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Sample records for chlormequat

  1. Chlormequat chloride retards rat embryo growth in vitro.

    PubMed

    Xiagedeer, Bayindala; Wu, Shuang; Liu, Yingjuan; Hao, Weidong

    2016-08-01

    Chlormequat chloride is the most widely used plant growth regulator in agriculture to promote sturdier growth of grain crops by avoidance of lodging. Therefore, human exposure to chlormequat chloride is very common, but its developmental toxicity has not been studied. Thus, we investigated the developmental toxicity of chlormequat chloride by applying rat whole embryo culture (WEC) model, limb bud micromass culture and 3T3 fibroblast cytotoxicity test. Chlormequat chloride at 150μg/ml (0.93mM) retarded the rat embryo growth without causing significant morphological malformations and at 500μg/ml (3.1mM) caused both retardation and morphological malformation of the embryos. However, the proliferation and differentiation of limb bud cells were not affected by chlormequat chloride at as high as up to 1000μg/ml (6.2mM) applied. This concentration of chlormequat chloride did not affect the cell viability as examined by 3T3 fibroblast cytotoxicity test either, suggesting that cellular toxicity may not play a role in chlormequat induced inhibition of rat embryo growth. Collectively, our results demonstrated that chlormequat chloride may affect embryo growth and development without inhibiting cell viability.

  2. Suicide by self-injection of chlormequat trademark C5SUN(®).

    PubMed

    Boumrah, Yacine; Gicquel, Thomas; Hugbart, Chloé; Baert, Alain; Morel, Isabelle; Bouvet, Renaud

    2016-06-01

    Chlormequat is a quaternary ammonium used as plant growth regulating agent. We report here the first suicide case involving a 45 year-old farmer man who intentionally self-injected C5SUN(®), containing chlormequat and choline. An original liquid chromatography high resolution mass spectrometry method (LC-HR-MS), using a hybrid quadrupole-orbitrap mass spectrometer, was developed for qualitative and quantitative analysis of chlormequat in different biological matrices. Toxicological analyses of post-mortem samples highlighted the presence of chlormequat in the blood (2.25mg/L) and the urine (4.45mg/L), in addition to ethanol impregnation blood (1.15g/L). The route of administration (subcutaneous injection) was confirmed by the detection of chlormequat in the abdominal fat sample (chlormequat: 10.04mg/g) taken from the traumatic injury location, as well as in the syringe found at the death scene, close to the victim's body. Based on the results of these post-mortem investigations, the cause of death was determined to be consecutive to cardiac dysrhythmia and cardiac arrest following chlormequat self-injection.

  3. No effect of the plant growth regulator, chlormequat, on boar fertility.

    PubMed

    Sørensen, M T; Poulsen, M E; Leffers, H; Vajta, G; Halekoh, U

    2009-05-01

    Chlormequat is a commonly used plant growth regulator in agriculture. Defined levels of chlormequat residue are allowed in food and an acceptable daily intake is defined for humans. However, there are results in the literature suggesting that a daily intake below the acceptable level for human is detrimental for mammalian reproduction. In the present experiment we investigated the effect of chlormequat at levels up to that acceptable for humans on reproduction in male pigs. Chlormequat (also known as chlorocholine chloride (CCC)) was mixed into the diet and given to the experimental animals at three levels (three treatment groups), i.e. 0 mg CCC/kg BW per day (Control), 0.025 mg CCC/kg BW per day and 0.05 mg CCC/kg BW per day. Eight mother sows per treatment group were used in the experiment. From the day of insemination, the mother sows received the experimental diets. The piglets were weaned at 4 weeks of age and two boar littermates continued on the same treatment as the dam until maturity and delivery of semen for in vitro fertilization (IVF) and in vivo fertilization. Semen volume, sperm concentration and fraction of live sperms were not (P 0.46) detrimentally affected by chlormequat intake. The fraction of oocytes developing to more than the one-cell stage at day 5 after IVF was not (P = 0.88) detrimentally affected by chlormequat intake. Chlormequat intake did not detrimentally affect the fraction of gilts being pregnant after one insemination (P = 0.65) or the number of embryos in the pregnant gilts (P = 0.36). Serum chlormequat concentration was 0.9 μg/kg in the 0.025 mg CCC/kg BW per day group and 1.8 μg/kg in the 0.05 mg CCC/kg BW per day group, but was below the detection limit in control animals. In conclusion, the plant growth regulator chlormequat could not be proven to be detrimental to the selected reproduction traits in male pigs. This is in contrast to existing results from the male mouse.

  4. Urinary biomarker concentrations of captan, chlormequat, chlorpyrifos and cypermethrin in UK adults and children living near agricultural land

    PubMed Central

    Galea, Karen S; MacCalman, Laura; Jones, Kate; Cocker, John; Teedon, Paul; Cherrie, John W; van Tongeren, Martie

    2015-01-01

    There is limited information on the exposure to pesticides experienced by UK residents living near agricultural land. This study aimed to investigate their pesticide exposure in relation to spray events. Farmers treating crops with captan, chlormequat, chlorpyrifos or cypermethrin provided spray event information. Adults and children residing ≤100 m from sprayed fields provided first-morning void urine samples during and outwith the spray season. Selected samples (1–2 days after a spray event and at other times (background samples)) were analysed and creatinine adjusted. Generalised Linear Mixed Models were used to investigate if urinary biomarkers of these pesticides were elevated after spray events. The final data set for statistical analysis contained 1518 urine samples from 140 participants, consisting of 523 spray event and 995 background samples which were analysed for pesticide urinary biomarkers. For captan and cypermethrin, the proportion of values below the limit of detection was greater than 80%, with no difference between spray event and background samples. For chlormequat and chlorpyrifos, the geometric mean urinary biomarker concentrations following spray events were 15.4 μg/g creatinine and 2.5 μg/g creatinine, respectively, compared with 16.5 μg/g creatinine and 3.0 μg/g creatinine for background samples within the spraying season. Outwith the spraying season, concentrations for chlorpyrifos were the same as those within spraying season backgrounds, but for chlormequat, lower concentrations were observed outwith the spraying season (12.3 μg/g creatinine). Overall, we observed no evidence indicative of additional urinary pesticide biomarker excretion as a result of spray events, suggesting that sources other than local spraying are responsible for the relatively low urinary pesticide biomarkers detected in the study population. PMID:26374656

  5. The skeletal developmental toxicity of chlormequat chloride and its underlying mechanisms.

    PubMed

    Huang, Dan; Wu, Shuang; Hou, Xiaohong; Jia, Lixia; Meng, Qinghe; Chu, Hongqian; Jiang, Jianjun; Shang, Lanqin; Hao, Weidong

    2017-04-15

    Chlormequat Chloride (CCC), a widely used plant growth regulator, could decrease body weight in animals; however, the mechanism has not been well studied. This study was designed to evaluate the skeletal development toxicity of CCC on pubertal male Sprague-Dawley (SD) rats and to investigate whether CCC impacts the development of chondrocyte, osteoblast and osteoclast through growth hormone (GH) and insulin like growth factor 1 (IGF-I). Rats from 23 to 70 on postnatal days were exposed to CCC daily by gavage at doses of 0, 75, 150, and 300mg/kg bw/d. The results showed that the size of femurs and tibias, bone mineral density and biomechanical parameters were significantly decreased in the 300mg/kg bw/d group compared with the control group. The concentration of osteocalcin (OCN) and C-terminal telopeptide of type I collagen (CTX-I) in blood in the 150mg/kg bw/d group was also changed. The mRNA expression ratio of the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) in 150 and 300mg/kg bw/d group was increased. Histological analysis of proximal and distal epiphyseal plates of the right femurs showed that both the proliferative zone and hypertrophic zone narrowed in CCC-treated groups. The concentration of IGF-I in blood was reduced with an increase in exposure doses of CCC. The mRNA expression of growth hormone receptor (GHR) in tibia was decreased in the CCC-treated group. The results indicated that CCC might indirectly impact the formation and activation of chondrocytes, osteoblasts and osteoclasts because of the decline of GHR and IGF-I, leading to skeletal development damage.

  6. Analysis of chlormequat and mepiquat by hydrophilic interaction chromatography coupled to tandem mass spectrometry in food samples.

    PubMed

    Esparza, X; Moyano, E; Galceran, M T

    2009-05-15

    In this work a LC-MS/MS method for the determination of two quaternary ammonium growth regulators (chlormequat and mepiquat) in food is reported. The separation was based on hydrophilic interaction liquid chromatography (HILIC) without the use of ion-pair reagents. A gradient elution of acetonitrile and formic acid/ammonium formate buffer from 60 to 40% acetonitrile was enough to achieve a resolution >1.5 in less than 4.0min. The HILIC system was coupled to a triple quadrupole mass spectrometer equipped with a heated electrospray probe (H-ESI) providing sub-pg LODs in SRM mode. A straightforward sample treatment (SPE C18 clean-up) was enough to provide MLODs at low ppb levels when analysing a range of food samples that covered different kinds of matrices such as fresh fruit, vegetables, fruit juices, baby food, bread, coffee and beer. Chlormequat was found in seven samples (0.8-126ng/g) but mepiquat was only detected in bread and coffee samples (0.9-166ng/g).

  7. Effect of chlormequat (cycocel) on the growth of ornamental cabbage and kale (Brassica oleracea) cultivars 'Kamome White' and 'Nagoya Red'.

    PubMed

    Gholampour, Abdollah; Hashemabadi, Davood; Sedaghathoor, Shahram; Kaviani, Behzad

    2015-01-01

    The effect of concentration and application method of chlormequat (cycocel), a plant growth retardant, on plant height and some other traits in Brassica oleracea cultivars 'Kamome White' and 'Nagoya Red' was assessed. Plant growth retardants are commonly applied to limit stem elongation and produce a more compact plant. The experiment was done as a factorial in randomized completely blocks design (RCBD) with four replications. Plants (40 days after transplanting) were sprayed and drenched with 500, 1000 and 1500 mg l(-1) cycocel. In each experiment, control untreated plants. Data were recorded the 60 and 90 days after transplanting. Based on analysis of variance (ANOVA), the effect of different treatments and their interaction on all traits was significant at 0.05 or 0.01 level of probability. Treatment of 1500 mg I(-1) cycocel resulted in about 50 and 20% shorter plants than control plants, 60 and 90 days after transplant. The growth of Brassica oleracea cultivar 'Kamome White' and 'Nagoya Red' decreased with increased cycocel concentration. Foliar sprays of cycocel controlled plant height of both cultivars. Results indicated that the shortest plants (9.94 and 11.59 cm) were those sprayed with 1500 mg l(-1) cycocel in cultivar 'Kamome White' after 60 and 90 days, respectively. The largest number of leaves (33.94) and highest leaf diameter (9.39 cm) occurred in cv. 'Nagoya Red', when drench was used. Maximum dry matter (14.31%) accumulated in cv. 'Nagoya Red', treated with spray.

  8. Comparison of residents' pesticide exposure with predictions obtained using the UK regulatory exposure assessment approach.

    PubMed

    Galea, Karen S; MacCalman, Laura; Jones, Kate; Cocker, John; Teedon, Paul; Cherrie, John W; van Tongeren, Martie

    2015-11-01

    The UK regulatory methods currently used for estimating residents' potential pesticide exposure were assessed to determine whether they provide sufficiently conservative estimates. A non-random sample of 149 residents living within 100 m of fields where pesticides were sprayed provided first morning void urine samples one and/or two days after spraying. Using farmers' spray information, regulatory exposure assessment (REA) models were applied to estimate potential pesticide intake among residents, with a toxicokinetic (TK) model used to estimate urinary biomarker concentrations in the mornings of the two days following the spray. These were compared with actual measured urinary biomarker concentrations obtained following the spray applications. The study focused on five pesticides (cypermethrin, penconazole, captan, chlorpyrifos and chlormequat). All measured cypermethrin urinary biomarker levels were lower than the REA-predicted concentrations. Over 98% and 97% of the measured urinary biomarker concentrations for penconazole and captan respectively were lower than the REA-predicted exposures. Although a number of the chlorpyrifos and chlormequat spray-related urinary biomarker concentrations were greater than the predictions, investigation of the background urinary biomarker concentrations suggests these were not significantly different from the levels expected had no pesticide spraying occurred. The majority of measured concentrations being well below the REA-predicted concentrations indicate that, in these cases, the REA is sufficiently conservative.

  9. Multi-residue determination of plant growth regulators in apples and tomatoes by liquid chromatography/tandem mass spectrometry.

    PubMed

    Xue, Jiaying; Wang, Suli; You, Xiangwei; Dong, Jiannan; Han, Lijun; Liu, Fengmao

    2011-11-15

    A sensitive and rapid multi-residue analytical method for plant growth regulators (PGRs) (i.e., chlormequat, mepiquat, paclobutrazol, uniconazole, ethephon and flumetralin) in apples and tomatoes was developed using high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). A homogenised sample was extracted with a mixture of methanol/water (90:10, v/v) and adjusted to pH <3 with formic acid. Primary secondary amine (PSA) adsorbent was used to clean up the sample. The determination was performed using electrospray ionisation (ESI) and a triple quadrupole (QqQ) analyser. Under the optimised method, the results showed that, except for ethephon, the recoveries were 81.8-98.1% in apples and tomatoes at the spiked concentrations of 0.005 to 2 mg/kg, with relative standard deviations (RSDs) of less than 11.7%. The limits of quantification (LOQs) were lower than their maximum residue limits (MRLs). The procedure was concluded as a practical method to determine the PGR residues in fruit and vegetables and is also suitable for the simultaneous analysis of the amounts of samples for routine monitoring. The analytical method described herein demonstrates a strong potential for its application in the field of PGR multi-residue analysis to help assure food safety.

  10. Currently used pesticides and their mixtures affect the function of sex hormone receptors and aromatase enzyme activity.

    PubMed

    Kjeldsen, Lisbeth Stigaard; Ghisari, Mandana; Bonefeld-Jørgensen, Eva Cecilie

    2013-10-15

    The endocrine-disrupting potential of pesticides is of health concern, since they are found ubiquitously in the environment and in food items. We investigated in vitro effects on estrogen receptor (ER) and androgen receptor (AR) transactivity, and aromatase enzyme activity, of the following pesticides: 2-methyl-4-chlorophenoxyacetic acid (MCPA), terbuthylazine, iodosulfuron-methyl-sodium, mesosulfuron-methyl, metsulfuron-methyl, chlormequat chloride, bitertanol, propiconazole, prothioconazole, mancozeb, cypermethrin, tau fluvalinate, malathion and the metabolite ethylene thiourea (ETU). The pesticides were analyzed alone and in selected mixtures. Effects of the pesticides on ER and AR function were assessed in human breast carcinoma MVLN cells and hamster ovary CHO-K1 cells, respectively, using luciferase reporter gene assays. Effects on aromatase enzyme activity were analyzed in human choriocarcinoma JEG-3 cells, employing the classical [(3)H](2)O method. Five pesticides (terbuthylazine, propiconazole, prothioconazole, cypermethrin and malathion) weakly induced the ER transactivity, and three pesticides (bitertanol, propiconazole and mancozeb) antagonized the AR activity in a concentration-dependent manner. Three pesticides (terbuthylazine, propiconazole and prothioconazole) weakly induced the aromatase activity. In addition, two mixtures, consisting of three pesticides (bitertanol, propiconazole, cypermethrin) and five pesticides (terbuthylazine, bitertanol, propiconazole, cypermethrin, malathion), respectively, induced the ER transactivity and aromatase activity, and additively antagonized the AR transactivity. In conclusion, our data suggest that currently used pesticides possess endocrine-disrupting potential in vitro which can be mediated via ER, AR and aromatase activities. The observed mixture effects emphasize the importance of considering the combined action of pesticides in order to assure proper estimations of related health effect risks.

  11. [Determination of 21 plant growth regulator residues in fruits by QuEChERS-high performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Huang, Hehe; Zhang, Jin; Xu, Dunming; Zhou, Yu; Luo, Jia; Li, Meiling; Chen, Shubin; Wang, Lianzhu

    2014-07-01

    A method for the simultaneous detection of 21 plant growth regulators in fruits by QuEChERS-high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was developed. The samples were initially extracted with acetonitrile containing 1% (v/v) acetic acid, followed by clean-up using the powder of magnesium sulfate and C18. The resulting samples were separated on a C18 column, and detected under positive and negative multiple reactions monitoring (MRM) mode through polarity switching between time segments. The matrix-matched external standard calibration curves were used for quantitative analysis. The linearities of chlormequat chloride, mepiquat chloride, choline chloride, cyclanilide, forchlorfenuron, thidiazuron, inabenfide, paclobutrazol, uniconazole and triapenthenol were in the concentration range of 0.1-500 microg/L, daminozide and 6-benzylaminopurine in the concentration range of 1.0-500 microg/L, 2,3,5-triiodobenzoic acid, 2,4-D, cloprop, 4-chlorophenoxyacetic acid (4-CPA) and trinexapac-ethyl in the concentration range of 2.0-1 000 microg/L, abscisic acid (ABA), gibberellic acid (GA3), 1-naphthaleneacetic acid (NAA) and indol-3-ylacetic acid (IAA) in the concentration range of 10-1000 microg/L, with the correlation coefficients higher than 0.990. The limits of detection and the limits of quantification of the method were 0.020-6.0 microg/kg and 0.10-15.0 microg/kg, respectively. For all the samples, the average spiked recoveries ranged from 73.0% to 111.0%, and the relative standard deviations (RSDs, n = 6) were in the range of 3.0% - 17.2%. The method is quick, easy, effective, sensitive and accurate, and can meet the requirements for the determination of the 21 plant growth regulator residues in fruits.

  12. Effects of currently used pesticides and their mixtures on the function of thyroid hormone and aryl hydrocarbon receptor in cell culture.

    PubMed

    Ghisari, Mandana; Long, Manhai; Tabbo, Agnese; Bonefeld-Jørgensen, Eva Cecilie

    2015-05-01

    Evidence suggest that exposure to pesticides can interfere with the endocrine system by multiple mechanisms. The endocrine disrupting potential of currently used pesticides in Denmark was analyzed as single compounds and in an equimolar mixture of 5 selected pesticides. The pesticides were previously analyzed for effects on the function of estrogen and androgen receptors, the aromatase enzyme and steroidogenesis in vitro. In this study, the effect on thyroid hormone (TH) function and aryl hydrocarbon receptor (AhR) transactivity was assessed using GH3 cell proliferation assay (T-screen) and AhR responsive luciferase reporter gene bioassay, respectively. Thirteen pesticides were analyzed as follows: 2-methyl-4-chlorophenoxyacetic acid, terbuthylazine, iodosulfuron-methyl-sodium, mesosulfuron-methyl, metsulfuron-methyl, chlormequat chloride, bitertanol, propiconazole, prothioconazole, mancozeb and its metabolite ethylene thiourea, cypermethrin, tau-fluvalinate, and malathion (currently banned in DK). In the T-screen, prothioconazole, malathion, tau-fluvalinate, cypermethrin, terbuthylazine and mancozeb significantly stimulated and bitertanol and propiconazole slightly reduced the GH3 cell proliferation. In the presence of triiodothyronine (T3), prothioconazole, tau-fluvalinate, propiconazole, cypermethrin and bitertanol significantly antagonized the T3-induced GH3 cell proliferation. Eleven of the tested pesticides agonized the AhR function, and bitertanol and prothioconazole inhibited the basal AhR activity. Bitertanol, propiconazole, prothioconazole and cypermethrin antagonized the TCDD-induced AhR transactivation at the highest tested concentration. The 5-component mixture had inducing effect but the combined effect could not be predicted due to the presence of bitertanol eliciting inhibitory effect. Upon removal of bitertanol from the mixture, the remaining four pesticides acted additively. In conclusion, our data suggest that pesticides currently used in Denmark

  13. Effects of currently used pesticides in assays for estrogenicity, androgenicity, and aromatase activity in vitro.

    PubMed

    Andersen, Helle Raun; Vinggaard, Anne Marie; Rasmussen, Thomas Hoj; Gjermandsen, Irene Marianne; Bonefeld-Jørgensen, Eva Cecilie

    2002-02-15

    Twenty-four pesticides were tested for interactions with the estrogen receptor (ER) and the androgen receptor (AR) in transactivation assays. Estrogen-like effects on MCF-7 cell proliferation and effects on CYP19 aromatase activity in human placental microsomes were also investigated. Pesticides (endosulfan, methiocarb, methomyl, pirimicarb, propamocarb, deltamethrin, fenpropathrin, dimethoate, chlorpyriphos, dichlorvos, tolchlofos-methyl, vinclozolin, iprodion, fenarimol, prochloraz, fosetyl-aluminum, chlorothalonil, daminozid, paclobutrazol, chlormequat chlorid, and ethephon) were selected according to their frequent use in Danish greenhouses. In addition, the metabolite mercaptodimethur sulfoxide, the herbicide tribenuron-methyl, and the organochlorine dieldrin, were included. Several of the pesticides, dieldrin, endosulfan, methiocarb, and fenarimol, acted both as estrogen agonists and androgen antagonists. Prochloraz reacted as both an estrogen and an androgen antagonist. Furthermore, fenarimol and prochloraz were potent aromatase inhibitors while endosulfan was a weak inhibitor. Hence, these three pesticides possess at least three different ways to potentially disturb sex hormone actions. In addition, chlorpyrifos, deltamethrin, tolclofos-methyl, and tribenuron-methyl induced weak responses in one or both estrogenicity assays. Upon cotreatment with 17beta-estradiol, the response was potentiated by endosulfan in the proliferation assay and by pirimicarb, propamocarb, and daminozid in the ER transactivation assay. Vinclozolin reacted as a potent AR antagonist and dichlorvos as a very weak one. Methomyl, pirimicarb, propamocarb, and iprodion weakly stimulated aromatase activity. Although the potencies of the pesticides to react as hormone agonists or antagonists are low compared to the natural ligands, the integrated response in the organism might be amplified by the ability of the pesticides to act via several mechanism and the frequent simultaneous exposure to

  14. Multi-residue analysis of pesticides, plant hormones, veterinary drugs and mycotoxins using HILIC chromatography - MS/MS in various food matrices.

    PubMed

    Danezis, G P; Anagnostopoulos, C J; Liapis, K; Koupparis, M A

    2016-10-26

    One of the recent trends in Analytical Chemistry is the development of economic, quick and easy hyphenated methods to be used in a field that includes analytes of different classes and physicochemical properties. In this work a multi-residue method was developed for the simultaneous determination of 28 xenobiotics (polar and hydrophilic) using hydrophilic interaction liquid chromatography technique (HILIC) coupled with triple quadrupole mass spectrometry (LC-MS/MS) technology. The scope of the method includes plant growth regulators (chlormequat, daminozide, diquat, maleic hydrazide, mepiquat, paraquat), pesticides (cyromazine, the metabolite of the fungicide propineb PTU (propylenethiourea), amitrole), various multiclass antibiotics (tetracyclines, sulfonamides quinolones, kasugamycin and mycotoxins (aflatoxin B1, B2, fumonisin B1 and ochratoxin A). Isolation of the analytes from the matrix was achieved with a fast and effective technique. The validation of the multi-residue method was performed at the levels: 10 μg/kg and 100 μg/kg in the following representative substrates: fruits-vegetables (apples, apricots, lettuce and onions), cereals and pulses (flour and chickpeas), animal products (milk and meat) and cereal based baby foods. The method was validated taking into consideration EU guidelines and showed acceptable linearity (r ≥ 0.99), accuracy with recoveries between 70 and 120% and precision with RSD ≤ 20% for the majority of the analytes studied. For the analytes that presented accuracy and precision values outside the acceptable limits the method still is able to serve as a semi-quantitative method. The matrix effect, the limits of detection and quantification were also estimated and compared with the current EU MRLs (Maximum Residue Levels) and FAO/WHO MLs (Maximum Levels) or CXLs (Codex Maximum Residue Limits). The combined and expanded uncertainty of the method for each analyte per substrate, was also estimated.

  15. Currently used pesticides and their mixtures affect the function of sex hormone receptors and aromatase enzyme activity

    SciTech Connect

    Kjeldsen, Lisbeth Stigaard; Ghisari, Mandana; Bonefeld-Jørgensen, Eva Cecilie

    2013-10-15

    The endocrine-disrupting potential of pesticides is of health concern, since they are found ubiquitously in the environment and in food items. We investigated in vitro effects on estrogen receptor (ER) and androgen receptor (AR) transactivity, and aromatase enzyme activity, of the following pesticides: 2-methyl-4-chlorophenoxyacetic acid (MCPA), terbuthylazine, iodosulfuron-methyl-sodium, mesosulfuron-methyl, metsulfuron-methyl, chlormequat chloride, bitertanol, propiconazole, prothioconazole, mancozeb, cypermethrin, tau fluvalinate, malathion and the metabolite ethylene thiourea (ETU). The pesticides were analyzed alone and in selected mixtures. Effects of the pesticides on ER and AR function were assessed in human breast carcinoma MVLN cells and hamster ovary CHO-K1 cells, respectively, using luciferase reporter gene assays. Effects on aromatase enzyme activity were analyzed in human choriocarcinoma JEG-3 cells, employing the classical [{sup 3}H]{sub 2}O method. Five pesticides (terbuthylazine, propiconazole, prothioconazole, cypermethrin and malathion) weakly induced the ER transactivity, and three pesticides (bitertanol, propiconazole and mancozeb) antagonized the AR activity in a concentration-dependent manner. Three pesticides (terbuthylazine, propiconazole and prothioconazole) weakly induced the aromatase activity. In addition, two mixtures, consisting of three pesticides (bitertanol, propiconazole, cypermethrin) and five pesticides (terbuthylazine, bitertanol, propiconazole, cypermethrin, malathion), respectively, induced the ER transactivity and aromatase activity, and additively antagonized the AR transactivity. In conclusion, our data suggest that currently used pesticides possess endocrine-disrupting potential in vitro which can be mediated via ER, AR and aromatase activities. The observed mixture effects emphasize the importance of considering the combined action of pesticides in order to assure proper estimations of related health effect risks

  16. Effects of currently used pesticides and their mixtures on the function of thyroid hormone and aryl hydrocarbon receptor in cell culture

    SciTech Connect

    Ghisari, Mandana; Long, Manhai; Tabbo, Agnese; Bonefeld-Jørgensen, Eva Cecilie

    2015-05-01

    Evidence suggest that exposure to pesticides can interfere with the endocrine system by multiple mechanisms. The endocrine disrupting potential of currently used pesticides in Denmark was analyzed as single compounds and in an equimolar mixture of 5 selected pesticides. The pesticides were previously analyzed for effects on the function of estrogen and androgen receptors, the aromatase enzyme and steroidogenesis in vitro. In this study, the effect on thyroid hormone (TH) function and aryl hydrocarbon receptor (AhR) transactivity was assessed using GH3 cell proliferation assay (T-screen) and AhR responsive luciferase reporter gene bioassay, respectively. Thirteen pesticides were analyzed as follows: 2-methyl-4-chlorophenoxyacetic acid, terbuthylazine, iodosulfuron-methyl-sodium, mesosulfuron-methyl, metsulfuron-methyl, chlormequat chloride, bitertanol, propiconazole, prothioconazole, mancozeb and its metabolite ethylene thiourea, cypermethrin, tau-fluvalinate, and malathion (currently banned in DK). In the T-screen, prothioconazole, malathion, tau-fluvalinate, cypermethrin, terbuthylazine and mancozeb significantly stimulated and bitertanol and propiconazole slightly reduced the GH3 cell proliferation. In the presence of triiodothyronine (T3), prothioconazole, tau-fluvalinate, propiconazole, cypermethrin and bitertanol significantly antagonized the T3-induced GH3 cell proliferation. Eleven of the tested pesticides agonized the AhR function, and bitertanol and prothioconazole inhibited the basal AhR activity. Bitertanol, propiconazole, prothioconazole and cypermethrin antagonized the TCDD-induced AhR transactivation at the highest tested concentration. The 5-component mixture had inducing effect but the combined effect could not be predicted due to the presence of bitertanol eliciting inhibitory effect. Upon removal of bitertanol from the mixture, the remaining four pesticides acted additively. In conclusion, our data suggest that pesticides currently used in Denmark