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At least 19 recordsLinked to original sources

Absorption and elimination of 14C-cis-chlordane and 14C-photo-cis-chlordane by goldfish Caraccius auratus.

Photo-cis-chlordane is accumulated by goldfish to a greater extent than cis-chlordane during a 16-hr exposure to 5 parts per billion (ppb) of each insecticide. However, the concentration of photo-cis-chlordane in vital organs (brain, nervous system, heart, liver, kidneys) during the 1-, 2-, and 4-day exposure is less than that of cis-chlordane. Only the swim bladder shows a much higher concentration of photo-cis-chlordane than cis-chlordane. These differences could hardly account for twice the higher toxicity of the former to goldfish. The transfer of pre-exposed fish to insecticide-free water resulted in faster elimination of photo-cis-chlordane than cis-chlordane; after five weeks, about 90% of the former was eliminated as compared with only 58% of the latter. High residues of both insecticides in the bile and the intestine during the initial period of exposure indicate a biliary route of elimination.

Absorption

On effect of chlordane on the blood glucose and of glucose administration on the acute chlordane toxicity in Meriones hurrianae Jerdon, the indian desert gerbil.

The effect of 25, 50 and 75 mg/kg body wt. chlordane on the blood glucose level and of glucose administration in chlordane intoxicated Indian desert gerbils are investigated. Chlordane produces hyperglycemia and lowers the glucose tolerance indicating an impairment in the uptake and utilization of glucose in intoxicated gerbils. The possible reasons for these effects are discussed.

Animals

Percutaneous absorption of [14C]chlordane from soil.

The objective was to determine percutaneous absorption of chlordane in vitro and in vivo from soil into and through skin. The data are needed to calculate the absorbed dose of chlordane from soil, which is then used to assess the toxicity risk. Chlordane, an insecticide for which residues exist in soil, is restricted currently to use for termite control. Chlordane is highly lipophilic with little or no movement out of soil. Soil (Yolo County 65-California-57-8; 26% sand, 26% clay, 48% silt, 0.9% organic) was passed through 10-, 20-, and 48-mesh sieves. Soil then retained by 80-mesh was mixed with 14C-labeled chemical at 67 ppm. Acetone solutions were prepared for comparative analysis. Human cadaver skin was dermatomed to 500 microns and used in glass diffusion cells with human plasma as the receptor fluid (3 ml/h flow rate) for a 24-h skin application time. Chlordane concentration within skin from in vitro studies was 0.34 +/- 0.31% from soil and 10.8 +/- 8.2% from acetone vehicle (p less than .01). Individual variation from human skin sources was evident (p less than .008). Chlordane accumulation in human plasma receptor fluid was the same for soil (0.04 +/- 0.05%) and acetone (0.07% +/- 0.06%) formulations. Most of the remaining chlordane was recovered in the soap and water skin surface wash. In contrast, in vivo percutaneous absorption of chlordane in the rhesus monkey was the same for soil (4.2 +/- 1.8%) and acetone (6.0 +/- 2.8%) formulations (p = .29, nonsignificant). Multiple soap and water washings were necessary to remove chlordane from skin, suggesting that a single wash may not adequately remove all the chlordane.

Administration, Topical

Persistence of residues in water and sediment of a fresh-water lake after surface application of technical chlordane.

A fresh-water lake, free from detectable pesticide residues before this study, was treated with a commercial formulation of technical chlordane. Water and sediment samples were analysed for chlordane residues 7, 24, 52, 279. and 421 days after treatment. Residues moved rapidly from the water to the lake bottom, supporting earlier results of a laboratory study with other organochlorines. In water, alpha- and gamma-chlordane concentrations remained proportional to total chlordane concentrations, as determined by total-peak area measurements of gas-liquid chromatogrammes. But in bottom sediments, alpha- and gamma-chlordane were more persistent than other constituents of technical chlordane, supporting recent evidence that quantification of technical chlordane residues on the basis of gamma-chlordane quantification only (or that of alpha- and gamma-chlordane only), can lead to incorrect results and that this method, although simple and fast, should no longer be recommended.

British Columbia

Evidence for the subcellular localization and specificity of chlordane inhibition in the marine bacterium Aeromonas proteolytica.

Sublethal levels (10 to 100 micrograms/ml) of the chlorinated insecticide chlordane (1,2,4,5,6,7,8,8-octachloro-3a,4,7,7a-tetrahydro-4,7-methanoindan) were introduced into the growth medium of the marine bacterium, Aeromonas proteolytica. Chlordane inhibited the synthesis of an extracellular endopeptidase by almost 40% but exhibited no such inhibition of the extracellular aminopeptidase also produced during the growth cycle. Studied with 14C-labeled chlordane demonstrated that the insecticide was not biologically degraded under the test conditions used and that up to 75% of the recoverable chlordane was cell associated within 48 h. Studied with uniformly labeled L[14C]valine and [2-14C]uracil established that neither the transport nor the incorporation of these protein and ribonucleic acid precursors was inhibited by chlordane. Separation of the membrane fractions using isopycnic centrifugation localized 14C-labeled chlordane in the cytoplasmic membrane. Also, chlordane inhibited the membrane-bound adenosine 5'-triphosphatase while the soluble (released) form of this enzyme remained unaffected. These data indicate that chlordane resides in the cytoplasmic membrane and may cause specific alterations in membrane-associated activities.

Adenosine Triphosphatases

Macrophage tumoricidal mechanisms are selectively altered by prenatal chlordane exposure.

Macrophages (m phi) derived from mice treated in utero with chlordane show a significant delay of tumoricidal induction activity. In this study, m phi from chlordane-treated animals required a 48 h in vitro period of induction with interferon-gamma and lipopolysaccharide (IFN/LPS) before they could kill P815 targets. Similarly, m phi from chlordane-treated animals also failed to produce an immediate H2O2 burst upon perturbation. Conversely, their stimulated control m phi counterparts were tumoricidal by 2 h and exhibited a respiratory burst without any delay. Moreover, levels of the second messenger, inositol triphosphate (IP3), were significantly delayed in chlordane-treated animals following interaction with IFN/LPS. When nitrate/nitrite production was analyzed as an alternate mechanism for killing tumors, stimulated m phi from both normal and chlordane-treated animals responded equally. The data show that chlordane differentially introduces defects in m phi biochemical mechanisms associated with tumor killing.

Animals

Metabolic fate of cis- and trans-chlordane in mice.

A single dose of a cis-chlordane and trans-chlordane mixture (1:1) was orally administered to mice (total dose: 40 mg/kg), and the metabolic fate of the two congeners administered and their major metabolite, oxychlordane, in various tissues, was studied from day 1 after dosing to week 52. Cis-chlordane and trans-chlordane showed the highest concentrations on day 1 after dosing, and disappeared on day 14 except in the liver. The half life in the tissues was approximately one day for both congeners. On the other hand, oxychlordane was observed in various tissues from day 1 after dosing, reaching the maximum concentration on day 1 or 2 showing considerably higher concentrations than those of the congeners. The rate of decrease of oxychlordane in the tissues was extremely slow compared to the congeners. It was found that oxychlordane remained in the tissues even in week 52 (year 1) after dosing. The regression curve for the tissue oxychlordane concentration was diphasic after or at around week 8 after dosing; the half life was approximately 20 days in the first phase and was prolonged to over 100 days in the second phase. These results suggest that the cis-chlordane and trans-chlordane taken into the human body via foods disappear rapidly from the tissues but that oxychlordane, their metabolite, remains in the body over a prolonged period of time.

Administration, Oral

In vivo prenatal chlordane exposure induces development of endogenous inflammatory macrophages.

Macrophages (m phi s), important cells in host resistance, undergo a series of biochemical changes during their progression from the resident to the fully activated stage. Both resident and inflammatory m phi s are characterized by some unique properties. In the present study, female BALB/c mice were prenatally treated with 8 mg/kg body weight of chlordane, a cyclodiene poly-chlorinated hydrocarbon that appears to reduce immunocompetence by selectively impairing m phi function. Therefore, we examined functions in m phi s from chlordane-treated mice that had been stimulated with thioglycollate. The 5'-nucleotidase activity, present in high levels in resident m phi s but low levels in inflammatory m phi s was elevated in resident m phi s from vehicle-exposed animals. Conversely, inflammatory m phi s from these animals showed significantly diminished levels of this function. Moreover, chlordane-exposed m phi s, regardless of whether they were resident or inflammatory, exhibited decreased 5'-nucleotidase responses. When a second function, transferrin receptor binding, was analyzed, vehicle-treated inflammatory m phi s displayed high levels of activity whereas the resident m phi s showed very little transferrin binding. However, both resident and inflammatory m phi s from the chlordane-exposed group demonstrated transferrin binding activity similar in magnitude to that of the vehicle-treated inflammatory m phi s. Finally, two-dimensional polyacrylamide gel electrophoresis analysis of m phi s from chlordane-exposed mice have characteristics of normal m phi s that have advanced to the inflammatory stage.

5'-Nucleotidase

Chlordane: effects on several estuarine organisms.

Dynamic marine toxicity tests were performed with technical grade chlordan and eastern oysters (Crassostrea virginica), pink shrimp (Penaeus duorarum), grass shrimp (Palaemonetes pugio), sheepshead minnows (Cyprinodon variegatus), and pinfish (Lagodon rhomboides). The 96-hr LC20S (and 95% confidence limits) based on measured concentrations of chlordane (in mug/liter) are: ping shrimp 0.4 (0.3-0.6); grass shrimp, 4.8 (4.0-6.0); sheepshead minnows, 24.5 (19.9-28.6); and pinfish, 6.4 (5.0-7.3). The 96-hr EC50 for eastern oysters was 6.2 (4.8-7.9). In a flow-through test, embryos and fry of sheepshead minnows were exposed to average measured concentrations of chlordane from 1.3 to 36.0 mug/liter for 28 days. Neither fertilization success nor embryo survival was affected by the concentrations of chlordane to which these life stages were exposed. However, sheepshead minnow fry did not survive for more than 10 days in chlordane concentrations greater than 7.1 mug/liter.

Animals

Effects of sub-chronic low-level dietary intake of chlordane on rats with cirrhosis of the liver.

Male rats, 60 days old, were treated with chlordane during or after induction of liver cirrhosis with carbon tetrachloride to determine the effect of treatment with chlordane on the response of the rats to the disease. When liver cirrhosis was induced simultaneously with chlordane treatment the disease symptoms were aggravated; the lipid content of the tissue was lowered significantly, growth rate was significantly lower than controls and there was no apparent replacement of damaged liver tissue by liver growth. The cytochrome P450 content of the liver was similar after both treatments. Continuation of the chlordane treatment after termination of the carbon tetrachloride treatment brought about a more rapid recovery from the induced cirrhotic condition. All these responses were to a dose range one tenth the recommended "no effect" level for healthy animals.

Animals

Postnatal endocrine dysfunction resulting from prenatal exposure to carbofuran, diazinon or chlordane.

Prenatal exposure to pesticides of three different classes initiated persistent postnatal endocrine dysfunction. Adrenal function and hepatic metabolism of corticosterone were studied in adult hybrid mice exposed during development to either an organophosphate (Diazinon), a carbamate (Carbofuran), or an organochlorine (Chlordane). Animals were exposed to relatively low levels of the toxins in utero and neonatally via the mothers' milk. Exposure to lower doses of the anticholinesterase compounds, Diazinon or Carbofuran, resulted in impairment of hepatic metabolism of corticosterone in vitro due to a loss in reductive capacity per unit liver weight. Plasma levels of corticosterone were also elevated in these animals, but without a concomitant increase in adrenal steroidogenesis in vitro. The effects of exposure to Chlordane were more complex. In male animals, exposure to lower doses of chlordane resulted in an increase in plasma corticosterone levels without an apparent increase in hepatic metabolism of corticosterone or adrenal steroidogenesis. In contrast, side-chain metabolism of corticosterone was decreased in female mice exposed to Chlordane. Similar effects on pituitary-adrenal function were not evident for the offspring of mice exposed to higher doses of the toxins. Possible mechanisms for this non-linear dose-response are discussed.

Adrenal Glands

Disposition of beta-hexachlorocyclohexane, p,p'-DDT, and trans-chlordane administered subcutaneously to monkeys (Macaca fascicularis).

To evaluate skin lipid analysis for the accumulation level of environmental pollutants, the correlations between organochlorine pesticide residues in adipose tissue, blood, and skin lipids of monkeys were studied. The mixture of beta-hexachlorocyclohexane (beta-HCH), p,p'-DDT, and trans-chlordane was subcutaneously given to monkeys once weekly for 5 weeks at dose levels of 1 and 10 mg/kg. The chemicals distributed in adipose tissue, blood, and skin lipids were determined six times after the last dosing at intervals of 4 to 9 weeks. Oxychlordane and p,p'-DDE were detected in all tissues together with the administered chemicals. In blood and adipose tissue, trans-chlordane decreased rapidly and oxychlordane and p,p'-DDE increased gradually and then remained at constant levels. beta-HCH and p,p'-DDT in adipose tissue increased until the 12th week and then decreased in all animals. The correlation coefficients between blood and adipose tissue regardless of dose level and collection time for each chemical ranged from 0.83 to 0.94. Correlation coefficients between skin lipids and adipose tissue varied with the chemical, namely, 0.31, 0.72, 0.81, 0.81, and 0.83 for p,p'-DDE, trans-chlordane, p,p'-DDT, beta-HCH, and oxychlordane, respectively. The results indicated that skin lipid analysis may be useful for the evaluation of specific pollutants in the body burden.

Adipose Tissue

Immune alterations in humans exposed to the termiticide technical chlordane.

Lymphocyte phenotype frequencies and in vitro functional assays were studied in 27 individuals who had been exposed to technical chlordane in their homes or at their places of work. A control group consisted of 118 individuals who were similar to the exposed group with respect to age and sex distribution, and who had not knowingly experienced exposure to technical chlordane, was chosen for study. A significantly increased frequency of cortical thymocytes in the circulation (CD1) (p less than .001) and a decreased frequency of the suppressor-inducer phenotype CD45RA/T4 (p less than .01) were noted in the exposed group. Both kappa and lambda light-chain frequencies were elevated (p less than .01). Proliferative responses to the three mitogens tested, PHA, CONA, PWM, and to allogeneic lymphocytes in the mixed-lymphocyte culture assay were significantly lower than in controls (p less than .01). Responses in assays of the natural killer function were not significantly different from those of controls, but Fc receptor-associated K cell function was significantly greater than responses in controls. Of 12 individuals tested for evidence of autoimmunity, 11 demonstrated some increased titer of a form of autoantibody. This cluster of significant findings demonstrates the emergence of aberrant peripheral T and B cell regulation and a potential for autoimmune activation, detectable up to 10 y after exposure to technical chlordane.

Adipose Tissue

Topical application of a chlordane-containing ectoparasiticide: effect on the plasma half-life of warfarin in dogs.

Brief exposure of dogs to topical chlordane solutions resulted in a significant and long-lasting decrease in the biological half-life of orally administered warfarin. The effect is presumed to be an expression of chlordane's well-documented inductive effect on hepatic microsomal drug metabolizing enzymes and its long-term storage in fat depots. The facility with which chlordane is absorbed through the intact skin of dogs may render casually-treated animals unsuitable for subsequent pharmacologic study for long periods of time.

Administration, Oral

Isolation and characterization of the photoalteration products of cis- and trans-chlordane.

Ultraviolet irradiation of cis- and trans-chlordane yielded 3 photolysis products. The expected half-caged analog of cis-chlordane was formed in high yield, and 2 minor photoproducts of trans-chlordane were observed. One of these products was a half-caged isomer. The individual photoproducts were isolated by thin layer chromatography and characterized by infrared, nuclear magnetic resonance, and mass spectrometry.

Chlordan

Gas-liquid chromatographic determination of technical chlordane residues in food crops: interpretation of analytical data.

An interlaboratory investigation of technical chlordane residues in food crops was carried out to determine the most practical and consistent method of reporting results. Using a technical chlordane reference standard, 8 gas chromatographic stationary phases were studied for their resolution capabilities. The best separations were obtained with SE-30 and its OV-1 equivalent. Using these columns and electron capture detection, potatoes and carrots from supervised field experiments were analyzed in duplicate and quantitated by using 4 methods of calculation. The data were statistically treated to determine the precision and bias for each method. Also, 1 sample was analyzed in duplicate on 2 different occasions by 6 laboratories to substantiate the initial conclusions. Based on the criterion of high precision it is suggested that a comparison of total area under the chromatogram of the sample with total area of standard technical chlordane be the method of quantitation. Only peaks which are common to both standard and sample have any significance in this type of calculation.

Chlordan

Histopathology of liver carcinomas in (C57BL/6N X C3H/HeN)F1 mice ingesting chlordane.

(C57BL/6N X C3H/HeN)F1 male mice that ingested 30 or 56 ppm chlordane and female mice that ingested 30 or 64 ppm chlordane in the diet had highly significant incidences of carcinomas of the liver. The carcinomas varied from well differentiated to poorly differentiated and undifferentiated and were capable of invasion and metastasis. They were more poorly differentiated in mice receiving chlordane than in controls.

Animals