Document 6wN4o15dkXnBMm3BJ9oLZerY6

,v Scientific Gommunications cm f If Polychlorinated Biphenyls . Storage, Distribution, Excretion, and Recovery: Liver Morphology After Prolonged Dietary Ingestion Virlyn \V. Burse; Renate D. Kimbrough, MD; Ellen C. Villanueva, MS; Ralph W. Jennings; Ralph E. Linder; G. Wayne Sovocool, PhD i \[ y< Rais were fed 100 ppm of Aroclor 1242 been restricted to closed systems. A served (Table 1); one control and four rats (6.6 to 3.89 mg/kg/day) or 100 ppm Aro new PCB, Aroclor 1016, which is a fed Aroclor 1016 or 1242 were killed two clor 1016 (6.9 to 3.5 mg/kg/day). Plasma, good dielectric and heat transfer fluid weeks after onset of the experiment. Four f kidneys, urine, brain, liver, and adipose tissue we-.ie analyzed for polychlorinated biphenyl (PCS) residues at 0.5, one, two, four, six, eight, and ten months of expo has been proposed. It contains a lower percentage of the higher PCBs and should prove to be less persistent in additional rats of each experimental group were killed one and two months after onset of the experiment The further killing of four experimental rats for each PCB mix sure. In adcUHpna! groups ted the experi the environment. The higher PCBs ture as well as four controls that served for mental diet for six months, PCB tissue appear to be more persistent, as evi both experimental groups were made four, levels were determined two, four, five, and denced by mass spectral residue anal six, eight, and ten months after onset of 4 11 $* \. \\ i jt iL six months after the exposure to PCBs . ysis of environmental samples.4-5 the experiment After six months feeding, was discontinued. PCBs were highest in It is the purpose of this paper to re the experimental diets were discontinued ! ; adipos tissue where a steady state was approached in two and reached in 4 months. Little PCB-derived material was excreted in urine. After discontinuing PCB exposure, Aroclor 1016 was eliminated more rapidly from the organs than Aroclor 1242. Measurabhs residue levels were still present ' 'after five (Aroclor 1016) and six (Aroclor port results of feeding studies con ducted in rats with Aroclor 1016 and Aroclor 1242. Aroclor 1242 in its gen eral make-up is very similar to Aro clor 1016, it only lacks the higher PCBs (Papageorge, written commu nication, June 1973). The Aroclors dif fer in the percentages of fixed chlo on 18 randomly selected rats for each PCB mixture. These rats were fed plain chow and four for each PCB mixture were killed together with four control rats at two, four, and five or six months (Table 2) of re covery. Twenty-four hours prior to each' killing the rats were housed in individual metabolism cages and urine was collected. During the 24-hour period prior to death, V 1242) months of recovery. Microscopic rine, 43% 0.5% (1242) vs 41.3% none of the rats in the study was fed a for examination of the liver showed enlarged 0.5% (1016). Aroclor 1242 contains 9% liver cdls with vacuolated cytoplasm and biphenyls with five or more chlorines Inclusions. and Aroclor 1016 contains 1% bi phenyls with five or more chlorines. The use and replaceability of polychibrinated biphenyls (PCBs) has recently been reviewed.1 Because of MATERIALS AND METHOD their extensive use in the past and their slaw biodegradability, PCBs are Aroclors 1242 and 1016 were of electrical gr-de, lot No. KB-05-415 and KB-06-756, tified diet Oxalated blood was obtained by cardiac puncture from rats anesthetized with ether. The animals were killed by exsanguination and liver, fat, kidney, and brain tissues were collected. The liver was weighed and the tissues were frozen for chemical analysis. Liver tissue from the animals killed at four months and at sub sequent killings were also fixed in buffered 4% formaldehyde for microscopic examina 1f 4 l. now widely distributed in the envi res lectively. The PCBs were fed in parallel tion, and stained with hematoxylin-eosin. ronment2'3 Recently the use of these materials in the United States has exj eriments to male Sherman strain rats, 611 > 73 days old. A total of 158 rats was dividt d into two groups of 27 and two groups Liver tissue at four months of exposure to Aroclor 1016 and at six months of exposure to Aroclor 1242 together with an equal \\ i of 52 rats each according to a table of ran number of controls for electron micro Submitted for publication May Iff, 1974; ac dom numbers. The rats were group caged scopic examination was fixed in chilled, cepted July 17. From tire Environmental Protection Agency, Chamblee Toxicology Laboratory, Chamblee, Ga and weighed weekly. Their food consump tion was measured, one week prior to each buffered 5% glutaraldehyde for two hours, postfixed in 1% osmium tetraoxide, dehy (Mr. Burse, Dr. Kimbrough, Ms. Villanueva, Mr. scheduled killing. The groups of 52 rats drated through changes of alcohol and Jennings, and Mr. Linder), and the NERC, EPA, were fed the experimental diets that con propylene oxide, and embedded in resin. Research Triangle Park, NC (Dr. Sovocool). Mr. tainer. 100 ppm of Aroclor 1016 or Aroclor Sections were cut with a glass knife, 4 Burse is currently with the US Consumer Prod uct Safety Commission, Atlanta; Dr. Kimbrough 1242. dhe control rats were fed ground lab- stained with lead citrate and uranyl ace is with the Center for Disease Control, Tox orator- chow ad libitum. tate, and examined with an electron micro icology Branch, Atlanta; Ms. Villanueva is with The PCBs were incorporated into the scope. the Coca-Cola Export Corporation, Atlanta; Mr. diets by dissolving them in ether and pour The analytical methods used for the de 1 Jennings is with the Environmental Protection Agency, Region IV, Atlanta; and Mr. Linder is ing this solution onto 100 gm of com termination of PCB-derived materials . i with the Pesticides and Toxic Substances Effects starch. The ether was evaporated and the have been described previously.6 Briefly, ; 3 Laboratory, 5ERC, EPA, Research Triangle PCB cornstarch mixture diluted with in 100 to 200 mg of fat, brain, kidney, and Park, NC. Reprint requests to the Toxicology Branch, Center for Disease Control, 1600 Clifton Rd, NTS, creasing amounts of ground chow in an electric mixer. liver or 1 to 2 ml of plasma were extracted with hexane. Brain was extracted with - Atlanta, GA 3033S: (Dr. Kimbrough). The following killing schedule was ob acetone, the solution evaporated tc dryness i i Ii i i ^. . . . . - j Arch Environ Health/Vol 29. Dec 1974 Polychlorinated RiDhenyls/Burse et at 301 I DSW 342353 STLCOPCB4083840 I containing 100 ppm Aroclor 1242 for eight months. Table 1,--Mean Concentration and Standard Error of PCB-Derived Materials in Tissues of Four Rats Per Killing Fed 100 ppm Aroclor 1242 or 1016 - - Plasma Kidneys Urine* Brain Liver Adipose Tissue on Diet 0.5 1 6 e ,10 Aro 1242 0.081 0.000 0.180 0.030 0.310 0.057 0.213 0.028 0.528 0.150 0.240 0.052 0.172 0.014 Aro 1016 0.182 0.017 0.175 0.028 0.331 0.010 0.372 0.040 0.384 0.024 0.394 0.014 0.334 0.040 Aro 1242 0.68 0.15 0.51 0.13 1.44 0.18 1.84 0.27 1.89 0.47 2.14 0.41 3.13 0.53 Aro 1016 0.63 0.08 1.58 0.11 2.74 0.19 4.76 0.24 3.21 0.48 2.07 0.06 1.84 0.38 Aro 1242 <0.02 <0.01 <0.02 0.030 0.02 0.028 0.000 0.168 0.04 <0.01 Aro 1016 0.075 0.042 0.008 0.000 0.162 0.038 0.259 0.083 0.275 0.112 0.057 0.017 0.021 0.000 Aro 1242 <0.25 <0.25 <0.25 0.56 0.08 1.69 . 0.25 1.63 0.24 2.05 0.08 Aro 1016 1.52 0.75 3.05 0.13 3.40 0.13 3.18 0.23 2.98 0.44 2.64 0.36 2.70 0.36 Aro 1242 Aro1016 0.55 1.46 0.08 0.24 1.46 3.05 0.10 0.26 3.24 3.86 0.30 0.36 3.94 7.40 0.72 0.79 4.21 7.86 0.57 0.75 4.56 * 5.97 0.61 0.94 6.39 6.70 0.68 0.34 Aro 1242 35 2.4 85 10 92 1.5 115 11 110 13 143 6 133 15 Aro 1016 69 4 103 8 182 12 214 18 236 9 221 10 188 9 * Confirmed qualitatively by Coulson conductometry. 'J Table 2.--Mean Concentration and Standard Error of PCB-Derived Material in Tissues of Four Rats -' Two, Four, Five, or Six Months After They Had Been Fed 100 ppm Aroclor 1242 or 1016 for Six Months Months Plasma Recovery Aro 1242 Aro 1016 0.438 0.154 0.091 0 034 0.149 0.193 0.000 0.050 0.062 . * " ... 0.011 0.122 0.026 ... Kidneys Aro 1242 2.07 0.40 1.84 0.27 0.34 0.06 Aro 1016 1.08 0.27 1.82 0.44 0.44 0.14 Urine Aro1242 Aro 1016 0.02 . 0.033 0.01 0.004 <0.01 0.008 0.002 0.006 0.002 0.004 0.000 Brain Aro 1242 1.06 0.24 1.22 0.53 0.51 0.06 Aro 1016 1.40 0.07 1.35 0.21 0.38 0.06 Liver A Aro 1242 Aro 1016 4.32 2.25 0.72 0.32 3.46 3.13 1.04 0.78 . . . 1.06 0.09 0.97 ... 0.35 Adipose Tissue Aro 1242 60 3.7 44 9 24 5 Aro 1016 104 13 36 6 28 1 * Experiment had to be prematurely terminated. 302 Atch Environ Health/Vol 29, Dec 1974 ' Polychlorinated Biphenyls/Burse et al DSW 342354 STLCOPCB4083841 I; . t I i w 1 v ! r Fig 2.--Chromatograms of Aroclor 1016:2.84 ng. extract of urine: 5.4 mg, and adipose tissue: 0.008 mg from a male rat fed a diet con taining 100 ppm Arodor 1016 for eight months. Table 3.--Incidence of Microscopic Changes Observed in Livers of Rats Fed Aroclor 1242 or 1016 Enlarged Length of Hepatocytee Exposure Aro 1242 Aro 1016 4 2/4 4/4 6 4/4 4/4 8 4/4 3/4 10 4/4 4/4 6 mo exp 2 mo rec 2/4 1/4 6 mo exp 4 mo rec 3/3 3/3 6 mo exp* 6 mo rec 3/4 Vacuolated Cytoplasm Aro 1242 i. . 3/4 3/4 4/4 Aro 1016 1/4 1/4 1/4 3/4 1/4 1/3 1/3 ... -- Inclusions Aro 1242 ... 3/4 3/4 1/4 Aro 1016 3/4 ... 1/4 ... 1/3 1/3 2/4 ... Brown Pigment Aro 1242 Aro 1016 2/4 ... 2/4 ... ... ... ... ... ... ... Foamy Cytoplasm Aro 1242 Aro 1016 ... ... ... ... 2/4 ... ... ... ... ... ... ... Foci of Necrosis Hemorrhage Aro 1242 Aro 1016 ... 1/4 1/4 ... ... ... ... ... ... ... * Only rats fed Aroclor 1242 were examined microscopically. : and the solute taken up in hexane. Urine, kinds of samples was based in each in ered to offer the best estimate of quantita i' 10 to 20 ml, was extracted at approxi- stance on total response in peak heights. tion. . < mately pH 7 with hexane. Each sample in a However, as reported more fully below, ; volume of 0.5 ml was eluted from a micro there were qualitative differences in the RESULTS > silica gel column using a 1:1 benzene- peaks for the standard, the urine, the tis- The rats did not suffer from any [ : hexane mixture. Samples were analyzed with a tritium sues collected during dosing, and the tissues collected after dosing was discontin- overt clinical symptoms of poisoning. source electron capture detector operated ued. Under these circumstances exact During the course of the experiment in the direct current mode at 12 v. Quar.ti- quantitation is impossible, but the use of five rats that were fed Aroclor 1016 tatior. at the standard and of the different total response in peak heights is consid and one rat that was fed Aroclor 1242 Arch Environ Health/Vol 29, Dec 1974 Polychlorinated Biphenyls/Burse et al 303 DSVV 342355 tv \ i:' i! I it. n iti,. STLCOPCB4083842 ! T i j j < $ .1 % ?; j j: ii Fig 3.--Chromatograms of adipose tissue: 0.011 mg from a rat fed a diet containing 100 ppm ArocSor 1242 for six months and six months of a control diet; 0.016 mg from a rat fed a diet containing 100 ppm Araclor 1016 for six months and a control diet for five months. (Relative retention times were computed relative to the most intense electron capturing peak present in Aroclor 1016 or 1242. All gas chromatographic columns were composed of 1.5% OV-17/1.95% QF-1 on 100/120 Gas Chrom Q.) died. The cause of death was not es weights of the experimental animals tablished. Jib difference between the did not differ from those of the con experimental and the control rats was trols. observed in the body weight gain and The concentrations of the PCB-de the food consumption. As the rats rived materials are given in Table 1. aged food consumption decreased The observed levels in adipose tissue relative to their body weight. The are also shown in Fig 1. The highest amount of Aroclor 1242 consumed by . concentrations for both compounds the rats ranged from 6.6 mg/kg body were found in adipose tissue, ranging weight/day to 3.89 mg/kg body from 35 to 143 ppm for Aroclor 1242 weight/day, and the amount of Aro- and 69 to 236 ppm for Aroclor 1016. dor 1016 consumed by the rats ranged The levels for brain, liver, and kidney from 6.9 mg/kg body weight/day to were lower. The concentrations in 3.5 mg/kg body weight/day. urine and plasma were always less At autopsy the organs appeared than 1 ppm. In adipose tissue a steady grossly normal except for one rat fed state of storage of both compounds Aroclor 1016 that had leukemia (a dis was approached in about two months ease that occulta, occasionally sponta and essentially achieved in four neously in our colony). The liver months. Gas chromatographic traces for ail tissues were similar to those obtained from adipose tissue. The traces ob tained from urine analysis had an en tirely different appearance. The dif ferent profiles obtained from adipose tissue, urine, and the PCB standards are illustrated in Fig 1 to 3. When the peaks in the PCB standards were compared with the peaks obtained from PCB-derived material stored in the adipose tissue, it was found that some of the early peaks were absent, the intensity of others was enhanced, and peaks also emerged that were ob served only as "shoulders" in the standard. This observation suggests either preferential absorption from the gastrointestinal tract, or preier- ls 304 Arch Environ Health/Vol 29, Dec 1974 Polychlorinated Biphenyls/Burse et al rt DSW 342356 yT- --v `Vf. V. STLCOPCB4083843 #* - . ential metabolism, distribution, and * excretion in the rata or both. ' The urine samples show a very dif ferent pattern. This suggests that certain isomers are excreted by the kidneys, that the products excreted in the urine are polar metabolites, or that nonchlorinated moieties re sponded to the electron capture de tector. However, a positive response was obtained with a conductometric detector (Coulson). Residue levels arising from Aroclor 1016 ingestion were generally found *r to be higher than for Aroclor 1242, 5 ** Fig 4.--Residues resulting from a con tinuous diet of a 100 ppm concentration of Arcelor 1016 () or Aroclor 1242 () for a period of ten months. Residues following a continuous diet for only six months and re covery for five months for Aroclor 1016 *A () and for six months for Aroclor 1242 (o) are illustrated by the broken lines. Each point represents the mean and stan dard error (I) oS four rats. - i Fig 5.--Liver of rat fed Aroclor 1016 for four months. Note dilated vesicles of smooth endoplasmic reticulum (SER). Some of the mito- chondria are degenerated and others show an increased number of parallel arranged cristae (lead citrate, uranyl acetate, x 35,000). ir i ? i {,: i i*r *4* ' 1 * C H."f I I * i T1 I i i 1 Arch Environ Health/Vol 29, Dec 1974 '-A .. . - '-.H .1 Y-- ; < /> jV. ii V . Polychlorinated Biphenyls/Burse et al 305 DSW 342357 STLCOPCB4083844  with the exception of the residues ob- electron capturing peak present in some of the livers of the experimental served in the kidneys. However, this Aroclor 1016 or 1242. All gas chro- rats fed Aroclor 1242 but not in rats was not true for all organs at every matographic columns were composed fed Aroclor 1016. killing. After a ten-month feeding of 1.5% OV-17/1.95% QF-1 on 100/120 Vacuolation of the cytoplasm of the period the concentration of both Gas Chrom Q.) If these results are liver cells was more consistently ob- PGBs in the liver was about the same, compared with those obtained earlier served in the livers of rats fed Aroclor while at four months almost twice as from adipose tissue, a slight decrease 1242. Generally not much difference snuch Aroclor 1016 as Aroclor 1242 in the number of peaks as well as a was seen in the incidence of the vari- was found. The levels found in adi- difference in the relative heights of ous changes between the two experi- pose tissue indicate a very sharp rise the peaks is noticed. mental groups. All of the observed during the first month for Aroclor Composite urine and fat samples changes have to be considered as mild 1242, while Aroclor 1016 also main- from rats fed Aroclor 1242 and 1016 alterations that have been observed tains a sharp rise through the second , continuously for varying time periods with a number of chlorinated cyclic month. After two months of exposure were analyzed by gas chromatogra- chemicals. no appreciable increase was observed phy-mass spectrometry. Spectra re- Four and six months after exposure in adipose tissue of rats exposed to ei- suiting from the composite adipose to the PCBs was discontinued the ther Aroclor 1016 or 1242. tissue analysis showed primarily tri- hepatocytes were still larger than Very little FCB-derived material and tetrachlorobiphenyls, for both those of the controls, but only one out was excreted in the urine, and the ex- PCB mixtures. Trace amounts of of three rats showed vacuolated cyto- cretion was very erratic. When rats penta- and hexachlorobiphenyls were plasm or inclusions within the cyto- were fed Aroclor 1242 they only ex- found in the Aroclor 1016 composites, plasm. Since the number of animais creted measurable amounts during . while significant amounts of pen- was small, these results have to be in- four to eight months of exposure. tachlorobiphenyls and hexachloro- terpreted with reservation; however, Rats fed Aroclor 1016 excreted mea- biphenyls were found in the com- it appears that the morphological surable amounts at each urine collec- posites obtained from rats that were changes encountered following expo tion. The variation in urinary excxe- fed Aroclor 1242. sure to Aroclor 1242 and 1016 are re turn of PCB-derived material has Spectra from urine composites of versible and disappear gradually af- been observed previously in this la-bo- rats fed Aroclor 1016 revealed the ter dosing is stopped. Except for the ratory* and by other workers in the presence of the same molecular ions hemorrhage and necrosis observed in field.7 observed in the adipose tissue compos- one animal in each experimental The data resulting from the analy- ites, with the exception of hexachlor- group no evidence of serious liver sis of tissues from rats that were fed obiphenyl. Dichlorohydroxybiphenyls damage was encountered, the respective PCB-containing diets (DGHB) and trichlorohydroxybiphen- The livers of rats from the controls for six months and were then costin- yls (TCHB) were also observed. Di- were normal when studied with the ued on plain, chow for various inter- chlorohydroxybiphenyl was more light microscope. Sections of four liv- vals up to six months are givei in abundant. era of rats fed Aroclor 1242 for six Table 2. The concentrations found in Spectra from urine composites of months and of four rats fed Aroclor adipose tissue are also illustrated in rats fed Aroclor 1242 revealed the 1016 for four months were also stu'd- Fig 4. Storage of material as detected presence of the same molecular ions ied under the electron microscope, to by gas chromatography decreased observed in adipose tissue, with the gether with the same number of con- i more rapidly following discontinua- noted absence of hexachlorobiphenyl. trols. The livers of the control animals i tion of dosing in rats previously fed In contrast to Aroclor 1016, hy- showed occasional lipid vacuoles but Aroclor 1016 than in those previously droxylated chlorobiphenyls were not no abnormal changes. The livers of fed Aroclor 1242. Following a reeov- observed in any of the spectra result- the experimental rats fed both PCB ery period of six months the residue ing from Aroclor 1242 urine compos- compounds showed an increase in levels in adipose tissue were 21.8% of ite analysis. smooth endoplasmic reticulum, an in- ii those observed after a six-month ex- The incidence of the various micro- crease in the number of lipid vacuoles, , posure period to Aroclor 1242. Follow- scopic changes observed in the liver is and atypical mitochondria. Stacking"^ ing a recovery period of five months given in Table 3. Light microscopic of membranes within the mito- the residue levels in adipose tissue of examination of the liver of rat3 fed chondria was also observed (Fig 5). rats fed Aroclor 1016 were only 11.8% the two PCBs showed enlarged hepa- Except for one animal that showed of the concentration found after six 1 tocytes predominantly in the center lymphocytic leukemia, no other ab- months of ingestion of this material. of the lobules. Occasional hepatocytes normal findings were made on gross The gas chromatographic traces ob- had coarsely vacuolated cytoplasm or inspection of the organs at autopsy, tainedfrom the adipose tissue follow- contained inclusions within the cyto- It must be emphasized, however, that ing recovery from exposure to the plasm. The cytoplasm of some of the the only organ examined microscopic- PCB mixtures are shewn in Fig 3. hepatocytes was finely vacuolated ally was the liver, since it was this or- (Relative retention times were com- and a brown pigment was noticed in gan that was primarily affected by puted relative to the most intense the Kupffer cells and macrophages of Aroclor 1254 and Aroclor 1260 as pre- 308 Arch Environ Health/Vol 29. Dec 1974 . Polychlorinated Biphenyls/Burse et ai DSW 342358 . .. .. ' STLCOPCB4083845  . - piously reported from our Iabora?' * tory.* - COMMENT > Levels of PCB-derived components found in adipose tissue reached a level of 92 ppm (Aroclor 1342) and of 182 ppm (Aroclor 1016.) after two months' exposure of rats to a diet - containing 100 ppm, with little in crease thereafter. JiLthough food con- . sumption of the rate was the same in both groups, rats on Aroclor 1016 had t higher residues. It is possible that t Aroclor 1016 is absorbed better from f- the gastrointestinal tract than Aro- clor 1242. Another possibility is that r - storage varies hetween the two com- It pounds. The higher residue levels of t Aroclor 1016 vs Aroclor 1242 could be attributable to PCB quantitation. It v is known that the degree of chlorina tion and the position of the chlorine V substitution contribute to the elec- i tron capturing properties of these ' compounds. In some instances their 4 electron capture responses are not i; proportional to their concentration.1011 { An alternative to quantitating the PCB derivatives in tissue could be complete ddorination of the bi phenyls to decachlorobiphenyl.11 ! Whether a combination of the various factors outlined contributed to the difference in the PCB concentration at similar exposure times is at pres ent not known. The concentrations in the other organs were often higher for Aroclor 1016, and the residues , that were built up in the tissues de creased faster for this compound once exposure to the PCBs was discontin ued. ` . From previous experience with Aroclor 1254* equilibrium seems to be reached sooner, and elimination after exposure has been discontinued is more rapid with Aroclors 1242 and 1016. , : Mass spectral identification of PCBs in composite fat and urine sam ples wasl>ased on: (1) the presence of the correct molecular ion, (2) charac teristic chlorine isotopic clusters, and (3) observed fragmentation patterns. These were all in agreement with previously published data. The presence of DCHB and TCHB in Aroclor 1016 urine composite is in keeping with published data on meta bolic products for these compounds.10 However, one would generally not ex pect the method of extraction em ployed here (hexane at pH 7) to ex tract these metabolic products since they are generally found bound in the urine as glucosiduronides," and are detected following hydrolysis of the urine. It is feasible that small amounts of hydroxylated compounds could be found as free phenols and could then be chromatographed under selected conditions. As could be ex pected, the concentrations of the PCBs were much lower in the liver, kidneys, and brain than in adipose tissue, and even lower in piasma. Plasma concentration probably is not a very good indicator of the amount of PCBs stored in adipose tissue. The morphological changes ob served in the liver are similar to those observed with other chlorinated hy drocarbons.15 They were generally mild, particularly when compared with findings made earlier with Aroclor 1254 and 1260.-9 Neither the pronounced lipid accumulation nor the adenofibrosis was observed in this study. However, some brown pigment was observed in the macrophages of the livers of some rats fed Aroclor 1242 but not Aroclor 1016. It was not determined whether the pigment rep resented ceroid or whether part of it was caused by an accumulation of hemosiderin and porphyrin in the liver. After feeding rats Aroclor 1242 and 1016 for six months, Goldstein et al1 found an increase in liver uro porphyrin for Aroclor 1242 at this die tary level but not Aroclor 1016 at the same dietary level. Unfortunately the number of rats was not large enough to determine if the occasional liver cell necrosis and hemorrhage that was seen was related to the exposure to Aroclor 1242. From this study it may be concluded that both Aroclor 1242 as well as Aroclor 1016 are less persistent in the rat and have also less of an effect on the liver than ei ther Aroclor 1254 or 1260. Aroclors 1242 and 1016 were supplied by Mon santo Chemical Company, St Louis. J. Cumey, R. Moore, J. Coule, and J. M. Jack gave technical assistance. References 1. Broadhurst MG: Use and replaceability of polychlorinated biphenyls. Environ Health Per- spect 2:81-102, 1972. 2. Koeman JH, Ten Noever De Brauw MC, et al: Chlorinated biphenyls in fish, mussels and birds from the river Rhine and the Netherlands coastal area. Nature 221:1126-1128, 1969. 3. Risebrough RW, Rieche P, Peakall DB, et al: Polychlorinated biphenyls in the global ecosystem. Nature 220:1098-1102.1968. 4. Bagley GE, Reichel WL, Cromartie E: Iden tification of polychlorinated biphenyls in two bald eagles by combined gas-liquid chromatogra phy-mass spectrometry. J Assoc Off Anal Chem 53:251-261,1970. 5. Zitko V, Hutzinger O, Choi PMK: Contami- Hitic2 cf the 3iy of of with polychlorinated biphenyls, polychlorinated terphenyls, chlorinated dibenzodioxins, and di- benzofurans. Environ Health Perspectives 1:47 50, 1972. 6. Curley A, Burse VW, Grim ME, et at Poly chlorinated biphenyls: Distribution and storage in body fluids and tissues of Sherman rats. Envi ron Res 4:481-495, 1971. 7. Plantonow NW, Liptrap RM, Geissinger HD: The distribution and excretion of poly chlorinated biphenyis (Aroclor 1254) and their effect on urinary gonadal steroid levels in the ' boar. Bull Environ Contain Toxicol 7:358-365, 1972. 8. Kimbrough RD, Linder RE, Burse VW, et al: Adenofibrosis in the rat liver. Arch Environ Health 27:390-395,1973. 9. Kimbrough RD, Linder RE, Gaines TB: . Morphological changes in livers of rats fed poly chlorinated biphenyls. Arch Environ Health 25:354-364, 1972. 10. Zitko V, Hutzinger O, Safe S: Retention times and electron capture detector responses of some individual chlorobiphenyls. Bull Environ Contain Toxicol 6:160-163, 1971. 11. Rote JW, Murphy PG: A method for quan titation of polychlorinated biphenyl (PCB) iso mers. Bull Environ Contain Toxicol 6:377-384, 1971. 12. Berg OW, Siosady PL, Rees GA: Column chromatographic separation of polychlorinated biphenyls from chlorinated hydrocarbon pesti cides, and their subsequent gas chromatographic quantitation in terms of derivatives. Bull Envi ron Contain Toxicol 7:338-347,1972 13. Hutzinger O, Nash DM, Safe S: Poly chlorinated biphenyls: Metabolic behavior- of ' pure isomers in pigeons, rats, and brook trout Science 178:312-314,1972 14. Block WD, Cornish HH: Metabolism of biphenyl and 4-chlorobiphenyl in the rabbit J Bid Chem 234:3301-3302 1959. 15. Kimbrough RD, Gaines TB, Linder RE: The ultrastructure of livers of rats fed DDT and dieldrin. Arch Environ Health 22:460-167, 1971. 16. Goldstein JA, Hickman P, Bergman H, et al: Induction of hepatic porphyria and drug me tabolism by two polychlorinated biphenyls (PCB) mixture containing 42% chlorine (Aroclor 1016 and 1242), abstract. Fed Proc 33219,1974. Atrc'n Environ Health/Vol 29, Dec 1974 Polychlorinated Biphenyls/Burse et al 307 DSW 342359 1: {; Jt : 5f l; i' 0 i ' i. (: U \\ )' w IV STLCOPCB4083846