Insecticides mammalian toxicity

Pyrethroids from Chiysanthemic Acid. The unsaturated side chains of the aHethrolone alcohol moieties of the natural pyrethrins are readily epoxidized by microsomal oxidases and converted to diols, thus detoxifying the insecticides. Esterification of chrysanthemic acid (9), R = CH3, with substituted ben2yl alcohols produces usehil insecticides barthrin [70-43-9J, 2-chloro-3,4-methylenedioxyben2yl (+)-i7j ,/n7 j -chrysanthemate, and dimethrin [70-38-2] 2,4-dimethylben2yl (+)-i7j ,/n7 j -chrysanthemate. These have alimited spectmm of insecticidal activity but are of very low mammalian toxicity, ie, rat oralLD s >20,000 mg/kg. 

Perthane [72-56-0] l,l-dichloro-2,2-bis-(4-ethyiphenyi)ethane (30) (mp 60—61°C) is a rapidly biodegradable insecticide with very low mammalian toxicity, rat oral LD q 8170 mg/kg. It has been used as a household insecticide. 

Insect Growth Regulators. These compounds (40—45), unlike most conventional insecticides, interfere with biochemical processes that are unique to arthropods eg, molting, ecdysis, and formation of the chitinous exoskeleton. Therefore, they are selective insecticides with very low mammalian toxicity. 

Oxime carbamates are generally applied either directly to the tilled soil or sprayed on crops. One of the advantages of oxime carbamates is their short persistence on plants. They are readily degraded into their metabolites shortly after application. However, some of these metabolites have insecticidal properties even more potent than those of the parent compound. For example, the oxidative product of aldicarb is aldicarb sulfoxide, which is observed to be 10-20 times more active as a cholinesterase inhibitor than aldicarb. Other oxime carbamates (e.g., methomyl) have degradates which show no insecticidal activity, have low to negligible ecotoxicity and mammalian toxicity relative to the parent, and are normally nondetectable in crops. Therefore, the residue definition may include the parent oxime carbamate (e.g., methomyl) or parent and metabolites (e.g., aldicarb and its sulfoxide and sulfone metabolites). The tolerance or maximum residue limit (MRL) of pesticides on any food commodity is based on the highest residue concentration detected on mature crops at harvest or the LOQ of the method submitted for enforcement purposes if no detectable residues are found. For example, the tolerances of methomyl in US food commodities range from 0.1 to 6 mg kg for food items and up to 40 mg kg for feed items. ... 

Trigard 75 WP is a new insecticide with a unique mode of action and a unique triazine structure. It is a solid formulated as a wettable powder and is packaged in water-soluble bags. The active ingredient in Trigard has the common name cyromazine. Cyromazine is a triazine, but, unlike the well-known triazine herbicides, this compound has insecticidal properties and no herbicidal activity. Cyromazine has low mammalian toxicity and low vapor pressure. It is hydrophilic, so dermal penetration is expected to be... 

The establishment of a common mechanism of mammalian toxicity for the pyrethroids is not a straight forward process, as it was for the organophosphorus and carbamate insecticides, due to the occurrence of multiple potential target sites and the varied action of pyrethroids at these sites as reviewed above. In view of... 

Abstract Metofluthrin (commercial name SumiOne, Eminence ) is a novel pyrethroid insecticide developed by Sumitomo Chemical Co., Ltd. Metofluthrin has extremely high insecticidal activity to various pest insects, especially to mosquitoes. In addition, Metofluthrin has relatively high volatility and low mammalian toxicity. Metofluthrin is therefore suitable for use not only in conventional mosquito control formulations such as coils and liquid vaporizers, but also in a variety of novel devices that do not require heating, such as fan vaporizers and paper and resin emanators. Here we describe the insecticidal activity of Metofluthrin mainly against mosquitoes in various formulations in both laboratory and field trials. 

Grain and foodstuffs are constantly attacked by weevils. Fumigation with carbon bisulfide, methyl bromide, and Chlorosol fumigant (a carbon tetrachloride-ethylene dibromide mixture) provides effective control where storage areas are built to handle these materials. Such storage equipment is limited, so there is need for an insecticide with low mammalian toxicity in order to achieve continuous protection by direct application. 

A newer class of insecticides is the pyrethroids. These are synthetic derivatives of pyrethrins, which are natural extracts from chrysanthemums. Pyrethroids have been developed to be more stable (and thus more effective as insecticides) than the pyrethrins, which are particularly instable in light. Pyrethroids are frequently used as broad-spectrum insecticides. They have high insect toxicity, but lower mammalian toxicity than their organophosphate or carbamate counterparts. Pyrethroids are still limited in effectiveness due to their environmental lability, their high cost, and their potential for resistance development. 

This has been particularly evident with the me thyIcarhamate and phosphoramidothioate insecticides where in almost all cases derivatization has resulted in improved mammalian toxicity. Further, in many cases, equal or greater insecticidal activity has also been observed although in some cases insecticidal activity may be substantially reduced. Improvement in mammalian toxicity has been attributed to the delayed factor provided by the derivatizing group, giving the animal the opportunity to metabolize the compound to non-toxic products. 

Synthetic derivatives such as the (S)-bioallethrin 89 or bioresmethrin 90 are known for their high insecticidal activity with low mammalian toxicity, Eq. (33, 34) [123]. 

The discovery in the early years of the 20 century that certain phosphate esters possess mammahan toxicity and insecticidal properties heightened interest in this class of compounds, both in agriculmre and as potential agents in chemical warfare. Parathion became the practical choice as a broad-spectrum insecticide because of its greater stability and lower mammalian toxicity compared to its P=0 analogue, paraoxon . 

Herbicides are designed to kill plants, not animals, and in general have lower mammalian toxicity than insecticides. Most herbicides interfere with plant hormones or enzymes that do not have any direct counterpart in animals. The most serious human health concerns have been related to contaminants of the primary chemical herbicide. There is an enormous amount of animal and some human toxicity data on 2,4-D and 2,4,5-T, but it now appears that much of this toxicity is caused by the contaminant TCDD. Military personnel exposed to Agent Orange, often contaminated with TCDD, reported birth defects, cancers, liver disease, and other illness. These concerns led to improvement in the manufacturing process to reduce TCDD contamination and ultimately to a reduction in use of 2,4-D herbicides. There is also concern that some herbicides may affect wildlife. For example, atrazine, a persistent herbicide, may adversely affect frogs. Persistence of herbicides may also... 

Among the different classes of organic insecticides in use today, the methylcarbamate esters rank at or near the top in acute mammalian toxicity and in many cases the methylcarbamates are as toxic to mammals as they are to insects O). For... 

In virtually all examples given, the derivatives were described as being lower in mammalian toxicity compared to the parent methylcarbamate but generally of equal insecticidal activity. 

These derivatives were described as having strong insecticidal, acaricidal, and netnatocidal activity, along with low mammalian toxicity. 

Hydrolytic reactions. There are numerous different esterases responsible for the hydrolysis of esters and amides, and they occur in most species. However, the activity may vary considerably between species. For example, the insecticide malathion owes its selective toxicity to this difference. In mammals, the major route of metabolism is hydrolysis to the dicarboxylic acid, whereas in insects it is oxidation to malaoxon (Fig. 5.12). Malaoxon is a very potent cholinesterase inhibitor, and its insecticidal action is probably due to this property. The hydrolysis product has a low mammalian toxicity (see chap. 7). 

Heptachlor [76-44-8] or l,4,5,6,7,8,8-heptachloro-3, 4,7,7 -tetrahydro-4,7-methano-lff-indene (33) (mp 95°C, vp 0.04 Pa at 25°C), is soluble in water to 56 //g/L. It is about 3—5 times more active than chlordane as an insecticide. The rat LD5Qs are 100, 162 (oral) and 195,250 (dermal) mg/kg. Heptachlor is oxidized readily to heptachlor epoxide [1024-57-3] (mp 159°C), rat oral LD5Q 47 mg/kg, which is an important and highly persistent environmental pollutant. Hydrogenation of heptachlor produces p-dihydroheptachlor [14168-01-5] (mp 135°C), which retains high insecticidal activity with very low mammalian toxicity, rat oral LD50 >5000 mg/kg. 

Malathion [121-75-5], 0,0-dimethyl -(l,2-dicarbethoxy)ethyl phosphorodithioate (60) (bp 156—157°C at 93 Pa, d 1.23, vp 5.2 mPa at 30°C), is soluble in water to 145 mg/L. The rat LDBOs are 1375,1000 (oral) and 4000 (dermal). Malathion readily hydrolyzes in water above pH 7.0 and below pH 5.0. It is one of the most widely used general-purpose insecticides by virtue of its low mammalian toxicity and its good persistence, and is effective for the home garden, household, and against insects of public health importance including flies, mosquitoes, and lice. It is used with protein hydrolysate bait to control fruitflies (Tephritidae). 

The hazards of human poisoning by the parathions have stimulated the development of safer analogues. Two chlorinated derivatives have greatly reduced mammalian toxicities. Dicapthon [2463-84-5], 0,0-dimethyl 0-(2-chloro-4-nitrophenyl) phosphorothioate (63) (mp 53°C), has ratLD5Qs of 400, 330 (oral) and 790,1250 (dermal) mg/kg. Chlorthion [500-20-8], 0,0-dimethyl 0-(3-cliloro-4-nitrophenyl) phosphorothioate (64) (mp 21°C, d 1.437), has rat LD5Qs of 890, 980 (oral) and 4500, 4100 (dermal) mg/kg. These compounds have been used as household insecticides. 

---