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Effects of insecticide synergists on microsomal oxidation of estradiol and ethynylestradiol and on microsomal drug metabolism.

1. Oxidation of estradiol and ethynylestradiol at ring A and ring B by rat liver microsomes and NADPH-regenerating system in vitro is inhibited by the two arylimidazole insecticide synergists, 3-bromophenyl-4(5)-imidazole and 1-naphthyl-4(5)-imidazole, but not by the benzothiadiazole insectide synergists 6-nitro-1,2,3-benzothiadiazole and 5,6-dimethyl-1,2,3-benzothiadiazole. The Ki of the most potent inhibitor, 1-naphthyl-4(5)-imidazole, was 3 X 10(-6) M. 2. 6-Nitro-1,2,3-benzothiadiazole (10(-6) M), which did not inhibit hydroxylation of the estrogens, inhibited oxidation of aniline and demethylation of ethylmorphine, p-nitroanisole, and aminopyrine by 30-70%. 5,6-Dimethyl-1,2,3-benzothiadiazole inhibited only demethylation of p-nitroanisole and aminopyrine. From these results the presence of different hepatic microsomal mixed function oxidases may be inferred. 3. 1-Naphthyl-4(5)-imidazole, the most potent inhibitor of hydroxylation of drugs and estrogen rings A and B, also inhibited microsomal estrogen-16alpha-hydroxylation. 4. These data show that insecticide synergists may effect the breakdown of estrogenic hormones in the organism.

Animals↗

Methoxychlor residues in milk of cattle treated with Marlate 50 insecticide as a dermal spray.

Lactating Holstein cattle were treated twice at an interval of 14 days with methoxychlor (Marlate 50 insecticide) as a 0, .25, or .50% dermal spray, with 2 quarts of spray mix applied to each animal. Residues of methoxychlor in whole milk were highest on the 1st or 2nd day after treatment and, when expressed as part per million equivalent in milk fat, were as high as 2.0 and 3.0 ppm in samples from the low and high dosage sprays. Residues in milk dropped rapidly after residues were at most only slightly above the sensitivity limit (.005 ppm in whole milk) of the analytical method. Applicative specifications for Marlate 50 insecticide use on lactating dairy cattle might result in violative methoxychlor residues in milk during the first 1 to 3 days after treatment.

Administration, Topical↗

[Synthetic pyrethroid insecticides and development of resistance to them].

After the structures of pyrethrins, the insecticidal components of pyrethrum flowers, were determined, syntheses of derivatives of them were undertaken, and first generation synthetic pyrethroids, such as allethrin, resmethrin and phenothrin, were produced. Due to lack of photostability in these compounds, their use was limited to the control of sanitary or household pests. The syntheses of second generation synthetic pyrethroids, i.e., permethrin and fenvalerate, overcame a lack of photostability. These are now widely employed in the areas of agriculture and public health. Development of resistance in insect pests is the only difficulty to the future success of ideal insecticides, or synthetic pyrethroides. In this review, information regarding the development of pyrethroid resistance is summerized, and also the importance of nerve insensitivity to the chemicals, as a mechanism of resistance in insects pests, is pointed out.

Animals↗

[Changes in the serum activity of lysosomal enzymes in rats after the use of propoxur (Baygon) insecticide. 2. The dynamics of beta-N-acetylglucosaminidase].

The influence of 1/50 and 1/10 LD50 of the monomethylcarbamate insecticide Propoxur (Baygon) on the lysosome enzyme beta-N-acetylglucose-aminidase serum activity is studied in white rats upon daily administration per os, over a period of 2, 4, 8, 15, 30, 60 and 90 days. A statistically significant increase of the enzyme activity is recorded at 15 days after introduction of 1/50 LD50, and at 15 and 30 days after 1/10 LD50 administration, followed by a reduction of the activity and returning to normal values. In all likelihood, the harmful effect of Propoxur on the lysosome and cellular membrane decreases after the 15th day because of activation of the microsome enzymes which, in turn, speed up the process of rendering innocuous the insecticide administered.

Acetylglucosaminidase↗

Responses of male and female mosquitoes to repellents in the World Health Organization insecticide irritability test system.

A study was conducted to compare responses of male and female Aedes aegypti (Linn.) and Aedes taeniorhynchus (Wiedemann) to 9 olfactory repellents in the World Health Organization insecticide irritability test system. An irritant insecticide (permethrin) and a control were included for comparison. Aedes aegypti exhibited significantly more takeoffs than Ae. taeniorhynchus, and female mosquitoes exhibited significantly more takeoffs than males. Permethrin induced significantly more takeoffs than the control, but olfactory repellents did not. Certain 2- and 3-factor interactions of test materials, species, and sexes were statistically significant. This study supports a previous conclusion that the World Health Organization test method does not measure contact repellency (irritancy) and olfactory repellency equally.

Aedes↗

Aircraft disinfection: the physical and insecticidal characteristics of (+)-phenothrin applied by aerosol at "blocks away".

A 2% formulation of (+)-phenothrin dispensed from 340-g or break-off tip aerosol cans was highly effective against mosquitos in aircraft disinsection trials. Two minutes after application at "blocks away", the mass median diameter of the dispersed drops was 5.1-6.2 mum. The concentration of the insecticide in the cabin fell to 10% of the original concentration after 9.2 min. No odour or irritation was caused by the use of this insecticide.

Aerosols↗

Analysis of bruchid resistance in the wild common bean accession G02771: no evidence for insecticidal activity of arcelin 5.

Arcelins are abundant seed storage proteins thought to be implicated in the resistance of wild Phaseolus vulgaris (L.) genotypes against Zabrotes subfasciatus (Boheman), an important storage insect pest of common bean. Here, the insecticidal activity of the arcelin-5 variant that is present in the highly resistant P. vulgaris accession G02771 was investigated. No correlation could be established between the presence of arcelin 5 and the insecticidal effects observed in G02771 seeds. Insect feeding assays with artificial seeds into which purified arcelin-5 protein was incorporated and with transgenic P. acutifolius (A. Gray) seeds in which the arcelin-5 genes were expressed, showed that the presence of arcelin-5 proteins, even at elevated levels, was not sufficient to achieve adequate resistance against Z. subfasciatus. The same might apply to other arcelin variants. Nevertheless, as resistance is clearly closely linked to the presence of the arcelin-1 or arcelin-5 locus, arcelins remain useful markers in breeding programmes aimed at introgressing high levels of resistance to Z. subfasciatus in P. vulgaris cultivars.

Animals↗

[Comparative evolution of blood antibodies in cattle infested with hypodermosis and treated with different insecticides (author's transl)].

Immunological response to hypodermosis is studied by a passive hemagglutination method in three groups of cattle naturally infested during the spring of 1972. In the autumn, one group was treated with fenthion and another with niclofolan, a drug generally used for distomatosis, but also efficient in hypodermosis and free from side-effects. The third group served as a control. Two kinds of immunological response are observed after use of the insecticide. In the group treated with fenthion, there is a rapid drop in antibodies during the 3 days following treatment; this increases for the next 2 months up to a very low level, which is stable for 3 months (fig. 3, 4, 5). During the same period, antibodies in the control group increase regularly to reach a maximum in April or May (fig. 1, 2). The immunological response of the host is closely related to the antigenic stimulation of the larvae. In the group treated with niclofolan, the slow drop in antibodies suggests that there is a parallel drop in the number of larvae during the month following treatment. A study of the other group shows that larvae are affected in the 24 hours following fenthion administration. This agent, as well as all organophosphorous compounds, are well-known to act efficiently on larvae and have anaphylactic-type side-effects on the host. The massive degradation of larvae should have induced an important antigenic reaction, but no increase in the antibodies of the host is observed; there is a even rapid drop in the number of larvae immediately after treatment. This fact is investigated further by experiments on guinea pig: the role of antigen-antibody complexes is studied by passive anaphylaxis. It appears that shock reactions, following use of organophosphorous insecticides, have a true-hyper-sensitivity origin, and are increased by the intrinsic toxicity of the first instar larvae.

Animals↗

[Isolation and characterization of a insecticidal protein from Pseudomonas pseudoalcaligenes].

A insecticidal protein was purified by gel-filtration chromatography on Sephadex G-100 and anion-exchange chromatography on DEAE-Sephadex A-50 from the suspension of Pseudomonas pseudoalcaligenes culture. Certain biophysical and biochemical properties were also studied. The molecular weight of the subunit of the insecticidal protein is 25,100 and pI is 5.16. Amino acid composition analysis showed that it is an acidic protein.

Amino Acids↗

[Synthesis and insecticidal activity of the novel hydroxylbenzenedisulfonanilides compounds].

AIM: To synthesize novel derivatives of hydroxylbenzenedisulfonanilide with high insecticidal activity against the Fasciola hepatica. METHODS: o-(m-, p-) Chlorphenol were used to synthesize the title compounds by sulphonation and nucleiphilic-substitution reaction. The uncoupling activity (insecticidal activity) of these compounds were tested by determining the influence on mitochondrial respiration control ratio (RCR) and the variation of inorganic phosphate in oxidative phosphorylation (delta Pi). RESULTS: Compounds 1-14 are new compounds. The structures of the compounds were determined by IR, HNMR and elemental analysis. Most new compounds have relatively high uncoupling activities, especially compounds 3, 5, 6 and 9. CONCLUSION: Compounds 3, 5, 6 and 9 will become novel fasciolicides and are worth further studying.

Anilides↗

Insecticide poisoning in pregnancy. A case report.

A 25-year-old multigravida drank an organochlorine insecticide in an attempt to commit suicide at 16 weeks of pregnancy. This resulted in the death of twin fetuses and vaginal bleeding. The pregnancy was terminated using gemeprost, syntocinon and later surgical evacuation of the uterus. She developed respiratory arrest after the fetuses were aborted and also after surgical evacuation. On both occasions, she was intubated and mechanically ventilated. We believe that organochlorine insecticides may be fetocidal. In addition, surges in blood levels may occur during termination of pregnancy, delivery or evacuation of retained products of conception.

Adult↗

Teratological examination of the insecticide methyl-parathion (Wofatox 50 EC) on pheasant embryos. 2. Biochemical study.

Fertile pheasant's eggs were treated with the insecticide Wofatox 50 EC (50% methyl-parathion) by injection technique on day 12 of the hatching period. Treatment consisted of inoculation of 0.1 ml of different concentrations of the insecticide into the air space of embryonated eggs. The following dose levels were employed: 0.00, 1.35, 13.5 and 135.0 mg/kg egg of active ingredient. Biochemical changes in the plasma were evaluated by micro (photometric) methods which rendered possible the determination of several blood plasma variables of the embryos. At the highest dose level applied, serum alkaline phosphatase (SAP) enzyme activity and inorganic P concentration of the treated embryos showed statistically differences (reduction) as compared to the control data. Macroscopic alterations were detected at necropsy.

Animals↗

Poisoning from oral ingestion of carbofuran (Furadan 4F), a cholinesterase-inhibiting carbamate insecticide, and its effects on cholinesterase activity in various biological fluids.

A case is presented of a fatal ingestion of Furadan (carbofuran), a cholinesterase-inhibiting carbamate insecticide. A 26-year-old white male was found dead with a partially filled 1-gal (3.8-L) container of Furadan 4F insecticide-nematocide (44.9% carbofuran). The individual had ingested approximately 345 mL of the mixture. Analysis of cholinesterase activity in various biological fluids was performed spectrophotometrically using propionylthiocholine and 5,5'-dithiobis-2-nitrobenzoic acid [Sigma Diagnostics, cholinesterase procedure No. 422 (PTC)] which was measured at 405 nm and 30 degrees C in a Gilford Stasar III Spectrophotometer. The cholinesterase activities were as follows: plasma, 245 units (U)/L (93% inhibition/7% normal activity); serum, 208 U/L (95.3% inhibition/4.7% normal activity); whole blood, 297 U/L (92.8% inhibition/7.2% normal activity); erythrocytes, 58 U/L (99% inhibition/1% normal activity); vitreous humor, 7 U/L; and bile, 148 U/L. Carbofuran was detected in the blood and gastric contents by thin-layer chromatography. No alcohol or other drugs were detected in the blood, urine, or gastric contents. Ingestion of the carbofuran produced acute visceral congestion and pulmonary edema. Death was caused by anoxia due to respiratory paralysis produced by cholinesterase inhibition from Furadan (carbofuran) ingestion.

Adult↗

Modulation by the insecticides heptachlor and chlordane of the cell-mediated immune proliferative responses of rhesus monkeys.

Peripheral blood mononuclear cells (PBMC) were isolated from heparinized blood samples from twelve young, healthy male rhesus monkeys. Triplicate cultures were made in RPMI 1640 with 10% heat-inactivated homologous plasma with or without the test mitogens (phytohemagglutinin, concanavalin A and pokeweed mitogen). Under a defined assay condition, although a different monkey responded to a different degree (3 to 4-fold difference in stimulation index) to a specific mitogen, the proliferative responses of all monkeys were affected significantly by the addition of the chlorinated hydrocarbon heptachlor or chlordane to the test cultures. The insecticides, at 10-40 microM, may also act as mitogens for the unstimulated monkey PBMC or stimulate the release of IL-2 from a mitogen-stimulated culture. At 80 microM, both heptachlor and chlordane completely suppressed the proliferation and IL-2 release of the monkey lymphocytes. These studies suggest immunomodulatory effects of the insecticides heptachlor and chlordane.

Animals↗

Biotransformation of the organophosphorus insecticides parathion and methyl parathion in male and female rat livers perfused in situ.

Although numerous previous reports have characterized the mammalian biotransformation of the organophosphorus insecticides parathion and methyl parathion, questions still remain regarding the toxicological significance of certain metabolic pathways in vivo. The present study utilized rat liver perfusions in order to better characterize the hepatic biotransformation of parathion and methyl parathion in intact liver. Single-pass liver perfusions with parathion and methyl parathion over a range of perfusate concentrations of 10-80 microM resulted in the appearance of paraoxon and methyl paraoxon, respectively, in effluent. Furthermore, rat blood did not have the capacity to prevent transport of paraoxon and methyl paraoxon to extrahepatic tissues, suggesting that oxon produced hepatically can distribute to extrahepatic tissues. In addition, striking sex differences were noted in the metabolite profile of parathion and methyl parathion in perfused livers. However, these differences could not account for the observation that females are more susceptible to parathion, but less susceptible to methyl parathion, compared to males. And finally, S-methyl glutathione or S-p-nitrophenyl glutathione could not be detected in effluent or bile of livers from either sex perfused with methyl parathion, suggesting that glutathione-dependent detoxification of this insecticide does not occur to any significant degree in intact rat liver.

Animals↗

Functional domains of Bacillus thuringiensis insecticidal crystal proteins. Refinement of Heliothis virescens and Trichoplusia ni specificity domains on CryIA(c).

Insecticidal crystal proteins (delta-endotoxins), CryIA(a) and CryIA(c), from Bacillus thuringiensis are 82% homologous. Despite this homology, CryIA(c) was determined to have 10-fold more insecticidal activity toward Heliothis virescens and Trichoplusia ni than CryIA(a). Reciprocal recombinations between these two genes were performed by the homolog-scanning technique. The resultant mutants had different segments of their primary sequences exchanged. Bioassays with toxin proteins from these mutants revealed that amino acids 335-450 on CryIA(c) are associated with the activity against T. ni, whereas amino acids 335-615 on the same toxin are required to exchange full H. virescens specificity. One chimeric protein toxin, involving residues 450-612 from CryIA(c), demonstrated 30 times more activity against H. virescens than the native parental toxin, indicating that this region plays an important role in H. virescens specificity. The structural integrity of mutant toxin proteins was assessed by treatment with bovine trypsin. All actively toxic proteins formed a 65-kDA trypsin-resistant active toxic core, similar to the parental CryIA(c) toxin, indicating that toxin protein structure was not altered significantly. Contrarily, certain inactive mutant proteins were susceptible to complete protease hydrolysis, indicating that their lack of toxicity may have been due to structural alterations.

Bacillus thuringiensis↗

Role of genetic polymorphism of human plasma paraoxonase/arylesterase in hydrolysis of the insecticide metabolites chlorpyrifos oxon and paraoxon.

Plasma paraoxonase is a polymorphic enzyme that hydrolyzes paraoxon, the neurotoxic, active metabolite of the insecticide parathion. This enzyme is specified by at least two alleles with frequencies of about .7 and .3 among Caucasoid populations. A specific assay was developed that measured the activity of human plasma paraoxonase without interference from serum albumin which contributes significantly to the hydrolytic breakdown of paraoxon at the high pH values used in many previous assays. There was an 11-fold variation in paraoxonase activities, and the population distribution was at least bimodal. However, this specific assay did not improve the discrimination between the three genetic classes: (1) homozygotes for the low-activity allele, (2) heterozygotes, and (3) homozygotes for the high-activity allele. Chlorpyrifos oxon--the neurotoxic metabolite of the organophosphorus insecticide chlorpyrifos (Dursban)--was hydrolyzed by the same plasma fraction that hydrolyzed paraoxon. There was only four- to fivefold variability in enzyme activity, and the population distribution was unimodal. Homozygotes for low paraoxonase activity ranged over almost the entire spectrum of chlorpyrifos oxonase activity. Possible differences in susceptibility to chlorpyrifos toxicity therefore are unlikely to be predicted by the paraoxonase genotype alone. The ratio of paraoxonase over that of chlorpyrifos oxonase provided an excellent method for genetic typing of the paraoxonase polymorphism, as did the substitution of phenylacetate for chlorpyrifos as the substrate.

Alleles↗

Pyrethroid insecticides evoke neurotransmitter release from rabbit striatal slices.

The effects of the synthetic pyrethroid insecticide fenvalerate ([R,S]-alpha-cyano-3-phenoxybenzyl[R,S]-2-(4-chlorophenyl)-3- methylbutyrate) on neurotransmitter release in rabbit brain slices were investigated. Fenvalerate evoked a calcium-dependent release of [3H]dopamine and [3H]acetylcholine from rabbit striatal slices that was concentration-dependent and specific for the toxic stereoisomer of the insecticide. The release of [3H]dopamine and [3H]acetylcholine by fenvalerate was modulated by D2 dopamine receptor activation and antagonized completely by the sodium channel blocker, tetrodotoxin. These findings are consistent with an action of fenvalerate on the voltage-dependent sodium channels of the presynaptic membrane resulting in membrane depolarization, and the release of dopamine and acetylcholine by a calcium-dependent exocytotic process. In contrast to results obtained in striatal slices, fenvalerate did not elicit the release of [3H]norepinephrine or [3H]acetylcholine from rabbit hippocampal slices indicative of regional differences in sensitivity to type II pyrethroid actions.

Acetylcholine↗