[Insecticides in metabolism. XI. Excretion, distribution and changes of aldrin-C14 and dieldrin-C14 in the rat].
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Adipose Tissue↗
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[Insecticides in metabolism. XII. Isolation and identification of metabolites of aldrin-C 14 from the urine of rabbits].
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Animals↗
Comparative effects of structurally related cyclodiene pesticides on ATPases.
Comparative effects of aldrin, dieldrin, endrin, isodrin and telodrin, on different ATPase activities in beef heart mitochondrial and rat brain synaptosomal fractions were determined in vitro. Beef heart mitochondrial fractions were prepared by the conventional centrifugation method and the rat brain synaptosomes were prepared by Ficoll-sucrose gradient centrifugation method. Na+-K+-ATPase, oligomycin-sensitive and -insensitive Mg2+-ATPases, and K+-paranitrophenylphosphatase were determined in rat brain synaptosomes. In beef heart mitochondria, only the Mg2+-ATPase activities were determined. Concentration response curves were determined by assaying the enzyme activities in the absence and presence of 10-120 microM concentrations of each test chemical. Beef heart mitochondrial (oligomycin-sensitive) Mg2+-ATPase activity was inhibited by all five chemicals at all the concentrations tested. Aldrin and telodrin were the most potent inhibitors with an IC50 of 40 and 80 microM, respectively. About 30% was observed with dieldrin, endrin and isodrin, and the inhibition was not concentration-dependent. Oligomycin-insensitive Mg2+-ATPase was not significantly inhibited by any chemical except aldrin. Rat brain synaptosomal ATPases were also sensitive to these compounds. Aldrin and telodrin were more effective than other compounds. A 50% inhibition of oligomycin-sensitive Mg2+-ATPase activity was obtained at 80 microM of aldrin and telodrin. Na+-K+-ATPase and oligomycin-insensitive Mg2+-ATPase activities showed a maximum inhibition of 40% at the highest concentration tested for aldrin and telodrin. K+-paranitrophenylphosphatase was not inhibited significantly by any compound tested. These results suggest that ATPase system in rat heart and CNS may be selectively inhibited by aldrin and telodrin, but not by their structural analogs.
Adenosine Triphosphatases↗
The dechlorination of cyclodiene pesticides by methanogenic granular sludge.
Cyclodiene pesticides: aldrin, isodrin, dieldrin and endrin were dechlorinated by methanogenic granular sludge in spiked batch tests. Initial pesticides concentration was 7 or 9 mgl(-1). Two monodechlorinated analogues were formed during the conversions of aldrin and isodrin. Dieldrin was transformed into two monodechlorinated products as well as into aldrin and two monodechlorinated derivatives of aldrin. In respect of endrin three monodechlorinated and three didechlorinated products were found. The dechlorination of endrin was the most rapid, and was almost complete within 28 days. The dechlorinations of aldrin, isodrin and dieldrin were much slower: over a period of 3 months only 59%, 70% and 88% was transformed, respectively. The amounts of released chloride corresponded 0.54 +/- 0.23, 1.05 +/- 0.25, 1.10 +/- 0.12 of theoretical value for suggested reactions, for aldrin, isodrin and dieldrin respectively. For endrin it was much higher. These transformations did not occur in control samples containing autoclaved granules or in control blank samples without sludge. However, in aldrin spiked blanks, a conversion into a six-chlorinated analogue was found.
Anaerobiosis↗
Impact of some chlorinated pesticides on the haematology of the fish Cyprinus carpio and Puntius ticto.
The effects of pesticides on blood characteristics and histological changes in erythrocytes of the fish species Cyprinus carpio and Puntius ticto were studied. The fishes were exposed to sub lethal concentrations of different chlorinated pesticides namely aldrin, dieldrin, DDT, BHC and chlordane for 10, 20 and 30 d in continuous flow-through test. The LC50 values were calculated based on acute toxicity tests and the sublethal doses were arrived at for chronic bioassay studies. Results showed an increase in haemoglobin content of both Cyprinus carpio and Puntius ticto in case of aldrin and dieldrin. Haemoglobin content reduced from an initial 13 g/100 ml to 8.07 and 10.15 g/100 ml in case of Cyprinus at the end of ten days exposure to aldrin and dieldrin respectively, and gradually increased to 8.7 g/100 ml and 10.15 g/100 ml after 20 d of exposure. The haemoglobin content after 30 d exposure to aldrin and dieldrin was 10.15 g/100 ml and 11.6 g/100 ml respectively. In case of Puntius ticto, the haemoglobin content in control fishes recorded was 12.8 g/100 ml while in case of fish exposed to aldrin, the haemoglobin content reduced initially on ten days exposure to 10.15 g/100 ml and increased to 11.6 g/100 ml and 13.0 g/100 ml during twenty days and thirty days exposure respectively. This trend was also observed with dieldrin in both the fishes studied. Red blood cells were also counted in case of all the pesticides and exposure periods with respect to Cyprinus carpio and Puntius ticto. Irrespective of the species and pesticide, the RBC counts uniformly showed decreasing trend with the increase in exposure period, while packed cell volume, PCV(%) showed increasing trend with respect to increase in exposure period in case of aldrin and dieldrin in both the fishes. But DDT, BHC and chlordane showed decreasing trend in PCV(%) values with increasing periods of exposure.
Animals↗
Determination of oxidative metabolism in Collembolan Proisotoma minuta (Tullberg).
An oxidative metabolism of Collembolan Proisotoma minuta was determined with a model compound of aldrin and dieldrin in this paper. The seven-day LD(50) values for aldrin, dieldrin, and piperonyl butoxide in salt solution were 0.496, 0.367, and 8.346 mg L(-1), respectively. When P. minuta were exposed to aldrin, dieldrin was the sole metabolite. The conversion of aldrin to dieldrin was known to be catalyzed by P450 monooxygenases system. It has been shown that the synergist piperonyl butoxide inhibited the metabolism of aldrin in P. minuta.
Aldrin↗
Interspecies differences in mixed function oxidase activity in birds: Relationship between feeding habits, detoxication activities and organochlorine accumulation.
The relationship between feeding habits and interspecies differences in the detoxication ability of the mixed function oxidase (MFO) system was investigated in birds. The role of MFO (particularly aldrin epoxidase activity) in the detoxication/bioaccumulation of organochlorines was also investigated. Euriphagic (yellow-legged herring gull (Larus cachinnans), black-headed gull (Larus ridibundus), jackdaw (Corvus monedula), magpie (Pica pica) and stenophagic (cormorant (Phalacrocorax carbo), coot (Fulica atra) and sparrow (Passer italiae)) species were collected in northern and central Italy. The following liver microsomal monooxygenase activities were measured: aldrin epoxidase, ethoxyresorufin dealkylation (EROD), benzyloxyresorufin dealkylation (BROD) and pentoxyresorufin dealkylation (PROD). NADPH-and NADH-cytochrome c reductase (NAD(P)H-CYT-CRED) and NADH-ferricyanide reductase (NADH-FERRIRED) activities were also measured in the liver microsomal fraction. Glutathione concentration (GSH) was measured in the liver cytosolic fraction. As a marker of liver damage gamma-glutamyl transpeptidase (GGTP) activity was assayed in the serum. The residues of organochlorines (HCB, pp'DDTs and PCBs) were determined in muscle samples. Omnivorous species, particularly the yellow-legged herring gull, had the highest aldrin epoxidase activities. In the yellow-legged herring gull the activity was approximately twice as high as in the jackdaw (p < 0.05), black-headed gull (p < 0.05) and coot (p < 0.05). Values five times lower were detected in the specialist fish-eater, the cormorant (p < 0.001). The lowest values of aldrin epoxidase activity were detected in the sparrow. Feeding habits were found to be related to evolutionary interspecies differences in MFO activity. A significant statistical correlation (r = 0.656) was found between the 'omnivore index' and MFO detoxication activity expressed as aldrin epoxidation. Organochlorines, and particularly PCBs, were higher in cormorants and yellow-legged herring gulls from a polluted lagoon than in the other species analysed (black-headed gull p < 0.01; sparrow p < 0.001; jackdaw p < 0.01; coot p < 0.001). Levels of pp'DDE were much higher in the cormorant and sparrow than in the other birds. Knowledge of the different species-specific detoxication abilities was found to be a useful tool for the identification of species potentially at risk in environments with high pollution by chlorinated hydrocarbons, or in general contaminants metabolized by the MFO system.
Journal Article↗
Isolation of four aquatic streptomycetes strains capable of growth on organochlorine pesticides.
Ninety-three wild-type isolates identified as actinomycetes were tested against 11 organochlorine pesticides (OPs): aldrin, chlordane, DDD, DDE, DDT, dieldrin, heptachlor, and heptachlor epoxides, lindane, and methoxychlor. Qualitative screening agar assays displayed 62-78% tolerance of strains to OPs. Four strains designed M4, M7, M9 and M15 were selected based on multi-OP-tolerance, and identified as members of the streptomycetes group. Different growth profiles were observed in cultures of the four selected streptomycetes cultured in synthetic medium containing 5-50 microg x l(-1) aldrin or chlordane or lindane. Increase of aldrin removal by the selected microorganisms was concomitant with the 4.8-36.0 microg x l(-1) pesticide concentration range. After 72 h of streptomycete M7 growth in synthetic medium containing 48.0 microg x l(-1) aldrin, the remaining OP concentration in the supernatant was approximately 10% of the initial concentration. Also, in stationary growth phase less than 2.5 microg x l(-1) aldrin residual concentration was detected in the medium.
Biodegradation, Environmental↗
A study of building structural features associated with high indoor air concentrations of organochlorine termiticides.
As part of a two-year study of post-treatment residential exposure to the termiticide, aldrin, the building structural features of ten houses with crawl-space-type floors were assessed by an independent inspector. Building attributes recorded on a checklist included the age of the dwelling, room characteristics, floor details and the nature of subfloor ventilation. At the end of each inspection, the inspector, who was blinded to data on airborne aldrin concentrations, provided a rating of expected indoor air contamination. Several of the building attributes, including the age of the house, the area of exterior subfloor vents, as well as the inspector's rating, were significantly correlated with airborne aldrin values. No single building variable, however, was highly correlated with every measure of aldrin concentration over a 12-month period. The observed data are consistent with poor subfloor ventilation and a 'leaky' floor being important contributors to indoor air pollution. It is recommended that pest control companies advise householders about any obvious floor and ventilation deficiencies before soil treatment work is undertaken. Pesticide exposure (by analogy with geological radon exposure) may be reduced by sealing gaps in floors and/or by improving subfloor ventilation.
Air Pollution, Indoor↗
Microwave-assisted extraction and mild saponification for determination of organochlorine pesticides in oyster samples.
A sample-preparation procedure (extraction and saponification) using microwave energy is proposed for determination of organochlorine pesticides in oyster samples. A Plackett-Burman factorial design has been used to optimize the microwave-assisted extraction and mild saponification on a freeze dried sample spiked with a mixture of aldrin, endrin, dieldrin, heptachlor, heptachorepoxide, isodrin, transnonachlor, p, p'-DDE, and p, p'-DDD. Six variables: solvent volume, extraction time, extraction temperature, amount of acetone (%) in the extractant solvent, amount of sample, and volume of NaOH solution were considered in the optimization process. The results show that the amount of sample is statistically significant for dieldrin, aldrin, p, p'-DDE, heptachlor, and transnonachlor and solvent volume for dieldrin, aldrin, and p, p'-DDE. The volume of NaOH solution is statistically significant for aldrin and p, p'-DDE only. Extraction temperature and extraction time seem to be the main factors determining the efficiency of extraction process for isodrin and p, p'-DDE, respectively. The optimized procedure was compared with conventional Soxhlet extraction.
Animals↗
Phase I and phase II xenobiotic biotransformation in cultures and co-cultures of adult rat hepatocytes.
The aim of this study was to measure the activity of phase I and II key enzymes in the biotransformation of xenobiotics and their inducibility by phenobarbital (2 mM) in two currently used in vitro models, namely adult rat hepatocytes, conventionally cultured or co-cultured with rat epithelial cells derived from primitive biliary duct cells. For phase I, the cytochrome P450 content and the enzymic activities of 7-ethoxycoumarin O-deethylase and aldrin epoxidase have been determined, for phase II glutathione S-transferase activity was measured. In conventional cultures, all phase I parameters investigated declined continuously as a function of culture time. Two mM phenobarbital had inducing effects on 7-ethoxycoumarin O-deethylase and glutathione S-transferases but not on aldrin epoxidase. In co-cultures, after an initial decrease, a steady state situation developed for all the parameters measured, lasting for at least 10 days. The cytochrome P450 content, the 7-ethoxycoumarin O-deethylase, aldrin epoxidase and glutathione S-transferase activities were maintained from 3 to 4 days on at 25, 100, 15 and 50%, respectively, of their corresponding value obtained for freshly isolated hepatocytes. After phenobarbital treatment, the parameters mentioned were significantly increased with the exception of the aldrin epoxidase activity of which the inducibility was nearly completely lost.
7-Alkoxycoumarin O-Dealkylase↗
Increasing serum levels of non-DDT-derivative organochlorine pesticides in the younger population of the Canary Islands (Spain).
Organochlorine pesticides are a lipophilic class of chemicals that persist in the environment and tend to accumulate in human tissues for years. They came into widespread use in the late 1940s. Because of their capacity to bioaccumulate and biomagnify in food chains and their toxic effects, most of them were banned in industrialized countries, among them Spain, in the late 1970s and 1980s. In 1998 organochlorine pesticides were determined in a representative sample of a Spanish population (around 690 serum samples from people 6 to 75years old from the Canary Islands). Serum levels of lindane aldrin, dieldrin and endrin, were determined. Our results showed that a high percentage of samples presented detectable levels of some of the organochlorines measured, endrin being the most frequently detected (72%) and at highest concentration (mean 136.7ng/g fat). Mean concentrations of the main cyclodiene evaluated, dieldrin, was lower to those found in other Western populations. However, serum levels of lindane were higher than those described in North European populations. Influence of geographical and sociodemographic factors was evaluated. Urban populations showed the highest levels of dieldrin, while non-urban population showed the highest serum values of lindane, aldrin and endrin. Unexpectedly, serum values of lindane, aldrin and dieldrin were higher in younger than in older people. Subjects under 18years showed almost twice as high serum levels of lindane, aldrin and dieldrin than subjects of 65-75years. These results may well suggest that people living in the Canary Islands have been and are currently exposed to non-DDT-organochlorine pesticides. The type and source of exposure could vary between islands and type of habitat. Contaminated food and/or the environment could be related with this situation.
Adolescent↗
Breast cancer risk and the combined effect of environmental estrogens.
OBJECTIVE: The present study aimed to determine whether the combined effects of environmental estrogens measured as the total effective xenoestrogen burden (TEXB-alpha) are a risk factor for breast cancer over and above the risk potentially linked to specific pesticides. METHODS: We measured the levels of 16 organochlorine pesticides as well as TEXB in adipose tissue of 198 women at the time of breast cancer diagnosis. These were compared with findings in 260 age and hospital matched control women without breast cancer. RESULTS: The median levels of p,p'-DDE (1,1-dichloro-2,2-bis( p -chlorophenyl)ethylene), aldrin, endosulfan ether and lindane (the pesticides detected in > 40% of the study population) were higher in cases than controls, although the differences did not reach statistical significance. After adjusting for potential confounders, the odds ratio (OR) for breast cancer in women with detectable levels of aldrin was 1.55 (95% confidence interval (CI) 1.00-2.40). Among the postmenopausal women, the OR for aldrin and lindane was 1.84 (95% CI 1.06-3.18) and 1.76 (95% CI 1.04-2.98), respectively. Among cases with body mass index (BMI) below the median (28.6 kg/m2), the OR was 3.42 (95% CI 1.22-9.58) for women in the highest quartile of TEXB-alpha versus those in the lowest. The subgroup of leaner postmenopausal women showed an increased risk (OR: 5.67; 95% CI 1.59-20.21) for those in the highest tertile versus those in the lowest. CONCLUSIONS: We found an increased risk for breast cancer in the leaner women, especially in the leaner postmenopausal subgroup, related to the TEXB-alpha. The pesticides aldrin and lindane are also individually associated with risk.
Adipose Tissue↗
Occupational exposure to organochlorine insecticides and cancer incidence in the Agricultural Health Study.
Organochlorine (OC) insecticides have been regulated as possible human carcinogens primarily on the basis of animal studies. However, the epidemiologic evidence is inconsistent. We investigated the relationship between cancer incidence and OC insecticide use among pesticide applicators enrolled in the Agricultural Health Study, a prospective cohort study of 57,311 licensed applicators in Iowa and North Carolina enrolled between 1993 and 1997. Information on ever use of 7 OC insecticides (aldrin, chlordane, DDT, dieldrin, heptachlor, lindane, toxaphene) was collected from a self-administered questionnaire at enrollment. Lifetime exposure-days to OC insecticides were calculated using additional data from a take-home questionnaire completed by 25,291 participants (44% of total). We found no clear evidence of an association between use of OC insecticides and incident cancers (N = 1,150) ascertained through December, 2002. When we focused on individual insecticides and structurally similar groups (aldrin and dieldrin; chlordane and heptachlor), significantly increased relative risks of some cancers were observed for use of some chemicals (rectal cancer and chlordane, lung cancer and dieldrin, non-Hodgkin lymphoma (NHL) and lindane, melanoma and toxaphene, leukemia and chlordane/heptachlor). Some significant decreased relative risks were also observed (colon cancer and aldrin; overall cancer and heptachlor). In conclusion, we did not observe any clear relationship between cancer risk and the use of OC insecticides. Our chemical-specific findings are based on small numbers and multiple comparisons, and should be interpreted with caution; however, some observed associations (lindane and NHL, chlordane/heptachlor and leukemia) are supported by previous evidence.
Adult↗
Hepatic vein thrombosis in mice ingesting chlorinated hydrocarbons.
Hepatic vein thrombosis, as well as hepatocellular carcinomas, was induced in inbred C3H male and female mice ingesting 10 ppm of dieldrin, aldrin, heptachlor, or heptachlor epoxide in the diet. Thrombosis was present in 5% of mice ingesting dieldrin or aldrin and in 10.5% of mice ingesting heptachlor or heptachlor epoxide. Occlusion of the hepatic vein often resulted in infarcts of the liver. Females ingesting heptachlor or heptachlor epoxide were slightly more susceptible than males. There was no difference between male and female mice ingesting dieldrin or aldrin. Hepatic vein thrombosis did not appear to be related to the development of carcinoma of the liver because it was present in livers without carcinomas as well. Thrombosis was usually seen only in the liver but also rarely was present in the atria of the heart.
Aldrin↗
Endogenous and exogenous factors modifying the activity of human liver cytochrome P-450 enzymes.
Cytochrome P-450 dependent monooxygenases play a dual role for xenobiotic metabolism. On one hand they initiate the primary rate limiting step for the elimination of a bulk of drugs and organic chemicals. On the other hand they catalyze the formation of toxic metabolites from chemical carcinogens and many other toxic chemicals. Numerous studies have shown that their activity in animals is subject to the influence of various modifying factors, such as strain, species, sex, age, diurnal rhythm and the effect of enzyme inducers. Less is known about the influence of these factors on human cytochrome P-450 enzymes. Here we report the results of an extended study on human liver cytochrome P-450 performed with liver biopsies of 178 individuals taken for diagnostic purposes. The enzymatic activity was determined by the aldrin epoxidase assay indicating a variety of enzymes inducible by phenobarbital and by glucocorticoid and androgenic hormones. The frequency histogram of individual aldrin epoxidase activities showed a unimodal distribution and a variation factor of 100 between maximal and minimal activity. Individuals with severe liver diseases, such as cirrhosis and fatty liver, exhibited a 50% loss of enzyme activity. Age and sex did not significantly influence the enzyme activity. No significant correlation was observable between the rate of aldrin epoxidation and debrisoquine 4-hydroxylation, a prototype of a genetically controlled cytochrome P-450 reaction. We assume that the broad interindividual variation of epoxidase activities is more likely due to the influence of exogenous and endogenous inducers rather than to a genetic polymorphism.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Substrate specificity of the mouse skin mixed-function oxidase system.
The metabolism of nine model substrates for the mixed-function oxidase system was studied in skin and liver microsomes from Balb/C mice. Rates of skin metabolism per mg microsomal protein ranged from 0.5-15% of liver rates depending on the substrate. Relative to liver, mouse skin preferentially metabolized ethoxyresorufin, benzo[alpha]pyrene and diphenyloxazole over aldrin, coumarin and the C1-C4 7-alkyl umbelliferone ethers. NADPH-cytochrome P-450-dependent metabolism of aldrin and ethoxyresorufin was differentially inhibited in skin microsomes by metyrapone and alpha-naphthoflavone, respectively. Biphasic Eadie-Hofstee plots were obtained in both skin and liver microsomes for the metabolism of aldrin, whereas metabolism of ethoxyresorufin in both systems was described by linear kinetics. It is concluded that mouse skin contains multiple forms of cytochrome P-450, and that forms functionally analogous to those induced by polycyclic hydrocarbons in rodent liver are present in untreated mouse skin.
Aldrin↗
Simple sensitive technique for detecting organochlorine pesticides on thin layer chromatograms.
Chlorinated hydrocarbon pesticides can be quickly detected using commercially available thin layer chromatographic plates dipped in an acetone solution of silver nitrate. The limits of detection are functions of the pesticide, adsorbent, developing system, and concentration of the silver nitrate in acetone solution. On exposure to ultraviolet light, 0.002 microgram 2,4,5-T produced clear darkening within 30 min on precoated silica gel plates (polyvinyl alcohol binder) coated with a solution of 0.1% silver nitrate in acetone. For this system, a 60-min detection period was necessary for a 0.05% coating solution. On the silica gel plates (polyvinyl alcohol binder, 0.1% silver nitrate), 0.02 microgram lindane is detected within 75 min. For alumina plates (polyvinyl alcohol binder, 0.1% silver nitrate), 0.025 microgram aldrin is detected within 10 min. Darkening of this plate prohibits the detection of 0.012 microgram aldrin. On silica gel plates (polyvinyl alcohol binder, 0.1% silver nitrate), 0.015 microgram aldrin can be detected within 45 min. The method described provides sensitivities equal to or exceeding literature values.
Aldrin↗