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Effect of occupational exposure to aldrin on urinary D-glucaric acid, plasma dieldrin, and lymphocyte sister chromatid exchange.

The effects of exposure to the chlorinated cyclodiene termiticide aldrin was evaluated in pest control workers potentially exposed to this material. Sister chromatid exchange (SCE) frequencies were not elevated in workers handling aldrin. This is consistent with the fact that chlorinated cyclodienes are not genotoxic. Plasma dieldrin concentrations (up to 250 ng/ml) confirmed exposure in workers actively performing termiticide treatments and in maintenance and store workers, when compared with unexposed control workers (median concentration, 4.8 ng/ml). Urinary D-glucaric acid (DGA), an index of hepatic enzyme activity, was elevated in pesticide-exposed groups but urinary DGA was poorly correlated with plasma dieldrin level. This indicates that concurrent exposures of these groups to other pesticides may have influenced mixed-function oxidase metabolic activity.

Adolescent↗

Distribution of HEOD (dieldrin) in mammals: II. some applications of the preliminary model.

The preliminary model of the lipid-phase pharmacokinetics of dieldrin in mammals is applied to evaluation of the probable role of auto-induction, the effect(s) of growth, and the role of compartmentalization. Realistic simulations and comparison to actual data permit the conclusion to be drawn that induction of its own metabolism plays a relatively monor role in the distribution and level of dieldrin residues. Although some of the effects of growth are resonably well simulated, the model as constructed does not permit compartmentalization. It was concluded that the model should be revised to include aspects of the as-yet quantitatively unknown intracellular binding and membrane transport within the flow-limited model.

Adipose Tissue↗

Distribution of HEOD (dieldrin) in mammals: III. Transport--transfer.

A mathematical model simulating the blood transport and tissue residue distributions of the highly toxic and highly lipid soluble pesticide dieldrin in mammals is presented. This model is a significant improvement over our previously published preliminary model for dieldrin distribution in mammals. The assumptions and working hypotheses of the model are presented and used in generating a set of differential equations based upon mass balance principles. Two simulation cases are examined. The first simply demonstrates the gross features of: 1) Transport limiting conditions; 2) equal transport-equal membrane transfer conditions, and 3) membrane transfer limit conditions. The second studies a single tissue (the blood-brain barrier case) example of the above mentioned conditions. All simulations made were conducted for a hypothetical mature male rate of the average Wistar type eating food ad lib.

Animals↗

Avian species differences in the intestinal absorption of xenobiotics (PCB, dieldrin, Hg2+).

Intestinal absorption of a polychlorinated biphenyl, dieldrin, and mercury (from HgCl2) was measured in adult Northern bobwhites, Eastern screech owls, American kestrels, black-crowned night-herons and mallards in vivo by an in situ luminal perfusion technique. bobwhites, screech owls and kestrels absorbed much more of each xenobiotic than black-crowned night-herons and mallards. Mallards absorbed less dieldrin and mercury than black-crowned night-herons. Mercury absorption by kestrels was more than twice that in screech owls and eight times that observed in mallards. Pronounced differences in xenobiotic absorption rates between bobwhites, screech owls and kestrels on the one hand, and black-crowned night-herons and mallards on the other, raise the possibility that absorptive ability may be associated with the phylogenetic classification of birds.

Animals↗

Effect of dieldrin injection on the level of certain amino acids and some enzymes in rat brain.

The present investigation revealed the effect of the organochlorine insecticide dieldrin at the dose level 0.25 LD50 at different time intervals on the concentration of 11 rat brain amino acids, on the activities of glutamic oxyacetic transaminase (GOT), glutamic pyruvic transaminase (GpT) and cholinesterase. The study was also extended to include the total protein content during the tested periods. The daily injection of dieldrin caused a marked decrease in the levels of glutamic acid, glutamine and taurine and an increase in the levels of aspartic acid, asparagine, GABA, glycine, lysine, serine, alanine and histidine. However, the maximal increase and decrease were recorded for most of the tested amino acids at the end of the tested period. The activity of the transaminases increased significantly. The recorded values of GOT were usually higher than GPT. Cholinesterase activity was inhibited thoroughly during all the experimental periods. Total protein content was decreased in the experiment; the minimal value was given 3 days after the injection.

Alanine Transaminase↗

Dieldrin transformation to photodieldrin in liver and kidney of broiler.

Dieldrin, a potent residual insecticide and common contaminant of the environment, is metabolized in liver and kidney of broiler to photodieldrin, a photoisomer of dieldrin. This metabolite has by gas-liquid chromatography (g.l.c.) analysis a retention time different to the aldrin. The analysis by thin-layer chromatography (t.l.c.) of metabolite shows an Rf of 0.37. The i.r. (infra-red) spectrum shows the band corresponding to the epoxide ring (800-1300 cm-1) and does not show the characteristics bands of C = O (1800 cm-1) and ClC = CCl (1600 cm-1).

Animals↗

Dieldrin modifies the hydrolysis of PIP2 and decreases the fertilization rate in Bufo arenarum oocytes.

Carbachol treatment in Bufo arenarum oocytes decreases the radioactivity in [32P]PIP2 in the following 20 min after stimulation and increases the [3H]glycerol labeling of 1,2-DAG at 1 min of stimulation. On the contrary, in Dieldrin treated oocytes carbachol stimulation produces an increase in [32P]PIP2 labeling without changes in [3H]1,2-DAG radioactivity. The sustained hydrolysis of PIP2 observed in Control oocytes is necessary to generate the intracellular second messengers which initiate the fertilization pathway. The lack of response to muscarinic stimulation in Dieldrin treated oocytes, may be associated with an early activation of PIP2-PLC by the insecticide, producing a depletion of the PIP2 pool previous to the stimulation with carbachol. These changes take place simultaneously with a decrease in the ability of Bufo arenarum oocytes to be fertilized in vitro, suggesting a correlation between impairment in the PIP2 cascade and a decrease in the fertilization rate.

1-Phosphatidylinositol 4-Kinase↗

Effects of methoxychlor, dieldrin and lindane on sea urchin fertilization and early development.

We have studied the effects of methoxychlor (MXC), dieldrin, and lindane on fertilization and early development of sea urchin egg. These organochlorine pesticides have often been found in polluted ground and water near agricultural sites, and have therefore been detected from time to time in the food chain and in drinking water. They have been reported to alter various reproduction functions in various animals including marine populations. We observed that the rate of fertilization decreased when the sperm was incubated with dieldrin or lindane. Treatment of eggs with each pesticide did not prevent fertilization, but increased the rate in polyspermy, delayed or blocked the first mitotic divisions, and altered early embryonic development. Moreover, all pesticides could alter several intracellular biochemical pathways that control first mitotic divisions and early development, including intracellular calcium homeostasis, MPF (mitosis promoting factor) activity and formation of the bipolar mitotic spindle. We found that lindane was the most potent of the three pesticides to alter all biochemical events. All these effects were observed at relatively high concentrations. However, bio-accumulation in sediments and aquatic organisms have been reported. Sea urchin eggs may then be in contact with very high concentrations of these pesticides in areas where these pesticides are not handled or stocked properly, and then develop into abnormal embryos.

Animals↗

The organochlorine pesticides gamma-hexachlorocyclohexane (lindane), alpha-endosulfan and dieldrin differentially interact with GABA(A) and glycine-gated chloride channels in primary cultures of cerebellar granule cells.

The neurotoxic organochlorine pesticides gamma-hexachlorocyclohexane, alpha-endosulfan and dieldrin induce in mammals a hyperexcitability syndrome accompanied by convulsions. They reduce the GABA-induced Cl(-) flux. The strychnine-sensitive glycine receptor also regulates Cl(-)-flux inhibitory responses. We studied the effects of these compounds on Cl(-) channels associated with glycine receptors in cultured cerebellar granule cells in comparison to the GABA(A) receptor. Both GABA (EC(50): 5 microM) and glycine (EC(50): 68 microM) increased (36)Cl(-) influx. This increase was antagonized by bicuculline and strychnine, respectively. Lindane inhibited with similar potency both GABA(A) (IC(50): 6.1 microM) and glycine (5.0 microM) receptors. alpha-Endosulfan and dieldrin inhibited the GABA(A) receptor (IC(50) values: 0.4 microM and 0.2 microM, respectively) more potently than the glycine receptor (IC(50) values: 3.5 microM and 3 microM, respectively). Picrotoxinin also inhibited the glycine receptor, although with low potency (IC(50)>100 microM). A 3D pharmacophore model, consisting of five hydrophobic regions and one hydrogen bond acceptor site in a specific three-dimensional arrangement, was developed for these compounds by computational modelling. We propose that the hydrogen bond acceptor moiety and the hydrophobic region were responsible for the affinity of these compounds at the GABA(A) receptor whereas only the hydrophobic region of the molecules was responsible for their interaction with the glycine receptors. In summary, these compounds could produce neuronal hyperexcitability by blocking glycine receptors besides the GABA(A) receptor. We propose that two zones of the polychlorocycloalkane pesticide molecules (a lipophilic zone and a polar zone) differentially contribute to their binding to GABA(A) and glycine receptors.

Animals↗

Cross-resistance with dieldrin of a novel tricyclic dinitrile GABA receptor antagonist.

A novel tricyclic dinitrile, KN244, blocked the wild-type (dieldrin-sensitive) homo-oligomeric gamma-aminobutyric acid (GABA)-gated chloride channel of Drosophila melanogaster expressed in Xenopus oocytes. Sensitivity to the block by KN244 of the response to 30 microM GABA (IC50=41.6 nM, wild-type RDLac) was reduced abut 100 fold (IC50=4.5 microM) in the dieldrin-resistant (RDLacA302S) form of RDL.

Animals↗

Polluting profiles of dieldrin and DDTs in laying hens of Osaka, Japan.

Contaminating/accumulating levels of organochlorine pesticides in extractable fats from a basal diet, eggs and seven tissues (adipose tissue, blood, kidney, liver, muscle, ovary and oviduct) and excreta of laying hens that were kept in a general poultry farm of Japan were examined. No benzene hexachlorides or aldrin was detected [< 1 part per billion (p.p.b.)] overall. Dieldrin and all DDTs (p,p'-DDE, o,p'-DDT, p,p'-DDD and p,p'-DDT) were contaminated in the dietary fats (mean range 10-70 p.p.b.). Although dieldrin (4-58 p.p.b.), p,p'-DDE (65-196 p.p.b.) and p,p'-DDT (30-73 p.p.b.) were found to be accumulated in all the tissue fats and egg yolk fats, they were not detected in the dried excreta. Accumulations of o,p'-DDT and p,p'-DDD were found only in the liver fat (92 p.p.b.) and in the kidney fat (27 p.p.b.), respectively. In all the samples, p,p'-DDE levels were highest in comparison with the other compounds. For all organochlorine pesticides detected, the accumulated levels were well below the practical residue limits.

Adipose Tissue↗

Relation between smoking and levels of DDT and dieldrin in human fat.

The adipose tissue of humans with known patterns of cigarette smoking was collected during 1973-74 and analyzed for DDT components and dieldrin. Although smokers are exposed to high levels of insecticides from smoke of cigarettes and some of these compounds can be stored in adipose tissue, it could not be demonstrated that a relationship exists between smoking habit and residual levels of DDT found in fat. Smokers seem able, through induction of enzymes by substances in tobacco smoke, to metabolize these insecticides at a rate approximately equal to the rate of their intake in the smoke. Dieldrin residues in black male subjects were found to be linearly related to the number of cigarettes smoked, but the factors governing this relationship were not obvious.

Adipose Tissue↗

Removal of aldrin, dieldrin, heptachlor, and heptachlor epoxide using activated carbon and/or Pseudomonas fluorescens free cell cultures.

Degradation of aldrin (1,2,3,4,10,10-Hexachloro-1,4,4a,5,8,8a-hexahydro-1,4:5-8-dimethanonaphthalene), heptachlor (1H-1,4,5,6,7,8,8-heptachloro-3a,4,7,7a-tetrahydro-4,7-methano indene), dieldrin (1aalpha,2beta,2aalpha,3beta,6beta,6aalpha,7beta,7aalpha)-3,4,5,6,9,9-Hexachloro-1a,2,2a,3,6,6a,7,7a-octahydro-2,7:3,6-d-methanonaphtha[2,3-b]oxirene, and heptachlor epoxide (1aalpha, 1bbeta,2alpha,5alpha,5alphabeta,6beta,6aalpha-2,3,4,5,6,7,7-Heptachloro-1a,1b,5,5a,6,6a-hexahydro-2,5-methano-2H-inden[1,2-b]-oxirene) was tested using free cultures of Pseudomonas fluorescens under controlled conditions. Pesticide concentrations were monitored by gas chromatography during 120 h. Percentages of degradation and biodegradation rates (BDR) were calculated. Data showed a trend suggesting a relation between chemical structure and degradability. Degradation kinetics for each pesticide tested showed that the highest degradation rates were found in the first 24 h. Kinetics data were adjusted to an empirical equation in order to predict their behavior, and the correlation coefficients obtained were satisfactory. Gas chromatography/mass spectrometry (GC/MS) analysis of the final extracts allowed the identification of chlordene and monodechlorodieldrin, which have been reported as final metabolite produced in the biodegradation of this kind of compounds. Regarding adsorption of pesticides on activated vegetal carbon, we concluded that removal efficiencies between 95.45 and 97.18% can be reached, depending on the pesticide and the carbon dose applied. The values for K from the Freundlich equation were quite similar for the four pesticides (between 1.0001 and 1.04), whereas the n values were quite different for each pesticide in the following order of affinity: dieldrin > aldrin > heptachlor epoxide > heptachlor. Equilibrium times, very important for scaling up the process, were between 43 min and 1 h, for the heptachlor epoxide and the heptachlor, respectively.

Adsorption↗

Reductive degradation of dieldrin and endrin in the field using acidified zinc.

The reductive dechlorination of dieldrin and endrin was investigated as a possible procedure for field disposal of small quantitites of these pesticides. The objective was to convert the parent compounds to environmentally less objectionable materials. Emulsifiable concentrate formulations of the pesticides in a soil slurry were mixed with powdered zinc, dilute acetic acid, and acetone to facilitate reaction. Analysis of the mixtures by GC-MS indicated essentially complete conversion of endrin and partial conversion of dieldrin to products probably formed by replacement of the bridge anti chlorines with hydrogen. Partial confirmation of the desired anti dechlorodieldrin product was made by nmr. Disappearance of the parent compounds and production of conversion products was monitored for 2 1/2 years by GC in an outside soil plot, and accelerated destruction of parent compounds was achieved by the treatment. By analogy to the bridge anti dechloro products of aldrin and isodrin, the anti dechloro products probably are much less toxic than the parent compounds and are therefore environmentally less objectionable.

Dieldrin↗

Dieldrin, heptachlor, and chlordane residues in soybeans in Illinois 1974, 1980.

The Illinois soybean crop was monitored in 1974 and 1980 for dieldrin, heptachlor, and chlordane residues resulting from the use of these compounds for corn soil insect control in the years before extensive soybean cultivation. Residue levels were compared with past published amounts. Dieldrin residue levels in soybeans declined between 1974 and 1980. Heptachlor and heptachlor epoxide levels remained level between 1974 and 1980. Chlorinated hydrocarbon residues were lower in the southern third of Illinois than for the remainder of the state.

Chlordan↗

Selection of dieldrin-resistant strains of Lucilia cuprina (Diptera: Calliphoridae) after ethyl methanesulfonate mutagenesis of a susceptible strain.

After ethyl methanesulfonate (EMS) mutagenesis of a susceptible strain (SWT), selective screening of Lucilia cuprina (Wiedemann) resulted in four strains that were resistant to the insecticide dieldrin. Concentrations used for selection were greater than LC99 of susceptible phenotypes. No resistant variants were screened from the standard laboratory strain (SWT) not treated with EMS. The resistance phenotypes of the four resistant strains were similar to each other and to that of a field-selected resistant strain. The genetic basis of resistance is monogenic in all strains and the data are consistent with the same locus, Rdl, determining resistance status in each strain. The Rdl locus maps to chromosome V, approximately 3.5 map units distal to the Sut locus. Dieldrin resistance may be caused by less effective blocking of insect neuronal GABA receptors by the chemical in resistant strains. The data indicate that the evolution of resistance to an insecticide in the field may be constrained by a limited number of genetical and biochemical options if a monogenic response is selected for and that the spontaneous mutation rate to the Rdl allele is less than 1 in 10(6) in the laboratory.

Animals↗

Dieldrin-induced chromosome damage in mouse bone-marrow and WI-38 human lung cells.

Several concentrations of the insecticide dieldrin were tested on in vivo bone marrow cells of STS mice and in vitro human embryonic lung cells of the WI-38 cell line. The insecticide caused pronounced mitotic inhibition and produced a 2 to 3-fold increase in chromosome abnormalities such as breaks and fragments in concentrations as low as 1 mg/kg in STS mice bone marrow cells, and 1 mug/ml in human WI-38 cells. The chemical also produced chromosome interchanges and rings. A few cells from the control groups exhibited breaks and fragments but not exchange figures and rings. Cytotoxic studies using the WI-38 cell line revealed dose-response and time-response reactions to dieldrin. Cell toxicity was most pronounced at the 50 mug/ml treatment level, producing 100 percent cell degeneration within 6 hours.

Animals↗

Epoxidation of aldrin to exo-dieldrin by soil bacteria.

Twenty-two strains of soil bacteria, including representatives of the genera Bacillus, Micromonospora, Mycobacterium, Nocardia, Streptomyces, Thermoactinomyces, and Pseudomonas and 10 unidentified gram-negative, motile, rod-shaped bacteria, were shown to degrade aldrin to its epoxide dieldrin. In every case, the exo-stereoisomer of dieldrin was produced exclusively.

Aldrin↗