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.     

Endocrine modifications produced by o,p′-DDT in the male adult rat

The action of o,p′-DDT on plasma steroids and steroidogenesis in adrenal and brain tissues has been studied using 26 Sprague-Dawley adult male rats. The animals were divided into three groups: the first was injected with sesame oil, the second injected with 20 mg of o,p′-DDT in 0.5 ml of sesame oil and the third group was not treated. The animals were sacrificed 8 hr after the injection; blood, adrenal, and brain were removed and used for plasma steroid determinations. A decrease in testosterone and an increase in estradiol were found in plasma of treated animals. The injection of o,p′-DDT produced also a decrease in corticosterone formed from progesterone and in unchanged progesterone in the adrenal glands, an increase in dihydrotestosterone and a decrease in androstenediol formation from testosterone in the brain. These results indicate that the effect of o,p′-DDT administration implies: (i) a general decrease in androgen biosynthesis, which is evident also from the lower level of plasma testosterone; (ii) a decrease of plasma estradiol level, which could indicate a binding of o,p′-DDT to estradiol receptor sites; (iii) a decrease in 11β-hydroxylase activity, which is evident from the lower amount of corticosterone formed from progesterone in the adrenal tissue.     

The effect of some DDT and methoxychlor analogs on temperature selection and lethality in brook trout fingerlings

The effects of several DDT and methoxychlor analogs on trout fingerling temperature selection and lethality were investigated. The molecular requirements for lethality and alteration of temperature selection were different. Only p, p′-DDT, p, p′-DDD, and p, p′-methoxychlor were toxic in the range 10–50 ppb used. All the compounds tested, except DDE-type analogs, altered temperature selection. The effect of p, p′-methoxychlor on temperature selection progressively decreased until normal values were obtained 5 days after exposure. The effect of p, p′-DDT was still pronounced 9 days after exposure.     

The effects of DDT analogs upon potassium conductance in synthetic membranes

The effects of p,p′-DDT and 13 analogs were studied upon the K⁺ conductance which valinomycin induces in a lecithin-octane bilayer. Eight compounds decreased conductance, 4 relatively polar analogs increased conductance, and one had no effect. A partial correlation of these variations with physiological effects upon cockroach nerve and crayfish giant axon was found. Evidence was presented that the effect on the bilayer was due to an effect of the compounds on the fluidity of the membrane's interior rather than a direct interaction with the valinomycin.     

Effects of DDT on the cockroach nervous system at three temperatures

Some effects of DDT on the cockroach nervous system have been correlated with poisoning symptoms, using free-walking cockroaches with implanted electrodes. Experiments at 16.5°C and 32°C used LD₉₅ doses and at 25°C, an estimated LD₉₅. DDT had excitant actions on each nerve studied; cercal afferent and efferent neurones, and abdominal interneurones. The effects on the central nervous system became more marked as temperature was reduced, despite the smaller quantity of DDT employed, but the excitant actions on the peripheral nervous system were not quantified. It is suggested that the effects of DDT on the cockroach nervous system could account for the negative temperature coefficient of toxicity of DDT.     

Carbofuran triggers flight motor output in pyrethroid-blocked reflex pathways of the house fly

The initiation of flight from loss of tarsal contact (flight reflex responses) and the tergotrochanteral muscle (TTM) responses evoked by brain stimulation were analyzed during carbofuran, permethrin, deltamethrin, and DDT poisoning in the house fly. Blockage of the flight reflex by LD₅₀ doses of permethrin or deltamethrin was rapid, but the effects of DDT on the flight reflex took hours to develop. In addition, carbofuran treatment induced spontaneous flight in blocked preparations by an action in the central nervous system. This result suggests that pyrethroid blockage of the flight reflex was due to an action on sensory nerves, since the central flight program and its associated efferent systems were functionally intact. The relevance of this finding in terms of pyrethroid knockdown is discussed. The TTM response was unaffected by permethrin or deltamethrin both early and late in the poisoning process, possibly because the evoked TTM response does not involve peripheral sensory nerves, which seem to be important sites of pyrethroid action early in poisoning. Carbofuran induced repetitive firing and blockage of the TTM response within 1 hr, but normal responses were observed late in poisoning, which is consistent with the reversibility of carbamate inhibition of acetylcholinesterase. DDT caused no change in the evoked TTM response until bursts were recorded about 15 hr after treatment; this was another example of a slowly developing DDT effect. The protracted development of various DDT actions was concordant with a hypothesis of reduced efficacy at a proposed target site, viz., the sodium channels of nerve membranes.     

Inhibition of acetyl-coenzyme a carboxylase by coenzyme a conjugates of grass-selective herbicides

A total of 146 samples of different kinds of cheeses produced in Spain were analysed in order to ascertain the specific contamination pattern. The organochlorine compounds studied were those most commonly investigated in previous surveys: α-HCH, β-HCH, γ-HCH (lindane), γ-HCH, chlordane, aldrin, dieldrin, endrin, heptachlor, heptachlor epoxide, and the isomers and metabolites of DDT. α-HCH, β-HCH, γ-HCH, chlordane, p,p′, DDT, and p,p′-DDE were found in more than 76% of samples; p,p′-DDE and γ-HCH were the most frequently detected, with frequencies of 100 and 97.9% respectively. γ-HCH, aldrin, dieldrin, heptachlor, heptachlor epoxide, o,p′-DDT, p,p′-DDD and o,p′-DDD were observed at lower frequencies. No residues of endrin were detected in any sample. Insecticides exceeding the maximum residue limits (MRLs) were chlordane, β-HCH, α-HCH and γ-HCH, with 42, 20, eight and six samples respectively. Mean residues of organochlorines found were as follows (μ kg^?1 butterfat): α-HCH = 46.3; β-HCH = 46.5; γ-HCH = 54.2; δ-HCH = 16.9; aldrin = 16.7; dieldrin = 9.7; heptachlor = 15.9; heptachlor epoxide = 14.8; chlordane = 50.2; o,p′-DDT = 5.1; p,p′-DDT = 12.4; o,p′-DDT = 19.6; p,p′-DDD = 46.7; o,p′-DDE = 6.9; p,p′-DDE = 40.7 (.DDT = 55.0). Estimated dietary intakes (EDIs) from cheese consumption were compared to acceptable daily intakes (ADIs) for the pesticides where residues exceeded the MRL. EDIs calculated were in all cases below ADIs, and, therefore, based on the ADIs, there is no health risk involved in the consumption of cheese from Spain arising from organochlorine residues.     

Comparative excretion of DDT analogues into milk of indian buffalo,Bubalus bubalis L. following oral administration

Four groups of Indian buffaloes were fed daily with 25 mg of p,p′-DDT p,p′-TDE p,p′-DDE or o,p′-DDT for 100 days. Milk was analysed for organochlorine residues during this period and also for 100 days after pesticide administration had been discontinued. For the period showing ‘plateau level’ residues, 17.2% of p,p′-DDE, 17% of p,p′-TDE, 14% of p,p′-DDT as p,p′-DDT (3.5%); p,p′-TDE (10.5%); 3.2% of p,p′-DDT as o,p′-DDT (1.3%) and o,p'-TDE (1.9%) of their administered amounts were excreted in the milk. Since these compounds were excreted at different rates, the residue levels in the milk expected from a given feed would depend on their concentration and proportional distribution in the feed. The maximum tolerable content of DDT analogues in feed was derived to be 0.1 mg kg^?1 (dry weight basis) by using the maximum accumulation coefficient and incorporation of the necessary safety margin. It is concluded that Indian buffaloes fed with rations contaminated with a total of DDT analogues below this limit will yield milk of acceptable quality. Following the termination of feeding with contaminated rations, the elimination of p,p′-DDE in the milk took the longest time and that of o,p′-DDT the shortest. These results suggest that the time required for the initial high residue concentration to decline to less than the legal limit would be determined by the relative amounts of DDE, TDE and DDT in the milk, after elimination of the potent source of contamination.     

Effects of deltamethrin on ventral nerve cord activity in the cockroach

The effects of varying concentrations of deltamethrin on a number of the parameters of electrophysiological activity in the cockroach ventral nerve cord have been studied. Deltamethrin, at concentrations greater than 100 nM, caused repetitive firing in the central nervous system (CNS), prior to conduction block, the effect getting faster as the concentration was increased. Whilst 10-nM deltamethrin eventually caused conduction block with no apparent increase in the level of CNS activity, it induced a gradual decrease in the amplitudes of all spike activity. Deltamethrin at 10μM induced a significant increase in the latency of electrically evoked responses, and this was attributed to a synaptic mechanism. It was shown for the first time that 10-μM deltamethrin causes a significant elevation of the extra-axonal K⁺ activity; the possible consequences of this are discussed.     

Neural effects of allethrin on the free walking cockroach Periplaneta Americana: An investigation using defined doses at 15 and 32°C

The action of allethrin has been studied in the free-walking cockroach, Periplaneta americana (L) using implanted electrodes, at 15 and 32°C, following topical application of an LD₉₅ dose (that at 32°C being approximately ten times the LD₉₅ at 15°C). At both temperatures there was marked hyperexcitation of the peripheral nervous system. At 32°C there was also hyperexcitation of the central nervous system but central effects at 15°C were probably secondary. Likewise, nerve blockage often did not occur until many hours after paralysis and could thus be a secondary consequence of allethrin poisoning.     

Dibromo addition products of (1R)-cis-permethrin and deltamethrin; evidence that debromination is an obligatory requirement for biological activity

3-Phenoxybenzyl (1R-)-cis-3-(1,2-dibromo-2, 2-dichloroethyl)-2, 2-dimethylcyclopropanecarboxylate [dibromo-(1R)-cis-permethrin] was >100 times less active than (1R)-cis-permethrin in causing repetitive firing in a cockroach cereal sensory nerve in vitro, although its toxicity, symptomology and nerve effects in vivo were comparable to the parent compound. Treatment of the in-vitro preparation with glutathione significantly increased the effectiveness of dibromo-(1R)-cis-permethrin in a concentration-dependent manner, while having no effect on the action of (1R)-cis-permethrin. Topical treatment of the cockroach with dibromo-(1R)-cispermethrin gave a similar time of onset of symptoms to that caused by (1R)-cis-permethrin (∼2 min). Pretreatment of the cockroach with N-ethylmaleimide (NEM) significantly (P<0.05) increased dose-dependently the latency of signs of poisoning caused by dibromo-(1R)-cis-permethrin, but had no significant effect on the latency following (1R)-cis-permethrin treatment. Deltamethrin and tralomethrin, applied to the cockroach at LD₉₅ doses of 0.03 and 0.07 m̈g g⁻¹ respectively, also had similar latencies for the development of symptoms. Moreover, pretreatment with NEM delayed the time of onset of symptoms for tralomethrin (P<0.02) but not for deltamethrin. The results strongly suggest that debromination is an obligatory requirement for the biological activity of dibromo-(1R)-cis-permethrin and tralomethrin.     

Excretion of DDT residues into milk of the Indian buffalo,Bubalus bubalis (L.) after oral and dermal exposure

Three groups of buffaloes were fed with 20, 100 and 400 mg of p,p′-DDT in their daily rations. The DDT residues in the milk fat of the treated animals showed an initial rapid rise but soon attained a dose-dependent equilibrium. The transfer coefficient of DDT residues in milk at ‘plateau’ levels showed an average value of about 12%. Half-life values for the rate of decline of DDT residues during the post-dosing period were computed according to a two-open-compartment model. Dermal application of p,p′-DDT to buffaloes also resulted in excretion of a significant amount of its residues in milk. TDE was the predominant compound present in milk when buffaloes had ingested p,p′-DDT, whilst p,p′-DDT itself was present in greater quantity than its metabolites when animals were treated dermally.     

Distinguishing between carbamate and organophosphate insecticide poisoning in house flies by symptomology

Three criteria, latency to convulsions, still period, and recovery are used to distinguish between carbamate and phosphate insecticide poisoning in house flies, Musca domestica. Because of shorter latencies with carbamate-treated flies, the central nervous system was considered more sensitive to the presence of carbamates than phosphates. Recovery from carbamate-induced tetany was considered correlated with reactivation of carbamylated cholinesterase. There appeared to be a fundamental difference between the insecticidal actions of carbamates and phosphates not wholly explainable by cholinesterase inhibition. Tethered or held house flies were less susceptible to poisoning than unrestrained flies.     

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.     

DDT-lipoprotein complex in the American cockroach hemolymph: A possible way of insecticide transport

The binding in vitro of ¹⁴C-DDT to proteins from the hemolymph of the American cockroach was shown by means of electrophoresis and isoelectric focusing on polyacrylamide gels. The study of ¹⁴C-DDT penetration into the insect implies the hemolymph as one of the possible manners by which this insecticide could penetrate the central nervous system, and other target organs. The possibility of DDT being transported by the hemolymph bound to lipoproteins is discussed.     

Neurophysiological activity and toxicity of pyrethroids derived by addition of methylene,sulfur or oxygen to the chrysanthemate 2-methyl-1-propenyl substituent

Conversion of chrysanthemates to their cyclopropane, episulfide, and epoxide derivatives by addition of methylene, sulfur, or oxygen, respectively, to the 2-methyl-1-propenyl double bond yields products generally of reduced toxicity but enhanced neurophysiological activity and photostability. The reduced toxicity is established with cis-cyphenothrin derivatives administered intracerebrally to mice and topically to house flies and with cis-phenothrin derivatives applied topically to American cockroaches and house flies, even in the presence of piperonyl butoxide for the house flies. In contrast, cyclopropane, episulfide, and epoxide derivatives of phenothrin are more potent than the parent compound in eliciting repetitive firing following stimulation of a cercal sensory nerve of the American cockroach in vitro. The individual 1′R and 1′S isomers of epoxides derived from (1R,cis,αS)cyphenothrin, (1R,cis)phenothrin, and (1R,trans)tetramethrin differ in potency by up to 20-fold for insecticidal activity, >30-fold for intracerebral toxicity to mice, and ～100,000-fold in the cercal sensory nerve assay. In each case the epoxide isomer of higher R_f is more potent than that of lower R_f when derived from a trans-chrysanthemate and vice versa from a cis-chrysanthemate.     

Distribution and breakdown of DDT in orchard soil

Amounts of DDT and its breakdown products were determined in soil in an apple orchard in Herefordshire. Samples were taken for a number of years (1972–79) after use of the insecticide in the orchard had ceased in 1969. The results were compared with those obtained in an investigation of the same orchard in 1968. From 1968 to 1979, soil residues of pp′-DDT, p′--DDT and pp′--TDE decreased gradually whereas those of pp′--DDE increased, and there were linear relationships between log (concentration) and time. The calculated time for 50% decrease in concentration (Dt₅₀) was 11.7 years for pp′--DDT, 3.3 years for pp′--TDE and 7.1 years for op′--DDT; the time for doubling the concentration for pp′--DDE was 9.1 years. Regression analysis on the two major components (pp′--DDT+pp′--DDE) indicated that the total amount (2.7 mg kg^?1) was not decreasing with time. It was concluded that during a post-spray era, the breakdown of pp′--DDT to pp′--DDE was a significant feature of the persistence of DDT, and that, in contrast to the findings of other workers who sampled when DDT was being used, there were no losses by volatilisation. There was an exponential decrease in the amount of DDT residues with increasing soil depth and approximately 90% was found in the top 10 cm of the undisturbed soil profile.     

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.     

Quantitative structure-activity studies of substituted benzyl chrysanthemates: 7. Relationship between induction of repetitive discharges and effects on the action potential

The effects of substituted benzyl (1R)-trans-chrysanthemates and related compounds on the action potential of the crayfish giant axon were investigated using an intracellular microelectrode. The effects are broadly classified into three types: deceleration of the falling-phase of the action potential (type A), elevation of the depolarizing after-potential (type B), and the combination type (type C). The potency of the type A compounds to decelerate the rate of the falling-phase was determined in terms of the concentration required for reducing the rate to a specified degree. This potency was shown to correlate with the potency to induce repetitive discharges in the cockroach central nerve cord in terms of minimum effective concentration, which was determined previously. The potency of the types B and C compounds to elevate the after-potential was, however, not related directly with the cockroach nerve repetitive activity. The elevation of the after-potential is one of the critical factors but other effects such as a depolarization of the resting potential may be involved in determining the repetitive activity.