Metabolism aldrin

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) ... 

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. 

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. 

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). 

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. 

These studies with aldrin and antipyrine are sufficient to document the in vivo oxidative metabolic capability of mussels. Limits of activity have not been established, but they will be explored by further varying dose and the duration of the test period. With these limits established, the influence of environmental stressors such as salinity, and dissolved and/or suspended particulate matter in water on biotransformation will be assessed. If biotransformation processes are affected by these conditions, their measurement may provide results which can be diagnostically used as indicators of environmental quality. 

Biochemical studies with mussel tissue homogenates and microsomal fractions have been conducted using viscera (whole mussel minus adductor muscles), green gland, gill, and mantle. Using aerobic conditions and an NADPH-generating system, the metabolism of aldrin and p-nitroanisole have been observed. 

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. 

The electron transfer system has not been studied in detail in fish, but the metabolism of compounds such as biphenyl (37), benzo(a)pyrene (21) and 2,5-diphenyloxazole (38) by fish liver microsomes has been shown to require oxygen and NADPH generating system. The metabolism of BP (21), 2,5-diphenyloxazole (Ahokas, unpublished observation) and aldrin (27.) by fish liver microsomal enzyme system is inhibited strongly by carbon monoxide. This information and the fact that cytochrome P-1+50, as well as NADPH cytochrome c reductase system are present in fish, suggest strongly that fish have a cytochrome P-1+50 mediated monooxygenase system which is very similar to that described in mammals. 

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... 

This epoxidation of AFB has been associated with aldrin epoxidase (AE) activity in trout (30). As with other epoxide carcinogens, OAFB may be a substrate 7or epoxide metabolizing enzyme systems such as epoxide hydrase (EH) (EC4.2.1.63) and glutathione-S-epoxide transferase (GTr) (EC4.4.1.7) found in mammals and fish (31, 32, 33, 34). AFB also undergoes a variety of other reactions, generally to less toxic metabolites depending on the species of animal involved (35, 36). The primary AFB metabolite in rainbow trout has been shown to be a reduced form of AFB, aflatoxicol (AFL) (24). 

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. 

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. ... 

As already mentioned, the pharmacological activity of certain drugs is lengthened in the female rat, and also the toxicity of certain compounds may be increased. Procaine is hydrolyzed more in male rats (chap. 4, Fig. 43), with consequently a lower toxicity in the sex, whereas the insecticides aldrin and heptachlor are metabolized more rapidly to the more toxic epoxides in males and are therefore less toxic to females (Fig. 5.16). 

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. 

Dieldrin and aldrin were first synthesized in 1948 and they were commercially manufactured as pesticides in 1950 (WHO, 1989). Technical grade aldrin contains 90% l,2,3,4,10,10-hexachloro-l,4,4a,5,8,8a-hexahydro-l,4-endo,exo-5,8-dimethanonaphthalene (HHDN). Technical-grade dieldrin contains 85% l,2,3,4,10,10-hexachloro-6,7-epoxy-l,4,4a,5,6,7,8,8a-octahy-dro-l,4-endo,exo-5,8-dimethanonaphthalene (HEOD). Dieldrin can be synthesized from aldrin (WHO, 1989). As aldrin is readily metabolized into dieldrin by both plants and animals, aldrin residues are only found in trace amounts in plants and animals, if at all (WHO, 1989). 

Tissues such as fat, blood or liver can be examined for residues of the more stable chlorinated hydrocarbon pesticides. In most cases these tissues are available as a result of elective survery, autopsy or biopsy. Exposure to DDT results in some storage of the parent compound in body fat. A large portion, however, is metabolized and stored as DDE (jJ). Aldrin and hepta-chlor are similarly transformed and stored as dieldrin and hepta-chlor epoxide. Levels of the urinary metabolite DDA have been used to assess exposure or body burden of DDT (10, 11, 12). Hexachlorobenzene and the various isomers of hexachlorocyclo-hexane are stored in fat as the parent compound but a small... 

In 1957 I devis jl the first syndeses of L 0 J isodr in and lendrin (26). f C aldrin and [ c3 dieldrin were later made at the Radiochemical Centre at Amersham, so it was possible to compare the fate of all these compounds in S- and R- houseflies. The well known epoxidation reaction occurred equally well in both strains but there appeared to be no other significant metabolism or any obvious differences to account for the resistance (27). 

Substrate specificity is reflected in that each CYP isozyme requires different molecular features of its substrates. Thus, CYP2E metabolizes substrates with an alcohol or keto moiety. For CACs, CYP1A1, CYP1A2 and CYP2B are the most important isozymes. CYP1A metabolizes mostly planar substrates like 2,3,7,8-tetrachlorodibenzo-p-dioxin, whereas CYP2B transforms the more globular substrates, e.g. the transformation of the pesticide aldrin into dieldrin. 

Chlorinated Pesticides. The major metabolic degradation pathways for toxaphene in all organisms are probably reductive dechlorination and reductive dehydrochlorination. In some cases, oxidative dechlorination has been observed to result in hydroxy derivatives, acids and ketones.76 Aldrin is transformed into dieldrin in biotic as well as abiotic transformation processes. 

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