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PubMed2006

Toxic effects of irgarol and diuron on sea urchin Paracentrotus lividus early development, fertilization, and offspring quality.

Irgarol and Diuron are the most representative "organic booster biocides" that replaced organotin compounds in antifouling paints. It cannot be assumed beforehand that their use will have no environmental impact: more ecotoxicological data and a significant environmental monitoring are required. Spermio and embryotoxicities of the biocides Irgarol and Diuron were investigated on Paracentrotus lividus, the dominant echinoid species of the Mediterranean Sea. Spermiotoxicity was studied by assessing the effects of sperm exposure on fertilization rate as well as on the induction of transmissible damages to the offspring. Embryotoxicity was studied by assessing the developmental defects in the exposed larvae. The experimental results show a Diuron EC50 of 2.39 (+/- 0.21) mg/L with a NOEL of 0.25 mg/L for embryos, and of 5.09 (+/- 0.45) mg/L with a NOEL of 0.5 mg/L for sperms, respectively. Data obtained from the embryotoxicity test on Irgarol [EC50 0.99 (+/- 0.69) mg/L] are of the same order of magnitude as the literature data about Japanese urchins. Spermiotoxicity tests show an Irgarol EC50 of 9.04 (+/- 0.45) mg/L with a NOEL of 0.1 mg/L. These data show the different sensitivities of the two tests: embryos are more sensitive than sperms for both the tested chemicals and Diuron seems to be the less toxic one. Moreover, as a major output of the experimental work, tested herbicides exert transmissible damage to spermatozoa evidenced by larval malformations in the offspring, mainly P1 type (skeletal alterations). The comparison of the endpoints results offers an interesting indication of a probable different mode of action (Irgarol seems to interact with calcium homeostasis) of the two biocides.

Animals↗
PubMed2006

Biodiversity of organotin resistant Pseudomonas from west coast of India.

Five bacterial isolates were screened for resistance to organotin compound, i.e. tributyltin chloride (TBTC) up to 2 mM. The optimum pH, temperature and salinity for the growth of the isolates were found to be 7, 28 degrees C and 2.5%, respectively. The isolates were tested for survival tolerance to heavy metals (mercury, cadmium and zinc) and co-resistance to antibiotics viz. ampicillin, kanamycin, rifampicin, streptomycin, penicillin, chloramphenicol, tetracycline, nalidixic acid and neomycin. Although our earlier study reported that these five bacterial strains are of different species of Pseudomonas, our present 16S rRNA gene sequence analysis revealed that all the strains are Pseudomonas aeruginosa. One of five isolates P. aeruginosa strain 25W could grow in mineral salt medium with 2 mM of TBTC as a sole source of carbon and survive up to 5 mM of TBTC. In presence of 2 mM of TBTC there was comparable up-regulation of 45 kDa protein in the cell extract of the 25W isolate was found indicating involvement of certain enzymes in TBTC resistance.

Anti-Bacterial Agents↗
PubMed1990

Tributyltin stimulates apoptosis in rat thymocytes.

Treatment of rat thymocytes with micromolar concentrations of tributyltin caused a rapid increase in the cytosolic free Ca2+ concentration that was inhibited by Ni2+, which blocks Ca2+ influx through membrane channels. The elevation of cytosolic Ca2+ was associated with extensive DNA fragmentation, which was prevented by pretreatment of the cells with either of the intracellular Ca2+ chelators quin-2 or 1,2-bis(2-amino-phenoxy)ethane-N',N',N',N',-tetraacetic acid. Loss of thymocyte viability, which followed DNA fragmentation, was also prevented by the two Ca2+ chelators or by removing extracellular Ca2+ with ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid. The pattern of DNA fragmentation was characteristic of that produced by agents which activate a Ca2(+)- and Mg2(+)-dependent endogenous endonuclease during apoptosis or programmed cell death. Additional studies showed that other organotin compounds, including trimethyltin, triphenyltin, and dibutyltin had minimal effects on cytosolic Ca2+, DNA fragmentation, and cell viability. These results are consistent with a greater susceptibility of thymocytes to tributyltin and provide a basis for understanding its selective immunotoxicity in vivo.

Animals↗
PubMed1984

Effect of triethyltin on autonomic and behavioral thermoregulation of mice.

The organotin compound, triethyltin (TET), produces toxic effects in a variety of physiological systems. Thermoregulatory control appears to be especially susceptible to TET toxicity, since TET administration has been shown to cause a pronounced hypothermia in rats. To further elucidate effects of TET on thermoregulation, we measured metabolic rate, evaporative water loss (EWL), body temperature, and preferred ambient temperature (Ta) of mice treated intraperitoneally with TET (bromide salt). At a Ta of 23 to 24 degrees C, TET (6 and 8 mg/kg) inhibited metabolic rate by 23 and 66%, respectively. TET resulted in hypothermia at Ta's of 20 and 30 degrees C but not 35 degrees C. TET had little effect on EWL. Mice given TET at doses of 4, 6, and 8 mg/kg selected a cooler Ta (ca. 25 degrees C) compared to controls (ca. 29 degrees C). Thus, the mice selected a Ta associated with a hypothermic body temperature. At a relatively cool Ta, mice treated with TET had a reduced rate of heat production and, consequently, were hypothermic. At a relatively warm Ta, TET had no effect on heat production and did not increase active heat dissipation (i.e., EWL), thus the mice remained normothermic. The behavioral data indicate that TET evokes a type of regulated hypothermia in mice.

Animals↗
PubMed1984

Organometal-induced antinociception: a time- and dose-response comparison of triethyl and trimethyl lead and tin.

Recent reports have demonstrated that organolead and -tin compounds can alter behavioral reactivity to noxious stimuli. To further define the dose response and temporal characteristics of these neurobehavioral effects, male Fischer 344 rats were injected sc with either one-fourth, one-half, or three-fourths the acute LD50 of triethyl lead (TEL), triethyl tin (TET), trimethyl lead (TML), trimethyl tin (TMT), or distilled water and tested on a 57.5 degrees C hot plate 1, 7, 14, 21, and 28 days after dosing. All four organometals altered hot plate latencies, but the magnitude and time course of these effects differed among the compounds. TEL produced a dose-related increase in latencies which was maximal 1 and 7 days postdosing and had dissipated by 28 days. In contrast, the group administered TML (3/4 LD50) exhibited a late developing antinocioception which became evident 14 days after dosing and persisted throughout the period of testing. The intermediate dose of TMT (1/2 LD50) also produced a delayed increase in response times which was observed 21 and 28 days post-treatment. The 3/4 LD50 dose of TMT produced increased hot plate latencies on all post-treatment test days except Day 14. TET (1/2 LD50) produced increased hot plate latencies 1, 7, 14, and 21 days postdosing and also induced a reversible ataxia and akinesia. Higher doses of TET proved lethal to 80% of the animals and lower doses failed to alter response times in the hot plate. These data demonstrate that trialkyl lead and tin compounds can produce time- and dose-related increases in hot plate latencies.

Animals↗
PubMed1988

Metal-induced alteration of the cell membrane/cytoplasm complex studied by flow cytometry and detergent lysis.

Flow cytometric analysis of the cell cycle is most effectively accomplished with membrane-/cytoplasm-free ("clean") nuclei. Non-ionic detergents (e.g. NP40 or Triton X-100) commonly are employed to solubilize cell membranes/cytoplasm to produce "clean" nuclei. Treatment of murine erythroleukemic cells (MELC) with tri-n-butyltin methoxide, cadmium acetate, zinc sulfate, or lead acetate alters the properties of the cell membrane/cytoplasm complex making it resistant to NP40 dissolution. On a molar basis, the organotin compound was more effective in inducing resistance to detergent-mediated dissolution than the inorganic metal compounds. Resistance to NP40-mediated dissolution was manifested as an increase in the flow cytometric parameters 90 degrees scatter and fluorescein isothiocyanate (FITC) fluorescence and was confirmed by light microscopy.

Acetates↗
PubMed1993

Induction of a 70-kDa protein in human lymphocytes exposed to inorganic heavy metals and toxic organic compounds.

Human peripheral blood lymphocytes synthesize a 70-kDa protein (p70) distinct from metallothionein (MT), in response to several inorganic heavy metals. Although Cd and Zn induce both p70 and MTs, Co induces only p70. On the other hand, Cu, Hg, Ni and Ag, which are the inducers of MTs, can not induce p70. This protein is indistinguishable in electrophoretic mobility from the 70-kDa heat shock protein, which is induced by incubation of lymphocytes at 42-45 degrees C. Several environmental pollutants other than the inorganic heavy metals, including organic tin compounds and organic phosphorus compounds, were also found to induce p70. The responsiveness to a variety of environmental stimuli suggests the involvement of p70 in the basic cellular defense mechanism.

Blood Proteins↗
PubMed1992

Ca(2+)-dependent mechanisms of cytotoxicity and programmed cell death.

There is increasing evidence that the calcium ion plays a critical role in both toxic cell killing and programmed cell death. Thus, in a variety of experimental systems a perturbation of intracellular Ca2+ homeostasis due to increased Ca2+ influx and/or inhibition of Ca2+ extrusion has been found to be an early event in the development of cell injury. It is clear that sustained increases in intracellular Ca2+ can activate cytotoxic mechanisms which result in perturbations of cellular structure and function. For example, the stimulation of Ca(2+)-dependent proteases can result in a disruption of cytoskeletal organization and the formation of surface protrusions (blebs) and Ca(2+)-mediated phospholipase activation can result in an impairment of mitochondrial function with collapse of membrane potential and cessation of ATP synthesis. The activation of a Ca2+, Mg(2+)-dependent nuclear endonuclease is associated with chromatin cleavage and appears to play a crucial role in programmed cell death (apoptosis) in the immune system and other tissues. There is also recent evidence that this process may be responsible for the immunotoxicity of dioxins and organotin compounds and involved in the killing of adenocarcinoma cells by tumor necrosis factor alpha. Although calcium ions appear to be required for endonuclease activity during apoptosis, this process is also influenced by other factors, e.g. protein kinase C activity, intracellular polyamine and Zn2+ levels, chromatin structure, etc. Thus, the regulation of endonuclease activity under both physiological and toxicological conditions appears to be complex and to involve multiple factors.

Animals↗
PubMedDate not supplied

Neonatal exposure to triethyltin disrupts olfactory discrimination learning in preweanling rats.

Triethyltin is an organotin compound that is known to produce neurotoxicity in both adult and developing organisms. Although this neurotoxicity has been documented with a variety of behavioral and biological measures, the effects of this compound on learning during early development have been less extensively studied. The present study reports four experiments that examined this question with an odor aversion learning paradigm in which pups received presentations of one odor paired with footshock and an alternate odor without shock. In Experiment 1, Long-Evans rat pups were injected IP on postnatal day 5 (PND 5) with either 0, 3 or 5 mg/kg TET and then tested for olfactory discrimination learning on PND 18. Only the 5-mg/kg dose impaired discrimination learning. In Experiment 2, PND 5 exposure to TET (5 mg/kg) disrupted olfactory learning on PND 18 but not on PND 12, whereas exposure on PND 10 disrupted learning at both ages of testing. In Experiment 3, PND 16 exposure to TET (5 mg/kg) also disrupted acquisition of olfactory learning on PND 18 but had no effect on retention of an olfactory discrimination that was acquired prior to TET exposure (i.e., on PND 14 and PND 15). Unconditioned responses to footshock were also unaffected by TET (Experiment 4). These findings indicate that neonatal exposure to TET impairs associative learning in developing rats and are discussed in relation to other studies of the developmental neurotoxicity of this compound.

Aging↗
PubMedDate not supplied

Neonatal exposure to trimethyltin disrupts spatial delayed alternation learning in preweanling rats.

Trimethyltin is an organotin compound that produces marked neurotoxicity in both adult and developing animals. The limbic system is a primary CNS target site for this toxicity, and a prominent behavioral effect of TMT is disruption of learning and memory. Impairment of cognitive development has also been suggested by studies showing that rats neonatally exposed to TMT cannot perform spatial working memory tasks during adulthood. However, the question of how early in ontogeny such deficits can be detected has not been addressed. The present study examined this question with a T-maze delayed alternation learning paradigm. Long-Evans rat pups, injected IP on Postnatal Day 10 (PND 10) with 6 mg/kg TMT and tested on PND 18, were unable to learn delayed alternation in the manner shown by vehicle control pups. However, TMT- and vehicle-treated groups were both able to learn a simple position discrimination. These findings indicate a selective impairment of spatial working memory by neonatal TMT exposure and show that this impairment can be demonstrated during the preweanling period in the rat.

Aging↗
PubMed2006

Inhibition of rainbow trout (Oncorhynchus mykiss) P450 aromatase activities in brain and ovarian microsomes by various environmental substances.

Aromatase, a key steroidogenic enzyme that catalyses the conversion of androgens to estrogens, represent a target for endocrine disrupting chemicals. However, little is known about the effect of pollutants on aromatase enzymes in fish. In this study, we first optimized a rainbow trout (Oncorhynchus mykiss) microsomal aromatase assay to measure the effects of 43 substances belonging to diverse chemical classes (steroidal and non steroidal aromatase inhibitors, pesticides, heavy metals, organotin compounds, dioxins, polycyclic aromatic hydrocarbons) on brain and ovarian aromatase activities in vitro. Our results showed that 12 compounds were able to inhibit brain and ovarian aromatase activities in a dose-dependent manner with IC50 values ranging from the low nM to the high microM range depending on the substance: steroidal and non steroidal inhibitors of aromatase (4-hydroxyandrostenedione, androstatrienedione, aminogluthethimide), imidazole fungicides (clotrimazole, imazalil, prochloraz), triazole fungicides (difenoconazole, fenbuconazole, propiconazole, triadimenol), the pyrimidine fungicide fenarimol and methylmercury. Overall, this study demonstrates that rainbow trout brain and ovarian microsomal aromatase assay is suitable for evaluating potential aromatase inhibitors in vitro notably with respect to environmental screening. The results highlight that methylmercury and some pesticides that are currently used throughout the world, have the potential to interfere with the biosynthesis of endogenous estrogens in fish.

Androstenedione↗
PubMed2005

Elevated Ca2+(i) transients induced by trimethyltin chloride in HeLa cells: types and levels of response.

Humans are exposed to organotins, like trimethyltin (TMT) chloride via air, water and food, and intoxication might result in severe health complications. Toxic effects of organotin compounds are well documented, but possible mechanisms remain unclear and only little information is available how organometallic species interact with calcium controlling mechanisms. Therefore, the aim of this work was to investigate the effects of TMT on calcium homeostasis in HeLa S3 cells. Dynamic changes of cytosolic calcium (Ca2+(i)) were monitored using laser-scanning microscopy and fluo-4 loaded cells. Application of TMT resulted in sustained as well as in transient elevations of Ca2+(i). The number of reacting cells was directly correlated to the concentration of TMT used: with 500 microM TMT all cells reacted, with 50 microM TMT 80% and with 5 microM 74%. The fast Ca2+(i)-transients (spikes), measured in single cells, occurred even with 0.25 microM TMT and varied in size and duration. The sustained increase of Ca2+(i), measured as the average over all cells, was dose dependent with an approximately 8% increase for 5 microM TMT, approximately 12.3% for 50 microM and approximately 145% for 500 microM TMT. Moreover, this effect was partly reversible. A second application resulted in a similar sustained rise of Ca2+(i) compared to the first application of TMT, there was also no difference when no calcium was added to the external solution (151+/-10% compared to 145+/-15%; 500 microM TMT). This rise of Ca2+(i) was highly reduced (<10% increase) when the internal calcium stores were depleted before TMT (500 microM) was applied. Our data suggest that TMT influences Ca2+(i)-homeostasis of HeLa S3 cells, which might be related to its toxicity in this cell line.

Aniline Compounds↗
PubMed2026

Environmentally relevant concentrations of DCOIT impaired lifespan and healthspan in Caenorhabditis elegans.

DCOIT (4,5-dichloro-2-n-octyl-4-isothiazolin-3-one) is an antifouling biocide widely used as an alternative to organotin compounds. While previous studies had focused on its effects on energy production, endocrine disruption, and lipid metabolism, its impact on aging and underlying mechanisms remained unclear. Here, we demonstrated that environmentally relevant concentrations of DCOIT (37, 370 and 3700 ng/L) significantly impaired both lifespan and healthspan in Caenorhabditis elegans. RNA-seq and validation assays revealed that DCOIT upregulated comt-4, a key gene in dopamine metabolism, leading to dopamine depletion and subsequent induction of oxidative stress. This redox imbalance critically contributed to accelerated aging phenotypes. Importantly, both genetic (comt-4 RNAi) and pharmacological (opicapone) interventions restored dopamine levels, alleviated oxidative stress, and reversed DCOIT-induced aging deficits. Our study established the comt-4/dopamine/oxidative stress axis as a central mechanism in DCOIT toxicity, suggesting dopamine modulation as a potential countermeasure against environmental toxicant-induced aging.

Animals↗
PubMed2005

Hazardous substances in separately collected grey- and blackwater from ordinary Swedish households.

The objective of this paper is to present the mass flows of a number of selected hazardous substances in raw, separate grey- and blackwater from ordinary Swedish households. The Vibyasen housing area was selected for the investigation since its wastewater system has separate flows for grey- and blackwater. Due to the high analytical costs, a limited number of hazardous substances had to be selected and the number of samples restricted. The greywater flow was manually measured and the samples were collected at set time intervals. The blackwater samples were randomly collected from a blackwater tank. A total of 105 selected hazardous substances were measured in both fractions. Of the 24 elements (Ca, Fe, K, Mg, Na, S, Al, Ag, As, Ba, Bi, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Pt, Sb, Sn, Te, Zn) measured in both fractions, 22 were detected in the greywater and 23 in the blackwater. 81 organic substances were selected and measured in both fractions (nonylphenol- and octylphenol ethoxylates, brominated flame-retardants, organotin compounds, PAH, PCB, phthalates, monocyclic aromatics, and triclosan). 46 organic substances were found in greywater and 26 in blackwater. PCB was the only group found in neither grey- nor blackwater. The greywater flow fluctuated, with a specific average flow of 66 L per person and day. The composition of blackwater also fluctuated, with shifting proportions of urine, faeces, and flush water. The specific average blackwater flow was 28.5 L per person and day. The mixture of substances in separate wastewater fractions from Swedish households was too complex to exactly distinguish their specific sources.

Hazardous Substances↗
PubMed2005

Abiotic methylation of mercury in the aquatic environment.

Methylation of inorganic mercury in the aquatic environment has been considered to be largely the result of biological processes, primarily involving sulfate-reducing bacteria. However, these processes cannot account for all of the methylmercury that is formed naturally. A growing body of evidence suggests that chemical reactions represent another possible pathway for mercury methylation in the aquatic environment. In order to assess the abiotic contribution to mercury methylation in the water column, and specifically the conditions under which this contribution may be significant, the current state of knowledge about environmentally significant methylation reactions is reviewed. Results of our laboratory-based investigations of aqueous mercury reactions with some potential methyl donors, including MeCo(dmg)(2)(H2O), a simple model for methylcobalamin, various methyltin compounds and methyl iodide, are presented. In each reaction, the yield of methylmercury and the rate of methylation depend strongly on environmental factors such as pH, temperature, and the presence of complexing agents, especially chloride.

Bacteria↗