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.DEC J? .vV E. P. Wheeler ON THE OPTICAL ACTIVITY OF POLYCHLORINATED BIPHENYLS Klaus L. E. Kaiser Environment Canada. Canaria Centre for Inland Waters. Burlington, Ontario, Canada ABSTRACT Commercial mixtures and residue samples of polychlorinated biphenyls comprise approximately one hundred individual chemical compounds. These differ in their physical and chemical nature and physiological effects. The existence of nine of the major, and ten of the miner, consft/ufntt of the Aroclors 1242. 1254 and 1260 m optically activeforms has notv been predicted. These molecules derive optical activity from the resistance to change conformation due to the interference of the chlorine substituents. The activation energy (A), required for the racenusation has been estimated to be greater (A - 25-58 kcal mole' ') than the thermal energy usually available in the ecosystem. The presence of these optical isomers nil! have a bearing on the toxicity and metabolic interactions of these chemicals. 1HTR0DUCT10N Environmental contamination by polychlorinated biphenyls (PCBs) has been established over the past few years (Pcakall & Lincer. 1970). Regional and inter national monitoring has proved their presence in many samples of aquatic origin (Risebrough et al1968; Anon., 1972; Harvey ct al., 1973). A variety of wildlife, as well as domestic animals, accumulated PCBs to sublcthal and even acute toxic levels. Due to their resistance to degradation and their accumulation in the food chain, PCBs have also been found in human adipose tissues in Europe and North America (Price & Welch, 1972; Presendorfcr et a/., 1973). The ubiquity of PCBs, their toxic and synergistic effects on biota have been studied widely and their chromatographic and biological aspects have been reviewed by Fishbcin (1972) and by Quinby (1972). Yet it is surprising that there has not been any investigation into the possibility of optical isomerism of these 93 F.m lrott. Peibiit. (7) (1974)-- Applied Science Publishers Ltd, England, 1974 Printed in Great Britain MONS 034631 94 KLAUS L. E. KA1SI.K chemicals and the difference with respect to toxicity, synergistic cfTccts and bio degradability which those optical isomers may provide. Thus. West *St Todd (l%l) State: `Most of the organic substances involved in the structure and metabolism of living organisms belong to the /3* or /.-series, An enzyme will act only upon one form of a substance (D or /,,). For example, certain of the />-sugars arc utilised in the animal body and by microorganisms, whereas the corresponding /.-sugars are not utilised'. This paper describes a qualitative and scmi-quantitaiive study oT molcculai optical isomerism within the group of polychlorinated biphenyls with p.ii hatlui reference to those isomers which will be stable under environmental anuiinnus OPTICAL ACTIVITY OF SUBSTITUTED DIPIILNYIS In unsubstituted biphenyl. C,jH,o (Fig- I). the intramolecular repulsion m hydrogen atoms in the 2 and 2' positions and in (he h and 6' positions are of minor influence on the conformation of the molecule. For the gaseous state, electron diffraction studies (Basliansen, 1949) indicate a structure wuh the planes of the benzene rings tilled against each other. 66 Fie. I* Biphenyl carbon skeleton, numbers indicating positions of subsiiruenis, |a relative angle between the phenyl rings. In the crystalline slate, however, the gain in lattice energy is greater than the energy required for surpassing the hydrogen-hydrogen repulsion force for a planar structure. This planar conformation has been confirmed by X-ray structuie analysis (Dhar, 1949). Atoms of greater sizes as substituents in the 2 and 2' positions strong!) increase the declination of the two rings from the planar form. This effect has been observed for the molecular structures of dihalogeno biphenyls and for several dihaiogeno and tetrahalogcno derivatives of dicarboxy biphenyl. Table l gives a compilation of biphenyl compounds, which have been investigated with respect to ihcir confor mation, optical properties resulting therefrom and activation energies for raccmisation of those optical antipodes. Further evidence for molecular ntropisomcrism in biphenyl derivatives has been found in 2,4t2',4'-tciranitro-6.6'-dicarboxy biphenyl and in 2,4,2'-trimtro-6,6'- MOMS 084632 ?^.s13?.. 3 aa -- rr m -S' ay S3. 2 82-^2`33-13- sI 5 n o *< v 3 a ? K- "g S'*=1- 2 - 2 ?s. a 5 * "* S I ^--2oS~ 2, ? " 3. i" 1 5 jf 8 & 3 ^-r 32 S s-Sti3ll3 fT o7' oa 3o Sa. 5o 5 L sr lit 4P 5 3. x|? _3 o^ '* 5 Ss So sS.1Z z> 5% i-y: | ? "3 O rll? , o 5. 5 I >3 If -- * S3. 5 j *5 5 * s < i: 93 2 O -- 3 tr: i"- 3 &3 3 Compound Conformation Ca Biphenyl 2,2'-Uichlofo bp.<*> 2,2'^Jibromo bp. 2,2 -diiodo bp. 3,3'-<Jibromo bp. 2,2'-dibromo-4,4-dic*rbo*y bp. 2,2'-dichlro-6.6'-dk^rboxy bp. 2.2 -dodo-J,J'-dicarbox)r bp. ?]i\? ,,'"*j<>do-33'8iairbor bp. 23.6.2 .4 ,6 -hcxachloro-3.3' if4rbbxy bp. 0* (planar)**) 45`*i 7<iJ73 5* 79 i 5* 54 5* ? ? 7 7 " biphenyl; (r) estimated. Potential optical activity Activation energy for raevmfsatian at (*C) &E{t,ca( moic ~') Reference No No Yes Yes Yc> Yes Yes Isomers isolated Isomers isolated Isomers isolated Isomers isolated <3'> (20) --St') > Jo :o-7 --5 -19 3 190 15") 21-6 20 7 28 >J0<HW) Basiiansen (1930) Basiianscn (1949) Basiianscn (1930) Basiianscn (1950) B.i>li3rrscn <1950) Harris & Cheung (J962) Basiianscn (1949) WcMhvimcr (1947) Harris & Cheung (1962) MeiyenhcuncrA liotingl 1927) Rcpcr A wL>ibcimer (1930) Harris A Cheung (1962) Rieger A \\ cslhomer (1950) ------- --------------------- - MQNS 084633 96 KLAUS L. E. KAISER dicnrboxy biphenyl, the latter in solution being slowly raccmtscd with an activation energy of AE 22 4 kcal mole'1 at 98 8fC (Kuhn & Albrecht, 1927). As was shown by Rieger Si Wesibcimer (1950). in the case of 2,3,2',3'-tctraiodo-dicafboxy acids, there is a considerable buttressing effect by large substituents in the 3 and 3' positions, which increases further the activation energy of the optica! isomers, as shown in Table l. A similar qualitative repulsion effect can be expected for adjacent chlorine substituents in 2 and 3 positions of the biphenyl structure. Its quantitative effect will be less than for the iodine-iodine pair and can be estimated to be AE z 2-5 kcal mole' 1 for each buttressing chlorine atom. Supporting evidence for the existence of optical isomerism of PCBs has been observed by White & Adams (1932) in the fact that 2,4,6,2\4\6'-hexachloro-3,3'dtcarboxy biphenyl could be resolved into stable optical antipodes. The acid did not raccmisc under reflux conditions in ethanol or glacial acetic acid nor as sodium salt in boiling water. j j ' ; OPTICAL ACTIVITY OF POLYCHLORINATED 01PHENYU Conformational changes in polychlorinated biphenyls As can be seen from the experimental and theoretical data presented in Tables I and 2, substitution of biphenyl with chlorine will influence the optical properties of these biphenyl compounds. Technical PCB mixtures are produced by catalytic chlorination of biphenyl with Lewis acid catalysts (Bcavcn et al., 1961). This procedure gives rise to approximately one hundred individual chemical isomers, dependent on the degree of chlorination. They range from unsubstittned biphenyl to polychloro biphenyls with at least eight chlorine atoms per molecule. While most of the commercial PCI! mixtures, obtained at certain chlorination levels, have been studied us to their exact composition (Sissons Si Welti, 1971; Webb St McCall, 1972), not all of the minor constituents arc yet identified and major com pounds have been identified only recently after application of combined gas chromaiogrnpliy-mass spectrometry (Sissons Si Welti. 1971). gas chromatographyinfrared spectroscopy (Webb & McGill, 1972) and proton nuclear magnetic resonance spcciroscopv (Sissons A Welti, 1971). In order to calculate on ;t semi-quantitative basis the rotational interference of atoms (without corrections for bond-stretching and distortion of bond angles), the bond lengths and structural relations of Fig. 2 were employed. For the planar conformation, die interatomic distancc/bctwccn substituents in the 2 and 2' positions can be calculated as: For: /-<*a + A*)1 c a + 2b cos 60* OPTICAL J Fig. ?. Bond lengths, bend at conformation. Bond lengths afti b I-40A:X - Cl:# - J TO, hmf S - /[<! In the case of x y, e m The results for /, calculatt presented in Table 2. INTtUKVCUAR DUTAXCri, Tiitm xttrrcmt si.mi or Subst. X Subu. Y HH H Ci H Be Ht Cl a Or Dr It 18) [}) 14? 1 64 J 20 1 04 0ST Ul Values after Cotton .1 NVilkinu U>\ Value, after Wcast nw. (rt A/ valuvi arc calculated at on tuceini\atn>n of ?,2'-dil)3tngeno bip <*/l Values estimated by enmpame and Van dcr Vruats radii am) sums HONS 08463C afy racemised with an activation uhn & Albrecht, 1927). As was : of 2,3,2\J'*tciraiodo-dicnrboxy large substituents in the 3 and 3' mergy of the optical isomers, as txpeeted for adjacent chlorine structure. Its quantitative effect an be estimated to he & z 2-5 rat isomerism of PCBs lias been hat 2.4.6,2'.4',6'-hc\achloro-3,3'r optical antipodes. The ncid did r glacial acetic ncid nor as sodium JSAUD BIPHT.NYLS ir/l eoretkal data presented in Tables siU influence the optical properties nixture* are produced by catalytic llysi* (Beoven tt ai, 1961). This tdred individual chemical isomers, rang* from unsubsiituted biphenyl (orine atoms per molecule. While tied at certain chlorination levels, n (Sittons ft Welti. 1971; Webb A i are yet identified and major com iter application of combined gas Welti, 1971), gas chromatography72) and proton nuclear magnetic >. basis the rotational interference of tig and distortion of bond angles), 2 were employed, distance/betneen substituents in OPTICAL ACTIVITY OF POLYCHLORINATED UIPHENYLS Fiji. 2. Rond lengths, bond angles and imernuclcar distance /in an idealised planar 6iphcn>l conformation, bond length?, after Ficscr & Fieser tl%5). Carbon indices as in Wg. I. a *- i-4g A. b - l-40A;jr-CI:< 1*70 A;X~ H:c- 1-09 A; Y * Br. A ~ l U6 A. Y l:rf * 2 0) \ h * c - e cos 60 - d cos 60* $ * * sin 6Q* - d sin 60" / ((i* - irf)1 + (c - 0-5e - 0&/)]* In the case of x m y, e ** d and g 0; /-*-* The results for /, calculated for several hydrogen-halogen combinations, are presented in Table 2. TABLE 1 IWTTRNUCLlAJt DttTANCTS/or arrHfKYL SCilTlTUINTS tN 2 AMO 1' TOStTtONS WVTH their respective sums of covalint raj>, van tun waali hadu asu activation ENCROtES FOR THE RACCMISA1 ION Subst. X Subrt Y H Ha H Br H1 aa Br Br II d> 181 133 147 164 120 1-04 087 If* (A) 056 ' 1-21 1-42 1-61 1-9B 2-28 266 I I.rf IVR (A)I'I 2-40 300 315 3-33 3-60 3-90 4-30 le + <t (A)* 2 18 2-79 295 3 12 340 3-72 406 AE'* <2 5't --2-5** 9 10-14 -~25<*i --40>> Slitt a\i?,UCiI *fV,eBrf Wwrcaasil (196W9)i.lk <e) At values arc calculated ns one half of experimentally observed activation energies for (he racemisation of 2,2'*dhaloy,cn<t biphenyl derivatives. (rf) Values estimated by comparison of the wtcrnuclcac distances / with the sums of covalent and Van der Waals radii and wmi ir + ti). fc * >*r MONS 084635 98 KLAUS L. E. KAISER As the values calculated in Table 2 indicate, distances /of hydrogen-hydrogen and hydrogen-chlorine pairs are greater than their respective sums of covalent radii. For the hydrogen-bromine pair and for the hydrogen-iodine pair both values are of the same magnitude, while for the halogen-halogen pairs the available inter* atomic space (neglecting molecule distortion) is considerably less than the sums of their covalent radii. This agrees with another empirical calculation, the 'Adams Rule', by which optical isomers of biphenyl derivatives can be obtained at ambient temperatures if the sum of the covalent nuclear distances (I e + d) is greater than or equal to 2-90 A (Wcsihcimcr, 1956). Concordant with those parameters arc the observed activation energies for the raecmisation of optical biphenyl isomers. It can therefore confidently be predicted that individual polychlorinated biphenyl isomers will exist in optical atrop antipodes, provided that they: 1, fulfil the general requirements for optical activity: i.c., absence of either a plane of symmetry, a symmetry axis or of a centre of inversion or a com bination thereof and 2. have chlorine substituents in the 2 and 6 positions of one phenyl ring and have a chlorine substituent in the 2' position of the second phenyl ring. As can be estimated by comparison with compounds referred to in Table l, PCBs meeting these requirements w ill have activation energies in excess of A 20 kcal mole"1; i.c., being sufficiently restrained from change of conformation through the planar form under most environmental conditions, where elevated temperatures are not usually encountered. This fact may be of special importance to the environmental behaviour of those chemicals, particularly to their biological activity towards toxic and synergetic ciTccts and to their biodeterioration in the aquatic ecosystems. Optically active PCBs in technical and environmental samples On examination of the substitution possibilities in biphenyl, it will be found that there arc 19 PCD isomers satisfying the above-mentioned conditions for optical activity and conformational stability. Including these, there arc 78 PCD isomers out of a total of 210 possible structural isomers which meet the basic requirements for optical activity alone. However, most of those have less strained conformational transition stales. A tabular summary of all PCB isomers, without any symmetry elcmcm in the non-planar conformation, with respect to the number of chlorine atoms in each ring is given in Table 3. The optical stability of the less strained isomers cannot readily be estimated, since there are buttressing and electronic ciTccts of unknown magnitude playing a role for the transition stale requirements. However, by comparison with the data of Tables I ami 2. one can assume their activation energies for raecmisation to be A6* 20 kcal mole"'. Thus, under ambient conditions, raecmisation of any optical isomers will occur. Most of the mentioned 19 optically stable PCD isomers with chlorine substituents OPTICAL ACT1V TlltOfttTICAl !* WITH OPTICAL ACTIV I | Number of : chlorine atoms in rinc B at least in the 2, 6 and 2' poi commercial PCB mixtures (Sisi. these isomers is predicted to l df S 25 kcal mole" Their c as ''ell as their presence in tl Table 4. For the estimation of " *** I ACTIV ATR chhtnnei prr motrcule rtfc*,, ' <;! Am., 236 236 236 2)6 2346 236 236 236 236 2346 2346 2346 2346 2346 2345 2346 2346 2346 2316 2' 2T 2'4' 2'5' r 234' 2)5' 2T6' 2'4'J' 23' 2'4' 2'5* 2'3'4' 2'3T 236' 2'J'6' 2'4'5' 2 3'4'6' 2'3'4'J' A Wd|| ()97| I/Vi 3 minor constituent. ' - mdica less major constituent. HONS 01*4636 stances/of hydrogen-hydrogen respective sums or covalent radii, tgefl-iodine pair both values arc lloftn pairs the available interconsiderably less than the sums mptrical calculation, the `Adams dives can be obtained at ambient stances (2* + d) is greater than nt with those parameters arc the of optical biphenyl isomers, lividual polychlorinated biphenyl ided that they: activity; /.<*,. absence of either n r a centre of inversion or a com positions of one phenyl ring and ion of the second phenyl ring, ipounds referred to in Table 1, ion enrrfiei in excess of HP. 20 from change of conformation ental conditions, where elevated act may be of special importance Is, particularly io their biological I to their biodcierioration in the twf samples ifi in biphenyl, it will be found mentioned conditions for optical these, there are 78 PCB isomers >hich meet the bosic requirements have less strained conformational t isomers, without any symmetry rspect to the number of chlorine ten cannot readily be estimated, of unknown magnitude play ing a vet, by comparison with the data in energies for raccmistiiion to be conditions, rncemisation of any isomers with chlorine substituents OPTICAL ACTIVITY OP POLYCHLORINATIvD UfPIIENYLS TABLE 3 TMT,rAL rOSSIHIt P&LYCHLORINATED mrilFNYL ISOM'RS WITH OPTICAL ACTIVITY WHEN IN A NON-PLANAR CONTORMATION Number of chlorine atunts in ring A Number of chlorine atoms in ring B 0 1 2 3 4 3 Total ?g 99 at least in the 2, 6 and 2' positions have been observed in one or more of the commercial PCB mixtures (Sissons & Welti. 1971; Webb & McCall, 1972). Each of these isomers is predicted to have an activation energy for the rnccmis.nion of HE ^ 25 kcai mole" *. Their exact substitution and cMimated activation energies, as well as their presence in three commercial PCB mixtures, arc compiled in Table 4. For the estimation of the activation energies, the following parameters I nDLC _____ POLYCMioaiNATrn RtPHrvvi % or rurmcno optically activ t and stahi r CONFORMATIONS, THflR PRLStNTF IN SOME rOMMIRCIAL MIXTtSrS AND THEIR LSTImIuo ________________ ACTIVATION ENERGIES IOR RaCIMISATION Number of chlorines per molecule Positions of chlorine substituents Presence in Aroeior*** 1234 Aft-arev* keel. mole 1 236 236 236 236 2346 236 236 236 236 2346 2346 2346 2346 2346 2345 2346 2346 2346 2346 2' TV 2'4' 2'5' 2' 2T4* 2'3'5' 2'3'6' 2'4'5' 2'3' 2'4' 2'5' 2'3'4' 2'3'5' 2'3'6` 2'3'6' 2'4'5' 2'3'4'< 2J-4-3 + ' + ? + (?) +(7) + MT) + +<*> ++ ? ++ + ++ -M?) + ? ++ T ++ ++ + +(?) ++ ++ + ++ + + 23 29 25 25 23 29 29 31 25 29 25 25 29 29 29 59 25 38 29 <) After Sissons A Welti (1971) and Webb A McCall (1972). (b) Estimates based on observed and estimated values, according to Tables ! and 2 at ambient temperatures. <r) + indicates a minor constituent. (d) +4- indicates a major constituent. '-'Vs*. HONS 034637 100 KLAUS L. E. KAISER serve as a basis. Derived from the imcrmtclcnr distance/(I-20 A) related to the sum of the covalent radii (1-98 A) ns in Table 2: the base value for turning a phenyl ring with chlorine in 2 or 6 position past chlorine in 2' or 6' position is estimated ns SE 25 kcnl * mole'*. For c.icli chlorine substituent in either 3, S, 3' or S' position, adjacent to chlorine in 2. 6. 2' or 6' positions a buttressing effect of A * 4 kcal mole"1 is added. For example, 2.3,6,2',3'*penuchloro biphenyl would have only one buttressing chlorine; /.r., in 3' position, since the molecule may change its conformation by turning the ring with chlorines in 2', 3' positions past the chlorine In 6 position. It should be pointed out in this context that European and Japanese products may have similar values for their overall chlorination levels, but do not necessarily represent the same combination of structural isomers in a given mixture. Unfor> tunnicly, basic comparative gas chromatographic studies on PCB mixtures from different origins are still missing. By the nature of the preparation, of course, commercial PCB mixtures will most likely contain optica) active isomers in form of their racemates. The separation of racemic isomers into their optical antipodes has as yet not been reported. CONCLUSION Of the major constituents in three commercial mixtures of PCBs; i.e., Aroclors 1242, 1254 and 1260, in total nine different PCB isomers are predicted to exist in environmentally stable optica) atropisomers. This fact is regarded to have a major influence on the biochemical activities and biodegradation of those antipodes. ACKNOWLEDGEMENT 1 wish to express my gratitude to Dr W. M. J. Strachan for helpful discussions and constructive criticism. OPTICAL DMAS. J. (1949V Structure of Fnsm. L. F. A Firwt. M. ( FtsHts. V. (1912V Chrom J. Chn<mmt.. M, J4S-42t Ham's, M. M. A Curtno. nilicance of ground Ml I37S-80. Harwy. G. R.. Stvinmacir. Ocean water. Seiner, X Koiin. R- A Alsmcmt, O. tl opiK'.itlv active diphcnic MtlUMUlMtR, J. & llOfttNO, 142503. Ft.vKALi. DBA LiNCta. J. chcmiri) in the cmtronm i'MSiNnoatt-n. It,. Ctrmtn, polychlorinated biphenyl Urn. HicAr.. IS, 21102. Prkt. H. A. A Warn, R. L.( Hiih Ptnprturn. 1,7)-| Qustv. G. E. PW></, anti enttronment. I. M US Department of Comn Knot A. M. A WtSlHltvltk. F etVcct for the racemiuiiw 72. 1*0*. Risibroich. R W , Rnrwr, f chlorinated biphemh n t Siisunv D & WiLtt. (S. 09T merciat mixture* by pt spectrometry J Chumme. Wiasi, K C. (1969) Hern** Company. Wtaa. R.G.4 McCau.A.C. J Asi off oimlxt. Chem., E. s A Toon. W. R. ( Wisrmtwta. F. H. (1947). a 2.2'*librcun>~i,4'*dicarbo' NVrsTMriMin. F. It. (1956). C: oijntue ehermurv, ed. bv I VNiim. J. A adavi*. R. HVJ2) hexachloio-J.J-dtc3boi>l REFERENCES Anon. (1972V Pin/ftipfcrirvf.t in thr Grral Lakes emiretnmettt. Unpublished report of rhe Canada Centre for inland Water*. HurUngton, Ontario, Feb. 1972. ' Dasiiansin, U, (194V). Molecular struct tire of bipiienyi and some of its derivatives. Aeta thtm. t<*</, 3, 408-14. Uasmansi n. o. (|9M. T1>e molecular structure of biphenyl and some of its derivatives, II. Aero chem. tcarnl., 926*36. Bcavi.s, O. II., Di I.A MA*r. P, n. D.. Haxxan. M . Johnson. E. A. A Kiassvn, N. V. (1961). The kinetic* ami inechaimm* ofaromatic halogen substitution, X. Products in thcchlorirutttoa of biphenyl in acetic acid. J. ehrnt. Sue., 1961. 2749-55. Cotton, F, A. A Wtt.uNStm, Q. (1907), Amrgunmhe Chemie. Vcrlag Chcmie GmbH. MONS oavb3a f .nut tr distance/(I-20 A) related to the : (lie bate value for turning a phenyl ht in 2` or 6' position is estimated substituent in either 3, 5,, 3' or 3' position! n buttressing clfcct of e, 2,3,6,2',3'-pcntachloro biphenyl hi y position, since the molecule ng with chlorines in 2'. 3' positions I European nrul Japanese products nation levels, but do not necessarily isomers in a given mixture. Unfor>hic studies on PCM mixtures from ure of the preparation, of course, nain optical active isomers in form isomers into their optical antipodes ri mixtures of PClis; i.r. Aroclors :isomers are predicted to exist in his fact is regarded to have a major degradation of those antipodes. strachan for helpful discussions and OPTICAL ACTIVITY OF POI.YCIILORINATL1) TJIPIIINYLS |0J Omar. J. (1949). Structure of birhenyl. Prnc natn. hut. Set. Intlia, IS. I 1-14. j'liiirn. L. F. A Fiism. M. (I9(iJ>. Advanced organic ehrmhtry, p. It56. New York, Kcinhnld. I ismrun. L. (1972). Chromatographic and biological aspects of polychlorinated bipltcnyls. J Chromat .. 6K. 345-426. Harris. M. M. A Chiuno. K. L. (1962). Mesoid and rnccmoid transition states and llic sic* nifcance of around state strain in certain configurational inversions. Clu-iny hut, 1902, 1378-110. Marviv, C. A., StTtNiiAiii *, \V, (. A Ti ai . J. M. (1973). Pol>-cldorubiphcnyls in north Atlantic Ocean wnirr. Seifnee. ,V V.. 1X0. 643-4 Kt'MN, R. A AlBNtnn. (). (1927). Stereochemistry of aromatic compounds. V. Raccmiration of optically active diphcnic acid. Justus /.iWi/pv . \unht Chvm.. 458. 221- 9. MlistNMUMiN, J. A lloxiNO, M. (1927). Stereochemistry of diphenyl. Dvr. dr. Chan. Ges., 60 ft. 1425-33. Pi akai.l. D. 0. A User*, J. L. (1970). Polychlorinated biphenyls. Another long-life widespread chemical in the cnvirs'nmcnt. flmSnrncr, 20,958-64. I'nrsi NDOMiiK, H.. Fumi ir, 1. fi Gt.onct, 11. (1973). Analyses of organochkwinc pcMieidc and polychlorinated biplK-iivi residues in human adipose tissue (from the area of Vienna). M me Uin. H'sehr., H5, 218-22. Pairc, M. A. A WiLt'M, R. L (1972). Occurrence of polychlorinated biphenyls in humans. Lnntan. tilth Perspectives, I. 73-8. Quinry, C. E. (1972). Po/ychhtrohiphenyls (PCBs) ami relatetl ehhtraphcnvh: Effects on health ami envivanntenl. I. (Ubhnftaphv, 1881-197). National Technical Information Seisiec. US Department of Commerce, Springfield. Virginia. April 1972 (Mimeographed). Ricgkn, M. A WrsTiiUMin. F. M. 1)950). The calculation ami dcicrnunaiion of ilsc hotircvmtg efTcct for the raccmi/ation of 2.2'.3,3'-tetraiodo-5.5'-dicarbos\ biplxnv 1. J. Am. chvm. Soc.. 72, 19-28. Rmrrrouom. R. W.. Rimir, P.. Pcakai.l, D. B.. iurman, S. C>. a Kimuv M n. U`>68). Poly* chlorinated biphenyls in the global ecosystem. A'autre. Load.. 220. 1098-102. Sissons, D. A Wilti, I), (1971). Structural identification of polychlorinated biphenyls in com mercial mixtures by gas-liuuid chromatography, nuclear magnetic resonance and mass spectrometry, J. Chromat., 60. 15-32. Wfast, R. C. (1969). Hattdbook of chemistry and physics. Cleveland. Ohio. Chemical Rubber Company. Wum, R. O. 4 McCall. A. C. 11972). Identities of polychlorinated biphenyl isomers in Aroclors. J. Ass. off- ana/yt. Cheat., 55. 746-56. WrsT. E. S. A Toon, W. R. (1961). Tc.\ti>ook of biochemistry. 3rd cd. New York. Macmillan. WcjmntMnt, t*. H. (1947). A calculation of the energy of activation for the raccmuation of 2,2'-dibromo*4,4'-dicarbo\y biphenyl. J. them. Phys.. 15, 252-60. WtsnuiMCR, F. H. (1956). Calculation of the magnitude of vieric effects. In Stent effects in ergeaie chemistry, ed. by H. S. Newman. 523-55. New York. J. Wiley A Sons. Whits. J. A Adams. R. (1932). Stereochemistry of Diphenyl. XXI. Resolution of 2,4,6,2',4,6'- hrxachloro-3,3'-dicarboxy) dipiteny). J. Am. chem. Soc., 54, 2104-8. foies emriroament. Unpublished report of Ootario. Feb. 1972. I and some of its derivatives. Acte them. m*)1 tad some of its derivatives, II. Aeta 'OHMON, E. A. A Klassi N. N. V. (1961). iNtiliuion, X. Products in thechlorination MS. Ckmk. Verlog Chemie Cmblf. MOMS 084639