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PubMed1995

Cytogenetic biomonitoring of a population of children allegedly exposed to environmental pollutants. Phase 2: Results of a three-year longitudinal study.

Our previous cytogenetic biomonitoring of a group of inhabitants in a village (Mellery, Belgium) where exposure to a mixture of toxic environmental pollutants, (probably originating from a neighbouring chemical waste disposal site) was suspected, showed that difference in the SCE and HFC bioassays was more pronounced for children. The results of follow-up study in 1992 confirmed this surprising conclusion by an even higher incidence. As very few studies have been performed on the levels of children's biomarkers, this group of exposed populations needed to be explored further. Do children residing in the vicinity of hazardous waste sites indeed represent a population at higher risk? In the present study, we compare the performance of various bioassays (SCE, HFC, SSB and MN) in extended exposed and reference children's groups. Simultaneously, in the exposed group, we followed variation in the lymphocyte SCE frequencies as a function of time. Reversibility of the latter biomarker was ascertained subsequent to a preliminary technical remediation of the disposal site. We compared these data with those obtained from a synchronous cross-sectional study on a group of children living near a similar chemical disposal site. The two exposed populations did not differ from the reference population regarding to the SCE and HFC mean levels. Comparisons of the mean levels of the two other biomarkers, SSB and MN, showed no difference between the Mellery exposed children and the reference group from Wavre whereas significant differences appeared when the Hensies group is compared either to the Mellery or to the Wavre reference group.

Adolescent↗
PubMed1988

Applications of the in vitro aryl hydrocarbon hydroxylase induction assay for determining "2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents": pyrolyzed brominated flame retardants.

The pyrolysis of brominated flame retardants FR 300 BA (decabromobiphenyl) ether, FireMaster BP-6 (polybrominated biphenyls), Bromkal 70-5-DE (primarily pentabromodiphenylether), Bromkal 70-DE (primarily penta and tetrabromodiphenylether) and Bromkal G1 (pentabromodiphenylether) resulted in the formation of relatively high levels of polybrominated dibenzofurans (PBDFs) and dibenzo-p-dioxins (PBDDs as determined by gas chromatography-mass spectrometric analysis. The dose response EC50 values for the induction of aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) by the flame retardant pyrolysates was determined in rat hepatoma H-4-II E cells and compared to the relative induction activities of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the concentrations of "2,3,7,8-TCDD equivalents" were calculated. The range of "2,3,7,8-TCDD equivalents" levels (micrograms/g or ppm) derived from values obtained from the AHH and EROD bioassays for each of the pyrolyzed flame retardant samples was: 174-194, 480-1400, 2140-4680, 6740-8780 and 3920-5260 ppm for FR 300 BA, FireMaster BP-6, Bromkal 70 DE, Bromkal 70-5 DE and Bromkal G1, respectively. The in vivo dose-response effects of 2 pyrolyzed flame retardants were determined in immature male Wistar rats and compared to the dose-response activities of 2,3,7,8-TCDD. The in vivo responses which were measured included hepatic microsomal AHH and EROD induction, body weight loss and thymic atrophy. For the pyrolyzed FireMaster BP-6 and Bromkal 70-5 DE samples, the range of calculated in vivo "2,3,7,8-TCDD equivalents" (ppm in sample) for the 4 in vivo bioassays was 520-1780 ppm and 3860-8960 ppm, respectively. The excellent overlap between the in vivo and in vitro 2,3,7,8-TCDD equivalents for the 2 flame retardant pyrolysate extracts supports the utility of the in vitro induction bioassay for quantitatively determining "2,3,7,8-TCDD equivalents" for mixtures containing toxic halogenated aryl hydrocarbons.

Animals↗
PubMed1984

Detoxication of industrial pollutants by the glutathione glutathione-S-transferase system in the liver of Anabas testudineus (Bloch).

The interrelationship of reduced glutathione (GSH) and glutathione-S-transferase in the liver of a freshwater climbing perch Anabas testudineus (Bloch) exposed to common industrial pollutants has been studied. In both short- and long-term treatments there was a concomitant decrease in reduced glutathione profile and an increase in glutathione-S-transferase activity. It may be surmised that the majority of xenobiotics of industrial origin are detoxicated by the glutathione glutathione-S-transferase pathways enabling the fish to survive exposure to the additive and/or synergistic toxicity of mixtures of poisons.

Ammonia↗
PubMed2004

Screening organic micropollutants in surface waters by SPE extraction and ecotoxicological testing.

Complex mixtures of toxic substances occurring in surface waters are difficult to characterise by chemical analyses because each compound occurs at a very low concentration and requires a specific analytical method to be identified. Ecotoxicological tests on water extracts can be used as a screening tool to evaluate quickly and simply the overall quality of a water body with regard to micropollutant contamination. In this work, a pre-concentration procedure based on solid-phase extraction (SPE), suitable for both biological testing and analytical determination, is proposed. The extraction procedure is an improved version of a methodology used to evaluate the toxicity of organic micropollutants occurring in surface waters. It offers the advantage of using disposable commercial cartridges, which are easier to manage than the columns prepared with macromolecular resins. Water extracts from two representative Italian rivers, characterised by a different gradient of potential contamination and prepared according to the new concentration techniques, are used. The acute toxicity of the water extracts is tested on Daphnia magna and the bioluminescence inhibition in Vibrio fischeri. Criteria based on the concentration factor (CF) are proposed for assessing the hazard to aquatic life due to the exposure to toxic substances in surface waters. The aim of hazard ranking is to focus analytical efforts towards those samples that show the highest toxic potential.

Animals↗
PubMed2003

Linking exposure to environmental pollutants with biological effects.

Exposure to ambient air pollution has been associated with cancer. Ambient air contains a complex mixture of toxics, including particulate matter (PM) and benzene. Carcinogenic effects of PM may relate both to the content of PAH and to oxidative DNA damage generated by transition metals, benzene, metabolism and inflammation. By means of personal monitoring and biomarkers of internal dose, biologically effective dose and susceptibility, it should be possible to characterize individual exposure and identify air pollution sources with relevant biological effects. In a series of studies, individual exposure to PM(2.5), nitrogen dioxide (NO(2)) and benzene has been measured in groups of 40-50 subjects. Measured biomarkers included 1-hydroxypyrene, benzene metabolites (phenylmercapturic acid (PMA) and trans-trans-muconic acid (ttMA)), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in urine, DNA strand breaks, base oxidation, 8-oxodG and PAH bulky adducts in lymphocytes, markers of oxidative stress in plasma and genotypes of glutathione transferases (GSTs) and NADPH:quinone reductase (NQO1). With respect to benzene, the main result indicates that DNA base oxidation is correlated with PMA excretion. With respect to exposure to PM, biomarkers of oxidative damage showed significant positive association with the individual exposure. Thus, 8-oxodG in lymphocyte DNA and markers of oxidative damage to lipids and protein in plasma associated with PM(2.5) exposure. Several types of DNA damage showed seasonal variation. PAH adduct levels, DNA strand breaks and 8-oxodG in lymphocytes increased significantly in the summer period, requiring control of confounders. Similar seasonal effects on strand breaks and expression of the relevant DNA repair genes ERCC1 and OGG1 have been reported. In the present setting, biological effects of air pollutants appear mainly related to oxidative stress via personal exposure and not to urban background levels. Future developments include personal time-resolved monitors for exposure to ultrafine PM and PM(2.5,) use of GPS, as well as genomics and proteomics based biomarkers.

Air Pollutants↗
PubMed2002

Characterization of dioxin exposure in firefighters, residents, and chemical workers in the Irkutsk Region of Russian Siberia.

The goal of this study was to characterize body burdens of polychlorinated dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) in three groups of Siberians living in the Irkutsk Region of Russia. These groups included firefighters exposed to a mixture of toxic substances extinguishing a large fire at the Shelekhovo Cable Factory in 1992, chemical workers from the Khimprom chemical plant, and residents living in proximity to large chemical factories in Sayansk and Angarsk. Blood samples from all groups were obtained in the fall of 1998. Dioxin analyses of samples were performed in Germany, Canada, and in a Russian dioxin laboratory in Ufa, Bashkortostan Republic. The average levels of dioxin toxic equivalents (TEQs) are 23.6 parts per trillion (ppt) total TEQ (PCDD/F only) in the disabled firefighters, 25.0 in the non-disabled firefighters, 28.7 in residents, and 45.6 in the Khimprom workers blood. Two workers did have elevated total TEQs of 91.4 and 102.2 ppt. Dibenzofurans and coplanar PCBs substantially contribute to the total elevated TEQ seen here. The average TEQs suggest levels of dioxin exposure in this part of the former Soviet Union not dissimilar to levels measured in industrialized countries of Europe and Northern America.

Adult↗
PubMed1987

Jellyfish envenomation syndromes updated.

Jellyfish venoms are mixtures of toxic and/or antigenic polypeptides and enzymes pathogenic to human beings. As newer therapeutic agents become available to treat the various reactions to stings caused by these animals, an accurate diagnosis of the type of reaction the patient experiences and of the offending species will be necessary. Fatal reactions may be caused either by anaphylaxis or by the action of toxins in the venom on the heart, respiratory center, or kidneys. Cutaneous eruptions after envenomation may be local, generalized, exaggerated, recurrent, delayed, persistent, or occur at sites distant from the primary sting. Fat atrophy, pigmentary changes, vasospasm, and contractures with gangrene can occur after jellyfish stings. Identification of the envenoming animal can be made by actual visualization, examination for nematocysts on skin scraping, or serologically. It may also be predicted based on knowledge of location, time, and environmental circumstances of the encounter. First-aid measures designed to prevent additional nematocyst rupture are species-specific. Anaphylaxis should be prevented by the appropriate lifesaving measures. Other syndromes, caused by the toxins of the venom or mediated by humoral or cellular immune mechanisms, should be treated specifically.

Animals↗
PubMed2001

Toxicological profile of pollutants in surface water from an area in Taihu Lake, Yangtze Delta.

The environment in urbanized areas is often contaminated with a complex mixture of toxic compounds originating from industries, agriculture and private households. Most of the contaminants end up in surface waters, such as lakes, rivers and finally the sea. Toxic contaminants may disturb the biological condition of aquatic ecosystems and be harmful for humans, if they are transported to human food or drinking water. A variety of biological tests have been introduced for monitoring the toxicological profile of aquatic ecosystems. In the present investigation, genotoxic, hormone disrupting and Ah-receptor activity was analyzed in water collected in January 1999 at Meiliang Bay, Taihu Lake, China, near to the city of Wuxi in the Shanghai area. Significant mutagenic activity could be detected in water extracts with the Salmonella/microsome assay and the arabinose resistance test. Frame shift mutations were the predominant mode of action. Ah-receptor active compounds were detected by using a luciferase reporter gene assay (CALUX-assay). The estimated toxic equivalent factor-values ranged between 134 and 232 pg TCCD-equivalents per liter lake water. The estrogen-like potential of Taihu water was estimated with two luciferase reporter gene assays using transgenic human cell lines expressing estrogen receptor alpha. Estradiol equivalents obtained with water extracts were in the range of 2.2-12.1 ng/l. We also analyzed the concentrations of 17-beta-estradiol and ethinylestradiol in the extracts using a high-pressure liquid chromatography-method. The values obtained correlated with the biologically determined estradiol equivalents, indicating that the estrogenic activity is mainly due to natural and synthetic hormones rather than xenoestrogens.

Cell Line↗
PubMed2002

Employment of on-line FT-IR spectroscopy to monitor the deprotection of a 9-fluorenylmethyl protected carboxylic acid peptide conjugate of doxorubicin.

A method for accurately determining the end-point, >98% conversion, of the deprotection reaction of a highly toxic 9-fluorenylmethyl (Fm) ester 1b to its corresponding carboxylate 1d in real time by FT-IR spectroscopy is reported. Advantages of this method over analysis by conventional chromatographic means include real time determination of the end-point of a reaction that is time sensitive to by-product formation, and elimination of sampling a highly toxic reaction mixture. The FT-IR method is based on monitoring, in real time, the disappearance of the Fm ester carbonyl band for 1b at 1737 cm(-1), during deprotection by piperidine, and calibration models were established by Partial Least Squares (PLS) regression analysis with high performance liquid chromatography (HPLC) as reference. The best calibration model was built with 5 PLS factors in the spectral range of 1780-1730 and 1551-1441 cm(-1) and resulted in a standard error of cross validation (SECV) of 0.63 mM 1b and a standard error of prediction (SEP) of 0.51 mM 1b in the range of 0-25 mM. This error of prediction is approximately 0.8% of the initial concentration of 1b and is well within our specifications of <2% initial concentration.

Antineoplastic Agents↗
PubMed2006

The evaluation of liposome-water partitioning of 8-hydroxyquinolines and their copper complexes.

Bioavailability and toxicity of mixtures are urgent research issues, but usually mixtures of exclusively organic chemicals or exclusively metals are investigated. In our study, we explored the role of combinations of hydrophobic ionogenic organic compounds (HIOCs) with copper (Cu2+)for uptake and bioavailability of metals and hydrophobic metal complexes in an in vitro membrane system. We investigated the influence of the interactions of copper and 8-hydroxyquinolines, both components used in formulations of pesticides, on their partitioning into liposomes, which are model systems for biological membranes and are composed of lipid bilayers made of phosphatidylcholine. The test set of compounds comprised the parent compound 8-hydroxyquinoline and 8-hydroxyquinolines with hydrophobic (e.g., 5-chloro-8-hydroxyquinoline, 5,7-dichloro-8-hydroxyquinoline, 5,7-dibromo-8-hydroxyquinoline) and with hydrophilic (e.g., 8-hydroxyquinoline-5-sulfonic acid) substituents. Hydrophobic 8-hydroxyquinolines facilitate the passive uptake of copper into phospholipid bilayers by complex formation. Not only the neutral species of the ligands and their neutral copper ligand complexes are significantly taken up into the membrane, but also the cationic and anionic species of the ligands and the cationic complexes. The neutral, anionic, and cationic species of 8-hydroxyquinoline and the hydrophobic substituted 8-hydroxyquinolines exhibit linear correlations between their logarithmic liposome-water partitioning coefficients (log Klipw) and the logarithmic octanol-water partitioning coefficients of their neutral species (log Kow, neutral). The neutral species show the strongest partitioning followed by the anionic and cationic species. The associated quantitative structure activity relationships describing the dependency of log Klipw of the various species from log Kow, neutral of the neutral ligand species have slopes between 0.9 and 1. In contrast, the partitioning of the neutral and cationic copper-8-hydroxyquinoline complexes is dependent on several factors including the hydrophobicity of the ligand, the effective molecular size, and the polarization of the complex itself. In consequence, there is no linear relationship between log Klipw of these complexes and log Kow of the neutral species of their ligands. The complexes with very bulky substituents showed a reduced uptake. The Klipw of the nominally neutral complexes, where Cu2+ is coordinated with two ligands, were a factor three to four higher than the Klipw of the positively charged complexes with only one ligand. Although liposome-water partitioning merely describes one element of the uptake process into biological membranes, it is a key process for bioavailability of hydrophobic compounds and, presumably, also plays a crucial role for biological uptake of the described metal organic complexes.

Biological Availability↗
PubMed2003

Alpha-oxoaldehyde metabolism and diabetic complications.

The factors responsible for variable susceptibility to diabetic nephropathy are not clear. According to the non-enzymatic glycation hypothesis, diabetes-related tissue damage occurs due to a complex mixture of toxic products, including alpha-oxoaldehydes, which are inherently toxic as well as serving as precursors for advanced glycation end-products. Protective mechanisms exist to control this unavoidable glycation, and these are determined by genetic or environmental factors that can regulate the concentrations of the reactive sugars or end-products. In diabetes these protective mechanisms become more important, since glycation stress increases, and less efficient defence systems against this stress could lead to diabetic complications. Some of these enzymatic control mechanisms, including those that regulate alpha-oxoaldehydes, have been identified. We have observed significant increases in production of the alpha-oxoaldehydes methylglyoxal and 3-deoxyglucosone in three human populations with biopsy-proven progression of nephropathy. The increase in methylglyoxal could be secondary to defects in downstream glycolytic enzymes (such as glyceraldehyde-3-phosphate dehydrogenase) that regulate its production, or in detoxification mechanisms such as glyoxalase. Other mechanisms, however, appear to be responsible for the observed increase in 3-deoxyglucosone levels. We present results of our studies on the mechanisms responsible for variable production of alpha-oxoaldehydes by measuring the activity and characteristics of these enzymes in cells from complication-prone and -resistant diabetic patients. New therapeutic interventions designed to control these endogenous mechanisms could potentially enhance protection against excessive glycation and prevent or reverse complications of long-term diabetes.

Aldehydes↗
PubMed2005

Toxicity of cadmium and zinc mixtures to the decaudized cercarial life span of Diplostomum spathaceum.

The effects of cadmium and zinc mixtures at concentrations ranging from 0.1 to 10,000 microg l(-1) on the life-span of decaudized cercarial bodies (cercariae that have shed their tails) of Diplostomum spathaceum (Trematoda: Diplostomatidae) was investigated. Cercariae were exposed to metal mixtures of equal and unequal concentrations, and a low-dose pre-treatment followed by a high-dose exposure mixtures. Metal mixtures demonstrated variable effects on decaudized cercariae either by increasing or reducing their life-span compared to single metal exposures dependent on concentration and the type of mixed metal treatment. Prolonged exposure to equal metal mixtures at low concentrations (0.1-100 microg l(-1)) resulted in a reduction in the life-span of decaudized cercariae at 0.1 and 100 microg l(-1) in those individuals decaudized during the initial 24 h exposure period compared with those decaudized during the final 24 h period of cercarial survival, whilst in controls there was no significant life-span change between the two time periods. Decaudized cercariae which were exposed to low concentrations (0.1-100 microg l(-1)) of equal metal mixtures were also evaluated for their role as an indicator of larval 'fitness' for migrating through the tissues of their target fish host for those individuals decaudized during the initial 24 h exposure period, and demonstrated only a limited change in their life-span compared to control and single metal exposures. The importance of metal mixtures in parasite establishment in the fish host is discussed.

Animals↗
PubMedDate not supplied

Intoxication by cyanide in fires: a study in monkeys using polyacrylonitrile.

It is suspected that hydrogen cyanide (HCN) may be an important factor in incapacitating fire victims, but the effects of sublethal exposures are not well characterized. Also, the incapacitating effects of fire atmospheres result from exposure to a mixture of toxic products so that the contribution from each component is difficult to determine. The mechanisms of incapacitation in monkeys exposed to the pyrolysis products of polyacrylonitrile (PAN) were compared to those resulting from low level HCN gas exposures. The physiological effects of the PAN atmospheres were almost identical to those of HCN gas alone. They consisted of hyperventilation, followed by loss of consciousness after 1-5 min, bradycardia with arrhythmias and T-wave abnormalities, and were followed by a rapid recovery after exposure. Hydrogen cyanide is considered to be the major toxic product formed by the pyrolysis of PAN. It is suggested that HCN may produce rapid incapacitation at low blood levels of cyanide in fires, while death may occur later due to carbon monoxide poisoning or other factors.

Acrylic Resins↗
PubMed2003

Gender-related early immune changes in mice exposed to airborne suspended matter.

Immunotoxicity of the airborne suspended matter (ASM) from Upper Silesia (Poland) was investigated. The effect of the mixture of toxic components from the air suspended matter on the distribution and expression of several surface markers on lymphoid cells from thymus, spleen and axillary lymph nodes of female and male mice were examined. Corticosterone, a stress related hormone and sex hormones concentration in the plasma of animals were evaluated to discuss the interplay between the immune and endocrine system. The route, dose and length of application of ASM were examined. Thymus was shown to be a very sensitive organ to the effect of airborne suspended matter. Profound changes were shown in the distribution of CD4+ CD8+, CD4+ and CD8+ thymocytes subsets and TCRbeta and CD3 expression on thymic cells in young mice of both sexes exposed to ASM. Gender-related differences between female and male thymuses are rather quantitative than qualitative. Changes observed in the peripheral lymphoid organs were not so dramatic. The decrease of the percentage of CD19+ and Thy-1.2- in female spleens was noted. None changes in the plasma level of corticosterone and testosterone was observed in mice exposed to ASM, while a profound decrease of estradiol in female mice was noted. An interpretation all of these documented changes is attempted.

Air Pollutants↗
PubMed2002

Toxicity study of an antidipsotropic Chinese herbal mixture in rats: NPI-028.

OBJECTIVES: To determine the potential toxicity and safety of the Chinese herbal medicine NPI-028 in rats following subchronic (3-month) exposure via daily oral consumption. DESIGN: Subchronic toxicity was evaluated in four groups of rats (n = 10 per group) receiving NPI-028 orally at a dose of either 0.0 (normal diet control), 0.5, 1.0, or 2.0 g/kg, ingested as part of their daily diet for 3 months. NPI-028 was incorporated into powdered rat chow diet as a specific percent of the total diet provided each day. The primary active isoflavone content of NPI-028 (puerarin) used in the rat diet was also determined. OUTCOME MEASURES: Subchronic toxicity was assessed over a 3-month period by biweekly measurement of water and food intake, weight gain, and visual inspection for maintenance of grooming and normal behavior. At the end of the study period rats were euthanized and blood was obtained for hematologic and chemical analysis. Organs were removed for histopathologic examination. RESULTS: Rats in all three NPI-028 dose groups were similar to the control group in weight gain, food intake, and water intake over the study period. Hematology, blood chemistries, and organ histology in rats at all three NPI-028 doses did not significantly differ from control rats. Minor exceptions were elevated urea nitrogen values at all NPI-028 doses, and increased triglyceride and thyroid-stimulating hormone values in the lowest NPI-028 dose-treated group. Puerarin (used as a dietary isoflavone marker) content of NPI-028 was 26 mg/g dry weight. CONCLUSIONS: NPI-028 ingested orally at doses up to 2.0 g/kg per day in the rat diet for up to 3 months resulted in normal growth with no changes in hematologic or hepatic parameters, and only minor alterations in renal and blood chemistry parameters. There was no evidence of abnormal histology. These data suggest the long-term daily oral consumption of NPI-028 as a part of the daily diet for 3 months, at the doses studied, is safe in rats. Thus, NPI-028 may potentially be safe for clinical use as an antidipsotropic agent.

Administration, Oral↗