Structure-Activity Relationships for the Action of Dihydropyrazole Insecticides on Mouse Brain Sodium Channels

Assays of radiosodium uptake into mouse brain vesicles and the binding of [³H]batrachotoxinin A 20-α-benzoate (BTX-B) were used to compare the actions of six dihydropyrazole (3-aryl-1-arylcarbamoyl-2-pyrazoline) insecticides on mouse brain sodium channels. The relative potencies of the six dihydropyrazoles as inhibitors of either pumiliotoxin B-stimulated sodium uptake measured in the presence of scorpion (Leiurus quinquestriatus) venom or veratridine-stimulated sodium uptake were closely correlated with the relative potencies of these compounds as inhibitors of the binding of BTX-B to mouse brain sodium channels. A comparison of the enantiomers of the most potent dihydropyrazole, RH 3421, as inhibitors of radiosodium uptake showed that the (−) enantiomer of RH 3421 was approximately six-fold more potent than the (+) enantiomer. The potencies of these dihydropyrazoles in these assays and the stereoselectivity observed in the action of enantiomers of RH 3421 are in good agreement with available information on insecticidal activity in this group of compounds. Assays of the combined effects of RH 3421 and dibucaine as inhibitors of BTX-B binding revealed mutually competitive interactions between these compounds. This finding is consistent with the existence of a common site of action for dihydropyrazoles and local anesthetics on the sodium channel. The results of these studies provide further evidence for the toxicological relevance of the effects of dihydropyrazoles on sodium channels.     

Comparison of symptomatic and neurophysiological activities of enantiomers of the insecticide 3-phenoxybenzyl 1-(4-ethoxyphenyl)-2,2-dichlorocyclopropane-1-carboxylate

The insecticidal activities of optical isomers of 3-phenoxybenzyl 1-(4-ethoxyphenyl)-2,2-dichlorocyclopropanecarboxylate and related compounds were measured with American cockroaches and their knockdown activities were evaluated with house flies. The activities of the S(?)-isomer of the dichlorocyclopropanecarboxylate were higher than those of the R(+)-isomer. The effects of the compounds on the inward membrane currents induced by a stepdepolarizing pulse in crayfish axonal membranes were examined under voltage clamp conditions by the sucrose gap method. The compounds induced a tail current upon step repolarization of the membrane. The tail current decayed to zero in each record, but developed with time after the start of application of the compound until a steady level was reached. The rate of decay of the tail current observed in axonal membranes treated with the S(?)-isomer was slower than with the R(+)-isomer. The rates of development of the tail current induced by the two isomers were not very different.     

The high potency of ME-5343 to aphids is due to a unique mechanism of action

ME-5343 (afidopyropen) is a new and promising insecticide with an unknown mechanism of action that is effective against sucking insects. ME-5343 was highly toxic to pea aphids (Acyrthosiphon pisum), being more toxic than six other widely used insecticides. In contrast, ME-5343 was practically non-toxic to eight other species of insects we tested. ME-5343 was not toxic to German cockroaches (topical application) or American cockroaches (injection), suggesting that lack of toxicity in these species is not due to lack of cuticular penetration. House flies are insensitive to ME-5343 by topical, residual and feeding exposure. Addition of synergists did not change this result, suggesting that insensitivity to ME-5343 in house flies is not due to rapid detoxification nor is it dependent on the method of bioassay used. ME-5343 did not cause firefly lanterns to glow, nor did it prevent the octopamine stimulated lantern glow. Extracellular recordings of action potentials from a tonically active motor nerve of crayfish in situ showed no effects of ME-5343 at concentrations up to 10⁻⁵ M. These results suggest that the target site of ME-5343 is not the voltage gated sodium channel, voltage gated potassium channel, GABA gated chloride channel, nicotinic acetylcholine receptor, acetylcholinesterase, octopamine receptor or glutamate receptor. ME-5343 injected into crayfish caused flextion of the legs and tail, similar to the symptoms induced by 5-HT (serotonin). We evaluated the effect of ME-5343 on 5-HT2-like receptors with intracellular recordings of excitatory post-synaptic potentials from the peripheral neuromuscular junction of the crayfish and found no effect of ME-5343. Thus, ME-5343 was neither an agonist nor antagonist of 5-HT2 receptors, did not affect neurotransmitter release and did not affect glutamate receptors. We conclude that ME-5343 is highly toxic to aphids and that this is due to a unique, and currently undefined mechanism of action.     

The metabolism of 1-naphthyl methylcarbamate by Periplaneta americana

The in vivo release of ¹⁴CO2 arising from decarbamoylation of l-naphthyl methyl [¹⁴C]carbamate (carbaryl) injected into male and female Periplaneta americana was measured over the range from 0.2 to 50 nmol carbaryl/g body weight. The amount of ¹⁴CO2 released was proportional to the dose of [¹⁴C]-carbaryl injected and was not significantly different between male and female cockroaches. Carbaryl was found to be more toxic to male (KD100, 12 nmol carbaryl/g) than female (KD100′ 57 nmol carbaryl/g) cockroaches, at any dose which caused knockdown, females showed a greater ability to recover from the toxic syndrome than did males. The [¹⁴C]-carbaryl metabolism (decarbamoylation) was temperature dependent and could be partially inhibited by sesamex, tri-orthocresyl phosphate and anoxia. Secondary effects of carbaryl poisoning were severe dehydration of the animals and in some cases abdominal swelling due to air being gulped into the crop. The amount of dehydration was essentially unaltered by the chemical inhibitors, but was partially reduced by anoxia and cooling. In the most severe cases of dehydration animals lost 18 % of their body water content.     

Cross-Resistance to Imidacloprid in Strains of German Cockroach (Blattella germanica) and House Fly (Musca domestica)

The toxicity of a promising new insecticide, imidacloprid, was evaluated against several susceptible and resistant strains of German cockroach and house fly. Imidacloprid rapidly immobilized German cockroaches followed by a period of about 72 h during which some cockroaches recovered. After 72 h there was no further recovery. Imidacloprid-treated houseflies were immobilized more slowly than treated cockroaches, with the maximum effect observed after 72 h, and there was no recovery. Based upon 72-h LD₅₀ values imidacloprid was moderately toxic to German cockroaches (LD₅₀ values were 6–8 ng mg^-1) and had only low toxicity to house flies (LD₅₀ 140 ng mg^-1). Piperonyl butoxide (PBO) blocked the observed recovery in German cockroaches. PBO also greatly enhanced the 72-h LD₅₀ of imidacloprid from 43- to 59-fold in cockroaches and 86-fold in house flies. Two strains of German cockroach (Baygon-R and Pyr-R) showed >4-fold cross-resistance to imidacloprid. This cross-resistance could not be suppressed by PBO, suggesting that P450 monooxygenase-mediated detoxication is not responsible for this cross-resistance. Variation in the level of synergism observed with PBO (between strains) suggests the ‘basal’ level of monooxygenase-mediated detoxication of imidacloprid is quite variable between strains of German cockroach. The AVER and LPR strains of house fly showed significant cross-resistance to imidacloprid. PBO reduced the level of cross-resistance in AVER from >4·2-fold to 0·5-fold (i.e. the AVER strain LD₅₀ was half that of the susceptible strain when both were treated with PBO), but PBO did not suppress the cross-resistance in LPR. These data suggest monooxygenases are the mechanism responsible for cross-resistance to imidacloprid in AVER, but not in the LPR strain. © of SCI.     

Depolarization of motor nerve terminals by pyrethroids in susceptible and kdr-resistant house flies

When applied at concentrations of one nM or higher to a house fly larval neuromuscular preparation, deltamethrin (DM) and fenvalerate (FV) greatly increased miniature excitatory postsynaptic potential (mepsp) rate and blocked neuromuscular transmission. The DM-induced mepsp discharge was abolished by tetrodotoxin (TTX), removal of Ca²⁺ from the saline, or by application of hyperpolarizing stimuli to the nerve, indicating that it was due to depolarization of the presynaptic terminals. Also, in the presence of TTX, K⁺ depolarization increased mepsp rate at the same external K⁺ concentration before and after DM treatment, confirming that DM released transmitter by depolarizing the nerve terminals rather than by altering the voltage dependence of transmitter release. The potassium channel blocker tetraethylammonium (TEA) increased mepsp rate somewhat, while aconitine (20 μM), which keeps sodium channels open, increased mepsp rate consistently. Pretreatment of nerves with a subthreshold dose of TEA greatly increased the mepsp rate-increasing activity of DM and aconitine, while a subthreshold level of aconitine did not synergize DM. These observations suggest that DM, like aconitine, depolarized nerves by modifying the sodium channels. Knockdown resistant (kdr) larvae were resistant to the depolarizing action of DM and aconitine but not to that of TEA, indicating that the kdr gene produced a modified sodium channel which was less sensitive to the action of pyrethroids and aconitine. During sustained transmitter release by DM, evoked release gradually declined, resulting in a condition called early block in which spontaneous release was high and release could be evoked by electrotonic depolarization of the nerve terminals, but not by a nerve action potential. Early block was probably due to conduction block in the nerve terminals. Early block eventually gave way to late block, characterized by the decline of spontaneous release to subnormal levels and complete failure of evoked release. After late block, the calcium ionophore X-537A could not release transmitter, suggesting that late block was due to depletion of available transmitter. DM did not have a direct effect upon extrasynaptic muscle membrane. However, after late block, muscles were left insensitive to the putative transmitters glutamate and aspartate when these were bath or iontophoretically applied. A low rate of mepsps persisted after late block, indicating that the muscles were still sensitive to the natural transmitters.     

Effects of organosilicon pyrethroid‐like insecticides on nerve preparations of American cockroaches and crayfish

Quaternary organosilicon pyrethroid‐like ethers (five compounds) and alkanes (three compounds) were used for neurophysiological tests. Their activities in inducing repetitive firing in the central nervous cord of the American cockroach (Periplaneta americana) were evaluated by an extra‐cellular recording method. The ethers were more active than the corresponding alkanes. The ability of the compounds to cause conduction blockage was also measured using the same nerve preparations, but the effects were too weak to allow definitive activity values to be determined. The compounds prolonged the sodium tail‐current in the crayfish giant axon under voltage clamp conditions. The rate of decay of the tail‐current changed in parallel with the reported insecticidal activity against P americana. These findings indicated that tail‐current activity was the most useful nerve parameter in predicting insecticidal activity. Regression analysis of the numerical data together with those reported for other alkanes revealed that the higher the tail‐current activity, the higher the insecticidal activity when a structural feature and the hydrophobicity were considered separately. The insecticidal activity of the ethers was about seven‐fold higher than that of the alkanes with equivalent tail‐current activity and hydrophobicity. Variations in insecticidal activity were parabolically correlated with the hydrophobicity [(log P)_opt = 9.1] when other factors were similar. © 2001 Society of Chemical Industry     

Insect background sodium channel as a new target for scorpion alpha toxin

The effects of an anti-insect scorpion alpha toxin, LqhαIT, isolated from the venom of the Israeli scorpion Leiurus quinquestriatus hebraeus was studied on isolated adult dorsal unpaired median (DUM) neurones isolated from the cockroach Periplaneta americana terminal abdominal ganglion. Using the cell-attached patch-clamp configuration, a new type of sodium channel, called background sodium channel (bNa), was recently characterized. At −50 mV, the channel activity was observed as unclustered brief single openings. For hyperpolarized steady-state holding potential (−100 mV) the patches contained large unitary current steps, appearing generally in bursts. The open probability (Po) calculated at −50 mV was low (0.008 (± 0.004), n = 5) and displayed a typical bell-shaped voltage dependence. LqhαIT (10⁻⁸ M ) altered the bNa activity in a time-dependent manner. At −50 mV the channel activity appeared in bursts. Po calculated at −50 mV was about 20 times greater than Po calculated in controls and also showed bell-shaped voltage dependence. At 10⁻⁷ M , LqhαIT induced longer silent periods interrupted by bursts of increased channel activity. Whole-cell recordings revealed that 10⁻⁷ M LqhαIT transformed regular beating DUM neurone pacemaker activity into a rhythmic bursting. In this paper we demonstrate, for the first time, that bNa is a new target for anti-insect scorpion toxin. © 1999 Society of Chemical Industry     

Use of natural pyrethrum to control the red swamp crayfish Procambarus clarkii in a rural district of Italy

BACKGROUND: The crayfish Procambarus clarkii inflicts severe ecological and economic damages in Europe. To develop an efficient method for its control, four experiments were carried out to assess the impact of natural pyrethrum (i.e. Pyblast) on crayfish: (1) the 24 h LC₁₀₀ and LC₅₀ were quantified on crayfish; (2) the breakdown time of the 24 h LC₁₀₀ was assessed using Daphnia magna as a bioindicator; the effects of 24 h LC₁₀₀ on crayfish were investigated by applying the biocide into burrows (3) and in a drainage channel (4). RESULTS: Pyblast concentrations of 0.05 and 0.02 mg L^?1 corresponded to 24 h LC₁₀₀ and LC₅₀ respectively. The concentration of 0.05 mg L^?1 broke down after 72 h, whereas 0.02 mg L^?1 did not cause any significant mortality in D. magna after 24 h. However, 0.05 mg L^?1 had no effect on crayfish when introduced into the burrows, but led to a mortality of 95% when applied in the water. CONCLUSION: Experimental evidence is provided for the efficacy of Pyblast to control invasive crayfish. Obviously, before its use on a large scale, further studies are needed to find a concentration that will achieve the target 100% mortality with the shortest recovery time of the environment. Copyright © 2012 Society of Chemical Industry     

Stereochemical basis for the insecticidal activity of carbamoylated and acylated pyrazolines

Methyl 3-(4-chlorophenyl)-1-[N-(4-chlorophenyl)carbamoyl]-4-methyl-2-pyrazoline-4-carboxylate was converted to corresponding (1R)- and (1S)-phenethyl esters via its carboxylic acid and acid chloride at the C-4 atom to separate the diastereomers. Their configurations were confirmed by X-ray analysis. Both isomers of the (1R)methylbenzyl ester were subjected to transesterification with sodium methoxide to obtain enantiomers of the starting methyl ester. Their insecticidal activity was measured against American cockroaches (Periplaneta americana (L.)) by injection and against house flies (Musca domestica L.) by topical application under various synergistic conditions with metabolic inhibitors. The activity values of the four α-methylbenzyl esters and the R-isomer of the starting methyl ester were similar. The S-enantiomer of the methyl ester was about 10 and 100 times more active than the R-isomer against the cockroach and the fly, respectively. Some N-arylacetyl and N-aryloxyacetyl derivatives of the starting N-(4-chlorophenyl)carbamoyl compound gave very low activity. Conformation-energy profiles for some compounds suggested that the conformation of substituents on the N-1 atom in the pyrazoline ring has a specific role for the potential insecticidal effects.     

Acute toxicity of chlorantraniliprole to non‐target crayfish (Procambarus clarkii) associated with rice–crayfish cropping systems

BACKGROUND: Chlorantraniliprole, a novel anthranilic diamide insecticide, was recently introduced into the United States where rice–crayfish crop rotations are practiced to control rice water weevil (Lissorhoptrus oryzophilus Kuschel) infestations. Chlorantraniliprole has high margins of mammalian safety and excellent insecticidal efficacy, but its toxicity to non‐target crayfish is uncertain. In this study, the acute toxicity of chlorantraniliprole to the red swamp crayfish Procambarus clarkii Girard was determined using aquatic and feeding assays. RESULTS: The aquatic 96 h median lethal toxicity (LC₅₀) data indicate that technical‐grade chlorantraniliprole is highly toxic (US EPA category) to crayfish with an LC₅₀ of 951 µg L^?1 (95% CL = 741–1118 µg L^?1). A no observed effect concentration (NOEC) of 480 µg L^?1 was recorded. Neither the 36 day chronic feeding study, where crayfish fed on chlorantraniliprole‐treated rice seed in aquaria, nor the 144 h acute feeding test, where crayfish fed on rice seeds treated with chlorantraniliprole, produced mortality or abnormal behavior. CONCLUSION: Chlorantraniliprole is three orders of magnitude less acutely toxic to P. clarkii than lambda‐cyhalothrin and etofenprox, two pyrethroid insecticides also used in rice, and is less likely to cause acute crayfish toxicity in rice pond ecosystems. Based on acute toxicity data, the use of chlorantraniliprole should be more compatible with rice–crayfish crop rotations than pyrethroids. Copyright © 2010 Society of Chemical Industry     

Comparative acute toxicity of neonicotinoid and pyrethroid insecticides to non‐target crayfish (Procambarus clarkii) associated with rice–crayfish crop rotations

BACKGROUND: Most insecticides used to control rice water weevil (Lissorhoptrus oryzophilus Kuscel) infestations are pyrethroids. However, pyrethroids are highly toxic to non‐target crayfish associated with rice–crayfish crop rotations. One solution to the near‐exclusive reliance on pyrethroids in a rice–crayfish pest management program is to incorporate neonicotinoid insecticides, which are insect specific and effective against weevils but not extremely toxic to crayfish. This study aimed to take the first step to assess neonicotinoids as alternatives to pyrethroids in rice–crayfish crop rotations by measuring the acute toxicities of three candidate neonicotinoid insecticides, clothianidin, dinotefuran and thiamethoxam, to juvenile Procambarus clarkii (Girard) crayfish and comparing them with the acute toxicities of two currently used pyrethroid insecticides, lambda‐cyhalothrin and etofenprox. RESULTS: Neonicotinoid insecticides are at least 2–3 orders of magnitude less acutely toxic (96 h LC₅₀) than pyrethroids to juvenile Procambarid crayfish: lambda‐cyhalothrin (0.16 µg AI L^?1) = etofenprox (0.29 µg AI L^?1) ? clothianidin (59 µg AI L^?1) > thiamethoxam (967 µg AI L^?1) > dinotefuran (2032 µg AI L^?1). CONCLUSION: Neonicotinoid insecticides appear to be much less hazardous alternatives to pyrethroids in rice–crayfish crop rotations. Further field‐level neonicotinoid acute and chronic toxicity testing with crayfish is needed. Copyright © 2009 Society of Chemical Industry     

The role of GABA and glutamate receptors in susceptibility and resistance to chloride channel blocker insecticides

Despite a point mutation in the pore-forming segment of the Rdl GABA receptor subunit that is widespread and persistent in insect populations and confers high levels of resistance to dieldrin and other polychlorocycloalkane (PCCA) insecticides, the phenylpyrazole insecticide fipronil, which binds at same site, has proven to be effective in controlling many insects, including dieldrin-resistant populations. Fipronil and its major sulfone metabolite are unique among chloride channel blocking insecticides in that they also potently block GluCls. We present here a patch clamp study of the action of fipronil sulfone on native GABA receptors and GluCl receptors from susceptible and dieldrin-resistant German cockroaches, to provide a better understanding of the effect of the Rdl mutation on the function and insecticide sensitivity of these two targets, and its role in resistance. Dieldrin blocked GABA currents with an IC₅₀ of 3 nM in wild-type cockroaches, and 383 nM in resistant insects, yielding a resistance ratio of 128. Fipronil sulfone blocked GABA currents with an IC₅₀ of 0.8 nM in susceptible insects and 12.1 nM, or 15-fold higher, in resistant insects. While both GluClD (desensitizing) and GluClN (non-desensitizing) receptors were found in German cockroach neurons, GluClN receptors were rare and could not be included in this study. GluClD receptors from resistant insects had reduced sensitivity to glutamate and a lower rate of desensitization than those from susceptible insects, but their sensitivity to block by fipronil sulfone was not significantly changed, with an IC₅₀ of 38.5 ± 2.4 nM (n = 8) in the susceptible strain and 40.3 ± 1.0 nM (n = 7) in the resistant strain. Fipronil sulfone also slowed the decay time course of GluClD currents. These results suggest that GluClD receptors contain the Rdl subunit, but their sensitivity to fipronil sulfone is not altered in resistant insects.     

Electrophysiological studies on the effect of sesamex upon the action of dieldrin in Blaberus discoidalis

Treatment of the metathoracic ganglion of the cockroach, Blaberus discoidalis, with dieldrin (HEOD) at a concentration of 10^?5M produced changes in spontaneous efferent activity and afterdischarge in efferent pathways. Pretreatment with sesamex markedly reduced the spontaneous activity caused by dieldrin and also reduced the latency of appearance of symptoms from 60 min to nearly 30 min. However, pretreatment with sesamex did not alter the intensity and duration of the dieldrin-induced synaptic afterdischarge. Pretreatment of cockroaches with sesamex did not measurably change the toxicity of dieldrin in vivo.     

Activity of some new pyrethroids against Blattella germanica L.

The activities of natural and synthetic pyrethroids against male German cockroaches (Blattella germanica) were examined by means of dusting and direct spraying techniques. NRDC 107 (5-benzyl-3-furylmethyl (+)-trans-chrysanthemate) was the most active compound in killing cockroaches. Pyrethrins gave the most rapid knockdown and were 60% as active as NRDC 107 (Bioresmethrin) in killing power. Tetramethrin and the corresponding (+)-trans-ester gave rapid knockdown. Only (+)-trans-allethrin [(+)-trans-chrysan-themate of (±)-allethrolone] provided useful knockdown and killing power together. Piperonyl butoxide had a relatively stronger synergistic action with less active killing agents. The rate of knockdown during the first few minutes of exposure was not altered greatly by piperonyl butoxide.     

Repellancy and contact toxicity of clove bud oil and its constituents against German cockroaches,Blatella germanica (Dictyoptera: Blattellidae), under laboratory conditions

Abstract

The German cockroach, Blattella germanica L. (Dictyoptera: Blattellidae), an invasive pest of human habitats, is distributed throughout the world, except in Antarctica. They have developed resistance against chemical pesticides used for the management of their populations. Numerous essential oils and their constituents have been tested; however, the insecticidal activities of clove bud powder, oil, and their constituents have not yet been tested against the German cockroaches. Thus, in this study, clove bud powder, oil, and their major constituents, eugenol and eugenol acetate, were evaluated for their contact toxicity and repellancy against adult German cockroaches under laboratory conditions. The clove bud powder applied at 30?mg/cm² killed 92% of German cockroaches at 6?hours after treatment (HAT). Similarly, clove bud oil, eugenol and eugenol acetate applied at 4.00?ml/cm² provided 95%, 85%, and 87% German cockroach mortality at 24, 6, and 24 HAT, respectively. At 2.0?ml/cm², clove bud oil repelled 80% of German cockroaches within 30?min. In contrast, eugenol and eugenol acetate repelled 85% at 1.0?ml/cm² and 2.5?ml/cm², respectively, at 0.5 HAT. Based on this study, clove bud powder, oil, eugenol, and eugenol acetate could be environmentally friendly tools for the management of German cockroaches.     

Response of the german cockroach Blattella germanica (L.) to a light source following exposure to surface deposits of insecticides

Adult male German cockroaches were exposed to surface deposits of insecticides for 5 min in the central compartment of a three-compartment choice chamber illuminated at one end. They were then allowed access to the escape compartments and their distribution recorded over the subsequent 60 min. Cockroaches exposed to pyrethroid insecticides rapidly accumulated in the escape compartment closest to the light source; the same effect was observed to a lesser extent following exposure to propoxur. Boric acid and bendiocarb deposits inhibited the movement of the cockroaches away from the light source, and fenitrothion deposits delayed it. Dieldrin had no effect on the distribution of cockroaches within the choice chamber. The reversal of the normal tendency of German cockroaches to move from a light area to a dark harbourage following exposure to pyrethroids may contribute to the flushing action observed when these chemicals are used for control of B. germanica populations.     

Difference in the picrotoxinin receptor between the cyclodiene-resistant and susceptible strains of the german cockroach

As a result of toxicity tests, it was established that all cyclodiene-resistant strains of the German cockroach are also resistant to picrotoxinin, a plant-origin neurotoxicant. Two of the cockroach strains which exhibit a distinct cross-resistance pattern to picrotoxinin (i.e., LPP and FRP) are the ones that have been purified genetically by backcrossing against the susceptible (CSMA) strain. This cross-resistance pattern appears to be specific to picrotoxinin and does not extend to other neuroexcitants such as bicuculline, beta-bungarotoxin, and DDT. The nervous system of the resistant cockroach was found to be less sensitive to picrotoxinin. Furthermore, it was determined that nerve components from the resistant cockroaches have significantly lower binding capacity to [³H]α-dihydropicrotoxinin. The most likely explanation for the above phenomenon is that these cockroaches have developed the cyclodiene resistance by altering the nerve receptor for picrotoxinin.     

The effects of dieldrin and isomeric aldrin diols on synaptic transmission in the American cockroach and their relevance to the dieldrin poisoning syndrome

Dieldrin and two of its metabolites, 6,7-trans-dihydroaldrindiol, and 6,7-cis-dihydroaldrindiol, were studied with regard to their toxicity to the American cockroach, effects on ganglia of the ventral nerve cord, and penetration into the ventral nerve cord of poisoned cockroaches. An approximate LD₅₀ for injected doses of dieldrin was 0.45 mg/kg. After injection at 115 mg/kg, the trans isomer of aldrin diol caused about 70%, and the cis isomer about 50% mortality. Injected doses of 40 mg/kg of the three compounds appeared in the ventral nerve cord to the extent of 0.13–0.26% of the doses. Dieldrin was more potent, but slower acting than the diols in causing synaptic after-discharge and elevated spontaneous activity in isolated nerve cords. The results are discussed in relation to other studies on these compounds. It was concluded that, in the American cockroach, dieldrin, rather than either of the diols, is the insecticidal agent in dieldrin poisoning, and that metabolic conversion of dieldrin to the cis and/or trans aldrindiol constitutes a detoxification.     

The in vivo sensitivity of ATPases to DDT,DDE, and physical immobilization in American cockroaches

American cockroaches injected with sublethal doses of DDT (0.75 μg/roach) at 5-day intervals showed a 40% reduction in oligomycin-sensitive Mg²⁺ATPase from muscle homogenates, and a 23% reduction of Na⁺-K⁺ATPase from nerve cords. Thus, the maximum effect measured occurred with the same enzyme and tissue as determined from in vitro studies. The metabolite, DDE, used at 15 μg per roach, gave no significant change in activity of the ATPase system following injection. In contrast, high single doses of DDT (7.5 μg/roach) and 100 μg DDE and dicofol per roach caused over 30% increase in oligomycin-sensitive Mg²⁺ATPase of muscle and a 10–15% increase in Na⁺-K⁺ATPase of nerve cords measured 24 and 48 hr later. While a similar response was observed for Mg²⁺ATPase activities in cockroaches that were immobilized, the increase in enzyme activities were much greater than that caused by the pesticides.