Abstract  Sprague-Dawley rats were fed diets containing Aroclor 1254 at o, 5, 50, or 500 ppm for 4 wk. The biologic half-life of Aroclor 1254 in adipose tissue of rats fed 500 ppm, as determined by a gas chromatographic method, was 8 wk in males and 12 wk in females. These results are in line with sex-linked differences reported previously for other chlorinated hydrocarbons. It appears that the lower chlorine homologs in the Aroclor mixture are metabolized while those with higher chlorine content are lost more slowly.

Abstract  The effects of feeding farm-raised mink (Mustela vison) diets containing polychlorinated biphenyl (PCB)-contaminated fish from the upper Hudson River (New York, USA) on adult reproductive performance and kit growth and mortality were evaluated. Diets contained 2.5 to 20% Hudson River fish, providing 0.72 to 6.1 µg ∑PCBs/g feed (4.8-38 pg toxic equivalents [TEQWHO 2005 ]/g feed). The percentage of stillborn kits per litter was significantly increased by dietary concentrations of 4.5 µg ∑PCBs/g feed (28 pg TEQWHO 2005 /g feed) and greater. All offspring exposed to dietary concentrations of 4.5 and 6.1 µg ∑PCBs/g feed (28 and 38 pg TEQWHO 2005 /g feed) died by 10 weeks of age, and all offspring exposed to 1.5 and 2.8 µg ∑PCBs/g feed (10 and 18 pg TEQWHO 2005 /g feed) died by 31 weeks of age, leaving juveniles in the control and 0.72 µg ∑PCBs/g feed (0.41- and 4.8 pg TEQWHO 2005 /g feed) groups only. The dietary concentration predicted to result in 20% kit mortality (LC20) at six weeks of age was 0.34 µg ∑PCBs/g feed (2.6 pg TEQWHO 2005 /g feed). The corresponding maternal hepatic concentration was 0.80 µg ∑PCBs/g liver, wet weight (13 pg TEQWHO 2005 /g liver, wet wt). Mink residing in the upper Hudson River would be expected to consume species of fish that contain an average of 4.0 µg ∑PCBs/g tissue. Thus, a daily diet composed of less than 10% Hudson River fish could provide a dietary concentration of ∑PCBs that resulted in 20% kit mortality in the present study.

Abstract  This study evaluates and quantifies the interactive hepatic tumor promoting effects of two PCBs, the Ah receptor agonist PCB 126 (3,3',4,4',5-pentachlorobiphenyl) and the constitutive androstane receptor (CAR) agonist PCB 153 (2,2',4,4',5,5'-hexachlorobiphenyl). Promotion of altered hepatic foci was evaluated utilizing a medium-term 8-week bioassay for promoters of hepatocarcinogenesis. The assay employs placental glutathione-S-transferase positive (GST-P+) liver cell foci as markers of preneoplasia in female Fischer 344 rats treated with the known initiator diethylnitrosamine followed by partial hepatectomy and by gavage exposure to test chemicals. GST-P+ foci were quantified by histomorphometry and were reported as areas and numbers of GST-P+ foci within the area of liver examined. For PCB 126, the doses were 0.1, 1.0, and 10 microg/kg body weight. For PCB 153, the doses were 10, 100, 1000, 5000, and 10,000 microg/kg body weight. Combined PCB 126 and 153 exposures were 0.1 + 10, 1 + 100, 10 + 1000, 10 + 5000, and 10 + 10,000 microg/kg, respectively. Individual PCB treatment resulted in dose dependent increases in liver and adipose concentrations. Hepatic PCB 153 levels were significantly increased (p < 0.01) after combined exposure. Treatment with PCB 126 or PCB 153 alone resulted in a significant (p < 0.01) dose dependent increase in GST-P+ foci area and number compared with controls. Treatment with the mixture of PCB 126 and 153 resulted in antagonistic GST-P+ focus formation (p < 0.001) for both foci area and number. The less than additive effect was present at all 5 PCB 126/PCB 153 dose combinations, including the low doses of PCB 126 and 153 that did not show significant promotional activity alone.

Abstract  BACKGROUND: PCBs are one of the environmental toxicants and neurotoxic compounds which induce the production of free radicals leading to oxidative stress. Vitamin C is well known as an outstanding antioxidant. We determined the protective role of ascorbate on hypothalamic antioxidant system of Aroclor 1254 exposed rats.

METHODS: The rats were injected Aroclor 1254 at a dose of 2 mg/kg bw/day intraperitoneally for 30 days. One group of rats received vitamin C (100 mg/kg bw/day) orally simultaneously with Aroclor 1254 for 30 days. Twenty-four hours after last treatment, the animals were killed and hypothalamic region was separated from brain tissue. Enzymatic and non-enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and vitamin C were estimated. Hydrogen peroxide (H(2)O(2)), lipid peroxidation (LPO) and acetylcholine esterase (AchE) activity were determined. Serum gonadotropins such as luteinizing hormone (LH) and follicle stimulating hormone (FSH) were also assayed.

RESULTS: Activities of SOD, CAT, GPx, GR, AchE and the concentration of vitamin C were decreased while an increase in H(2)O(2) and LPO were observed in hypothalamus of PCB treated animals. LH and FSH concentrations were also decreased in serum of PCB exposed animals. Vitamin C administration retrieved all the parameters significantly except serum hormonal profiles.

CONCLUSION: PCB induces oxidative stress in hypothalamus by decreasing the activities of antioxidant enzymes, which can be protected by vitamin C treatment.

Abstract  Minks (Mustela vison) fed diets based on either freshwater fish or marine fish were exposed to 1 mg of polychlorinated biphenyls (PCBs) (Aroclor 1242®) daily for 28 d. To minks on the freshwater diet, copper (62 mg/kg food) was also given with or without PCBs. The marine diet (vitamin-rich plus additional supplements) included more vitamin A1 and E than the freshwater diet. We studied how the exposures affected levels of vitamins A1, A2, and E in liver and adipose tissues and levels of vitamins A1 and A2 in plasma. In females and males on the freshwater diet, the hepatic level of vitamin A2 was decreased because of the PCBs, and in these males the hepatic levels of vitamin E also decreased. Interestingly, with coexposure to PCBs and copper, the vitamin levels were, in general, close to the control values. In adipose tissues also, the PCBs induced significant changes in the concentrations of vitamins A1 and A2. In plasma, vitamins A1 and A2 were decreased in all patterns of exposure and on both diets. However, plasma thyroxine was slightly increased, a finding opposite to that reported previously in rodent studies. The results suggest that, in mink, diet greatly modulates the responses to PCBs, which may also differ in males and females. Furthermore, vitamins A1 and A2 may not be metabolized equally during PCB administration.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. Experiments were conducted with growing rats to investigate the effects of dietary 0.05% polychlorinated biphenyls (PCB), 0.3% chlorobutanol (Chloretone), and 0.2% phenobarbital sodium on intestinal absorption of alpha-tocopherol and serum and tissue lipids, and the influence of dietary 5% pectin and 0.2% ethyl p-chlorophenoxyisobutyrate (clofibrate) on the changes in these lipids due to dietary 0.4% Chloretone. Dietary addition of PCB increased serum concentrations of alpha-tocopherol, cholesterol, and phospholipids. These were mainly attributed to the increments in the fraction of high-density lipoproteins. PCB intake increased tissue alpha-tocopherol and apparent absorption of alpha-tocopherol from intestine. Similar changes in serum and tissue lipids and in intestinal absorption of alpha-tocopherol were observed with dietary Chloretone and phenobarbital. Dietary clofibrate and pectin depressed the increase in serum concentrations of these lipids by Chloretone. Change

Abstract  PCBs are a family of persistent environmental toxicants with a wide spectrum of toxic features, such as immunotoxicity, hepatoxicity, endocrine disruption effects, and oncogenic effects. To date, little has been done to investigate the potential influence of PCB exposure on iron metabolism. Deregulated iron would lead to either iron deficiency or iron excess, coupled with various diseases such as anemia or hemochromatosis. Iron metabolism is strictly governed by the hepcidin-ferroportin axis, and hepcidin is the key regulator that is secreted by hepatocytes. Here, we found that PCB-77 could go through plasma membrane and accumulate in hepatocytes. PCB-77 was demonstrated to suppress hepcidin expression in HepG2 and L-02 hepatocytes. Moreover, hepatic hepcidin was observed to be inhibited in mice upon administration of PCB-77. Due to reduced hepcidin concentration, serum iron content was increased, with a significant reduction of splenic iron content. Together, we deciphered the molecular mechanism responsible for PCB-conducted disturbance on iron homeostasis, i.e. through misregulating hepatic hepcidin expression.

Abstract  Evidence from recent epidemiological studies has emerged implicating exposure to environmental toxicants as a novel risk factor for the development of type 2 diabetes (T2D) and the metabolic syndrome in the general population. Humans and other organisms in high trophic levels of the food chain consume persistent organic pollutants (POP) through their diet. Few experimental studies demonstrating cause and effect are available and evidence for a direct association between accumulation of POP and T2D is preliminary; however, the possibility exists that lipophilic chemicals that accumulate in fatty tissue may disrupt cellular function and metabolic homeostasis. Chronic exposure of diabetes-prone C57B/6 mice to a polychlorinated biphenyl (PCB) mixture (Aroclor 1254, 36 mg/kg/wk, 20 wk) alone or in combination with high-fat diet impairs carbohydrate metabolism was compared to vehicle-treated control animals. Specifically, PBC exposure was found to produce hyperinsulinemia in both lean and diet-induced obese mice and exacerbated whole-body insulin resistance in obese mice. These changes in carbohydrate metabolism in response to Aroclor 1254 occurred without marked effect on body weight in both lean and obese mice. Our results demonstrate a causative association between PCB exposure and obesity-induced insulin resistance and hyperinsulinemia independent of body weight changes, an observation that contributes to a growing body of evidence suggesting that exposure to environmental pollutants represents a novel risk factor contributing to the diabetes epidemic.

Abstract  The developing nervous system is a potential target of environmental contaminants such as polybrominated diphenylethers (PBDE), which accumulate in the biosphere. We compared effects of 2,2',4,4',5-pentabromo-BDE (PBDE99), a PBDE congener present in environmental samples, and PCB on brain development. Time-pregnant rats were subcutaneously injected with PBDE99 (1 or 10mg/kg), the PCB mixture Aroclor 1254 (10mg/kg), or vehicle from gestational day 10-18. mRNA levels of genes involved in central control of reproductive functions and sexual behavior were analyzed by real time RT PCR in two sexually dimorphic brain regions, medial preoptic area (MPO) and ventromedial hypothalamus (VMH) of adult offspring of both sexes. Exposure to PBDE99 or the PCB mixture during pre- and postnatal development affected mRNA expression levels in a treatment-, region- and sex-specific manner, and changed the sensitivity of target genes to estradiol. The sex difference in progesterone receptor mRNA levels of VMH normally seen in untreated controls was abolished by both, PBDE99 and PCB. Estrous cycles were significantly affected, and preliminary experiments suggest an impairment of female sexual behavior. Our data indicate that developmental exposure to PBDE99 at doses below signs of general toxicity affects the regulation of estrogen target genes in rat brain. Since PBDE99 was detected in blood and adipose tissue of adult offspring, these effects may result from interactions with developmental processes, with adult functions, or a combination of both.

Abstract  Administration of PCB to rats resulted in an increase in lever weight, hypertrophy with foam-like changes in cytoplasm of individual liver cells, an increase in liver cholesterol levels, an increase in lever aniline hydroxylase activity and a decrease in liver Na-K-Mg-dependent APTase activity. When ABS was simultaneously administered with PCB, most of the above-mentioned abnormalities were observed to increase and were dependent on administration time and dosage. Testicular abnormalities were observed only in rats on long term co-administration of PCB and ABS.

Abstract  The effects of p,p'-DDT (50293) or PCB (polychlorinated biphenyls) on the hepatic cytochrome P-450 contents and on the weights of androgen dependent male sex organs in intact and castrated testosterone treated male mice have been studied. The results obtained show that hepatic cytochrome P-450 contents are significantly higher in the DDT or PCB treated animals than in the controls; that dry weights of the seminal vesicles in the DDT or PCB treated castrated animals are significantly lower than in the castrated controls, whereas no such difference exists in the intact animals; and that dry weights of the testes in the DDT or PCB treated animals do not differ significantly from those in the controls.

Abstract  Poorly metabolized polychlorinated biphenyl (PCB) congeners are bioaccumulated in the bodies of rodents and humans. Little is known about the continuing biological effects of these persistent chemicals. To determine whether a single high dose of a PCB mixture to mice would have long-term effects on liver enzymes, Aroclor 1254 was given at a single dose of 500 mg/kg to (C57BL/6 × DBA/2)F1 female mice. Paired controls received olive oil. Mice were killed at intervals of 0.5 to 55 weeks after treatment and liver assessed for aminopyrine demethylase activity. At selected time points, blood and homogenates of liver and of whole carcass were analyzed for content of PCBs by gas chromatography with electron capture detection. Hepatic aminopyrine demethylase activity was significantly elevated in Aroclor-treated mice, relative to controls, for 42 weeks after treatment. A three- to fourfold increase persisted for at least 14 weeks, with a convergence of treated and control values thereafter. Significant amounts of nine PCB congeners were detected in carcass, liver, and blood; total carcass PCB, estimated on the basis of these congeners, correlated significantly with liver aminopyrine demethylase elevation, and a similar trend was noted for liver. At 42 weeks after treatment, total PCB levels were 70 mg/kg for carcass, 2.4 mg/kg for liver and 0.28 mg/kg for blood. Congener profiles were similar in all three compartments, with the majority of the retained chemical being 2,3′,4,4′,5- and 2,3,3′,4,4′-pentachlorobiphenyl and 2,2′,4,4′,5,5′-and 2,2′,3,4,4′,5′-hexachlorobiphenyl. These results suggest that congeners bioaccumulated after a high PCB dose retain biological activity in the body for nearly a year after treatment.

Abstract  Polychlorinated biphenyls (PCBs) are complex mixtures of congeners that exhibit carcinogenic and toxicant activities in a variety of mammalian tissues. Here, we studied the acute in vivo and in vitro effects of a commercially used PCB product, Aroclor 1248 (A1248), a mixture of tri-, tetra-, and pentachloro congeners. Single intraperitoneal (i.p.) or bilateral intratesticular (i.t.) injections of A1248 decreased serum androgen levels in both groups 24 h after injection. Chorionic gonadotropin-stimulated androgen production by acute testicular cultures from both groups was also reduced, and progesterone production was attenuated in cultures from i.t.-treated animals. The capacity of the postmitochondrial fractions from testes of i.t.-treated animals to convert pregnenolone to progesterone and progesterone to testosterone was reduced as well. In vitro studies revealed that a 10- to 15-min exposure of postmitochondrial testicular fractions and intact interstitial cells from normal animals to A1248 in a subnanomolar concentration range was sufficient to attenuate the conversion of pregnenolone to progesterone and progesterone to testosterone. At micromolar concentrations, A1248 added in vitro also inhibited the conversion of Delta(4)-androstendione to testosterone without affecting the viability of interstitial cells. These results indicate that A1248 down-regulates the testicular androgenesis by an acute inhibition of 3beta-hydroxysteroid dehydrogenase, 17alpha-hydroxylase/lyase, and 17beta-hydroxysteroid dehydrogenase activities.

Abstract  The frequent observation of intra-individual variability (IIV) in the expression of ADHD symptoms suggest that IIV is an integral component of the disorder. We tested IIV in ADHD-like phenotype from five different studies of rodent models of ADHD, including studies with Spontaneous Hypertensive Rats (SHR/NCrl and SHR/N), Wistar-Kyoto Hyperactive Rats (WKHA/N), Wistar-Kyoto Hypertensive rat (WKHT), PCB-126 and -153-treated Lewis rats and behaviorally normal Wistar/Mol, Wistar-Kyoto (WKY/N and WKY/NMol), and untreated Lewis rats. Averages of the absolute residual deviation of ADHD-like behavior from individual means ("individual phenotypic dispersion," PD(i)) were used to represent IIV in the fixed-interval (FI) and extinction (EXT) phases of operant behavioral activity. Across all studies, SHR rats had higher PD(i) than WKY rats (P < 0.0001) for all ADHD-like traits, and higher PD(i) for hyperactivity than WKHT and WKHA/N rats. Male SHR rats in particular had higher PD(i) for hyperactivity than male or female WKYs, SHR females for EXT hyperactivity, and higher dispersion for inattention than WKY females. These findings strongly suggest the genetic control of IIV, and suggest that the SHR may be a useful model for the identification of genes for IIV in human ADHD. These findings also obliquely support the SHR as a useful model for ADHD overall.

Abstract  Polychlorinated biphenyls (PCB environmental and food contaminants) were administered for 12 days in the diet as Aroclor 1254 to male Osborne-Mendel rats at concentrations of 0, 75 or 400 ppm, and effects on body weight gain, food consumption and adipose tissue weights were determined. Concentrations of intermediary metabolites in the liver were also determined; cytoplasmic and mitochondrial redox states and cytoplasmic phosphorylation states were calculated from these concentrations. Rats given 400 ppm of Aroclor 1254 had significantly decreased body weight gains and adipose tissue weights with respect to controls; rats given 75 ppm showed no significant differences in these parameters. Significant differences in the concentrations of intermediary metabolites were found in the livers of rats fed Aroclor 1254 at both the 75 and 400 ppm levels. These concentration changes resembled those occurring as a consequence of thiamine deficiency. The cytoplasmic redox state of liver was greatly shifted toward a highly oxidized condition, as evidenced by significantly increased (NADP+): ratios, in rats receiving Aroclor at 400 ppm; this effect was less pronounced in rats receiving 75 ppm. A similar increase in (NADP+): in the cytosol had been observed in livers from thiamine-deficient rats. No significant differences could be observed in the liver cytoplasmic (NAD+): ratio with respect to control values in either experimental group. The mitochondrial (NAD+): ratio was significantly increased in the group given 400 ppm. The phosphorylation state of liver cytoplasm was significantly increased in rats receiving 400 ppm of Aroclor, and somewhat less in rats receiving 75 ppm.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. We investigated the combined effects of ethanol and polychlorinated biphenyls (PCB) on ascorbic acid metabolism, liver drug-metabolizing enzymes, and lipid metabolism in rats fed on a diet containing by 36% by energy of ethanol and 0.005% of PCB, either singly or in combination, for 49 days. Ethanol and PCB given together synergistically affected the amount of ascorbic acid excreted in the urine and the serum concentration of ascorbic acid. This synergistic effect was also observed in the activity of aniline hydroxylase in the liver. Ethanol and PCB given together seem to have had different effects on lipid metabolism. These results suggest that the effect of ethanol on the metabolism of ascorbic acid and of drugs may be enhanced by combined administration with PCB, and that the ascorbic acid deficiency and/or modification of the drug metabolism may become more serious.

Abstract  A large multi-disciplinary study was conducted to investigate the systemic, neurodevelopmental, neurochemical, endocrine, and molecular pathological effects of a mixture of reconstituted persistent organochlorine pollutants (POP) based on the blood profiles of Canadians residing in the Great Lakes/St. Lawrence region. This report outlines the overall study design and describes the systemic effects in rat offspring perinatally exposed to the POP mixture. Maternal rats were administered orally 0, 0.013, 0.13, 1.3, or 13 mg/kg bw/day of the mixture from gestational day (GD) 1 to postnatal day (PND) 23. Positive and negative controls were given Aroclor 1254 (15 mg/kg bw/day) and corn oil (vehicle), respectively. The rat pups were reared, culled to 8 per litter, and killed on postnatal days 35, 70, and 350, at which time tissues were collected for analysis. Exposure to high doses of the mixture elicited clinical, biochemical, and pathological changes and high mortality rates in rat offspring. Aroclor 1254 produced similar effects but a lower mortality than was seen in POP mixture groups. Biochemical changes consisted of increased liver microsomal activities and elevated serum cholesterol. Hepatomegaly was observed in the highest dose group of the mixture and in the positive control. Liver, thymus, and spleen were the target organs of action. Microscopic changes in the liver consisted of vacuolation and hypertrophy, and those in the thymus were characterized by reduced cortical and medullary volume. The spleen showed a treatment-related reduction in lymphocyte density and lymphoid areas. This study demonstrates that exposure to the POP mixture up to 13 mg/kg/day perinatally produced growth suppression, elevated serum cholesterol, increased liver microsomal enzyme activities, and immunopathological changes in the thymus and spleen, and lethality. Most of the effects were seen at dose levels much higher than expected human exposure.

Abstract  HEEP COPYRIGHT: BIOL ABS. The interaction between PCB (polychlorinated biphenyl) toxicity and dietary fats was examined. Weanling Sprague Dawley male rats received experimental diets containing 0.1% PCB in which the tetrachloride isomer was dominant. When rats were fed the 0.1% PCB diets containing different fats at 10% levels for 6 wk, the growth rate of the lard group was significantly lower than that of the other 3 groups, soybean oil, olive oil and crisco. The weight gains of experimental animals given 0.1% PCB for 6 wk varied by the different fat levels which were kept at 5% and 25% in the diet. The growth rates of the 5% soybean oil group and 5% lard group were lower than that of the 25% fat groups. The weight gain of the 5% lard group was the lowest and only 4 of 9 rats in this group survived over 38 days after PCB treatments started. The significant increase of phospholipid and cholesterol concentration in the serum and liver of rats given 0.1% PCB was shown regardless of the quality and level of dietary fats. Triglyceride concentration in the serum and liver of the PCB-fed group tended to decrease, but it tended to increase in the liver of rats fed a 0.1% PCB diet with 25% level of soybean oil. Unmetabolized PCB accumulated more in the liver of 25% fat groups than that of 5% fat groups. The possible mechanism in the severe toxic effect of PCB in low lard group was discussed in connection with the relative increase of linoleic acid requirement followed by phospholipid elevation in PCB-treated animals.

Abstract  HEEP COPYRIGHT: BIOL ABS. Effect of dietary vitamin E levels on the depression of vitamin A storage and lipid peroxide formation in rats given PCB (polychlorinated biphenyls) was studied. Weanling male Sprague Dawley rats were fed experimental diets containing 0, 0.01 and 0.025% PCB and 10 and 25 mg% vitamin E (as alpha-tocopheryl acetate) for 10 days. PCB and vitamin E added to the diets showed no significant effect on body weight gain. Hepatic hypertrophy was observed as PCB content in the diet increased but it was not depressed by ingestion of diet containing 25 mg% vitamin E. PCB administration with vitamin E at a higher level (25 mg%) enhanced concentrations of vitamin E in the liver. No significant difference in vitamin E content of the liver was observed between animals fed diets containing 10 mg% and 25 mg% vitamin E without PCB. Vitamin A content in the liver decreased with increased PCB in diet and a larger supply of dietary vitamin E did not prevent the depression of vitamin A storage. TBA value in the liver of rats fed a 0.025% PCB diet increased significantly and the value was not depressed by the larger supply of dietary vitamin E (2.5-fold usual level). Glutathione peroxidase activities in the whole liver were not varied by PCB administration and levels of dietary vitamin E. Activities/gram of the tissue were lowered in the liver enlarged by PCB. The larger supply of dietary vitamin E depressed the content of cytochrome P-450 in the liver microsome which was significantly induced by ingestion of PCB.

Abstract  Effect of feeding xenobiotics on serum cholesterol and high density lipoprotein (HDL)-cholesterol in rats was examined. Dietary addition of 0.05% PCB (polychlorinated biphenyls), 0.3% chloretone, 0.05% DDT, 0.3% BHA (3-tert-butyl-4-methoxyphenol), 0.3% caffeine, 0.2% BHT (2,6-di-tert-butyl-p-cresol) or 0.2% sodium pentobarbital resulted in a significant increase in serum total cholesterol and HDL-cholesterol. A good correlation between serum total cholesterol and HDL-cholesterol was also observed. Dietary PCB, chloretone, caffeine and pentobarbital decreased the ratio of low density lipoprotein and very low density lipoprotein-cholesterol vs. HDL-cholesterol, but dietary BHA and BHT increased the ratio.

Abstract  Syngeneically and allogeneically mated CBA mice were daily given orally either pure peanut oil or peanut oil containing 0.5 mg 2,2', 4,4', 5,5'-hexachlorobiphenyl (HCB) beginning at the day of implantation. The mice were dissected on day 12 and 18 of gestation when the weight of thymus, spleen, and liver were recorded. The spontaneous mitotic activity of spleen cells was evaluated in vitro, and the number of resorbed foetuses was recorded. Neither spleen weight nor thymus weight was altered, but the liver weight was significantly increased by HCB treatment. The spontaneous mitotic activity of spleen cells did not differ significantly between HCB-treated and control mice. The frequency of resorbed foetuses was not increased by HCB treatment either in syngeneically or allogeneically mated mice, but it was observed that mice fed HCB were less sensitive to environmental disturbance than control mice.

Abstract  Metabolic changes in lipids, ascorbic acid, and hepatic microsomal cytochrome P-450 by feeding polychlorinated biphenyls (PCB) were investigated in streptozotocin-induced diabetic rats. Streptozotocin (STZ, 60 mg/kg body weight) was injected in Wistar male rats intraperitoneally. Diabetic and non-diabetic rats were fed ad libitum a 20% casein-based control diet or a PCB-containing diet (200 mg/kg diet) for 9 days. Body weight decreased significantly in STZ-induced diabetic rats with or without PCB (groups PD and D, respectively). In rats of group D, urinary ascorbic acid excretion was 15 times higher than that in non-diabetic rats fed a control diet (group C). Dietary PCB caused 30-fold higher urinary ascorbic acid excretion in non-diabetic rats (group P) than that in group C. In group PD, urinary ascorbic acid was nearly 60 times higher than that in group C. Ascorbic acid in liver and kidney was significantly lower in group D than in group C, and it was significantly lower in group PD than in group P. Liver microsomal cytochrome P-450 and b5 were both increased by dietary PCB in group P. Addition increase in these enzymes was observed in diabetic rats by PCB. Serum total cholesterol was 1.8 times higher in group P than in group C. Further increase in serum total cholesterol was observed in group PD. These data suggest that metabolic changes in lipids and ascorbic acid induced by the dietary xenobiotic were magnified in STZ-induced diabetic rats.

Abstract  One-day-old cockerels were fed: (J) 3,10,30,100, and 300 ppm of 3,4,5,3',4',5'-hexachlorobiphenvl (HCB); (II) 400 ppm of 2,3,4,2',3',4'-HCB; (III) 400 ppm of 2,4,5,2',4',5'-HCB; (IV) 400 ppm of 2,3,6,2',3',6'-HCB; and (V) 400 ppm of 2,4,6,2',4',6'-HCB. Surviving chicks were sacrificed at 21 days. Male mice were fed 10,30, 100 and 300 ppm of three of the above isomers (I, III, V), and survivors were sacrificed at 28 days, HCB's levels in adipose tissue and liver were determined. There were variations among the isomers as to dose and pathologic effects. Isomer (I) showed the greatest effect of those studied on mortality, body weight gain, liver, thymus, and spleen; it also attained the highest tissue concentration. It was the only isomer which produced porphyrin accumulation; and, in the chicks, produced hydropericardium, ascites, and edema. The decreasing order of overall toxicity was I >> V > II, III, I V. A general similarity of response was observed in both chicks and mice.