Phenoxyacetic Acid Herbicides Research Articles

Influence of reversed‐ and normal‐phase liquid chromatographic eluents in the fragmentation of selected chlorinated herbicides in thermospray liquid chromatography‐mass spectrometry

AbstractThe effect of two completely different mobile phase compositions, reversed‐phase acetonitrile‐water + ammonium acetate and normal‐phase cyclohexane, were compared in filament‐on thermospray liquid chromatography‐mass spectrometry (LC‐MS) for the determination of selected chlorinated herbicides such as chloroatrazines and chlorinated phenoxyacetic acids. By using acetonitrile‐water + 0.05 M ammonium acetate mixtures in positive ion mode thermospray LC‐MS, the chloroatrazine herbicides showed the acetonitrile adduct ion [M + (CH3CN)H]+ as the base peak, whereas the chlorinated phenoxyacetic acids showed no signal. In contrast, when cyclohexane, which is reported for the first time as an eluent in the thermospray technique, was used as the mobile phase the chlorinated phenoxyacetic acid herbicides exhibited [M – H]+, [M – Cl]+ and M+˙ as the main ions.Negative ion mode thermospray LC‐MS showed [M – H]− as the base peak for the chloroatrazines in the different mobile phases, whereas the chlorinated phenoxyacetic acids exhibited [M + H]−, [M + Cl]− or [M – HCl]− as the base peaks in cyclohexane and [M + acetate]− in acetonitrile‐water‐ammonium acetate.

Effect of ammonium formate as ionizing additive in thermospray liquid chromatography‐mass spectrometry for the determination of triazine, phenylurea and chlorinated phenoxyacetic acid herbicides

AbstractA comparison between the use of ammonium acetate and ammonium formate in thermospray liquid chromatography‐mass spectrometry with positive and negative ion modes using ‘filament‐on’ mode has been applied for the determination of simazine, atrazine, propazine, monuron, diuron, linuron, 2,4,‐D, 2,4,5‐T and silvex. By using ammonium formate, the positive ion mode showed for triazine and phenylurea herbicides [M + H]+ and [M + NH4]+, respectively, and the formation of other adduct ions different from ammonium acetate. In the negative ion mode, chlorinated phenoxyacetic acid herbicides exhibited [M + acetate]− or [M + formate]−, depending on the ionizing additive. Applications are reported for the determination of triazine and chlorinated phenoxyacetic acid herbicides in spiked soil and water samples, respectively.

2,4-Dichlorophenoxyacetic acid intoxication increases its accumulation within the brain

Exposure to the phenoxyacetic acid herbicides has been shown to produce neurotoxicity. Therefore, adult mice (pregnant) and rabbits were used to examine the accumulation and regional distribution of 2,4-dichlorophenoxyacetic acid (2,4-D) within the brain following intraperitoneal injection of a low dose (0.2–0.4 mg/kg) of [ 14C]2,4-D. Controls, i.e. animals not previously exposed to 2,4-D, were compared to animals acutely pretreated with higher doses (40–160 mg/kg) of unlabeled 2,4-D. Both autoradiography and direct tissue analysis showed that in control animals brain levels were much lower than plasma in both adult (∼4%) and fetus (∼8%). In both species, small variations were seen between the brain regions, with brainstem and cerebellum somewhat higher than other regions. Pretreatment with unlabeled 2,4-D caused a 5- to 10-fold increase in accumulation of [ 14C]2,4-D in both mice and rabbits. On the other hand, 2-deoxyglucose entry into the brain was not altered by 2,4-D pretreatment. Thus, there was no generalized increase in blood-brain barrier permeability. Instead, increased 2,4-D accumulation appeared to be caused by its decreased elimination from the brain. Pretreatment with 40 mg/kg led to a CSF 2,4-D concentration of 10 μM, a concentration sufficient to inhibit choroid plexus transport of [ 14C]2,4-D by nearly 50% in vitro. These results suggest that exposure to organic anions like 2,4-D may lead to the retention of potentially toxic anions within the CNS via competitive inhibition of the organic anion transport system which normally reduces their brain and CSF concentrations to very low levels.

Agricultural Herbicide Use and Risk of Lymphoma and Soft-Tissue Sarcoma

A population-based case-control study of soft-tissue sarcoma (STS), Hodgkin's disease (HD), and non-Hodgkin's lymphoma (NHL) in Kansas found farm herbicide use to be associated with NHL (odds ratio [OR], 1.6; 95% confidence interval [CI], 0.9, 2.6). Relative risk of NHL increased significantly with number of days of herbicide exposure per year and latency. Men exposed to herbicides more than 20 days per year had a sixfold increased risk of NHL (OR, 6.0; 95% CI, 1.9, 19.5) relative to nonfarmers. Frequent users who mixed or applied the herbicides themselves had an OR of 8.0 (95% CI, 2.3, 27.9) for NHL. Excesses were associated with use of phenoxyacetic acid herbicides, specifically 2,4-dichlorophenoxyacetic acid. Neither STS nor HD was associated with pesticide exposure. This study confirms the reports from Sweden and several US states that NHL is associated with farm herbicide use, especially phenoxyacetic acids. It does not confirm the case-control studies or the cohort studies of pesticide manufacturers and Vietnam veterans linking herbicides to STS or HD.

Herbicide Exposure and Cancer

The case-control study in Kansas reported by Hoar et al1in this issue has importance beyond its population of agriculture workers to the highly controversial and adversarial issue of health effects associated with herbicide exposure in Vietnam. The well-designed and carefully executed Kansas study adds substantially to the cumulating body of evidence concerning the following question: Does human exposure to phenoxyacetic acid herbicides increase the risk of soft-tissue sarcomas (STS), Hodgkin's disease (HD), and non-Hodgkin's lymphoma (NHL)? The findings among Kansas farmers are in accord with "no" answers to the first two malignancies and a "yes" answer to the third. Most relevant to the Kansas study are the series of case-control investigations undertaken by Hardell and colleagues2-4in rural Sweden in the mid- and late 1970s. Hardell's studies found highly significant relative risks, of magnitude fivefold and sixfold, for exposure to phenoxyacid herbicides in association with STS, HD,

Effects of phenoxyacetic acids on the induction of chromosome aberrations in vitro and in vivo.

The effects of phenoxyacetic acid herbicides were investigated on the induction of chromosome aberrations in human peripheral lymphocyte cultures in vitro and in lymphocytes of exposed workers in vivo. Pure 2,4-dichlorophenoxyacetic acid (2,4-D; 0.125, 0.150, 0.200 and 0.350 mM) did not increase the number of aberrations, whereas the commercial 2,4-D formulation (0.125, 0.250, 0.500, 1.000 and 1.250 mM, with respect to phenoxyacetic acid concentration) significantly increased the number of chromosome aberrations in vitro (without exogenous metabolic activation). The phenoxy acid levels in the breathing zone of the workers varied between 0.3 and 0.4 mg/m3, and the concentrations of phenoxyacetic acids in the urine of the workers after exposure varied from 0.000 to 0.055 mmol/l. There were no increases in chromosome aberrations in peripheral lymphocytes of the exposed subjects.

Qualitative and quantitative cancer risk assessment of 2, 3, 7, 8-tetrachloro-dibenzo-p-dioxin (2, 3, 7, 8-TCDD)

The carcinogenicity of 2,3,7,8-TCDD at multiple organ sites in animals has been well established by several cancer bioassays. Results of two of the most notable of these, the Kociba et al. (1978) rat feeding study and the National Toxicology Program (1980) gavage study in rats and mice showed hepatocellular carcinomas in two strains of female rats and male and female mice. Other tumor sites included carcinomas of the lung, tongue, hard palate and nasal turbinates, thyroid, and subcutaneous tissue. The evidence for carcinogenicity of 2,3,7,8-TCDD in animals is regarded as “sufficient” using the classification system of the International Agency for Research on Cancer (IARC). Two Swedish epidemiologic case-control studies (Hardell and Sandstrom, 1979; Eriksson et al. 1979, 1981) reported a significant five- to sevenfold excess risk of soft-tissue sarcomas (STS) from occupational exposure to chlorinated phenoxyacetic acid herbicides and/or chlorophenols. Additionally, several small cohort studies collectively exhibited an unusual cluster of STS, significantly increased over combined expected incidence. Problems with these studies do not appear to be sufficient to discount this excess risk. The human evidence alone for the carcinogenicity of 2,3,7,8-TCDD is “inadequate” using the IARC classification. However, for 2,3,7,8-TCDD in combination with chlorinated phenoxyacetic acid herbicides and/or chlorophenols, the human evidence is considered to be “limited.” The overall evidence for carcinogenicity considering both animal and human studies would place 2,3,7,8-TCDD alone in the IARC category 2B, meaning that the substance is probably carcinogenic in humans. The overall weight of evidence for 2,3,7,8-TCDD in combination with chlorinated phenoxyacetic acid herbicides and/or chlorophenols is regarded as IARC category 2A, also meaning that they are probably carcinogenic for humans. Using current EPA methodology for quantitatively estimating cancer risks, several animal data sets have been analyzed. Comparing the results, the upper-limit incremental unit risk estimate is 1.6 × 10 −2 for a lifetime exposure of 1 ng/kg/day. This estimate is derived from a lifetime feeding study (Kociba et al., 1978) in which 2,3,7,8-TCDD induced tumors of the liver, lungs, hard palate, and nasal turbinates in female rats. Incremental unit cancer risks are also extrapolated for lifetime 2,3,7,8-TCDD exposures in water and air. Based on continuous lifetime exposure to 1 ng/L 2,3,7,8-TCDD in drinking water, the upper-limit estimate of extra cancer risk per individual is 4.5 × 10 −3. For lifetime exposure to 1 pg 2,3,7,8-TCDD/m 3 in the ambient air, the upper-limit individual risk is 3.3 × 10 −5.

Transformation of phenoxyacetic acid herbicides by Phaseolus vulgaris L. callus cells

The auxin herbicide (4-chloro-2-methylphenoxy)-acetic acid (MCPA) was absorbed by liquid cultured callus cells of Phaseolus vulgaris L. and subsequently became hydroxylated at the methyl group. The alcohol remained largely unconjugated and was partly released to the culture medium. Several glycosides and an ether-soluble conjugate of MCPA appeared as minor metabolites. Unsubstituted phenoxyacetic acid (POA) was metabolised primarily by 4-hydroxylation and subsequent phenolic glucoside formation. Metabolites of POA were retained by the cells. In the case of both substrates, metabolism in cells correlated well with that observed in apical buds excised from etiolated seedlings.

The effects of hypolipidemic peroxisome proliferators on the induction of sister chromatid exchanges.

A novel class of suspected chemical carcinogens has been recently introduced by Reddy et al. (1). Characteristically, all the agents in the group possess hypolipidemic properties, induce proliferation of peroxisomes in the liver cells, and enhance the peroxisomal ß-oxidation of fatty acids in the liver and kidneys of rodents (2–7). They have been shown to cause liver tumors in experimental animals (1,8–12), but, are not mutagenic in the Ames Salmonella mutagenicity assay (13,14). The induction of peroxisome proliferation was first introduced by the hypolipidemic drug, clofibrate (ethyl-α-p-chlorophenoxyisobutyrate), and some of its structural analogs (15). At present, however, the number of known peroxisome proliferators is about 20, and the group includes several structurally diverse compounds of great industrial importance (e.g., phthalates which are used as plasticiders in the plastic industry) (15). Quite recently, we have also shown that the widely used weed and brush killers, phenoxyacetic acid herbicides 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-methylphenoxyacetic acid (MCPA) induce peroxisome proliferation and hypolipidemia in the liver cells of rodents (16,17). Similar to the previously known peroxisome proliferators, phenoxyacid herbicides are suspected carcinogens (18), even though they are not mutagenic in the Ames Salmonella assay (19).

The effect of the phenoxyacetic acid herbicides 2,4,5-trichlorophenoxyacetic acid and 2,4-dichlorophenoxyacetic acid as ascertained by direct experimentation.

In a recent discussion on the social responsibility of the scientist, J. T. Edsall made the point that it is difficult to resolve disputes or issues which involve technology as well as basic science (Edsall 1981). Most public policy issues on the use of technology may be placed in this category. The problems arise because scientific facts and value judgements are so closely interwoven it is exceedingly difficult to disentangle them, and the inferences that are drawn are inconclusive (Edsall 1981).KeywordsIndole Acetic AcidCleave PalateButyl EsterNMRI MousePhenoxyacetic AcidThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Hypolipidemia and peroxisome proliferation induced by phenoxyacetic acid herbicides in rats

Male Wistar rats were treated daily by gavage with two phenoxy herbicides, 2,4-dichloro-phenoxyacetic acid (2,4-D)(100–200 mg/kg body wt) and 4-chloro-2-methylphenoxyacetic acid (MCPA) (100–200 mg/kg body wt), and with the chemically different glyphosate N-phosphonomethyl glycine (300 mg/kg body wt) 5 days per week for 2 weeks. A hypolipidemic drug, clofibrate [ethyl-2-(4-chlorophenoxy)-2-methylpropionate], which is structurally related to phenoxy acids, was used as a positive control (200 mg/kg body wt), 2,4-D and MCPA had several effects similar to those of clofibrate: all three compounds induced proliferation of hepatic peroxisomes, decreased serum lipid levels, and increased hepatic carnitine acetyltransferase and catalase activities. 2,4-D and MCPA, but not clofibrate, decreased lipoprotein lipase activity in the adipose tissue to about a third of the control value but did not change the lipoprotein lipase activity in the heart muscle. The data suggest that these compounds cause hypolipidemia not by enhancing the storage of peripheral lipids in adipose tissue but by preferentially increasing lipid utilization in the liver. Glyphosate caused no peroxisome proliferation or hypolipidemia, suggesting that these effects are associated with the structural similarity between phenoxy acid herbicides and clofibrate.

Ternary complexes of some phenoxyacetic acid herbicides and pyridines with metal ions of biological interest

Ternary complexes of Co(II), Ni(II) and Cu(II) with pyridine (Py) or 2-methyl pyridine (2-MePy) (primary ligand) and some phenoxyacetic acid herbicides, such as phenoxyacetic acid (PAA), 2-chlorophenoxyacetic acid (2-CPA), 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) (secondary ligands) have been studied in solution using a potentiometricpH-titration technique in order to test a complexation hypothesis of plant growth regulating activities of these herbicides. From stability constant data, the species distribution have been computed and it was found that the percentage of ternary complex (MAL) is about 60% of the totalM 2+ present at highpH indicating greater stability of these ternary complexes. TheMA + species (M 2+-Py andM 2+-2-MePy) have shown discriminating behaviour towards the next incoming secondary ligand containing O as donor atoms. Since the stabilities of biologically active (2-CPA, 2,4-D and2,4,5-T) and inactive (PAA) phenoxyacetic acid herbicides in binary (ML 2) and ternary (MAL) metal complexes were found approximately of the same magnitude, chelation may not thus be the probable mode of action of these plant growth regulators.

Effects of anionic xenobiotics on rat kidney: I—tissue and mitochondrial respiration

The polar 1,1,1-trichloro-2,2-bis( p-chlorophenyl)ethane (DDT) metabolite, 2,2-bis p-chlorophenyl)acetic acid ( DDA), and the phenoxyacetic acid herbicides, 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), were previously shown to be accumulated to high levels in liver and kidney via the organic acid transport system, raising the possibility of organ-specific toxicity secondary to transport. In these studies, accumulation of DDA was shown to depress oxygen consumption by renal cortical slices at high doses (0.1 and 1 mM). Isolated renal and hepatic mitochondria were uncoupled by low doses of DDA (5–10 nmoles/mg mitochondrial protein). Maximal uncoupling was seen at 50–70 nmoles/mg. 2,4-D and 2,4,5-T also produced uncoupling, but at doses of 70 nmoles/mg or higher. All agents were more effective with α-ketoglutarate or pyruvatemalate as substrate than with succinate. With succinate as substrate (but not α-ketoglutarate or pyruvate-malate), all three agents also depressed State 3 (ADP-stimulated) respiration. Again. DDA was more effective than 2,4-D or 2,4,5-T. These results suggest that accumulation of these or other anionic xenobiotics may lead to toxicity in those tissues possessing the organic anion transport system.

The adsorption of phenoxyacetic acid herbicides on goethite

The adsorption behavior of the phenoxyacetic acid herbicides on goethite has been studied as a function of solution pH and concentration of herbicide. Adsorption of these compounds, which are negatively charged over the pH range of interest, occurs only at pH values below the point of zero charge (PZC) of the goethite, indicating that they are not specifically adsorbed in this system. The amount of herbicide adsorbed, however, is in general much greater than would be expected purely on the basis of the coulombic interaction with the surface. This observation has been attributed to the existence of a favorable contribution to the adsorption free energy arising from van der Waals interactions between the adsorbed molecules themselves. It is believed that the van der Waals interactions are also responsible for the observed variation in adsorption behavior within the group of compounds studied, where adsorption was observed to increase with increasing degree of ring substitution.

Gas—liquid chromatographic method with electron-capture detection for the determination of residues of some phenoxyacetic acid herbicides in water as their 2,2,2-trichloroethyl esters

A gas—liquid chromatographic method with electron-capture detection was developed for the determination of residues of 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-methylpenoxyacetic acid (MCPA) in water as their 2,2,2-trichloroethyl esters, and the sensitivity was compared with that for 2-chloro- and 2,2,2-trifluoroethyl esters. The residue is isolated by sorption of the phenoxy acid on Amberlite XAD-4, eluted with benzen and then esterified with 20% (v/v) 2,2,2-trichloroethanol in trifluoroacetic anhydride in the presence of sulphuric acid. The recoveries at the 0.4 ppb * level are 92.1 ± 3.4% (2,4-D) and 87.8 ± 2.1% (MCPA) and the detection limits for a 1-1 sample of water are 0.096 ppb (2,4-D) and 0.06 ppb (MCPA).

Application of a new glass capillary chromatographic technique in the analysis of phenoxyacetic acid herbicides.

Application of a new glass capillary chromatographic technique in the analysis of phenoxyacetic acid herbicides.

Injury to City Plants from Industrial Emissions of Herbicides1

Abstract Injury typical of the phenoxyacetic acid herbicides 2,4-D and 2,4,5-T was observed in a large area of St. Louis in the spring of 1969. Screening of chemicals from a local manufacturer of these herbicides revealed that at least 7 chemicals involved in the production of these herbicides produce symptoms similar to those observed in the field. Injury occurred from aqueous concn as low as 1 ppm as well as from vapors of the isobutyl ester of 2,4-D. The uniqueness of plant injury due to industrial emissions of herbicides demonstrates the need for using biological parameters in assessing air quality.

Injury to City Plants from Industrial Emissions of Herbicides1

Abstract Injury typical of the phenoxyacetic acid herbicides 2,4-D and 2,4,5-T was observed in a large area of St. Louis in the spring of 1969. Screening of chemicals from a local manufacturer of these herbicides revealed that at least 7 chemicals involved in the production of these herbicides produce symptoms similar to those observed in the field. Injury occurred from aqueous concn as low as 1 ppm as well as from vapors of the isobutyl ester of 2,4-D. The uniqueness of plant injury due to industrial emissions of herbicides demonstrates the need for using biological parameters in assessing air quality.

Effect of ethyl p-chlorophenoxyisobutyrate on rat adipose lipoprotein lipase activity.

Effect of ethyl p-chlorophenoxyisobutyrate on rat adipose lipoprotein lipase activity.

The Auxinic Activity of Thioglycollic Acid Derivatives of β‐Di‐ketones

Abstract2,2′‐Di(carboxymethylthio) pentan ‐4‐one was found to increase the stem height of intact tomato plants growing in pots under glass. Stem height was increased by 60 percent although this was accompanied by malformations in lamina development, leaf epinasty, and a final reduction in shoot weight. Stem growth of tobacco and potato were also stimulated by this compound but the deleterious effects on leaf development were less marked. Subsequent screening of chemical analogues, using as an assay the growth response of intact tomato plants revealed that 3,3′‐di(carboxymethylthio)heptan‐5‐one initially stimulated stem growth but then produced severe shoot damage, similar to that caused by phenoxyacetic acid herbicides. Both chemicals stimulated extension growth in a wheat coleoptile section test though to a lesser extent than indole‐3‐acetic acid.Like the carboxymethyl‐N:N‐dialkyldithiocarbamates, these straight chain compounds appear to possess true auxin activity that could be related to the formation of an incomplete unsaturated “ring” system.