Elimination Of Hexachlorobenzene Research Articles

Excretion of Hexachlorobenzene and Metabolites in Feces in a Highly Exposed Human Population

A set of 53 individuals from a population highly exposed to airborne hexachlorobenzene (HCB) were selected to study the elimination kinetics of this chemical in humans. The volunteers provided blood, 24-hr urine, and feces samples for analysis of HCB and metabolites. The serum HCB concentrations ranged from 2.4 to 1,485 ng/mL (mean +/- SD, 124 +/- 278), confirming that this human population has the highest HCB blood levels ever reported. All analyzed feces samples contained unchanged HCB (range, 11-3,025 ng/g dry weight; mean +/- SD, 395 +/- 629). The HCB concentration in feces strongly correlated with HCB in serum (r = 0.85; p < 0.001), suggesting an equilibrium in feces/serum that is compatible with a main pulmonary entrance of the chemical and low intestinal excretion of nonabsorbed foodborne HCB. The equilibrium is also compatible with a nonbiliary passive transfer of the chemical to the intestinal lumen. Two HCB main metabolites, pentachlorophenol (PCP) and pentachlorobenzenethiol (PCBT), were detected in 51% and 54% of feces samples, respectively. All urine samples contained PCP and PCBT, confirming the conclusions of a previous study [Environ Health Perspect 105:78-83 (1997)]. The comparison between feces and urine showed that whereas daily urinary elimination of metabolites may account for 3% of total HCB in blood, intestinal excretion of unchanged HCB may account for about 6%, thus showing the importance of metabolism in the overall elimination of HCB. The elimination of HCB and metabolites by both routes, however, appears to be very small (< 0.05%/day) as compared to the estimated HCB adipose depots. Features of HCB kinetics that we present in this study, i.e., nonsaturated intestinal elimination of HCB and excretion in feces and urine of inert glutathione derivatives, may explain, in part, the absence of porphyria cutanea in this human population heavily exposed to HCB.

Bioaccumulation and toxicity of hexachlorobenzene in Chlorella vulgaris and Daphnia magna

Algae play a major role in the accumulation of hydrophobic pollutants. The accumulation of hexachlorobenzene (HCB) in algae is very rapid, reaching equilibrium after a few hours. The elimination of HCB from algae has been described by a two-compartment nonequilibrium model. This paper describes the elimination kinetics of HCB from the second (slow rate) compartment in Chlorella vulgaris, and the bioavailability of the HCB bound to algae on Daphnia magna. First-order elimination kinetics was observed. The elimination rate constant and the half life were 0.43 day −1 and 1.6 days, respectively. The algal growth curve showed a growth rate constant of 0.27 day −1 and a duplication time of 2.56 days. Comparisons among these values indicate that the dilution effect associated with algal growth accounts for more than 60% of the observed reduction. Daphnia magna fed for 6 days with contaminated Chlorella, 4.4 μg HCB kg −1 dry weight, accumulated 1.7 μg HCB kg −1 dry weight. Feeding with HCB-contaminated Chlorella led to 49% and 41% reductions, respectively in the number and biomass of juvenile daphnids produced during the time span of the experiment. The HCB concentration in the juveniles was 0.28 μg HCB kg −1 dry weight. Calculations based on these results and published bioconcentration factors for Chlorella, 124000 on a dry-weight basis, indicated that Chlorella growing in an HCB concentration equal to the actual European Water Quality Objective for HCB (0.01 μg 1 −1), will accumulate HCB at a level within the same order of magnitude as that found toxic for Daphnia feeding on the algal population.

Physiological pharmacokinetic model of hexachlorobenzene in the rat.

A physiologically based pharmacokinetic model was developed to describe the distribution of hexachlorobenzene (HCB) in the rat after oral administration or injection. The model was based on flow-limited blood perfusion of HCB to tissues and organs of the body. A set of simultaneous differential equations were solved for the different tissue concentrations as a functions of time. The model allowed for elimination of HCB by excretion. The model also allowed for differential growth of various tissues over the course of an experiment. Computer simulations using the model indicated that growth of animals during the course of dosing experiments can greatly increase the apparent half-life of HCB.

Distribution and elimination of hexachlorobenzene, octachlorostyrene and decachlorobiphenyl in rainbow trout, Salmo gairdneri

In two experiments rainbow trout, Salmo gairdneri, were injected intraperitoneally with an oil solution containing hexachlorobenzene (HCB) and octachlorostyrene (OCS), or a mixture of chlorinated hydrocarbons extracted from fish in a contaminated area. HCB and OCS were determined by gas chromatography in fat, liver and muscle, and decachlorobiphenyl (DCB) was determined in fat. The water temperature was 7°C and both experiments lasted for 37 wk. In most cases significant correlations were observed between the logarithm of the concentrations of HCB, OCS and DCB, and time from the start of the experiment. The fish increased their body weight during the experiments. Therefore a simple correction of the concentrations was accomplished. From the weight-corrected concentrations the apparent half lives were calculated to be: HCB in liver, 81 days; OCS in liver, 143 days; and HCB in fat, 146 days. In fat the weight-corrected concentrations of OCS increased with time. The biological half life was calculated to be of the order of 60–70 days for HCB and 90–120 days for OCS. The elimination of OCS in rainbow trout at 7°C seems to be slightly lower than in the rat.

Distribution and elimination of [14C]-hexachlorobenzene after single oral exposure in cod (Gadus morhua) and flounder (Platichthys flesus).

Distribution and elimination of hexachlorobenzene (HCB) after administration to COD (Gadus morhua) of a single oral dose of 5 microCi [14C]HCB/100 g body weight were studied by whole-body autoradiography and liquid scintillation counting. To obtain some information on the physicochemical properties of the radiolabeled compounds, whole-body autoradiography was performed exposing parallel sagittal sections, treated at -20 degrees C, evaporated at 50 degrees C, and extracted separately with polar and nonpolar solvents. The highest concentration of radioactivity was found in the liver, the bile, and the central nervous system (CNS). Radioactivity in the liver and CNS, which was completely evaporable, was considered to represent the highly volatile HCB itself, and/or metabolites with high vapor pressure. No part of radioactivity in bile was evaporable, but it was completely extractable with water. Radioactivity in the intestinal content, the skin, and the uveal tract of the eye was partly evaporable. No radioactivity remained in any tissue after extraction with polar and nonpolar solvents. The rate of elimination was slow, and substantial amounts remained in the body 60 d after administration. In addition to bile excretion of nonevaporable, water-soluble radioactivity, a possible excretion through the intestinal mucosa was suggested. Whole-body autoradiography of female flounders (Platichthys flesus) revealed a high content of radioactivity in the developing eggs.

Uptake, accumulation, and elimination of HCB and 2,4-D by the terrestrial slug, Deroceras reticulatum (Müller).

The earthworms, snails, slugs and other soil invertebrates are considered to be important components in food chain as they form a significant proportion ol the diet of other animals. Therefore, monitoring of these organisms for the source oi pesticide residues to other animals *eeding on them, and as well as for establishing the contamination levels of agricultural soils is an approach well documented (WHEATLEY & HARDMAN, 1968; DAVIS, 1968; DAVIS & FRENCH, 1969; GISH, 1970; EDWARDS & THOMPSON, 1973; KUHR et al., 1974; BEYER & GISH, 1980; YADAV et al., 1981). Amongst these organisms, terrestrial slugs and snails appear to be relatively resistant to pesticides but have the capacity to accumulate organochlorine (STRINGER & PICKARD, 1965; GISH, 1970; DINDAL & WURZINGER, 1971; KUHR et al., 1974) and organophosphorus insecticide residues (EDWARDS, 1976) in their body tissues. Since slugs in their natural habitates are in direct contact with the soil and the vegetation, they are therefore exposed to the pesticides applied in the field and to other xenobiotics in the environment. It is not yet clear as to which route(s) pesticides get entry into the slugs body, and whether there are any diiferences in the quantities oi the residues taken up from different sources and in the retention of these residues if there are more than one route of intake. To understand more about the behaviour of slugs we studied the uptake of two test pesticides, namely [14C]-hexachloro benzene (HCB) and [14C]2,4-dichlorophen oxyacetic acid (2,#-D); (i) by ieeding the slugs via carrot discs daily for a period of five to ten days, and (ii) exposing the Mugs continuously to the contaminated soil. HCB was chosen for its persistent and lipophilic property, and 2,#-D for its polarity and hydrophilic property. With this preliminary approach it was possible to determine the excretion rates and retention of HCB and 2,4-D residues and their metabolites in slug tissues upon ingestion and exposure.

Distribution and elimination of [14C] hexachlorobenzene after single oral exposure in the rainbow trout (Salmo gairdneri).

Distribution and elimination of hexachlorobenzene (HCB) after administration to rainbow trout (Salmo gairdneri) of a single oral dose of 5 microCi [14C] HCB/100 g body weight were studied by whole-body autoradiography and liquid scintillation counting. To obtain some information on the physicochemical properties of the radiolabelled compounds, whole-body autoradiography was performed exposing parallel sagittal sections, treated at -20 degrees C, evaporated at 50 degrees C, and extracted separately with polar and nonpolar solvents. At d 1, radioactivity was distributed throughout the body. The highest concentration of radioactivity was found in adipose tissue. In the abdominal fat, the peak level of radioactivity was measured at d 30. No part of the radioactivity in the bile was evaporable. Radioactivity in the intestinal content, the skin, and the uveal tract was partly evaporable, while only traces of radioactivity remained in adipose tissue after evaporation. Radioactivity in the bile was extractable with water only. No radioactivity remained in any tissue after extraction with polar and nonpolar solvents. The rate of elimination was slow, and substantial amounts of radioactivity remained in the body 120 d after administration. In addition to bile excretion of nonevaporable, water-soluble radiolabeled compounds, a possible excretion over the intestinal mucosa was suggested.

Distribution and excretion of hexachlorobenzene in bobwhite (Colinus virginianus).

After a single dose of [14C]hexachlorobenzene (HCB) via gavage into the crop, the accumulation of [14C]HCB in female bobwhite (Colinus virginianus) tissues occurred to the greatest extent in adipose tissue followed by skin, liver, brain, heart and kidney, whole blood, and muscle. There was a general relation between increasing HCB concentration and increasing fat content of the tissue. Absorption of [14C]-HCB was rapid with peak radioactivity occurring at 4 h in all tissues except for fat and skin, where it continued to rise until 32 and 16 h after dosing, respectively. Elimination of HCB from tissue was biphasic with phase I representing the combination of HCB excretion and HCB redistribution from tissue into fat stores. Phase II represented solely HCB excretion, which appeared to be a first-order process. The half-life of [14C]HCB in tissues, feces, and eggs ranged from 9-13 d regardless of HCB concentration. Radioactive HCB accumulation in egg yolk was a significant mechanism for the removal of this chemical from bobwhite and accounted for 50% of the total HCB excreted.

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.

Effects of dietary paraffin, squalane and sucrose polyester on residue disposition and elimination of hexachlorobenzene in rats

Previous studies have shown addition of light liquid paraffin to enhance the elimination of organochlorine xenobiotics. In the present study the effect of paraffin on the elimination of [ 14C]hexachlorobenzene (HCB) was compared with the effect of possible alternative compounds, squalane and sucrose polyester (SPE). Four groups of 7 rats were fed a diet containing 1.5 ppm [ 14C]HCB for 4 days followed by 10 days on HCB-free diet. Thereafter one group (control) remained on this diet whereas the other 3 groups received a diet supplemented with 8% (w/w) paraffin, squalane or SPE, respectively. Radioactivity in urine and faeces was measured daily and at the end of the experiment in samples of abdominal fat, muscle, liver, kidney and blood. Dietary treatment with either paraffin, squalane or SPE markedly enhanced faecal excretion of [ 14C]HCB, whereas urinary excretion was not affected. Both the time course as well as the extent of faecal [ 14C]HCB elimination were similar in the treated groups. After 3 weeks of treatment the amount of [ 14C]HCB excreted with faeces was about three times higher in treated animals than in controls. The half-life ( t 1 2 ) of [ 14C]HCB elimination from the body was markedly decreased in treated animals (mean 34–38 days) compared to controls (110 days). [ 14C]HCB concentrations in some major tissues were significantly reduced to the same extent by all three dietary regimens. Thus squalane and SPE are as effective as paraffin in removing HCB from contaminated animals.

Elimination of Hexachlorobenzene (HCB) by Rainbow Trout (Salmo gairdneri), and an Examination of its Kinetics in Lake Ontario Salmonids

Subadult rainbow trout (Salmo gairdneri) were fed diets containing hexachlorobenzene (HCB) to establish mean body burdens of 225 and 440 μg HCB per fish. They were sampled after 0, 24, 55, and 110 d to estimate the rate of elimination. The biological half-life or T[Formula: see text] of HCB for trout under the prescribed laboratory conditions was estimated to be at least 7 mo, and perhaps as long as several years. T[Formula: see text] was calculated using body burden or μg HCB per fish, and tissue concentrations or μg/kg HCB. Estimates of T[Formula: see text] derived from tissue concentrations ranged from 61 to 117 d, but this was shown to be due to a relative increase in body weight over the study period. The implications of increasing body weight on kinetics measurements are discussed, and an equation is presented that adjusts for changes in body weight where estimates of T[Formula: see text] are calculated using tissue concentrations.The results of this and other studies on HCB were used to examine the kinetics of HCB in salmonids collected from Lake Ontario. Using the information derived from laboratory studies on rainbow trout, good agreement was achieved between the expected level and that monitored in field samples of rainbow trout, but only a fair agreement was suggested for lake trout (Salvelinus namaycush) and coho salmon (Oncorhynchus kisutch). Differences in the HCB kinetics of these species may be attributed to body weight, age, and perhaps feeding habits. Concentrations of HCB reported in field sampling programs generally range from 1 to 100 μg/kg in fish, and it is suggested that these levels are primarily due to the limited availability of HCB in the Lake Ontario environment.Key words: contaminants, hexachlorobenzene (HCB), half-life, elimination, depuration, rainbow trout, Salmo gairdneri; Lake Ontario

Studies on the toxicology of hexachlorobenzene

The pharmacokinetics of hexachlorobenzene and its metabolites, as well as its influence on the clinical behavior of female rats, their weight increase, the weight of their organs, and the metabolism of the porphyrins were investi- gated over a period of 53 weeks. From the 1st through the 15th week of the experiment hexachlorobenzene was given orally to the animals at a dosage of 178 pxmoles/kg (50 mg/kg) every other day. 9 weeks after the start of the experiment, an equilibrium was observed be- tween intake and elimination of hexachlorobenzene and its metabolites. At this time, 1 g of liver contained approximately 1 ~xmole of hexachlorobenzene, 50 nmoles of pentachlorophenol, 5 nmoles of tetrachlorohydroquinone and approx- imately 0.1 nmole of pentachlorothiophenol. The elimination of hexachlorobenzene took place at a decreasing rate. 38 weeks after cessation of administration, the biological half-life, determined on the basis of the substance eliminated from the tissues, amounted to 4--5 months. The increase in body weight of the treated animals did not differ during the entire course of the experiment from that of untreated animals. During the peri- od of treatment, the liver, spleen, kidneys and adrenal glands showed a relative increase in weight. At the end of the 38 week period, in which no hexachloro- benzene was administered, the organs of the treated animals exhibited normal weights. The content of porphyrins in the liver and urine, and that of delta-aminolevu- linic acid and porphobilinogen in the urine increased up to the 15th week of the experiment. At the end of the 38-week period (during which no hexachloroben- zene was given), the porphyrin content of the liver was higher than after the 15 week period of administration, but the porphyrin content of the urine had de- creased to almost normal values. The amount of porphyrin precursors in the urine had likewise reached normal values.

IV. Accumulation and elimination of HCB in pigs after oral dosing

Abstract Pigs were fed for 16 weeks on diets containing 0.1, 1.0, and 10.0 ppm of hexachlorobenzene (HCB). Back fat was sampled during the dosing period and the following 22 weeks. Maximum concentrations of HCB attained in the fat were approximately proportional to the dose rates and were 0.68 ppm, 6.0 ppm, and 56 ppm (group means) respectively, with a biological half life of 10–12 weeks for all levels of administration. The trial indicated that HCB-treated cereals, fed to pigs either accidentally or as a supplementary ration, would give high residues of HCB in body fat.