Pyrethrin Synergists Research Articles

Molecular pathological analysis for determining the possible mechanism of piperonyl butoxide-induced hepatocarcinogenesis in mice

Piperonyl butoxide (PBO), α-[2-(2-butoxyethoxy)ethoxy]-4,5-methylene-dioxy-2-propyltoluene, is widely used as a synergist for pyrethrins. In order to clarify the possible mechanism of non-genotoxic hepatocarcinogenesis induced by PBO, molecular pathological analyses consisting of low-density microarray analysis and real-time reverse transcriptase (RT)-PCR were performed in male ICR mice fed a basal powdered diet containing 6000 or 0 ppm PBO for 1, 4, or 8 weeks. The animals were sacrificed at weeks 1, 4, and 8, and the livers were histopathologically examined and analyzed for gene expression using the microarray at weeks 1 and 4 followed by real-time RT-PCR at each time point. Reactive oxygen species (ROS) products were also measured using liver microsomes. At each time point, the hepatocytes of PBO-treated mice showed centrilobular hypertrophy and increased lipofuscin deposition in Schmorl staining. The ROS products were significantly increased in the liver microsomes of PBO-treated mice. In the microarray analysis, the expression of oxidative and metabolic stress-related genes—cytochrome P450 ( Cyp) 1A1, Cyp2A5 (week 1 only), Cyp2B9, Cyp2B10, and NADPH-cytochrome P450 oxidoreductase ( Por) was over-expressed in mice given PBO at weeks 1 and 4. Fluctuations of these genes were confirmed by real-time RT-PCR in PBO-treated mice at each time point. In additional real-time RT-PCR, the expression of Cyclin D1 gene, key regulator of cell-cycle progression, and Xrcc5 gene, DNA damage repair-related gene, was significantly increased at each time point and at week 8, respectively. These results suggest the possibility that PBO has the potential to generate ROS via the metabolic pathway and to induce oxidative stress, including oxidative DNA damage, resulting in the induction of hepatocellular tumors in mice.

Cytogenetic effects of piperonyl butoxide and safrole in CHO-K1 cells

Recently, hepatocarcinogenicity in rats and mice was reported with regard to the methylenedioxyphenyl compound, piperonyl butoxide (PB), which is used as a synergist for pyrethrins and related insecticides. Induction of sister-chromatid exchanges (SCEs) and chromosomal aberrations (CAs) due to PB were investigated using CHO-K1 cells with or without rat liver S9 fraction (S9); at the same time, the effects of safrole (SF), a methylenedioxyphenyl compound and a weak hepatocarcinogen, were also examined. PB (0.25 and 0.3 mM) and SF (0.8 mM) caused a slight but significant increase in SCEs followed by a cell-cycle delay in the 3-h treatment without S9. In the presence of S9 (4.5%), the cytotoxicity of PB or SF was weakened greatly or slightly, the top dose capable of cell division was raised to 0.6 mM (2-fold) or 1 mM, respectively. PB with S9 induced SCE at doses of 0.4 and 0.5 mM, and caused endoreduplications (ERDs, 7%) at a dose of 0.6 mM, while SF caused a dose-related significant increase in SCE at all doses used (0.4–1 mM) with S9. Genotoxicity of the metabolites of PB or SF was cleared by changing the dose of S9 (1.5–9%) while holding the dose of each chemical constant. In the case of SF (0.6 mM), induction of SCE, ERD and cell-cycle delay intensified almost in a dose-effect relationship, and CAs and a high level of ERD (14%) were caused by a 9% dose of S9. The concentration of unchanged SF in the incubated medium was certainly in inverse proportion to the dose of S9. This strongly suggests that the metabolites of SF are genotoxic. In the case of PB (0.3 mM), no positive responses were produced in the cultures, even with a high level of S9, though the amount of unchanged PB left in the incubated medium was very slight. This indicates that the metabolites of PB may not be genotoxic. In conclusion, PB and SF are possible to somewhat induce SCE at high dose(s) in the absence of S9, and the genotoxic effects of SF are more intensified in the presence of S9 than in its absence, while PB is probably no genotoxic in the presence of sufficient metabolic activation.

Fenvalerate cross-resistance in a resmethrin-selected strain of the house fly (Diptera: Muscidae).

Resmethrin-selected house flies, Musca domestica L., were cross-resistant to fenvalerate. Fenvalerate was between 30- and 100-fold less toxic to resmethrin-selected flies (R) than to susceptible flies (S). While both DEF (S,S,S-tributyl phosphorotrithionate) and piperonyl butoxide (PB) significantly synergized fenvalerate ( P < 0.05) in R flies, PB was 8-fold more effective than DEF. PB was not a good synergist in S flies. In R flies, PB did not affect the rate of fenvalerate penetration as measured by unpenetrated insecticide. GA4-282, (2,6-dichlorobenzyl-2 propynyl) ether, and PB synergized pyrethrins, resmethrin, and the carbamates Mobam™, propoxur, and mexacarbate; the propynyl ether was more effective than PB with the carbamates, whereas PB was the better synergist for pyrethrins and resmethrin was synergized equally. GA4-282 had no effect on fenvalerate toxicity, although PB was markedly synergistic.

Evaluation of some Insecticides with three Pyrethrin Synergists against the Mosquito Culex pipiens fatigans Wied. in Egypt

AbstractFenitrothion, dichlorvos, chlorthion and bidrin were tested for their toxicity against the adult stage of Culex pipiens fatigans. Fenitrothion and dichlorvos were the most toxic which had LC50 values of 0.0042 % and 0.005 % respectively. These two values fall within the range of 0.001 to 0.01 % which is used for practical space spray for adult female mosquito control.No synergistic effect was noticed for piperonyl butoxide, sulfoxide or bucarbolate on the toxicity of the four organophosphorus compounds fenitrothion, dichlorvos, chlorthion and bidrin for adult females of the same mosquito strain. Bucarbolate shows strong antagonism only with bidrin.ZusammenfassungWirkung einiger Insektizide mit drei Pyrethrin‐Synergisten auf Culex pipiens fatigans Wied. in Ägypten. II. Adulte TiereDie Insektizide Fenithrotion und Dichlorvos wirkten auf die Adulten von C. pipiens am stärksten toxisch (LC50 = 0,0042 % und 0,005 %). Diese zwei Werte fallen in den Bereich von 0,001 bis 0,01 %, der für die praktische Anwendung von Mosquito‐Bekämpfungsmitteln vorgeschrieben ist.Ein synergistischer Effekt von Piperonylbutoxyd, Sulfoxyd und Bucarbolat zur toxischen Wirkung dieser vier Insektizide wurde nicht beobachtet. Bucarbolat zeigte einen strengen Antagonismus zu Birdin.

Evaluation of Nine Insecticides with Three Pyrethrin Synergists against the Mosquito Culex pipiens quinquefasciatus Say in Egypt

AbstractThree pyrethrin synergists with two chlorinated hydrocarbons and seven organophosphorus insecticides were tested against larvae, eggs and pupae of Culex pipiens quinquefasciatus in Egypt under laboratory conditions. Chlorthion, Sumithion, Dichlorvos and Malathion were the most toxic as larvicides, respectively. Actually only Chlorthion and Malathion may be regarded as toxic since the LC50 of good mosquito larvicides is considered to range between 0.001 and 0.01 p.p.m. Bidrin was less toxic and may be grouped with DDT and Thiodan. Roxion and Daphene, which contains primarily Dimethoate, were insufficient for the required very high concentrations to give any practical control.Combinations of DDT with Thiodan, Sumithion, Dichlorvos and Malathion were found to give slight effect on the tested mosquito larvae. Sulfoxide, Piperonyl butoxide and Bucarpolate were found to be active synergists only for Bidrin against larvae of the present DDT‐resistant strain. The antagonistic effect of these three compounds was observed for each of Chlorthion, Malathion, Roxion and Daphene total.All of the used insecticides showed a slight ovieidal effect, but Sumithion was the only insecticide that may be caused as C. pipiens ovicide to the low concentrations required (LC50 = 0.19 p.p.m.). The pupal stage was more tolerant than either the egg or the larval stages.ZusammenfassungVersuche mit 9 Insektiziden und 3 Pyrethrin‐Synergisten gegen die Stechmücke Culex pipiens quinquefasciatus Say in ÄgyptenEs wurden 3 Pyrethrin‐Synergisten in Kombination mit 2 Chlorkohlenwasserstoffen und 7 Organophosphaten gegen die Eier, Larven und Puppen von C. p. quinquefasciatus im Labor getestet. Nur Chlorthion und Malathion erfüllten die an ein Larven‐Insektizid bei Mosquitos zu stellenden Anforderungen (LD50 zwischen 0,001 und 0,01 ppm). Weniger wirksam waren Bidrin, DDT und Thiodan. Die Dimethoate Roxion und Daphen waren ungenügend, da sie nur bei sehr hoher Konzentration Wirkung zeigten.Kombinationen von DDT und Thiodan, Sumithion, Dichlorphos und Malathion waren nur wenig besser als die Einzelkomponenten.Sulphoxyd, Puperonylbutoxyd und Bucarpholat wirkten als gute Synergisten nur im Zusammenhang mit Bidrin gegen die Larven DDT‐resistenter Mückenstämme. In Kombination mit Chlorthion, Malathion, Roxion und Daphen zeigten sie antagonistische Effekte.Alle verwendeten Insektizide hatten geringe ovizide Wirkung, jedoch verdient nur Sumithion als wirkliches Ovizid bezeichnet zu werden.Das Puppenstadium erwies sich als weniger empfindlich als Ei und Larven.

Juvenile Hormone Activity of Sesamex and Related Compounds in Tests on the Yellow Mealworm12

Sesamex (2-(2-ethoxyethoxy) ethyl 3,4-(methylenedioxy) phenyl acetal of acetaldehyde), a synergist for pyrethrins and carbamates, and 82 related compounds were tested against Tenebrio molitor L. for juvenile hormone activity. Six of the compounds were as active or more active than sesamex or farnesyl methyl ether, the standard. Since 4 of the 6 did not have a (methylenedioxy) phenyl group but did have other meta - or para -substituted phenyl groups, high juvenile hormone activity in the yellow mealworm can be obtained with compounds having phenyl substituents other than the methylenedioxy group.

The inhibition of drug metabolism enzymes by some naturally occurring compounds

The ability of a series of naturally occurring pyrethrin synergists to inhibit various pathways of drug metabolism has been studied in the rat and mouse. These compounds were effective in vitro inhibitors of the oxidative metabolism of aniline, aminopyrine, diphenyl and hexobarbital by liver preparations. Reduction of the azo dye neoprontosil was not inhibited. In vivo inhibition of hexobarbital oxidation in the mouse, as shown by an increase in sleeping times, was also observed. Some considerations of structure-activity relationships are discussed. Several of the compounds studied produced dilation of the endoplasmic reticulum and the Golgi apparatus of liver cells as well as depleting glycogen deposits. These effects did not appear to be related to inhibitory power. These substances can alter membrane permeability, as shown by measurements of glucose exit from red blood cells. The effects on the liver and red blood cell may be a function of lipid solubility or, more likely, ability to bind to protein.

Reactions of larvae of Plodia interpunctella (HB) (LEP., pyralidae) to insecticidal droplets.

In tests of the reactions of freshly hatched larvae of Plodia interpunctella (Hb.) to droplets of liquids containing an insecticnde, 16 droplets of the test material were disposed in a ting 23 mm. in diameter on a glass surface. The mean diameter of dtoplets of the different oils used as solvents varied from about 330 to 615 μ. Minute glass beads about 680 μ in diameter were used as controls. The larvae were tested individually by placing them at the ecntre of the ring and noting whether ot not they succeeded in escaping from it without making contact with a droplet, and their time to do so, termed the avoiding-time.Six petroleum hydrocarbon oils, and pyerthrin at different concentrations in one of them (Shell Risella Oil 17) and pyrethrin synergists, piperonyl butoxide and Bucarpolate (2-(2-n-butoxyethoxy)ethyl 3,4-methylenedioxybenzoate), were tested. Droplets containing 20 per cent. pyrethrins proved the most repellent, over 98 per cent. of the larvae avoiding contact with them, whereas only 47.5 per cent. avoided the glass beads. The degree of avoidance elicited by the oils was inversely related to the values of their physical characteristics, such as initial boiling point and mean molecular weight. Increasing concentrations of pyrethrins increased both the degree of avoidance and the avoidingtime, and the addition of piperonyl butoxide or Bucarpolate enhanced both these reactions.

Detector cell for measuring picogram quantities of organophosphorus insecticides, pyrethrin synergists, and other compounds by gas chromatography

Detector cell for measuring picogram quantities of organophosphorus insecticides, pyrethrin synergists, and other compounds by gas chromatography

Structure-activity Relationships among Insecticidal Compounds derived from Chlordene

RECENT investigations1–3 demonstrated the value of metabolic inhibitors such as pyrethrin synergists as tools in the investigation of structure-activity relationships among the ‘cyclodiene’ type insecticides. Thus, the wide variations in toxicity to the housefly found in several groups of related cyclodienes were found to be reduced in the presence of the pyrethrin synergist ‘Sesamex’2, a phenomenon accompanied, in the case of compounds examined in vivo, by inhibition of metabolic conversions1,3.

The effect of pyrethrin synergists, especially sesamex, on the insecticidal potency of hexachlorocyclopentadiene derivatives (“cyclodiene” insecticides) in the adult housefly, Musca Domestica L

The toxicity of fifty-one cyclodiene compounds has been examined on strains of houseflies resistant and susceptible to dieldrin. The results demonstrate the marked cross-resistance of houseflies selected only with dieldrin to other compounds having the hexachloronorbornene nucleus (or variants of it) in common, only seven of the compounds tested being noticeably active against the resistant strains. The toxicities of compounds tested to susceptible flies fall into six groups of which the first two contain the highly toxic cyclodienes which are mostly not markedly synergized by sesamex. The third and fourth groups include compounds of moderate or low toxicity which are synergized and the remaining groups contain compounds which are virtually non-toxic and are not synergized. With a few exceptions, none of the compounds were synergized by sesamex against resistant flies. Moderately toxic compounds which were strongly synergized in susceptible flies but not in resistant flies were of particular interest since stabilisation of these compounds in vivo has been demonstrated in both strains. Assuming that the enhanced poisoning effect in susceptible strains is due to the observed inhibition by sesamex of the breakdown of the poison, then the absence of poisoning effects in resistant strains suggests that the resistance is not dependent solely on the metabolism. That sesamex was able to delay not only the conversion of aldrin to dieldrin but also the degradation of other members of this series demonstrates its versatility as a metabolic inhibitor. If the assumption concerning the action of sesamex is valid, the synergized toxicity of compounds is an indication of their intrinsic toxicities, which give a truer indication of structure-toxicity relationships than the toxicities normally observed; the difference between toxicities with and without synergist gives a measure of the amount of metabolism occurring. The cyclodiene compounds of low toxicity which were not synergized may have low intrinsic toxicity or ability to reach their site(s) of action. Houseflies recovered from poisoning by some mildly toxic cyclodiene compounds which were metabolized, and appeared normal except for permanent wing damage. This suggests that cyclodiene poisoning is at least partly reversible with the severity of the effect depending on the persistence of the poison in the tissues.

Hibalactone (Savinin) as a Synergist for Pyrethrins and Allethrin

Hibalactone (Savinin) as a Synergist for Pyrethrins and Allethrin

Hibalactone (Savinin) as a Synergist for Pyrethrins and Allethrin

(1957). Hibalactone (Savinin) as a Synergist for Pyrethrins and Allethrin. Bulletin of the Agricultural Chemical Society of Japan: Vol. 21, No. 2, pp. 132-133.