Polychlorinated Biphenyls Group Research Articles

Effect of polychlorinated biphenyls on tissue distribution and intestinal absorption of .ALPHA.-tocopherol in rats.

We conducted experiments to elucidate the mechanism by which alpha-tocopherol (alpha-toc) concentration in the liver remarkably increases in rats treated with polychlorinated biphenyls (PCB) when excess amounts of DL-alpha-tocopheryl-acetate (alpha-toc-ac) were given. First, diets containing 5 and 50 mg of alpha-toc-ac per 100 g were respectively added with 0.05% of PCB and given to rats for 10 days, and alpha-toc distributions in tissues were determined. Next, the disappearance of alpha-toc from a ligated intestine of vitamin E (E)-deficient rats was then studied. There were no significant differences between the control and the PCB groups in alpha-toc concentrations in the liver and other tissues except a few tissues when a lower level of alpha-toc-ac (5 mg) was given. Conversely, when a higher level of alpha-toc-ac (50 mg) was given, alpha-toc concentration in the liver of the PCB group significantly increased compared to that of the control group. This agrees with the result previously reported, showing a remarkable reproducibility. In addition, alpha-toc concentrations in tissues other than the liver were also significantly higher in the PCB group than in the control group. Transmigration of alpha-toc to the liver from other tissues was therefore excluded. The alpha-toc absorption test using the ligated intestine of E-deficient rats revealed that alpha-toc disappears from the intestine at a higher rate in the presence of PCB compared to the untreated control group. This may indicate that alpha-toc absorption by passive diffusion is accelerated in the coexistence of PCB.

Hyperlipoproteinemia in rats fed polychlorinated biphenyls.

Hypercholesterolemia due to feeding of polychlorinated biphenyls (PCB) and due to feeding of high cholesterol was compared. Rats in control group were fed a 25% casein diet, and those in PCB group or cholesterol group were fed the 25% casein diet supplemented with 0.03% PCB or 1% cholesterol and 0.25% cholic acid, respectively. Lipoprotein mass (d less than 1.21 g/ml) was higher 1.9- and 1.3-fold in rats fed PCB and cholesterol, respectively, as compared with controls. In rats fed PCB, protein, cholesterol, and phospholipid in the lipoprotein fraction markedly increased. Cholesterol-feeding resulted in the increase in pre-beta-lipoprotein cholesterol, while PCB-feeding increased alpha-lipoprotein cholesterol and slightly slow migrated pre-beta-lipoprotein cholesterol. PCB-treated rats had more apolipoprotein A-I in the lipoprotein fraction than control and cholesterol-fed rats. The data demonstrated that hyperlipoproteinemia induced by PCB is a novel alpha-lipoproteinemia and a useful model for investigating metabolism of high density lipoprotein.

Development after exposure to polychlorinated biphenyls and dichlorodiphenyl dichloroethene transplacentally and through human milk.

To determine whether exposure to polychlorinated biphenyls (PCBs) or dichlorodiphenyl dichloroethene (DDE), either transplacentally or through breast feeding, affected scores on the Bayley Scales of Infant Development at 6 or 12 months of age. Cohort followed from birth to 1 year of age. General community. Volunteer sample of 858 infants, of whom 802 had Bayley scores available at either 6 months or 12 months or both. None. Bayley scales and chemical measurements were done independently. Higher transplacental exposure to PCBs was associated with lower psychomotor scores at both 6 and 12 months of age; the difference between the mean scores in the lowest and highest PCB groups was 7 points at 6 months and 8 points at 12 months. Higher transplacental exposure to DDE was associated with higher mental scores at 6 months of age (the difference between the mean scores in the lowest and highest DDE groups was 6 points), but no relationship was seen at 12 months. Exposure to either chemical through breast feeding was apparently unrelated to Bayley scores. Transplacental exposure to PCBs was associated with lower psychomotor scores. No deleterious effects were associated with breast feeding.

PCBs: structure-function relationships and mechanism of action.

Numerous reports have illustrated the versatility of polychlorinated biphenyls (PCBs) and related halogenated aromatics as inducers of drug-metabolizing enzymes and the activity of individual compounds are remarkably dependent on structure. The most active PCB congeners, 3,4,4',5-tetra-, 3,3',4,4'-tetra-, 3,3',4,4',5-penta- and 3,3',4,4',5,5'-hexachlorobiphenyl, are substituted at both para and at two or more meta positions. The four coplanar PCBs resembled 3-methylcholanthrene (3-MC) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) in their mode of induction of the hepatic drug-metabolizing enzymes. These compounds induced rat hepatic microsomal benzo(a)pyrene hydroxylase (aryl hydrocarbon hydroxylase, AHH) and cytochromes P-450a, P-450c and P-450d. 3,4,4',5-Tetrachlorobiphenyl, the least active coplanar PCB, also induced dimethylaminoantipyrine N-demethylase and cytochromes P-450b+e and resembled Aroclor 1254 as an inducer of the mixed-function oxidase system. Like Aroclor 1254, all the mono-ortho- and at least eight di-ortho-chloro analogs of the coplanar PCBs exhibited a "mixed-type" induction pattern and induced microsomal AHH, dimethylaminoantipyrine NM-demethylase and cytochromes P-450a-P-450e. Quantitative structure-activity relationships (QSARs) within this series of PCBs were determined by comparing their AHH induction potencies (EC50) in rat hepatoma H-4-II-E cells and their binding affinities (ED50) for the 2,3,7,8-TCDD cytosolic receptor protein. The results showed that there was an excellent correlation between AHH induction potencies and receptor binding avidities of these compounds and the order of activity was coplanar PCBs (3,3',4,4' -tetra-, 3,3',4,4',5-penta- and 3,3',4,4',5,5'-hexachlorobiphenyls) greater than 3,4,4',5-tetrachlorobiphenyl approximately mono-ortho coplanar PCBs greater than di-ortho coplanar PCBs. It was also apparent that the relative toxicities of this group of PCBs paralleled their biological potencies. The coplanar and mono-ortho coplanar PCBs also exhibit differential effects in the inbred C57BL/6J and DBA/2J mice. These compounds induce AHH and cause thymic atrophy in the former "responsive" mice whereas at comparable or higher doses none of these effects are observed in the nonresponsive DBD/2J mice. Since the responsiveness of these two mice strains is due to the presence of the Ah receptor protein in the C57BL/6J mice and its relatively low concentration in the DBA/2J mice, the results for the PCB cogeners support the proposed receptor-mediated mechanism of action.

PCBs: Structure-Function Relationships and Mechanism of Action

Numerous reports have illustrated the versatility of polychlorinated biphenyls (PCBs) and related halogenated aromatics as inducers of drug-metabolizing enzymes and the activity of individual compounds are remarkably dependent on structure. The most active PCB congeners, 3,4,4',5-tetra-, 3,3',4,4'-tetra-, 3,3',4,4',5-penta- and 3,3',4,4',5,5'-hexachlorobiphenyl, are substituted at both para and at two or more meta positions. The four coplanar PCBs resembled 3-methylcholanthrene (3-MC) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) in their mode of induction of the hepatic drug-metabolizing enzymes. These compounds induced rat hepatic microsomal benzo(a)pyrene hydroxylase (aryl hydrocarbon hydroxylase, AHH) and cytochromes P-450a, P-450c and P-450d. 3,4,4',5-Tetrachlorobiphenyl, the least active coplanar PCB, also induced dimethylaminoantipyrine N-demethylase and cytochromes P-450b+e and resembled Aroclor 1254 as an inducer of the mixed-function oxidase system. Like Aroclor 1254, all the mono-ortho- and at least eight di-ortho-chloro analogs of the coplanar PCBs exhibited a "mixed-type" induction pattern and induced microsomal AHH, dimethylaminoantipyrine NM-demethylase and cytochromes P-450a-P-450e. Quantitative structure-activity relationships (QSARs) within this series of PCBs were determined by comparing their AHH induction potencies (EC50) in rat hepatoma H-4-II-E cells and their binding affinities (ED50) for the 2,3,7,8-TCDD cytosolic receptor protein. The results showed that there was an excellent correlation between AHH induction potencies and receptor binding avidities of these compounds and the order of activity was coplanar PCBs (3,3',4,4' -tetra-, 3,3',4,4',5-penta- and 3,3',4,4',5,5'-hexachlorobiphenyls) greater than 3,4,4',5-tetrachlorobiphenyl approximately mono-ortho coplanar PCBs greater than di-ortho coplanar PCBs. It was also apparent that the relative toxicities of this group of PCBs paralleled their biological potencies. The coplanar and mono-ortho coplanar PCBs also exhibit differential effects in the inbred C57BL/6J and DBA/2J mice. These compounds induce AHH and cause thymic atrophy in the former "responsive" mice whereas at comparable or higher doses none of these effects are observed in the nonresponsive DBD/2J mice. Since the responsiveness of these two mice strains is due to the presence of the Ah receptor protein in the C57BL/6J mice and its relatively low concentration in the DBA/2J mice, the results for the PCB cogeners support the proposed receptor-mediated mechanism of action.

Effect of the degradation of cytochrome P-450 heme by secobarbital on polychlorinated biphenyls (PCB)-induced hepatic vitamin A reduction and lipid peroxide formation in rats.

The present studies were conducted to characterize the relevance of a microsomal mixed function oxidase system to the polychlorinated biphenyls (PCB)-induced vitamin A reduction and endogenous lipid peroxide formation in the liver of rats. And also, this study dealt with an influence of scavengers on the hepatic lipid peroxide formation stimulated by PCB. Rats were given a 0.01% PCB diet supplemented with adequate nutrients, for 14 days. In an experiment, secobarbital was injected subcutaneously for the degradation of hepatic microsomal cytochrome P-450 heme. A marked liver enlargement and a significant increase of total liver lipid content were observed in the PCB group. The secobarbital enhanced the PCB-induced liver enlargement but no effect of secobarbital on the lipid content was recognized. PCB significantly induced hepatic microsomal cytochrome P-450, but not both cytochrome b5 and NADPH-cytochrome c reductase. The secobarbital suppressed the induction of cytochrome P-450 caused by PCB to approximately one-half. The hepatic vitamin A content significantly decreased on PCB administration and the secobarbital slightly enhanced the PCB-induced vitamin A reduction. However, the vitamin A content in the secobarbital-injected control group decreased to nearly the same levels as in the PCB groups. Therefore, it was presumed that the hepatic microsomal mixed function oxidase system, especially the cytochrome P-450, was possibly not directly involved in the PCB-induced hepatic vitamin A reduction or that a metabolic system related to mixed function oxidase system was involved in the reduction. On the other hand, the hepatic lipid peroxide content tended to increase on PCB administration though no significant difference was recognized. In contrast, the hepatic lipid peroxide content significantly increased in the secobarbital-injected PCB group as compared with the secobarbital-injected control group. However, there was no difference in the lipid peroxide contents between the control groups with and without the injection of secobarbital, and also between the PCB groups. The hepatic vitamin E contents lowered in the secobarbital-injected groups but no effect was observed on PCB administration. The glutathione peroxidase activity decreased significantly on PCB administration and the secobarbital further decreased the activity. Therefore, it was suggested that the significant increase and tendency of increase in hepatic lipid peroxide contents in the PCB groups with and without injection of secobarbital were ascribed to an insufficiency of lipid peroxide scavengers in the liver.(ABSTRACT TRUNCATED AT 400 WORDS)

Influence of dietary antioxidants on polychlorinated biphenyls (PCB)-induced hepatic lipid peroxide formation and vitamin A reduction in rats.

This paper describes experiments designed to characterize the effect of dietary antioxidants on lipid peroxide formation and vitamin A reduction in the liver of rats fed on diets containing polychlorinated biphenyls (PCB). Rats were given 0.025% PCB diets supplemented with dietary antioxidants, for 2 weeks. The antioxidants used were as follows: 10mg% (basal and usual level), 50mg% and 100 mg% of vitamin E, and 50mg% of DPPD and tinoridine respectively. A marked liver enlargement and a significant increase of total liver lipid content were observed in the PCB-fed groups irrespective of the levels of vitamin E and kinds of antioxidants, suggesting that antioxidants were ineffective in preventing the development of fatty liver. Endogeneous lipid peroxide contents in the liver of rats receiving the diets containing 10 mg% vitamin E, DPPD, and tinoridine with PCB increased significantly, whereas no increase was found with the 50 and 100 mg % vitamin E diets with PCB. Hepatic glutathione peroxidase activity was unaffected by PCB and dietary antioxidants. No increase in hepatic vitamin E content occurred in the PCB groups with the addition of 10mg% vitamin E, DPPD, and tinoridine. However, dietary supplementation of vitamin E at higher levels caused an elevation of hepatic vitamin E content and a further increase was observed on the addition of PCB. These results suggest that a sufficiently high level of vitamin E suppresses the increment of the endogeneous lipid peroxide content in the liver of rats fed PCB. On the other hand, the administration of PCB to rats resulted in a significant decrease in hepatic vitamin A content regardless of the levels of vitamin E and kinds of dietary antioxidants. The antioxidants used in this experiment failed to suppress the hepatic vitamin A reduction caused by PCB administration. In addition, an absence of a significant difference in hepatic vitamin A contents among PCB-fed groups was observed. This suggests that the hepatic vitamin A level was independent of PCB-induced lipid peroxidation. Thus lipid peroxidation probably did not mediate the hepatic vitamin A reduction caused by PCB, especially in vivo.

PCBs in the Housatonic River: Determination and Distribution

AbstractAn understanding of the mechanisms for the transport of polychlorinated biphenyls (PCBs) as well as their reactions with sediments should help in developing strategies for removal and disposal of sediments in contaminated rivers. We have developed a convenient procedure, based on multiple linear regression of peak heights (or areas) from gas chromatograms, for estimating individual members (Aroclors) for the PCB group of chemicals. Analysis of the bottom sediments of the Housatonic River system along a 20‐km section revealed that the sediments contained Aroclors 1248, 1254, and 1260 in the ratio of 1.0:0.6:1.9. PCB concentrations were highly correlated with clay and organic matter, suggesting that fine particles consisting of clay‐organo complexes in the sediments may provide a primary means of retention and transport of PCBs. Laboratory sorption of PCBs by clay minerals, humic acid, and the river sediments further substantiate these conclusions.

Some Effects of DDE and PCB on Mallards and Their Eggs

In 1971, 4 groups of mallards (Anas platyrhynchos), each consisting of 4 drakes and 10 hens equally divided into 2 replicates per group, were fed untreated feed or feed containing 40 ppm p,p'DDE, 40 ppm PCB, or 40 ppm DDE + 40 ppm PCB. The feeding period began a month before egg laying, which started in February and continued through June. All eggs were collected daily, and mean shell thickness indices were alike in the control and PCB groups. They were reduced by 17 percent in the DDE group and 19 percent in the DDE + PCB group. The contents of 12 eggs randomly selected from the DDE group contained 373 ppm DDE lipid-basis, and 13 eggs from the DDE + PCB group contained mean residues of 344 ppm DDE + 364 ppm PCB. Egg production was similar in all groups for about the first seven weeks, then it dropped markedly in the DDE + PCB group. Part, but not all, of this group's lower production of intact eggs was due to egg eating. This behavior accounted for 18 of 282 eggs observed lost in the DDE + PCB group, 6 of 394 eggs in the PCB group, and none in the control and DDE groups. Although there was no significant change in shell-thinning or DDE residues when PCB was added to the diet, the reduction in the number of intact eggs produced by the DDE + PCB group suggests that the two compounds may nevertheless interact to influence reproductive success. J. WILDL. MANAGE. 39(3):508-513 Pesticide-induced eggshell thinning has been reported for a number of birds (Anderson and Hickey 1972, Cooke 1973). This generally has been attributed to p,p'-DDE ( 1,1-dichloro-2,2-bis [p-chlorophenyl] ethylene), a metabolite of p,p'-DDT (1,1, 1-trichloro-2,2-bis [p-chlorophenyl]ethane). However, it has not been established satisfactorily whether other environmental pollutants interact with DDE to enhance eggshell thinning, or to create additional problems. Anderson and Hickey (1972) stressed the potential complications of mixtures of pollutants in nature. One group of chemicals logically suspected to interact with DDE is the polychlorinated biphenyl (PCB) complex. PCBs, together with DDE, are among the most commonly reported environmental pollutants (Risebrough et al. 1968, Peakall and Lincer 1970, Dustman et al. 1971). Laboratory studies with combinations of these two compounds in gallinaceous birds have demonstrated simple additive effects in direct toxicity (Heath et al. 1972, Kreitzer and Spann 1973). PCB alone has not induced significant eggshell thinning in experimental studies involving at least five species of birds (Peakall and Peakall 1973). The experiment described here was undertaken (1) to determine if a PCB would enhance DDE-induced eggshell thinning in mallards, and (2) to explore the possibility of other effects on reproduction by exposure to a combination of DDE and PCB. This research was supported by the Denver Wildlife Research Center of the U.S. Fish and Wildlife Service and National Science Foundation Grant GB-11649 to the Institute of Marine Resources, University of California, Berkeley. We thank A. H. Jones, C. P. Breidenstein, and M. Friend for critical advice. Additional assistance was provided by I. T. Anderson, L. R. DeWeese, M. Evett, M. A. Haegele, D. B. Knapp, M. A. MacDonald, C. J. Nasman, and R. E. White. 508 J. Wildl. Manage. 39(3):1975 This content downloaded from 157.55.39.183 on Thu, 26 May 2016 04:54:11 UTC All use subject to http://about.jstor.org/terms DDE AND PCB EFFECTS ON MALLARDS * Risebrough and Anderson 509

Some Effects of DDT, Toxaphene and Polychlorinated Biphenyl on Thyroid Function in Bobwhite Quail

Bobwhite quail were given technical grade DDT, Toxaphene (Tox), or Polychlorinated Biphenyl (PCB) at 5, 50 or 500 p.p.m. in their feed for 4 months. At monthly intervals groups of quail (usually 10) from each experimental group were tested and compared with control birds. Thyroid, adrenal, liver, and body weights were measured as were the 2-hour thyroidal I131 uptakes. Generally, only the higher dosages were effective in producing changes. DDT: DDT early increased the uptake of I131 by the thyroid and by 4 months the 2-hour uptake had returned toward control levels. The thyroid gland was found to be significantly enlarged after 3 months on treatment and remained enlarged thereafter. DDT produced no consistent effect on body or adrenal weights, but the livers were enlarged after 2 months on high dosage treatment. Toxaphene: Toxaphene stimulated thyroid growth and I131 uptake. In the former case, the effects were statistically significant only at the 4-month period while the total thyroid uptake of I131 was significantly increased at 3 and 4 months on treatment. When expressed as percentage of dose of I131 taken up per mg. of thyroid, the uptake was significantly greater after 2 and 3 months on treatment. Toxaphene in high dose rate significantly decreased body weights at all time periods studied. At all dose levels used, Tox seemed to produce adrenal hypertrophy by 3 months. The effects of this chemical on liver weights was slight or none at all. PCB: PCB seemed to depress thyroid size at low dose levels or early in the experiment and to stimulate growth at higher dose levels or later in the experiment. The enlarged glands of the high PCB group took up more iodide than the controls, but each unit weight of these thyroids took up the same amount of iodide as the controls. On the other hand, the thyroids from birds receiving the lower two doses of PCB took up the same amount of iodide as the controls, but each mg. of thyroid took up less. PCB had no consistent effect on body weight or adrenal weight, but produced a very dramatic increase in liver weight. These results are discussed.