Distribution and excretion of [14CH3S]methamidophos after intravenous administration of a toxic dose and the relationship with anticholinesterase activity

The tissue distribution and excretion of [¹⁴CH₃S]methamidophos was followed in female Sprague-Dawley rats after intravenous injection at a toxic, but nonlethal, dose (8 mg/kg). Radiolabel was rapidly distributed to all tissues at approximately equal concentrations. Peak tissue levels were achieved within 1–10 min except in the central and peripheral nervous system where peak levels (40 nmol/g) were found between 20 and 60 min, corresponding to peak signs of toxicity. Within 24 hr of dosing, 47% of the radioactivity was recovered in the urine and 34% as ¹⁴CO₂ with <5% in the feces over 7 days. Cholinesterase (ChE) inhibition was measured in erythrocytes, plasma, and various regions of the central nervous system (CNS) at selected times after administration of methamidophos at 8 mg/kg. The degree of acetylcholinesterase (AChE) inhibition in the three CNS regions was similar, reaching a minimum of 15–20% of control values at 30–60 min, when toxicity was most severe. The degree of erythrocyte AChE inhibition was less than that of the CNS although the time course was similar. Plasma ChE inhibition was more rapid than that of the CNS or erythrocytes and reactivation was slower. When similar concentrations of methamidophos to those found in vivo were incubated with CNS homogenates, plasma, or erythrocytes in vitro (5 × 10^?5M) a similar degree of inhibition occurred over the same time course. It is, therefore, concluded that the cholinergic toxicity produced by methamidophos is a result of the in vivo stability of this compound combined with its entry into the nervous system in sufficiently high concentrations to inhibit AChE.     

Breakdown rates of dimethoate in fruit and vegetable dips

In order to determine the effect of pH and temperature on post-harvest dip solutions of dimethoate (500 mg litre^?1), the half-lives and pseudo first-order rate constants were calculated from measurements at pH 4, 6, 8, 10, 11.5, and at two temperatures 25 and 52°C. The half-lives ranged from 206 days to 39.3 min at 25°C, and from 5.6 days to 205s at 52°C; the rate constants ranged from 3.9 × 10^?8 s^?1 to 2.9 × 10^?4 s^?1 at 25°C, and from 1.4 × 10^?6 s^?1 to 3.4 × 10^?3 s^?1 at 52°C. The results show that the water used in dips should have a pH≤7. The addition of benomyl to the dip solutions at two concentrations (0.5 and 1.0 g litre^?1) had no effect on the half-lives and rate constants. The use of hard and salted waters in dips also showed no major effect. A formula was developed that gives the half-life of the dimethoate as a function of the pH and temperature.     

Rapid effects of a thiocarbamate herbicide and its dichloroacetamide protectant on macromolecular syntheses and glutathione levels in maize cell cultures

The rapid effects of the thiocarbamate herbicide S-ethyl dipropyl thiocarbamate (EPTC) and the herbicide protectant N,N-diallyl-2,2-dichloroacetamide (DDCA) on macromolecular syntheses and glutathione (GSH) levels in maize cell cultures were studied to determine whether stimulation of GSH could be the primary mechanism of action of DDCA. EPTC (0.5 and 1 mM) reduced incorporation of radioactive precursors within 1 hr after treatment, and affected incorporation of [³H]acetate into lipids more than incorporation of [³H]adenosine into acid-precipitable nucleic acids, or [¹⁴C]protein hydrolysate into protein. [¹⁴C]EPTC was rapidly biotransformed within 8 hr by maize cell suspensions. Measureable decreases in GSH levels following treatment with 1 mM EPTC occurred after 15 hr. DDCA stimulated incorporation of [³H]acetate into lipids within 4 hr but did not affect incorporation of [¹⁴C]protein hydrolysate into protein or [³H]adenosine incorporation into nucleic acids. Measureable increases in GSH following DDCA treatment began after 12 hr. Treatment with EPTC and DDCA in combination inhibited incorporation of [³H]acetate into lipids less than EPTC given alone. Increases in GSH levels could be observed following pretreatments with glutathione precursors, but no protectant activity could be detected, in contrast to treatments with DDCA. It is suggested that DDCA has an initial rapid effect on lipid metabolism followed by a slower effect involving increases in cellular GSH.     

Effect of 2,4,5-T and picloram on the regeneration of blackberry (Rubus procerus P.J. Muell) from root segments

The formation of roots and shoots on root segments of Rubus procerus P.J. Muell was prevented by soaking the segments for 24 h in a 10^?4M solution of 2,4,5-T or a 10^?5M solution of picloram. Shoot numbers were significantly increased after treatment with 10^?9M and 10^?10M 2,4,5-T, but picloram did not cause a significant increase in shoot numbers. Measurement of the concentration of 2,4,5-T in the extracambial tissue showed that roots treated with 10^?4M 2,4,5-T contained 5× 10^?8 mmole 2,4,5-T per mg dry weight, and by extrapolation, roots treated with 10^?9M 2,4,5-T contained 2× 10^?10 mmole/mg dry weight. Action du 2,4,5-T et du piclorame sur la régénération de la ronce (Rubus procerus P.J. Muell) è partir de fragments de racines La formation de racines et de tiges è partir de fragments de racines dc Ruhus procerus P.J. Muell a été supprimée par trempage des fragmenls pendant 24 heures dans une solution a 10^?4M et de 2.4,5-T, ou dans une solution 10^?5M de piclorame. Le nombre de pousses s'est accru significativement après traitement avec le 2,4,5.-T è 10^?9M et 10^?10M, mais le piclorame n'a pas provoqué d'accroissemcnt significatif du nombre de pousses. La mesure de la concentration de 2,4,5-T dans le tissu extra-cambial a montré que les racines trailées avec du 2,4,5-T è 10^?4M contenaient 5×10^?8 mmole de 2.4,5-T par mg de poids sec et par extrapolation, quc les racines traitées avec du 2,4,5-T k 10^?9M devaient contenir 2 × 10^?12 mmole/mg de poids sec. Die Wirkiing von 2,4,5-T und Picloram auf den Wuchs der Wurzehegmenten von Bromheeren (Rubus procerus P.J. Muell). Die Bildung von Wurzeln und Sprossen aus Wurzelsegmen-ten von Ruhu.i procerus P.J. Muell wurde durch 24-stündiges Einlegen der Wurzelstücke in 10^?4M 2,4,5-T bzw 10^?5M Picloram verhindert. Die Anzahl neugebiideter Sprosse wurde nach Einlegen in 10^?9M und 10^?10M 2,4,5-T, nicht jedoch durch Picloram, signifikant erhöht. Im extracambialen Gewebe von Wurzeln, die mit 10^?4M 2,4,5-T behand-elt worden waren, wurden 5×10^?8mMol 2,4,5-T je mg Trockengewiclu bestimmt. Durch Extrapolation wurde ermittclt. dass mit 10^?9M 2,4,5-T behandelte Wurzeln 2× 10^?12mMol/mg Trockengewicht cnthielten.     

Enhanced excretion of DDT and metabolites in rats treated with trans,trans-muconate

The interactions between trans,trans-muconate and p,p′-DDT were examined. Male Wistar rats were injected intraperitoneally with 6.67 mg kg^?1 [¹⁴C]p,p′-DDT. Two hours later the experimental animals received orally a solution of sodium muconate (75 mg kg^?1, 0.3 ml) in physiological saline, pH 7.2; control animals received an equal volume of physiological saline. Treatment was repeated every 12 hr for 10 days. Sodium muconate does not modify urinary excretion of labeled compounds, yet it reduces body burden by accelerating the excretion rate of these compounds in rat feces. This action was observed only during the first 24 hr after the animals were exposed to p,p′-DDT.     

Mode of action of the delayed toxicity of O,O,S-trimethyl phosphorothioate in the rat

As preliminary probes to determine the mode of delayed toxic action of O,O,S-trimethyl phosphorothioate (I) in the rat, the effect of I on rat tissue and organs, and on blood, urine, and pharmacokinetic parameters was investigated. Following oral administration, 30 to 200 mg/kg I caused liver necrosis as a major pathological effect. Morphological changes were also observed in the heart, adrenal, tissues of the small intestine, and kidney. Most animals treated with I developed bronchopneumonia after 3 days. Blood samples taken from rats poisoned with 60 mg/kg I showed severe hemoconcentration; however, serum Na⁺, Cl^?, albumin, and total carbonate/bicarbonate varied only slightly. Na⁺ and Cl^? concentrations in the urine showed a steady decline with time following poisoning but K⁺ levels remained relatively constant. Pharmacokinetic studies showed that ¹⁴C levels in the blood following intraperitoneal or intravenous administration of 60 mg/kg [CH₃O¹⁴C]I were not affected when the animals were cotreated with 5% of the antagonist O,O,O-trimethyl phosphorothioate. However, lower levels of ¹⁴C were found in antagonized animals following oral administration.     

Biliary secretion of 14C and identification of 5,6-dihydro-5,6-dihydroxycarbaryl glucuronide as a biliary metabolite of [14C]carbaryl in the rat

The biliary secretion of ¹⁴C was observed in conscious, bile-fistulated rats given single oral doses of [¹⁴C]carbaryl (1.5, 30, and 300 mg/kg). Over 94% of the ¹⁴C was absorbed after 12 hr. From 15 to 46% of the ¹⁴C was secreted in bile, 10–40% in urine, and less than 1% in feces 12 hr after dosing. Three metabolites were isolated from bile and identified by mass and/or NMR spectrometric methods. These metabolites were: 5,6-dihydro-5,6-dihydroxycarbaryl glucuronide (12–18% of the biliary ¹⁴C), a conjugate(s) of carbaryl (12% of the biliary ¹⁴C), and conjugated isomers of hydroxy-carbaryl (2% of the biliary ¹⁴C). The majority of the biliary ¹⁴C remains to be identified.     

Increased activity and reduced sensitivity of glutamine synthetase in glufosinate‐resistant vetiver (Vetiveria zizanioides Nash) cells

Vetiver (Vetiveria zizanioides Nash) cells derived from an inflorescence were cultured in a modified N6 liquid medium supplemented with 10 µm 2,4‐D and 10 mm proline. Exponentially growing cell suspensions were subcultured with a selection medium containing glufosinate (ammonium dl ‐homoalanin‐4‐yl(methyl)phosphinate). The glufosinate‐resistant cells which can grow in a medium containing 5 × 10^?5 M glufosinate was selected by a stepwise selection, and its I₅₀ value was determined to be 4.2 × 10^?5 M. The growth of susceptible cells was inhibited by lower concentrations of glufosinate and its I₅₀ value was 2.5 × 10^?7 M. This indicated that the selected cells were 170‐fold resistant compared with the susceptible cells. Glutamine synthetase (GS) activity of the resistant cells was twice as high as that of the susceptible cells. The I₅₀ values of glufosinate were 3.2 × 10^?5 M and 9.0 × 10^?7 M for GS from the resistant and susceptible cells, respectively. The accumulation of ammonia caused by GS inhibition was higher in the susceptible cells. Absorption of [3,4–¹⁴C]glufosinate was not significantly different between the resistant and susceptible cells. Both cell types did not metabolize glufosinate. These results suggest that the resistance of the selected vetiver cell suspension to glufosinate is mainly due to increased GS activity and its decreased sensitivity to the herbicide.     

Inhibition of fatty acid biosynthesis in isolated bean and maize chloroplasts by herbicidal phenoxy-phenoxypropionic acid derivatives and structurally related compounds

The effects of nine phenoxy-phenoxypropionic acid derivatives and structurally related compounds on the incorporation of [¹⁴C]-acetate into free fatty acids in isolated bean and maize chloroplasts were studied. The compounds tested were esters and the corresponding free acids, OH-diclofop, a nonherbicidal metabolite of diclofop in plants, and d and l enantiomers of diclofop. Fatty acid biosynthesis in bean chloroplasts was not affected by all compounds. OH-Diclofop had a weak inhibitory effect on fatty acid synthesis in maize chloroplasts, while free acids were stronger inhibitors than the corresponding esters in the same system. Uptake studies with diclofop-methyl and diclofop indicated that the esters showed higher uptake rates in chloroplasts suspension. d-Diclofop (I₅₀, 9 × 10^?8M) was a more potent inhibitor than l-diclofop (I₅₀, 4 × 10^?6M). This agrees with the low herbicidal activity of the l enantiomer in vivo. The results suggest that the mode of action in this type of herbicide may be closely linked with the inhibition of fatty acid biosynthesis. The tolerance of beans could be based on an insensitivity of the target site.     

Comparative metabolism and disposition of [14C-benzyl] cypermethrin in quail,rat and mouse

The excretion and metabolism of cis + trans-[¹⁴C-benzyl] cypermethrin has been compared in quail, rat and mouse. Radioactivity was rapidly eliminated by quail dosed orally with [¹⁴C]cypermethrin (2 mg kg^?1), as was the case in the rat and the mouse. When the birds were dosed intraperitoneally (IP) with the ¹⁴C-labelled pyrethroid, radioactivity was excreted more slowly than after oral dosing, and almost 20% of the IP dose of ¹⁴C remained in the tissues after 7 days. Both mammalian species excreted [¹⁴C]cypermethrin more rapidly than did the avian species after IP administration, and less than 6% of the dose remained in their tissues after several days. The biotransformation of the pyrethroid was more complex in the avian species (34 metabolites) than in the two mammals (some 10 metabolites in each species). In quail the predominant reactions were ester bond cleavage of cypermethrin together with either aromatic hydroxylation or amino acid conjugation of the 3-phenoxybenzyl moiety. The hydroxylated derivatives were eliminated mainly as sulphates. 3-Phenoxybenzoic acid was conjugated with a variety of amino acids including glycine, taurine, glutamic acid, serine, α-N-acetylornithine and the dipeptide glycylualine. The last two conjugations are unique to avian species. The major metabolite of cypermethrin in the rat was the sulphate conjugate of 3-(¹⁴-hydroxyphenoxy)benzoic acid, whereas in the mouse the major products were 3-phenoxybenzoic acid and its taurine conjugate. Thus, in the mammalian species where hydroxylation was maximal, amino acid conjugation was a minor metabolic route und vice versa. However, in the quail, aromatic hydroxylation and amino acid conjugation of the 3-phenoxybenzyl moiety of cypermethrin were both major reactions. The influence of the rates and sites of metabolism, and of the enzymology of amino acid conjugation, in determining this species difference are discussed. The rapid metabolism of cypermethrin to a variety of polar conjugates that are readily excreted, together with the low brain sensitivity of birds compared with mammals to its neurotoxic effects, explains the low acute toxicity of this pyrethoid to avian species.     

Laboratory trials of fatty acids as repellents or antifeedants against houseflies,horn flies and stable flies (Diptera: Muscidae)

BACKGROUND: Straight‐chain, saturated fatty acids (particularly C8, C9 and C10) have some known behavioral effects on insects such as mosquitoes, and were tested in combination for potential repellency/antifeedant activity in bioassays against three significant muscoid flies of medical/veterinary importance: houseflies, horn flies and stable flies. RESULTS: Mixtures of C8, C9 and C10 (1:1:1; 15% total actives in formulation) were highly repellent to houseflies and horn flies at or below 1 mg formulation cm^?2. Repellency time varied from < 1 day for houseflies to usually at least 3 days for horn flies. Individual longer‐chain‐length fatty acids were tested, and C11 repelled houseflies for up to 5–8 days, while C12 lasted 2 days. Minimum statistically significant repellency levels of the C8, C9 and C10 mixture (3 h after application) against horn flies were 0.06–0.12 mg cm^?2. A liquid formulation of the 15% C8, C9 and C10 mixture in a silicone oil carrier (at 2.8 mg AI cm^?2) was highly repellent against hungry stable flies in a blood‐feeding membrane bioassay for at least 8 h. CONCLUSION: The low toxicity and reasonable activity and persistence of these carboxylic acids make them good candidates for development as protective materials against pest flies in livestock settings. Copyright © 2009 Society of Chemical Industry     

Cholinesterase inhibition by methamidophos and its subsequent reactivation

Methamidophos (O,S-dimethylphosphoramidothioate, Monitor) is an organophosphorus, cholinesterase-inhibiting insecticide. The rate constant (k_i) for inhibiting rat plasma cholinesterase (ChE) was 1.57 ± 0.03 × 10³M^?1 min^?1, for rat erythrocyte ChE was 8.86 ± 1.10 × 10³M^?1 min^?1, and for rat brain ChE was 6.58 ± 0.42 M^?1 min^?1. Brain and plasma cholinesterases spontaneously recovered from over 90% inhibition at 30 min to 50% inhibition in 4 and 14 hr, respectively. Pralidoxime increased the rate of reactivation in vitro. In vivo, rats poisoned with methamidophos exhibited signs of cholinergic stimulation. The LD₅₀ of ip methamidophos in male rats was 15 ± 0.7 mg/kg. Pralidoxime (60 mg/kg) and atropine (10 mg/kg) given with the methamidophos increased the LD₅₀ to 52 ± 4.9 mg/kg and 60 ± 0.4 mg/kg, respectively. In rats given 12.5 mg methamidophos (an LD₂₀), ChE activity was depressed 95 ± 12.5% in plasma, 92 ± 0.6% in stomach, and 88 ± 1% in brain at 1 hr after injection. At 48 hr after injection ChE activity had returned to 60% or more of control values in each of the tissues. Administration of a single dose of 60 mg/kg of pralidoxime along with methamidophos did not increase ChE activities at the times and places it was measured.     

Metabolism of amitrole in apple: III. Model systems

Excised shoots from apple trees and cell suspension cultures were used as model systems to study the metabolism of [3,5-¹⁴C]amitrole in Malus domestica Borkh. Significant differences in the metabolism of the compound applied were observed with excised shoots, cultured cells and whole apple trees. The major metabolite in excised shoots was aminotriazolylalanine which occurred both in the free form and as conjugates. The major metabolite from whole plants. triazolylalanine, was detected in shoots in minor amounts only. In cell suspension cultures, the type of metabolism strongly depended on the concentration of amitrole when initially applied. At 10 ^?3 m or lower, mainly aminotriazolylalanine was formed. Depending on the concentration of the active ingredient, this metabolite predominantly occurred in free form or as glycosides. At concentrations above 5 × 10^?4 M a new metabolite, 3,5-dihydroxytriazole, was detected which was the only metabolite found at 5 × 10^?3M. Significant amounts of nonmetabolized amitrole remained in the medium.     

Degradation and adsorption of 14C-MCPA in soil—influence of concentration, temperature and moisture content on degradation

MCPA was weakly absorbed in soils with 2.4, 3.0 and 2.9% humus. K_d-values were 0.7, 0.9 and 1.0, respectively. In soil, not previously treated with MCPA, the degradation of 0.05 mg kg^?114C-MCPA followed first-order reaction kinetics whereas degradation of 5 mg kg^?1 was only first-order for 2 weeks; exponentially increasing degradation rates followed indicating enrichment of the soil with MCPA decomposers. Degradation was monitored by evolution of ¹⁴CO₂. The influence of temperature on degradation of MCPA (4 mg kg^?1) could initially be described by Q₁₀ values or by the Arrhenius equation. After 1 day of incubation in two field soils Q₁₀ values were 3.3 and 2.9, respectively, between 0°C and 29°C; the activation energies were 87 and 76 kj mol^?1. Exponentially increasing degradation rates followed with doubling times of about 4.0, 1.8, 1.2 and 0.6 days at 6,10, 15 and 21°C, respectively. After 51 days of incubation, at temperatures between 6°C and 29°C, about 60%¹⁴C was evolved in CO₂ and only traces of MCPA were left in the soil. At 0°C and at 40°C only 1% and 10%¹⁴C, respectively, were evolved as CO₂ after 51 days. ¹⁴C-MCPA (4 mg kg^?1) was incubated at moisture contents from that in air-dried soil to 2.3 times field capacity. Optimum for degradation was from 0.6 to 1.2. field capacity. Degradation was very slow where water contents were below the level of wilting point and was nil in air-dried soil. In wet soil degradation was delayed, but even in water-logged soil (2.3 times field capacity) MCPA was decomposed after 4 to 5 weeks at 10°C.     

Acute toxicity to zebrafish of two organophosphates and four pyrethroids and their binary mixtures

BACKGROUND: Environmental pollutants, including metals, pesticides and other organics, pose serious risks to many aquatic organisms. The acute toxicities to zebrafish (Brachydanio rerio Hamilton & Buchanan) were determined for two organophosphorus insecticides, four pyrethroid insecticides and 50:50 binary mixtures. RESULTS: At 24, 48, 72 and 96 h after treatment, LC₅₀ of permethrin, tetramethrin, bifenthrin, etofenprox, dichlorvos and phoxim to zebrafish were 0.0052–0.0025, 0.0782–0.0460, 0.0065–0.0032, 0.0969–0.0791, 51.3–13.0 and 1.28–0.469 mg L^?1 respectively. LC₅₀ of permethrin + dichlorvos, permethrin + phoxim, tetramethrin + dichlorvos, tetramethrin + phoxim, bifenthrin + dichlorvos, bifenthrin + phoxim, etofenprox + dichlorvos and etofenprox + phoxim were 0.0082–0.0046, 0.0078–0.0042, 0.264–0.124, 0.141–0.121, 0.0251–0.0154, 0.0154–0.0087, 0.396–0.217 and 0.213–0.0391 mg L^?1. CONCLUSION: Toxicity levels of all pyrethroid insecticides to the zebrafish were high or very high. The organophosphate dichlorvos showed low toxicity, but phoxim showed high or intermediate toxicities to zebrafish, and the toxicities of binary mixtures of permethrin and dichlorvos or phoxim, bifenthrin and dichlorvos or phoxim and etofenprox and phoxim (48, 72 and 96 h exposure) were very high. The toxicities of binary mixtures of tetramethrin and dichlorvos or phoxim, etofenprox and dichlorvos and etofenprox and phoxim (24 h exposure) were high. Copyright © 2009 Society of Chemical Industry     

Metabolic studies of 14C-labeled propham and chlorpropham in the female rat

The tissue distribution and excretion of ¹⁴C-labeled propham and chlorpropham were investigated in the adult female rat after a single oral dosage. The average 3-day urinary excretions of radioactivity were 55.9%, 82.6%, 79.5%, and 85.4% of an oral dose of chain [¹⁴C] chlorpropham, ring [¹⁴C] chlorpropham, chain [¹⁴C] propham, and ring [¹⁴C] propham, respectively. With chain [¹⁴C] chlorpropham 35.4 ± 7.5% of the administered radioactivity appeared in the respired air, whereas only 5.0 ± 0.8% was found in CO₂ from chain [¹⁴C] propham. There was no significant difference in the rate of excretion or the route of elimination among rats receiving different oral dosages, ranging from less than 4 mg/kg to 200 mg/kg. The radioactivity was distributed in all tissues with highest concentration found in the kidney. The average biological half-life of ¹⁴C from chlorpropham and propham in most organs was short, ranging between 3 and 8 hr; however, in brain, fat, and muscle, the half-life was about twice the value for other organs.Both compounds were metabolized by hydrolytic and oxidative mechanisms and the resulting metabolites were excreted either as free forms or as conjugates.Subcellular distribution of ¹⁴C in the rat liver and kidney after an oral administration of chlorpropham and propham was investigated. The percentage distribution of ¹⁴C in the particulate and soluble fractions was dependent on the elapsed time after dosing.     

Influence of monuron on photosystem II and light-dependent 14CO2 fixation in isolated cells of C3 and C4 plants

Cells were isolated from the developing leaves of Ipomoea aquatica (water spinach), a C₃ plant, and three kinds of C₄ plants, namely, Digitaria sanguinalis (NADP⁺-specific malate dehydrogenase type), Panicum miliaceum (NAD⁺-specific malic enzyme type), and Panicum texanum (phosphoenopyruvate carboxy kinase type), to study the effect of monuron on light-dependent ¹⁴CO₂ fixation and oxygen evolution. Bundle sheath cells, except for those of D. sanguinalis, and mesophyll cells of all plants fixed approximately the same amount of ¹⁴CO₂. Monuron, at the range used (2 to 10 × 10^?7M), showed strong inhibition in the mesophyll cells of water spinach and in bundle sheath cells of P. miliaceum and P. texanum and moderate inhibition in the mesophyll cells of all C₄ plants. In the bundle sheath cells of D. sanguinalis the low rate of ¹⁴CO₂ fixation was stimulated to some extent by the addition of malate and ribose 5-phosphate. The I₅₀ value was 6 × 10^?7M for the sensitive cells. Monuron inhibited the oxygen evolution of all seven cell types and their I₅₀ values varied between 3 × 10^?7 to 6 × 10^?7M. The differential response of isolated plant cells from different species to light-dependent CO₂ fixation in the presence of monuron may also be involved in urea herbicide selectivity and undoubtedly is due to the differential photosynthetic pathways present nn them.     

Metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide] inhibition of gibberellin precursor biosynthesis

[2-¹⁴C]Mevalonic acid incorporation into gibberellic acid precursors was measured in cell-free extracts from sorghum [Sorghum bicolor (L.) Moench var. G-522 DR] coleoptiles. ¹⁴C incorporation into ent-kaur-16-ene was inhibited ca. 90% by 10^?7 to 10^?4M metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide]. [¹⁴C]Geranylgeraniol (GG) content increased. [¹⁴C]Farnesol content was not altered and [¹⁴C]geraniol content decreased. Total ¹⁴C incorporation was decreased by metolachlor. In the safener [α-(cyanomethoximino)benacetonitrile]-treated sorghum seed coleoptile cell-free system, total ¹⁴C incorporation increased, [¹⁴C]kaurene and relative kaurence content increased 4× up to 10⁵M metolachlor, and [¹⁴C]farnesol, and [¹⁴C]GG contents increased while relative farnesol and relative GG contents were not influenced by metolachlor. Thus, the inhibition of kaurene synthesis by metolachlor was reversed by the safener. Since the biosynthetic processes are mevalonic acid → geraniol → farnesol → GG → copalylol → kaurene, these data corroborate a proposed gibberellic acid biosynthesis inhibition between GG and kaurene as well as a partial blockage between mevalonic acid and geraniol. Thus, a portion of metolachlor-induced growth inhibitions of sorghum could be explicable on the basis of gibberellic acid biosynthesis inhibitions.     

The action of insecticides on neurosecretory neurons in the stick insect, Carausius morosus

The action of insecticides on the spontaneous electrical activity of neurohemal tissue in the stick insect, Carausius morosus, has been studied using extracellular electrodes. The pyrethroid, permethrin, causes a massive increase in the frequency of the spontaneously generated action potentials at concentrations between 5 × 10^?5 and 5 × 10^?8M. Concentrations as low as 5 × 10^?11M are still effective in producing bursting activity.DDT, at concentrations between 5 × 10^?5M and 5 × 10^?6M, produces an overall increase in activity although the bursting activity is less violent than that shown with permethrin. DDT, 5 × 10^?7M, is ineffective at altering the resting pattern.Carbaryl and coroxon cause a transitory increase in electrical activity at 1 × 10^?4M, but are ineffective at 1 × 10^?5M.It is concluded that insecticides could have a direct effect upon the neurohormonal balance in insects.