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Factors in the accumulation of dieldrin in broiler organs: doses administered with feed; dose-organ-dieldrin accumulated relationship; toxicological consequences.

The quantity of dieldrin accumulated in liver, kidney, heart, gizzard, lung, muscle, and intestine with contents, of broiler chickens fed with feed contaminated by this insecticide, was determined by gas chromatography analysis. The doses used were 60, 90, 120, 200 and 240 ppm. The influence of the doses used in the quantity of dieldrin accumulated in the different organs, the relationship between the doses administered, organs and quantity accumulated, and the toxicological consequences of the contamination were studied. The results show that the doses used did not significantly affect the quantity of dieldrin accumulated by the different organs. The relationship doses-organ-quantity accumulated shows that the muscle accumulates equal dieldrin at all the doses used. The differences in the dieldrin accumulated at different doses increases with the metabolic function of the organs. The principal symptoms of intoxication were anorexia, convulsions and tremors, which indicated that the nervous system is a major site of activity.

Animal Feed

Dieldrin activates rat neutrophils in vitro.

Suppression of phagocytic cell function has been proposed as a possible mechanism for the enhanced sensitivity to certain infectious agents exhibited by animals exposed to the organochloride insecticide, dieldrin. In the present study, we examined the effects of dieldrin on superoxide production by glycogen-elicited peritoneal neutrophils (PMNs) from the rat. Dieldrin caused a concentration-dependent increase in superoxide production by PMNs incubated in vitro at 37 degrees C. Superoxide release was increased significantly with 10 microM dieldrin and reached a maximum of 17 nmol/10 min/2.0 X 10(6) PMNs at a dieldrin concentration of 35 microM. Preincubation of PMNs for 5 min at room temperature with a barely suprathreshold concentration of either phorbol 12-myristate 13-acetate (PMA) or N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) enhanced dieldrin-stimulated superoxide release by as much as ninefold or threefold, respectively. Maximum enhancement was obtained with 10 microM dieldrin for both PMA and FMLP. Time course studies with PMA-pretreated cells revealed that the rate of superoxide release was dependent on the concentration of dieldrin. Extracellular calcium played an important role in dieldrin-stimulated superoxide release, since PMNs treated with dieldrin in the absence of extracellular calcium did not release superoxide. Also, pretreatment with calcium ionophore A23187 greatly enhanced superoxide release from dieldrin-stimulated PMNs. These results show that dieldrin has a stimulatory effect on superoxide release from rat PMNs in vitro and that this stimulation is dependent on extracellular calcium.

Animals

Accumulation and elimination of dieldrin in muscle tissue of channel catfish.

Dieldrin accumulation and elimination in muscle tissue of channel catfish (Ictalurus punctatus) from water and food was determined in the laboratory. Twenty-eight-day exposure of fish 150-225 mm and 350-400 mm long to 75 parts per trillion (ng/liter) dieldrin resulted in the larger catfish consistently accumulating more dieldrin than the smaller fish. After 28 days of elimination, dieldrin levels in both size groups were nearly equal. Catfish exposed to 2 ppm (mg/kg) dieldrin through their diets accumulated significantly more dieldrin in muscle than did fish exposed to 75 pptr in water. When fish were exposed to dieldrin both in food and water, dieldrin from both sources contributed to the total dieldrin load. Large catfish accumulated more dieldrin from food and water than did smaller catfish. After 28 days of elimination, levels of dieldrin were not significantly different in muscles of 150-225 mm and 350-440 mm catfish exposed via both food and water.

Animal Feed

Metabolism of aldrin to dieldrin by rat skin following topical application.

Metabolism of the pesticide aldrin to dieldrin in the rat was studied following topical and ip administration of 0.1-10 mg aldrin/kg body weight. When aldrin was applied topically to the dorsal skin at a dose of 10 mg/kg body weight, absorption was less efficient than after ip administration; lower blood levels of aldrin and dieldrin were seen and peak dieldrin levels were delayed. After ip administration of 1 or 10 mg aldrin/kg body weight, dieldrin was found at similar concentrations in the dorsal and ventral skin 7 hr later, whereas 7 hr after topical administration of 10 mg aldrin/kg, the dieldrin concentration in the skin at the dorsal site of application was four times higher than that at a ventral skin site. Similar differences in dieldrin concentrations between dorsal and ventral skin persisted throughout the 7-hr period following topical application. The results indicate that topically applied aldrin is metabolized to dieldrin in the skin during absorption, but the overall proportion of metabolism that takes place in the skin is small compared with the contribution of the liver. Dieldrin was not detected in the ventral skin remote from the application site 1 hr after topical application of aldrin, whereas a dieldrin concentration of 2.2 nmol/g was detected in the skin of the application site at this time; more than 99% of this dieldrin was probably formed locally by dermal metabolism of percutaneously absorbed aldrin. The efficiency of conversion of applied aldrin to dieldrin decreased with increasing aldrin dose in the range 0.1 to 10 mg/kg.

Administration, Topical

Teratogenesis, toxicity, and bioconcentration in frogs exposed to dieldrin.

Teratogenesis, acute and chronic toxicity, growth and bioconcentration were investigated in various life stages (embryos, tadpoles, juveniles, adults) of the frogs Xenopus laevis (African clawed frog), Rana catesbeiana (bullfrog) and Rana pipiens (leopard frog) exposed to aqueous dieldrin in static-renewal and flow-through systems in a study on the development of wildlife-based water quality criteria. R. catesbeiana was the most sensitive tadpole in acute tests; X. laevis was the most sensitive in embryo-larval and chronic tadpole tests. Tadpole 96-h LC50s ranged from 40.4 to 49.5 micrograms/L dieldrin for X. laevis, from 8.7 to 30.3 micrograms/L for R. catesbeiana and was 71.3 micrograms/L for R. pipiens. The 24-day LC50 for X. laevis tadpoles was 5.5 micrograms/L dieldrin; the 28-day LC50 for R. pipiens tadpoles was 8.3 micrograms/L. Adult R. pipiens had a 28-day LC50 of 53.4 micrograms/L dieldrin. Gross spinal deformities in embryo-larval tests were observed at dieldrin concentrations as low as 1.3 micrograms/L after 10-days exposure to X. laevis and at 25.4 micrograms/L for a 21-day exposure to R. catesbeiana. Mean X. laevis 14 to 21-day LOAEL (Lowest Observed Adverse Effect Level) and NOAEL (No Observed Adverse Effect Level) values for embryo-larval tests (25.5 and 11.0 micrograms/L dieldrin, respectively) were virtually the same as the 21-day single test values obtained for R. catesbeiana (25.1 and 11.0 micrograms/L dieldrin). Mean 14 to 24-day X. laevis LOAEL and NOAEL values for tadpole chronic tests (1.6 and less than 1.4 micrograms/L dieldrin, respectively) were lower than the 28-day single test values obtained for R. pipiens (4.1 and 1.9 micrograms/L, respectively). Tissue dieldrin levels at the LC50, LOAEL and NOAEL in the tadpole acute tests were fairly similar between X. laevis (11, 24 and 7 micrograms/g, respectively) and R. catesbeiana (means of 8.6, 12.0 and 1.2 micrograms/g, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effect of dieldrin and calcium on the performance of adult Japanese quail (Coturnix coturnix japonica).

Two experiments were conducted to determine the effects of dieldrin and calcium on reproductive performance of quail. At 25% egg production the quail received diets containing 0,10 or 25 p.p.m. of dieldrin for 6, 28-day periods in experiment 1 and 0, 5, or 25 p.p.m. of dieldrin for 4, 28-day periods in experiment 2. Pesticide treatments were employed with diets containing 0.5% and 3.0% calcium. The results show that egg shell thickness, cracked eggs, egg production, feed consumption, egg weights, fertility, hatchability and body weights were not affected by dieldrin treatments. However, egg shell thickness, cracked eggs, egg production and hatchability were adversely affected by the lower calcium level. Female body weights were consistently heavier for the low calcium diet. Mortality increased in the presence of 10 and especially 25 p.p.m. of dieldrin. Livability of chicks from hens receiving rations with 10 and 25 p.p.m. of dieldrin was significantly lower than those fed no dieldrin. In summary, dieldrin was without effect on egg shell quality or other reproductive factors but did exert a detrimental effect on adult mortality and livability of progeny.

Animals

Dieldrin-induced changes in isoenzyme composition in the livers of CF-1 mice.

The isoenzyme composition of lactic dehydrogenase (LDH), pyruvate kinase (PK) and alanine-aminotransferase was determined in the livers of CF-1 mice exposed to 0, 5 or 10 ppm dieldrin in the diet, over a period of 14 months. This study was carried out to evaluate whether the liver tumor promoter dieldrin advances the biological age of CF-1 mouse liver. Oral dieldrin exposure induced a dose-dependent shift towards the fetal types of lactic dehydrogenase and pyruvate kinase, within 1.5 months of initiation of treatment. After the initial shift, no additional dieldrin-dependent changes were found in CF-1 mouse liver throughout the experimental observation period. Thus, the initial shifts in isoenzyme composition of LDH and PK appear to reflect the adaptation of the liver to increased functional demands imposed by dieldrin treatment. The expression of the cytoplasmic A-alanine-aminotransferase isoenzyme decreased with age in untreated control mice. Dieldrin treatment enhanced this process in a dose-dependent manner. These data suggest that dieldrin treatment can accelerate age-dependent changes in gene expression.

Aging

Comparative behavior of dieldrin and carbofuran in the field.

To measure the amounts of dieldrin and carbofuran lost to the environment, we incorporated them into soils in small (0.6-1.1 ha) watersheds in separate years. The disappearance of each was monitored by periodically measuring residues in the soil, runoff, maize plants, and overlying air (dieldrin only). Soil residues were nonuniformly distributed. Best estimate for the time for 95% disappearance of dieldrin from the soil was 12.8 years. Carbofuran disappearance conformed to a first-order reaction and gave 95% disappearance times ranging from 145 to 434 days, depending on soil pH, moisture, and temperature. Runoff losses of both pesticides were highest in rainfalls during the first month after application. Over the season, dieldrin losses ranged up to 2.3% of that applied and were concentrated in the solids. Carbofuran losses in runoff occurred largely in the water and comprised up to 1.9% of the application. More than twice as much carbofuran (and metabolites) as dieldrin was accumulated in the maize plants, mainly in the leaves. Volatilization was an important route of dieldrin loss, amounting in the first year to 4.5% of that applied. Volatility of carbofuran, which was only 1/18th that of dieldrin in a laboratory test, was not measured in the field. The data show that use of optimum management practices can substantially reduce the environmental impact of agricultural applications of these pesticides.

Air

Dieldrin-14C elimination from chickens.

A series of experiments was conducted with chickens contaminated with dieldrin-14C to find ways of accelerating the elimination of dieldrin from their bodies. The results of these experiments indicated that charcoal, imbiber beads, and the anion exchanges resins, Dowex XFS-4022 and Dowex SBR-C1, would not be useful agents for increasing the amount of dieldrin eliminated via feces (droppings) of chickens. Further, imbiber beads coalesced in the gizzard of the chickens and reduced their appetites. The anion exchange resin, cholestyramine, might be useful as gastrointestinal absorbant for increasing dieldrin elimination in chickens because it increased carbon-14 elimination in droppings, but its effect on carbon-14 residues in carcasses was not clear. We elected not to investigate this compound further. Probucol, investigated because it might alter gastrointestinal absorption or blood physiology that would affect dieldrin elimination, did not increase dieldrin elimination. Severe starvation was the only method investigated that clearly was useful for increasing dieldrin elimination because it increased carbon-14 elimination in droppings and reduced carbon-14 residues in carcasses.

Animals

Suppression of avidin processing and presentation by mouse macrophages after sublethal exposure to dieldrin.

The molecular events in macrophage antigen processing and presentation were examined to determine the possible site(s) of cell-xenobiotic interaction. Antigenic processing by mouse peritoneal macrophages of a single protein antigen, avidin, was significantly suppressed following sublethal exposure of animals to an organochlorine pesticide, dieldrin. Exposure of C57B1/6 female mice to dieldrin affected the in vitro uptake of [methyl-14C]avidin by peritoneal macrophages and markedly decreased phagocytosis of fluorescein-labelled microspheres and Salmonella typhimurium. Release of the processed avidin, determined by immunochemical quantification of immunogenic avidin and by bioassay of immunogenicity of the released antigen, was also markedly affected. Dieldrin markedly affected presentation of avidin on the macrophage surface, observed by cytoimmunochemical staining of the antigen with fluorescent antibody and flow cytometry. Inhibition of the release of processed avidin was dieldrin dose- and time-dependent, following single sublethal intraperitoneal (ip) exposure to the pesticide. The antigenic properties of processed avidin, determined by biological assay using lymphocyte cultures of normal C57B1/6 mice primed with avidin, were proportional to the antigen concentration in supernatants of macrophage cultures, for both vehicle controls and dieldrin-exposed animals. This observation and analysis of the kinetics of release of processed avidin by macrophages from control and dieldrin-exposed animals suggested that the release of processed avidin, but not the immunogenicity of the antigen itself, was affected by the pesticide exposure. Generally, impairment of avidin processing and presentation appeared to be more dramatic than other pesticide-related injuries to macrophages, such as the uptake of the antigen. In conclusion, antigen processing could be a sensitive target for dieldrin-related injury of macrophage functional activities, which, in consequence, could produce suppression of the humoral immune response.

Animals

Strategies, systems, value judgements and dieldrin in control of locust hoppers.

The physiology and field biology of locusts have been extensively studied, and ecological control of Red Locusts has been investigated by field experiment. No fruitful or even promising non-insecticidal method of control has emerged. An effective and economical system requires an insecticide that is: (i) effective at very small area dosages, as a stomach poison placed on the natural vegetation can be, if it is also cumulative; (ii) persistent enough in sunshine and rain to retain effectiveness over the locust's non-feeding periods; (iii) capable of being well distributed by well-tried methods; and (iv) not dangerous to users or consumers and posing a minimal overall risk. Only one insecticide, dieldrin, satisfies all these requirements. Dieldrin is not in the small class of insecticides that are dangerous to man by skin absorption (such as parathion, arsenicals, DNC) and, at the area dosages needed for locust control, is not dangerous to stock. The Sayer exhaust sprayer in a Land Rover, with work rates of the order of square kilometres per hour is excellent for many situations; aircraft spraying at he rate of square kilometres per minute is quicker and less subject to difficulties of terrain, but requires trained and appropriately directed aircrew. Apart from checking, aircraft methods require no party on the ground to find, assess and control locust hoppers. Several ideas about dieldrin are found to be based on insufficient evidence and are probably not true: for example that dieldrin in the atmosphere at a few parts in a million million (10(12)) becomes concentrated in a food web and harmful to man, or that dieldrin is carcinogenic in man. It is noteworthy, however, that one species of antelope in South Africa is exceptionally susceptible to dieldrin poisoning, though harm occurs at area dosages considerably greater than are required in the method of aircraft spraying of Courshee & McDonald (1963). To attack tsetse flies, emissions two orders of magnitude greater have been used. Care must be taken with any insecticide, but the risks of using dieldrin as properly used in locust hopper control have been exaggerated by propaganda. If harm is to be expected, then a quantitative comparison of that with the undoubted benefits of locust control is required to enable one to make a value judgement.

Aircraft

Uptake and disposition of aldrin and dieldrin by isolated perfused rabbit lung.

The uptake, metabolism, and release of aldrin and dieldrin by the lungs were studied by use of isolated perfused rabbit lungs that were artificially ventilated and perfused through the pulmonary artery. Both recirculating and single-pass experiments were conducted using an artificial medium as perfusate. Aldrin accumulated in the lung from the perfusate through two distinct phases of uptake: a rapid phase involving simple diffusion and nonspecific binding and a slower phase representing its metabolic turnover as dieldrin. Dieldrin was not metabolized but accumulated in the lungs by a saturable and a nonsaturable process. Single-pass experiments with aldrin indicated that the initial velocity of uptake could be fitted to one component and a constant representing the rate of metabolism. Uptake of dieldrin was biphasic: one phase independent of the perfusate concentration and the other saturable with respect to the perfusate concentration. By the application of Michaelis-Menten kinetics, the maximum amount of dieldrin accumulation attributable to the saturable component was calculated to be 0.64 mumol/lung. Our results indicate that the accumulation of these chlorinated xenobiotics takes place through the processes of simple diffusion followed by nonspecific tissue binding. There was no evidence for irreversible binding of aldrin or dieldrin, its epoxide, in the lung. While the lung plays a role in metabolizing aldrin to dieldrin followed by a transient storage, neither substrate has the potential for long-term storage in the lung.

Aldrin

Toxicity of dieldrin to bobwhite quail in relation to sex and reproductive status.

In a study of dieldrin toxicity to breeding and nonbreeding bob-white quail (Colinus virginianus), breeding birds of both sexes on long photoperiods were more susceptible to dieldrin poisoning than nonbreeding birds, although some differences were not statistically significant at the .10 level. Shortened photoperiods caused gonadal regression, weight loss, and additional mortalities among dieldrin-treated birds previously in breeding condition. Dieldrin did not influence food consumption, body weight, or egg production until about a week or less before death of individual birds. Dieldrin brain residues were higher among birds that died during the study than among survivors sacrificed at its termination. Among those that died, neither dieldrin treatment level, reproductive status, nor sex seemed related to brain residue levels. Nevertheless, within those factors, levels were slightly higher in the birds that died later in the test.

Animals

A pesticide (dieldrin)-induced immunohemolytic anemia.

The unusual presentation of a factory worker with severe hemolytic anemia which remitted following splenectomy prompted a search for an environmental cause for red cell injury. The investigation showed the presence of an immunoglobulin in the patient's serum and on the red cells and small amounts of complement on red cells. The patient's serum caused agglutination of a normal person's red cells only when dieldrin-coated, a reaction blocked by first reacting the serum with dieldrin. The spleen of the patient had a greater than normal concentration of dieldrin, the source of dieldrin being dietary. It is concluded that dieldrin became immunogenic and provoked a chemical immunohemolytic anemia. The spleen played a major role in destruction of red cells injured by the immunopathic process and in accumulation of the antigenic substance dieldrin.

Anemia, Hemolytic

Quantitative aspects of accelerated nuclear polyploidization and tumour formation in dieldrin treated CF-1 mouse liver.

Nuclear polyploidization in the livers of CF-1 mice, exposed to dieldrin (0, 1, 5 and 10 ppm in the diet), was studied up to the median time of liver tumour development (ranging from 15 to 27 months) in the respective treatment groups. In untreated controls nuclear polyploidization is characterized by a linear increase of octaploid nuclei with age. Approximately 4 months before tumour development a reduction in the tetraploid to diploid ratio is observed. Dieldrin treatment was found to enhance nuclear polyploidization in the initial phases of treatment, as expressed by a dose-dependent increase in octaploid nuclei. In 'steady-state' situations all age dependent changes in the level of polyploidization found in controls were also found in dieldrin treated mice. However, these changes occurred at an increasingly earlier age with higher dieldrin treatment levels. The decrease in the tetraploid:diploid ratio always takes place a few months before tumour development. This change in the ploidy level may thus be related to the subsequent liver tumour formation. The liver tumours themselves appear to originate from a diploid stem line, and were found to increase their degree of polyploidization during growth, eventually developing aneuploid nuclei. A comparison of nuclear polyploidization and liver tumour formation in CF-1 mouse liver for the given dietary dieldrin concentrations showed that liver tumour formation was associated with a constant level of polyploidization. Since polyploidization is an age-dependent process, these findings suggest that liver tumour formation is imminent at a constant biological age and that dieldrin may advance the biological age of CF-1 mouse liver.

Administration, Oral

Circadian rhythm changes in toxicity of the insecticide dieldrin on larvae of the migratory locust Locusta migratoria migratorioides.

Circadian changes in toxicity of the insecticide dieldrin were documented in the larvae (fifth stage) of the migratory locust, Locusta migratoria migratorioides. Insects were housed under light (L): dark (D) = 12:12, with L from 0800 to 2000 h. Topical applications of dieldrin at fixed clock hours, with doses ranging from 0.1 to 8 micrograms/gm body weight, were carried out in a series of experiments on male and female larvae. Twenty-four h after dosing, mortality was recorded to quantify the median lethal dose (LD50) values with reference to time of treatment. Experiments were performed during February, early and late June, and August. Larvae were more susceptible to dieldrin when dosed during the night rather than during the day [analysis of variance (ANOVA); p less than 0.05]. Moreover, female larvae were less susceptible to dieldrin than were male larvae (ANOVA; p less than 0.05). Cosinor analysis revealed circadian rhythms in susceptibility-resistance to the insecticide in all experiments except no. 2. Toxicity was found to be greatest during the nighttime. Cosinor analysis of pooled data of the four experiments documented circadian rhythmicity to toxicity of dieldrin in female but not in male larvae. Regardless of sex, the timing of least susceptibility (greatest resistance and highest LD50 value) to the insecticide, dieldrin, was around 1500.

Animals

Seasonal concentrations of dieldrin in water, channel catfish, and catfish-food organisms, Des Moines River, Iowa--1971-73.

Concentrations of dieldrin in aquatic insects, crayfish, minnows, and small carpsuckers, and muscle tissue of channel catfish (Ictalurus punctatus) were compared with the dieldrin content of Des Moines River water in 1971-73. Monthly mean concentrations of dieldrin in river water and most aquatic organisms were highest in June and July, soon after aldrin had been applied to corn land in the watershed. Several groups of aquatic organisms also exhibited high dieldrin levels in the fall when the dieldrin content of river water was seasonally low. The influence of temperature on metabolic rate and enzyme activity and the differences in body fat content were suggested as probable causes of variations observed in the dieldrin content of aquatic organisms.

Agriculture