Polybrominated biphenyls, polychlorinated biphenyls, pentachlorophenyl--and all that.
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Dietary polychlorinated biphenyls in feeds at concentrations of 20 ppm given to swine and sheep between weaning and time of their reaching market weight reduced feed efficiency and rate of gain. These effects were of the same magnitude as those observed in swine and sheep fed sub-optimal diets, and in swine, there was a highly significant interaction between diet and polychlorinated biphenyl effects. Gross and microscopic lesions were few, consisting of increased frequency of pneumonia in swine and sheep and of increased frequency and severity of gastric lesions in swine. The gastric lesions in swine consisted of erosions of surface mucosa; these lesions were greater in the swine given the higher dose levels when they included hypertrophy, hyperplasia, and deep ulcerative lesions.
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Polychlorinated biphenyls (Aroclor 1221, 1242 and 1254) at concentrations up to 0.1% in glucose did not inhibit the growth of lake water bacteria. The bacteria used Aroclor 1221 and 1242 but not 1254 as sole carbon and energy sources for growth. Less than 1% of lake water bacteria, however, possess this ability. Seven bacterial isolates from Aroclor agar plates were identified; five belonged to Achromobacter sp. and two were Pseudomonas sp. The metabolic breaksown of Aroclor 1221 was followed. THE MIXTURE WAS COMPLETELY DEGRADED INTO SEVERAL LOW MOLECULAR WEIGHT COMPOUNDS AFTER ONE MONTH INCUBATION. Unchlorinated biphenyl was degraded at a faster rate than 2-chlorobiphenyl and 4-chlorobiphenyl isomers.
The effects of polychlorinated biphenyls were studied in eight germfree pigs. Beginning at fourteen days of age, two pigs each were fed daily 12.5, 25, 50 and 100 mg/kg body weight of polychlorinated biphenyls as Aroclor 1254. Three germfree pigs were negative controls. Clinically the treated pigs had inappetance, a hemorrhagic diarrhea, erythema of the nose and the anus, retarded growth, distended abdomen and at the higher dose levels, incoordination and coma followed by death. Deaths occurred in 11 to 35 days after exposure. At necropsy, the piglets exhibited grossly enlarged mottled liver, erosions of the gastric mucosa, hemorrhages through the mesentery and the intestinal wall, a fibrinous pericarditis, a hypoplastic thymus and congested swollen thyroid glands. The histopathological lesions included hepatic centrolobular necrosis, interstitial myocarditis, endocarditis, myopathy of the muscles, gastric erosions and colitis. All of the organs examined for polychlorinated biphenyls had elevated residue levels which were particularly high in the fat, liver, psoas muscle, brain and kidney and were higher than has been reported in conventional pigs fed approximately equal concentrations of polychlorinated biphenyls. The severity of clinical signs, pathological changes and tissue concentrations were directly related to the dose administered and were more pronounced in the germfree pigs than has been described in conventional pigs.
Rats fed a polychlorinated biphenyl (PCB) mixture in a high- or low-iodine diet (HID or LID respectively) for 15 days had thyroid enlargement, low serum thyroxine (T4), and high serum thyrotropin concentrations. Although binding of thyroid hormones to serum proteins was reduced in PCB-fed animals, the free T4 index (reflecting free T4 in serum) was less in these rats. Both serum triiodothyronine (T3) and the free T3 index were elevated in rats fed PCB in HID. LID-maintained rats elevated serum T3 concentrations but the free T3 index was similar to that in HID-fed rats, owing to enhanced binding of thyroid hormone to serum proteins. Addition of PCB to LID reduced serum T3 levels but did not alter the free T3 index because binding was less. In rats fed HID containing PCB, thyroid 131I uptake was increased.
Administration of the polychlorinated biphenyls (PCBs) mixture, Aroclor 1016, to rats elicited a barbiturate type of inducing effect on the hepatic microsomal oxidative enzyme system. Aroclor 1016 caused significant increases in liver cytochrome P-450 content, microsomal protein, and ethylmorphine N-demethylase activity; its effect on benzo(a)pyrene hydroxylase activity was minimal. Unlike the widely studied PCBs mixture, Aroclor 1254, Aroclor 1016 did not induce cytochrome P-448 in liver microsomes. Five workers occupationally exposed to Aroclor 1016 in a capacitor-manufacturing plant showed a significantly lower mean antipyrine half-life (10.8 hr) than the mean half-life of 15.6 hr in non-PCBs-exposed normal subjects. These differences in half-life were accompanied by increased metabolic clearance rates in workers exposed to the PCBs, which strongly suggests that PCBs accelerate the rate of drug metabolism in man. Our studies show that Aroclor 1016 elicits the barbiturate type of inducing effects on drug metabolism in man as well as animals.
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Of 36 pure isomers (chlorine numbers 1 to 5) of polychlorinated biphenyls examined, 23 compounds were metabolized by Alcaligenes sp. strain Y42, and 33 compounds were metabolized by Acinetobacter sp. strain P6. The major pathway of many polychlorinated biphenyl isomers examined was considered to proceed through 2',3'-dihydro-2',3'-diol compounds, concomitant dehydrogenated 2',3'-dihydroxy compounds, subsequently the 1',2'-meta-cleavage compounds (chlorinated derivatives of 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acids), and then chlorobenzoic acids. The meta-cleavage products were usually converted to chlorobenzoic acids upon further incubation in many polychlorinated biphenyls, but they accumulated specifically in the metabolism of 2,4'-, 2,4,4'-, and 2,5,4'-chlorobiphenyls, which are all chlorinated at the 2,4'-position in the molecules in common. Dihydroxy compounds accumulated mainly in the metabolism of 2,6-, 2,3,6-, 2,4,2',5'-, 2,5,2',5'-, and 2,4,5,2',5'-chlorobiphenyls by Acinetobacter sp. P6. The 2,3,2',3'-, 2,3,2',5'-, and 2,4,5,2',3'-chlorobiphenyls, which are chlorinated at the 2,3-position of one of the rings, were metabolized in a different fashion. Two major metabolites of a chlorobenzoic acid and an unknown compound accumulated always in the metabolism of this group of polychlorinated biphenyls. 2,4,6-Trichlorobiphenyl was metabolized quite differently between the two organisms. Alcaligenes sp. Y42 metabolized this compound very slowly to trichlorobenzoic acid by the major oxidative route. In contrast, Acinetobacter sp. P6 metabolized it to a trihydroxy compound via a dihydroxy compound.
Single-dose oral administration of a commercial polychlorinated biphenyl product containing 54% chlorine provided data with which to plot the time course of total polychlorinated biphenyl and individual components in the blood of swine and sheep. Pharmacokinetic parameters describing absorption from the gut and elimination from a two-compartment body system were determined for the components in swine and sheep. The absorption half-time for total polychlorinated biphenyl in swine was 1.13 hr while that for sheep was 3.83 hr. The half-time for disposition of total polychlorinated biphenyl from the central compartment was 4.4 hr in swine and 7.7 hr in sheep; the apparent biological half-life was 62.4 hr in swine and 78.8 hr in sheep. Individual components varied significantly from each other and from total polychlorinated biphenyl in all parameters.
Polychlorinated biphenyls (Aroclor 1221, 1232, 1242, 1248, 1254, 1260, 1262, and 1268), polychlorinated terphenyls (Aroclor 5460), a mixture of polychlorinated biphenyls and terphenyls (Aroclor 4465) and polybrominated biphenyls (BP-6) were administered in a single dose, 100 mg/kg body weight injected orally, to mature male and female Japanese quail. Two hr after Aroclor treatment, pentobarbital sleeping times were prolonged (2 to 3 times control) in both male and female quail. Twenty-four hr after treatment, sleeping times were similar to those of controls. However, 48 hr after treatment with Aroclor 1248 through Arolcor 5460 and with BP-6, sleeping times of males were only 1/2 those of controls, whereas after treatment with Aroclor 1221, 1232 and 1242, sleeping times were similar to those of controls. The reduction in sleeping times of male quail 48 hr after administration of PCBs was correlated with the percentage of chlorine in the PCB with greater reductions in male than female quail. The response after three days ad libitum feeding of 300 ppm of each substance was the same as the response 48 hr after a single oral injection. Although very few birds died from the toxicity of the Aroclors and BP-6, mortality was greatly increased during anesthesia when the pentobarbital was administered two hr after single oral dosing.
Polychlorinated biphenyl (PCB) compounds were administered in the diet to White Leghorm pullets for 10 weeks. Average embryonic mortality in eggs from pullets fed Aroclor 1242, Aroclor 1254 and 2,4,5,3',4',-pentachloro-biphenyl was 54.7, 59.2 and 74.0 percent, respectively, which was significantly high (p less than .001) compared to controls; however, these three feeds were shown qualitatively to have dibenzodioxin contamination. Degree of chlorination of PCB analogs may not infer that they are toxic, but rather, the position of substitution may be the factor that determines the toxicity to developing embryos.
Polychlorinated biphenyls (PCBs) are a group of compounds which have many industrial uses and have become an environmental pollutant. In the rhesus monkey, an unusual type of gastric hyperplasia has been produced by feeding the animals small amounts of these chemicals. By using a double contrast gastrogram with simultaneous pneumoperitoneum, we studied the development of the lesions radiographically. Over a period of several months the gastric abnormality progressed from minimal thickening of the gastric wall, with normal appearing mucosa, to extensive nodularity and irregularity in the area of involvement. This technique provides a method for studying the characteristics of the gastric hyperplasia over an extended time, and therefore has several advantages over autopsy studies or surgical biopsies. Although no similar lesions related to PCB exposure have been seen in humans, no survey of possible gastric changes has been done among persons exposed to these materials.