Tissue distribution and fate of persistent organic pollutants in Indo-Pacific humpback dolphins from the Pearl River Estuary, China.

Eleven persistent organic pollutant (POP) compounds including ∑PCBs, ∑DDTs, ∑HCHs, aldrin, mirex, endrin, ∑CHLs, dieldrin, HCB, heptachlor and pentachlorobenzene were measured in the kidney, liver, muscle, melon and other tissues of Sousa chinensis stranded on the western coast of the Pearl River Estuary in China during 2007-2013. For most parameters of POPs measured, melon tissues contained the highest mean concentrations with the exception of aldrin, which was higher in the kidney and liver tissues. The concentrations of PCBs, DDTs, heptachlor and endrin in the melon tissue exhibited significant correlations with body length, whereas PCBs and heptachlor also displayed significant regression with age. Our studies showed hepatic concentrations of ∑DDTs, ∑HCHs and mirex in S. chinensis were generally higher than those found in cetaceans from other geographic locations. The high levels of POP residues in the testis of one male dolphin suggested an increasing risk of infertility in the species.

Bioaccumulation studies of organochlorinated pesticides in tissues of Cyprinus carpio.

Freshwater fish Cyprinus carpio was selected for the study of bioaccumulation of organochlorinated pesticides in tissues like gills, muscle, intestine, kidney, and liver in a continuous fed system. The pesticides used were Aldrin, Dieldrin, BHC, and DDT. The bioaccumulation of Dieldrin was maximum of 85.0 microg g(-1) wet weight in liver tissue while minimum of 7.30 microg g(-1) wet weight for DDT at 30 days exposure time. Bioconcentration factor (BCF) has followed the same trend in liver tissue for Dieldrin and DDT. The rate of bioaccumulation was found to be maximum of 4.3879 microg g(-1) wet weight in liver tissue and minimum of 0.0021 microg g(-1) wet weight in gill tissue for 30 days exposure. As evidenced by the increasing values of BCF, pesticide uptake also showed increased trend with the increase in exposure time. A high correlation coefficient ranging between 0.7247 and 0.9616 between the pesticide concentration and exposure time was observed. Based on actual BCF values, log Kow were calculated and the values are well within the reported values of 6.5 indicating efficient relationship between BCF and log Kow because beyond the 6.5 the bioconcentration levels off.

Bioaccumulation kinetics and bioconcentration factor of chlorinated pesticides in tissues of Puntius ticto (Ham.).

Bioaccumulation kinetics and bioconcentration factor (BCF) of chlorinated pesticides like Aldrin, Dieldrin, Benzene hexachloride (BHC), and Dichlorodiphenyl-dichloro-ethane (DDT) in fish tissues of Puntius ticto was studied in detail in a continuous fed system. The bioconcentration process is summarized by using a first order uptake model and the steady-state BCF is calculated based on the 30 days exposure. Rate of bioaccumulation of DDT was maximum of 4.6432 microg g(-1) wet weight per day in liver tissue whereas it was minimum of 0.0002 microg g(-1) wet weight per day in case of Dieldrin in the muscle tissue among the pesticides. It was observed that DDT showed maximum BCF of 89.010 in case of liver tissue of the fish exposed to 30 days. The regression coefficient (r2) between pesticide concentration and exposure time varied between 0.6212 and 0.9817 indicating high correlation. Based on actual calculated BCF values, the octanol water partition coefficient (Kow) values were predicted. In order to prove the hydrophobic property of chlorinated compounds and its affinity towards lipid, the Kow is predicted. Results showed that pesticide burden differ from tissue to tissue and can be correlated to the lipid content, size, exposure time, and species.

Distribution of aldrin and its epoxide (dieldrin) in egg-forming tissues and eggs of laying hens following an oral application.

Laying hens were treated orally with a single dose of aldrin (1,2,3,4,10,10-hexachloro-1,4,4a,5,8,8a-hexahydro-1,4:5,8-dimethanonaphthalene, AD) 1 mg kg(-1) bw. Concentrations (microg g(-1)) of AD or its epoxide, dieldrin (1,2,3,4,10,10-hexachloro-6,7-epoxy-1,4,4a,5,6,7,8,8a-octahydroendo-,exo-1,4:5,8-dimetha-nonaphthalene, DD), in the main tissues involved in egg formation (blood, liver, ovary, and oviducts) and egg yolk, collected at 1 day after AD dosing, were determined by normal-phase high-performance liquid chromatography. The limits of determination were 0.07 microg g(-1) for AD and 0.08 microg g(-1) for DD, respectively. In extractable fats from the above tissues and egg yolk, AD was found in the egg yolk; however, no AD was found in tissues involved in egg formation. DD was found in all tissues examined here. The DD level was highest in the liver and was lowest in the blood (P<0.01). These results suggest that the epoxidation of AD to DD occurred rapidly in the hen.

The mammalian testis accumulates lower levels of organochlorine chemicals compared with other tissues.

Tissues were obtained from three separate experiments in order to quantify the tissue distribution of organochlorine chemicals that are thought to be potential reproductive toxicants in males: 1) Sprague Dawley rats received 1 microCi of 14C-Aldrin or 14C-Dieldrin (20.6 microCi/micromole) i.p. once a week for three weeks. One week and four weeks after the last injection, tissues were harvested and stored at -80 degrees C. Tissue 14C levels were quantified by scintillation spectrometry. 2) Cis- or trans-nonachlor (0, 0.25, 2.5, 25 mg/kg body weight) were administered daily in corn oil to male rats by gavage for 28 days. Tissues were harvested and frozen at -80 degrees C on the 29th day. Organochlorine residues were extracted and quantified by gas chromatography with electron capture detection. 3) Technical grade toxaphene (0, 0.1, 0.4 or 0.8 mg/kg body weight) was ingested daily by female cynomolgus monkeys of reproductive age for 18 months prior to being mated with control males. Dosing continued during pregnancy and lactation. Their infants received toxaphene via breast milk, and upon weaning, they ingested the same dose as their mothers for 48 to 49 weeks until, at 77 to 80 weeks of age, tissues were harvested and stored at -80 degrees C. Organochlorine residues were extracted and quantified as previously stated. In all three experiments, organochlorine residues in the testis were lower than in most of the other reproductive tract and nonreproductive tract tissues we examined. For example, testicular aldrin and dieldrin levels were <5% the epididymal content; testicular cis- and trans-nonachlor were <25% the epididymal content and, testicular toxaphene levels were <15% of the epididymal content. The reasons for the low degree of accumulation by the testis in comparison with other tissues are unknown. However, the lower testicular content may afford germ cells some protection from the potentially toxic effects of these chemicals.

Decreasing half-life of dieldrin in egg yolk following a single oral administration of aldrin to laying hens.

Laying hens were treated orally with a single dose of aldrin (AD) 1 mg/kg body weight. Concentrations (microgram/g) of AD or its epoxide (= dieldrin, DD) in the yolk of eggs laid for 21 days after AD treatment were determined by normal-phase high-performance liquid chromatography. The limits of determination were 0.02 microgram/g for AD and 0.03 microgram/g for DD, respectively. After AD treatment, although the low levels of AD (mean 0.02-0.03 microgram/g) were observed only during a three-day period (from 4th to 6th days), DD (mean 0.15 microgram/g) was found already on the 2nd day, indicating that the epoxidation of AD to DD in the hen's body is rapid. The highest level of DD (mean 0.40 microgram/g) was detected on the 6th day, and then DD levels decreased slowly and were detected up to the 21st day. In this decreasing phase, the half-life of DD in the yolk was estimated to be 25.6 days with a 95% confidence interval from 22.7 to 29.4 days.

Monograph: reassessment of human cancer risk of aldrin/dieldrin.

In 1987, the US Environmental Protection Agency (EPA) classified aldrin and dieldrin as category B2 carcinogens, i.e. probable human carcinogens, based largely on the increase in liver tumors in mice fed either organochlorine insecticide. At that date, the relevant epidemiology was deemed inadequate to influence the cancer risk assessment. More time has now elapsed since early exposures of manufacturing workers to aldrin/dieldrin; therefore, updated epidemiological data possess more power to detect exposure-related differences in cancer risk and mortality. Also, recent experimental studies provide a plausible mode of action to explain the mouse specificity of dieldrin-induced hepatocarcinogenesis and call into question the relevance of this activity to human cancer risk. This monograph places this new information within the historic and current perspectives of human cancer risk assessment, including EPA's 1996 Proposed Guidelines for Carcinogen Risk Assessment. Updated epidemiological studies of manufacturing workers in which lifetime exposures to aldrin/dieldrin have been quantified do not indicate increased mortality or cancer risk. In fact, at the middle range of exposures, there is evidence of a decrease in both mortality from all causes and cancer. Recent experimental studies indicate that dieldrin-induced hepatocarcinogenesis in mice occurs through a nongenotoxic mode of action, in which the slow oxidative metabolism of dieldrin is accompanied by an increased production of reactive oxygen species, depletion of hepatic antioxidant defenses (particularly alpha-tocopherol), and peroxidation of liver lipids. Dieldrin-induced oxidative stress or its sequelae apparently result in modulation of gene expression that favors expansion of initiated mouse, but not rat, liver cells; thus, dieldrin acts as a nongenotoxic promoter/accelerator of background liver tumorigenesis in the mouse. Within the framework of EPA's Proposed Guidelines for Carcinogen Risk Assessment, it is proposed that the most appropriate cancer risk descriptor for aldrin/dieldrin, relating to the mouse liver tumor response, is 'not likely a human carcinogen', a descriptor consistent with the example of phenobarbital cited by EPA.

Absorption by sheep of dieldrin from contaminated soil.

OBJECTIVE: To study the accumulation of dieldrin residues in sheep from ingestion of contaminated soils was studied in two experiments. DESIGN: A controlled feeding study of sheep fed contaminated soils of different type at varying intervals. ANIMALS AND PROCEDURE: Thirty-four 2-year-old wethers were divided into four groups (one control sheep only) and fed water-soluble dieldrin or soil contaminated with aldrin and dieldrin at varying intervals in the first study. In a second study 34 similar sheep were divided into four treatments with one being a control. Sheep were fed sandy, high clay or high organic matter soils with similar dieldrin and aldrin concentrations. RESULTS: In the first study the concentration of dieldrin in the body fat of sheep dosed with dieldrin-contaminated soil was about half that in the body fat of sheep dosed with an equivalent amount of water-soluble dieldrin. The concentration of dieldrin was almost the same in sheep fed 500 micrograms of total dieldrin per day as it was in sheep fed 5000 micrograms every tenth day, over a 50-day period. In the second experiment sheep accumulated nearly three times as much pesticide from a soil with a high organic matter content, and about four times as much from a soil with a high clay content, as from a sandy soil with the same dieldrin content, over a 100-day period. The half-life of dieldrin in the fat of all sheep varied between 96 and 116 days after sheep caused ingesting contaminated soil. CONCLUSIONS: Dieldrin concentrations in the fat of sheep that consume dieldrin contaminated soil fall within 10 days of removal from the source of contamination. However, dieldrin accumulates in the wool of sheep that consume dieldrin contaminated soil.

Aldrin intoxication and clearance of associated dieldrin residues in a group of feedlot cattle.

A sudden onset of bizarre neurologic dysfunction was found in 8 of 90 mixed-breed feeder calves. Seven other calves were dead, and 3 more died during the next week. A diagnosis of organochlorine toxicosis was made when rumen and abomasal contents from 1 of the calves revealed 22.4 and 20.6 micrograms of aldrin/g of ingesta, respectively. Complete feeds retrieved from self-feeders contained 54 and 528 micrograms of aldrin/g of feed. The initial concentration range in fat from 40 live calves was 6.01 to 42.44 micrograms of dieldrin/g of fat. Additional fat samples were analyzed to verify residue compliance until the entire herd was clear of residue 18 months after removal of the contaminated ration. The range of apparent half-lives for dieldrin in body fat of heifers and steers was 69 to 231 and 53 to 116 days, respectively. These findings demonstrate the considerable variability in apparent half-life of dieldrin in field cases. In cases of dieldrin-contaminated livestock, veterinarians and regulatory personnel must accurately determine the necessary slaughter withholding times so that informed economic decisions are made in the best interest of the producer while enhancing the probability of a safe food supply. Excretion rates of dieldrin from field-contaminated cattle may not be consistent with results obtained under experimental conditions.

Aldrin epoxidation. Catalytic potential of lipoxygenase coupled with linoleic acid oxidation.

Epoxidation of aldrin was studied using highly purified soybean lipoxygenase in the presence of linoleic acid. Dieldrin, the primary stable reaction product, was quantified by electron-capture gas chromatography. The oxidation of aldrin to dieldrin was dependent on the concentration of linoleic acid, aldrin, and enzyme. The epoxidation was linear with time and exhibited a pH optimum of 7.4. The optimal conditions to observe maximum enzyme velocity included the presence of 0.25 mM linoleic acid, 200 microM aldrin, and 20 nM enzyme. Lipoxygenase inhibitors nordihydroguaiaretic acid, phenidone, 5,8,11-eicosatriynoic acid, and 5,8,11,14-eicosatetraynoic acid significantly inhibited epoxidation in a dose-dependent manner. Catalytic potential of lipoxygenase as expressed in terms of its turnover numbers was approximately 4.0 nmol/min/nmol of enzyme, and it appears that lipoxygenase is up to 20 times a better catalyst of aldrin epoxidation than cytochrome P-450. These results suggest that lipoxygenase, which is widely distributed in plants and animals, may represent yet another important pathway for epoxidation of aldrin.

Percutaneous absorption and metabolism of aldrin by rat skin in diffusion cells.

Using a static diffusion cell with varying receptor fluids the viability of isolated rat skin mounted as whole skin or as split thickness skin has been studied. Skin viability decreased with time with phosphate buffer or Eagles MEM and was not supported with ethanol/water as the receptor fluid. The pesticide aldrin was absorbed through the skin into ethanol/water but not the aqueous receptor fluids. With viable skin preparations aldrin was metabolised to dieldrin and absorbed aldrin and the metabolite remained in the skin. Viable skin preparations must be used to assess in vitro, the degree of metabolism of xenobiotics which occurs during percutaneous absorption.

Hepatic metabolism of cyclodiene insecticides by constitutive forms of cytochrome P-450 from lower vertebrates.

1. Multiple forms of cytochrome P-450 were separated from the hepatic microsomes of untreated male rats, pigeons (Columbia livia), razorbills (Alca torda), puffins (Fratercula arctica), and rainbow trout (Salmo gairdnerii), using anion exchange chromatography and DEAE-cellulose. 2. In some cases cytochrome P-450 forms were further purified on hydroxylapatite and carboxymethyl-sephadex columns. 3. Considerable differences in the distribution of forms between these five species were evident from elution profiles on DEAE cellulose, and on analysis of the cytochrome P-450 containing pools by SDS-PAGE. 4. The metabolism of two organochlorine compounds, aldrin and the dieldrin analogue HCE, were studied in (a) intact microsomes and (b) reconstituted systems containing cytochrome P-450, from each of the five species. 5. In spite of their close structural similarity, significant differences were found between the two substrates in the distribution of catalytic activity between the cytochrome P-450 isozymes of each species.