Degradation of the Organochlorinated Herbicide Diuron by Rainforest Basidiomycetes.

The main organochlorinated compounds used on agricultural crops are often recalcitrant, affecting nontarget organisms and contaminating rivers or groundwater. Diuron (N-(3,4-dichlorophenyl)-N',N'-dimethylurea) is a chlorinated herbicide widely used in sugarcane plantations. Here, we evaluated the ability of 13 basidiomycete strains of growing in a contaminated culture medium and degrading the xenobiotic. Dissipation rates in culture medium with initial 25 mg/L of diuron ranged from 7.3 to 96.8%, being Pluteus cubensis SXS 320 the most efficient strain, leaving no detectable residues after diuron metabolism. Pycnoporus sanguineus MCA 16 removed 56% of diuron after 40 days of cultivation, producing three metabolites more polar than parental herbicide, two of them identified as being DCPU and DCPMU. Despite of the strong inductive effect of diuron upon laccase synthesis and secretion, the application of crude enzymatic extracts of P. sanguineus did not catalyzed the breakdown of the herbicide in vitro, indicating that diuron biodegradation was not related to this oxidative enzyme.

Urine glyphosate level as a quantitative biomarker of oral exposure.

BACKGROUND: Since the classification of glyphosate as a Group 2A substance "probably carcinogenic to humans" by the IARC in 2015, human health concerns have been raised regarding the exposure of operators, bystanders, and consumers. Urine measurement studies have been conducted, but since toxicokinetic data on glyphosate in humans is lacking, a meaningful interpretation of this data regarding exposure is not possible. OBJECTIVE: This study aims to determine the fraction of glyphosate and AMPA excretion in urine after consuming ordinary food with glyphosate residue, to estimate dietary glyphosate intake. METHODS: Twelve participants consumed a test meal with a known amount of glyphosate residue and a small amount of AMPA. Urinary excretion was examined for the next 48 h. RESULTS: Only 1% of the glyphosate dose was excreted in urine. The urinary data indicated the elimination half-life was 9 h. For AMPA, 23% of the dose was excreted in urine, assuming that no metabolism of glyphosate to AMPA occurred. If all of the excreted AMPA was a glyphosate metabolite, this corresponds to 0.3% of the glyphosate dose on a molar basis. CONCLUSION: This study provides a basis for estimating oral glyphosate intake using urinary biomonitoring data.

Evaluation of non-invasive biomonitoring of 2,4-Dichlorophenoxyacetic acid (2,4-D) in saliva.

The objective of this study was to evaluate the potential for non-invasive biomonitoring of 2,4-Dichlorophenoxyacetic acid (2,4-D) in saliva. Using an in vitro rat salivary gland epithelial cell (SGEC) system, a collection of experiments investigating chemical protein binding, temporal and directional transport, as well as competitive transport with para-aminohippuric acid (PAH), a substrate for renal organic anion transporters, was conducted to identify cellular transport parameters required to computationally model salivary transport of 2,4-D. Additionally, a physiological protein gradient was implemented to mimic physiologically relevant concentrations of protein in rat plasma and saliva, and under these conditions the transfer of 2,4-D was markedly slower, driven by increased protein binding (i.e. reduced free 2,4-D species available to cross salivary barrier). The rate of transfer was directly proportional to the amount of unbound 2,4-D and demonstrated no indication of active transport. An in vivo assessment of 2,4-D exposure in rats revealed non-linear protein binding in plasma, indicating saturated protein binding and increased levels of unbound 2,4-D species at higher doses. A strong correlation between 2,4-D concentrations in saliva and unbound 2,4-D in plasma was observed (Pearson correlation coefficient = 0.95). Saliva:plasma 2,4-D ratios measured in vivo (0.0079) were consistent within the linear protein binding range and expected 2,4-D levels from occupational exposures but were significantly different than ratios measured in vitro (physiological conditions) (0.034), possibly due to 2,4-D concentrations in saliva not being at equilibrium with 2,4-D concentrations in blood, as well as physiological features absent in in vitro settings (e.g. blood flow). We demonstrated that 2,4-D is consistently transported into saliva using both in vitro and in vivo models, making 2,4-D a potential candidate for human non-invasive salivary biomonitoring. Further work is needed to understand whether current sensor limits of detection are sufficient to measure occupationally relevant exposures.

Co-expression of GR79 EPSPS and GAT yields herbicide-resistant cotton with low glyphosate residues.

Glyphosate-resistant (GR) crops have been adopted on a massive scale by North and South American farmers. Currently, about 80% of the 120 million hectares of the global genetically modified (GM) crops are GR crop varieties. However, the adoption of GR plants in China has not occurred at the same pace, owing to several factors including, among other things, labour markets and the residual effects of glyphosate in transgenic plants. Here, we report the co-expression of codon-optimized forms of GR79 EPSPS and N-acetyltransferase (GAT) genes in cotton. We found five times more resistance to glyphosate with 10-fold reduction in glyphosate residues in two pGR79 EPSPS-pGAT co-expression cotton lines, GGCO2 and GGCO5. The GGCO2 line was used in a hybridization programme to develop new GR cottons. Field trials at five locations during three growing seasons showed that pGR79-pGAT transgenic cotton lines have the same agronomic performance as conventional varieties, but were USD 390-495 cheaper to produce per hectare because of the high cost of conventional weed management practices. Our strategy to pyramid these genes clearly worked and thus offers attractive promise for the engineering and breeding of highly resistant low-glyphosate-residue cotton varieties.

Vegetated Ditches for the Mitigation of Pesticides Runoff in the Po Valley.

In intensive agricultural systems runoff is one of the major potential diffuse pollution pathways for pesticides and poses a risk to surface water. Ditches are common in the Po Valley and can potentially provide runoff mitigation for the protection of watercourses. The effectiveness depends on ditch characteristics, so there is an urgent need for site-specific field trials. The use of a fugacity model (multimedia model) can allows recognition of the mitigation main processes. A field experiment was conducted in order to evaluate the mitigation capacity of a typical vegetated ditch, and results were compared with predictions by a fugacity model. To evaluate herbicide mitigation after an extreme runoff, the ditch was flooded with water containing mesotrione, S-metolachlor and terbuthylazine. Two other subsequent floods with uncontaminated water were applied 27 and 82 days later to evaluate herbicides release. Results show that the ditch can immediately reduce runoff concentration of herbicides by at least 50% even in extreme flooding conditions. The half-distances were about 250 m. As a general rule, a runoff of 1 mm from 5 ha is mitigated by 99% in 100 m of vegetated ditch. Herbicides retention in the vegetated ditch was reversible, and the second flood mobilized 0.03-0.2% of the previous one, with a concentration below the drinking water limit of 0.1 µg L(-1). No herbicide was detected in the third flood, because the residual amount in the ditch was too low. Fugacity model results show that specific physical-chemical parameters may be used and a specific soil-sediment-plant compartment included for modelling herbicides behaviour in a vegetated ditch, and confirm that accumulation is low or negligible for herbicides with a half-life of 40 days or less. Shallow vegetated ditches can thus be included in a general agri-environment scheme for the mitigation of pesticides runoff together with wetlands and linear buffer strips. These structures are present in the landscape, and their environmental role can be exploited by proper management.

Identification of transcriptome involved in atrazine detoxification and degradation in alfalfa (Medicago sativa) exposed to realistic environmental contamination.

Plants are constantly exposed to a variety of toxic compounds (or xenobiotics) such as pesticides (or herbicides). Atrazine (ATZ) as herbicide has become one of the environmental contaminants due to its intensive use during crop production. Plants have evolved strategies to cope with the adverse impact of ATZ. However, the mechanism for ATZ degradation and detoxification in plants is largely unknown. Here we employed a global RNA-sequencing (RNA-Seq) strategy to dissect transcriptome variation in alfalfa (Medicago sativa) exposed to ATZ. Four libraries were constructed including Root-ATZ (root control, ATZ-free), Shoot-ATZ, Root+ATZ (root treated with ATZ) and Shoot+ATZ. Hierarchical clustering was performed to display the expression patterns for all differentially expressed genes (DEGs) under ATZ exposure. Transcripts involved in ATZ detoxification, stress responses (e.g. oxidation and reduction, conjugation and hydrolytic reactions), and regulations of cysteine biosynthesis were identified. Several genes encoding glycosyltransferases, glutathione S-transferases or ABC transporters were up-regulated notably. Also, many other genes involved in oxidation-reduction, conjugation, and hydrolysis for herbicide degradation were differentially expressed. These results suggest that ATZ in alfalfa can be detoxified or degraded through different pathways. The expression patterns of some DEGs by high-throughput sequencing were well confirmed by qRT-PCR. Our results not only highlight the transcriptional complexity in alfalfa exposed to ATZ but represent a major improvement for analyzing transcriptional changes on a large scale as well.

Toxicity endpoint selections for a simazine risk assessment.

BACKGROUND: California uses simazine at one of the highest levels for states in the United States (approximately 2.5 million lbs 2006-2010). Simazine causes neuroendocrine disruption and mammary cancer in test animals. A risk assessment was prioritized by the California Department of Pesticide Regulation because of the nondietary concern for simazine exposure to occupational/nonoccupational simazine users, resident nonusers, and bystanders (especially children and children exhibiting pica) at greatest risk. METHODS: No observed effect levels (NOELs) from animal studies as well as human exposure data were used to determine nondietary values for the above populations. Registrant-submitted and open literature studies focusing on oral (major human route) effects for simazine and the major metabolites desisopropyl-s-atrazine and diaminochlorotriazine were reviewed as part of the hazard identification process. RESULTS: Developmental, reproduction, and chronic studies provided the lowest NOELs for the acute (5 mg/kg/day), subchronic (0.56 mg/kg/day), and chronic (0.52 mg/kg/day) exposure durations, respectively. A benchmark dose (95th percentile) was calculated for mammary tumorigenesis, assuming a threshold mechanism in rats (benchmark dose lower limit [95th percentile; BMDL05 ]: 2.9 mg/kg/day). Margins of exposure and uncertainty factors (100-300×, depending on exposure scenario) were used to characterize risk for designated population subgroups. CONCLUSIONS: Fetal developmental delays, endocrine disruption, and mammary tumors resulted from simazine treatment. Systemic and maternal/fetal effects determined the critical NOELs used in risk assessment. Margins of exposures for most scenarios were below acceptable levels, especially for children who may be bystanders where simazine is applied and children who exhibit pica. This risk characterization raises a concern for long-term effects in humans.

Novel molecular events associated with altered steroidogenesis induced by exposure to atrazine in the intact and castrate male rat.

Toxicology is increasingly focused on molecular events comprising adverse outcome pathways. Atrazine activates the hypothalamic-pituitary adrenal axis, but relationships to gonadal alterations are unknown. We characterized hormone profiles and adrenal (intact and castrate) and testis (intact) proteomes in rats after 3 days of exposure. The adrenal accounted for most of the serum progesterone and all of the corticosterone increases in intact and castrated males. Serum luteinizing hormone, androstenedione, and testosterone in intact males shared a non-monotonic response suggesting transition from an acute stimulatory to a latent inhibitory response to exposure. Eight adrenal proteins were significantly altered with dose. There were unique proteomic changes between the adrenals of intact and castrated males. Six testis proteins in intact males had non-monotonic responses that significantly correlated with serum testosterone. Different dose-response curves for steroids and proteins in the adrenal and testis reveal novel adverse outcome pathways in intact and castrated male rats.

Diuron-induced rat urinary bladder carcinogenesis: mode of action and human relevance evaluations using the International Programme on Chemical Safety framework.

Diuron, a high volume substituted urea herbicide, induced high incidences of urinary bladder carcinomas and low incidences of kidney pelvis papillomas and carcinomas in rats exposed to high doses (2500 ppm) in a 2-year bioassay. Diuron is registered for both occupational and residential uses and is used worldwide for more than 30 different crops. The proposed rat urothelial mode of action (MOA) for this herbicide consists of metabolic activation to metabolites that are excreted and concentrated in the urine, leading to cytotoxicity, urothelial cell necrosis and exfoliation, regenerative hyperplasia, and eventually tumors. We show evidence for this MOA for diuron using the International Programme on Chemical Safety (IPCS) conceptual framework for evaluating an MOA for chemical carcinogens, and the United States Environmental Protection Agency (USEPA) and IPCS framework for assessing human relevance.

Absence of P-glycoprotein transport in the pharmacokinetics and toxicity of the herbicide paraquat.

Genetic variation in the multidrug resistance gene ABCB1, which encodes the efflux transporter P-glycoprotein (P-gp), has been associated with Parkinson disease. Our goal was to investigate P-gp transport of paraquat, a Parkinson-associated neurotoxicant. We used in vitro transport models of ATPase activity, xenobiotic-induced cytotoxicity, transepithelial permeability, and rhodamine-123 inhibition. We also measured paraquat pharmacokinetics and brain distribution in Friend leukemia virus B-type (FVB) wild-type and P-gp-deficient (mdr1a(-/-)/mdr1b(-/-)) mice following 10, 25, 50, and 100 mg/kg oral doses. In vitro data showed that: 1) paraquat failed to stimulate ATPase activity; 2) resistance to paraquat-induced cytotoxicity was unchanged in P-gp-expressing cells in the absence or presence of P-gp inhibitors GF120918 [N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide] and verapamil-37.0 [95% confidence interval (CI): 33.2-41.4], 46.2 (42.5-50.2), and 34.1 µM (31.2-37.2)-respectively; 3) transepithelial permeability ratios of paraquat were the same in P-gp-expressing and nonexpressing cells (1.55 ± 0.39 and 1.39 ± 0.43, respectively); and 4) paraquat did not inhibit rhodamine-123 transport. Population pharmacokinetic modeling revealed minor differences between FVB wild-type and mdr1a(-/-)/mdr1b(-/-) mice: clearances of 0.47 [95% confidence interval (CI): 0.42-0.52] and 0.78 l/h (0.58-0.98), respectively, and volume of distributions of 1.77 (95% CI: 1.50-2.04) and 3.36 liters (2.39-4.33), respectively; however, the change in clearance was in the opposite direction of what would be expected. It is noteworthy that paraquat brain-to-plasma partitioning ratios and total brain accumulation were the same across doses between FVB wild-type and mdr1a(-/-)/mdr1b(-/-) mice. These studies indicate that paraquat is not a P-gp substrate. Therefore, the association between ABCB1 pharmacogenomics and Parkinson disease is not attributed to alterations in paraquat transport.

Comparisons of metabolic and physiological changes in rats following short term oral dosing with pesticides commonly found in food.

¹H Nuclear Magnetic Resonance spectroscopy has been used to profile urinary metabolites in male Fischer F344 rats in order to assess the metabolic changes induced by oral exposure to two benzimidazole fungicides (carbendazim and thiabendazole) and two bipyridyllium herbicides (chlormequat and mepiquat). Exposure levels were selected to be lower than those expected to cause overt signs of toxicity. We then compared the sensitivity of the metabolomics approach to more traditional methods of toxicity assessment such as the measurement of growth and organ weights. Separate, acute exposure experiments were conducted for each pesticide to identify potential metabolic markers of exposure across four doses (and a control). Growth, organ weights and feeding/drinking rates were not significantly affected by any compounds at any dose levels tested. In contrast, metabolic responses were detected within 8 and 24h for chlormequat and mepiquat, and after 24h for carbendazim and thiabendazole. These results demonstrate the potential for the use of metabolomics in food toxicity testing.

[Paraquat poisoning. Case report and overview]. / Paraquatintoxikation : Fallbericht und Literaturüberblick.

Paraquat poisoning in Germany is rare. Because plasma levels do not necessarily match the ingested amount of paraquat, repeated measurement of plasma levels is imperative. There is a large potential in the prehospital phase to improve prognosis: further resorption must be terminated by rigorous charcoal administration and early tracheal intubation if necessary. Because paraquat can be resorbed by dermal contact, steps to ensure sufficient protection of emergency medical personnel must be taken.As soon as further resorption has been prevented sufficiently, forced diuresis, renal replacement therapy, and hemoperfusion can be of help, but still remain controversial. To reduce pulmonary fibrosis, inspiratory oxygen concentrations must be adjusted to the minimal amount needed to ensure satisfactory tissue oxygenation. Data supporting the advantageous use of cyclophosphamide combined with methylprednisolone for the treatment of pulmonary fibrosis were recently published. Since the toxic mechanism implies a mismatch of oxidants and anti-oxidants, co-administration of ascorbic acid and N-acetylcysteine are simple treatments with few side effects.

A comparative study on the interference of two herbicides in wheat and italian ryegrass and on their antioxidant activities and detoxification rates.

A study was carried out to compare the effects of treating wheat (Triticum aestivum) and Italian ryegrass (Lolium multiflorum) with atrazine and fluorodifen. The herbicides interfered with photosynthesis and dark respiration, depending on the species. Atrazine decreased photosynthesis in both species and dark respiration in wheat, while fluorodifen caused decrements of photosynthetic activity of wheat. Antioxidant enzymes, such as ascorbate peroxidase (APX), dehydroascorbate reductase (DHAR), and glutathione reductase (GR), were generally more active in untreated and treated wheat with respect to Italian ryegrass, which explains why oxidative damage, expressed as malondialdehyde (MDA) content, was only found in ryegrass. Investigations on the activity of herbicide-detoxifying enzyme, glutathione S-transferase (GST), and on the accumulation and persistence of the herbicides in the plants showed higher detoxification rates in wheat than in the grass.

[Effect of antioxidant responsive element inducing phenol on D. melanogaster life span].

The effect of water-soluble synthetic antioxidant TS-13 (sodium 3-(3'-tert-butyl-4'-hydroxyphenyl) propyl thiosulfonate) on life span of different lines of Drosophila melanogaster under normal conditions and survival under oxidative stress induced by hydrogen peroxide and paraquat has been investigated. Introduction to the diet of 1% TS-13 prolonged the life span of males and females of D. melanogaster long-living line Canton S, had no effect on short-living Oregon R life span and reduced the life span of male D. melanogaster line IgI(558)OR/Cy, heterozygous on tumor suppressor recessive lethal mutation. When flies were exposed to hydrogen perexide, TS-13 significantly enhanced Canton Smale and Oregon R female survival. Under the influence of paraquat antioxidant protected Canton S female and Oregon R flies of both sexes. Despite the fact that the anti-aging and protective properties of synthetic phenol antioxidant TS-13 depend essentially on the genotype and gender, in the extreme conditions of oxidative stress its positive effect pronounced.

Mechanisms of olfactory toxicity of the herbicide 2,6-dichlorobenzonitrile: essential roles of CYP2A5 and target-tissue metabolic activation.

The herbicide 2,6-dichlorobenzonitril (DCBN) is a potent and tissue-specific toxicant to the olfactory mucosa (OM). The toxicity of DCBN is mediated by cytochrome P450 (P450)-catalyzed bioactivation; however, it is not known whether target-tissue metabolic activation is essential for toxicity. CYP2A5, expressed abundantly in both liver and OM, was previously found to be one of the P450 enzymes active in DCBN bioactivation in vitro. The aims of this study were to determine the role of CYP2A5 in DCBN toxicity in vivo, by comparing the extents of DCBN toxicity between Cyp2a5-null and wild-type (WT) mice, and to determine whether hepatic microsomal P450 enzymes (including CYP2A5) are essential for the DCBN toxicity, by comparing the extents of DCBN toxicity between liver-Cpr-null (LCN) mice, which have little P450 activity in hepatocytes, and WT mice. We show that the loss of CYP2A5 expression did not alter systemic clearance of DCBN (at 25 mg/kg); but it did inhibit DCBN-induced non-protein thiol depletion and cytotoxicity in the OM. Thus, CYP2A5 plays an essential role in mediating DCBN toxicity in the OM. In contrast to the results seen in the Cyp2a5-null mice, the rates of systemic DCBN clearance were substantially reduced, while the extents of DCBN-induced nasal toxicity were increased, rather than decreased, in the LCN mice, compared to WT mice. Therefore, hepatic P450 enzymes, although essential for DCBN clearance, are not necessary for DCBN-induced OM toxicity. Our findings form the basis for a mechanism-based approach to assessing the potential risks of DCBN nasal toxicity in humans.

Biotransformation of the diphenyl ether herbicide lactofen and purification of a lactofen esterase from Brevundimonas sp. LY-2.

The diphenyl ether herbicide lactofen is commonly used to control broadleaf weeds. Once released into the environment, this herbicide is subject to microbial reactions. This study describes the biotransformation of lactofen by Brevundimonas sp. LY-2 isolated from enrichment cultures inoculated with soil sample. This strain degraded about 80% of 50 mg L(-1) lactofen in 5 days of incubation in flasks. The metabolic behaviors of the herbicide in the media are described. The results show a transformation pathway of lactofen by the bacterium leading to the formation of 1-(carboxy)ethyl-5-(2-chloro-4-(trifluoromethyl)phenoxy)-2-nitrobenzoate and ethanol. An esterase, which could cleave the right ester bond of the alkanoic side chain of lactofen, was purified 113.3-fold to homogeneity with 6.83% recovery. The current results suggested that Brevundimonas sp. LY-2 degraded lactofen via the ester bond cleavage catalyzed by esterase.

Environmental levels of atrazine decrease spatial aggregation in the freshwater mussel, Elliptio complanata.

The commonly used herbicide atrazine (ATR), may cause estrogen-like alterations and, like other xenoestrogens, may alter behavior. Here effects on animal aggregation were tested in freshwater mussels exposed short-term to ecologically relevant ATR concentrations between 1.5 and 150microg/L. The aggregation index (AI), the fraction of mussels in the most densely populated tank section, was evaluated and showed higher AI at later times in both 6- and 72-h trials (p<0.001). After 72h, there was also less aggregation in estradiol- and mid-ATR-treated animals, 26% and 24% less than control, respectively (p<0.04). These data suggest that freshwater mussels tend to aggregate, that 72-h exposure to ecologically relevant ATR concentrations decreases aggregation, and that estradiol exposure has a similar effect. Given that bivalve aggregation may be related to reproduction, the results suggest that low concentrations of ATR may have ecological consequences on animal populations in this species.

Estimating absorbed dose of pesticides in a field setting using biomonitoring data and pharmacokinetic models.

Linking biomarker data to pharmacokinetic (PK) models permits comparison of absorbed dose with a toxicological benchmark, which is an important step to understanding the health implications of pesticide exposure. The purpose of this analysis was to evaluate the feasibility of reconstructing the absorbed dose of two pesticides using PK models developed from biomarker data in a study of occupational application of these compounds. Twenty-four-hour urine samples were collected from farmers 24 h before through 96 h after a typical application of chlorpyrifos or 2,4-D. PK models were used to link the amounts found in urine samples to absorbed dose. Modeled total body dose estimates (in micrograms) were compared to measured dose from time 0-96 h. Despite the complexities surrounding the interpretation of biomonitoring data from a field setting, the models developed as part of this analysis accurately estimated the absorbed dose of 2,4-D and chlorpyrifos when collection of urine samples was largely complete. Over half of the farmers were excluded from modeling due to suspected noncompliance with urine collection or confounding exposure events, which highlights the importance of these issues for designing and interpreting biomonitoring data in future studies. Further evaluation of PK models in scenarios using single void samples is warranted for improving field-based dose assessments.

Ethoxylated rapeseed oil derivatives as non-ionic adjuvants for glyphosate.

In a study aimed at finding environmentally benign adjuvants for glyphosate, ethoxylates of rapeseed oil and of methylated rapeseed oil were synthesized, with ethylene oxide (EO) content up to 40 and 8 respectively. They had less influence on spray retention by barley shoots than ethoxylated (15 EO) tallow amine (ETA). At 10 g L(-1), ethoxylated rapeseed oil with 30 or 40 EO and ethoxylated methylated rapeseed oil with 6 or 8 EO promoted glyphosate uptake by barley leaves to a greater extent than ETA at the same concentration. However, uptake rates were similar when the concentration was lowered to 2.8 and 3.1 g L(-1) for rapeseed oil derivatives and ETA respectively. In the case of ethoxylated methylated rapeseed oil with 8 EO (MeOil-8), glyphosate uptake increased when MeOil-8 concentration was raised from 5 to 10 g L(-1). In bioassays under controlled conditions, ethoxylated rapeseed oil with 40 EO (Oil-40) and MeOil-8 were slightly less effective than ETA in favouring the efficacy of glyphosate on barley. The same was found on ryegrass. However, both rapeseed oil derivatives compared well with glyphosate formulants such as ethoxylated diethylamine and alkyl ethoxy phosphate. In one field experiment, the efficacy of glyphosate in the presence of Oil-40, MeOil-8 or ETA was comparable with that of a commercial formulation. In another trial, MeOil-8 was as effective as ETA, but Oil-40 performed less well. It is concluded that ethoxylates of rapeseed oil and of methylated rapeseed oil are a promising chemistry for glyphosate adjuvants, provided that their ethylene oxide content is high.

Tissue distribution and urinary excretion of dimethylated arsenic and its metabolites in dimethylarsinic acid- or arsenate-treated rats.

Adult female Fisher 344 rats received drinking water containing 0, 4, 40, 100, or 200 parts per million of dimethylarsinic acid or 100 parts per million of arsenate for 14 days. Urine was collected during the last 24 h of exposure. Tissues were then taken for analysis of dimethylated and trimethylated arsenicals; urines were analyzed for these arsenicals and their thiolated derivatives. In dimethylarsinic acid-treated rats, highest concentrations of dimethylated arsenic were found in blood. In lung, liver, and kidney, concentrations of dimethylated arsenic exceeded those of trimethylated species; in urinary bladder and urine, trimethylated arsenic predominated. Dimethylthioarsinic acid and trimethylarsine sulfide were present in urine of dimethylarsinic acid-treated rats. Concentrations of dimethylated arsenicals were similar in most tissues of dimethylarsinic acid- and arsenate-treated rats, including urinary bladder which is the target for dimethylarsinic acid-induced carcinogenesis in the rat. Mean concentration of dimethylated arsenic was significantly higher (P<0.05) in urine of dimethylarsinic acid-treated rats than in arsenate-treated rats, suggesting a difference between treatment groups in the flux of dimethylated arsenic through urinary bladder. Concentrations of trimethylated arsenic concentrations were consistently higher in dimethylarsinic acid-treated rats than in arsenate-treated rats; these differences were significant (P<0.05) in liver, urinary bladder, and urine. Concentrations of dimethylthioarsinic acid and trimethylarsine sulfide were higher in urine from dimethylarsinic acid-treated rats than from arsenate-treated rats. Dimethylarsinic acid is extensively metabolized in the rat, yielding significant concentrations of trimethylated species and of thiolated derivatives. One or more of these metabolites could be the species causing alterations of cellular function that lead to tumors in the urinary bladder.