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At least 19 recordsLinked to original sources
PubMed1997

Toxaphene congeners differ from toxaphene mixtures in their dysmorphogenic effects on cultured rat embryos.

The presence of persistent organic pollutants, including the pesticide toxaphene has been reported even in remote regions such as the Arctic and is becoming a health concern. The technical mixture of toxaphene contains over 800 different congeners. The numbers of prevalent congeners, however, decrease along the food chain. About 20 major congeners are found in fish, eight in marine mammals and only two major ones in human, 2-exo,3-endo,5-exo,6-endo,8,8,10,10-octachlorobornane (T2) and 2-exo,3-endo,5-exo,6-endo,8,8,9,10,10-nonachlorobornane (T12). Embryotoxicity of these individual congeners is not known, as previous studies focused on the toxaphene technical mixture. We studied the relative dysmorphogenic activity of toxaphene technical mixture and individual congeners (T2 and T12) using rat embryo culture. Explanted embryos (0-2 somites) were treated for 48 h with concentrations of 0 (DMSO 0.01%), 100, 1000 and 5000 ng/ml of either (a) toxaphene technical mixture; (b) T2; (c) T12; or (d) a 50:50 mixture of T2 and T12. The treatment period corresponds to gestational days (GD) 10-12, a period within the critical time of morphogenesis and organogenesis. Both the technical mixture and the two individual congeners had a significant adverse effects on the total morphological score, somite number, head and crown rump length and the central nervous system scores of embryos. All treatments caused a high incidence of central nervous system defects. The T2 and T12 congeners differed in their spectrum of abnormalities as exposure to T2 caused limb and flexion defects which were not observed with the T12 congener. Differences were also observed in the type of toxicity and the target sites between the technical mixture and the congeners. T2 showed a more potent adverse effect on the morphological score as compared to the technical mixture. Both T2 and T12 were less inhibitory on growth than the technical mixture as indicated by crown-rump length but they showed a stronger inhibitory effect on otic system development. The mixture of T2 + T12 showed a synergistic effect on decreasing crown-rump and head length. Conversely, the combination of T2 and T12 inhibited the strong adverse effect of the individual congeners on otic development. The results suggest environmentally predominant toxaphene congeners can have organ specific embryotoxic effects not predicted by the toxaphene technical mixture.

Animals↗
PubMed1980

Excretion and storage of [14C]toxaphene and two isolated [14C]toxaphene fractions.

The 7-d urinary and fecal excretions of [14C]toxaphene and two isolated [14C]toxaphene fractions (polar fraction 7 and nonpolar fraction 2) were determined in orally dosed rats. The urinary, fecal, and total excretions of toxaphene were, respectively, 22.5, 35.7, and 58.2% of the administered dose. The total excretions of fractions 2 and 7 were, respectively, 69.4 and 65.0%, and the overall order of excretion was fraction 2 greater than toxaphene greater than fraction 7. All three groups had low toxaphene levels (below 0.2 ppm) in all tissues analyzed except for fat, where significant levels were detected. Hexane and chloroform extracts of the urine revealed that the activity was more polar than the parent material for all three groups. Apparently, toxaphene must be metabolized before it can be excreted in the urine. When fat extracts were analyzed by thin-layer chromatography and autoradiography, differences were found between the parent material and the extracted activity. There was an increase in polar activity in the residue obtained from toxaphene-treated rats. The fat from the fraction 2 group contained fraction 2 and two additional more polar spots, which represented about 11% of the total activity. The fat from the fraction 7 group also contained two additional spots, but they were less polar than fraction 7. Apparently, the metabolism of fraction 7 results in some products that are less polar and, perhaps, more persistent.

Adipose Tissue↗
PubMed2005

Congener-specific concentrations and carbon stable isotope ratios (delta13C) of two technical toxaphene products (Toxaphene and Melipax).

In this study we compared the contribution of individual congeners and the ratios of stable carbon isotopes of two technical toxaphene products. The former US-American product Toxaphene was from 1978 and the East-German product Melipax from 1979. Both technical products showed the known complexity in GC/ECD measurements. Contributions of 24 peaks to each of the technical products were determined by gas chromatography in combination high resolution electron capture negative ion mass spectrometry (GC/ECNI-HRMS). The percentages of the compounds studied in the technical mixtures ranged from approximately 0.05% to approximately 2.5% but showed some individual differences. 2,2,5,5,8,9,9,10,10-nonachlorobornane (B9-1025 or P-62) was identified as a major congener in both mixtures. 2-Endo,3-exo,5-endo,6-exo,8,8,10,10-octachlorobornane (B8-1413 or P26) and 2-endo,3-exo,5-endo,6-exo,8,8,9,10,10-nonachlorobornane (B9-1679 or P-50) were found at similar concentration in both technical products. Identical amounts of Melipax or Toxaphene were combusted to CO2 in an element analyzer and their delta13C values were determined relative to the international standard Vienna PeeDee belemnite (VPDB). The mean delta13C values of both products varied by 2.8% (determined at two different locations) which is roughly one order of magnitude more than the precision obtained in repetitive analyses of the individual products. Thus, both investigated products could be unequivocally distinguished by stable isotope ratio mass spectrometry (IRMS). IRMS analyses may thus be a suitable tool for tracing back toxaphene residues in environmental and food samples to the one or both of the products.

Carbon Isotopes↗
PubMed2002

Interactive dysmorphogenic effects of toxaphene or toxaphene congeners and hyperglycemia on cultured whole rat embryos during organogenesis.

Both diabetes mellitus and exposure to environmental contaminants are becoming health hazards to many indigenous populations in the world. In earlier work, we established the embryopathy of the chlorinated pesticide, toxaphene technical mixture (TOX) and its two physiologically most important congeners, T(2) (2-exo,3-endo,5-exo,6-endo,8,8,10,10-octachlorobornane) and T(12) (2-exo,3-endo,5-exo,6-endo,8,8,9,10,10-nonachlorobornane). In this study, the combined effects of toxaphene or its two congeners and high glucose concentrations were studied using rat embryo culture in order to investigate the potential interactions between hyperglycemia and toxaphene exposure. Whole rat embryos (0-2 somite) were explanted and cultured into a normal (8 mM) or hyperglycemic 12.5 mM (12.5 G) or 18.75 mM (18.75 G) culture medium containing TOX, T(2), or T(12) at various concentrations (0, 100, 1000, 5000 ng/ml) for 48 h at 37 degrees C. All treatments, except mild hyperglycemic exposure (12.5 G), had significant adverse effects on the total morphological score, head and crown-rump length, yolk sac diameter and yolk sac circulation. Embryos exposed to 18.75 G did not show malformations but when hyperglycemia at 18.75 G was combined with higher doses of TOX or T(2) synergistic effects on the incidence of neural tube defects were observed. The embryos cultured with T(12) under severe hyperglycemic conditions of 18.75 G showed an inhibition of T(12)-induced neural tube defects, but there was a concurrent underdevelopment of forelimbs or hindlimbs at the highest T(12) dose. The results suggest that there is a site-specific and dose-related interactive dysmorphogenesis elicited by TOX or its congeners with high levels of glucose on rat embryonic development. Because of the relatively high TOX doses used in this study, the drastic growth retardation and malformation observed are unlikely to be observed in human populations. More subtle effects, however, may not be ruled out.

Animals↗
PubMed2005

Tracking toxaphene in the North American Great Lakes basin. 1. Impact of toxaphene residues in United States soils.

A coupled atmospheric transport model was employed to study six scenarios to assess the contribution of reemission and long-range transport of toxaphene from different sources in the United States to its environmental fate in the Great Lakes ecosystem in the year 2000. Modeled air concentrations at the first model level (1.5 m) range from less than 5 pg m(-3) over the upper Great lakes (Lakes Superior and Huron) to several tens of picograms per cubic meter over the lower Great Lakes (Lakes Erie and Ontario) in the summer but drop off to the range from 0.05 to 2 pg m(-3) in the wintertime. The modeled toxaphene depositions to the lakes suggest a decreasing trend from the mid-1990s to 2000. Modeling results showed that, on an annual basis, for the Great Lakes basin as a whole, the southeast U.S. sources made the largest contribution to the toxaphene air concentrations and dry and wet depositions at 72%, 78%, and 88% respectively. The model results also showed that a significant proportion of these contributions occur during relatively short episodic events due primarily to the interseasonal changes in atmospheric circulation patterns.

Atmosphere↗
PubMed1983

Rat hepatic microsomal enzyme induction by pretreatment with toxaphene and toxaphene fractions.

The levels of hepatic microsomal induction caused by toxaphene were determined. Young Sprague-Dawley rats (70 g) were administered toxaphene (ip injection, daily for 5 d) at 0, 5, 25, and 100 mg/kg. All doses caused increases in liver/body weight ratio, cytochrome P-450 level, aminopyrine demethylation, and aldrin epoxidation. The aldrin epoxidase activity increased almost 700% at the 100-mg/kg dose. Toxaphene was separated into nonpolar (S-A) and polar (S-B) fractions and administered as before at 25 mg/kg. All treatments caused significant increases in cytochrome P-450, aminopyrine demethylation, and aldrin epoxidation. A comparison of the treatments, however, did not reveal any significant differences between the treatments.

Animals↗
PubMed2002

A GCMSD/ECD method for the simultaneous determination of toxaphene and toxaphene congeners.

The methodology presented combines mass selective detection technology for routine automated total toxaphene determinations with electron capture detection confirmation of congener results. Total toxaphene values were calculated using a custom developed series of data analysis macroinstructions (macros) that eliminate potential interferences and collate peak areas. These macros create multi-level calibration tables with results automatically corrected for surrogate and performance standards. It is possible to produce congener data that provides results from both detectors in one report from a single injection.

Gas Chromatography-Mass Spectrometry↗
PubMed1991

Toxaphene: chemistry, biochemistry, toxicity and environmental fate.

The chemistry of toxaphene is now well developed; 20 isomers have been isolated and identified. The molecular weight and molecular formula are known for the remaining major components. The major metabolic degradation mechanisms for toxaphene in all organisms from bacteria to primates are now believed to the reductive dechlorination, reductive dehydrochlorination, and in some cases, oxidative dechlorination to produce hydroxyl derivatives, acids or ketones. Earlier reports that toxaphene was biodegradable were published before the advent of state-of-the-art analytical methodology which has permitted detection at levels in the range of ppb. Toxaphene residues have recently been documented throughout the biosphere as well as in human milk, even though its use was banned in 1982. This global persistence is against previous beliefs that toxaphene was easily biodegradable. During the last decade advances have been achieved in the selectivity, accuracy, and sensitivity of detection techniques so that the presence of toxaphene throughout the biosphere has been extensively documented. Through the use of GC/MS and electron capture GC, toxaphene can now be detected at ppb levels, making possible a more consistent and accurate assessment of the compound's presence in organisms as well as in soil, water, and ground water. Toxaphene residues have been detected in human populations, fish and wildlife, soil, water, and ground water as well as in food. An FDA Food Survey study found residues of toxaphene exceeding regulatory limits in only 1% of the 14,492 food samples. Toxaphene was reported to be among the most frequently occurring residues found in total dietary foods for the period 1982-84. It was found 48 times based on two food consumption surveys, a level higher than the frequency of DDT, DCPA, pentachloroaniline, and methoxychlor. Toxaphene has been detected in two large, pooled samples of human milk collected from mothers living in Uppsala and Stockholm at a concentration of 0.1 mg/kg of milk fat. Accumulation of toxaphene occurs in water in areas where the insecticide is in use, and it may be quite persistent. In some Canadian lakes it was found in toxic concentrations up to five yr after fish have been killed. Several studies have documented the presence of toxaphene in rain water, e.g. 9 ng/L in rain samples from Lake Michigan. It is now clear that toxaphene is a global pollutant like DDT, PCBs, and other organochlorines. Toxaphene is persistent in soils and lake sediments and has been found in fish, in the ringed seal, in rain water, and in human milk.(ABSTRACT TRUNCATED AT 400 WORDS)

Air Pollutants↗
PubMed2000

Toxaphene is antiestrogenic in a human breast-cancer cell assay.

Toxaphene is a complex mixture of chlorinated bornanes, bornenes, and bornadienes and was a heavily used insecticide in the United States until its use was restricted in 1982. There are conflicting reports regarding the potential for toxaphene to induce estrogenic responses in human and nonhuman animals. Due to the public concern over environmental estrogens, the estrogenicity of toxaphene was examined in a human breast-cancer cell assay, the MCF-7 focus assay, which is based on in vitro postconfluent cell proliferation and tissue restructuring. In this assay, 0.1-1 nM 17beta-estradiol (E2) produces maximum postconfluent proliferation and formation of multicellular nodules or foci. Toxaphene was also tested for its ability (1) to bind the estrogen receptor (ER) in a competitive binding assay using recombinant human ERalpha (rhER) and in a whole-cell competitive ER binding assay, and (2) to alter the catabolism of E2 in MCF-7 cell cultures. Results from the MCF-7 focus assay showed: (1) Toxaphene alone was not estrogenic between the concentrations of 0.5 nM and 10 microM, (2) toxaphene in binary combinations with chlordane, dieldrin, or endosulfan (alpha or beta) was not estrogenic, and (3) toxaphene was weakly antiestrogenic (it reduced the number of foci induced by 0.1 nM and 0.01 nM E2). Results from the competitive binding assays showed that (1) toxaphene alone did not bind rhER or ER in MCF-7 cells, and (2) toxaphene in binary combinations with other pesticides did not bind rhER. Results from the growth assay and radiometric analysis of E2 catabolism showed that (1) toxaphene did not alter the growth rate of MCF-7 cell cultures over 13 d, and (2) toxaphene did not alter the catabolism of E2. In conclusion, results from the MCF-7 focus assay demonstrate that toxaphene is weakly antiestrogenic rather than estrogenic.

Binding, Competitive↗
PubMed2004

Polybrominated diphenyl ether congeners and toxaphene in selected marine standard reference materials.

Polybrominated diphenyl ether (PBDE) congeners and components of the complex mixture toxaphene are stable in the environment and readily bioaccumulated into wildlife and human tissues. PBDEs are presently used in large quantities worldwide as flame retardants in textiles, furniture, computer equipment, and cables. Toxaphene is a complex mixture of chlorinated bornanes and bornenes that was the most heavily used pesticide in the United States until it was banned in 1982; however, some countries continue to use toxaphene. The National Institute of Standards and Technology has quantified PBDE congeners and toxaphene in several available Standard Reference Materials (SRMs) using methods of gas chromatography with electron impact mass spectrometry (GC-EI-MS) and GC negative chemical ionization (NCI) MS, respectively. SRM 1588a Organics in Cod Liver Oil and SRM 1945 Organics in Whale Blubber were examined for PBDE congeners 47, 99, 100, 153, and 154, total toxaphene, and toxaphene congeners 26, 50, and 62. SRM 1946 Lake Superior Fish Tissue was also examined for total toxaphene and toxaphene congeners. The sum of the PBDE congeners (mean, (1 SD) wet basis) for SRM 1945 was 150 ng g(-1) (7 ng g(-1)). The concentration of PBDE 47 in SRM 1588a was 82.7 ng g(-1) (2.8 ng g(-1)). Other PBDEs were detected in SRM 1588a but were not quantified due their low levels. The total toxaphene (wet mass basis) was 1,210 ng g(-1) (127 ng g(-1)), 1,960 ng g(-1) (133 ng g(-1)), and 3,980 ng g(-1) (248 ng g(-1)) in SRMs 1945, 1946, and 1588a, respectively. The values for PBDEs and toxaphene determined in the SRMs, while not certified, indicate that the SRMs will be suitable control materials for PBDE and toxaphene analyses.

Adipose Tissue↗
PubMed1983

Effect of toxaphene on the binding of 3H-labeled ouabain and dopamine to rat brain synaptosomes.

The effects of toxaphene, a chlorinated hydrocarbon pesticide, on the binding of ouabain and dopamine to rat brain synaptosomes enriched with Na+-K+ ATPase were investigated. For in vitro assessment of the effects of toxaphene, the synaptosomes prepared from normal rats were used. For in vivo effects the rats were fed on 0, 50, 100, 150 and 200 ppm toxaphene mixed in their daily ration for 8 weeks. At the end of treatment the rats were killed and synaptosomes were prepared. Toxaphene inhibited Na+-K+ and Mg2+ ATPases of synaptosomes in vitro and the inhibition was significant and concentration-dependent. The IC50 values were about 30 and 12 microM toxaphene for Na+-K+ and Mg2+ ATPases, respectively. However, much higher concentrations of toxaphene were required to inhibit the binding of [3H]ouabain and [3H]dopamine to synaptosomes. A 50% inhibition of ouabain and dopamine binding was obtained at 150 and 200 microM of toxaphene. The enzyme activities of synaptosomes in toxaphene-pretreated rats were decreased significantly. However, a dose-dependent decrease was not observed. The rats receiving dosages of 100 ppm and above showed a 30-40% decrease in enzyme activities. The binding of ouabain and dopamine to synaptosomes of toxaphene-pretreated rats showed no significant changes as compared to controls. The present in vitro results suggest that toxaphene may be an effective inhibitor of ATPases with substantial effects on the binding of ouabain and dopamine to rat brain synaptosomes. However, data obtained through in vivo studies do not support this contention. The reason for this discrepancy may be that the toxaphene is being rapidly metabolized or might not have reached the site of action.

Adenosine Triphosphatases↗
PubMed1999

Environmental occurrence, analysis, and toxicology of toxaphene compounds.

Toxaphene production, in quantities similar to those of polychlorinated biphenyls, has resulted in high toxaphene levels in fish from the Great Lakes and in Arctic marine mammals (up to 10 and 16 microg g-1 lipid). Because of the large variabiliity in total toxaphene data, few reliable conclusions can be drawn about trends or geographic differences in toxaphene concentrations. New developments in mass spectrometric detection using either negative chemical ionization or electron impact modes as well as in multidimensional gas chromatography recently have led researchers to suggest congener-specific approaches. Recently, several nomenclature systems have been developed for toxaphene compounds. Although all systems have specific advantages and limitations, it is suggested that an international body such as the International Union of Pure and Applied Chemistry make an attempt to obtain uniformity in the literature. Toxicologic information on individual chlorobornanes is scarce, but some reports have recently appeared. Neurotoxic effects of toxaphene exposure such as those on behavior and learning have been reported. Technical toxaphene and some individual congeners were found to be weakly estrogenic in in vitro test systems; no evidence for endocrine effects in vivo has been reported. In vitro studies show technical toxaphene and toxaphene congeners to be mutagenic. However, in vivo studies have not shown genotoxicity; therefore, a nongenotoxic mechanism is proposed. Nevertheless, toxaphene is believed to present a potential carcinogenic risk to humans. Until now, only Germany has established a legal tolerance level for toxaphene--0.1 mg kg-1 wet weight for fish.

Animals↗
PubMedDate not supplied

Investigation of hepatic cytochrome P-450 enzyme induction and DNA adduct formation in male CD/1 mice following oral administration of toxaphene.

Exposure of experimental animals to toxaphene induces hepatic cytochrome P-450 (CYP). Although chronic administration of toxaphene to mice was found to cause an increased incidence of liver tumors, a mechanism for its carcinogenicity has yet to be elucidated. We investigated two potential mechanisms of toxaphene-induced carcinogenicity: peroxisomal proliferation and DNA binding. Peroxisomal proliferation was evaluated by measuring the level of immunodetectable CYP 4A1, an isozyme of CYP that is specifically induced by peroxisomal proliferators, in hepatic microsomes from CD1 mice that were treated by oral gavage for seven consecutive days with corn oil vehicle or 10, 25, 50 or 100 mg kg(-1) toxaphene. In comparison to control mice, toxaphene-treated mice had increased liver weight, increased liver/body weight ratios and increased levels of total hepatic CYP and cytochrome b5. No increase in the level of immunodetectable levels of CYP 4A1 was found in hepatic microsomes from toxaphene-treated mice when compared to controls. In contrast, increases in immunodetectable CYP 4A1 were detected in hepatic microsomes from mice treated with the peroxisomal proliferator clofibrate. These findings suggest that toxaphene-induced induction of CYP may not involve CYP 4A1 and that peroxisomal proliferation may not be involved in toxicity. Significant increases in immunodetectable levels of CYP 2B were, however, detected in toxaphene-treated mice, and are consistent with earlier reports demonstrating that toxaphene, like many other pesticides, induces the phenobarbital-inducible subfamily of CYP. Analysis of DNA adduct levels in the livers of toxaphene-treated mice by DNA 32P-post-labeling showed no evidence of DNA adduct formation.

Animals↗
PubMed2001

Activation of human neutrophils by technical toxaphene.

Toxaphene is a persistent organic pollutant (POP) known to be composed of numerous congeners. Toxaphene technical mixture applied as a pesticide consists of over 800 congeners. Among these, T(2) and T(12) are the two environmentally prevalent forms found in humans. Although toxaphene is known to exert some toxic effects, including potential proinflammatory properties, little is known concerning its action on cells of the human immune system, especially neutrophils. In the present study, we found that toxaphene was not necrotic for human neutrophils incubated for up to 24 h with concentrations ranging from 0.1 to 50 microg/ml. Toxaphene was found to induce neutrophil superoxide production (O(-)(2)) in a concentration-dependent manner. The potency and the kinetics of toxaphene-induced O(-)(2) by neutrophils were found to be similar to that of the classical neutrophil agonists phorbol 12-myristate 13-acetate (PMA). Furthermore, the use of various transduction signal inhibitors (genistein, pertussis toxin, staurosporine, H-7, and HA-1077), suggests that, as for PMA, toxaphene mediates its effect primarily via PKCs and, to a lesser extend, via tyrosine kinases. In this respect, staurosporine, H-7, and genistein were found to inhibit toxaphene- and PMA-induced O(-)(2) production by 52, 72, and 31% and by 63, 62, and 23%, respectively. Toxaphene was also found to significantly enhance neutrophil phagocytosis of opsonized sheep red blood cells and to induce neutrophil apoptosis. The induction of neutrophil apoptosis was paralleled with a decrease in CD16 expression. T(2) and T(12), the two prevalent congeners found in humans, were also found to significantly increase the O(-)(2) production in neutrophils at a concentration of 5 microg/ml. We conclude that neutrophils are important targets for toxaphene, as this POP can activate O(-)(2) production by a PKC- and tyrosine kinase-dependent mechanism, induce phagocytosis, and accelerate the apoptotic rate. This is the first study that focuses on toxaphene/human neutrophil interactions.

Apoptosis↗
PubMed2004

Toxaphene detoxification and acclimation in Daphnia magna: do cytochrome P-450 enzymes play a role?

Toxaphene is a persistent environmental contaminant that has been shown to alter male production in Daphnia magna and to induce P-450 activity in mammals. Cytochrome P-450-mediated metabolism may lead to xenobiotic detoxification resulting in acclimation. To determine if D. magna acclimate to toxaphene via P-450 pathways, chronic and acute toxicity tests were conducted with D. magna exposed to toxaphene in the presence and absence of piperonyl butoxide (PBO), an inhibitor of cytochrome P-450 enzymes. Toxaphene exposure increased male production in acute but not chronic assays, indicating that D. magna may acclimate to chronic toxaphene exposure. Upon co-administration of toxaphene and PBO in chronic tests, D. magna exhibited a decline in growth rate, fecundity and survival. The observed toxaphene acclimation in chronic tests, along with its increased toxicity in the presence of a P-450 suppressor, suggests that P-450 enzymes may contribute to detoxification and subsequent acclimation of D. magna to chronic toxaphene exposure. Additional chronic toxicity tests indicated that toxaphene acclimation occurs between 7 and 12 days following initial exposure, at which time sex determination is no longer affected. Thus, sublethal toxaphene toxicity effects such as reproductive impairments may be detectable with acute but not chronic tests, potentially due to the upregulation of P-450 isozymes.

Acclimatization↗