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PubMed1991

Responses of the L5178Y mouse Lymphoma cell forward mutation assay. V: 27 coded chemicals.

Twenty-seven chemicals were tested for their mutagenic potential in the L5178Y tk+/tk- mouse lymphoma cell forward mutation assay using procedures based upon those described by McGregor et al. (McGregor DB, Martin R, Cattanach P, Edwards I, McBride D, Caspary WJ (1987): Environ Mol Mutagen 9:143-160). Cultures were exposed to the chemicals for 4 hr, then cultured for 2 days before plating in soft agar with or without trifluorothymidine (TFT), 3 micrograms/ml. The chemicals were tested at least twice. Statistically significant responses were obtained with acid orange 10, aniline, benzaldehyde, o-chloroaniline, chlorodibromomethane, cytembena, 1,2-dibromo-4-(1,2-dibromomethyl) cyclohexane, dieldrin, lithocholic acid, oxytetracycline, phenazopyridine HCl, 1-phenyl-3-methyl-5-pyrazolone, sodium diethyldithiocarbamate, solvent yellow 14, tetraethylthiuram disulfide (disulfiram), 2,4-toluene diisocyanate, and 2,6-toluene diisocyanate. Apart from phenazopyridine HCl, acid orange 10, and solvent yellow 14, rat liver S9 mix was not a requirement for the mutagenic activity of these compounds. Chemical not identified as mutagens were N-4-acetylaminofluorene, chlorpheniramine maleate, chloropropamide, 1,4-dioxane, endrin, ethylene glycol, iron dextran, methapyrilene, sodium(2-ethylhexyl)alcohol

Animals↗
PubMed1991

[Residues of organochlorine pesticides, PCB's and chlorophenols in fish from commercial ponds and fish hatcheries from the waters in the area of Frankfurt (Oder)].

Fishes from fish-hatcheries, lakes and the river Oder in the area of the former district Frankfurt (Oder) were analysed for organochlorine pesticides (HCB, aldrin, HCH-isomeres, DDD, DDE, DDT, endrin, toxaphen and dieldrin), polychlorinated biphenyles and penta- and tetrachlorophenole. A clean up-procedure using acidic digestion mixture has been compared with a column-extraction-procedure followed by column chromatography on aluminia. Furthermore the simultaneous determination of the organochlorine pesticides, PCB's and chlorophenoles by acidic silicagel-extraction is described. The identification and quantification was realized by packed-column and capillary-gaschromatography including electron-capture-detection. The investigations show, that the permissible levels were only reached up to 2 to 10% with exception of toxaphen and pentachlorophenole. Average 50% of the toxaphen- and pentachlorophenole-values were found near the tolerance levels settled for these substances. The application of both substances in the area of the former German Democratic Republic until today can be regarded as a reason for this. The results of our investigations are comparable to last publications on fish contamination in the area of the previous Federal Republic of Germany.

Animals↗
PubMed1985

Dermal absorption of pesticides calculated by deconvolution.

Using published human data on skin-to-urine and blood-to-urine transfer of 12 pesticides and herbicides, the skin-to-blood transfer rates for each compound were estimated by two numerical deconvolution techniques. Regular constrained deconvolution produced an estimated upper limit on cumulative dermal absorption of the radiolabel, while minimized deconvolution produced an upper bound on cumulative dermal absorption of parent compound. Dermal absorption rate was largest within 8 h of dosing for all pesticides examined. Only carbaryl showed a lag (3.5 h) in penetration. This may indicate a prolonged transit time through skin or a chemical transformation in skin has occurred. After onset, absorption occurred rapidly with 45% of the 120 h cumulative absorption occurring in 8 h. For parathion and dieldrin, over 50% of the 120 h total absorption occurred in the first 4 h. The deconvolution technique described here permits the calculation of the temporal aspect of dermal absorption for linear systems.

Humans↗
PubMed1990

Chlordecone interaction of calmodulin binding with phosphodiesterase.

The effects of organochlorine (O.C.) compounds, such as aldrin, dieldrin, endrin, isodrin, chlordecone and mirex, on calmodulin (CaM) activity were investigated. Changes induced by O.C. compounds on biological and physical properties of CaM were monitored in terms of phosphodiesterase stimulation and tyrosine fluorescence, respectively. None of the O.C. compounds altered tyrosine fluorescence of CaM in the presence of Ca2+. Except for chlordecone, none of the O.C. compounds inhibited CaM-activated phosphodiesterase (PDE). Chlordecone significantly decreased (P less than 0.05) CaM-activated PDE in a concentration-dependent manner without affecting the basal enzyme. Combination of chlordecone with W-7 (CaM antagonist) increased the inhibitory effect of W-7 on CaM activity. These results suggest that O.C. compounds may not be changing the tyrosine fluorescence of CaM. Among the O.C. compounds tested, chlordecone is a specific inhibitor of CaM-activated PDE.

Binding, Competitive↗
PubMed1992

The Ca(2+)-transport-ATPase of human erythrocytes as an in vitro toxicity test system--acute effects of some chlorinated compounds.

Investigations to determine the inhibitory activity on the Ca(2+)-transport-ATPase of human erythrocyte membranes were performed with various compounds of toxicological significance, mostly chlorinated and mainly used as biocides, such as phenol, 4-chlorophenol, 2,4-dichlorophenol, 2,6-dichlorophenol, 3,4-dichlorophenol, 2,3,4-trichlorophenol, 2,3,4,5-tetrachlorophenol, pentachlorophenol (PCP), captan, folpet, captafol, (+)-camphene, toxaphene, dichlorodiphenyltrichloroethane (DDT), lindane, endrin, dieldrin, alpha-endosulfan, beta-endosulfan, paraquat, diallate, 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). Some of the compounds investigated display an inhibitory effect on the Ca(2+)-transport-ATPase at very low concentrations. The in vitro results obtained in this enzyme assay can be correlated directly with the results of other in vitro assays and with the results of in vivo investigations in different species in which an inhibitory effect on various biological functions is observed. Therefore, an inhibitory effect on the Ca(2+)-transport-ATPase indicates a toxic effect of these compounds to cell functions. Since the inhibitory effect of these compounds can be measured rapidly and the enzyme is easy to handle, it might be a useful tool to screen the toxic effects of various compounds on cell function. The aim of the authors was to investigate the usefulness of this screening test system for the characterization of the cellular toxicity of various compounds.

Calcium-Transporting ATPases↗
PubMedDate not supplied

Toxicological evaluation of mixtures of ten widely used pesticides.

Toxicities of pesticidal mixtures in biological systems have not been explored adequately. Therefore, mixtures of ten widely used pesticides were evaluated for their toxicity in ICR male mice (21-24 g). Mice were given four mixtures of alachlor, aldrin, atrazine, 2,4-dichlorophenoxyacetic acid, DDT, dieldrin, endosulfan, lindane, parathion and toxaphene, at 0.01, 0.1, 1.0 and 10 ppm of each of these pesticides, in drinking water for 90 days ad libitum. Also, two mixtures at 2.5 and 5 mg kg-1 of each pesticide in 7.5% Tween-80 in water were administered to additional groups of mice by oral intubation daily for up to 14 days. In relation to the control, the 90-day exposure caused a dose-dependent increase in the liver/body weight ratio (3-44%), a decrease in the pentobarbital (60 mg kg-1, i.p.)-induced sleep time (11-79%) and an increase in the metabolism of aniline (233-399%), amidopyrine (79-231%), phenacetin (127-318%) and benzo[a]pyrene (286-1633%) in the 9000 g hepatic supernatants from the mixture-treated mice. Proliferation, dilatation and fragmentation of the endoplasmic reticulum and scattering of ribosomes were noticed with mixture livers. In the 5 mg kg-1 group, 90% of the animals died by Day 8; incidence of death was considerably less in the 2.5 mg kg-1 group. The serum cholinesterase activity was inhibited by ca. 50% in the 2.5 and 5 mg kg-1 groups on either one or both of Days 8 and 15; the liver/body weight ratio increased by 24-79% and the pentobarbital-induced sleep time decreased by 80-96%.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

Activation of gamma-aminobutyric acid insensitive chloride channels in mouse brain synaptic vesicles by avermectin B1a.

The interaction of avermectin B1a (AVMB1a) with mouse brain chloride channels was characterized using a radiochloride efflux assay. The loss of intravesicular chloride from synaptoneurosomes preloaded with 36Cl involved an initial rapid phase followed by a slower phase that approached equilibrium within 10 min. AVMB1a stimulated a 30% loss of intravesicular chloride within the first 2 s of exposure; however, AVMB1a had no effect on the rate of the slower phase of chloride loss. Experiments with lysed synaptoneurosomes showed that both chloride loading and basal and AVMB1a-stimulated chloride release required the presence of intact vesicles. The efflux of 36Cl from mouse brain synaptosomes and the stimulation of efflux by AVMB1a were qualitatively similar to the results obtained with synaptoneurosomes but involved much lower overall levels of chloride loading and release. AVMB1a produced half-maximal stimulation of chloride efflux from synaptoneurosomes at a concentration of 2.1 +/- 0.3 microM and a 35.4 +/- 1.4% maximal loss of intravesicular chloride at saturating concentrations. gamma-Aminobutyric acid (GABA), bicuculline, or the chloride channel blockers picrotoxinin, t-butylbicyclophosphorothionate (TBPS) 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), and anthracene 9-carboxylic acid (9-CA) had little or no effect on the loss of chloride from synaptoneurosomes either in the presence or the absence of AVMB1a. However, the chlorinated cycloalkane insecticides dieldrin and lindane were equally effective as inhibitors of GABA-dependent chloride uptake and AVMB1a-stimulated chloride efflux. These data demonstrate that AVMB1a-stimulated chloride efflux from mouse brain synaptic vesicles results from the activation of GABA-insensitive chloride channels and that this action is distinct from their previously documented effects on GABA-gated chloride channels in mouse brain preparations. Our findings imply that both GABA-gated and GABA-insensitive chloride channels may be toxicologically significant targets for the action of avermectins.

Animals↗
PubMed2005

Ultratraces analysis of organochlorine pesticides in drinking water by solid phase extraction coupled with large volume injection/gas chromatography/mass spectrometry.

This study describes an SPE coupled with large volume injection (LVI) analytical method for the analysis of organochlorine pesticides, BHC (alpha, beta, delta), aldrin, endosulfan (alpha, beta), endrin, dieldrin, and DDT, from aqueous samples. Determination was carried out by GC with MS. The LODs of organochlorine pesticides were determined at 10 ng/L concentration levels, and the results show that SPE-LVI-GC/MS has the potential to accurately determine organochlorine pesticides in water, as it avoids analyte classes in the various steps of a typical extraction procedure.

Chromatography, Gas↗
PubMed2004

Identification of the Rdl mutation in laboratory and field strains of the cat flea, Ctenocephalides felis (Siphonaptera: Pulicidae).

In many insect species, resistance to cyclodiene insecticides is caused by amino acid substitutions at a single residue (A302) within the M2 transmembrane region of the gamma-aminobutyric acid (GABA) receptor sub-unit termed Rdl (resistance to dieldrin). These mutations (A302S and A302G) have also been shown to confer varying levels of cross-resistance to fipronil, a phenylpyrazole insecticide with a similar mode of action to cyclodienes. To investigate the possible occurrence of these mutations in the cat flea, Ctenocephalides felis (Bouché), a 176-bp fragment of the cat flea Rdl gene, encompassing the mutation site, was PCR amplified and sequenced from nine laboratory flea strains. The A302S mutation was found in eight of the nine strains analysed, although the relative frequency of the mutant allele varied between strains. Only one strain (R6) was found to be homozygous for the S302 allele in all the individuals tested, and this correlated with previous reports of low-level fipronil resistance in this strain. A PCR-based diagnostic assay, capable of screening individual fleas for this mutation, was developed and used to survey a range of fleas collected at random from veterinary clinics in the UK and USA. The A302S mutation was present at a high frequency in these domestic pet populations.

Alleles↗
PubMed2005

Benzene-assisted atmospheric-pressure chemical ionization: a new liquid chromatography/mass spectrometry approach to the analysis of selected hydrophobic compounds.

Charge-exchange reactions involving benzene have been successfully exploited to increase the sensitivity of atmospheric-pressure chemical ionization mass spectrometry (APCI-MS) towards hydrophobic compounds of significant environmental relevance which are not detectable with the ordinary APCI techniques. Among them, good sensitivity have been found for (a) highly chlorinated biphenyl derivatives such as dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethane (DDD) and dichlorodiphenyldichloroethene (DDE); (b) cyclopentadienes such as Aldrin and its epoxy derivatives Dieldrin and Endrin; and (c) dibenzofurans and dibenzo-para-dioxins such as 2,3,7,8-tetrachlorodibenzofuran (2,3,7,8-TCDF) and 2,3,7,8-tetrachloro-dibenzo-para-dioxin (2,3,7,8-TCDD). The reactant benzene molecules were introduced into the source either through the nebulizer gas or by direct post-column addition of neat liquid, whereas the targeted compounds were analyzed using a high-performance liquid chromatography (HPLC) RP-18 column using methanol/water solutions as mobile phase. By using benzene as post-column reagent, positive ion mode detection was proven to be significantly enhanced as compared with APCI measurements carried out without benzene assistance.

Air Pollutants↗
PubMed1993

Presentation of a general algorithm to include effect assessment on secondary poisoning in the derivation of environmental quality criteria. Part 1. Aquatic food chains.

Effect assessment on secondary poisoning can be an asset to effect assessments on direct poisoning in setting quality criteria for the environment. This study presents an algorithm for effect assessment on secondary poisoning. The water-fish-fish-eating bird or mammal pathway was analyzed as an example of a secondary poisoning pathway. Parameters used in this algorithm are the bioconcentration factor for fish (BCF) and the no-observed-effect concentration for the group of fish-eating birds and mammals (NOECfish-eater). For the derivation of reliable BCFs preference is given to the use of experimentally derived BCFs over QSAR estimates. NOECs for fish eaters are derived by extrapolating toxicity data on single species. Because data on fish-eating species are seldom available, toxicity data on all birds and mammalian species were used. The proposed algorithm (MAR = NOECfish-eater/BCF) was used to calculate MARS (maximum acceptable risk levels) for the compounds lindane, dieldrin, cadmium, mercury, PCB153, and PCB118. By subsequently, comparing these MARs to MARs derived by effect assessment for aquatic organisms, it was concluded that for methyl mercury and PCB153 secondary poisoning of fish-eating birds and mammals could be a critical pathway. For these compounds, effects on populations of fish-eating birds and mammals can occur at levels in surface water below the MAR calculated for aquatic ecosystems. Secondary poisoning of fish-eating birds and mammals is not likely to occur for cadmium at levels in water below the MAR calculated for aquatic ecosystems.

Algorithms↗
PubMed1994

Presentation of a general algorithm to include effect assessment on secondary poisoning in the derivation of environmental quality criteria. 2. Terrestrial food chains.

In a previous study a simple algorithm was presented for effect assessment on secondary poisoning of birds and mammals. This algorithm (MPC = NOECfish-eater/BCFfish) was drawn up by analyzing a two-step aquatic food chain (water-fish-bird/mammal). The algorithm was used to test whether quality criteria set for surface water, based on effect assessment for aquatic organisms, constitute a "safe" level for secondary poisoning. The present study analyzes whether this algorithm can equally well be used for effect assessment in a terrestrial food chain. The pathway soil-earthworm-bird/mammal was used as an example for a terrestrial food chain. Literature data of six selected compounds (lindane, dieldrin, DDT, PCP, cadmium, and mercury) on both bioconcentration factors for earthworms and toxicity data for birds and mammals were studied. Important differences were found between BCFs for this terrestrial pathway and BCFs for the aquatic pathway analyzed in the previous study. It was found that BCFs for earthworms were more dependent on soil-related properties than on compound-specific properties. Hence, it was concluded that the algorithm MPC = NOECworm-eater/BCFworm can be used only for effect assessment on terrestrial food chain in defined situations. By calculating maximum permissible concentrations for secondary poisoning (MPCsp) for a standard soil situation and comparing these to MPCs for soil organisms, it was concluded that secondary poisoning could be a critical pathway for cadmium and methyl mercury. For methyl mercury secondary poisoning in an aquatic food chain was also a critical pathway. Secondary poisoning of fish-eating birds and mammals is not likely to occur for cadmium at concentrations in water below the MPC calculated for aquatic organisms.

Algorithms↗
PubMed1996

Hierarchical cluster analysis of environmental pollutants through P450 induction in cultured hepatic cells.

Environmental pollutants are classically associated with increased drug metabolism. Cultures of rat hepatocytes, quail hepatocytes, and human hepatoma (Hep G2) cells were used to study the effects of pesticides on drug-metabolizing enzymes. Membrane integrity and mitochondrial activity were evaluated and induction of ethoxycoumarin-O-deethylase and ethoxyresorufin-O-deethylase activities were measured. Induced P450s were identified by immunoblotting. Pentachlorophenol and lindane appeared as the strongest inducers. On the immunoblots, specific antibodies revealed induced CYP1A1 in fetal rat hepatocytes, CYP2B in quail hepatocytes, and CYP3A7 in Hep G2 cells. Pesticide effects on these different activities in each type of cultured cells were compared by cluster analysis. Results obtained under similar conditions with reference inducers phenobarbital (PB) and benzo[a]anthracene and other environmental pollutants (polychlorobiphenyls) were added to previous data prior to multivariate analysis. The tested products fell into four major groups: a first group with pentachlorophenol, identified as a CYP3A inducer; a second group containing the methylcholanthrene-type inducers that increase CYP1A-related activities; a third class represented by dieldrin, a PB-type inducer; a fourth group including inert compounds or weak inducers. Lindane shares the criteria of the second and third groups and seems to induce both CYP1A and CYP2B activities. The current study results highlight the advantage of using several types of cultured hepatocytes to evaluate the short-term toxicity of environmental pollutants in vitro and constitute a useful model for predicting the potential toxicity of pesticides in humans (Hep G2 cells) and wildlife (fetal quail hepatocytes).

7-Alkoxycoumarin O-Dealkylase↗
PubMed1996

Uptake of organochlorine pesticides by solvent-filled cellulose and polyethylene membranes.

Membrane-based passive samplers were used to study the uptake of organochlorine pesticides (lindane, aldrin, dieldrin, and chlorpyriphos) in a continuous-flow system. The membranes were filled with cyclohexane and a mixture of cyclohexane and triolein. Uptake of the chemicals was 24-84 times faster in polyethylene membranes compared to that in cellulose membranes. This is a clear indication that polar cellulose membrane hinders the transport of lipophilic compounds. Though uptake rates in polyethylene membranes were much higher, they were unable to retain the receiving solvent for longer time periods. The diffusion rate of chemicals through polyethylene membranes was dependent not only on their lipophilicity but their molecular mass as well.

Cellulose↗
PubMed2000

Organochlorine pesticides in wolves from Galicia.

Levels of seven organochlorine pesticides (heptachlorepoxide, dieldrin, endrin, p,p'-DDE, o-p'-DDT, p,p'-DDT, and methoxychlor) and DDE/DDT ratios were determined in spleen, liver, muscle, kidney and suprarenal from 12 wolves from three provinces of Galicia (eight male and four female). Analysis was carried out by GC-ECD. Heptachlorepoxide was in found only 25% of samples, while p,p'-DDE was the most dominant of the organochlorine compounds analyzed. DDE/DDT ratios higher than 1 were found in liver and muscle.

Adrenal Glands↗
PubMed2000

Dietary exposures to food contaminants across the United States.

Food consumption is an important route of human exposure to pesticides and industrial pollutants. Average dietary exposures to 37 pollutants were calculated for the whole United States population and for children under age 12 years by combining contaminant data with food consumption data and summing across food types. Pollutant exposures were compared to benchmark concentrations, which are based on standard toxicological references, for cancer and noncancer health effects. Average food ingestion exposures for the whole population exceeded benchmark concentrations for arsenic, chlordane, DDT, dieldrin, dioxins, and polychlorinated biphenyls, when nondetects were assumed to be equal to zero. For each of these pollutants, exposure through fish consumption accounts for a large percentage of food exposures. Exposure data for childhood age groups indicated that benchmark concentrations for the six identified pollutants are exceeded by the time age 12 years is reached. The methods used in this analysis could underestimate risks from childhood exposure, as children have a longer time to develop tumors and they may be more susceptible to carcinogens; therefore, there may be several additional contaminants of concern. In addition, several additional pollutants exceeded benchmark levels when nondetects were assumed to be equal to one half the detection limit. Uncertainties in exposure levels may be large, primarily because of numerous samples with contaminant levels below detection limits.

Adolescent↗
PubMed2000

PCDDs, PCDFs, PCBs, and other organochlorine compounds in human milk from Rio de Janeiro, Brazil.

The levels of polychlorinated dibenzo-p-dioxins (PCDDs) and -furans (PCDFs), polychlorinated biphenyls (PCBs), and other organochlorine compounds were determined in a pooled sample of breast milk from 40 mothers (first lactation: 33; second lactation: 7, age: 15-38 years) living in the urban area of Rio de Janeiro County, Brazil, in 1992. Mothers were breastfeeding only one infant and milk was collected between 4 and 6 weeks after delivery. The results showed a dioxin equivalent concentration of 8.1 pg I-TEq/g milk fat. The levels of other chlorinated compounds (micrograms per gram of milk fat) were as follows: PCBs (total), 0.15; alpha-HCH, 0.001; beta-HCH, 0.27;gamma-HCH, 0.005; HCB, 0.012; DDT (total), 1.7; dieldrin, 0.023, and cis-heptachlor epoxide, 0.008. These results suggest that human background contamination by PCDD/Fs, PCBs, and HCB in Rio de Janeiro is lower than that generally found in industrialized countries.

Adolescent↗
PubMed1998

Diorthosubstituted polychlorinated biphenyls in caudate nucleus in Parkinson's disease.

As it had previously been demonstrated that there were reduced brain dopamine concentrations in monkeys who had been given polychlorinated biphenyls (PCBs) chronically, we hypothesized that organochlorine compounds in general, and PCBs in particular, might be important in the pathogenesis of Parkinson's disease (PD). In a study of caudate nucleus obtained post mortem from patients with Parkinson's disease and from controls, there were significantly higher concentrations of the organochlorine insecticide dieldrin and the PCB congener 153 in the PD tissue. DDE, PCB congener 180, and total PCBs (matched with a commercial preparation) also tended to be higher in Parkinson's disease tissue. We think that this is important preliminary evidence that diorthosubstituted PCBs may contribute to the pathogenesis of Parkinson's disease, and a greater presence of organochlorine insecticides in the PD tissue suggests that this may be in part the explanation for the association between PD and rural living.

Animals↗