Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Hexachlorobenzene”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1989

Interaction of hexachlorobenzene with the receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin in vitro and in vivo. Evidence that hexachlorobenzene is a weak Ah receptor agonist.

Hexachlorobenzene (HCB) produces hepatic porphyria and induces the hepatic cytochrome P450 isozymes P450c (P450IA1) and P450d (P450IA2) in rodents. These and other effects of HCB resemble those of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which acts via its binding to the aromatic hydrocarbon (Ah) receptor. We therefore examined the ability of HCB to interact with this receptor in vitro and in vivo. HCB, at concentrations of 1 microM or higher, inhibited the specific binding of [3H]TCDD (0.3 nM) to the Ah receptor in vitro, whereas the solubility of [3H]TCDD was affected only at 100 microM HCB. The inhibition was competitive, with a KI of approximately 2.1 microM. In rats fed a diet containing 3000 ppm HCB for varying times (4 h to 7 days), the specific binding of [3H]TCDD in hepatic cytosol was reduced by up to 40%, as observed previously for known Ah receptor agonists. The decrease in [3H]TCDD specific binding in cytosol of HCB-treated rats was due principally to a decrease in the number of binding sites for [3H]TCDD rather than competition from residual HCB. As shown by immunoblotting and radioimmunoassay, HCB induced the cytochrome P450 isozymes P450c and P450d, which are regulated by the Ah receptor, as well as the phenobarbital-inducible isozymes P450b and P450e. Together these results indicate that HCB is a weak agonist for the Ah receptor, and suggest that some of its effects may be mediated by its interaction with this gene-regulatory protein.

Animals↗
PubMed2000

Heme metabolism after discontinued hexachlorobenzene administration in rats: possible irreversible changes and biomarker for hexachlorobenzene persistence.

The aim of the present study was to determine whether short-term administration of hexachlorobenzene (HCB) (1 g/kg body wt., suspended in water, 5 days/week), could cause and maintain marked porphyria in the absence of the exogenous drug, and whether porphyria parameters can be useful as biomarkers of HCB persistence in rats. Hepatic uroporphyrinogen decarboxylase activity, its inhibitor formation, porphyrin content and composition were studied in Wistar rats treated with the fungicide for 1, 2, 3, or 4 weeks and then withdrawn for a 20-week period. The time course of urinary porphyrin excretion was studied for 7 weeks either by continuous treatment for the entire period, or a 1-week HCB administration. The degree of porphyria achieved by rats after 20 weeks of suspended HCB administration was severe, independent of the length of the treatment, and even higher than that observed in animals analysed immediately at the end of each treatment. Rats treated with HCB for 1 week showed a modest decrease in uroporphyrinogen decarboxylase and low inhibitor formation, and exhibited a greater enzyme inhibition, inhibitor formation, hepatic porphyrin accumulation, and an altered pattern of porphyrin composition in the absence of the exogenous drug. Independent of the treatment, urinary porphyrins rose after a delay of 5 weeks. Substantial amounts of HCB were still found in fat of rats treated with HCB for 1 week, after a withdrawal period of 20 weeks. These results suggest that the high persistence of HCB in tissues acts as a continuous source of the xenobiotic, and stimulus for heme biosynthesis derangement. The alterations induced by HCB within 1 week of treatment could be regarded as an initial trigger for irreversible damage on heme metabolism. Thus, abnormalities in heme biosynthesis can be considered effective markers of HCB persistence in rats or of irreversible HCB-induced damage. Taking into account the delayed and enhanced metabolic effects of HCB, it is advisable that porphyria parameters should be evaluated not only immediately after exposure, but also some time afterwards, especially in susceptible and occupationally-exposed populations.

Adipose Tissue↗
PubMed2006

An updated physiologically based pharmacokinetic model for hexachlorobenzene: incorporation of pathophysiological states following partial hepatectomy and hexachlorobenzene treatment.

Physiologically based pharmacokinetic (PBPK) modeling is generally used for describing xenobiotic disposition in animals and humans with normal physiological conditions. We describe here an updated PBPK model for hexachlorobenzene (HCB) in male F344 rats with the incorporation of pathophysiological conditions. Two more features contribute to the distinctness of this model from the earlier published versions. This model took erythrocyte binding into account, and a particular elimination process of HCB, the plasma-to-gastrointestinal (GI) lumen passive diffusion (i.e., exsorption), was incorporated. Our PBPK model was developed using data mined from multiple pharmacokinetic studies in the literature, and then modified to simulate HCB disposition under the conditions of our integrated pharmacokinetics/liver foci bioassay. This model included plasma, erythrocytes, liver, fat, rapidly and slowly perfused compartments, and GI lumen. To account for the distinct characteristics of HCB absorption, the GI lumen was split into an upper and a lower part. HCB was eliminated through liver metabolism and the exsorption process. The pathophysiological changes after partial hepatectomy, such as alterations in the liver and body weights and fat volume, were incorporated in our model. With adjustment of the transluminal diffusion-related parameters, the model adequately described the data from the literature and our bioassay. Our PBPK model simulation suggests that HCB absorption and exsorption processes depend on exposure conditions; different exposure conditions dictate different absorption and exsorption rates. This model forms a foundation for our further exploration of the quantitative relationship between HCB exposure and development of preneoplastic liver foci.

Animals↗
PubMedDate not supplied

Hexachlorobenzene I. Uptake, distribution and excretion of hexachlorobenzene (HCB) in growing lambs.

The uptake, distribution, and excretion of hexachlorobenzene (HCB) was studied in young male (castrated) lambs. Lambs were exposed for 90 days at a dietary concentration of 0, 0.01, 0.1 and 1.0 ppm. Tissue concentration of HCB were monitored by periodic omental biopsy and by post-slaughter collection of tissues at 90 and at 300 days. Blood samples were collected by venipuncture each time that biopsies or sacrifice occurred. Findings of the 300 days duration study were: (1) the growth rate of the exposed lambs was unaffected by the exposure to the dietary HCB, (2) adipose tissue concentrations reached a level approximately ten times that in the diet at the end of the 90-day exposure period, (3) HCB concentration was higher in the omental fat than in the perirenal fat at 90 days but not at 300 days, (4) a good portion of the apparent decresae in HCB in the fat following cessation of exposure is due to dilution (by increasing carcass fat), (5) the apparent half-life of HCB was approximately 90 days and was not dose-dependent at the exposure rates studied, and (6) the highest HCB concentrations in other tissues were in the brain and liver. The study demonstrated that the omental biopsy provides an excellent means of estimating body fat burden of this lipid soluble pesticide, although it tends to provide an overestimate during actual dietary exposure. The finding that the bioconcentration of and the depletion from the adipose tissues were independent of dose enables prediction of the degree to which food animals might become contaminated if allowed to feed on HCB-contaminated pastures or feed stuffs, and of the time which will be required for such residues to decrease to negligible levels. This predictive ability is of obvious benefit to both the food animal producer and the consumer. Since the HCB is apparently much more stable in the body than is indicated by the depletion half-life of 90 days in these growing lambs, it follows that environmental contamination of grazing lands or animal feeds is of far greater consequence for adult animals which would not be likely to experience the growth dilution of carcass residues.

Animals↗
PubMedDate not supplied

Hexachlorobenzene II. Effects on growing lambs of prolonged low-level oral exposure to hexachlorobenzene (HCB).

Fifty growing male (castrated) lambs were exposed to hexachlorobenzene in the diet at levels of 0, 0.01, 0.1 and 1.0 ppm for 90 days. They were then moved to clean quarters and the study continued for an additional 210 days. Growth rates, certain plasma enzyme activities and hepatic microsomal enzyme activities were studied to detect subclinical effects related to the exposure. A 19-day acute exposure at 100 ppm was done and the same parameters except for growth rate, measured. Hematocrit and plasma protein concentrations were also monitored. No significant changes were seen in the growth rates (90 days exposure), in the plasma enzymes alkaline phosphatase, glutamic oxaloacetic transaminase, glucose 6-phosphate dehydrogenase or succinic dehydrogenase, or in the hematocrit or plasma protein concentrations after either the 90-day or 19-day exposures. However, in vivo metabolism of antipyrine was increased in both the 1.0 ppm (90-day) and the 100 ppm (19-day), but was significantly increased (p less than 0.01) in only the 100-ppm exposure. Additionally, hepatic microsomal N-demethylase was increased significantly by the 90-day exposure at 1.0 ppm and the 19-day exposure at 100 ppm, but the hepatic microsomal O-demethylase was significantly increased only after the 1.0-ppm exposure. Histopathologic examination of tissues (brain, lung, myocardium, large and small intestines, liver, kidneys, adrenals, mesenteric lymph nodes) collected from animals sacrificed at 90 days and at the termination of the study (300 days) revealed no lesions suggestive of harmful HCB exposure.

Animals↗
PubMed1980

Improved method for hexachlorobenzene and mirex determination with hexachlorobenzene confirmation in adipose tissue: collaborative study.

A previously published method for determination and confirmation of hexachlorobenzene (HCB) in adipose tissue was also applied to mirex residues. A modified procedure for both residues was collaboratively studied by 12 laboratoires. The procedure specifies direct application of an extracted or rendered fat sample to a Florisil cleanup column and one-fraction elution. Mirex and HCB are determined by direct GLC of the concentrated eluate. HCB residues are then confirmed by reaction with isopropanol to form the disubstituted bis-isopropoxytetrachlorobenzene (BITB) derivative. Mirex residues are destroyed by this reaction. All participants were asked to analyze an unknown standard mixture of HCB and mirex and 10 rendered chicken fat samples consisting of one blank and 9 samples fortified samples represented 3 samples at each of 3 fortification levels. The HCB fortifications of 20.0, 33.3, and 50.0 ppb yielded average interlaboratory recoveries of 89.6, 87.4, and 92.6%, respectively. The respective coefficients of variation (CV) for HCB results were 9.1, 6,8, and 10.0%. The mirex fortifications of 150, 300, and 500 ppb yielded average interlaboratory recoveries of 89.0, 90.2, and 92.3%, respectively. The respective CV values for mirex results were 7.6, 16.5, and 18.1%. The method has been adopted official first action.

Adipose Tissue↗
PubMed1989

Hepatic mitochondrial oxidative metabolism and lipid peroxidation in experimental hexachlorobenzene-induced porphyria with dietary carbonyl iron overload.

Both human porphyria cutanea tarda and experimental hexachlorobenzene-induced porphyria are associated with hepatic injury and are potentiated by excess hepatic iron. The mechanisms whereby cellular injury occurs and the synergistic role of iron overload are unknown. In the present experiments, we studied hepatic mitochondrial function and lipid peroxidation in rats with hexachlorobenzene-induced porphyria in which iron loading was achieved by dietary carbonyl iron supplementation. Female rats were treated for 8 weeks, receiving a chow diet supplemented with hexachlorobenzene (0.2%, w/w), carbonyl iron (1.0%, w/w) or hexachlorobenzene + iron. Hepatic total porphyrins were increased 100-fold in rats receiving hexachlorobenzene (hexachlorobenzene alone and hexachlorobenzene + Fe), and total hepatic iron was increased approximately 10-fold in rats receiving iron supplementation (Fe alone and hexachlorobenzene + Fe). There was a significant increase in mitochondrial lipid peroxidation in rats treated with hexachlorobenzene alone and hexachlorobenzene + Fe. A significant reduction in mitochondrial respiratory control ratios and in oxidative phosphorylation (ADP/O ratios) using glutamate and succinate as substrates was demonstrated when rats were treated with hexachlorobenzene + iron. The reductions in respiratory control ratios were due to a combination of an inhibitory defect in electron transport as evidenced by an irreversible decrease in State 3 respiration and an uncoupling effect as evidenced by an increase in State 4 respiration. These findings suggest that lipid peroxidation and mitochondrial dysfunction may contribute to the hepatotoxicity seen in hexachlorobenzene-induced porphyria.

Animals↗
PubMed2006

[16S rDNA-RFLP analysis of structure and diversity of an aerobic microbial community degrading hexachlorobenzene].

Hexachlorobenzene is a chlorinated aromatic hydrocarbon that was widely used as a seed dressing for prevention of fungal growth on crops, and is also a component of fireworks, ammunition, and synthetic rubbers. Because of the bioaccumulation and persistence of hexachlorobenzene as well as its potential toxicity, hexachlorobenzene must be removed from environment. The potential for aerobic dechlorination of hexachlorobenzene by a hexachlorobenzene-adapted mixed culture was investigated. An aerobic microbial community which was able to grow at the presence of hexachlorobenzene was enriched from sediment from contaminated site after incubating about 2 months. During the growth of the mixed microorganisms on hexachlorobenzene, the accumulating consumption of oxygen, the microbial population curve and the release of Cl- were investigated. The data suggest the rapid degradation of hexachlorobenzene to support microbial growth and the aerobic decholrination of hexachlorobenzene was observed. The result showed that the mixed microorganisms were able to utilize hexachlorobenzene as sole carbon and energy source. It was shown that up to 55% of HCB could be degraded during 18 days incubation at 30 degrees C in mineral salts medium (pH 7.0) with 4.5mg/L HCB. The calculated rate of hexachlorobenzene biodegradation was 137.5 microg/ (L x d). The 16S rDNA genes were amplified from community DNA by using primers specific to bacteria and were subsequently cloned. The cloned 16S rDNA fragments were reamplified, and restriction analysis was performed following separate digestion with enzymes Hae III and Rsa I. Application of restriction fragment length polymorphism screening approach revealed 9 clusters, and 3 major clusters were sequenced. Nearly complete 16S rDNA sequence analysis show that the microbial community was dominated by Alcaligenes and Azospirillum groups. This is the first report describing aerobic dechlorination of hexachlorobenzene via dehalorespiration by a microbial community which was enriched from contaminated site. The microbial community can be used to degrade highly recalcitrant chlorinated pollutants.

Bacteria, Aerobic↗
PubMed1986

The microsomal metabolism of hexachlorobenzene. Origin of the covalent binding to protein.

The microsomal metabolism of hexachlorobenzene is studied, with special attention to the covalent binding to protein. The metabolites formed are pentachlorophenol and tetrachlorohydroquinone. In addition, a considerable amount of covalent binding to protein is detected (250 pmoles pentachlorophenol, 17 pmoles tetrachlorohydroquinone and 11 pmoles covalent binding in an incubation containing 50 mumoles of hexachlorobenzene). In order to establish the potential role of reductive dechlorination in the covalent binding, the anaerobic metabolism of hexachlorobenzene was investigated. At low oxygen concentrations no pentachlorobenzene was detected, and only very small amounts of pentachlorophenol as well as covalent binding, indicating a relationship between covalent binding and the microsomal oxidation of hexachlorobenzene. Incubations with 14C-pentachlorophenol at low concentrations showed that a conversion-dependent covalent binding occurs to the extent of 75 pmole binding per nmole pentachlorophenol. This is almost enough to account for the amount of label bound to protein observed in hexachlorobenzene incubations. This indicates that less than 10% of the covalent binding occurs during conversion of hexachlorobenzene to pentachlorophenol, and the remainder is produced during conversion of hexachlorobenzene to pentachlorophenol, and the remainder is produced during conversion of pentachlorophenol. The major product of microsomal oxidation of pentachlorophenol is tetrachlorohydroquinone, which is in redox-equilibrium with the corresponding semiquinone and quinone (chloranil). The covalent binding is inhibited by addition of ascorbic acid or glutathione to the hexachlorobenzene incubations. Ascorbic acid decreases the covalent binding with a simultaneous increase in formation of tetrachlorohydroquinone, probably due to a shift in the redox-equilibrium to the reduced side. Glutathione does not act as a reducing agent, since the inhibition of covalent binding is not accompanied by an increase in tetrachlorohydroquinone formation. Instead, glutathione reacts with chloranil, producing at least three stable products, probably in a Michael-type reaction. These results strongly indicate the involvement of chloranil or the semiquinone radical in the covalent binding during microsomal hexachlorobenzene metabolism.

Animals↗
PubMed1989

The relation between the oxidative biotransformation of hexachlorobenzene and its porphyrinogenic activity.

The relation between the major toxic effect of hexachlorobenzene, hepatic porphyria, and its oxidative biotransformation was studied in vivo, by observing the effect of modulating its biotransformation on the expression of porphyria. This modulation was achieved by selective in vivo inhibition of the major cytochrome P450 isoenzyme involved in both the hydroxylation of hexachlorobenzene and its primary oxidative metabolite, pentachlorophenol. The involvement of this isoenzyme, cytochrome P450p, was established by in vitro biotransformation studies using microsomes derived from rats treated with various inducers of cytochrome P450 isoenzymes and selective in vitro inactivation of cytochrome P450p by triacetyloleandomycin (TAO), resulting in a strong inhibition of the microsomal conversion of hexachlorobenzene and pentachlorophenol. In vivo inactivation of cytochrome P450p was achieved by coadministration of hexachlorobenzene and TAO. Female rats which were treated with this diet for 10 weeks showed a strongly diminished urinary excretion of the major oxidative metabolites, pentachlorophenol and tetrachloro-1,4-hydroquinone, as compared to rats treated with hexachlorobenzene alone. The TAO coadministration was found to result in complexation of 70% of the total amount of hepatic microsomal cytochrome P450. The group treated with hexachlorobenzene alone displayed a 600-fold increase in the amount of hepatic porphyrins, whereas an almost complete absence of hepatic porphyrins was observed after administration of hexachlorobenzene together with TAO. The urinary excretion of porphyrins was also significantly lowered by cotreatment with TAO. A strong correlation was found to exist between the amount of porphyrins excreted and the amount of oxidative metabolites excreted, as a function of exposure time. Glucuronidation of pentachlorophenol was observed to an average extent of 30%. This percentage was not influenced by either TAO or phenobarbital. These results suggest that oxidative biotransformation, and thus the formation of the very reactive tetrachloro-1,4-benzoquinone, is directly related to the porphyrinogenic action of hexachlorobenzene.

Animals↗
PubMed1983

Enhanced intestinal excretion of hexachlorobenzene in rats by intraluminal injection of hexadecane.

The effect of hexadecane on the intestinal excretion of hexachlorobenzene was studied in female Sprague-Dawley rats dosed twice with 14C-hexachlorobenzene at 50 mg kg-1 per os. Injection of 75 mg n-hexadecane into ligated and unligated segments of the intestine increased concentrations of hexachlorobenzene in intestinal contents by about two- or three-fold in jejunal and ileal segments, and about two-fold in the cecal-colon segment. The jejunum appeared to be the site of greatest excretion of hexachlorobenzene followed by the ileum, the cecum and the colon. This order is opposite to our previous data from animals with an undisturbed intestinal passage. The apparently greater excretion of hexachlorobenzene into the small intestine is probably due to its much larger surface area than that of the large intestine. However, the residency time of luminal contents in the large intestine normally exceeds that in the small intestine by about 20--40-fold, which apparently more than compensates for the difference in relative surface area between small and large intestine. Thus, residency time appears to be a more important factor than surface area in determining the intestinal elimination of hexachlorobenzene. These results with hexachlorobenzene are probably typical of physiological disposition of lipophilic halogenated hydrocarbons generally.

Alkanes↗
PubMed2003

Dehalorespiration with hexachlorobenzene and pentachlorobenzene by Dehalococcoides sp. strain CBDB1.

The chlororespiring anaerobe Dehalococcoides sp. strain CBDB1 used hexachlorobenzene and pentachlorobenzene as electron acceptors in an energy-conserving process with hydrogen as electron donor. Previous attempts to grow Dehalococcoides sp. strain CBDB1 with hexachlorobenzene or pentachlorobenzene as electron acceptors failed if these compounds were provided as solutions in hexadecane. However, Dehalococcoides sp. strain CBDB1 was able to grow with hexachlorobenzene or pentachlorobenzene when added in crystalline form directly to cultures. Growth of Dehalococcoides sp. strain CBDB1 by dehalorespiration resulted in a growth yield ( Y) of 2.1+/-0.24 g protein/mol Cl(-) released with hexachlorobenzene as electron acceptor; with pentachlorobenzene, the growth yield was 2.9+/-0.15 g/mol Cl(-). Hexachlorobenzene was reductively dechlorinated to pentachlorobenzene, which was converted to a mixture of 1,2,3,5- and 1,2,4,5-tetrachlorobenzene. Formation of 1,2,3,4-tetrachlorobenzene was not detected. The final end-products of hexachlorobenzene and pentachlorobenzene dechlorination were 1,3,5-trichlorobenzene, 1,3- and 1,4-dichlorobenzene, which were formed in a ratio of about 3:2:5. As reported previously, Dehalococcoides sp. strain CBDB1 converted 1,2,3,5-tetrachlorobenzene exclusively to 1,3,5-trichlorobenzene, and 1,2,4,5-tetrachlorobenzene exclusively to 1,2,4-trichlorobenzene. The organism therefore catalyzes two different pathways to dechlorinate highly chlorinated benzenes. In the route leading to 1,3,5-trichlorobenzene, only doubly flanked chlorine substituents were removed, while in the route leading to 1,3-and 1,4-dichlorobenzene via 1,2,4-trichlorobenzene singly flanked chlorine substituents were also removed. Reductive dehalogenase activity measurements using whole cells pregrown with different chlorobenzene congeners as electron acceptors indicated that different reductive dehalogenases might be induced by the different electron acceptors. To our knowledge, this is the first report describing reductive dechlorination of hexachlorobenzene and pentachlorobenzene via dehalorespiration by a pure bacterial culture.

Biodegradation, Environmental↗
PubMed1982

Hexadecane enhances non-biliary, intestinal excretion of stored hexachlorobenzene by rats.

[14C]Hexachlorobenzene (100 mg/kg) was orally administered to 4 groups of rats. Ten days later the effects of hexadecane (3 x 5 ml/kg by gavage) and/or bile duct ligation on urinary and fecal excretion and tissue levels of hexachlorobenzene were examined. Hexadecane did not affect urinary excretion of hexachlorobenzene, whereas bile duct ligation tripled it. Each of the 3 treatments (n-hexadecane, bile duct ligation and the combination of the two) resulted in a significant increase in fecal excretion of hexachlorobenzene. Moreover, the combination of hexadecane and bile duct ligation produced a greater increase in fecal excretion of hexachlorobenzene than either treatment alone. Concentrations of hexachlorobenzene in blood, fat and kidney were not affected by any of the treatments, but liver concentrations were reduced significantly by bile duct ligation. Concentrations of hexachlorobenzene in intestinal contents indicate that intestinal-wall passage is the primary route of elimination from the body and that enhancement of elimination occurs mostly distal to the jejunum.

Alkanes↗
PubMed1988

Reductive dechlorination of hexachlorobenzene to tri- and dichlorobenzenes in anaerobic sewage sludge.

Hexachlorobenzene was dechlorinated to tri- and dichlorobenzenes in anaerobic sewage sludge. The complete biotransformation of 190 microM hexachlorobenzene (approximately 50 ppm) occurred within 3 weeks. The calculated rate of hexachlorobenzene dechlorination was 13.6 mumol liter-1 day-1. Hexachlorobenzene was dechlorinated via two routes, both involving the sequential removal of chlorine from the aromatic ring. The major route was hexachlorobenzene----pentachlorobenzene----1,2,3,5-tetrachlorobenzene--- -1,3,5- trichlorobenzene. Greater than 90% of the added hexachlorobenzene was recovered as 1,3,5-trichlorobenzene, and there was no evidence for further dechlorination of 1,3,5-trichlorobenzene. The minor route was hexachlorobenzene----pentachlorobenzene----1,2,4,5-tetrachlorobenzene--- -1,2,4- trichlorobenzene----dichlorobenzenes. These results extend reductive dechlorination to poorly water soluble aromatic hydrocarbons which could potentially include other important environmental pollutants like polychlorinated biphenyls.

Bacteria, Anaerobic↗
PubMed1981

[The effect of some hexachlorobenzene catabolites on the porphyrin metabolism of rats (author's transl)].

In answering the question as to what role possible metabolites of hexachlorobenzene play in the procreation of toxic hexachlorobenzene porphyria in rats, both pure hexachlorobenzene and different mixtures were fed to them. In each case 20% of the hexachlorobenzene was replaced by pentachlorophenol, 1,2,4,5-tetrachlorobenzene, 1,2,3,4-tetrachlorobenzene, 1,2,3,5-tetrachlorobenzene, 2,3,4,5-tetrachlorophenol, 2,3,5,6-tetrachlorophenol, 2,3,4,6-tetrachlorophenol or chloranil. The determination of porphyrins at different intervals once the feeding had started did not give rise to an increase in the porphyria in any of these substances--which are seen as metabolites of hexachlorobenzene. Instead there was a distinct decrease in individual cases. From this the conclusion is drawn that none of the tested substances is the metabolite of hexachlorobenzene, which is in fact responsible for the hexachlorobenzene porphyria.

Animals↗
PubMed1981

Effects of hexachlorobenzene and iron loading on rat liver mitochondria.

The effects of hexachlorobenzene treatment and simultaneous iron-overload on the iron and porphyrin content of rat liver and rat liver mitochondria have been examined. In order to assess damages to the mitochondrial membrane occurring with these treatments, the content of malondialdehyde and selected functional properties of mitochondria were compared with those from control animals. Prolonged intake of hexachlorobenzene (8 weeks) resulted in a strikingly increased level of porphyrins together with a moderate increase in iron concentration. Simultaneous administration of hexachlorobenzene and iron-dextran caused the porphyrin level to reach 25% of the amount induced by hexachlorobenzene alone. The iron concentrations in liver as well as in liver mitochondria are also decreased under these conditions, as compared to the effect of iron-dextran. In contrast, the effects of hexachlorobenzene combined with iron-dextran on mitochondrial oxidative phosphorylation and malondialdehyde content are greater than those of either hexachlorobenzene or iron-dextran. These data suggest that porphyrin accumulation per se causes little deleterious effect and that both agents administered together act synergistically in causing damage to the mitochondrial membrane.

Animals↗
PubMed1993

Hexachlorobenzene toxicity in the monkey primordial germ cell without induced porphyria.

Hexachlorobenzene is a persistent chlorinated organic chemical that has been detected in many tissues from a variety of species including human ovary and human ovarian follicular fluid. When administered in high dosage to nonhuman primates, hexachlorobenzene causes destruction of ovarian primordial germ cells in association with systemic toxicity. The purpose of these experiments was to assess relative ovarian germ cell sensitivity at much lower dosages of hexachlorobenzene that do not produce systemic effects and additionally to evaluate oocyte function by means of the response to superovulation, fertilization, and embryo cleavage during a cycle of in vitro fertilization in the cynomolgus monkey. Hexachlorobenzene in dosages of 0.1, 1.0, and 10.0 mg/kg/day was administered orally by gelatin capsule for 90 days. There was a dose-dependent accumulation of HCB in serum and other tissues without any change in the serum estradiol response to human menopausal gonadotropin, oocyte recovery, oocyte maturation, oocyte fertilization in vitro, and early embryo cleavage rate. There was a dose-related toxic effect observed in primordial germ cells at the lowest dose despite no evidence of systemic or hepatic effects. As there were no changes in the urinary porphyrin excretion, the mechanism of hexachlorobenzene ovotoxicity may be distinct from hexachlorobenzene-induced cytochrome P-450-dependent inhibition of uroporphobilinogen decarboxylase in the liver, although such intraovarian metabolism cannot be excluded.

Animals↗