Topical LD50 Research Articles

Structure and insecticidal activity of picrotoxinin analogs

Picrotoxinin, a convulsant in mammals, was nontoxic when topically applied on whole house flies. When synergized with piperonyl butoxide, the topical LD 50 of picrotoxinin on house flies was 6.50 μg/g or 260 times less toxic on house flies than the synergized insecticide, carbofuran, a carbamate cholinesterase inhibitor. When perfused on the isolated thoracic ganglion of house fly, picrotoxinin was less potent in producing convulsions than carbofuran; however, when assayed on the desheathed thoracic ganglion, picrotoxin was more potent than carbofuran. This suggested a substantial barrier to picrotoxinin preventing diffusion into the house fly central nervous system. Of several picrotoxinin analogs synthesized the 2-iodo,4-isopropyl, 6-methylenebromidecyclohexane-γ-lactone was the most potent convulsant.

Susceptibility of Four Species of Diabrotica to Insecticides1

Topical LD50, values were determined for 15 insecticides to adult northern corn rootworm, Diabrotica longicornis (Say), southern corn rootworm D. undecimpunctata howardi Barber, western corn rootworm, D. virgifera LeConte, and striped cucumber beetle, Acalymma (=Diabrotica) vittata (F.). All species, collected in Illinois, showed substantial resistance to aldrin and heptachlor but resistance patterns to the carbamates and organophosphates were variable. The southern corn rootworm showed higher resistance to DDT, fensulfothion, fonofos, malathion, and diazinon compared to the other species, The striped cucumber beetle showed higher resistance to malathion than the other species.

Correlation of toxicity and acetylcholinesterase (AChE) inhibition in 2-alkyl substituted 1,3-benzodioxolyl-4 N-methylcarbamates and related compounds

2-Alkyl substituted-1,3-benzodioxolyl-4 and 1,3-benzodioxolyl-5 N-methylcarbamates; 2-methyl substituted indanyl-4 and indanyl-5 N-methylcarbamates; and 2-methyl substituted quinolinyl-8 N-methylcarbamates were examined in this study. Oral toxicity (LD 50) to female mice and topical LD 50 values to the housefly were determined. Main's kinetic constants (affinity, carbamylation, and overall inhibition rate) on acetylcholinesterase (AChE, EC3.1.1.7) were also determined. Good correlations were found between the in vivo toxicity to mice (without synergist) or houseflies (with synergist) and in vitro overall enzyme inhibition rate. Increasing the number or the size of the alkyl substitution (i.e., unsubstituted vs monomethyl, monomethyl vs dimethyl, or dimethyl vs diethyl) increased the toxicity and the overall enzyme inhibition. The increase in the enzyme inhibition by substitution was mainly due to the increase in the affinity of the enzyme-inhibitor complex. It is interpreted that the substituted alkyl groups interact with the anionic or hydrophobic site of the AChE through van der Waal's forces or hydrophobic bonding. The enzyme inhibition and toxicity were maximal when the second ring of these bicyclic compounds was attached in the 2,3-position in relation to the hydroxyl group of the phenyl ring.

Chlorcyclizine and SKF 525A Effects on Parathion Toxicity and Midgut Tissue Structure in Alkali Bees, Nomia melanderi1

The organophosphate insecticides, parathion, monocrotophos, dicrotophos, and Gardona® [2-chloro-1-(2,4,5-trichlorophenyl) vinyl dimethylphosphate], were highly toxic to adult alkali bees, Nomia melanderi Cockerell. The topical LD 50 values for these ranged from 0.83 (monocrotophos) to 2.69 (Gardona) micrograms per gram of bees. Two carbamate insecticides, however, were much less toxic. The LD 50 values for these ranged from 47.90 [Landrin® (4:1 mixture of 3,4,5– and 2,3,5–isomers of trimethylphenyl methylcarbamate)] to 86.37 (carbaryl) micrograms per gram of bees. The alkali bees were fed and topically treated with the drugs SKF 525A (2-diethylaminoethyl 2,2-diphenyl pentanoate) and chlorcyclizine [ N -methyl- N -(4-chlorbenzhydryl) piperazine] to determine if they could protect the bees from parathion. Chlorcyclizine made the bees generally more susceptible, whereas SKF 525A either had no effect or protected one sex without protecting the other. The protective effects with SKF 525A were small as well as inconsistent and therefore such drug treatments probably have little potential for protecting alkali bees from parathion in the field. Electron micrographs of the gut tissue of the insects showed that chlorcyclizine and SKF 525A had significant effects upon the cellular ultrastructure. Some of these effects were similar to those observed in other insects treated with different drugs in which detoxication measurements or biological assay tests had shown that the drug had limited potential for induction of protective detoxication mechanisms.

Evaluation of cholinesterases in strains of Heliothis virescens with widely differing responses to insecticides.

Topical LD-50 values for 8 insecticides were determined for 3 strains of tobacco budworms collected from Texas, Louisiana, and North Carolina. The strains most different in response to organophosphate insecticides (North Carolina-susceptible and Texas-resistant) were examined for possible differences in esterase activity using both whole body and nerve cord homogenates. Activity of esterases to 6 substrates did not indicate differences great enough to account for a major mechanism of resistance. Neither could differences in cholinesterase inhibition (PI50 values using acetylthiocholine as substrate) account for resistance.

Selective Toxicity of Carbophenothion and Trichlorfon to the Honey Bee1 and the Alfalfa Leafcutting Bee23

Selective toxicity of carbophenothion and trichlorfon to the honey bee, A pis mellifera L., and the alfalfa leafcutting bee, Megachile rotllndata F., was established in dosage-mortality studies using the topical drop method. LD30 values of trichlorfon for the honey bee, the male leafcutting bee, and the female leafcutting bee were 28.5, 250.0, and 515.0 μg/g, respectively. LD30 values for carbophenothion were 12.6, 4.3, and 6.2 μg/g. Trichlorfon was 18–34 times more toxic to the honey bee than to the female leafcutter at LD30 and LD95. Carbophenothion was 2–3 times more toxic to the leafcutting bee at both dosage levels. The differential toxicity of trichlorfon may be related to pH of the body fluid, which was 6.0 for the honey bee and 6.8 for the leafcutting bee. Trichlorfon is known to be highly unstable at neutral or higher pH levels. Trichlorfon at the topical LD50 levels was a stronger acetylcholinesterase inhibitor than carbophcnothion to both test insects.

Toxicity of certain insecticide standards against the southern armyworm.

Thirty-one insecticide standards in commercial use were tested topically against 4th instars of Spodoptera eridania (Cramer). The toxicity trend among organophosphorus compounds was phosphates. > phosphorothionates > phosphorothiolates > phosphorodithioates. However, topical LD50 values for monocrotophos and chlorpyrifos were 93.52 and 5.68 µg/g, respectively. The same 2 compounds have LC50 values of 11.3 and 11.0 ppm when tested, using the leaf-spray method. Monocrotophos apparently penetrates the cuticle more slowly than does chlorpyrifos.

Chemosterilant effects of metepa and tretamine on larvae, pupae, and adults of Drosophila melanogaster.

Neither metepa nor tretamine when used in the larval food completely prevented larval development and pupal formation in drosophila melanogaster Meigen. When pupae were immersed in a solution of either chemical, the percent of adults that emerged was dependent on concentration and length of the dipping period. Adult females treated orally with 1.0% metepa showed 96.5% sterility and with 1.0% tretamine, 96.8% sterility. Metepa failed to induce complete sterility when orally treated females were paired with untreated males. To obtain complete sterility females required 1.5 times the amount of tretamine applied topically as treated males. Complete sterility could be obtained when metepa was applied topically in equal amounts to both sexes. Males treated with either chemosterilant and then mated with different ages of unfertilized females showed effective sterilization, regardless of what age they were mated or treated. The topical LD50 for metepa was 10.15 µg/male fly, at which concentration the sterility was 99.99%. The LD50 tretamine was 3.9 µg/male fly resulting in a sterility of 99.99%.

Mechanisms of Insecticide Resistance in Musca domestica: Carboxylesterase and Degradative Enzymes1

The topical and injection LD50 values for diazinon, in vitro carboxylesterase (3.1.1.1) activity (methyl butyrate), and in vitro degradation of diazoxon (diethyl 2-isopropyl-6-methyl-4-pyrimidinyl phosphate) were established, respectively, for a susceptible and 7 resistant strains of Musca domestica L. All resistant strains were resistant to diazinon administered by either route and exhibited lower carboxylesterase activity and greater diazoxon-degrading capability than the susceptible strain. Carboxylesterase activity was inversely correlated with resistance values among the less resistant strains, but the internal protective mechanism associated with carboxylesterase decline was limited in its effect which fact indicated the presence of other internal resistance factors in the most highly resistant strains. One strain, selected with DDT-synergist and highly resistant to diazinon, did not completely conform to the inverse relationship. Carboxylesterase activity was correlated inversely with the capacity to degrade diazoxon among all resistant strains (with 1 exception). However, the total resistance of the most highly resistant flies was not completely explained on the basis of toxicant breakdown, which provided more evidence for the presence of an additional internal protective mechanism. In an earlier report, cuticular penetration was shown to be a significant factor in resistant flies, and in the present study its effect was evident. All of these findings are discussed in relation to earlier experiments with some of the same strains and with other resistant strains. It is concluded that total diazinon resistance in these house flies is the product of several protective mechanisms that act in an integrated manner.

The synergistic ratio of carbaryl with piperonyl butoxide as an indicator of the distribution of multifunction oxidases in the insecta.

The synergistic ratio of carbaryl with piperonyl butoxide has been evaluated from LD50values with 54 species of insects from 8 orders and 37 families. The topical LD50 for carbaryl in µg per g ranged from 0.3 for the red milkweed beetle, Tetraopes tetrophthalmus (Forster), to 4000 for Sarcophaga bullata Parker and the synergistic ratio from 1.5 for the convergent lady beetle, Hippodamia convergens Guerin Meneville, to 400 for S. bullata . The wide ranges of susceptibility to carbaryl and of synergistic ratio are interpreted as response to differences in the activities of multifunction oxidase detoxication which is inhibited by piperonyl butoxide. It is evident that these factors are highly variable in the Insecta.

Physiological factors influencing the toxicity of carbamate insecticides to insects.

The toxicity of 6 carbamate insecticides, alone and synergized with several methylenedioxyphenyl synergists, has been evaluated against the housefly, Musca domestica L., the honey bee, Apis mellijera L.; and the German cockroach, Blattella germanica (L.). The topical LD50 values of the carbamates were markedly affected by the age and sex of the house fly and cockroach, but the differences were almost completely abolished by synergism with piperonyl butoxide, sesamex, and methylene-dioxynaphthalene. The variations in the toxicity of the carbamates to the house fly and German cockroach were well correlated with the titre of soluble phenolases in the various life stages, sexes, and in adults of different ages. However, the honey bee is extremely susceptible to these carbamate insecticides, and little synergism occurs with the methylenedioxyphenyl compounds. In the honey bee only a very low titre of phenolase could be demonstrated.

Selective Toxicity of Four O-(methylcarbomyl) Oximes to the House Fly and the Honey Bee1

Selectivity between the house fly, Musca domestica L., and the honey bee, Apis mellifera L., was investigated with 4 O -(methylcarbamoyl) oxime compounds including Temik® (2-methyl-2-(methylthio) proprionaldehyde O -(methylcarbamoyl) oxime), UC 28982 (2-norbornanone O-(methylcarbamoyl) oxime), DC 27609 ( exo -3-chloro-2-norborna-none O -(methylcarbomoyl) oxime), and Tranid®, (exo-5-chloro-6-oxo- endo -2-norbornanecarbonitrile O -(methylcar-bamoyl) oxime. On the basis of both topical drop and oral LD50’s and LD05’s, Temik, UC 28982, UC 27609, and Tranid were significantly more toxic to the honey bee than to the house fly, indicating an unfavorable selectivity for the bee. With topical drop application, selectivity ratios (house fly/honey bee) ranged from 16.5 with Tranid to 2.5 with Temik. The compounds ranked: Tranid>UC 27609>UC 28982>Temik. With oral administration, selectivity ratios varied from 7.9 with DC 27609 to 2.5 with Tumid. At LD50 the compounds ranked DC 27609>Tranid>UC 28982> Temik; at LD95, DC 27609>DC 28982>Tranid>Temik. Temik was the most toxic material tested based on both oral and topical drop studies. Tranid was the least toxic material tested, and demonstrated little, if any insecticidal action. DC 27609 and 28982 were intermediate. Temik, DC 28982, DC 27609, and Tranid were more toxic by the oral route than by topical drop application to both test insects.