing with the effects of these agents under in vitro conditions on human natural killer (NK) cell cytotoxic function. NK cells play a central role in immune defense against tumor development and viral infections. Thus, any agent that interferes with the ability of NK cells to lyse their targets could increase the risk of tumor incidence and/or viral infections. In this study, we examined the effects of organochlorine pesticides and some of their breakdown products on the ability of human NK cells to lyse tumor cells. A total of 11 compounds were tested. The compounds were tested in both purified NK cells as well as a cell preparation that contained other mononuclear cells (predominantly T cells) and NK lymphocytes (referred to as T/NK cells). Lymphocytes were exposed to the compounds for periods of time ranging from 1 hour to 6 days. Exposure of highly purified NK cells to 5 microM alpha-chlordane, gamma-chlordane, 4,4'-DDT, heptachlor, oxychlordane, or pentachlorophenol (PCP) inhibited their ability to destroy K562 tumor-cells by 88+/-5, 92+/-8, 61+/-13%, 64+/-10%, 69+/-11%, 76+/-12%, respectively, after a 24 h exposure. The loss of cytotoxic function seen with alpha-and gamma-chlordane remained essentially constant out to 6 days, while that seen with 4,4'-DDT, oxychordane and PCP increased with longer exposures (6 d). PCP was the most effective of the compounds tested at decreasing NK function. Of the compounds that caused decreased lytic function when tested in purified NK cells, only PCP and oxychordane decreased the lytic function of the T/NK cell preparation after any exposure. The results provide evidence of relative toxic potential for the 11 compounds and their immunomodulatory effects on other mononuclear cells (such as T-cells, B-cells, and monocytes) as well as NK lymphocyte function.

Adult↗
PubMed2001

Response of MCF-7 human breast cancer cells to some binary mixtures of oestrogenic compounds in-vitro.

The effects of simultaneous administration of some binary mixtures of seven natural and synthetic oestrogenic substances (17beta-estradiol, estrone, bisphenol A, butylbenzyl phthalate, endosulfan, methoxychlor and pentachlorophenol) on the cellular proliferation of human breast cancer MCF-7 cells in-vitro (a modified E-screen assay) have been measured. To assess the presence or absence of interactions of the two agents, the data were analysed on the basis of a graphical method in which the types and extents of interactions were described by response-surface diagrams. Of the nine combinations of the agents examined, synergistic interaction was evident for the combination of 17beta-estradiol and bisphenol A, whereas the remaining eight combinations were weakly synergistic, additive and/or weakly antagonistic in the dose-range tested.

Benzhydryl Compounds↗
PubMed1979

Morphological alterations in the mitochondria of Amoeba proteus induced by uncoupling agents.

Ultrastructural changes in mitochondrial morphology were observed in amoebae exposed to the uncoupling agents dinitrophernol (DNP), pentachlorophenol (PCP), and m-chlorocarbonyl cyanide phenylhydrazone (CCCP). These alterations occurred with rapidity and were present before whole-cell activity changes could be detected. They included changes in profile shape and overall dimensions, matrix density changes, and alterations to the cristal membranes, so that distinction between control Type I and Type II conformations was eliminated and a form with intermediate characters generated. It is proposed that, in producing these altered forms, the uncoupling agents are acting by suppressing the control functional states of the mitochondria. At the end of the uncoupler treatment all alterations were shown to be reversible, i.e. in cells transferred back to normal culture medium, mitochondrial profiles identical to those in control cells were again evident with time. These effects on the mitochondria could be produced whether the uncoupler was introduced externally by total cell exposure, or to the inside of the cell by microinjection. The importance of precisely defining conditions for treatments and at disrupting cell activity was evident. Thus, an uncoupler, which is a weak acid, proved to be more effective in whole cell treatments if applied at a pH near to it pKa - so ensuring its penetration across the outer cell membrane.

Amoeba↗
PubMed2006

Intron-dependent accumulation of mRNA in Coriolus hirsutus of lignin peroxidase gene the product of which is involved in conversion/degradation of polychlorinated aromatic hydrocarbons.

The homobasidiomycete Coriolus hirsutus coding sequences of a lignin peroxidase (LiP) gene (lip, containing six (I-VI) introns), a lip cDNA (lipc), and three lipc derivatives containing one (I), three (I-III), or five (I-V) introns were inserted into chromosome-integrating expression vector. These recombinant plasmids were introduced into C. hirustus monokaryotic strain. The transformant carrying the promoter-lipc-terminator cassette did not contain enough mRNA molecules to be detectable by Northern-blot analysis. On the other hand, all the transformants carrying cassettes of genomic lip and intron(s)-containing lipc sequences contained sufficient amounts of mRNAs to be easily detected by Northern-blot analysis. LiP activities in the culture supernatants of these transformants were found to be about five times as high as those of transformants carrying the lipc cassette (or no cassette). The culture supernatants of the transformants with high LiP activity showed remarkably high conversion activity toward pentachlorophenol (PCP) and degradation activity toward 2,7-dichlorodibenzo-p-dioxin (2,7-DCDD). These results indicate that at least one intron (intron I) is required for accumulation of lip mRNA and its subsequent translational expression in C. hirsutus.

Base Sequence↗
PubMed2002

Structure of genes for Hsp30 from the white-rot fungus Coriolus versicolor and the increase of their expression by heat shock and exposure to a hazardous chemical.

We isolated and analysed two genomic DNAs that encode the heat-shock protein Hsp30 from Coriolus versicolor. The amino acid sequences substitute only three amino acid substitutions. The promoter regions contain the consensus heat-shock element, a xenobiotic-response element, a stress-response element, and a metal-response element. The levels of mRNAs for Hsp30 increased markedly after exposure of C. versicolor to pentachlorophenol and levels were higher than those after heat shock.

5' Flanking Region↗
PubMed2003

Exposure to indoor pesticides during pregnancy in a multiethnic, urban cohort.

Evidence is growing that indoor pesticide exposure is of considerable magnitude in the United States and that pesticide concentrations may be especially high in urban areas. Of particular concern is exposure of pregnant women because animal data suggest that exposure to pesticides during pregnancy and early life may impair neurodevelopment in the offspring. To investigate the relationship between prenatal exposure to indoor pesticides and infant growth and development, we are conducting a prospective, multiethnic cohort study of mothers and infants delivered at Mount Sinai Hospital in New York City. This article provides data on pesticide exposure based on questionnaire items and analysis of maternal urinary metabolite levels among 386 women. Both the questionnaire and laboratory data revealed that exposure to indoor pesticides was considerable. The proportion of women estimated from questionnaire data as having been exposed during pregnancy to indoor pesticides (approximately 70%) was somewhat lower than the 80-90% of American households who reportedly used pesticides in previous surveys, but some of the latter surveys included both indoor and outdoor pesticide use. Urinary metabolite levels of 3,5,6-trichloro-2-pyridinol (TCPy; median = 11.3 micro g/g creatinine), phenoxybenzoic acid (PBA; median =19.3 micro g/g creatinine), and pentachlorophenol (PCP; median =7.3 micro g/g creatinine) were higher than those reported in other studies of adults in the United States. Furthermore, no associations were evident between the pesticide questionnaire data and the urinary metabolites. Assessments of sociodemographic and building characteristics with questionnaire data and the metabolite levels revealed no consistent trends. Significant temporal variations were observed for urinary PBA but not TCPy or PCP. The temporal variations for PBA were consistent with seasonal spraying of pyrethroid pesticides. These data underscore the need to assess the potentially adverse effects of pesticide exposure on fetuses and infants and the importance of finding alternative methods for pest management to reduce pesticide exposures.

Adult↗
PubMed1980

Prioritization of chemicals according to the degree of hazard in the aquatic environment.

Chemicals designated as "priority pollutants" or "toxics" have received special attention recently because the discharge of these compounds into public water is to be restricted to the maximum possible with little regard to water quality or economics. The selection of many of the 129 priority cemicals was not based on an objective scientific assessment of the exposure and effect data. In fact, for some compounds, including acenaphthene and 4-chlorophenyl-phenyl ether, the necessary data for listing were non-existent. As an alternative to arbitrarily listing or delisting chemicals for the purpose of prioity control, this paper suggests a promising scientific approach to selecting priority chemicals based on the principles of hazard assessment for chemicals in the aquatic environment. According o the hypothesis, the highest priority chemicals are those with the least margin of safety, defined as the gap between the no-observable-effect concentrations and the ambient exposure concentrations. The no-observable-effect concenrations are based on the results of chronic or sensitive life stage tests with aquatic organisms and the acceptable daily intake rate for fish eates. The ambient exposure concentrations are levels either measured in fish and water, or roughly estimated from a simple nomogram that requires only two of the following three factors: environmental release rate, ratio of dissipation to bioconcentration potential, or ambient residues in fish. THE CHEMICALS STUDIED TO ILLUSTRATE THIS APPROACH TO PRIORITIZING CHEMICALS BASED ON HAZARD ASSESSMENT ARE: polychlorinated biphenyls, di-2-ethylhexyl phthalate, linear alkylbenzene sulfonate, and pentachlorophenol.

Animals↗
PubMed1982

Effects of transplacental exposure to chlorinated phenols.

Female rats were exposed to 0, 5, 50 or 500 ppm of 2-chlorophenol (2-CP) or pentachlorophenol (PCP). The study was designed to produce progeny which were exposed to the chlorophenolic compounds both prenatally and postnatally. Percent conception, litter size, birth weight, and number of stillbirths was determined at parturition. Hematologic parameters and body weights of the progeny were recorded at weaning age (3 weeks). Effects on reproduction were observed in both the 2-CP and PCP-exposed groups, as indicated by decreased litter sizes and increased number of stillborn. The data indicate that these chlorinated phenolic compounds may be feto- or embryotoxic at high doses. Effects on hematologic parameters were not observed. Further study involving transplacental and chronic exposures to these chlorophenolic compounds appears warranted.

Animals↗
PubMed1983

Sulfation and glucuronidation as competing pathways in the metabolism of hydroxamic acids: the role of N,O-sulfonation in chemical carcinogenesis of aromatic amines.

Aromatic amines can be metabolized by N-acetylation and N-hydroxylation to hydroxamic acids; these subsequently are conjugated to form the N,O-sulfonate and N,O-glucuronide conjugates. The N,O-sulfonates are highly labile metabolites that generate reactive intermediates involved in the covalent binding of the parent compound to protein, RNA and DNA, as well as to low molecular compounds like glutathione. This paper discusses methods used to decrease sulfation in vivo, and thereby to enhance the formation of the more stable N,O-glucuronides from N-hydroxy-2-acetylaminofluorene and N-hydroxy-4-acetylamino-4'-fluorobiphenyl. Acetaminophen pretreatment decreases the sulfate availability, but results in many side effects that complicate the analysis of the results. An 8% casein diet reduces the sulfate availability in the rat to approximately 20% of control and thus offers an effective approach to decrease sulfation. The most effective selective inhibition of sulfation is by pentachlorophenol, which very strongly reduces N,O-sulfonation of both hydroxamic acids, and selectively inhibits the formation of DNA adducts that have retained the N-acetyl group. This inhibitor and the related 2,6-dichloro-4-nitrophenol can be employed to study the role of sulfation of hydroxamic acids in initiation and promotion of tumor formation by aromatic amines.

Acetaminophen↗
PubMed1995

Reduced birthweight and length in the offspring of females exposed to PCDFs, PCP, and lindane.

The objective of this study was to investigate a broad range of adverse health outcomes and their potential association to wood preservative used in daycare centers. This article focuses on reproductive effects. A sample of 221 exposed teachers was provided by the employer's liability insurers. A comparison group (n = 189) insured by the same two organizations was recruited from nonexposed daycare centers. In a face-to-face interview, job history and reproductive history of 398 female teachers were ascertained. Data on exposure were provided, including measurements on concentration of pentachlorophenol (PCP) and lindane in wood panels, and of PCP, lindane, polychlorinated dibenzo-p-dioxins and dibenzofurans in indoor air. An exposure matrix based on individual job history, independent exposure information from each center, and reproductive history was set up with regard to the vulnerable time windows for each pregnancy. Using this approach, 49 exposed and 507 nonexposed pregnancies were identified, including 32 exposed and 386 nonexposed live births. For subgroup analyses the observations were restricted to independent pregnancies, excluding multiple and consecutive births. The data were analyzed with linear regression techniques, taking confounders into account. The crude median difference between exposed and nonexposed was 175 g in birthweight and 2 cm in length. Controlling for confounders, the results show a significantly reduced but weight (p = 0.04) and length (p = 0.02) in exposed pregnancies, even after restricting the data to independent pregnancies and pregnancies for which data could be validated from the mother's health cards. These differences were not explained by differences in gestational age indicating that a toxic effect, which could cause small-for date newborns, might have affected the fetus.

Adult↗
PubMed1998

Chlorinated hydrocarbons in women with repeated miscarriages.

This study was conducted to investigate a possible etiological role of chlorinated hydrocarbons in the pathogenesis of repeated miscarriages. The blood levels of chlorinated hydrocarbons [CHCs: pentachlorophenol, hexachlorocyclohexane, hexachlorobenzene, the dichlorodiphenyltrichloroethane (DDT) group, polychlorinated biphenyls] were determined in 89 women with repeated miscarriages, who were referred to the University Hospital of Obstetrics and Gynecology of Heidelberg for investigations between 1989 and 1993, and compared to a previously investigated reference population. In more than 20% of the women, at least one of the CHC levels exceeded the reference range. CHC levels did not differ significantly between women with primary or secondary and early or late miscarriages; neither did they differ between women with hormonal or immunological disorders as causes of repeated miscarriages or women with idiopathic repeated miscarriages. No significant associations were detected between CHC levels and further conceptions or the outcome of further pregnancies. As significant associations were found between increasing CHC blood concentrations and immunological and hormonal changes, CHCs may have an impact on the pregnancy course in certain cases.

Abortion, Habitual↗
PubMed2001

Evaluation for Hsp70 as a biomarker of effect of pollutants on the earthworm Lumbricus terrestris.

Induction of heat shock proteins (Hsps) is often associated with a cellular response to a harmful stress or to adverse life conditions. The main aims of the present study were (1) to assess if stress-induced Hsp70 could be used to monitor exposure of the earthworm species Lumbricus terrestris to various soil pollutants, (2) to assess the specificity of pollutants in their tissue targeting and in Hsp70 induction, and (3) to evaluate if dose-response relationships could be established and if the stress-response observed was specific. The midgut/intestinal tissues of L. terrestris are shown to express an inducible member of the Hsp70 family after heat shock treatment in vitro and exposures to different soil toxicants in vivo (re: artificial soil). Short-term (24-72 hours) and long-term (14-16 days) exposures to the chemical standards chloroacetamide and pentachlorophenol and to heavy metals (Pb++, Cd++, Cu++, and Hg++) also affected the earthworms, and Hsp70 was induced in their midgut/intestinal tissues. After a 3-day exposure to heavy metals, the level of Hsp70 induction in the midgut/intestinal tissues appears to correlate well with the reported in vivo and in vitro toxicity data. Comparatively, in proximal and midbody wall muscle tissues of animals exposed to the heavy metals, a decrease in expression of Hsp70 was sometimes detected. Thus Hsp analysis by Western blot in L. terrestris tissues and particularly in the midgut/intestine proved to be a suitable and sensitive assay for adverse effects in earthworms and showed a good level of reproducibility despite some individual variations. The use of pristine/nonexposed animals transposed into contaminated environments as in the present study should therefore be of high ecological relevance. Induction of Hsp70 in earthworms should represent not only a good wide-spectrum biomarker of exposure but also a biomarker of effect since known toxicants altered gene expression in tissues of these animals, as contrasted with a simple accumulation of Hsp. Hence, the detection of Hsp70 in earthworms can constitute an early-warning marker for the presence of potentially deleterious agents in soils, with L. terrestris in particular and earthworms in general acting as potential sentinel animal species.

Acetamides↗