Biodegradation of Aldrin and Dieldrin by the White-Rot Fungus Pleurotus ostreatus.

Aldrin and its metabolite dieldrin are persistent organic pollutants that contaminate soil in many parts of the world. Given the potential hazards associated with these pollutants, an efficient degradation method is required. In this study, we investigated the ability of Pleurotus ostreatus to transform aldrin as well as dieldrin in pure liquid cultures. This fungus completely eliminated aldrin in potato dextrose broth (PDB) medium during a 14-day incubation period. Dieldrin was detected as the main metabolite, and 9-hydroxylaldrin and 9-hydroxyldieldrin were less abundant metabolites. The proposed route of aldrin biotransformation is initial metabolism by epoxidation, followed by hydroxylation. The fungus was also capable of degrading dieldrin, a recalcitrant metabolite of aldrin. Approximately 3, 9, and 18% of dieldrin were eliminated by P. ostreatus in low-nitrogen, high-nitrogen, and PDB media, respectively, during a 14-day incubation period. 9-Dihydroxydieldrin was detected as a metabolite in the PDB culture, suggesting that the hydroxylation reaction occurred in the epoxide ring. These results indicate that P. ostreatus has potential applications in the transformation of aldrin as well as dieldrin.

Organochlorine Pesticides Residues in Human Breast Milk from the Middle Governorates in Jordan in 2013/2014.

One hundred samples of mother breast milk were gathered from six middle governorates and districts in Jordan in 2013/2014 to monitor Organochlorine pesticides pollutants. The results showed clearly that banned organochlorine pesticides are still detected in the monitored samples in low concentration despite banning of these persistent pollutants in Jordan since 36 years ago. However, the results indicated that 1% of the contaminated samples contained ß-HCH, 5% γ-HCH, 3% p,p'-DDD, 2% heptachlor, 45% p,p'-DDE and 3% p,p'-DDT. In addition, these monitored samples had no residues of aldrin, dieldrin, α-endosulfan, ß-endosulfan, HCB, o,p'-DD, o,p'-DDT and o,p'-DDE. In conclusion, there was a decline in the residues of Organochlorine pesticides, particularly DDT group members.

Aldrin epoxidation in flathead mullet (Mugil cephalus): possible involvement of CYP1A and CYP3A.

The primary objective of this study was to determine specific cytochrome P450 isozyme(s) involved in the metabolism of aldrin to its toxic metabolite dieldrin in flathead mullet (Mugil cephalus) liver microsomes. To identify the cytochrome P450 isozyme responsible for the aldrin metabolism in mullet liver, the effects of mammalian-specific cytochrome P450 inhibitors and substrates were determined in the epoxidation reaction of aldrin. CYP3A-related inhibitors, ketoconazole, SKF-525A, and cimetidine, inhibited the metabolism of aldrin. The contribution of CYP1A to the aldrin metabolism was shown by the inhibition of 7-ethoxyresorufin-O-deethylase activity in the presence of aldrin. The results indicate that CY1A and CYP3A are the cytochrome P450s involved in aldrin epoxidase activity in mullet. In addition, the suitability of aldrin epoxidase activity for monitoring of environmental pollution was also assessed in the fish samples caught from four different locations of the West Black Sea coast of Turkey.

Organochlorine pesticides in green mussel, Perna viridis, from the Cienfuegos Bay, Cuba.

The green mussel, Perna viridis, was used to measure bioaccumulated levels of organochlorine pesticides in the marine environment of Cuba. Samples were collected in the Cienfuegos Bay between January and December 2010. The organochlorine pesticides (i.e. DDT, Dieldrin, Chlordane, Endosulfan, HCB, Aldrin, Heptachlor and Lindane) were quantified by gas chromatography. The sum of all organochlorine pesticides in P. viridis was 6.31 ng g(-1). The concentration ranged from 3.53 to 4.42 ng g(-1) dry weight (dw) for DDTs (i.e. sum of pp' DDT, pp' DDD, op' DDE and pp' DDE); 1.7-1.9 ng g(-1) dw for Dieldrin; 0.17-0.20 ng g(-1) dw for Chlordanes; 0.14-0.16 ng g(-1) dw for Endosulfan; 0.11-0.17 ng g(-1) dw for HCB; 0.07-0.11 ng g(-1) dw for Aldrin; 0.046-0.054 ng g(-1) dw for Heptachlor and 0.035-0.039 ng g(-1) dw for Lindane. These levels can be considered as low when compared to reported values from similar studies conducted elsewhere in the world. The concentrations of all organochlorines residues detected in this study fell below the EU Maximum Residue Limits.

Involvement of CYP2 and mitochondrial clan P450s of Helicoverpa armigera in xenobiotic metabolism.

Insect CYP2 and mitochondrial clan P450s are relatively conserved genes encoding enzymes generally thought to be involved in biosynthesis or metabolism of endobiotics. However, emerging evidence argues they have potential roles in chemical defense as well, but their actual detoxification functions remain largely unknown. Here, we focused on the full complement of 8 CYP2 and 10 mitochondrial P450s in the generalist herbivore, Helicoverpa armigera. Their varied spatiotemporal expression profiles were analyzed and reflected their specific functions. For functional study of the mitochondrial clan P450s, the redox partners, adrenodoxin reductase (AdR) and adrenodoxin (Adx), were identified from genomes of eight insects and an efficient in vitro electron transfer system of mitochondrial P450 was established by co-expression with Adx and AdR of H. armigera. All CYP2 clan P450s and 8 mitochondrial P450s were successfully expressed in Sf9 cells and compared functionally. In vitro metabolism assays showed that two CYP2 clan P450s (CYP305B1 and CYP18A1) and CYP333B3 (mito clan) could epoxidize aldrin to dieldrin, while CYP305B1 and CYP339A1 (mito clan) have limited but significant hydroxylation capacities to esfenvalerate. CYP303A1 of the CYP2 clan exhibits high metabolic efficiency to 2-tridecanone. Screening the xenobiotic metabolism competence of CYP2 and mitochondrial clan P450s not only provides new insights on insect chemical defense but also can give indications on their physiological functions in H. armigera and other insects.

An evaluation of the levels of organochlorine compounds (OCPs and PCBs) in cultured freshwater and wild sea fish eggs as an exposure biomarker for environmental contamination.

In this study, the eggs of 30 wild Black Sea whiting (Merlangius merlangus euxinus, Nordmann, 1840) and 30 farmed freshwater rainbow trout (Oncorhynchus mykiss, Walbaum, 1792) collected from Samsun Province in Turkey were analyzed to determine the level of contamination by nine organochlorine pesticides (OCPs), namely α-hexachlorocyclohexane (α-HCH), ß-HCH, γ-HCH (lindane), hexachlorobenzene (HCB), aldrin, 2,4'-dichlorodiphenyltrichloroethane (DDT), 4,4'-DDT, 2,4'-dichlorodiphenyldichloroethylene (DDE), 4,4'-DDE, and 15 polychlorinated biphenyls (PCBs) (PCB-28, -70, -74, -81, -99, -101, -118, -138, -153, -156, -170, -180, -183, -187, and -208), and their potential use as biomarkers to monitor levels of environmental contamination. OCPs and PCBs in the fat of fish eggs were extracted cryogenically and their concentrations were determined with a gas chromatography-electron capture detector (GC-ECD). The whiting eggs showed high OCP and PCB levels compared to the rainbow trout eggs. The median ∑ DDT values for whiting and rainbow trout eggs were 1601.62 ng g-1 fat (range 824.87-5049.81) and 406.49 ng g-1 fat (range 199.88-588.82); median ∑Indicator PCBs were 1264.24 ng g-1 fat (range 520.05-6140.32) and 82.11 ng g-1 fat (range 2.85-215.97); and median ∑ HCHs were 155.66 ng g-1 fat (range 35.45-330.40) and 13.48 ng g-1 fat (range 4.44-66.44), respectively. In the whiting eggs, the ∑Indicator PCB level was above the maximum residue limit (MRL) of 200 ng g-1 fat stated in the European Commission Regulation (EC) and Turkish Food Codex (TFC). In addition, there was a significant difference between the contamination levels of the eggs of the two species. In conclusion, it appears that fish eggs can serve as a valuable biomarker for the level of contamination of persistent organochlorine contaminants in different aquatic environments.

Aldrin epoxidation and dihydroisodrin hydroxylation as probes of in vivo and in vitro oxidative metabolic capability of some caterpillars.

Comparative biochemical studies are productive means to study factors that limit both beneficial and harmful effects of chemicals. Reactions such as aldrin epoxidation and dihydroisodrin hydroxylation are valuable assays of oxidative metabolism in scientific studies of chemical biology in insects, subhuman primates and other living things. The tissue distribution of activity in caterpillars may have functional significance. Localization of relatively high concentrations of these cytochrome P450 monooxygenases in gut tissue of lepidoptera may represent an important means to minimize absorption of lipophilic foreign chemicals in food. Some polychlorocycloalkanes permit in vivo and in vitro studies owing to their stability, acceptable toxicity and relatively simple pattern of metabolism. In vivo studies to assess the significance of in vitro findings are feasible with substrates such as aldrin, dihydroisodrin (DHI) and oxidative methylenedioxyphenyl inhibitors such as piperonyl butoxide (PBO) or carbon monoxide. Biphasic dose-dependent decreased and increased DHI-OH formation resulted from PBO pretreatment by gut, fat body, head and Malpighian tubule homogenates of cutworms and gut and fat body (the only tissues tested) of cabbage looper Trichplusia ni (Hübner) and black cutworm Agrotis ipsilon (Hüfnagel). The biphasic in vivo responses of caterpillars to PBO are a reminder of the complexity of biochemical and physiological responses of organisms coexposed to chemicals that are classified, often glibly, as toxic substances and metabolic inhibitors and inducers. Knowledge of dose and time relationships demands very careful evaluation in living things in the environment.

Phylogenetic and functional characterization of ten P450 genes from the CYP6AE subfamily of Helicoverpa armigera involved in xenobiotic metabolism.

The cotton bollworm, Helicoverpa armigera, is a generalist herbivore widely distributed over the world and is a major lepidopteran pest on cotton. Studies, especially from Asia, show that it relies on cytochrome P450 monooxygenases with broad substrate specificities to protect itself from pesticides. The number of P450s may have expanded in the processes of coping with the wide diversity of phytochemicals that the insect encounters among its numerous host plants. In order to examine the metabolic capabilities of these P450s, we focused here on all ten P450s of the Helicoverpa armigera CYP6AE subfamily, which can be easily induced by plant toxins and pyrethroids. These P450s, along with cytochrome P450 reductase, were heterologously expressed in insect cells and compared functionally. In vitro metabolism showed that all CYP6AE subfamily members can convert esfenvalerate to 4'-hydroxyesfenvalerate efficiently except CYP6AE20. In contrast, none of the recombinant CYP6AE enzymes could metabolise gossypol under our experimental conditions. Epoxidation capabilities were observed in the CYP6AE subfamily, aldrin can be converted to dieldrin at rates up to 0.45 ±â€¯0.04 pmol/min/pmol P450. Seven P450s in this subfamily can metabolise imidacloprid, but with lower efficiency than Bemisia tabaci CYP6CM1vQ. CYP6AE20 had virtually no metabolic competence to these four compounds but could metabolise several model fluorogenic substrates. These results showed the broad substrate spectrum of H. armigera CYP6AE P450s and suggest a limited role of gossypol upon the evolution of H. armigera CYP6AE genes.

Benzo[a]pyrene- and aldrin-metabolizing activities in cultured human and rat hepatoma cell lines.

Five established hepatoma cell lines, 1 of rat origin and 4 derived from human liver carcinoma, were compared for their capacity to perform metabolic activation of one polycyclic hydrocarbon, benzo[a]pyrene (BP), and one cyclodiene chlorinated insecticide, aldrin. The results of these investigations indicated both species and individual differences among these cell lines. Aldrin was found to be converted into dieldrin much more efficiently by the rat hepatoma cell line than by any human cell lines, whereas 2 human lines displayed the highest BP-metabolizing activity whether measured as the amounts of water-soluble products or estimated by cytotoxic cell-mediated assays. Results also showed that one particular human cell line can replace, advantageously, V79 hamster cells as target in a cell-mediated assay owing to its incapability to metabolize BP and its high sensitivity to BP metabolites.

Relationship between oxidative metabolism of 2-acetylaminofluorene, debrisoquine, bufuralol, and aldrin in human liver microsomes.

The capacity of human liver microsomes from 28 individuals to metabolize debrisoquine and bufuralol, two drugs oxidized polymorphically in humans, as well as the carcinogen 2-acetylaminofluorene (AAF), was determined. In addition, the cytochrome P-450 content and the capacity of these microsomes to carry out the epoxidation of aldrin were measured. Interindividual differences in debrisoquine 4-hydroxylation, bufuralol 1-hydroxylation, and aldrin epoxidation were 12-, 20-, and 2.4-fold, respectively. The metabolism of debrisoquine was not correlated with cytochrome P-450 content (r = 0.26), whereas both the metabolism of bufuralol (r = 0.45; r2 = 0.20) and the epoxidation of aldrin (r = 0.72; r2 = 0.52) were correlated. Rates of debrisoquine and bufuralol metabolism were significantly correlated (r = 0.73), whereas only weak correlations existed between debrisoquine:aldrin (r = 0.49) and bufuralol:aldrin (r = 0.51). Because biphasic kinetics have been observed in human liver microsomes for the 7- and 5-hydroxylation of AAF, two concentrations of this substrate were used. The disappearance of AAF at either 0.37 or 50 microM was not correlated with debrisoquine, bufuralol, or aldrin metabolism. Similarly, at 0.37 microM AAF, no correlation existed between the formation of N-, 1-, 3-, 5-, 7-, and 9-hydroxylation products of AAF and debrisoquine, bufuralol, or aldrin metabolism. At 50 microM AAF, only the 7-hydroxylation of this substrate correlated with bufuralol metabolism (r = 0.47). This lack of, or weak correlation between pathways leading to metabolic activation (N-hydroxylation) or detoxication (C-hydroxylation) of the carcinogen AAF and debrisoquine, bufuralol, and aldrin metabolism strongly suggests that different forms of cytochrome P-450 are involved in these pathways. In contrast, exceptionally high correlations (r greater than 0.94) existed between N-OH-AAF:1-OH-AAF. N-OH-AAF:7-OH-AAF, and 7-OH-AAF:1-OH-AAF at the low concentration of AAF, and imply that similar forms of cytochrome P-450 produce these metabolites. However, at 50 microM AAF, these correlations are considerably weaker and explain less than 35% of the variance in the data. It is concluded, based on these multiple cross-correlations, that common cytochrome P-450 isoenzymes are involved in the formation of AAF metabolites, while the metabolism of debrisoquine, bufuralol, and aldrin is unrelated to the metabolism of this carcinogen in human liver microsomes.

Inflammatory and cardiometabolic risk on obesity: role of environmental xenoestrogens.

CONTEXT: Some chemicals used in consumer products or manufacturing (eg, plastics, pesticides) have estrogenic activities; these xenoestrogens (XEs) may affect immune responses and have recently emerged as a new risk factors for obesity and cardiovascular disease. However, the extent and impact on health of chronic exposure of the general population to XEs are still unknown. OBJECTIVE: The objective of the study was to investigate the levels of XEs in plasma and adipose tissue (AT) depots in a sample of pre- and postmenopausal obese women undergoing bariatric surgery and their cardiometabolic impact in an obese state. DESIGN AND PARTICIPANTS: We evaluated XE levels in plasma and visceral and subcutaneous AT samples of Portuguese obese (body mass index ≥ 35 kg/m(2)) women undergoing bariatric surgery. Association with metabolic parameters and 10-year cardiovascular disease risk was assessed, according to menopausal status (73 pre- and 48 postmenopausal). Levels of XEs were determined by gas chromatography with electron-capture detection. Anthropometric and biochemical data were collected prior to surgery. Adipocyte size was determined on tissue sections obtained during surgery. RESULTS: Our data show that XEs are pervasive in this obese population. Distribution of individual and concentration of total XEs differed between plasma, visceral AT, and subcutaneous AT, and the pattern of accumulation was different between pre- and postmenopausal women. Significant associations between XE levels and metabolic and inflammatory parameters were found. In premenopausal women, XEs in plasma seem to be a predictor of 10-year cardiovascular disease risk. CONCLUSIONS: Our findings point toward a different distribution of XE between plasma and AT in pre- and postmenopausal women, and reveal the association between XEs on the development of metabolic abnormalities in obese premenopausal women.

Aldrin epoxidase and dimethylhydrazine demethylase activities in tumorous and non-tumorous tissue of the human colon and rectum.

High activities of aldrin epoxidase and dimethylhydrazine demethylase were found in human colon and rectum mucosa, the first being as high as in human liver biopsy specimens. Comparisons between tumorous (adenocarcinomas) and non-tumorous tissues of the same individuals revealed loss of activities in tumorous specimens. The presence of epoxidizing enzymes and demethylation of the organ-specific colon carcinogen dimethylhydrazine (DMH) in the intestinal muscosa of tumor-bearing patients implicate them with chemical carcinogenesis also in humans.

Rat liver cytochrome P-450 isozymes as catalysts of aldrin epoxidation in reconstituted monooxygenase systems and microsomes.

To explore which rat liver cytochrome P-450 species are involved in aldrin epoxidation, we have studied the catalytic activities of a series of cytochrome P-450 isozymes purified from untreated and inducer-treated Sprague-Dawley rats. Of ten cytochrome P-450 forms analyzed, seven isozymes, listed in order of decreasing activity, catalyzed aldrin epoxidation: P-450UT-A, P-450PB-C, P-450UT-H, P-450PB-B, P-450PCN-E, P-450UT-F, and P-450PB-D. P-450UT-I, P-450BNF-B, and P-450ISF-G were not very active at all. A novel aldrin metabolite, endo-dieldrin, was formed by cytochrome P-450UT-F in a 6-fold excess over dieldrin, which is the exo-isomer. The activity of aldrin epoxidase furthermore was assayed in liver microsomes from Sprague-Dawley rats of diverse physiological status and after pretreatment with various inducers resulting in a peculiar pattern of cytochrome P-450 isozymes. Untreated animals, at an age of 3 weeks, showed similar enzyme activities in both genders. During maturation, the activity of males increased by 3-fold, while the activity in females did not significantly change during this period. Pretreatment with pregnenolone-16-alpha-carbonitrile or dexamethasone strongly increased the activity in females. Pretreatment with dexamethasone did not increase the activity of males. A 50% depression of epoxidase activity was noted for males pretreated with 5,6-benzoflavone. Phenobarbital pretreatment increased the activity of females by 12-fold and of males by 2-fold. Males responded to pretreatment with polychlorinated biphenyls in a strain dependent fashion: enzyme activity was increased 2-fold in Sprague-Dawley rats but was not altered in Wistar rats. "Theoretical" values of microsomal epoxidase activity were calculated for weanling and adult Sprague-Dawley rats from turnover numbers and published data on the relative abundance of aldrin epoxidizing P-450 isozymes (Waxmann et al., Biochemistry 24, 4409, 1985). These values agreed with the activities determined. A similar statement can be made for male rats of both strains pretreated with inducers, when the ratio of enzyme activity of pretreated to control animals was used as a basis of comparison. The activity ratio of females pretreated with pregnenolone-16-alpha-carbonitrile, dexamethasone and phenobarbital, however, was much higher than the ratio calculated. Our results reveal that aldrin epoxidation is a reaction indicative of male specific and of phenobarbital-inducible cytochrome P-450 isozymes in rat liver.(ABSTRACT TRUNCATED AT 400 WORDS)

Identification of the cyanopregnenolone-inducible form of hepatic cytochrome P-450 as a catalyst of aldrin epoxidation.

In light of recent suggestions that hepatic microsomal aldrin expoxidation activity selectively reflects the phenobarbital (PB)-inducible form(s) of cytochrome P-450 (P-450PB), we tested the effect of pregnenolone-16 alpha-carbonitrile (PCN), a synthetic steroid that induces P-450PCN, a form of the cytochrome biochemically and immunochemically distinguishable from P-450PB. In hepatic microsomes prepared from rats receiving PB, 3-methylcholanthrene (3-MC), or PCN, the latter compound produced a greater increase in aldrin epoxidation activity relative to control than did PB, whereas 3-MC decreased enzyme activity. Moreover, the aldrin epoxidation activity in microsomes prepared from PCN- or PB-pretreated rats was selectively inhibited by form-specific antibodies directed against P-450PCN or P-450PB, respectively, whereas anti-P-450MC antibodies gave no inhibition with microsomes prepared from induced or control animals. We conclude that P-450PCN, P-450PB, and probably other cytochromes P-450 catalyze aldrin epoxidation, precluding use of this enzyme as a specific marker of a single form of the cytochrome.

Use of a direct high performance liquid chromatography method for multiple testosterone hydroxylations in studies of microsomal monooxygenase activities.

A high performance liquid chromatography method is described for separation of the products of testosterone monooxygenation . The method involves direct injection onto a reverse phase octadecylsilane column of the supernatant from incubations containing as little as 25 micrograms microsomal protein. Isocratic elution with formate buffer/acetonitrile and detection at 254 nm permits the separation and simultaneous quantitation of multiple discrete testosterone-derived peaks on the chromatogram. The production of the eight major oxygenated testosterone metabolites in hamster liver microsomes was determined. This profile was altered uniquely after pretreatment with either phenobarbitone, beta-naphthoflavone, rifampicin or pregnenolone 16 alpha-carbonitrile. These changes reflected analogous dissimilar effects of the enzyme inducers on the metabolism of the exogenous cytochrome P-450 substrates aldrin, acetanilide, benzo[alpha]pyrene and ethylmorphine. Therefore, the testosterone assay provides a sensitive and effective method for separating and quantitating testosterone monooxygenation products and may offer a single alternative to the use of multiple exogenous substrates for categorizing and defining the metabolic activity of cytochromes P-450.

The effect of ethanol on the absorption, accumulation and biotransformation of xenobiotics by the isolated perfused rabbit lung.

The effects of acutely administered ethanol on absorption, accumulation and biotransformation of several model compounds were examined in the isolated perfused lung (IPL). To determine pulmonary accumulation imipramine and paraquat were studied. To determine the effect of ethanol on the absorption of substances from the airways into the blood sulfanilic acid was used as an example of a relatively lipid soluble compound while mannitol was chosen as a non-lipid soluble compound. Aldrin was chosen to demonstrate the effects of circulating ethanol on pulmonary biotransformation. The results obtained with imipramine and paraquat indicate that after a 60-min perfusion period 93% and 20% of the original amount added are respectively lost from the blood perfusate. Ethanol at an initial concentration of 300 mg/100 ml has no apparent effect either on the rate or the quantities accumulated by the lungs. When sulfanilic or mannitol were administered into the airways both compounds appeared in the perfusate and ethanol had no effect on this absorption. Finally we obtained evidence that aldrin is converted to dieldrin by the IPL but that the quantities metabolized are not modified by the presence of ethanol.

Purification and properties of cytochrome P-450 from liver microsomes of phenobarbital-treated marmoset monkeys (Callithrix jacchus).

One form of cytochrome P-450 from phenobarbital-induced marmoset liver was purified to apparent electrophoretic homogeneity and compared with the major inducible form isolated from rat liver. Whereas spectral properties and molecular weights, as well as catalytic activities towards aminopyrine and ethylmorphine N-demethylation are quite similar, rates of O-dealkylation with enzymes from the two species are considerably different. While ethoxycoumarin deethylation for the marmoset cytochrome is about one-fortieth of that for the rat, ethoxyresorufin and even pentoxyresorufin dealkylations for the marmoset form are not detectable. By contrast, aldrin epoxidation as catalyzed by this cytochrome is about three times as high as that obtained from the rat.

Oxidation of pesticides by purified cytochrome P-450 isozymes from mouse liver.

5 cytochrome P-450 isozymes were purified from the livers of uninduced mice and reconstituted with purified NADPH cytochrome P-450 reductase and phospholipid. The pesticides parathion, fonofos, DEF, Mocap and profenofos were oxidized by the reconstituted monooxygenase system to form acetylcholinesterase (AChE) inhibitors. The bioactivation varied with the pesticide substrate and the cytochrome P-450 isozyme. Aldrin epoxidation occurred with all 5 isozymes, with cytochrome P-450 A1 being the most active. All fraction metabolized the pesticide synergist piperonyl butoxide (PBO) to form an inhibitory cytochrome P-450-PBO-metabolite complex. The reduced complex produced a spectrum in the Soret region which was characteristic for each of the cytochrome P-450 isozymes. Inhibition of aldrin epoxidation by PBO was found to be unrelated to the nature of the Soret spectrum.

Effect of intratracheally administered lindane on aldrin and benzo(a)pyrene contents in lungs of rats.

Pretreatment with lindane resulted in inhibition of benzo(a)pyrene hydroxylase activity in the lungs of rats. The enzyme activity tended to return to normal 5 days after the administration of lindane. Studies with benzo(a)pyrene and aldrin indicated reduced elimination of these compounds from the lungs of lindane-treated animals, suggesting that lindane may alter the clearance of certain substances or compounds from lungs. The delayed clearance of these compounds from lungs may be an indirect effect of lindane related to inhibition of certain metabolizing enzymes.

Biotransformation of drugs: quantitative structure-activity relationships for barbiturates, tertiary amines, and substituted imidazoles.

When using free energy-related physicochemical parameters, stimulation of NADPH oxidation by barbiturates and the N-oxidation of tertiary amines was found to be primarily dependent upon the lipophilic character of the substrates as measured by log P, where P is the partition coefficient from either 1-octanol-water or corn oil-water solvent systems. In contrast, the inhibition of epoxidation of aldrin by a series of substituted imidazoles appears to be much more dependent on electronic (sigma) and steric (Es) effects of the inhibitors.