Metabolism dieldrin

A drin and Dieldrin Metabolism.— The in vivo metabolism of the chlorinated alicyclic insecticides, aldrin and dieldrin, has been measured. Fish were exposed to l c-labelled aldrin or dieldrin for 6 hours. The metabolism of each compound was monitored by thin layer chromatography of hexane and chloroform-methanol extracts of liver homogenates, followed by liquid scintillation counting of the spots (5,15,16). 

Figure 3. Photodieldrin, found by Matsumura et al. (12) as a product of dieldrin metabolism by microorganisms from several...

As mentioned earlier (Figure 5.5), aldrin and heptachlor are rapidly metabolized to their respective epoxides (i.e., dieldrin and heptachlor epoxide) by most vertebrate species. These two stable toxic compounds are the most important residues of the three insecticides found in terrestrial or aquatic food chains. In soils and sediments, aldrin and heptachlor are epoxidized relatively slowly and, in contrast to the situation in biota, may reach significant levels (note, however, the difference between aldrin and dieldrin half-lives in soil shown in Table 5.8). The important point is that, after entering the food chain, they are quickly converted to their epoxides, which become the dominant residues. 

Resistance to DDT has been developed in many insect species. Although there are some cases of metabolic resistance (e.g., strains high in DDT dehydrochlorinase activity), particular interest has been focused on kdr and super kdr mechanisms based upon aberrant forms of the sodium channel—the principal target for DDT. There are many examples of insects developing resistance to dieldrin. The best-known mechanism is the production of mutant forms of the target site (GABA receptor), which are insensitive to the insecticide. 

Chipman, J.K. and Walker, C.H. (1979). The metabolism of dieldrin and two of its analogues the relationship between rates of microsomal metabolism and rates of excretion of metabolites in the male rat. Biochemal Pharmacology 28, 1337-1345. 

Korte, F. and Arent, H. (1965). Metabolism of Insecticides IX Isolation and identification of dieldrin metabolites from urine of rabbits after oral administration of C-14 dieldrin. Life Sciences 4, 2017-2026. 

Patil KC, Matsumura F, Boush GM. 1972. Metabolic transformation of DDT, dieldrin, aldrin, and endrin by marine microorganisms. Environ Sci Technol 6 629-632. 

The biotransformation systems involved in insecticide metabolism have been studied in the R and S populations to determine any differences which might be potential contributory factors to or results of insecticide resistance. In addition, the possibility of mixed-function oxidase induction has been investigated. Specifically, the studies have encompassed a seasonal study of microsomal mixed-function oxidase (mfo) components, and studies of aldrin, dieldrin and DDT metabolism. 

No metabolites of dieldrin were observed in organic extracts of livers of either S or R fish exposed to 30 yg/l 4c-dieldrin for 6 hr (5j (Table IX). A small percentage of the radioactivity was found in the water-soluble fraction. Therefore, it appears that little metabolism of dieldrin occurs in mosquitofish livers in either population. In addition, the degree of intoxication in S fish did not appear to affect the metabolism either qualitatively or quantitatively. 

Hepatic mixed-function oxidase activities demonstrated seasonal trends, with higher specific activities in the cold weather months in both populations with few differences in enzyme activities or cytochrome levels between the two populations. Metabolism of aldrin, dieldrin and DDT was similar between the two populations. R fish have larger relative liver size and, therefore, a greater potential for xenobiotic metabolism. However, biotransformation appears to be of minor importance in chlorinated alicyclic insecticide resistance in mosquitofish barriers to penetration appear to be of greater importance and an implied target site insensitivity appears to be the most important factor in resistance. 

Aldrin and dieldrin have similar physical and chemical properties, and hence exhibit similar behavior in animals and during analysis. The following relationship is used as an indicator of oxidative metabolic capability, and it is termed the aldrin metabolic index (AMI) ... 

During a 30 minute incubation period, low levels of aldrin epoxidation (30-150 picomoles dieldrin/mg protein) were measured compared to those observed using enzyme sources such as aquatic Trichoptera Limnephilus sp. gut homogenates (1 pmole/mg protein 28) or rat liver homogenates (3000 pmoles/mg protein unpublished) under similar incubation conditions. Anisole metabolism based upon substrate disappearance was detectable but less than 5 picomoles/mg protein were transformed during the incubation period. Characteristics of the enzyme system are incompletely described owing to the low and variable levels of activity which have been obtained. 

Experiments in this study, done exclusively with midge larvae, include 1) 24-hr toxicity data for representative insecticides, with and without synergists 2) in vivo absorptive uptake and metabolic studies of aldrin and dieldrin, with and without piperonyl butoxide (PBO) 3) body depuration rate (loss to water) for dieldrin 4) determination of optimal in vitro... 

Heptachlor is formed through the metabolism of chlordane. Heptachlor epoxide is formed through the epoxidation of heptachlor and has been shown to be a cosubstrate of the same enzyme responsible for the epoxidation of aldrin to dieldrin (Gillett and Chan 1968). Heptachlor epoxide is considered more toxic than its parent compound and, like heptachlor, is primarily stored in adipose tissue (Barquet et al. 1981 Burns 1974 Greer etal. 1980 Harradine and McDougall 1986). 

Since the metabolized form of heptachlor, heptachlor epoxide, is the most toxic, it may be possible to reduce the toxic effects of heptachlor by inhibiting the enzyme catalyzing this conversion. This is the same enzyme that catalyzes the epoxidation of aldrin to dieldrin (Gillett and Chan 1968). Further research into the specificity of this enzyme, drugs that could inhibit the enzyme, and any side effects of these drugs could help to determine the feasibility of such a treatment strategy. 

Neudorf, S. and Khan, M.A.Q. Pick up and metabolism of DDT, dieldrin, and photodieldrin by a freshwater alga Ankistrodesmus amalloide and a microcrustacean (Daphnia pule, Bull. Environ. Contain. Toxicol, 13(4) 443-450,1975. 

Chaturvedi (1993) also examined the effect of mixtures of 10 pesticides (alachlor, aldrin, atrazine, 2,4-D, DDT, dieldrin, endosulfan, lindane, parathion, and toxaphene) administered by oral intubations or by drinking water on the xenobiotic-metabolizing enzymes in male mice. He concluded, The pesticide mixtures have the capability to induce the xenobiotic-metabolizing enzymes, which possibly would not have been observed with individual pesticides at the doses and experimental conditions used in the study. ... 

Once aldrin is absorbed, it is rapidly metabolized to dieldrin. In a study of five workers exposed to concentrations of aldrin of up to 8.5mg/m who had suffered convulsive seizures or myoclonic limb movements, the probable concentration of dieldrin in the blood during intoxication ranged from 16 to 62 pg/lOOg of blood in healthy workers the concentration of dieldrin ranged up to 22 pg/lOOg of blood. ... 

Aliphatic Epoxidation. Many aliphatic and alicylcic compounds containing unsaturated carbon atoms are thought to be metabolized to epoxide intermediates (Figure 7.4). In the case of aldrin the product, dieldrin, is an extremely stable epoxide and represents the principle residue found in animals exposed to aldrin. Epoxide formation in the case of aflatoxin is believed to be the final step in formation of the ultimate carcinogenic species and is, therefore, an activation reaction. 

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