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Chlorinated benzenes in the environment
ECOTOXICOLOGYANDENVIRONMENTALSAFETY 1, l-6(1977)
Chlorinated
Benzenes
in the Environment
MASATOSHI Tokyo
Metropolitan
Research
Laboratory Received
MORITA
of Public December
Health,
Shinjuku-ku,
Tokyo,
160 Japan
28,1975
Chlorinated benzenesare composedof twelve chemical species:one mono-, three di-, three tri-, three tetra-, one penta-, and one hexachlorobenzene. Most of these are not only important intermediates for various kinds of chemicals but are also extensively employed for various applications singly or in combination. For example, 1,4-dichlorobenzene is used for household purposes in insect repellents and deodorants; 1,2dichlorobenzene is used chiefly against termites in soil; trichlorobenzenes are used as solvents for pesticides and also as heat transfer agents with PCBs; the mixture of trichlorobenzene and tetrachlorobenzene is applied in controlling shellfish predators; and hexachlorobenzene is applied to wheat as a fungicide in somecountries and as an additive to rubber products. The annual production (1973) of monochlorobenzene, 1,2-dichlorobenzene, and 1,4dichlorobenzene in Japan was about 23,000, 9000, and 20,000, tons, respectively. Production volumes of other chlorinated benzenesare not well known but are assumed to be smaller than those of the above three compounds. The total annual production of chlorinated benzenes far surpassesthe peak production of PCBs (7000 tons/year) which are known as a ubiquitous pollutant in this country. Since chlorinated benzenes have a chemical structure and properties similar to those of PCBs and PCTs, it seemed necessary to direct our attention to environmental contamination by these materials. The present paper describes only the occurrence and the fate of these materials. Toxicity and biological impact are not referred to here. CHLORINATED
BENZENES
IN
AIR AND
WATER
Only limited information is available on the level of chlorinated benzenes in air and water. Chlorinated benzenesare more volatile than PCBs and are likely to constitute atmospheric contaminants, especially in lower-chlorinated benzenes. Morita and Ohi (1975) determined the level of l$dichlorobenzene in the atmosphere of the Tokyo metropolitan area. As might be expected from its use, l&dichlorobenzene concentrations were higher in indoor than in outdoor air. Outdoor levels in and around Tokyo were almost 2.4 ,&m3. Grob and Grob (1971) and Grob et al. (1974) identified monochlorobenzene, dichlorobenzene, and trichlorobenzene isomers and its precursor in drinking water in Geneva. Morita determined the levels of 1,4-dichlorobenzene and hexachlorobenzene in the intake, effluent, and activated sludge in several sewage plants in Tokyo (unpublished Copyright
@ 1977 by Academic Press, Inc. All rights of reproduction in any form reserved. Printed in Great Britain
1
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MASATOSHI
MORITA
observations). The averages were 1.0, 1.1 and 1200 ppb (1,4-dichlorobenzene) 0.00 13,O.OO 11, and 38 ppb (hexachlorobenzene), respectively. Pentachlorobenzene also found in the samples at a lower concentration than hexachlorobenzene.
and was
CHLORINATEDBENZENESINBIOLOGICALSAMPLES As with air and water, only a few data are reported for chlorinated benzene pollution of biological samples except for hexachlorobenzene. Morita and Ohi (1975) demonstrated that 1,4-dichlorobenzene accumulated in the fat tissue of pigeons in concentrations as high as 1.85 ppm. Although l&dichlorobenzene was also detected in several kinds of fish, 0.1 ppm in carp, 0.04 ppm in harvest fish, and 0.05 ppm in horse mackerel, on the basis of fat content, the level is generally low. Schwartz et al. (1963) detected low levels of those chlorinated benzene pesticides used for controlling molluscan pests in clams and oysters. In the samples of fish and birds in Japan, the pentachlorobenzene peak usually appears on gas chromatograms of hexachlorobenzene, although the level is usually low (about one-tenth that of hexachlorobenzene). Hexachlorobenzene has been found in fish from a number of river systems in Canada (Zitko, 1971) and in the United States (Holden, 1970, 1973; Johnson et al., 1971). Johnson et al. (197 1) reported an extremely high contamination by hexachlorobenzene in carp (62 pug/g wet weight). The source of hexachlorobenzene in that case was tentatively identified as runoff from an industrial chemical storage area. Koeman et al. (1969) demonstrated a hexachlorobenzene residue of 0.067 ppm (wet weight) in bladders of juvenile seals collected in coastal waters off the Netherlands. A low level of hexachlorobenzene residue was found in Japanese fish and shellfish (Morita, unpublished observations). Hexachlorobenzene contamination of wild birds is reported in the Netherlands (Vos et al., 1968; Koeman et al., 1969). Hexachlorobenzene was also found in the eggs of terns collected in Canada and the Netherlands (Gilbertson and Reynolds, 1972; Holden, 1973). In general, hexachlorobenzene pollution is slight in Japan compared with the United States or Canada. CHLORINATEDBENZENES IN HUMANTISSUES Morita et al. (1975) searched systematically for chlorinated benzenes in adipose tissues of Japanese by mass fragmentography and gas chromatograhy equipped with electron capture detectors. The species identified were l&dichlorobenzene, 1,2,4,5tetrachlorobenzene, pentachlorobenzene, and hexachlorobenzene. Above the detection limit (0.01 ppm), no other chlorinated benzenes were detected (Morita et al., 1975). Dowty et al. (1975) identified three isomers of dichlorobenzene in blood plasma of residents of Louisiana. Morita et al. (1975) determined 1,4-dichlorobenzene levels in human fat and blood in the Tokyo area. The 1,4-dichlorobenzene concentration in 34 human adipose tissue samples was 2.1 ppm on the basis of fat content, and that in blood samples averaged 9.5 ppb. No peak corresponding to 1,2-dichlorobenzene was found after gas
CHLORINATED
BENZENES
3
chromatography in spite of the fact that the annual production of 1,2-dichlorobenzene is about one-half that of 1,4-dichlorobenzene. The average levels of 1,2,4,5tetrachlorobenzene and pentachlorobenzene in 15 Japanese human adipose tissue samples were 0.019 and 0.009 ppm, respectively (Morita et al., 1975). Several studies have reported the presence of hexachlorobenzene in human fat tissues, blood, and milk. An Australian study of occupationally exposed individuals showed levels in blood ranging from 0 to 0.41 ppm. A control group with no known exposure showed blood levels ranging from 0 to 0.095 ppm. Hexachlorobenzene was detected in 95% of the people (Siyali, 1972). Another Australian study revealed that all perrenal fat samples examined contained hexachlorobenzene at an average concentration of 1.25 ppm with a range from a trace to 8.2 ppm (Brady and Siyali, 1972). A German study detected hexachlorobenzene residues of 6.3 ppm in fat and 5.3 ppm in the fat from human milk (Acker and Schulte, 1972). A survey in the United Kingdon showed that hexachlorobenzene residues ranged from 0.01 to 0.29 ppm with a mean of 0.05 ppm in 201 samples occurred generally in the population (Abbott et al., 1972). The plasma hexachlorobenzene residues in a Louisiana population were determined for individuals exposed during the transportation and disposal of chemical wastes containing hexachlorobenzene, and the residues averaged 3.6-4.3 ppb in the sample of 86 people. The highest level was 345 ppb in a waste disposal facility worker while the highest level in the general population was 23 ppb (Burns and Miller, 1975). Carley et al. (1973) analyzed human adipose tissues from Japan and reported hexachlorobenzene levels ranging from 0.30 to 1.48 ppm. Another survey of Japanese human adipose tissues showed lower levels of hexachlorobenzene residue, ranging from 0.10 to 0.42 ppm with a mean of 0.2 1 ppm. (Morita et al., 1975). Significant residues of hexachlorobenzene are reported in human milk from the Netherlands (Tuinstra, 1971) Australia (Siyali, 1973), and Germany (Acker and Schulte, 1970). A Swedish study has shown levels in breast milk ranging from 0.07 to 0.22 ppm expressed on a fat content basis (Westoo et al., 1974). METABOLISMANDBIODEGRADATION
Williams and his co-workers reported the metabolic fate of monochlorobenzene (Smith et al., 1950), dichlorobenzene (Azouz et al., 1955; Parke and Williams, 1955), trichlorobenzene (Jondorf et al., 1955), tetrachlorobenzene (Jondorf et al., 1958), and pentachlorobenzene and hexachlorobenzene (Parke and Williams, 1960) in rabbits. These studies suggested that the more chlorine the halogenated benzene contained, the less rapidly it was metabolized. Pentachlorobenzene is only slightly altered in uivo, and hexachlorobenzene seems to be metabolically inert. Metabolites of the chlorinated benzenes indicate that oxidative hydroxylation and reductive dechlorination are the main routes of conversion. Hydroxylation is a rapid reaction in mono- and dichlorinated benzenes, and the contribution of dechlorination seems to be negligibly small in these systems. Most of the metabolites are the corresponding phenols and their derivatives. 14Dichlorobenzene is least rapidly metabolized among these materials, and this may be related to the predominance of 14dichlorobenzene in human adipose tissue.
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MASATOSHI
MORITA
On the other hand, hydroxylation is difficult in pentachlorobenzene, due to steric hindrance by adjacent chlorine atoms, and is impossible in hexachlorobenzene. In this case, a very slow dechlorination reaction occurs as a first step of metabolism. Since dechlorination is a very slow reaction, these compounds appear to be metabolically inert. In the case of tri- and tetrachlorobenzenes, both reactions proceed competitively, phenols having the same and fewer numbers of chlorine substitutions are produced through metabolism. The reaction rate of hydroxylation depends on the configuration of the chlorine substitutions in the benzene ring. The 1,3,5substitution blocks the reaction site well and results in the least rapid metabolism among the three trichlorobenzene isomers (Jondorf et al., 1955). In the series of tetrachlorobenzenes, the 1,2,4,5-substitution seems to be most resistant to hydroxylation because of steric factors. In fact, 1,2,4,5tetrachlorobenzene appears to be the most slowly metabolized of the three isomers, and 48% of the dose was found unchanged in the tissues of rabbits after 6 days of administration. Furthermore, the metabohtes were composed mainly of dechlorinated products. Though Parke and Williams (1960) reported that hexachlorobenzene is metabolically inert, Mehendale et al. (1975) recently reported the metabolism of hexachlorobenzene using isotope techniques. Metabolites of hexachlorobenzene included pentachlorobenzene, tetrachlorobenzene, pentachlorophenol, and four unknowns. Mehendale et ~1. found that the reductive dechlorination of hexachlorobenzene was catalyzed by an enzyme located in the microsomal fraction of liver, lung, kidney, and intestine. They also reported that 70% of the total dose was found remaining in the body 7 days after administration. Morita and Ohishi (1975) applied a single dose of hexachlorobenzene to male Wistar rats and estimated the biological half-life of the material to be about 60 days. Borzelleca et al. (197 1) found that hexachlorobenzene and pentachlorobenzene, contaminants of technical pentachloronitrobenzene (PCNB), were stored in the tissues of rats, dogs, and cows given food containing PCNB; the chlorobenzenes were present at levels paralleling their content in the PCNB, indicative of a slower rate of metabolism of these compounds. Food chain magnification is suggested in hexachlorobenzene contamination (Metcalfe et al., 1973). There is a possibility that the food chain magnification is operative in other chlorinated benzenes with slow rates of metabolism, such as pentachlorobenzene. In parallel with the rate of metabolism, the rate of biodegradation is reported to be fast in lower-chlorinated benzenes and extremely slow in hexachlorobenzene. No information is available for the biodegradability of tetra- and pentachlorobenzene. Photochemical decomposition of chlorinated benzenes is not well known in the environment. AN OVERVIEW
It is worthwhile to compare 1,4-dichlorobenzene and hexachlorobenzene. 1,4Dichlorobenzene is metabolized and biodegraded relatively rapidly but its high rate of production gives rise to extensive contamination and in some casesresiduesof a high
CHLORINATED
BENZENES
5
level in biological samples. On the other hand, hexachlorobenzene is a compound which is characterized as hard to biodegrade. Phthalate esters may be related to the former compound, and DDT is similar to the latter type. The author has tried to delineate the pollution pattern of chlorinated benzenes. It may not have been entirely successful due to the limited information available. Further investigations are necessary in this area.
REFERENCES D. C., in the United ACKER, L.. AND ACKER, L., AND
G. B., AND GOULDING, R. (1972). Organochlorine pesticide residue in human fat 1969-71. Brit. Med. J. 2,553-556. SCHULTE, F. (1972). Ernaehrungsforschung 16,559. SCHULTE, L. (1970). Naturwissenschaften 57,497. Azouz, W. M., PARKE, D. V., AND WILLIAMS, R. T. (1955). Studies in detoxication. 62. The metabolism of halogenobenzenes. Ortho- and para-dichlorobenzenes. Biochem. J. 59,41&4 15. BORZELLECA, J. F., LARSON, P. S., CRAWFORD, E. M., HENNINGAR, G. R., JR., KUCHAR, E. J.. AND KLEIN, H. H. (197 1). Toxicologic and metabolic studies on penta-chloronitrobenzene. Toxicol. Appl. Pharmacol. l&522-534. BRADY,M. N., AND SIYALI, D. S. (1972). Hexachlorobenzene in human body fat. Med.J.Aust. 1,158-161. BURNS, J. E., AND MILLER, F. M. (1975). Arch. Environ. Health 30,44. CURLEY, A., BURSE, V. W., JENNINGS, R. W. VILLANUEVA, E. C., TOMATIS L., AND AKAZA~I K. (1973). Chlorinated hydrocarbon pesticides and related compounds in adipose tissue from people of Japan. Nature (London) 242,338-340. DOWTY, B., CARLISLE, D., LASETER, J. L.. AND STORER, J. (1975). Halogenated hydrocarbons in New Orleans drinking water and blood plasma. Science 187,75-77. GILBERTSON, M., AND REYNOLDS, L. M. (1972). Hexachlorobenzene (HCB) in the eggs of common terns in Hamilton Harbour, Ontario. Bull. Environ. Contam. Toxicol. 7,37 l-373. GROB, K., AND GROB, G. (1971). Gas-liquid chromatographic-mass spectrometric investigation of C,-C,, organic compounds in an urban atmosphere. An application of ultra trace analysis on capillary columns. J. Chromatogr. 62, 1-13. GROB, K.. AND GROB, G. (1974). Organic substances in potable water and its precursor. Part 11. Applications in the area of Zurich. J. Chromatogr. 90,303-3 13. HOLDEN, A. V. (1970). Pestic. Monit. J. 4, 117. HOLDEN, A. V. (1973). International cooperative study of organochlorine and mercury residues in wildlife, 196991971. Pestic. Monit. J. 7,37-52. JOHNSON, J. L., STALLING, D. L., AND HOGON, J. W. (197 1). Bull. Environ. Contamin. Toxicol. 6,464. JONDORF, W. R., PARKE, D. V., AND WILLIAMS, R. T. (1955). Studies in detoxication. 66. The metabolism of halogenobenzenes. 1: 2 : 3-, 1: 2 :4- and 1 : 3 : 5-trichlorobenzenes Biochem. J. 61, S 12-52 1. JONDORF, W. R., PARKE, D. V., AND WILLIAMS, R. T. (1958). Studies in detoxication. 76. The metabolism of halogenobenzenes. 1: 2 : 3 : 4-, 1: 2 : 3 : 5- and 1: 2 : 4 : 5-tetrachlorobenzenes. Biochem. J. 69, 18 l-l 89. KOEMAN, J. H., TEN NOEVER DE BRAW, M. C., AND DE Vos R. H. (1969). Chlorinated diphenyls in fish. mussels and birds from the River Rhine and the Netherlands coastal area. Nuture (London) 221, 11261128. MEHENDALE, H., FIELDS. M., AND MATTHEWS, H. B. (1975). J. Agr. Food Chem. 23,26 1. METCALFE, R. L., KAPOOR, I. P., Lo, P. Y., SCHUTH, C. K., AND SHERMAN, P. (1973). Model ecosystem studies of the environmental fate of six organochlorine pesticides. Environ. Health Perspect. 4,35-44. MORITA, M., MIMURA, S., OHI, G., YAGYU, H., AND NISHIZAWA. T. (1975). Environ. Polk. 9, 175. MORITA, M., AND OHI, G. (1975). Environ. Pollut. 8, 269. MORITA. M.. AND OISHI, S., (1975). Clearance and tissue distribution of hexachlorobenzene in rats. Bull. Environ. Contam. Toxicol. 14,3 13-3 18. PARKE. D. V., AND WILLIAMS, R. T. (1955). Studies in detoxication. 63. The metabolism of halogenobenzenes. (a) Meta-dichlorobenzene. (b) Further observations on the metabolism of chlorobenzene. Biochem. J. 59,4 15-422. ABBOTT,
COLLINS,
Kingdom
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PARKE, D. V., AND WILLIAMS, R. T. (1960). Studies in dextoxication. 81. The Metabolism of halogenobenzenes: (a) Penta- and hexa-chlorobenzenes. (b) Further observations on 1: 3 : 5. trichlorobenzene. Biochem. J. 74,5-g. SCHWARTZ, N., GAFFNEY, H. E., SCHMUTZER,M. S., AND STEFANO, F. D. (1963). J. Assoc. UfJ. Agr. Chem. 46,893. SIYALI, D. S. (1972). Hexachlorobenzene and other organochloride pesticides in human blood. Med. J. Aust. 2,1063-1066. SIYALI, D. S. (1973). Polychlorinated biphenyls, hexachlorobenzene and other organochlorine pesticides in human milk. Med. J. Aust. 2,815-818. SMMITH,J. N., SPENCER,B., and WILLIAMS, R. T. (1950). Studies in detoxication. 34. The metabolism of chlorobenzene in the rabbit. Isolation of dihydrodihydroxychlorobenzene,p-chlorophenylglucuronide, 4. chlorocatechol glucuronide andp-chlorophenyl-mercapturic acid. Biochem. J. 47,284-293. TUINSTRA, L. G. N. (1971). Milk Dairy J. 25,24. Vos, J. G., BREEMAN, H. A., BENSHOP, H., AND RIJKSFAC, M. (1968). Landbouwwetensch. Gent. 33, 1263. WESTOO, et al. (1974). WHO Pestic. Residues Ser. No. 3, 294. ZITKO, V. (197 1). Bull. Environ. Contam. Toxicof. 6,464.
Chlorinated
Benzenes
in the Environment
MASATOSHI Tokyo
Metropolitan
Research
Laboratory Received
MORITA
of Public December
Health,
Shinjuku-ku,
Tokyo,
160 Japan
28,1975
Chlorinated benzenesare composedof twelve chemical species:one mono-, three di-, three tri-, three tetra-, one penta-, and one hexachlorobenzene. Most of these are not only important intermediates for various kinds of chemicals but are also extensively employed for various applications singly or in combination. For example, 1,4-dichlorobenzene is used for household purposes in insect repellents and deodorants; 1,2dichlorobenzene is used chiefly against termites in soil; trichlorobenzenes are used as solvents for pesticides and also as heat transfer agents with PCBs; the mixture of trichlorobenzene and tetrachlorobenzene is applied in controlling shellfish predators; and hexachlorobenzene is applied to wheat as a fungicide in somecountries and as an additive to rubber products. The annual production (1973) of monochlorobenzene, 1,2-dichlorobenzene, and 1,4dichlorobenzene in Japan was about 23,000, 9000, and 20,000, tons, respectively. Production volumes of other chlorinated benzenesare not well known but are assumed to be smaller than those of the above three compounds. The total annual production of chlorinated benzenes far surpassesthe peak production of PCBs (7000 tons/year) which are known as a ubiquitous pollutant in this country. Since chlorinated benzenes have a chemical structure and properties similar to those of PCBs and PCTs, it seemed necessary to direct our attention to environmental contamination by these materials. The present paper describes only the occurrence and the fate of these materials. Toxicity and biological impact are not referred to here. CHLORINATED
BENZENES
IN
AIR AND
WATER
Only limited information is available on the level of chlorinated benzenes in air and water. Chlorinated benzenesare more volatile than PCBs and are likely to constitute atmospheric contaminants, especially in lower-chlorinated benzenes. Morita and Ohi (1975) determined the level of l$dichlorobenzene in the atmosphere of the Tokyo metropolitan area. As might be expected from its use, l&dichlorobenzene concentrations were higher in indoor than in outdoor air. Outdoor levels in and around Tokyo were almost 2.4 ,&m3. Grob and Grob (1971) and Grob et al. (1974) identified monochlorobenzene, dichlorobenzene, and trichlorobenzene isomers and its precursor in drinking water in Geneva. Morita determined the levels of 1,4-dichlorobenzene and hexachlorobenzene in the intake, effluent, and activated sludge in several sewage plants in Tokyo (unpublished Copyright
@ 1977 by Academic Press, Inc. All rights of reproduction in any form reserved. Printed in Great Britain
1
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MASATOSHI
MORITA
observations). The averages were 1.0, 1.1 and 1200 ppb (1,4-dichlorobenzene) 0.00 13,O.OO 11, and 38 ppb (hexachlorobenzene), respectively. Pentachlorobenzene also found in the samples at a lower concentration than hexachlorobenzene.
and was
CHLORINATEDBENZENESINBIOLOGICALSAMPLES As with air and water, only a few data are reported for chlorinated benzene pollution of biological samples except for hexachlorobenzene. Morita and Ohi (1975) demonstrated that 1,4-dichlorobenzene accumulated in the fat tissue of pigeons in concentrations as high as 1.85 ppm. Although l&dichlorobenzene was also detected in several kinds of fish, 0.1 ppm in carp, 0.04 ppm in harvest fish, and 0.05 ppm in horse mackerel, on the basis of fat content, the level is generally low. Schwartz et al. (1963) detected low levels of those chlorinated benzene pesticides used for controlling molluscan pests in clams and oysters. In the samples of fish and birds in Japan, the pentachlorobenzene peak usually appears on gas chromatograms of hexachlorobenzene, although the level is usually low (about one-tenth that of hexachlorobenzene). Hexachlorobenzene has been found in fish from a number of river systems in Canada (Zitko, 1971) and in the United States (Holden, 1970, 1973; Johnson et al., 1971). Johnson et al. (197 1) reported an extremely high contamination by hexachlorobenzene in carp (62 pug/g wet weight). The source of hexachlorobenzene in that case was tentatively identified as runoff from an industrial chemical storage area. Koeman et al. (1969) demonstrated a hexachlorobenzene residue of 0.067 ppm (wet weight) in bladders of juvenile seals collected in coastal waters off the Netherlands. A low level of hexachlorobenzene residue was found in Japanese fish and shellfish (Morita, unpublished observations). Hexachlorobenzene contamination of wild birds is reported in the Netherlands (Vos et al., 1968; Koeman et al., 1969). Hexachlorobenzene was also found in the eggs of terns collected in Canada and the Netherlands (Gilbertson and Reynolds, 1972; Holden, 1973). In general, hexachlorobenzene pollution is slight in Japan compared with the United States or Canada. CHLORINATEDBENZENES IN HUMANTISSUES Morita et al. (1975) searched systematically for chlorinated benzenes in adipose tissues of Japanese by mass fragmentography and gas chromatograhy equipped with electron capture detectors. The species identified were l&dichlorobenzene, 1,2,4,5tetrachlorobenzene, pentachlorobenzene, and hexachlorobenzene. Above the detection limit (0.01 ppm), no other chlorinated benzenes were detected (Morita et al., 1975). Dowty et al. (1975) identified three isomers of dichlorobenzene in blood plasma of residents of Louisiana. Morita et al. (1975) determined 1,4-dichlorobenzene levels in human fat and blood in the Tokyo area. The 1,4-dichlorobenzene concentration in 34 human adipose tissue samples was 2.1 ppm on the basis of fat content, and that in blood samples averaged 9.5 ppb. No peak corresponding to 1,2-dichlorobenzene was found after gas
CHLORINATED
BENZENES
3
chromatography in spite of the fact that the annual production of 1,2-dichlorobenzene is about one-half that of 1,4-dichlorobenzene. The average levels of 1,2,4,5tetrachlorobenzene and pentachlorobenzene in 15 Japanese human adipose tissue samples were 0.019 and 0.009 ppm, respectively (Morita et al., 1975). Several studies have reported the presence of hexachlorobenzene in human fat tissues, blood, and milk. An Australian study of occupationally exposed individuals showed levels in blood ranging from 0 to 0.41 ppm. A control group with no known exposure showed blood levels ranging from 0 to 0.095 ppm. Hexachlorobenzene was detected in 95% of the people (Siyali, 1972). Another Australian study revealed that all perrenal fat samples examined contained hexachlorobenzene at an average concentration of 1.25 ppm with a range from a trace to 8.2 ppm (Brady and Siyali, 1972). A German study detected hexachlorobenzene residues of 6.3 ppm in fat and 5.3 ppm in the fat from human milk (Acker and Schulte, 1972). A survey in the United Kingdon showed that hexachlorobenzene residues ranged from 0.01 to 0.29 ppm with a mean of 0.05 ppm in 201 samples occurred generally in the population (Abbott et al., 1972). The plasma hexachlorobenzene residues in a Louisiana population were determined for individuals exposed during the transportation and disposal of chemical wastes containing hexachlorobenzene, and the residues averaged 3.6-4.3 ppb in the sample of 86 people. The highest level was 345 ppb in a waste disposal facility worker while the highest level in the general population was 23 ppb (Burns and Miller, 1975). Carley et al. (1973) analyzed human adipose tissues from Japan and reported hexachlorobenzene levels ranging from 0.30 to 1.48 ppm. Another survey of Japanese human adipose tissues showed lower levels of hexachlorobenzene residue, ranging from 0.10 to 0.42 ppm with a mean of 0.2 1 ppm. (Morita et al., 1975). Significant residues of hexachlorobenzene are reported in human milk from the Netherlands (Tuinstra, 1971) Australia (Siyali, 1973), and Germany (Acker and Schulte, 1970). A Swedish study has shown levels in breast milk ranging from 0.07 to 0.22 ppm expressed on a fat content basis (Westoo et al., 1974). METABOLISMANDBIODEGRADATION
Williams and his co-workers reported the metabolic fate of monochlorobenzene (Smith et al., 1950), dichlorobenzene (Azouz et al., 1955; Parke and Williams, 1955), trichlorobenzene (Jondorf et al., 1955), tetrachlorobenzene (Jondorf et al., 1958), and pentachlorobenzene and hexachlorobenzene (Parke and Williams, 1960) in rabbits. These studies suggested that the more chlorine the halogenated benzene contained, the less rapidly it was metabolized. Pentachlorobenzene is only slightly altered in uivo, and hexachlorobenzene seems to be metabolically inert. Metabolites of the chlorinated benzenes indicate that oxidative hydroxylation and reductive dechlorination are the main routes of conversion. Hydroxylation is a rapid reaction in mono- and dichlorinated benzenes, and the contribution of dechlorination seems to be negligibly small in these systems. Most of the metabolites are the corresponding phenols and their derivatives. 14Dichlorobenzene is least rapidly metabolized among these materials, and this may be related to the predominance of 14dichlorobenzene in human adipose tissue.
4
MASATOSHI
MORITA
On the other hand, hydroxylation is difficult in pentachlorobenzene, due to steric hindrance by adjacent chlorine atoms, and is impossible in hexachlorobenzene. In this case, a very slow dechlorination reaction occurs as a first step of metabolism. Since dechlorination is a very slow reaction, these compounds appear to be metabolically inert. In the case of tri- and tetrachlorobenzenes, both reactions proceed competitively, phenols having the same and fewer numbers of chlorine substitutions are produced through metabolism. The reaction rate of hydroxylation depends on the configuration of the chlorine substitutions in the benzene ring. The 1,3,5substitution blocks the reaction site well and results in the least rapid metabolism among the three trichlorobenzene isomers (Jondorf et al., 1955). In the series of tetrachlorobenzenes, the 1,2,4,5-substitution seems to be most resistant to hydroxylation because of steric factors. In fact, 1,2,4,5tetrachlorobenzene appears to be the most slowly metabolized of the three isomers, and 48% of the dose was found unchanged in the tissues of rabbits after 6 days of administration. Furthermore, the metabohtes were composed mainly of dechlorinated products. Though Parke and Williams (1960) reported that hexachlorobenzene is metabolically inert, Mehendale et al. (1975) recently reported the metabolism of hexachlorobenzene using isotope techniques. Metabolites of hexachlorobenzene included pentachlorobenzene, tetrachlorobenzene, pentachlorophenol, and four unknowns. Mehendale et ~1. found that the reductive dechlorination of hexachlorobenzene was catalyzed by an enzyme located in the microsomal fraction of liver, lung, kidney, and intestine. They also reported that 70% of the total dose was found remaining in the body 7 days after administration. Morita and Ohishi (1975) applied a single dose of hexachlorobenzene to male Wistar rats and estimated the biological half-life of the material to be about 60 days. Borzelleca et al. (197 1) found that hexachlorobenzene and pentachlorobenzene, contaminants of technical pentachloronitrobenzene (PCNB), were stored in the tissues of rats, dogs, and cows given food containing PCNB; the chlorobenzenes were present at levels paralleling their content in the PCNB, indicative of a slower rate of metabolism of these compounds. Food chain magnification is suggested in hexachlorobenzene contamination (Metcalfe et al., 1973). There is a possibility that the food chain magnification is operative in other chlorinated benzenes with slow rates of metabolism, such as pentachlorobenzene. In parallel with the rate of metabolism, the rate of biodegradation is reported to be fast in lower-chlorinated benzenes and extremely slow in hexachlorobenzene. No information is available for the biodegradability of tetra- and pentachlorobenzene. Photochemical decomposition of chlorinated benzenes is not well known in the environment. AN OVERVIEW
It is worthwhile to compare 1,4-dichlorobenzene and hexachlorobenzene. 1,4Dichlorobenzene is metabolized and biodegraded relatively rapidly but its high rate of production gives rise to extensive contamination and in some casesresiduesof a high
CHLORINATED
BENZENES
5
level in biological samples. On the other hand, hexachlorobenzene is a compound which is characterized as hard to biodegrade. Phthalate esters may be related to the former compound, and DDT is similar to the latter type. The author has tried to delineate the pollution pattern of chlorinated benzenes. It may not have been entirely successful due to the limited information available. Further investigations are necessary in this area.
REFERENCES D. C., in the United ACKER, L.. AND ACKER, L., AND
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