Penetration and metabolism of topically applied permethrin and cypermethrin in pyrethroid-tolerant Wiseana cervinata larvae

The penetration, excretion, and metabolism of topically applied [¹⁴C]permethrin and [¹⁴C]cypermethrin have been examined in larvae of the porina moth Wiseana cervinata to determine the factors which affect body levels of unchanged pyrethroids. Metabolism was by hydrolysis and to a lesser extent oxidation and the primary metabolites were quickly conjugated to water-soluble products. Little excretion occurred and body levels of unchanged pyrethroids were dependent on the interaction of penetration and metabolism. cis-Cypermethrin was more resistant to metabolism than trans-cypermethrin and cis- and trans-permethrin. trans-Permethrin most readily penetrated into larvae. The body levels of unchanged permethrin were enhanced by pretreatment of larvae with the metabolic inhibitors carbaryl or piperonyl butoxide. Tolerance of the pasture pest porina to the synthetic pyrethroids is discussed in relation to these findings.     

Structure-related effects of pyrethroid insecticides on the lateral-line sense organ and on peripheral nerves of the clawed frog, Xenopus laevis

The effects of seven different pyrethroid insecticides on the lateral-line sense organ and on peripheral nerves of the clawed frog, Xenopus laevis, were investigated by means of electrophysiological methods. The results show that two classes of pyrethroid can be clearly distinguished. (i) Pyrethroids without an α-cyano group (permethrin, cismethrin, and bioresmethrin). These noncyano pyrethroids induce short trains of nerve impulses in the lateral-line sense organ. In peripheral nerve branches they induce a depolarizing afterpotential and repetitive firing. These effects are very similar to those previously reported for allethrin. (ii) Pyrethroids with an α-cyano-3-phenoxybenzyl alcohol (cypermethrin, fenpropathrin, deltamethrin, and fenvalerate). In the lateral-line sense organ these α-cyano pyrethroids induce very long trains of nerve impulses which may last for seconds and may contain hundreds or even thousands of impulses. The α-cyano compounds do not cause repetitive activity in peripheral nerves. Instead they induce a quickly reversible, stimulus frequency-dependent suppression of the action potential. Since the chemical structure of cypermethrin differs from that of permethrin only in the α-cyano group and because all four α-cyano compounds act in a very similar way, it is concluded that the α-cyano substituent is responsible for the large differences in neurotoxic effects. In the lateral-line sense organ the duration of nerve impulse trains induced by the noncyano as well as the α-cyano pyrethroids increases dramatically when the temperature is lowered. Further, in sensory fibers the effects of both classes of pyrethroid on the nerve action potential are more pronounced compared to their effects on motor fibers. It is argued that the different neurotoxic effects reported here originate from a common mechanism of action of pyrethroids, which is a prolongation of the transient increase of sodium permeability of the nerve membrane associated with excitation.It is concluded that the sodium channel in the nerve membrane is the major target site of noncyano and α-cyano pyrethroids.     

Two classes of pyrethroid action in the cockroach

Pyrethroids are divided into two classes (Types I and II) based on their effects on the cercal sensory nerves recorded in vivo and in vitro and on the symptomology they produce in dosed cockroaches, Periplaneta americana. Type I compounds include pyrethrins, S-bioallethrin, [1R,cis]resmethrin, kadethrin, the 1R,trans and 1R,cis isomers of tetramethrin, phenothrin, and permethrin, and an oxime O-phenoxybenzyl ether. Electrophysiological recordings from dosed individuals reveal trains of cercal sensory spikes and sometimes also spike trains from the cercal motor nerves and in the CNS. Low concentrations of these pyrethroids act in vitro to induce repetitive firing in a cercal sensory nerve following a single electrical stimulus. This in vitro measurement, standardized for evaluating structure-activity relationships, shows that only 1R, insecticidal isomers are highly effective neurotoxins. The most potent compounds on the isolated nerve are [1R,trans]- and [1R,cis]tetramethrin, each active at 3 × 10^?13M. The poisoning symptoms of Type I compounds are restlessness, incoordination, hyperactivity, prostration, and paralysis. Type II compounds include [1R,cis,αS]- and [1R,trans,αS]cypermethrin, deltamethrin, and [S,S]fenvalerate. These α-cyanophenoxybenzyl pyrethroids do not induce repetitive firing in the cercal sensory nerves either in vivo or in vitro; moreover, they cause different symptoms, including a pronounced convulsive phase. Two other pyrethroids with an α-cyano substituent, i.e., fenpropathrin and an oxime O-α-cyanophenoxybenzyl ether, are classified as Type I based on their action on a cercal sensory nerve but the symptoms with these compounds resemble Type II. The two classes of pyrethroid action evident with the cockroach are discussed relative to their neurophysiological effects and symptomology in other organisms.     

Multifactorial resistance to transpermethrin in field-collected strains of the tobacco budworm Heliothis virescens F.

The penetration, degradation and excretion of [³H]transpermethrin were examined in susceptible and field-collected pyrethroid-resistant strains of the tobacco budworm Heliothis virescens. No consistent differences in labelled materials excreted or recovered in cuticle rinses were found between the resistant (R) and susceptible (S) larvae. Considerably lower levels of the parent compound were present internally in R compared with S larvae after 24h (P <0.01), clearly identifying a metabolic resistance mechanism in Meloland and Westmorland larvae. Moderate levels of absorbed permethrin accompanied by an absence of poisoning symptoms were observed in certain individuals of both R strains, suggesting a second resistance mechanism. Neurobioassays of R larvae showed a consistently lower sensitivity of the neuromuscular system to pyrethroids when compared with the S larvae, thus confirming the indication from metabolic studies of the additional (site-insensitive) mechanism. Toxicity values suggest a cross-resistance to other pyrethroids.     

Decreased nerve sensitivity and decreased cuticular penetration as mechanisms of resistance to pyrethroids in a (1R)-trans-permethrin-selected strain of the house fly

A fenthion-resistant strain of the house fly (Musca domestica L.) was selected with bioresmethrin resulting in ca. 90-fold resistance to the selecting agent. This strain was subsequently selected with (1R)-trans-permethrin producing ca. 140-fold resistance to this latter insecticide. The permethrin-resistant (147-R) strain was highly cross-resistant to several other pyrethroids and demonstrated resistance to knockdown by these insecticides as well as by DDT. The sensitivity of the central nervous system to four pyrethroids was investigated. The 147-R strain was 2.6-fold less sensitive to (1R)-trans-ethanoresmethrin than the susceptible (NAIDM-S) strain, and >43-fold and >67-fold less sensitive to (1R,S)-cis, trans-tetramethrin and (1R)-trans-permethrin, respectively. It also displayed decreased penetration of (1R,S)-trans-[¹⁴C]permethrin when compared to the NAIDM-S strain. Lower nerve sensitivity and decreased cuticular penetration are potential mechanisms of resistance to pyrethroids in house flies in the United States.     

Action of pyrethroids on a nerve-muscle preparation of the clawed frog,Xenopus laevis

The effects of a range of pyrethroids on end-plate potentials and muscle action potentials were studied in the pectoralis nerve-muscle preparation of the clawed frog, Xenopus laevis. The noncyano pyrethroids allethrin, cismethrin, bioresmethrin, and IR-cisphenothrin caused moderate presynaptic repetitive activity only, resulting in the occurrence of multiple end-plate potentials (epps). Trains of repetitive muscle action potentials without presynaptic repetitive activity were observed after the α-ethynyl pyrethroid S-5655 and after the α-cyano pyrethroids cypermethrin, deltamethrin, FCR 1272, and FCR 2769. An intermediate group of pyrethroids consisting of the non-cyano compounds 1R-permethrin, des-cyano-deltamethrin, NAK 1901 and NAK 1963, and the α-cyano pyrethroids cyphenothrin and fenvalerate caused both types of effect. The insecticidally inactive S-enantiomers of permethrin had no effect on the nerve-muscle preparation. Trains of repetitive action potentials in pyrethroid-treated muscle fibers were followed by a depolarizing afterpotential which in general decayed more rapidly for the non-cyano pyrethroids than for the α-cyano pyrethroids. The rate of decay of the depolarizing afterpotential decreased gradually as the temperature was lowered, whereas the pre- and postsynaptic repetitive activity remained largely unaffected over a large temperature range. It is concluded that in muscle membrane like in nerve membrane the pyrethroid-induced repetitive activity is due to a prolongation of the sodium current and that a clear distinction between non-cyano pyrethroids on the one hand and α-cyano compounds on the other cannot be made on the basis of the present results.     

Absence of enhanced detoxication of permethrin in pyrethroid-resistant house flies

The mechanisms of resistance to pyrethroids were studied in a permethrin-selected (147-R) strain of the house fly, Musca domestica L. Approximately 12-fold synergism was obtained with a mixture of (1R)-trans-permethrin:piperonyl butoxide (1:5) so that the resistance decreased from 97-fold to 22-fold. Tests with the esterase inhibitor S,S,S-tributyl phosphorotrithioate produced very little synergism in either the resistant (R) strain (1.6-fold) or the susceptible (S) strain (1.9-fold). An investigation of the microsomal components revealed that compared to the S strain, the R strain demonstrated twice as much cytochrome P-450 and cytochrome b₅ and double the rate of NADPH-cytochrome c reductase activity. In addition, the rate of p-nitroanisole O-demethylation was found to be six times greater in the R strain. An in vivo accumulation study showed that the R strain displayed a decreased rate of penetration of trans-[¹⁴C]permethrin. When treated at equitoxic doses the R strain was found to tolerate 50-fold more internal permethrin than the S strain. An in vitro metabolism study indicated that there was no difference between strains in the overall rate of metabolism of trans-[¹⁴C]permethrin. The evidence obtained supports the conclusion that several resistance factors are involved but that decreased sensitivity of the nervous system to the action of pyrethroids is the principal mechanism of resistance in the 147-R strain.     

Cytochrome P450 monooxygenase-mediated permethrin resistance confers limited and larval specific cross-resistance in the southern house mosquito, Culex pipiens quinquefasciatus

The cytochrome P450-dependent monooxygenases (P450s) are an important enzymatic system that metabolizes xenobiotics (e.g., pesticides), as well as endogenous compounds (e.g., hormones). P450-mediated metabolism can result in detoxification of insecticides such as pyrethroids, or can be involved in the bioactivation and detoxification of insecticides such as organophosphates. We isolated (from the JPAL strain) a permethrin resistant strain (ISOP450) of Culex pipiens quinquefasciatus, having 1300-fold permethrin resistance using standard backcrossing procedures. ISOP450 is highly related to the susceptible lab strain (SLAB) and the high resistance to permethrin is due solely to P450-mediated detoxification. This is the first time in mosquitoes that P450 monooxygenase involvement in pyrethroid resistance has been isolated and studied without the confounding effects of kdr. Resistance in ISOP450 is incompletely dominant (D = +0.3), autosomally linked, and monofactorally inherited. It is expressed in the larvae, but not in adults. Cross-resistance to pyrethroids lacking a 3-phenoxybenzyl moiety (tetramethrin, fenfluthrin, bioallethrin, and bifenthrin) ranged from 1.5- to 12-fold. ISOP450 had only limited (6.6- and 11-fold) cross-resistance to 3-phenoxybenzyl pyrethroids with an α-cyano group (cypermethrin and deltamethrin, respectively). Examination of cross-resistance patterns to organophosphate insecticides in ISOP450 showed an 8-fold resistance to fenitrothion, while low, but significant, levels of negative cross-resistance were found for malathion (RR = 0.84), temephos (RR = 0.73), and methyl-parathion (RR = 0.55). The importance and uniqueness of this P450 mechanism in insecticide resistance is discussed.     

The importance of nerve terminal depolarization in pyrethroid poisoning of insects

The effects of several pyrethroids and DDT were examined on neuromuscular preparations from larvae of Musca domestica, Culex quinquefasciatus, Anopheles stephensi, and Trichoplusia ni, in order to determine the importance of the type I effect (repetitive firing) and the type II effect (increased miniature excitatory postsynaptic potential (mepsp) rate, indicating nerve terminal depolarization) in the poisoning process. α-Cyano pyrethroids were very potent in increasing mepsp rate, and although DDT and non-α-cyano compounds were more potent at inducing repetitive firing, all these compounds increased mepsp rate at higher concentrations. A variety of evidence showed that the mepsp rate-increasing activity could be an important factor in toxicity: among all of the compounds, there was a positive correlation between toxicity and mepsp rate-increasing activity; mepsp rate-increasing activity had a negative temperature dependence; nerves of kdr larvae in vitro were resistant to the mepsp rate-increasing activity, commensurate with resistance level; and finally, increased mepsp rate and neuromuscular block were observed in poisoned insects, associated with paralysis. Among type I compounds, repetitive firing activity was correlated negatively with toxicity, but positively with knockdown activity.     

Pharmacokinetics of pyrethroids in twospotted spider mites

The penetration and degradation of six pyrethroids were examined in the twospotted spider mite, Tetranychus urticae Koch, and the results were related to their toxicity as measured by inhibition of respiration using the Warburg technique and mortality using the slide-dip bioassay. FMC-54800 [1,1′-biphenyl-3ylmethyl cis-3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethylcyclopropanecarboxylate] was the most toxic pyrethroid to the mites based on both respiration and mortality studies. It and flucythrinate had the highest pharmacokinetic efficiency as determined by delivery and maintenance of internal levels of parent compounds. Permethrin, fenvalerate, and fluvalinate were intermediate in pharmacokinetic efficiency, whereas cypermethrin was significantly lower. The highest intrinsic activity, as estimated by the percentage inhibition of respiration per microgram of internal parent, was possessed by cypermethrin and FMC-54800. Fenvalerate and fluvalinate had intermediate levels, while permethrin and flucythrinate had significantly lower capacities to inhibit respiration. The combination of relatively high pharmacokinetic efficiency and intrinsic activity of FMC-54800 appeared to be responsible for its high toxicity. In addition to these findings, differences in the kinetics for cis and trans isomers were observed for permethrin but not cypermethrin. This study has yielded evidence that acaricidal activity of pyrethroids can be enhanced by optimizing the structure for increased pharmacokinetic efficiency and increased intrinsic activity.     

Antifeeding effect of cypermethrin and permethrin at sub-lethal levels against Pieris brassicae larvae

An antifeeding (feeding deterrent) response by first- and fifth-instar larvae of Pieris brassicae was shown to be significant at sub-lethal levels of cypermethrin and permethrin, using leaf-discs treated with the pyrethroids by dipping. Permethrin was slightly more effective than cypermethrin both as an insecticide and as an antifeedant against fifth-instar larvae, but the reverse order of effectiveness was observed, with a marked difference in mortality, against newly-hatched larvae. When 1-day-old fifth-instar larvae were continuously given leaf discs treated with a solution of the pyrethroid (1 mg litre^?1), up to the time of pupation, both cypermethrin and permethrin induced a significant extension of the larval period, with a reduction in the maximum larval and pupal weights, as well as a reduction in the total leaf-area consumed. However, at higher levels of both pyrethroids, lowering the temperature induced some irritancy, as indicated by regurgitation and frequent uncoordinated wriggling movements of the fifth-instar larvae. The advantages of cypermethrin as a protectant and as an antifeedant over permethrin are discussed.     

Binary mixtures of pyrethroids produce differential effects on Ca influx and glutamate release at isolated presynaptic nerve terminals from rat brain

Isolated rat brain synaptosomes were used to evaluate the action of pyrethroid mixtures on Ca²⁺ influx and subsequent glutamate release under depolarizing conditions. In equipotent binary mixtures at their respective and/or estimated EC₅₀s with deltamethrin always as one of the two components, cismethrin, λ-cyhalothrin, cypermethrin, esfenvalerate and permethrin were additive and S-bioallethrin, fenpropathrin and tefluthrin were less-than-additive on Ca²⁺ influx. In binary mixtures with deltamethrin always as one of the two components, esfenvalerate, permethrin and tefluthrin were additive and λ-cyhalothrin was less-than-additive on glutamate release. Binary mixture of S-bioallethrin and cismethrin was additive for both Ca²⁺ influx and glutamate release. Only a subset of pyrethroids (S-bioallethrin, cismethrin, cypermethrin, and fenpropathrin) in binary mixtures with deltamethrin caused a more-than-additive effect on glutamate release. These binary mixtures were, however, only additive (cismethrin and cypermethrin) or less-than-additive (S-bioallethrin and fenpropathrin) on Ca²⁺ influx. Therefore, increased glutamate release evoked by this subset of pyrethroids in binary mixture with deltamethrin is not entirely occurring by Ca²⁺-dependent mechanisms via their action at voltage-sensitive calcium channels. These results suggest that pyrethroids do not share a common mode of toxicity at presynaptic nerve terminals from rat brain and appear to affect multiple target sites, including voltage-sensitive calcium, chloride and sodium channels.     

Pyrethroid action on the nicotinic acetylcholine receptor/channel

The interactions of natural pyrethrins and nine pyrethroids with the nicotinic acetylcholine (ACh) receptor/channel complex of Torpedo electric organ membranes were studied. None caused significant reduction in [³H]ACh binding to the receptor sites, but all inhibited [³H]perhydrohistrionicotoxin ([³H]H₁₂-HTX) binding to the channel sites in presence of carbamylcholine. Allethrin inhibited [³H]H₁₂-HTX binding noncompetitively, but [³H]imipramine binding competitively, suggesting that allethrin binds to the receptor's channel sites that bind imipramine. The pyrethroids were divided into two types according to their actions: type I, which included pyrethrins, allethrin, bioallethrin, resmethrin, and tetramethrin, was more potent in inhibiting [³H]H₁₂-HTX binding and acted more rapidly (i.e., in <30 sec). Type II, which included permethrin, fluvalinate, cypermethrin and fenvalerate, was less potent and their potency increased slowly with time. Also, inhibition of the initial rate of [³H]H₁₂-HTX binding by type I compounds increased greatly by the presence of the agonist carbamylcholine, but this was not so with type II compounds. The receptor-regulated ⁴⁵Ca²⁺ flux into Torpedo microsacs was inhibited by pyrethrins and pyrethroids, suggesting that their action on this receptor function is inhibitory. There was very poor correlation between the potencies of pyrethrins and pyrethroids in inhibiting [³H]H₁₂-HTX binding and their toxicities to house flies, mosquitoes, and the American cockroach. However, the high affinities that several pyrethroids have for this nicotinic ACh receptor suggest that pyrethroids may have a synaptic site of action in addition to their well known effects on the axonal channels.     

Mechanisms of resistance to diflubenzuron in the house fly, Musca domestica (L.)

The mechanisms of resistance to the chitin synthesis inhibitor diflubenzuron were investigated in a diflubenzuron-selected strain of the house fly (Musca domestica L.) with > 1000 × resistance, and in an OMS-12-selected strain [O-ethyl O-(2,4-dichlorophenyl)phosphoramidothioate] with 380 × resistance to diflubenzuron. In agreement with the accepted mode of action of diflubenzuron, chitin synthesis was reduced less in larvae of the resistant (R) than of a susceptible (S) strain. Cuticular penetration of diflubenzuron into larvae of the R strains was about half that of the S. Both piperonyl butoxide and sesamex synergized diflubenzuron markedly in the R strains, indicating that mixed-function oxidase enzymes play a major role in resistance. Limited synergism by DEF (S,S,S-tributyl phosphorotrithioate) and diethylmaleate indicated that esterases and glutathione-dependent transferases play a relatively small role in resistance. Larvae of the S and R strains exhibited a similar pattern of in vivo cleavage of ³H- and ¹⁴C-labeled diflubenzuron at N₁C₂ and N₁C₁ bonds. However, there were marked differences in the amounts of major metabolites produced: R larvae metabolized diflubenzuron at considerably higher rates, resulting in 18-fold lower accumulation of unmetabolized diflubenzuron by comparison with S larvae. Polar metabolites were excreted at a 2-fold higher rate by R larvae. The high levels of resistance to diflubenzuron in R-Diflubenzuron and R-OMS-12 larvae are due to the combined effect of reduced cuticular penetration, increased metabolism, and rapid excretion of the chemical.     

Pyrethroid insecticide resistance in Rhipicephalus bursa (Acari, Ixodidae)

Rhipicephalus bursa is one of the most common hard tick species in Iran. It is a vector of animal and human diseases. Tick control strategies in Iran rely heavily on pyrethroid insecticide use. Hence, susceptibility status of multiple field collected populations to λ-cyhalothrin and cypermethrin was investigated using the FAO recommended larval packet test. Resistance ratios at the LC₉₉ of field populations of R. bursa compared to a susceptible strain ranged from 0.95 to 4.78 for λ-cyhalothrin and 1.43-8.6 for cypermethrin. They were 2- to 6.9-fold higher than the maximum dose recommended by the acaricide formulating companies. Biochemical assays on different field collected populations showed significant elevation in esterase and glutathione S-transferase activities and monooxygenase contents compared with the susceptible strain. Therefore, close monitoring and resistance management strategies should be employed to delay the operational loss of pyrethroids for tick control in Iran.     

Linkage group analysis of nerve insensitivity in a pyrethroid-resistant strain of house fly

Nerve insensitivity was a major factor of mechanism of resistance to pyrethroids in the 228e2b strain of house fly. Reciprocal crosses between the resistant and susceptible SRS strains showed that resistance to permethrin was recessive in nerve sensitivity. Linkage group analysis by the F₁ male backcross method using multichromosomal marker strains was investigated electrophysiologically, following 10⁻⁵ M permethrin application to the exposed thoracic ganglia of the backcross progenies. Results of the experiment showed that the recessive genetic factor responsible for nerve insensitivity to permethrin in the resistant strain is located only on the third chromosome.     

Cross-resistance to pyrethroids and other insecticides in Aedes aegypti

Two substrains of Aedes aegypti, already resistant to DDT and pyrethroids, were further selected using either DDT or permethrin by mass exposure of the females only. DDT selection over 14 generations raised the resistance to DDT so far that no accurate LC₅₀ values could be determined. Selection with permethrin raised the tolerance to an irregular plateau 7–10 times the original. DDT selection in the adults raised the DDT resistance of the larvae, but this could be partly overcome using a dehydrochlorinase inhibitor. The resistance to pyrethroids was increased but tolerance of dieldrin, malathion and propoxur compounds was little changed. Permethrin selection of the adults raised resistance to pyrethroids more than DDT selection but also increased DDT resistance. Similar patterns were found for the larval insects. A strain from Demerara in Guyana showed both DDT and pyrethroid resistance, including strong resistance to pyrethrins together with dieldrin and propoxur. It was concluded that two major independent resistance mechanisms existed in the selected strains, a dehydrochlorinase affecting DDT alone, and an unknown mechanism, probably nerve insensitivity (kdr) affecting both DDT and pyrethroids.     

Neural and behavioral correlates of pyrethroid and DDT-type poisoning in the house fly, Musca domestica L

Intact house flies were observed during poisoning caused by several pyrethroid and DDT-type insecticides. The two insecticide classes could be generally distinguished from each other based on differences in symptoms and several physiological correlates. Both insecticide types caused motor unit repetitive backfiring, but the temporal development and stability of repetitiveness were distinctly different between the two classes. Repetitive backfiring always disappeared at low temperatures, but DDT-type backfiring disappeared at lower temperatures than the pyrethroids. trans-Tetramethrin caused a threshold increase in flight motor nerve endings which did not occur in DDT or trans-Barthrin poisoning. Pyrethroids caused “uncoupling” of the flight motor pattern, while DDT-types did not. trans-Barthrin, a methylenedioxyphenyl pyrethroid, was unique in causing both symptoms and physiological aberrations which more closely resembled those of the DDT-types than the pyrethroids.     

The crayfish stretch receptor organ: A useful model system for investigating the effects of neuroactive substances: I. The effect of DDT and pyrethroids

The crayfish stretch receptor organ is a useful model system for investigating the effects of neuroactive compounds on an invertebrate sensory cell. The receptor neuron is very sensitive to pyrethroids, DDT, and veratridine, and comparisons were made between the effects of α-cyano substituted pyrethroids (cypermethrin and deltamethrin) and pyrethroids without a cyano group (permethrin and bioallethrin). A comparison of the effects of pyrethroids on this single sensory cell with those recorded from the flight muscles of a whole insect (Lucilia sericata) indicates that the effects are similar in both preparations.     

Comparative effects of DDT,allethrin, dieldrin and aldrin-transdiol on sense organs of Xenopus laevis

The effects of DDT, allethrin, dieldrin and aldrin-transdiol were studied in two different sense organs of Xenopus laevis; the lateral-line organ and the cutaneous touch receptors. DDT and allethrin produced pronounced repetitive firing in both preparations. Dieldrin and aldrin-transdiol, on the other hand, failed to induce any sign of repetitive activity. Aldrin-transdiol, however, caused a marked increase in the rate of spontaneous firing of the lateral-line organ, later followed by a blockade. The repetitive activity in the cutaneous touch receptors, whether induced by DDT or allethrin, was not distinguishable from repetitive firing of the afferent nerve fibers and showed no marked dependence on temperature. This contrasts sharply with the know negative temperature coefficient of the DDT- or allethrin-induced repetitive activity in the lateral-line organ.