Evaluating the impact of synthetic herbicides on soil dwelling macrobes and the physical state of soil in an agro-ecosystem.

This study evaluated three herbicides active ingredients: Paraquat, Glyphosate and 2,4-D Amine in commercial formulations as Frankoquat, Roundup and Agriherb respectively under field conditions to determine their influence on soil dwelling macrobes and the physical state of soil. Herbicides were serially diluted to three treatment concentrations for each plus three controls. Herbicide concentrations were applied to the demarcated field on three consecutive occasions in splits. Macrobes extraction from soil was done under a stereo microscope at 20 × magnification. The Simpson's diversity index was used to calculate the soil macrobes diversity. Soil water content, bulk density and total porosity of sampled soils were determined. The study revealed that both herbicides and non-herbicides treatment had no statistical significance (p > 0.05) on the soil dwelling macrobes. Also, a Simpson's index of diversity, estimated as 53.46%, showed how the experimental area is lowly diverse in the specific soil dwelling macrobes identified. Significant correlations existed between the soil water content, bulk density, total porosity and number of soil macrobes at p < 0.05. This level of significance showed in most instances for Frankoquat herbicide concentration treatments as well as Roundup. For Agriherb and control treatments the correlations were present but majority was not significant. In most situations, the soil dwelling macrobes decreased with increasing soil physical conditions. Thus, the dynamics in soil physical properties affected macrobes abundance in soil, with the slightest influence coming from the herbicides concentrations used in the experiment. The study recommended that Frankoquat and Roundup herbicides could be used to control weeds on farmer's field because, their influence were slightly felt on the soil macrobes and also, quite a number soil dwelling macrobes recovered after application.

Importance of the Dimethylamino Functionality on a Multifunctional Framework for Regulating Metals, Amyloid-ß, and Oxidative Stress in Alzheimer's Disease.

The complex and multifaceted pathology of Alzheimer's disease (AD) continues to present a formidable challenge to the establishment of long-term treatment strategies. Multifunctional compounds able to modulate the reactivities of various pathological features, such as amyloid-ß (Aß) aggregation, metal ion dyshomeostasis, and oxidative stress, have emerged as a useful tactic. Recently, an incorporation approach to the rational design of multipurpose small molecules has been validated through the production of a multifunctional ligand (ML) as a potential chemical tool for AD. In order to further the development of more diverse and improved multifunctional reagents, essential pharmacophores must be identified. Herein, we report a series of aminoquinoline derivatives (AQ1-4, AQP1-4, and AQDA1-3) based on ML's framework, prepared to gain a structure-reactivity understanding of ML's multifunctionality in addition to tuning its metal binding affinity. Our structure-reactivity investigations have implicated the dimethylamino group as a key component for supplying the antiamyloidogenic characteristics of ML in both the absence and presence of metal ions. Two-dimensional NMR studies indicate that structural variations of ML could tune its interaction sites along the Aß sequence. In addition, mass spectrometric analyses suggest that the ability of our aminoquinoline derivatives to regulate metal-induced Aß aggregation may be influenced by their metal binding properties. Moreover, structural modifications to ML were also observed to noticeably change its metal binding affinities and metal-to-ligand stoichiometries that were shown to be linked to their antiamyloidogenic and antioxidant activities. Overall, our studies provide new insights into rational design strategies for multifunctional ligands directed at regulating metal ions, Aß, and oxidative stress in AD and could advance the development of improved next-generation multifunctional reagents.

Predicting acute and chronic effects of wood preservative products in Daphnia magna and Pseudokirchneriella subcapitata based on the concept of concentration addition.

The current European legislation requires that combined effects of the active substances and any substance of concern contained in biocidal products are taken into account in environmental risk assessment. The hypothesis whether the consideration of active substances together with all formulation additives that are labeled as presenting an environmental hazard is sufficient for a reliable environmental risk assessment was tested in the present study by investigating 3 wood preservative products. Relevant single substances in the products, some of their generic mixtures, the biocidal products themselves, and aqueous eluates prepared from the products (representing potential environmental mixtures) were tested for effects on algal growth and Daphnia acute immobilization as well as reproduction. Predictions for the products and the eluates were based on the concept of concentration addition and were mostly found to provide reliable or at least protective estimates for the observed acute and chronic toxicity of the mixtures. The mixture toxicity considerations also indicated that the toxicity of each product was dominated by just 1 of the components, and that assessments based only on the dominating substance would be similarly protective as a full-mixture risk assessment. Yet, there remained uncertainty in some cases that could be related to the toxicity of transformation products, the impact of unidentified formulation additives, or synergistic interaction between active substances and formulation additives.

Screening for potential hazard effects from four nitramines on human eye and skin.

Amines have potential to be used in CO2 capture and storage (CCS) technology, but as they can be released into the environment and be degraded into more toxic compounds, such as nitrosamines and nitramines, there have been concerns about their negative impact on human health. We investigated the potential toxic effects from acute exposure to dimethylnitramine (DMA-NO2), methylnitramine (MA-NO2), ethanolnitramine (MEA-NO2) and 2-methyl-2-(nitroamino)-1-propanol (AMP-NO2). The eye irritation, and skin sensitization, irritation and corrosion potential of these substances have been evaluated in vitro using the Bovine Corneal Opacity and Permeability (BCOP) assay, VITOSENS® assay, Reconstructed Human Epidermis (RHE) skin irritation test and Corrositex Skin corrosion test, respectively. Exposure to DMA-NO2 induced a mild eye irritation response, while MA-NO2, MEA-NO2 and AMP-NO2 were shown to be very severe eye irritants. MA-NO2 and MEA-NO2 were tested for skin sensitization and found to be non-sensitizers to the skin. In addition, none of the four test substances was irritant or corrosive to the skin.

Behenamidopropyl Dimethylamine: unique behaviour in solution and in hair care formulations.

SYNOPSIS: The rise of ecological awareness among consumers and industry has impacted the cationic surfactants market. The most used cationic surfactants present some drawbacks in this sense. Therefore, new molecules are being studied and developed which fulfil eco-toxicological requirements without losing performance. One of these surfactants is Behenamidopropyl Dimethylamine (BAPDMA). This biodegradable amidoamine, which converts into a cationic surfactant at acidic pH, shows outstanding water solubility, despite its very long alkyl chain. Its behaviour in solution has been exhaustively studied. The conditioning performance of this product is superior to that of commonly used cationic surfactants, providing a superior sensorial profile and improved combing force reductions on hair. Moreover, other applications for this product in the non-ionic form have been studied, such as conditioning agent in 2 in 1 shampoos, where it also shows colour protection effects, and as gelling agent in hair colouration creams. This multifunctional and high performance profile, together with an improved biodegradation and aquatic toxicity compared with currently used cationic surfactants, make this product a very interesting eco-friendly alternative for the hair care market.

Trimethylamine oxide, dimethylamine, trimethylamine and formaldehyde levels in main traded fish species in Hong Kong.

Levels of trimethylamine oxide (TMAO), dimethylamine (DMA), trimethylamine (TMA) and formaldehyde (FA) were studied in 266 different fishes, including fresh/frozen raw whole fishes of 89 different species that traded in Hong Kong, China. Determination of TMAO can confirm the source of DMA and FA if present in the sample. These samples were purchased from different commercial outlets between April and August 2007. All samples of raw whole fish were identified for their species by the Agriculture, Fisheries and Conservation Department. The content of TMAO was determined by high-performance liquid chromatography (HPLC) coupled with a chemiluminescent nitrogen detector. The possible decomposition products of TMAO, DMA and TMA were analysed by headspace solid-phase micro-extraction gas chromatography-mass spectrometry (HS-SPME-GC-MS), while FA was conducted by steam distillation then quantified by a HPLC. The range for TMAO of all samples was <5-3800 mg kg(-1) with median of 970 mg kg(-1), while the endogenous enzymatic cleavage products DMA, TMA and FA were in the range of <2-320, <1-190 and <1-160 mg kg(-1), respectively. These cleavage products were mainly found in three fish species, Harpadon nehereus, Saurida elongata and Saurida tumbil, that belong to the family Synodontidae (Lizardfishes) and subfamily Harpadontinae. Besides, freshwater fish species, namely, Micropterus salmoides, Oreochromis niloticus niloticus and Siniperca chuatsi, were found to contain TMAO in the range of 510-760, 85-720 and 400-640 mg kg(-1), respectively.

Biodegradability and ecotoxicity of amine oxide based surfactants.

The aerobic and anaerobic biodegradability as well as the aquatic toxicity of two fatty amine oxides and one fatty amido amine oxide were investigated. Aerobic biodegradation was evaluated using the CO(2) headspace test (ISO 14593) and biodegradation under anaerobic conditions was assessed employing a standardised batch test. The three amine oxide based surfactants tested were readily biodegradable under aerobic conditions but only the alkyl amido amine oxide was found to be easily biodegradable under anaerobic conditions. Toxicity to Photobacterium phosphoreum and Daphnia magna was evaluated. Bacteria (EC(50) from 0.11 to 11 mg l(-1)) proved to be more sensitive to the toxic effects of the amine oxide based surfactants than crustacea (IC(50) from 6.8 to 45 mg l(-1)). The fatty amido amine oxide showed the lowest aquatic toxicity.

Case report: the clinical toxicity of dimethylamine borane.

CONTEXT: Dimethylamine borane (DMAB) is a reducing agent used in nonelectric plating of semiconductors. Exposures are usually through occupational contact. We report here four cases of people who suffered from work-related exposure to DMAB. CASE PRESENTATION: Three patients exposed to DMAB decontaminated immediately by drinking a lot of water; they reported dizziness, nausea, diarrhea 6-8 hr later. The other patient did not decontaminate at once, and he suffered from more severe symptoms, including dizziness, nausea, limb numbness, slurred speech, irritable mood, and ataxia 13 hr later. Magnetic resonance imaging showed symmetric lesions with hyperintensity on T2WI and FLAIR in bilateral cerebellar dantate nuclei. This patient was readmitted to the hospital due to difficulty in walking and climbing 18 days after exposure. Lower leg weakness and drop foot were found bilaterally. A nerve conduction study revealed polyneuropathy with motor-predominant axonal degeneration. This patient receives regular outpatient followups and still walks with a clumsy gait and has difficulty with hand-grasping activity. DISCUSSION: This case study demonstrates that DMAB is highly toxic to humans through any route of exposure, and dermal absorption is the major route of neurotoxicity. DMAB induces acute cortical and cerebellar injuries and delayed peripheral neuropathy. RELEVANCE: Further investigation of the toxic mechanism of DMAB is warranted. Early decontamination with copious water is the best current treatment for exposure to DMAB.

Characterization of thymic atrophy and the mechanism of thymocyte depletion after in vivo exposure to a mixture of herbicides.

3,4-Dichloropropionanilide (propanil) and 2,4-dichlorophenoxyacetic acid (2,4-D) are two commonly used herbicides that are marketed as a chemical mixture. It was hypothesized that the interaction between these two herbicides, when administered as a mixture, would result in a greater effect on the immune system than the individual components of the mixture. The present study demonstrates in a murine model that a mixture of propanil and 2,4-D, when compared to single herbicide exposures, exacerbates decreases in thymocyte populations 2 d postexposure and inhibits the repopulation of T-cells in the thymus 7 d postexposure. Exposure to 150 mg herbicide/kg body weight of propanil or 2,4-D alone had no effect on thymus weight. In contrast, decreases in the ratio of thymus weight to body weight (TW:BW) occurred 2 d after treatment with the mixture of 150 mg propanil/kg body weight + 150 mg 2,4-D/kg body weight (150/150). Thymic atrophy was associated with a decrease in the double-positive thymocyte population (CD4+CD8+) and correlated with sera corticosterone levels from 600 to 1000 pg/ml. Therefore, the hypothesis was tested that glucocorticoids, induced after exposure to herbicides, were responsible for the thymic atrophy and depletion of thymocytes. However, similar levels of corticosterone were induced after exposure to 50, 100, or 150 mg propanil/kg body weight, and 50/50 or 100/100 mixture treatments, doses that did not produce thymic atrophy or cell loss. In addition, RU 486, a glucocorticoid receptor blocker, only partially abrogated the thymic atrophy in mice exposed to the 150/150 mixture of herbicides. These results suggest that glucocorticoids are only partially responsible for herbicide-induced thymic atrophy. This study demonstrates that the effects of exposure to a mixture of chemicals cannot always be predicted based on single exposure data and emphasizes the importance of mixture-based studies.

Genotoxicity of the herbicide 2,4-dichlorophenoxyacetic and a commercial formulation, 2,4-dichlorophenoxyacetic acid dimethylamine salt. I. Evaluation of DNA damage and cytogenetic endpoints in Chinese Hamster ovary (CHO) cells.

Genotoxicity of the 2,4-dichlorophenoxyacetic acid (2,4-D) and a commercially-used derivative, 2,4-D dimethylamine salt (2,4-D DMA), was evaluated in CHO cells using SCE and single cell gel electrophoresis (SCGE) assays. Log-phase cells were treated with 2.0-10.0 microg/ml of herbicides and harvested 24 and 36 h later for SCE analysis. Both agents induced significant dose-dependent increases in SCE, regardless of the harvesting time (2,4-D: r=0.98 and r=0.88, P<0.01, for 24 and 36 h harvesting times; 2,4-D DMA: r=0.97 and r=0.88, P<0.01, for 24 and 36 h harvesting times). Neither test compound altered cell-cycle progression or proliferative replication index (P>0.05), but the higher doses of both compounds reduced the mitotic index of cultures harvested at 24 and 36 h (P<0.05). A 90-min treatment with 2.0-10.0 microg/ml 2,4-D and 2,4-D DMA produced dose-dependent increases in the frequency of DNA-strand breaks detected in the SCGE assay, both in cultures harvested immediately after treatment and in cultures harvested 36 h later. The doses of 2,4-D and 2,4-D DMA were equally genotoxic in all of the assays. The results indicate that 2,4-D induces SCE and DNA damage in mammalian cells, and should be considered as potentially hazardous to humans.

Toxicological evaluation of mixtures of nonionic surfactants, alone and in combination with oil.

The toxicity to human bronchial (16-HBE14o-) epithelium cells of nonionic surfactants, polyoxyethylene-10-oleyl ether (C(18:1)E(10)), polyoxyethylene-10-dodecyl ether (C(12)E(10)), and N,N-dimethyl-dodecylamine-N-oxide (C(12)AO) alone or in combination with a range of pharmaceutically acceptable oils (namely, ethyl esters and triglyceride oils), was determined with the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Regardless of the presence of oil, all C(12)E(10)- and C(12)AO-containing systems were toxic at concentrations around or below their critical aggregation concentrations (as determined by surface tension measurements), suggesting that surfactant toxicity was due to the disruption caused by the partitioning of monomeric surfactant into the cell membrane. Systems prepared from C(18:1)E(10) alone or in combination with a low-molecular-weight oil, such as ethyl butyrate or tributyrin, were toxic above their critical aggregation concentration. In contrast, systems prepared from C(18:1)E(10) in combination with a high-molecular-volume oil (e.g., ethyl oleate, Miglyol 812, or soybean oil) were toxic only at concentrations significantly greater than their critical aggregation concentration, suggesting that in these cases surfactant toxicity was mediated by the aggregated form of the surfactant solubilizing components of the cell membrane. In the C(18:1)E(10)-stabilized system, it is proposed that toxicity was significantly reduced on incorporation of high-molecular-volume oils because these oils cause formation of a distinct oil core in the aggregates that leads to a reduction in the ability of the system to solubilize components of the cell membrane.

Haploinsufficiency of p18(INK4c) sensitizes mice to carcinogen-induced tumorigenesis.

The INK4 family of cyclin-dependent kinase (CDK) inhibitors negatively regulates cyclin D-dependent CDK4 and CDK6 and thereby retains the growth-suppressive function of Rb family proteins. Mutations in the CDK4 gene conferring INK4 resistance are associated with familial and sporadic melanoma in humans and result in a wide spectrum of tumors in mice. Whereas loss of function of other INK4 genes in mice leads to little or no tumor development, targeted deletion of p18(INK4c) causes spontaneous pituitary tumors and lymphoma late in life. Here we show that treatment of p18 null and heterozygous mice with a chemical carcinogen resulted in tumor development at an accelerated rate. The remaining wild-type allele of p18 was neither mutated nor silenced in tumors derived from heterozygotes. Hence, p18 is a haploinsufficient tumor suppressor in mice.

Gadolinium chloride reverses dimethylnitrosamine (DMN)-induced rat liver fibrosis with increased matrix metalloproteinases (MMPs) of Kupffer cells.

The aim of this study was to investigate whether matrix metalloproteinases (MMP-13, 9) of Kupffer cells induced by gadolinium chloride (GdCl(3)) treatment can reverse dimethylnitrosamine (DMN)-induced liver fibrosis (in vivo) and the effect of GdCl(3) on MAP kinase activity (in vitro). Male Wistar rats 6 weeks of age received DMN (10 mg/kg) three successive days a week for 4 weeks. Then two groups of rats (n = 6 each) were treated twice weekly with either GdCl(3) (7 mg/kg) or saline solution intravenously for the next 4 weeks. Animals were sacrificed to estimate the degree of liver fibrosis. Isolated Kuppfer cells were treated with GdCl(3) and the expressions of MMPs, MAP kinase activity (ERK, SAPK/JNK, P38) as well as apoptosis were also examined. Rats that received DMN for 4 weeks followed by GdCl(3) injection for 4 weeks showed an reduced liver hydroxyproline content compared to rats treated with DEN followed by saline (277 +/- 22 VS 348 +/- 34 microg/g, n = 6 each, P < 0.01). There were significantly increased MMP-13 mRNA levels in GdCl(3)-treated rats. However, no significant change was observed in procollagen type I mRNA levels. Isolated Kuppfer cells treated with GdCl(3) showed increased MAP kinase activity, especially P38 pathway as well as MMP-13, 9 mRNA and type I collagen-degrading activity leading to apoptosis. SB203580, inhibitor of P38 pathway diminished these activation and prevented apoptosis. These results suggest that Kuppfer cells can reverse liver fibrosis via the expression of MMPs mainly through P38 pathway.

[Participation of dexamethasone and E and C vitamins in the modulation of the hepatotoxic effect induced by fomesafen and 2,4-D amino herbicides, in rats ]. / Participacion de la dexametasona y las vitaminas E y C en la modulacion del efecto hepatotoxico inducido por los herbicidas fomesafen y 2,4-D amino, en ratas.

The fomesafen and 2,4-D amine herbicide induce cytotoxic effects at hepatic level in rats, such as: hepatomegaly, hyperplasia and increase in the enzymes activity which participate in the processes of peroxisomal beta-oxidation of fatty acids. In this work, the effect of vitamin E and C was evaluated, as well as, the dexamethasone in the modulation of these hepatotoxic effects. Sprague-Dawley rats were treated with the herbicides and with the agents to be evaluated. The different treatments were given during 15 days orally route. The herbicides combined with the dexamethasone and antioxidant agents were administrated only and simultaneously with the herbicides. Once concluded the different treatment, the rats were weighed and sacrificed. It was evaluated the liver size and liver fragments were obtained to determine the enzymatic activity of Fatty Acyl CoA-oxidase (FACO) and cellular number. The results showed that the hepatomegaly induced by fomesafen was inhibited by the vitamins and by the dexamethasone, while any effect was not observed in the group of rats treated with 2,4-D amine. None of the agents modulated the FACO activity induced by herbicides in treated rats. However, the dexamethasone showed a protective effect in the hyperplasia induced by two herbicides. The hepatotoxic effects induced by the herbicides responded to a different mechanism due to the differences of the effects observed at the antioxidant agents. On the other hand, the inhibition of the cellular proliferation by the dexamethasone does not keep relation with the responsible mechanisms of inducing the oxidant stress into FACO activity. Under experimental conditions of this study, the use of these agents does not guarantee protection against the hepatotoxic effects induced by the herbicides.

Toxicity and pharmacokinetics of 2-(2-dimethylaminoethoxy)ethanol following cutaneous dosing.

A 9-day repeated cutaneous toxicity study in the New Zealand White rabbit was conducted using 6-h occluded contact with 0 (water control), 50, 250 and 500 mg dimethylaminoethoxyethanol (DMEE)/kg. There were no clinical signs, and no effects on body weight, food consumption or serum chemistry. Hematological effects were limted to increased leukocyte count due to heterophil leukocytosis, increased platelet count, and decreased hemoglobin and hematocrit at the high dose. These findings are typical of the response of cutaneous inflammation. Histopathological findings were limited to the DMEE-treated skin, and consisted of acanthosis and ulcerative/necrotizing dermatitis. Thus, there was no evidence for cumulative percutaneous systemic toxicity for DMEE. The pharmacokinetics of DMEE was investigated in the Fischer 344 rats. Rats were given an intravenous dose of 15 or 150 mg/kg, or an occluded cutaneous dose of 150 mg/kg [14C]DMEE, and its fate was followed for 48-72 h. DMEE was readily absorbed through the skin (bioavailability=72-80%). Concentration in plasma rose steadily to a maximum at about 3.5 h after dosing, and then declined in a biphasic manner. 14C-DMEE-derived radioactivity was distributed throughout the body, with no apparent sequestration in any particular organ. The highest concentrations were observed in the kidney, liver and lung, and the lowest concentrations were found in the brain and fat. Urine was the major route of excretion, with minor amounts eliminated in the feces and as expired CO(2). The rate of excretion was moderate, with about 30% of the applied dose eliminated in the first 12 h, and by 72 h after dosing, less than 4% of the dose remained in the carcass. Unchanged DMEE was the principal component detected in the urine. This observation, together with the less than 1% of the dose excreted as CO(2), showed that metabolism was not an important process in the elimination of DMEE in the rat.

Effects of 2,4-dichlorophenoxy acetic acid dimethyl amine salt on dental hard tissue formation in rats.

2,4-Dichlorophenoxy acetic acid dimethyl amine salt (2,4-D DMA), as one of the phenoxy acids, is used as a herbicide mainly against broad-leaf weeds in cereal crops, sugar cane, and on turf, pasture, and non-crop land. Some formulations of 2,4-D may be contaminated with dioxins. Recently, it has been shown that chlorinated organic compounds, dioxins, and furans are present in mother's milk and may cause developmental defects in children's teeth. Therefore, we aimed to evaluate the effects of 2,4-D DMA on odontogenesis in rats. 2,4-D DMA was given orally combined with rat food to pregnant albino rats. Each group consisted of two pregnant rats and, 0 (control, group A), 25 ppm (group B), 50 ppm (group C), and 100 ppm (group D) 2,4-D DMA was given to each pregnant rat as daily intake. 2,4-D DMA affected young rat's dental development and dose-related findings were found in experimental groups. The odontoblast layer was irregular and globular dentin formation was present in Groups B, C, and D but not in the control group. Thickness of enamel decreased in Groups C and D. The results of the study have shown that 2,4-D DMA could disturb dental development in rats even in relatively low doses. It is concluded that environmental contaminants such as chlorinated organic pesticides may play an important role in infant's dental development when taken via mother's milk.