MASS SPECTROMETRIC ANALYSIS AND CHARACTERIZATION OF KEPONE IN ENVIRONMENTAL AND HUMAN SAMPLES

EPA Science Inventory

A specific portion of our environment has been contaminated with Kepone, or chlordecone. Additionally, some specific human exposures to high concentrations of Kepone have been confirmed. Gas chromatography mass spectrometry involving chemical ionization and high resolution mass s...

IN VITRO AND IN VIVO TOXICITY: A COMPARISON OF ACRYLAMIDE, CYCLOPHOSPHAMIDE, CHLORDECONE, AND DIETHYLSTILBESTROL

EPA Science Inventory

Four chemicals that had been tested in an in vivo toxicological screen were tested in a Chinese hamster ovary (CHO) cytotoxicity assay. Cell density, viability, ATP concentration, rate of protein synthesis, and cellular protein concentration were decreased by exposure to acrylami...

Chlordecone disappearance in tissues of growing goats after a one month decontamination period--effect of body fatness on chlordecone retention.

PubMed

Lastel, Marie-Laure; Lerch, Sylvain; Fournier, Agnès; Jurjanz, Stefan; Mahieu, Maurice; Archimède, Harry; Feidt, Cyril; Rychen, Guido

2016-02-01

Chlordecone (CLD) is an organochlorine pesticide whose extended use led to the contamination of at least 20% of agricultural soils from the French West Indies. Livestock reared on polluted areas are involuntary contaminated by CLD and their level of contamination may exceed the threshold values set by the European Union. Thus, characterizing the CLD behaviour in farm animals appear as a real issue in terms of food safety for local populations. The aim of this experiment was (i) to characterize the CLD disappearance in various tissues after exposure cessation and (ii) to evaluate the potential effect of body fatness on this process. Two groups of eight growing goats were submitted to either a basal diet or a high energy diet for 50 days before being intravenously contaminated with 1 mg CLD kg(-1) body weight. Two days after CLD contamination, half of the kids of each experimental group were slaughtered in order to determine pollutant levels in the serum, liver, adipose tissues, and empty carcass. The remaining animals were submitted to a 30-day decontamination period before slaughtering and measurements as described above. The implemented nutritional plan resulted in both groups of kids with significant differences in terms of body fatness. CLD was mainly concentrated in the liver of animals as described in the literature. It was found also in kids' empty carcass and adipose tissues; however its levels in the empty carcass (muscles and bones) were unexpected since they were higher than in fat. These results indicate that the lipophilic pollutant CLD is found mainly in liver but also in muscles and fat. Concerning the animals' depuration, a 30-d decontamination period was sufficient to observe a decrease of CLD levels by more than 75% in both experimental groups and neither CLD concentrations nor CLD amounts were significantly affected by kids' body fatness.

Growth parameters influencing uptake of chlordecone by Miscanthus species.

PubMed

Liber, Yohan; Létondor, Clarisse; Pascal-Lorber, Sophie; Laurent, François

2018-05-15

Because of its high persistence in soils, t 1/2 =30years, chlordecone (CLD) was classified as a persistent organic pollutant (POP) by the Stockholm Convention in 2009.The distribution of CLD over time has been heterogeneous, ranging from banana plantations to watersheds, and contaminating all environmental compartments. The aims of this study were to (i) evaluate the potential of Miscanthus species to extract chlordecone from contaminated soils, (ii) identify the growth parameters that influence the transfer of CLD from the soil to aboveground plant parts. CLD uptake was investigated in two species of Miscanthus, C4 plants adapted to tropical climates. M. sinensis and M.×giganteus were transplanted in a soil spiked with [ 14 C]CLD at environmental concentrations (1mgkg -1 ) under controlled conditions. Root-shoot transfer of CLD was compared in the two species after two growing periods (2 then 6months) after transplantation. CLD was found in all plant organs, roots, rhizomes, stems, leaves, and even flower spikes. The highest concentration of CLD was in the roots, 5398±1636 (M.×giganteus) and 14842±3210ngg -1 DW (M. sinensis), whereas the concentration in shoots was lower, 152±28 (M.×giganteus) and 266±70ngg -1 DW (M. sinensis) in soil contaminated at 1mgkg -1 . CLD translocation led to an acropetal gradient from the bottom to the top of the plants. CLD concentrations were also monitored over two complete growing periods (10months) in M. sinensis grown in 8.05mgkg -1 CLD contaminated soils. Concentrations decreased in M. sinensis shoots after the second growth period due to the increase in organic matters in the vicinity of the roots. Results showed that, owing to their respective biomass production, the two species were equally efficient at phytoextraction of CLD. Copyright © 2017. Published by Elsevier B.V.

Chlordecone Transfer and Distribution in Maize Shoots.

PubMed

Pascal-Lorber, Sophie; Létondor, Clarisse; Liber, Yohan; Jamin, Emilien L; Laurent, François

2016-01-20

Chlordecone (CLD) is a persistent organic pollutant (POP) that was mainly used as an insecticide against banana weevils in the French West Indies (1972-1993). Transfer of CLD via the food chain is now the major mechanism for exposure of the population to CLD. The uptake and the transfer of CLD were investigated in shoots of maize, a C4 model plant growing under tropical climates, to estimate the exposure of livestock via feed. Maize plants were grown on soils contaminated with [(14)C]CLD under controlled conditions. The greatest part of the radioactivity was associated with roots, nearly 95%, but CLD was detected in whole shoots, concentrations in old leaves being higher than those in young ones. CLD was thus transferred from the base toward the plant top, forming an acropetal gradient of contaminant. In contrast, results evidenced the existence of a basipetal gradient of CLD concentration within leaves whose extremities accumulated larger amounts of CLD because of evapotranspiration localization. Extractable residues accounted for two-thirds of total residues both in roots and in shoots. This study highlighted the fact that the distribution of CLD contamination within grasses resulted from a conjunction between the age and evapotranspiration rate of tissues. CLD accumulation in fodder may be the main route of exposure for livestock.

Effects of chlordecone on 20-hydroxyecdysone concentration and chitobiase activity in a decapod crustacean, Macrobrachium rosenbergii.

PubMed

Lafontaine, Anne; Gismondi, Eric; Boulangé-Lecomte, Céline; Geraudie, Perrine; Dodet, Nathalie; Caupos, Fanny; Lemoine, Soazig; Lagadic, Laurent; Thomé, Jean-Pierre; Forget-Leray, Joëlle

2016-07-01

Chlordecone (CLD) is an organochlorine insecticide abundant in aquatic environment of the French West Indies. However, few studies have investigated its impact on freshwater invertebrates. Whereas CLD is suspected of inducing endocrine disruption, this work aimed to study the effects of environmentally relevant concentrations of CLD on the 20-hydroxyecdysone (20-HE) hormone concentration and on the chitobiase activity, both having key roles in the molting process of crustaceans. In addition, the bioaccumulation of CLD was measured in the muscle tissue of Macrobrachium rosenbergii to underline potential dose-response relationship. The results have shown that CLD was bioaccumulated in exposed organisms according to a trend to a dose-response relationship. Moreover, it was observed that CLD decreased the 20-HE concentration in exposed prawns when compared to control, whatever the duration of exposure, as well as it inhibited the chitobiase activity after 30days of exposure. The present study indicates that CLD could interfere with molting process of M. rosenbergii by disturbing the 20-HE concentration and the activity of chitobiase, suggesting consequences at the long term on the shrimp development. This study also confirmed that CLD could be an endocrine disruptor in decapod crustaceans, as it was already observed in vertebrates. Copyright © 2016 Elsevier B.V. All rights reserved.

Molecular cloning of two human liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase isoenzymes that are identical with chlordecone reductase and bile-acid binder.

PubMed Central

Deyashiki, Y; Ogasawara, A; Nakayama, T; Nakanishi, M; Miyabe, Y; Sato, K; Hara, A

1994-01-01

Human liver contains two dihydrodiol dehydrogenases, DD2 and DD4, associated with 3 alpha-hydroxysteroid dehydrogenase activity. We have raised polyclonal antibodies that cross-reacted with the two enzymes and isolated two 1.2 kb cDNA clones (C9 and C11) for the two enzymes from a human liver cDNA library using the antibodies. The clones of C9 and C11 contained coding sequences corresponding to 306 and 321 amino acid residues respectively, but lacked 5'-coding regions around the initiation codon. Sequence analyses of several peptides obtained by enzymic and chemical cleavages of the two purified enzymes verified that the C9 and C11 clones encoded DD2 and DD4 respectively, and further indicated that the sequence of DD2 had at least additional 16 residues upward from the N-terminal sequence deduced from the cDNA. There was 82% amino acid sequence identity between the two enzymes, indicating that the enzymes are genetic isoenzymes. A computer-based comparison of the cDNAs of the isoenzymes with the DNA sequence database revealed that the nucleotide and amino acid sequences of DD2 and DD4 are virtually identical with those of human bile-acid binder and human chlordecone reductase cDNAs respectively. Images Figure 1 PMID:8172617

Investigating apical adverse effects of four endocrine active substances in the freshwater gastropod Lymnaea stagnalis.

PubMed

Giusti, Arnaud; Lagadic, Laurent; Barsi, Alpar; Thomé, Jean-Pierre; Joaquim-Justo, Célia; Ducrot, Virginie

2014-09-15

The hermaphroditic gastropod Lymnaea stagnalis is proposed as a candidate species for the development of OECD guidelines for testing of the reprotoxicity of chemicals, including endocrine active substances (EASs). Up to now, only a few putative EASs have been tested for their reproductive toxicity in this species. In this study, we investigate the effects of four EASs with different affinities to the vertebrate estrogen and androgen receptors (chlordecone as an estrogen; cyproterone acetate, fenitrothion and vinclozolin as anti-androgens) on the reproduction of L. stagnalis in a 21-day semi-static test. Testosterone and 17α-ethinylestradiol (EE2) were used as the reference compounds. The tested EASs had no significant effect on growth and survival at the tested concentration ranges (ng to μg/L). Classical reproduction endpoints (i.e., oviposition and fecundity) were not responsive to the tested chemicals, except for chlordecone and 17α-ethinylestradiol, which hampered reproduction from 19.6 μg/L and 17.6 μg/L, respectively. The frequency of polyembryonic eggs, used as an additional endpoint, demonstrated the effects of all compounds except EE2. The molecular pathways, which are involved in such reproduction impairments, remain unknown. Our results suggest that egg quality is a more sensitive endpoint as compared to other reproductive endpoints commonly assessed in mollusk toxicity tests. Copyright © 2014 Elsevier B.V. All rights reserved.

Co-transport of chlordecone and sulfadiazine in the presence of functionalized multi-walled carbon nanotubes in soils.

PubMed

Zhang, Miaoyue; Engelhardt, Irina; Šimůnek, Jirka; Bradford, Scott A; Kasel, Daniela; Berns, Anne E; Vereecken, Harry; Klumpp, Erwin

2017-02-01

Batch and saturated soil column experiments were conducted to investigate sorption and mobility of two 14 C-labeled contaminants, the hydrophobic chlordecone (CLD) and the sulfadiazine (SDZ), in the absence or presence of functionalized multi-walled carbon nanotubes (MWCNTs). The transport behaviors of CLD, SDZ, and MWCNTs were studied at environmentally relevant concentrations (0.1-10 mg L -1 ) and they were applied in the column studies at different times. The breakthrough curves and retention profiles were simulated using a numerical model that accounted for the advective-dispersive transport of all compounds, attachment/detachment of MWCNTs, equilibrium and kinetic sorption of contaminants, and co-transport of contaminants with MWCNTs. The experimental results indicated that the presence of mobile MWCNTs facilitated remobilization of previously deposited CLD and its co-transport into deeper soil layers, while retained MWCNTs enhanced SDZ deposition in the topsoil layers due to the increased adsorption capacity of the soil. The modeling results then demonstrated that the mobility of engineered nanoparticles (ENPs) in the environment and the high affinity and entrapment of contaminants to ENPs were the main reasons for ENP-facilitated contaminant transport. On the other hand, immobile MWCNTs had a less significant impact on the contaminant transport, even though they were still able to enhance the adsorption capacity of the soil. Copyright © 2016 Elsevier Ltd. All rights reserved.

Uptake and distribution of chlordecone in radish: different contamination routes in edible roots.

PubMed

Létondor, Clarisse; Pascal-Lorber, Sophie; Laurent, François

2015-01-01

Chlordecone (CLD) was an organochlorine insecticide mainly used to struggle against banana weevils in the French West Indies. Forbidden since 1993, it has been a long-term contaminant of soils and aquatic environments. Crops growing in contaminated soils lead to human exposure by food consumption. We used radiolabeled [(14)C]-CLD to investigate the contamination ways into radish, a model of edible roots. Radish plants were able to accumulate CLD in both roots (RCF35d 647) and tubers (edible parts, CF35d 6.3). CLD was also translocated to leaves (CF35d 1.7). The contamination of tuber was mainly due to peridermic adsorption or CLD systemic translocation to the pith. TSCF was 3.44×10(-)(3). CLD diffused across periderm to internal tissues. We calculated a mean flux of diffusion J through periderm about 5.71×10(-)(14)gcm(-)(2)s(-)(1). We highlighted different contamination routes of the tuber, (i) adsorption on periderm followed by diffusion of CLD towards underlying tissues, cortex, xylem, and pith (ii) adsorption by roots and translocation by the transpiration stream followed by diffusion from xylem vessels towards inner tissues, pith, and peripheral tissues, cortex and periderm. Concerning chemical risk assessment for other tubers, contamination would depend on various parameters, the thickness of periderm and CLD periderm permeance, the origin of secondary tissues - from cortex and/or pith - , the importance of xylem flow in tuber, and the lipid amount within tuber. Copyright © 2014 Elsevier Ltd. All rights reserved.

Two dechlorinated chlordecone derivatives formed by in situ chemical reduction are devoid of genotoxicity and mutagenicity and have lower proangiogenic properties compared to the parent compound.

PubMed

Legeay, Samuel; Billat, Pierre-André; Clere, Nicolas; Nesslany, Fabrice; Bristeau, Sébastien; Faure, Sébastien; Mouvet, Christophe

2018-05-01

Chlordecone (CLD) is a chlorinated hydrocarbon insecticide, now classified as a persistent organic pollutant. Several studies have previously reported that chronic exposure to CLD leads to hepatotoxicity, neurotoxicity, raises early child development and pregnancy complications, and increases the risk of liver and prostate cancer. In situ chemical reduction (ISCR) has been identified as a possible way for the remediation of soils contaminated by CLD. In the present study, the objectives were (i) to evaluate the genotoxicity and the mutagenicity of two CLD metabolites formed by ISCR, CLD-5a-hydro, or CLD-5-hydro (5a- or 5- according to CAS nomenclature; CLD-1Cl) and tri-hydroCLD (CLD-3Cl), and (ii) to explore the angiogenic properties of these molecules. Mutagenicity and genotoxicity were investigated using the Ames's technique on Salmonella typhimurium and the in vitro micronucleus micromethod with TK6 human lymphoblastoid cells. The proangiogenic properties were evaluated on the in vitro capillary network formation of human primary endothelial cells. Like CLD, the dechlorinated derivatives of CLD studied were devoid of genotoxic and mutagenic activity. In the assay targeting angiogenic properties, significantly lower microvessel lengths formed by endothelial cells were observed for the CLD-3Cl-treated cells compared to the CLD-treated cells for two of the three tested concentrations. These results suggest that dechlorinated CLD derivatives are devoid of mutagenicity and genotoxicity and have lower proangiogenic properties than CLD.

Decision support tool for soil sampling of heterogeneous pesticide (chlordecone) pollution.

PubMed

Clostre, Florence; Lesueur-Jannoyer, Magalie; Achard, Raphaël; Letourmy, Philippe; Cabidoche, Yves-Marie; Cattan, Philippe

2014-02-01

When field pollution is heterogeneous due to localized pesticide application, as is the case of chlordecone (CLD), the mean level of pollution is difficult to assess. Our objective was to design a decision support tool to optimize soil sampling. We analyzed the CLD heterogeneity of soil content at 0-30- and 30-60-cm depth. This was done within and between nine plots (0.4 to 1.8 ha) on andosol and ferralsol. We determined that 20 pooled subsamples per plot were a satisfactory compromise with respect to both cost and accuracy. Globally, CLD content was greater for andosols and the upper soil horizon (0-30 cm). Soil organic carbon cannot account for CLD intra-field variability. Cropping systems and tillage practices influence the CLD content and distribution; that is CLD pollution was higher under intensive banana cropping systems and, while upper soil horizon was more polluted than the lower one with shallow tillage (<40 cm), deeper tillage led to a homogenization and a dilution of the pollution in the soil profile. The decision tool we proposed compiles and organizes these results to better assess CLD soil pollution in terms of sampling depth, distance, and unit at field scale. It accounts for sampling objectives, farming practices (cropping system, tillage), type of soil, and topographical characteristics (slope) to design a relevant sampling plan. This decision support tool is also adaptable to other types of heterogeneous agricultural pollution at field level.

Study of chlordecone desorption from activated carbons and subsequent dechlorination by reduced cobalamin.

PubMed

Ranguin, Ronald; Durimel, Axelle; Karioua, Reeka; Gaspard, Sarra

2017-11-01

Since 1972, the French departments of Guadeloupe and Martinique have intensively used organochlorinated pesticides such as chlordecone (CLD) and hexachlorocyclohexane (HCH) isomers to prevent the proliferation of banana weevil (Cosmopolite sordidus). These molecules are stable in the environment, leading to a continuous contamination of soils, water, and food chain in the banana-producing areas. In these polluted areas, water treatment plants are equipped with activated carbon (AC) filters. In order to improve treatment of CLD-contaminated waters by AC, CLD adsorption and desorption kinetic studies are carried out using different ACs produced from sugar cane bagasse as adsorbents and subsequent CLD degradation is performed using reduced vitamin B12 (VB12). A GC-MS method for CLD quantification is as well optimized. This study shows that bagasse ACs are able to capture the pollutant, leading to a CLD concentration decrease from 1 to 73 μg L -1 , with an adsorption capacity of 162 μg mg -1 . Adsorption capacity increase with the temperature indicates an endothermic process. Polar solvents favor CLD desorption from ACs, suggesting hydrogen bonding between CLD and surface groups of ACs, the best solvent for chemical desorption being ethanol. Subsequent degradation of CLD in ethanol is performed using vitamin B12 reduced by either 1,4-dithiotreitol (DTT) or zerovalent zinc, leading to 90% of CLD removal and to the molecule cage structure opening for formation of a pentachloroindene intermediate product, characterized by GC MS/MS. A pathway for pentachloroindene formation from CLD is proposed.

Persistent Organochlorine Pollutants with Endocrine Activity and Blood Steroid Hormone Levels in Middle-Aged Men

PubMed Central

Emeville, Elise; Giton, Frank; Giusti, Arnaud; Oliva, Alejandro; Fiet, Jean; Thomé, Jean-Pierre; Blanchet, Pascal; Multigner, Luc

2013-01-01

Background Studies relating long-term exposure to persistent organochlorine pollutants (POPs) with endocrine activities (endocrine disrupting chemicals) on circulating levels of steroid hormones have been limited to a small number of hormones and reported conflicting results. Objective We examined the relationship between serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulphate, androstenedione, androstenediol, testosterone, free and bioavailable testosterone, dihydrotestosterone, estrone, estrone sulphate, estradiol, sex-hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone as a function of level of exposure to three POPs known to interfere with hormone-regulated processes in different way: dichlorodiphenyl dichloroethene (DDE), polychlorinated biphenyl (PCB) congener 153, and chlordecone. Methods We collected fasting, morning serum samples from 277 healthy, non obese, middle-aged men from the French West Indies. Steroid hormones were determined by gas chromatography-mass spectrometry, except for dehydroepiandrosterone sulphate, which was determined by immunological assay, as were the concentrations of sex-hormone binding globulin, follicle-stimulating hormone and luteinizing hormone. Associations were assessed by multiple linear regression analysis, controlling for confounding factors, in a backward elimination procedure, in multiple bootstrap samples. Results DDE exposure was negatively associated to dihydrotestosterone level and positively associated to luteinizing hormone level. PCB 153 was positively associated to androstenedione and estrone levels. No association was found for chlordecone. Conclusions These results suggested that the endocrine response pattern, estimated by determining blood levels of steroid hormones, varies depending on the POPs studied, possibly reflecting differences in the modes of action generally attributed to these compounds. It remains to be investigated whether this response pattern is predictive of the subsequent occurrence of disease. PMID:23785499

Cytotoxic effects and aromatase inhibition by xenobiotic endocrine disrupters alone and in combination.

PubMed

Benachour, Nora; Moslemi, Safa; Sipahutar, Herbert; Seralini, Gilles-Eric

2007-07-15

Xenobiotics may cause long-term adverse effects in humans, especially at the embryonic level, raising questions about their levels of exposure, combined effects, and crucial endpoints. We are interested in the possible interactions between xenobiotic endocrine disrupters, cellular viability and androgen metabolism. Accordingly, we tested aroclor 1254 (A1254), atrazine (AZ), o,p'-DDT, vinclozolin (VZ), p,p'-DDE, bisphenol A (BPA), chlordecone (CD), nonylphenol (NP), tributylin oxide (TBTO), and diethylstilbestrol (DES) for cellular toxicity against human embryonic 293 cells, and activity against cellular aromatase, but also on placental microsomes and on the purified equine enzyme. Cellular viability was affected in 24 h by all the xenobiotics with a threshold at 50 microM (except for TBTO and DES, 10 microM threshold), and aromatase was inhibited at non-toxic doses. In combination synergism was observed reducing the threshold values of toxicity to 4-10 microM, and aromatase activity by 50% in some cases. In placental microsomes the most active xenobiotics rapidly inhibited microsomal aromatase in a manner independent of NADPH metabolism. Prolonged exposures to low doses in cells generally amplified by 50 times aromatase inhibition. These xenobiotics may act by inhibition of the active site or by allosteric effects on the enzyme. Bioaccumulation is a feature of some xenobiotics, especially chlordecone, DDT and DDE, and low level chronic exposures can also affect cell signaling mechanisms. This new information about the mechanism of action of these xenobiotics will assist in improved molecular design with a view to providing safer compounds for use in the (human) environment.

Contamination of free-range ducks by chlordecone in Martinique (French West Indies): a field study.

PubMed

Jondreville, Catherine; Lavigne, Anaïs; Jurjanz, Stefan; Dalibard, Christophe; Liabeuf, Jean-Marie; Clostre, Florence; Lesueur-Jannoyer, Magalie

2014-09-15

The former use of chlordecone (CLD) in the French West Indies has resulted in long-term pollution of soils and subsequently of food chains. In contaminated areas, free-range ducks used to control weeds in orchards may be exposed to CLD through polluted soil ingestion. The question arises whether they may be consumed. Muscovy ducks were raised on a guava orchard planted on a soil moderately contaminated (410 μg CLD/kg dry matter). Ducks were raised indoor up to 6 weeks of age and allowed to range freely outdoors thereafter. Twenty-nine females were sequentially slaughtered by groups of 2 to 5 ducks, after 4, 16, 19, 22 or 26 weeks spent in the orchard or after 16-17 weeks in the orchard followed by 3, 6 or 9 weeks in a closed shelter for depuration. CLD concentration increased from 258 to 1051, 96 to 278, 60 to 169 and 48 to 145 μg/kg fresh matter (FM) as the exposure through grazing increased from 4 to 22 weeks, in liver, abdominal fat and leg with and without skin, respectively. Eggs collected in the orchard contained up to 1001 μg CLD/kg FM. All these values exceeded the Maximum Residue Limit (MRL) of 20 μg/kg FM. CLD concentration in all tissues was divided by around 10 within the 9-week confinement period. Despite this quite rapid decontamination, it is estimated that 12-13 weeks would be required to achieve the MRL in liver and in eggs, and 5-6 weeks in leg muscle. Such durations would be too long in practice. Thus, the consumption of products from free-range ducks should be avoided, even in areas mildly contaminated with CLD. Copyright © 2014 Elsevier B.V. All rights reserved.

Toxicokinetics of chlordecone in goats: Implications for risk management in French West Indies.

PubMed

Fournier, Agnès; Feidt, Cyril; Lastel, Marie-Laure; Archimede, Harry; Thome, Jean-Pierre; Mahieu, Maurice; Rychen, Guido

2017-03-01

The former use of chlordecone (CLD) in the French West Indies has resulted in long-term pollution of soils. CLD is known to be potentially transferred towards animal products of animals reared outdoors, mainly through accidental soil ingestion. Several studies indicate that soil bound CLD is bioavailable when administered to farm animals. Currently there is a need to quantify the level of CLD absorption and its toxicokinetic characteristics in the ruminant and particularly in the goat. These are considered as important farm species in the French West Indies. The objective of this study was to evaluate the absorption rate and the half-life of CLD in the non-lactating goat. The goats were administered either intravenously (i.v., n = 6) or orally (p.o., n = 6) one dose (1 mg kg -1 body weight) of CLD. Blood samples were collected at defined times up to 160 days post-dosing. CLD was analyzed in serum by high-resolution gas chromatography. A comparison of the area under the serum concentration-time curves (AUC) showed that the i.v. route is equivalent to the oral route. Thus, CLD is considered almost completely absorbed after p.o. administration, as shown by the mean absolute bioavailability. The comparison between the pharmacokinetic profiles of CLD following oral and intravenous dose showed a difference during the first 14 days and a similar kinetic after this period. The half-life of CLD in serum was close to 20 days. These results highlight a possible strategy of decontamination due to the short half-life of CLD, obtained in dry goats that did not excrete fat matter. Copyright © 2016 Elsevier Ltd. All rights reserved.

Kinetic study of chlordecone orally given to laying hens (Gallus domesticus).

PubMed

Jondreville, Catherine; Fournier, Agnès; Mahieu, Maurice; Feidt, Cyril; Archimède, Harry; Rychen, Guido

2014-11-01

The former use of chlordecone (CLD) in the French West Indies has resulted in long-term pollution of soils. In this area, CLD may be transferred into eggs of hens reared outdoors, through soil ingestion. In order to assess this risk, a kinetic study involving the contamination of laying hens (22 weeks of age) with a diet containing 500 μg CLD kg(-1) during 42 d, followed by a depuration period of 35 d was carried out. Forty-four hens were sequentially slaughtered all over the experimental period and their liver, egg, abdominal fat and serum were collected. Two additional edible tissues, pectoral and leg muscles, were collected in hens slaughtered at the end of the contamination period. The depuration half-life of CLD in liver, egg, abdominal fat and serum was estimated at 5.0 ± 0.38 (mean ± SE), 5.5 ± 0.29, 5.3 ± 0.37 and 5.1 ± 0.66 d, respectively. CLD concentration at the end of the contamination period reached 1640 ± 274, 460 ± 41, 331 ± 23, and 213 ± 8.5 μg kg(-1) fresh matter (FM), respectively. The corresponding concentrations in pectoral and leg muscles were 119 ± 8.4, 127 ± 11 μg kg(-1) FM, respectively. The steady state carry over rate of CLD in eggs reached 43 ± 7.6%. This experiment demonstrates the preferential accumulation of CLD in liver, its significant transfer to eggs and its quite short half-life. It is concluded that raising hens on even mildly contaminated areas would lead to products exceeding the regulatory maximum residue limit of 20 μg CLD kg(-1). Copyright © 2014 Elsevier Ltd. All rights reserved.

Activated carbon, a useful medium to bind chlordecone in soil and limit its transfer to growing goat kids.

PubMed

Yehya, Sarah; Delannoy, Matthieu; Fournier, Agnès; Baroudi, Moomen; Rychen, Guido; Feidt, Cyril

2017-01-01

Chlordecone (Kepone) (CLD) is a highly persistent pesticide which was extensively used in the French West Indies; high levels of CLD can still currently be found in large agricultural areas. As CLD transfers from soil to animals mainly via involuntary ingestion, the consumption of foodstuffs derived from animals raised in contaminated areas may significantly contribute to exposure of humans to CLD. The present study was designed to test the efficacy of two different activated carbons (ACs) sources in limiting CLD transfer from soil to animal. Three soils (ASs) were prepared according to the OECD guideline 207. One standard soil (SS) lacking AC, and two modified preparations of SS supplemented with 2% coconut-based activated carbon (ORBO), SSO or with 2% lignite-based one (DARCO), SSD. All three soils were spiked with 10 μg of kepone per g of dry matter and aged for three weeks. This study involved 15 goat kids randomly assigned to the 3 experimental groups (n = 5/group), which were fed the experimental matrices at an exposure dose of 10 μg CLD per kg of body weight per day. After 21 d of oral exposure, CLD in adipose tissue and liver were analysed by LC-MS-MS. A significant decrease of 63.7% and 74.7% of CLD concentrations in adipose tissue and liver, respectively, were obtained from animals exposed using SS containing DARCO as compared to those receiving only SS. Decreases in CLD levels of 98.2% (adipose tissue) and 98.7% (liver) were obtained for animals exposed using SS containing ORBO. This study leads us to conclude that (i) the presence of AC in CLD-contaminated soil strongly reduces CLD bioavailability, and (ii) the efficacy depends on the nature and characteristics of the AC used.

Chlordecone Altered Hepatic Disposition of [14C]Cholesterol and Plasma Cholesterol Distribution but not SR-BI or ABCG8 Proteins in Livers of C57BL/6 Mice

PubMed Central

Lee, Junga; Scheri, Richard C.; Curtis, Lawrence R.

2011-01-01

Organochlorine (OC) insecticides continue to occur in tissues of humans and wildlife throughout the world although they were banned in the United States a few decades ago. Low doses of the OC insecticide chlordecone (CD) alter hepatic disposition of lipophilic xenobiotics and perturb lipid homeostasis in rainbow trout, mice and rats. CD pretreatment altered tissue and hepatic subcellular distribution of exogenous [14C]cholesterol (CH) equivalents 4 and 16 h after a bolus intraperitoneal (ip) injection of 5 ml corn oil/kg that contained 10 mg CH/kg. CD pretreatment altered tissue distribution of exogenously administered [14C]CH by decreased hepatic and renal accumulation, and increased biliary excretion up to 300%. Biliary excretion of polar [14C]CH metabolites was not altered by CD. CD pretreatment decreased subcellular distribution of [14C]CH equivalents in hepatic cytosol and microsomes and lipoprotein-rich fraction-to-homogenate ratio. CD pretreatment increased the ratio of [14C]CH equivalents in high density lipoprotein (HDL) to that in plasma and reduced [14C]CH equivalents in the non-HDL fraction 4 h after a bolus lipid dose. CD pretreatment increased plasma non-HDL total CH by 80% 4 h after a bolus lipid dose. Scavenger receptor class B type I (SR-BI) and ATPbinding cassette transporter G8 (ABCG8) proteins were quantified by western blotting in hepatic membranes from control and CD treated mice. Liver membrane contents of SR-BI and ABCG8 proteins were unchanged by CD pretreatment. The data demonstrated that a single dose of CD altered CH homeostasis and lipoprotein metabolism. PMID:18387646

Chlordecone altered hepatic disposition of [14C]cholesterol and plasma cholesterol distribution but not SR-BI or ABCG8 proteins in livers of C57BL/6 mice.

PubMed

Lee, Junga; Scheri, Richard C; Curtis, Lawrence R

2008-06-15

Organochlorine (OC) insecticides continue to occur in tissues of humans and wildlife throughout the world although they were banned in the United States a few decades ago. Low doses of the OC insecticide chlordecone (CD) alter hepatic disposition of lipophilic xenobiotics and perturb lipid homeostasis in rainbow trout, mice and rats. CD pretreatment altered tissue and hepatic subcellular distribution of exogenous [(14)C]cholesterol (CH) equivalents 4 and 16 h after a bolus intraperitoneal (ip) injection of 5 ml corn oil/kg that contained 10 mg CH/kg. CD pretreatment altered tissue distribution of exogenously administered [(14)C]CH by decreased hepatic and renal accumulation, and increased biliary excretion up to 300%. Biliary excretion of polar [(14)C]CH metabolites was not altered by CD. CD pretreatment decreased subcellular distribution of [(14)C]CH equivalents in hepatic cytosol and microsomes and lipoprotein-rich fraction-to-homogenate ratio. CD pretreatment increased the ratio of [(14)C]CH equivalents in high density lipoprotein (HDL) to that in plasma and reduced [(14)C]CH equivalents in the non-HDL fraction 4 h after a bolus lipid dose. CD pretreatment increased plasma non-HDL total CH by 80% 4 h after a bolus lipid dose. Scavenger receptor class B type I (SR-BI) and ATP-binding cassette transporter G8 (ABCG8) proteins were quantified by western blotting in hepatic membranes from control and CD treated mice. Liver membrane contents of SR-BI and ABCG8 proteins were unchanged by CD pretreatment. The data demonstrated that a single dose of CD altered CH homeostasis and lipoprotein metabolism.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soileau, S.D.

Chlordecone (CHLO, 1-30 uM) and chlordecone alcohol (CHLO ALC, 1-23 uM) altered the permeability of isolated ovine erythrocytes (OE) as evidenced by a concentration- and time-dependent induction of K/sup +/ efflux and hemolysis. Hemolysis, but no K/sup +/ efflux, was markedly delayed when OE were suspended in isotonic sucrose. Low concentrations of both compounds (1-4 uM) protected OE against hypotonic hemolysis. Neither CHLO (30 uM) nor CHLO ALC (23 uM) induced the release of trapped K/sup +/ from KSCN-loaded, OE-lipid, unilamellar liposomes. CHLO- and CHLO ACL-induced hemolysis and K/sup +/ efflux were dependent upon the pH of the external media.more » CHLO ALC-induced K/sup +/ efflux and hemolysis showed a slight pH dependence, with increased potency of the compound detected over the pH range 8.3-9.4 CHLO ALC-induced protection against hypotonic hemolysis was pH independent. The potency of CHLO in all three assays decreased as the pH was raised from 6.4 to 9.4. (/sup 14/C)-CHLO and (/sup 14/C)-CHLO ALC binding to OE and OE membranes was pH independent. However, the binding of (/sup 14/C)-CHLO to polypropylene and glass was pH dependent. (/sup 14/C)-CHLO binding to polypropylene and glass decreased from pH 6.4 to pH 10.4. The pKa of CHLO was estimated to be 8.9. After the CHLO results were corrected for the fraction of CHLO present in the unionized form, it was estimated the ionized CHLO possessed 1/3 to 1/20 of the activity of the unionized species.« less

Comparison of chlordecone and NDL-PCB decontamination dynamics in growing male kids after cessation of oral exposure: Is there a potential to decrease the body levels of these pollutants by dietary supplementation of activated carbon or paraffin oil?

PubMed

Lastel, Marie-Laure; Fournier, Agnès; Jurjanz, Stefan; Thomé, Jean-Pierre; Joaquim-Justo, Célia; Archimède, Harry; Mahieu, Maurice; Feidt, Cyril; Rychen, Guido

2018-02-01

Sixteen weaned male Alpine kids (Capra hircus) were subjected to a 21-day oral daily exposure of 0.05 mg kg -1 BW. d -1 of chlordecone (CLD) and 0.30 μg kg -1 BW. d -1 of each non-dioxin-like polychlorinated biphenyls (NDL-PCBs, congeners 28, 52, 101, 138, 153 and 180). Four kids, identified as the CONTA group, were slaughtered at the end of the exposure, while the remaining animals (n = 12) were fed with specific diets for an additional 21-day decontamination period before slaughtering. Kids from the DECONTA (n = 4) group were fed a control diet, while those from the AC10% and PO8% group received pellets supplemented with 10% activated carbon (AC) and 8% paraffin oil (PO), respectively. CLD and NDL-PCB levels in blood, liver, peri-renal fat and muscles from different groups were analysed to compare the decontamination dynamics of the pollutants and to determine the efficiency of AC and PO to decrease the body levels of pollutants. After the decontamination period, the CLD levels considerably decreased (more than 60%) in blood, liver, muscles and fat. Concerning NDL-PCBs, the decontamination process was much lower. Overall, CLD appeared to be less retained in kids' organism compared with NDL-PCBs, and the decontamination dynamics of these pollutants appeared to be different because of their specific physicochemical properties and lipophilicity. Furthermore, the dietary supplementation with AC or PO did not significantly affect the decontamination dynamics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chlordecone, a mixed pregnane X receptor (PXR) and estrogen receptor alpha (ERα) agonist, alters cholesterol homeostasis and lipoprotein metabolism in C57BL/6 mice

PubMed Central

Lee, Junga; Scheri, Richard C.; Zhang, Yuan; Curtis, Lawrence R.

2008-01-01

Chlordecone (CD) is one of many banned organochlorine (OC) insecticides that are widespread persistent organic pollutants. OC insecticides alter lipid homeostasis in rodents at doses that are not neurotoxic or carcinogenic. Pretreatment of mice or rats with CD altered tissue distribution of a subsequent dose of [14C]CD or [14C]cholesterol (CH). Nuclear receptors regulate expression of genes important in the homeostasis of CH and other lipids. In this study, we report that CD suppresses in vitro reporter systems for human liver X receptors (LXRs) and activates those for human farnesoid X receptor (FXR), pregnane X receptor (PXR) and estrogen receptor α (ERα) in a concentration-dependent manner (0–50 μM). Consistent with human PXR activation in vitro, three days after a single dose of CD (15 mg/kg) hepatic microsomal CYP3A11 protein increases in C57BL/6 mice. CD decreases hepatic CH ester content without altering total CH concentration. Apolipoprotein A-I (apoA-I) contents of hepatic lipoprotein-rich and microsomal fractions of CD-treated mice are higher than controls. There is a significant reduction in non-high density lipoprotein CH but not apolipoprotein B-48/100 (apoB-48/100) in plasma from CD-treated mice after a 4 h fast. At 14 days after 15 mg CD/kg apoA-I and apoB-100 proteins but not CYP3A11 protein in hepatic microsomes are similar to controls. This work indicates that altered CH homeostasis is a mode of OC insecticide action of relevance after a single dose. This at least partially explains altered CH tissue distribution in CD-pretreated mice. PMID:18789348

Natural transformation of chlordecone into 5b-hydrochlordecone in French West Indies soils: statistical evidence for investigating long-term persistence of organic pollutants.

PubMed

Devault, Damien A; Laplanche, Christophe; Pascaline, Hélène; Bristeau, Sébastien; Mouvet, Christophe; Macarie, Hervé

2016-01-01

Chlordecone (CLD) was an organochlorine insecticide whose previous use resulted in an extensive pollution of the environment with severe health effects and social consequences. A closely related compound, 5b-hydrochlordecone (5b-hydroCLD), has been searched for and often detected in environmental matrices from the geographical area where CLD was applied. The current consensus considered that its presence was not the result of a biotic or abiotic dechlorination of CLD in these matrices but rather the consequence of its presence as impurity (synthesis by-product) in the CLD released into the environment. The aim of the present study was to determine if and to what extent degradation of CLD into 5b-hydroCLD occurred in the field. To test this hypothesis, the ratios of 5b-hydroCLD and CLD concentrations in a dataset of 810 soils collected between 2006 and 2012 in Martinique were compared to the ratios measured in 3 samples of the CLD dust commercial formulations applied in the banana fields of French West Indies (FWI) and 1 sample of the technical-grade CLD corresponding to the active ingredient used in such formulations. Soil data were processed with a hierarchical Bayesian model to account for random measurement errors and data censoring. Any pathway of CLD transformation into 5b-hydroCLD occurring over the long term in FWI soils would indeed change the ratio of 5b-hydroCLD/CLD compared to what it was in the initially applied formulations. Results showed a significant increase of the 5b-hydroCLD/CLD ratio in the soils-25 times greater in soil than in commercial formulations-which suggested that natural CLD transformation into 5b-hydroCLD over the long term occurred in these soils. Results from this study may impact future decisions for the remediation of the polluted areas.

Activated carbon, a useful medium to bind chlordecone in soil and limit its transfer to growing goat kids

PubMed Central

Yehya, Sarah; Delannoy, Matthieu; Fournier, Agnès; Baroudi, Moomen; Rychen, Guido; Feidt, Cyril

2017-01-01

Chlordecone (Kepone) (CLD) is a highly persistent pesticide which was extensively used in the French West Indies; high levels of CLD can still currently be found in large agricultural areas. As CLD transfers from soil to animals mainly via involuntary ingestion, the consumption of foodstuffs derived from animals raised in contaminated areas may significantly contribute to exposure of humans to CLD. The present study was designed to test the efficacy of two different activated carbons (ACs) sources in limiting CLD transfer from soil to animal. Three soils (ASs) were prepared according to the OECD guideline 207. One standard soil (SS) lacking AC, and two modified preparations of SS supplemented with 2% coconut-based activated carbon (ORBO), SSO or with 2% lignite-based one (DARCO), SSD. All three soils were spiked with 10 μg of kepone per g of dry matter and aged for three weeks. This study involved 15 goat kids randomly assigned to the 3 experimental groups (n = 5/group), which were fed the experimental matrices at an exposure dose of 10 μg CLD per kg of body weight per day. After 21 d of oral exposure, CLD in adipose tissue and liver were analysed by LC-MS-MS. A significant decrease of 63.7% and 74.7% of CLD concentrations in adipose tissue and liver, respectively, were obtained from animals exposed using SS containing DARCO as compared to those receiving only SS. Decreases in CLD levels of 98.2% (adipose tissue) and 98.7% (liver) were obtained for animals exposed using SS containing ORBO. This study leads us to conclude that (i) the presence of AC in CLD-contaminated soil strongly reduces CLD bioavailability, and (ii) the efficacy depends on the nature and characteristics of the AC used. PMID:28723966

Proteomic analysis of the reproductive organs of the hermaphroditic gastropod Lymnaea stagnalis exposed to different endocrine disrupting chemicals.

PubMed

Giusti, Arnaud; Leprince, Pierre; Mazzucchelli, Gabriel; Thomé, Jean-Pierre; Lagadic, Laurent; Ducrot, Virginie; Joaquim-Justo, Célia

2013-01-01

Many studies have reported perturbations of mollusc reproduction following exposure to low concentrations (ng/L range) of endocrine disrupting chemicals (EDCs). However, the mechanisms of action of these molecules on molluscs are still poorly understood. Investigation of the modifications of protein expression in organisms exposed to chemicals using proteomic methods can provide a broader and more comprehensive understanding of adverse impacts of pollution on organisms than conventional biochemical biomarkers (e.g., heat-shock proteins, metallothioneins, GST, EROD). In this study we have investigated the impacts of four chemicals, which exhibit different endocrine disrupting properties in vertebrates, on the proteome of the hermaphroditic freshwater pulmonate gastropod Lymnaea stagnalis after 21 days of exposure. Testosterone, tributyltin, chlordecone and cyproterone acetate were chosen as tested compounds as they can induce adverse effects on the reproduction of this snail. The 2D-DIGE method was used to identify proteins whose expression was affected by these compounds. In addition to modifying the expression of proteins involved in the structure and function of the cytoskeleton, chemicals had impacts on the expression of proteins involved in the reproduction of L. stagnalis. Exposure to 19.2 µg/L of chlordecone increased the abundance of ovipostatin, a peptide transmitted during mating through seminal fluid, which reduces oviposition in this species. The expression of yolk ferritin, the vitellogenin equivalent in L. stagnalis, was reduced after exposure to 94.2 ng Sn/L of tributyltin. The identification of yolk ferritin and the modification of its expression in snails exposed to chemicals were refined using western blot analysis. Our results showed that the tested compounds influenced the abundance of yolk ferritin in the reproductive organs. Alteration in proteins involved in reproductive pathways (e.g., ovipostatin and yolk ferritin) could constitute relevant evidence of interaction of EDCs with reproductive pathways that are under the control of the endocrine system of L. stagnalis.

Theoretical study on the interactions between chlordecone hydrate and acidic surface groups of activated carbon under basic pH conditions.

PubMed

Melchor-Rodríguez, Kenia; Gamboa-Carballo, Juan José; Ferino-Pérez, Anthuan; Passé-Coutrin, Nady; Gaspard, Sarra; Jáuregui-Haza, Ulises Javier

2018-05-01

A theoretical study of the influence of acidic surface groups (SG) of activated carbon (AC) on chlordecone hydrate (CLDh) adsorption is presented, in order to help understanding the adsorption process under basic pH conditions. A seven rings aromatic system (coronene) with a functional group in the edge was used as a simplified model of AC to evaluate the influence of SG in the course of adsorption from aqueous solution at basic pH conditions. Two SG were modeled in their deprotonated form: carboxyl and hydroxyl (COO - and O - ), interacting with CLDh. In order to model the solvation process, all systems under study were calculated with up to three water molecules. Multiple Minima Hypersurface (MMH) methodology was employed to study the interactions of CLDh with SG on AC using PM7 semiempirical Hamiltonian, to explore the potential energy surfaces of the systems and evaluate their thermodynamic association energies. The re-optimization of representative structures obtained from MMH was done using M06-2X Density Functional Theory. The Quantum Theory of Atoms in Molecules (QTAIM) was used to characterize the interaction types. As result, the association of CLDh with acidic SG at basic pH conditions preferentially occurs between the two alcohol groups of CLDh with COO - and O - groups and by dispersive interactions of chlorine atoms of CLDh with the graphitic surface. On the other hand, the presence of covalent interactions between the negatively charged oxygen of SG and one hydrogen atom of CLDh alcohol groups (O - ⋯HO interactions) without water molecules, was confirmed by QTAIM study. It can be concluded that the interactions of CLDh with acidic SG of AC under basic pH conditions confirms the physical mechanisms of adsorption process. Copyright © 2018 Elsevier Inc. All rights reserved.

Soil thresholds and a decision tool to manage food safety of crops grown in chlordecone polluted soil in the French West Indies.

PubMed

Clostre, Florence; Letourmy, Philippe; Lesueur-Jannoyer, Magalie

2017-04-01

Due to the persistent pollution of soils by an organochlorine, chlordecone (CLD also known as Kepone © ) in the French West Indies, some crops may be contaminated beyond the European regulatory threshold, the maximum residue limit (MRL). Farmers need to be able to foresee the risk of not complying with the regulatory threshold in each field and for each crop, if not, farmers whose fields are contaminated would have to stop cultivating certain crops in the fields concerned. To help farmers make the right choices, we studied the relationship between contamination of the soil and contamination of crops. We showed that contamination of a crop by CLD depended on the crop concerned, the soil CLD content and the type of soil. We grouped crop products in three categories: (i) non-uptakers and low-uptakers, (ii) medium-uptakers, and (iii) high-uptakers, according to their level of contamination and the resulting risk of exceeding MRL. Using a simulation model, we computed the soil threshold required to ensure the risk of not complying with MRL was sufficiently low for each crop product and soil type. Threshold values ranged from 0.02 μgkg -1 for dasheen grown in nitisol to 1.7 μgkg -1 for yam grown in andosol in the high-uptake category, and from 1 μgkg -1 for lettuce grown in nitisol to 45 μgkg -1 for the leaves of spring onions grown in andosol in the medium-uptake category. Contamination of non-uptakers and low-uptakers did not depend on soil contamination. With these results, we built an easy-to-use decision support tool based on two soil thresholds (0.1 and 1 μgkg -1 ) to enable growers to adapt their cropping system and hence to be able to continue farming. Copyright © 2017 Elsevier Ltd. All rights reserved.

Proteomic Analysis of the Reproductive Organs of the Hermaphroditic Gastropod Lymnaea stagnalis Exposed to Different Endocrine Disrupting Chemicals

PubMed Central

Giusti, Arnaud; Leprince, Pierre; Mazzucchelli, Gabriel; Thomé, Jean-Pierre; Lagadic, Laurent; Ducrot, Virginie; Joaquim-Justo, Célia

2013-01-01

Many studies have reported perturbations of mollusc reproduction following exposure to low concentrations (ng/L range) of endocrine disrupting chemicals (EDCs). However, the mechanisms of action of these molecules on molluscs are still poorly understood. Investigation of the modifications of protein expression in organisms exposed to chemicals using proteomic methods can provide a broader and more comprehensive understanding of adverse impacts of pollution on organisms than conventional biochemical biomarkers (e.g., heat-shock proteins, metallothioneins, GST, EROD). In this study we have investigated the impacts of four chemicals, which exhibit different endocrine disrupting properties in vertebrates, on the proteome of the hermaphroditic freshwater pulmonate gastropod Lymnaea stagnalis after 21 days of exposure. Testosterone, tributyltin, chlordecone and cyproterone acetate were chosen as tested compounds as they can induce adverse effects on the reproduction of this snail. The 2D-DIGE method was used to identify proteins whose expression was affected by these compounds. In addition to modifying the expression of proteins involved in the structure and function of the cytoskeleton, chemicals had impacts on the expression of proteins involved in the reproduction of L. stagnalis. Exposure to 19.2 µg/L of chlordecone increased the abundance of ovipostatin, a peptide transmitted during mating through seminal fluid, which reduces oviposition in this species. The expression of yolk ferritin, the vitellogenin equivalent in L. stagnalis, was reduced after exposure to 94.2 ng Sn/L of tributyltin. The identification of yolk ferritin and the modification of its expression in snails exposed to chemicals were refined using western blot analysis. Our results showed that the tested compounds influenced the abundance of yolk ferritin in the reproductive organs. Alteration in proteins involved in reproductive pathways (e.g., ovipostatin and yolk ferritin) could constitute relevant evidence of interaction of EDCs with reproductive pathways that are under the control of the endocrine system of L. stagnalis. PMID:24363793

The Chlordecone crisis in the French West Indies : Its fate in soils and water

NASA Astrophysics Data System (ADS)

Voltz, Marc; Cattan, Philippe; Saison, Carine; Berns, Anne E.; Colin, François; Crabit, Armand; Crevoisier, David; Fernandez-Bayo, Jesus; Levillain, Joseph; Pak, Lai-Ting; Samouelian, Anatja; Cabidoche, Yves-Marie

2013-04-01

In the French West Indies, chlordecone (CLD), an organochlorine pesticide, which is highly persistent in the environment, was applied in banana plantations from 1972 to 1993 against the banana weevil Cosmopolites sordidus. Pollution surveys conducted in 2001 by the French Department of Health revealed the presence of chlordecone in soils, rivers, springs over large areas in Guadeloupe and Martinique islands. Contamination of drinking water, food crops, aquatic species by CLD has been observed as well as its presence in blood of men, pregnant women and newborns. There is therefore a large social concern about the extent and evolution of CLD pollution in the French West Indies and its impact on human health and ecosystems. From 2008 to 2012 a multidisciplinary project CHLORDEXCO took place to study the CLD fate in water, soils and the contamination characteristics of aquatic species and food crops. Here, we summarize results obtained on the processes controlling the spatial and temporal patterns of soil and water contamination at the scale of the banana cropping area in Guadeloupe and of the Perou catchment. The main soils in the contaminated areas are andosols and nitisols and formed from the weathering of volcanic ashes. They have a high organic carbon content and high content of secondary minerals, allophane for andosols and halloysite for nitisols. An analysis of the spatial distribution of CLD in soil over 1045 field plots showed that the soil type had a strong impact. Andosols, with a high sorption capacity (Koc 20 000 L/kg), had the highest CLD concentrations and stocks, unlike Nitisols, which had 10-fold lower sorption capacities. A significant « farm effect », due to between-farm variations of application times and amounts, was also noticed. The observed stocks of CLD clearly correspond to the accumulation in soil of successive treatments and thereby confirm the high persistence of CLD in soil also observed in incubation studies in soil microcosms. Soil column studies of the transport of aged CLD however showed that CLD concentration in percolation water varied little (5 to 10 μg/L) and were of same magnitude for both soils although their sorption properties and hydrodynamic behaviours differed with larger macropore flow in the andosols. At catchment scale, contamination of surface waters was permanent with CLD concentrations one order of magnitude less than in percolation water. Temporal variations of contamination were due to dilution effects caused by water from uncontaminated uphill areas. CLD concentrations were highest in base flow indicating that the main pathway of applied CLD to surface waters is by percolation and groundwater flow. In conclusion, contamination of soil and water in the banana cropped areas of the French West Indies is general and permanent. If no soil remediation strategies can be elaborated this severe environmental contamination will last over centuries as estimated by Cabidoche et al. (2009, Environ. Poll., 57, 1697-1705). Since CLD propagates mainly by subsurface flow, buffer strips, usually recommended in many regions to limit the pollution of water by pesticides, will not be useful.

Behavioral toxicology, risk assessment, and chlorinated hydrocarbons.

PubMed Central

Evangelista de Duffard, A M; Duffard, R

1996-01-01

Behavioral end points are being used with greater frequency in neurotoxicology to detect and characterize the adverse effects of chemicals on the nervous system. Behavioral measures are particularly important for neurotoxicity risk assessment since many known neurotoxicants do not result in neuropathology. The chlorinated hydrocarbon class consists of a wide variety of chemicals including polychlorinated biphenyls, clioquinol, trichloroethylene, hexachlorophene, organochlorine insecticides (DDT, dicofol, chlordecone,dieldrin, and lindane), and phenoxyherbicides. Each of these chemicals has effects on motor, sensory, or cognitive function that are detectable using functional measures such as behavior. Furthermore, there is evidence that if exposure occurs during critical periods of development, many of the chlorinated hydrocarbons are developmental neurotoxicants. Developmental neurotoxicity is frequently expressed as alterations in motor function or cognitive abilities or changes in the ontogeny of sensorimotor reflexes. Neurotoxicity risk assessment should include assessments of the full range of possible neurotoxicological effects, including both structural and functional indicators of neurotoxicity. PMID:9182042

Current Status and Regulatory Aspects of Pesticides Considered to be Persistent Organic Pollutants (POPs) in Taiwan

PubMed Central

Tsai, Wen-Tien

2010-01-01

Organochlorine pesticides (OCPs) are capable of persisting in the environment, transporting between phase media and accumulating to high levels, implying that they could pose a risk of causing adverse effects to human health and the environment. Consequently, most OCPs are designated as persistent organic pollutants (POPs) and even as endocrine disrupting chemicals (EDCs). The objective of this paper was to review the current status of pesticide POPs in Taiwan, including aldrin, chlordane, chlordecone, DDT, dieldrin, endrin, heptachlor, hexachlorobenzene, α/β-hexachlorocyclohexanes, lindane, mirex, pentachloro-benzene, and toxaphene. The information about their environmental properties, banned use, carcinogenic toxicity and environmental levels, can be connected with the regulatory infrastructure, which has been established by the joint-venture of the central competent authorities (i.e., Environmental Protection Administration, Department of Health, Council of Agriculture, and Council of Labor Affairs). The significant progress to be reported is that the residual levels of these pesticide-POPs, ranging from trace amounts to a few ppb, have declined notably in recent years. PMID:21139852

Current status and regulatory aspects of pesticides considered to be persistent organic pollutants (POPs) in Taiwan.

PubMed

Tsai, Wen-Tien

2010-10-01

Organochlorine pesticides (OCPs) are capable of persisting in the environment, transporting between phase media and accumulating to high levels, implying that they could pose a risk of causing adverse effects to human health and the environment. Consequently, most OCPs are designated as persistent organic pollutants (POPs) and even as endocrine disrupting chemicals (EDCs). The objective of this paper was to review the current status of pesticide POPs in Taiwan, including aldrin, chlordane, chlordecone, DDT, dieldrin, endrin, heptachlor, hexachlorobenzene, α/β-hexachlorocyclohexanes, lindane, mirex, pentachloro-benzene, and toxaphene. The information about their environmental properties, banned use, carcinogenic toxicity and environmental levels, can be connected with the regulatory infrastructure, which has been established by the joint-venture of the central competent authorities (i.e., Environmental Protection Administration, Department of Health, Council of Agriculture, and Council of Labor Affairs). The significant progress to be reported is that the residual levels of these pesticide-POPs, ranging from trace amounts to a few ppb, have declined notably in recent years.

Tolerance of aged Fischer 344 rats against chlordecone-amplified carbon tetrachloride toxicity.

PubMed

Murali, B; Korrapati, M C; Warbritton, Alan; Latendresse, John R; Mehendale, Harihara M

2004-06-01

We have investigated the effects of chlordecone 1(CD)+CCl4 combination in adult (3 months), middle aged (14 months), and old aged (24 months) male Fischer 344 (F344) rats. After a non-toxic dietary regimen of CD (10 ppm) or normal powdered diet for 15 days, rats received a single non-toxic dose of CCl4 (100 microl/kg, i.p., 1:4 in corn oil) or corn oil (500 microl/kg, i.p.) alone on day 16. Liver injury was assessed by plasma ALT, AST, and histopathology during a time course of 0-96 h. Liver tissue repair was measured by [3H-CH3]-thymidine (3H-T) incorporation into hepatic nuclear DNA and proliferating cell nuclear antigen (PCNA) immunohistochemistry. Hepatomicrosomal CYP2E1 protein, enzyme activity, and covalent binding of 14CCl4-derived radiolabel were measured in normal and CD fed rats. Exposure to CCl4 alone caused modest liver injury only in 14- and 24-month-old rats but neither progression of injury nor mortality. The CD+CCl4 combination led to 100% mortality in 3-month-old rats by 72 h, whereas none of the 14- and 24-month-old rats died. Both 3- and 14-month-old rats exposed to CD+Cl4 had identical liver injury up to 36 h indicating that bioactivation-mediated CCl4 injury was the same in the two age groups. Thereafter, liver injury escalated only in 3-month-old while it declined in 14-month-old rats. In 24-month-old rats initial liver injury at 6 h was similar to the 3- and 14-month-old rats and thereafter did not develop to the level of the other two age groups, recovering from injury by 96 h as in the 14-month-old rats. Neither hepatomicrosomal CYP2E1 protein nor the associated p-nitrophenol hydroxylase activity or covalent binding of 14CCl4-derived radiolabel to liver tissue differed between the age groups or diet regimens 2 h after the administration of 14CCl4. Compensatory liver tissue repair (3H-T, PCNA) was prompt and robust soon after CCl4 liver injury in the 14- and 24-month-old rats. In stark contrast, in the 3-month-old rats it failed allowing unabated progression of liver injury. These findings suggest that stimulation of early onset and robust liver tissue repair rescue the 14- and 24-month-old F344 rats from the lethal effect of the CD+CCl4 combination.

Expression and kinetic properties of a recombinant 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase isoenzyme of human liver.

PubMed

Deyashiki, Y; Tamada, Y; Miyabe, Y; Nakanishi, M; Matsuura, K; Hara, A

1995-08-01

Human liver cytosol contains multiple forms of 3 alpha-hydroxysteroid dehydrogenase and dihydrodiol dehydrogenase with hydroxysteroid dehydrogenase activity, and multiple cDNAs for the enzymes have been cloned from human liver cDNA libraries. To understand the relationship of the multiple enzyme froms to the genes, a cDNA, which has been reported to code for an isoenzyme of human liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase, was expressed in Escherichia coli. The recombinant enzyme showed structural and functional properties almost identical to those of the isoenzyme purified from human liver. In addition, the recombinant isoenzyme efficiently reduced 5 alpha-dihydrotestosterone and 5 beta-dihydrocortisone, the known substrates of human liver 3 alpha-hydroxysteroid dehydrogenase and chlordecone reductase previously purified, which suggests that these human liver enzymes are identical. Furthermore, the steady-state kinetic data for NADP(+)-linked (S)-1-indanol oxidation by the recombinant isoenzyme were consistent with a sequential ordered mechanism in which NADP+ binds first. Phenolphthalein inhibited this isoenzyme much more potently than it did the other human liver dihydrodiol dehydrogenases, and was a competitive inhibitor (Ki = 20 nM) that bound to the enzyme-NADP+ complex.

Residential surface soil guidance applied worldwide to the pesticides added to the Stockholm Convention in 2009 and 2011.

PubMed

Jennings, Aaron A; Li, Zijian

2015-09-01

Due to the widespread use of agricultural and residential pesticides, the potential for pesticide soil contamination is a worldwide concern. In response, regulatory jurisdictions in at least 54 nations have promulgated guidance values to specify the maximum allowable concentration of pesticides in soils. Guidance values may be found for more than 700 pesticides. A previous analysis examined the values applied to the original "dirty dozen" persistent organic pollutant (POP) pesticides that were addressed in the 2001 Stockholm Convention (Aldrin, Chlordane, DDT, Dieldrin, Endrin, Heptachlor, Mirex, and Toxaphene). Results are presented here for the "new POP" pesticides that were added to the Stockholm Convention in 2009 and 2011 (isomers of Hexachlorocyclohexane, Chlordecone, and isomers of Endosulfan). The guidance value extremes used worldwide for these pesticides vary by as much as 8.5 orders of magnitude and the randomness in their distributions resembles that of lognormal random variables. However, there are nonrandom value clusters in some distributions that may identify values around which consensuses are forming. The current value distributions imply that a wide range of human health risks are being accepted. Hopefully, the results presented will help regulatory jurisdictions and the regulated communities identify values that should be revised to be adequately protective of human health. Copyright © 2015 Elsevier Ltd. All rights reserved.

Biodegradability of HCH in agricultural soils from Guadeloupe (French West Indies): identification of the lin genes involved in the HCH degradation pathway.

PubMed

Laquitaine, L; Durimel, A; de Alencastro, L F; Jean-Marius, C; Gros, O; Gaspard, S

2016-01-01

Banana has been a main agricultural product in the French West Indies (Guadeloupe and Martinique) since the 1960s. This crop requires the intensive use of pesticides to prevent attacks by insect pests. Chlorinated pesticides, such as hexachlorocyclohexane (HCH), chlordecone and dieldrin, were used until the beginning of the 1990s, resulting in a generalized diffuse contamination of the soil and water in the areas of banana production, hence the need to develop solutions for cleanup of the polluted sites. The aims of this work were (i) to assess lindane degradation in soil slurry microcosms treated with lindane at 10 mg/L and (ii) to detect the catabolic genes involved in the HCH degradation pathway. The soil slurry microcosm system showed a 40% lindane degradation efficiency at the end of a 30-day experiment. Lower lindane removal was also detected in the abiotic controls, probably caused by pesticide adsorption to soil particles. Indeed, the lindane concentration decreased from 6000 to 1330 ng/mL and from 800 to 340 ng/mL for the biotic and abiotic soils, respectively. Nevertheless, some of the genes involved in the HCH degradation pathway were amplified by polymerase chain reaction (PCR) from crude deoxyribonucleic acid (DNA) extracted from the Guadeloupe agricultural soil, suggesting that HCH degradation is probably mediated by bacteria closely related to the family Sphingomonadaceae.

Xenobiotic interaction with and alteration of channel catfish estrogen receptor.

PubMed

Nimrod, A C; Benson, W H

1997-12-01

In teleostean in vivo studies, the vitellogenin response to environmental estrogens is not completely predicted by mammalian literature. One possible explanation for differences is heterogeneity of the estrogen receptor (ER) structure between species. Therefore, ER from channel catfish (Ictalurus punctatus) hepatic tissue was characterized by binding affinity for several compounds. Affinity was indirectly measured as potency of the chemical for inhibiting binding of radiolabeled estradiol (E2) to specific binding sites. The order of potency among therapeutic chemicals was ethinylestradiol > unlabeled E2 = diethylstilbestrol > mestranol > tamoxifen > testosterone. Unlabeled E2 had an IC50 of 2.2 nM. Several environmentally relevant chemicals were evaluated in a similar manner and the order of potency established was the o-demethylated metabolite of methoxychlor (MXC) > nonylphenol (NP) > chlordecone > MXC > o,p'-DDT > o,p'-DDE > beta-hexachlorocyclohexane. Demethylated MXC had an IC50 1000-fold greater than that of E2. Of the most potent inhibitors, NP appeared to be a competitive inhibitor for the same binding site as E2, while o-demethylated MXC had a more complex interaction with the receptor protein. ER from nonvitellogenic females was determined to have a Kd value of 1.0 to 1.3 nM. Because E2 has been reported to up-regulate teleostean ER, the hepatic ER population following in vivo xenobiotic exposure was assessed. NP significantly increased ER per milligram hepatic protein almost to the same extent as E2, but did not increase Kd to the same extent as E2.

Study on the structure, vibrational analysis and molecular docking of fluorophenyl derivatives using FT-IR and density functional theory computations

NASA Astrophysics Data System (ADS)

Al-Tamimi, Abdul-Malek S.; Mary, Y. Sheena; Hassan, Hanan M.; Resmi, K. S.; El-Emam, Ali A.; Narayana, B.; Sarojini, B. K.

2018-07-01

The density functional calculations were performed at the B3LYP/6-311++G (5D, 7F) level to find the geometrical parameters, vibrational wavenumbers and various molecular properties of three fluorophenyl derivatives, methyl 4,4″-difluoro-5‧-methoxy-1,1':3‧,1″-terphenyl-4‧-carboxylate (MDFMTPC), 2,2'-(disulfanediyl)bis[4,6-(4-fluorophenyl)pyrimidine] (DFFPPY) and (6Z)-3,5‧-bis(4-fluorophenyl)-6-(1-hydroxyethylidene)cyclohex-2-en-1-one (FPHYCY). The phenyl ring Csbnd C, Cdbnd O and Csbnd H stretching modes produces VCD spectrum and these modes are efficient configuration markers. Using natural bond orbital analysis the stability of the molecules due to hyper-conjugative interactions were discussed. From the HOMO and LUMO energies, the chemical descriptors are compared for the title compounds. The first hyperpolarizabilities of MDFMTPC, DFFPPY and FPHYCY are respectively, 41.08, 69.27 and 38.38 times that of urea. Molar refractivity values are increasing in the order, FPHYCY > MDFMTPC > DFFPPY and this is responsible for the binding nature of the molecular assembly and can be used for the cure of different diseases. PASS analysis of the title compounds predicts chlordecone reductase inhibitor activity for MDFMTPC, thioredoxin inhibitor activity for DFFPPY and testosterone 17beta-dehydrogenase (NADP+) inhibitor activity for FPHYCY. Docking studies reveal that MDFMTPC, DFFPPY and FPHYCY can be lead compounds for developing new anti-cancerous, anti-tumor, prostate cancer drugs. Using Hirshfeld surface and 2D-finger print plots, the type and nature of intermolecular interactions were reported.

Relationships between past and present pesticide applications and pollution at a watershed outlet: The case of a horticultural catchment in Martinique, French West Indies.

PubMed

Mottes, Charles; Lesueur Jannoyer, Magalie; Le Bail, Marianne; Guéné, Mathilde; Carles, Céline; Malézieux, Eric

2017-10-01

The understanding of factors affecting pesticide transfers to catchment outlet is still at a very early stage in tropical context, and especially on tropical volcanic context. We performed on-farm pesticide use surveys during 87 weeks and monitored pesticides in water weekly during 67 weeks at the outlet of a small catchment in Martinique. We identified three types of pollution. First, we showed long-term chronic pollution by chlordecone, diuron and metolachlor resulting from horticultural practices applied 5-20 years ago (quantification frequency higher than 80%). Second, we showed peak pollution. High amounts of propiconazole and fosthiazate applied at low frequencies caused river pollution peaks for weeks following a single application. Low amounts of diquat and diazinon applied at low frequencies also caused pollution peaks. The high amounts of glyphosate applied at high frequency resulted into pollution peaks by glyphosate and aminomethylphosphonic acid (AMPA) in 6 and 20% of the weeks. Any intensification of their uses will result in higher pollution levels. Third, relatively low amounts of glufosinate-ammonium, difenoconazol, spinosad and metaldehyde were applied at high frequencies. Unexpectedly, such pesticides remained barely detected (<1.5%) or undetected in water samples. We showed that AMPA, fosthiazate and propiconazole have serious leaching potential. They might result in future chronic pollution of shallow aquifers alimenting surface water. We prove that to avoid the past errors and decrease the risk of long-term pollution of water resources, it is urgent to reduce or stop the use of pesticides with leaching potential by changing agricultural practices. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sequence of the cDNA of a human dihydrodiol dehydrogenase isoform (AKR1C2) and tissue distribution of its mRNA.

PubMed Central

Shiraishi, H; Ishikura, S; Matsuura, K; Deyashiki, Y; Ninomiya, M; Sakai, S; Hara, A

1998-01-01

Human liver contains three isoforms (DD1, DD2 and DD4) of dihydrodiol dehydrogenase with 20alpha- or 3alpha-hydroxysteroid dehydrogenase activity; the dehydrogenases belong to the aldo-oxo reductase (AKR) superfamily. cDNA species encoding DD1 and DD4 have been identified. However, four cDNA species with more than 99% sequence identity have been cloned and are compatible with a partial amino acid sequence of DD2. In this study we have isolated a cDNA clone encoding DD2, which was confirmed by comparison of the properties of the recombinant and hepatic enzymes. This cDNA showed differences of one, two, four and five nucleotides from the previously reported four cDNA species for a dehydrogenase of human colon carcinoma HT29 cells, human prostatic 3alpha-hydroxysteroid dehydrogenase, a human liver 3alpha-hydroxysteroid dehydrogenase-like protein and chlordecone reductase-like protein respectively. Expression of mRNA species for the five similar cDNA species in 20 liver samples and 10 other different tissue samples was examined by reverse transcriptase-mediated PCR with specific primers followed by diagnostic restriction with endonucleases. All the tissues expressed only one mRNA species corresponding to the newly identified cDNA for DD2: mRNA transcripts corresponding to the other cDNA species were not detected. We suggest that the new cDNA is derived from the principal gene for DD2, which has been named AKR1C2 by a new nomenclature for the AKR superfamily. It is possible that some of the other cDNA species previously reported are rare allelic variants of this gene. PMID:9716498

Hydrological and pesticide transfer modeling in a tropical volcanic watershed with the WATPPASS model

NASA Astrophysics Data System (ADS)

Mottes, Charles; Lesueur-Jannoyer, Magalie; Charlier, Jean-Baptiste; Carles, Céline; Guéné, Mathilde; Le Bail, Marianne; Malézieux, Eric

2015-10-01

Simulation of flows and pollutant transfers in heterogeneous media is widely recognized to be a remaining frontier in hydrology research. We present a new modeling approach to simulate agricultural pollutions in watersheds: WATPPASS, a model for Watershed Agricultural Techniques and Pesticide Practices ASSessment. It is designed to assess mean pesticide concentrations and loads that result from the use of pesticides in horticultural watersheds located on heterogeneous subsoil. WATPPASS is suited for small watershed with significant groundwater flows and complex aquifer systems. The model segments the watershed into fields with independent hydrological and pesticide transfers at the ground surface. Infiltrated water and pesticides are routed toward outlet using a conceptual reservoir model. We applied WATPPASS on a heterogeneous tropical volcanic watershed of Martinique in the French West Indies. We carried out and hydrological analysis that defined modeling constraints: (i) a spatial variability of runoff/infiltration partitioning according to land use, and (ii) a predominance of groundwater flow paths in two overlapping aquifers under permeable soils (50-60% of annual flows). We carried out simulations on a 550 days period at a daily time step for hydrology (Nashsqrt > 0.75). Weekly concentrations and loads of a persistent organic pesticide (chlordecone) were simulated for 67 weeks to evaluate the modeling approach. Pesticide simulations without specific calibration detected the mean long-term measured concentration, leading to a good quantification of the cumulative loads (5% error), but failed to represent the concentration peaks at the correct timing. Nevertheless, we succeed in adjusting the model structure to better represent the temporal dynamic of pesticide concentrations. This modification requires a proper evaluation on an independent dataset. Finally, WATPPASS is a compromise between complexity and easiness of use that makes it suited for cropping system assessment in complex pedological and geological environment.

Amplified interactive toxicity of chemicals at nontoxic levels: Mechanistic considerations and implications to public health

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mehendale, H.M.

1994-11-01

It is widely recognized that exposure to combinations or mixtures of chemicals may result in highly exaggerated toxicity even though the individual chemicals might not be toxic. Assessment of risk from exposure to combinations of chemicals requires the knowledge of the underlying mechanism(s). Dietary exposure to a nontoxic dose of chlordecone (CD; 10 ppm, 15 days) results in a 67-fold increase in lethality of an ordinarily inconsequential dose of CCl{sub 4} (100 {mu}l/kg, ip). Toxicity of closely related CHCl{sub 3} and BrCCl{sub 3} is also enhanced. Phenobarbital (PB, 225 ppm, 15 days) and mirex (10 ppm, 15 days) do notmore » share the propensity of CD in this regard. Exposure to PB + CCl{sub 4} results in enhanced liver injury similar to that observed with CD, but the animals recover and survive in contrast to the greatly amplified lethality of CD + CCl{sub 4}. Investigations have revealed that neither enhanced bioactivation of CCl{sub 4} nor increased lipid peroxidation offers a satisfactory explanation of these findings. Additional studies indicate that exposure to a low dose of CCl{sub 4} (100 {mu}l/kg, ip) results in limited jury, which is accompanied by a biphasic response of hepatocellular regeneration (6 and 36 hr) and tissue repair, which enables the animals to recover from injury. Exposure to CD + CCl{sub 4} results in suppressed tissue repair owing to an energy deficit in hepatocytes as a consequence of excessive intracellular influx of Ca{sup 2+} leading initially to a precipitous decline in glycogen and ultimately to hypoglycemia. Supplementation of cellular energy results in restoration of the tissue repair and complete recovery from the toxicity of CD + CCl{sub 4} combination. In contrast, only the early-phase hepatic tissue repair (6 hr) is affected in PB + CCl{sub 4} treatment, but this is compensated for by a greater stimulation of tissue repair at 24 and 48 hr resulting in recovery from liver and animal survival. 85 refs., 7 figs., 7 tabs.« less

Genomic structure of rat 3alpha-hydroxysteroid/dihydrodiol dehydrogenase (3alpha-HSD/DD, AKR1C9).

PubMed

Lin, H K; Hung, C F; Moore, M; Penning, T M

1999-11-01

Rat liver 3alpha-hydroxysteroid/dihydrodiol dehydrogenase (3alpha-HSD/DD) is a member of the aldo-keto reductase (AKR) superfamily. It is involved in the inactivation of steroid hormones and the metabolic activation of polycyclic aromatic hydrocarbons (PAH) by converting trans-dihydrodiols into reactive and redox-active o-quinones. The structure of the 5'-flanking region of the gene and factors involved in the constitutive and regulated expression of this gene have been reported [H.-K. Lin, T.M. Penning, Cloning, sequencing, and functional analysis of the 5'-flanking region of the rat 3alpha-hydroxysteroid/dihydrodiol dehydrogenase gene, Cancer Res. 55 (1995) 4105-4113]. We now describe the complete genomic structure of the rat type 1 3alpha-HSD/DD gene. Charon 4A and P1 genomic clones contained at least three rat genes (type 1, type 2 and type 3 3alpha-HSD/DD) each of which encoded for the same open reading frame (ORF) but differed in their exon-intron organization. 5'-RACE confirmed that the type 1 3alpha-HSD/DD gene encodes for the dominant transcript in rat liver and it was the regulation of this gene that was previously studied. The rat type 1 3alpha-HSD/DD gene is 30 kb in length and consists of nine exons and eight introns. Exon 9 encodes +931 to 966 bp of the ORF and the 1292 bp 3'-UTR implicated in mRNA stability. This genomic structure is nearly identical to the homologous human genes, type 1 3alpha-HSD (chlordecone reductase/DD4, AKR1C4), type 2 3alpha-HSD (AKR1C3) and type 3 3alpha-HSD (bile-acid binding protein, AKR1C2) genes. Three different cDNA's containing identical ORFs for 3alpha-HSD have been reported suggesting that all three genes may be expressed in rat liver. Using 5' primers corresponding to the 5'-UTR's of the three different cDNA's only one PCR fragment was obtained and corresponded to the type 1 3alpha-HSD/DD gene. These data suggested that the type 2 and type 3 3alpha-HSD/DD genes are not abundantly expressed in rat liver. It is unknown whether the type 2 and type 3 3alpha-HSD/DD genes represent pseudo-genes or whether they represent genes that are differentially expressed in other rat tissues.

Clustering pesticides according to their molecular properties and their impacts by considering additional ecotoxicological parameters in the TyPol method

NASA Astrophysics Data System (ADS)

Traore, Harouna; Crouzet, Olivier; Mamy, Laure; Sireyjol, Christine; Rossard, Virginie; Servien, Remy; Latrille, Eric; Benoit, Pierre

2017-04-01

The understanding of the fate of pesticides and their environmental impacts largely relies on their molecular properties. We recently developed 'TyPol' (Typology of Pollutants), a clustering method based on statistical analyses combining several environmental endpoints (i.e. environmental parameters such as sorption coefficient, degradation half-life) and one ecotoxicological one (bioconcentration factor), and structural molecular descriptors (number of atoms in the molecule, molecular surface, dipole moment, energy of orbitals…). TyPol has been conceived on the available knowledge on QSAR of a wide diversity of organic compounds (Mamy et al., 2015). This approach also allows to focus on transformation products present in different clusters and to infer possible changes in environmental fate consecutively to different degradation processes (Servien et al., 2014; Benoit et al., 2016). The initial version of TyPol did not include any ecotoxicological parameters except the bioconcentration factor (BCF), which informs more on the transfer along the trophic chain rather than on the effects on non-target organisms. The objective was to implement the TyPol database with a data set of ecotoxicological data concerning pesticides and several aquatic and terrestrial organisms, in order to test the possibility to extend TyPol to ecotoxicological effects on various organisms. The data analysis (available literature and databases) revealed that relevant ecotoxicological endpoints for terrestrial organisms such as soil microorganisms and macroinvertebrates are lacking compared to aquatic organisms. We have added seven parameters for acute (EC50, LC50) and chronic (NOEC) toxicological effects for the following organisms: Daphnia, Algae, Lemna and Earthworm. In this new configuration, TyPol was used to classify about 45 pesticides in different behavioural and ecotoxicity clusters. The clustering results were analyzed to reveals relationships between molecular descriptors, environmental parameters and the added toxicological parameters. Some trends between soil adsorption or Kow coefficient and the acute toxicity towards earthworms or algae were highlighted, and discussed on the basis of the concept of contaminant bioavailability. This proof-of-concept study also showed that the in silico clustering method TyPol can successfully address new questions and can be expanded with other parameters of interest. Keywords: pesticides, toxicity, QSAR, clustering, PLS References : Servien R., Mamy L., Li Z., Rossard V., Latrille E., Bessac F., Patureau D., Benoit P., 2014. TyPol - A new methodology for organic compounds clustering based on their molecular characteristics and environmental behavior. Chemosphere, 111, 613-622. Mamy L., Patureau D., Barriuso E., Bedos C., Bessac F., Louchart X., Martin-Laurent F., Miege C., Benoit P., 2015. Prediction of the fate of organic compounds in the environment from their molecular properties: A review. Critical Reviews in Environmental Science and Technology, 45, 12, 1277-1377 (Open access). Benoit P., Mamy L., Servien R., Li Z., Latrille E., Rossard V., Bessac F., Patureau D., Martin-Laurent F. 2017. Categorizing chlordecone potential degradation products to explore their environmental fate. Science of the Total Environment, 574, 781-795.