Quantification by ELISA of Aldrin/Dieldrin in river Nile water and tap water samples collected in Egypt

An indirect competitive ELISA was developed for the quantitative analysis of aldrin/dieldrin. This has been used to monitor the levels of these pesticides in water samples collected in Egypt. The detection range of the aldrin/dieldrin assay in water was 5–10 ppm without enhancement. River Nile water samples and tap water samples (n = 25) were collected from 25 stations in 16 different governorates in Egypt. Pesticides were detected in 10 of the 25 Nile water samples (40%) at levels from 10 to 110 ppb. In tap water samples, pesticides were not detected at levels greater than the lower limit of the assay. The technique described provides a rapid, economical, highly sensitive and specific method of analysis that is relatively simple to perform and interpret. It will be extremely useful in monitoring levels of pesticides in water used for human consumption.     

Effects of [3H]-BIDN,a novel bicyclic dinitrile radioligand for GABA-gated chloride channels of insects and vertebrates

1. The radiolabelled bicyclic dinitrile, [³H]-3,3-bis-trifluoromethyl-bicyclo[2.2.1]heptane-2,2-dicarbonitrile ([³H]-BIDN), exhibited, specific binding of high affinity to membranes of the southern corn rootworm (Diabrotica undecimpunctata howardi) and other insects. A variety of γ-aminobutyric acid (GABA) receptor convulsants, including the insecticides heptachlor (IC₅₀, 35±3 nM) and dieldrin (IC₅₀, 93±7 nM), displaced [³H]-BIDN from rootworm membranes. When tested at 100 μM, 1-(4-ethynylphenyl)-4-n-propyl-2,6,7-trioxabicyclo[2.2.2]octane(EBOB), 4-t-butyl-2,6,7-trioxa-1-phosphabicyclo[2.2.2]octane-1-thione (TBPS), 1-phenyl-4-t-butyl-2,6,7-trioxabicyclo[2.2.2]octane (TBOB) and picrotoxin failed to displace 50% of [³H]-BIDN binding to rootworm membranes indicating that the bicyclic dinitrile radioligand probes a site distinct from those identified by other convulsant radioligands.
2. Dissociation studies showed that dieldrin, ketoendrin, toxaphene, heptachlor epoxide and α and β endosulphan displace bound [³H]-BIDN from rootworm membranes by a competitive mechanism.
3. Rat brain membranes were also shown to possess a population of saturable, specific [³H]-BIDN binding sites, though of lower affinity than in rootworm and with a different pharmacological profile. Of the insecticidal GABAergic convulsants that displaced [³H]-BIDN from rootworm, cockroach (Periplaneta americana) and rat brain membranes, many were more effective in rootworm.
4. Functional GABA-gated chloride channels of rootworm nervous system and of cockroach nerve and muscle were blocked by BIDN, whereas cockroach neuronal GABA_B receptors were unaffected.
5. Expression in Xenopus oocytes of either rat brain mRNA, or cDNA-derived RNA encoding a GABA receptor subunit (Rdl) that is expressed widely in the nervous system of Drosophila melanogaster resulted in functional, homo-oligomeric GABA receptors that were blocked by BIDN. Thus, BIDN probes a novel site on GABA-gated Cl⁻ channels to which a number of insecticidally-active molecules bind.

     

Aldrin poisoning of Sarus cranes (Grus antigone) and a few granivorous birds in Keoladeo National Park,Bharatpur, India

Between 1987–88 and 1989–90, 18 Sarus cranes (Grus antigone), more than 50 collared doves (Streptopelia decaocto) and a few blue rock pigeons (Columba livia) were found dead during winter in Keoladeo National Park, Bharatpur, which coincided with the application of aldrin in the crop fields around the Park. Brain tissue of Sarus cranes, collared doves and blue rock pigeons contained an average of 19.33 (3.56–43.46), 15.19 (7.40–20.70), and 20.42 (14.61–26.23) ppm, wet weight, of dieldrin, respectively. Dieldrin in other tissues ranged from 0.78 ppm to 92.26 ppm in Sarus cranes, 3.44 ppm to 66.17 ppm in collared doves and 16.92 ppm to 20.99 ppm in blue rock pigeons. Residues of aldrin were as high as 89.75 ppm in the gastrointestinal tract of a Sarus crane and 104.00 ppm in a collared dove. Very high residues of aldrin in the gastrointestinal tract, and dieldrin at much higher quantities in the brain than the lethal level (4–5 ppm) clearly indicate that dieldrin, after being metabolized from aldrin, was responsible for the deaths. A decline in the breeding population of Sarus cranes in Keoladeo National Park has been noticed, and is suspected to be an indication of its general population trend. The Registration Committee under the Indian Insecticide Act of 1968 has decided to include aldrin in the banned list with the ban taking effect from January 1994.     

Effects of Cyclodiene Insecticides on the Sparrowhawk (Accipiter Nisus) in Britain – a Reappraisal of the Evidence

Cyclodiene insecticides were introduced in Britain in the mid-1950s, after which there was a rapid decline of sparrowhawk populations in agricultural areas associated with the lethal toxicity of these compounds. Subsequently the recovery of sparrowhawk populations was studied in different areas of Britain following the ban on dieldrin seed dressings in 1975. Frequency distribution diagrams of dieldrin residues in sparrowhawk livers were constructed for different geographical areas over specified periods. During 1963–1975, biphasic distributions were found, with some 50% of the entire sample contained within a second peak of geometric mean 20 p.p.m. in an eastern area where cylodiene exposure was greatest and populations were most depressed. A similar second peak was found in a sample from another area where the cyclodiene exposure was less, although it only represented 5% of the individuals found dead. These individuals with high dieldrin levels had evidently received lethal doses of insecticide. In a sample from the eastern area taken during 1976–1982, the peak at 20 p.p.m. had virtually disappeared, to be replaced by another peak centred on 4.8 p.p.m. This latter peak may have represented individuals dying as a consequence of sublethal neurotoxic effects. The distribution diagrams for 1983–1986 showed single peaks of dieldrin centring on 0.55–0.75 p.p.m., with no clear evidence of other peaks which might represent poisoned individuals. By this time, the populations in both areas had either fully recovered or were rapidly recovering.     

The action of cyclodiene pesticides on oxidative phosphorylation in rat liver mitochondria.

The effects of a number of chlorinated hydrocarbon pesticides have been studied on isolated rat liver mitochondria. Inhibition of mitochondrial function was found to be dependent upon the ratio of pesticide to protein, and to some extent upon the type of pesticide. Most of the pesticides tested exerted more than one effect depending upon the concentration. At low concentrations (less than 20–25 nmoles/mg protein). State 3 respiration, DNP-activated respiration and valinomycin-induced swelling were inhibited by certain cyclodienes. These results cannot be explained by inhibition of the electron transport chain or uncoupling. They appear to be associated with restrictions of ion movements across the membrane (DNP, valinomycin-K⁺ complex, ADP). On increasing the concentration of pesticide, lysis of the membranes and uncoupling can be induced. The electron transport chain can also be inhibited, but only with 5–10 times greater concentrations of pesticide than required for uncoupling. In general, the cyclodiene pesticides are slightly more effective inhibitors than the non-cyclodienes tested.2 The effectiveness of the cyclodienes is, however, dependent upon its stereochemical properties. These findings suggest that the cyclodienes may inhibit mitochondria in a common, and, perhaps, specific manner. The specificity and mode of action of cyclodienes was found to be similar to that described earlier (B.D. Nelson and C. Williams, Agric. fd Chem.19, 339 (1971)), using growing yeast cells as the test system.     

Organochlorine pesticide residues in commercial infants’ milk formulas on the Kenyan market

Organochlorine contaminants were not detected in any of the 5 commercial infant formulas examined. This is in contrast to the high levels of some organochlorine pesticide residues which have been found in mothers’ milk and some agricultural products in Kenya. Nevertheless, the practice of breast‐feeding is still to be strongly recommended because of its many advantages,     

Detection of aldrin/dieldrin in milk by competitive enzyme‐linked immunosorbent assay (ELISA)

Polyclonal antibodies raised against 6,7‐dihydro‐6‐carboxyaldrin can be used to detect aldrin and dieldrin. These analytes are preferentially fat soluble. An immunoassay is described which provides a method for detecting these pesticides in milk, a fat‐rich matrix. The enzyme‐linked immunosorbent assay (ELISA) can detect aldrin/dieldrin in milk in the range 1 ng ml^‐1‐5 μg ml^‐1 simply and reliably. The detection range differs in skimmed and semi‐skimmed milk and in cream, reflecting the differences in fat content between these samples.     

Numerical simulation of a compartmental system for the distribution of lipid soluble chemicals in mammalian tissues.

An analysis of the stability and accuracy of a particular numerical scheme used in the mathermatical modeling of the flow limit pharmacodynamics of highly lipid soluble drugs in mammalian tissue systems is presented. The necessary definitions and theorems together with their proofs are included. A typical example of the flow limit pharmacodynamics of the highly lipid soluble drug dieldrin (HEOD) is also presented.     

Organochlorines, p53 mutations in relation to breast cancer risk and survival. A Danish cohort-nested case-controls study

Epidemiological studies integrating genetic susceptibility with biological measurements of organochlorine exposure may provide new clues regarding these substances influence on breast cancer etiology. Initial attempts pursuing this avenue has dealt with polymorphisms in the carcinogen-metabolizing enzymes cytochrome P450 (CYPlAl). This study examined if mutations in the tumor suppressor gene p53 affected organochlorine exposure related breast cancer risk and survival. The material consisted of 162 breast cancer cases and 316 matched controls, who had participated, in the Copenhagen City Heart Study (CCHS) between 1976 and 1978. Cases diagnosed between study initiation and 1993 were identified by linkage to the Danish Cancer Registry. The case group served as a cohort in the survival analyses. Information on known and suspected breast cancer risk factors was obtained from CCHS, and the Danish Breast Cancer Cooperative Group provided information on tumor characteristics. Lipid adjusted serum concentrations of selected organochlorines were compared between cases and controls while stratifing by p53 mutation status. A non-significant increased risk of breast cancer was observed in the highest exposure level of dieldrin and polychlorinated biphenyls among women who developed a tumor with mutant p53 (odds ratio (OR)=3.53, 95% confidence interval (CI)=0.79–15.79 and OR=3.00, 95% CI=0.66–13.62). There was no clear difference in overall survival between breast cancer cases with 'wild-type' and mutant p53, although a significant dose-response relationship appeared for dieldrin exposure in tumors with 'wild-type' p53. These preliminary results suggest that p53 mutations may have a modifying effect on at least the breast cancer risk associated with exposures to organochlorines.     

Dieldrin stimulates biliary excretion of 14C-benzo[a]pyrene polar metabolites but does not change the biliary metabolite profile in rainbow trout (Oncorhyncus mykiss).

Activities of hepatic microsomal and cytosolic epoxide hydrolases, accumulation of dieldrin in liver, and in vivo metabolism and disposition of the polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BP), were examined in rainbow trout pretreated with dieldrin, a chlorinated cyclodiene insecticide. Rainbow trout were fed 0.3 mg dieldrin/kg/day for 9 weeks and the same dose of dieldrin for 9 weeks, followed by 3 weeks on control diet (12 weeks). Fish then received an intraperitoneal (ip) challenge dose of 14C-BP (10 micromol/kg). Dieldrin pretreatment significantly elevated the concentration of 14C-BP in bile (142% and 200% at 9 and 12 weeks, respectively), but not liver or fat. Extraction of bile subsamples confirmed dieldrin pretreatment significantly stimulated total biliary excretion of 14C-BP polar metabolites (244% and 221% at week 9 and 12, respectively). The complex metabolism of BP characterized the in vivo state of the CYP system, UDP-glucuronyltransferases, and sulfotransferases. Bile was extracted and then hydrolyzed by beta-glucuronidase and arylsulfatase to regenerate BP metabolites conjugated by phase II enzymes. Evaluation of biliary polar metabolite profiles of 14C-BP revealed no significant differences between control and dieldrin-fed fish. There was no selective enhancement of any particular metabolite, or formation of a novel metabolite with dieldrin pretreatment. This research confirmed that enhanced biliary excretion, following chronic dieldrin exposure, was not explained by induction of xenobiotic metabolizing enzymes. The results are consistent with induction of hepatic intracellular trafficking proteins in dieldrin-fed fish.