PART
Ix.
SURVEILLANCE FOR
FUTUREENVIRONMENTAL CONTAMINANTS
FDA’S CHEMICAL CONTAMINANTS PROGRAM: THE SEARCH FOR THE UNRECOGNIZED POLLUTANT Pasquale Lombard0 Division of Chemical Technology Food and Drug Administration Washington, D.C. 20204
During the past decade, it has become increasingly evident that industrial chemicals can contaminate foods even though they are not intentionally used on agricultural products or processed foods. Extensive contamination of fish by mercury was revealed in 1969, and widespread pollution of the environment by polychlorinated biphenyls (PCBs) was uncovered at about the same time. Government regulatory agencies were caught by surprise. Much had to be learned about these chemicals, and in order to determine the extent to which foods were contaminated, it was necessary to gain familiarity with analytic methods suitable for their detection and quantification. Considerable time and effort went into standardizing and simplifying the methods so that results would be comparable, and analyses could be run routinely. To provide better preparation for future occurrences of this nature, FDA launched its Chemical Contaminants Program in 197 1. The program covers industrial chemicals, pesticides, and metals, and its principal objectives are: (1) to develop sufficient information to establish guidelines for recognized industrial chemical contaminants of foods; (2) to anticipate and search for as yet unrecognized contaminants; (3) to evaluate their hazards if found in foods; and (4) to take steps to eliminate or minimize the problem. The basic aims, of course, are to accumulate background information in a noncrisis atmosphere, provide FDA an early warning system, and enable the agency to react rapidly in “emergency” situations. Although the program also encompasses pesticides and metals, emphasis here will be placed on industrial chemicals. The prime responsibility for research on industrial chemicals lies with the Division of Chemical Technology of FDA’s Bureau of Foods. Fundamentally, our charge is to determine which industrial chemicals have the greatest potential to become food contaminants, what areas are most likely to be affected, and to check likely target foods. The main criteria used in the selection of industrial chemical types for study are the same as those used by most agencies concerned with the environment. They include volume of production, associated impurities or by-products, predicted environmental stability, pattern of use, oil-water partition coefficients, bioaccumulation potential, known toxicity, and means of disposal. Background information is gathered chiefly through industry and government contacts, trade journals, and the literature. One of the chief groups with which we exchange information is, of course, the Environmental Protection Agency (EPA). Among the classes of materials under investigation are flame retardants, plasticizers, electrical fluids, halogented solvents, various chemical intermediates, functional fluids, lubricating oil additives, replacements for PCBs, and chemicals present in sewage sludge and wastewaters. Once it is decided that particular chemicals or groups of chemicals should be looked into, we determine if our traditional pesticide methodology can adequately recover them from foods. If not, our laboratory attempts to develop the necessary means for the detection of these compounds. Reference compounds are essential for
67 3 0077-8923/79/032&0673 $01.75/0 0 1919, NYAS
674
Annals N e w York Academy of Sciences
this, and we have established a collection of some 500 different industrial chemicals for our use. (These materials are also made available to our field units, other government agencies and selected researchers on request.) With analytic methodology in hand, our usual approach is to obtain food samples from geographic locations thought likely to contain the potential contaminant. The vast majority of our samples are obtained through the cooperative efforts of other federal and state agencies, whose help has proved invaluable. Our prime indicator organism is the fresh water fish, as most problem contaminants eventually find their way into this segment of the human food chain. If we are successful in finding the suspect pollutant, our monitoring activities are expanded, up to and including nationwide surveys of various foods by our field laboratories. On the basis of the results, our toxicologists may then judge whether the chemical contaminant constitutes a hazard to the consuming public. Ultimately, regulatory limits may be set for the chemical or chemicals in question. As a result of our investigations, we have been able to detect some of the less commonly encountered industrial chemicals in foods. These are summarized in TABLE 1. Unless otherwise indicated, the findings have been made in fish. Since almost all the samples were from inland waters near manufacturer or user sites, the residues are not necessarily reflective of what the general public is exposed to. I will comment briefly on some of these findings. A. Chlorinated benzenes. Annual production is large, totaling well over 500 million pounds. As the table illustrates, residues of these compounds have been found in fish from many different geographic locations. The chlorobenzenes are used for a variety of purposes, including chemical intermediates, dye carriers, electrical fluids, solvents, and pesticides. The findings of tri- and tetrachlorobenzenes are not surprising, as these chemicals have been used for many years in combination with PCBs in transformers. Leakage of the transformers would provide direct entry into the environment. Hexachlorobenzene, of course, is now a widely recognized environmental contaminant. B. Chlorinated benzyl chlorides and benzotrifluorides. Thus far, we have found these chemical intermediates solely in fish from the lower Niagara River in New York. C. Other chlorinated aromatics. We have detected the chloronitrobenzenes in fish only recently, and we intend to collect samples near other manufacturing sites to determine if these compounds are more widespread in the environment. Pentachloroaniline and pentachlorophenyl methyl sulfide are associated with the pesticide pentachloronitrobenzene (PCNB). Pentachloroanisole is derived from the pesticide pentachlorophenol, and is frequently found as a residue in fish. Octachlorostyrene is a by-product of many chlorination processes, and we have detected this compound in fish from the two locations shown. D. Chlorinated cycloaliphatics. The chlorinated norbornene and norbornadiene compounds are precursors of the pesticide endrin, and have been found in Mississippi River fish below a manufacturing plant in Memphis, T N . Epoxy hexachloronorbornene is an apparent environmental conversion product of one or both of these compounds. The chlorocyclopentenes were found in fish near a plant manufacturing hexachlorocyclopentadiene (HCP), and are probably by-products. We have never detected HCP itself in fish, although the compound is an important intermediate for several pesticides and flame retardants. It has been concluded by us and others that H C P is environmentally unstable a t low concentrations. (We were involved to some extent in the Louisville, KY problem, where large amounts of still bottoms from H C P production were dumped into the sewer system. In this case, we had no problem detecting HCP, octachlorocyclopentene, and a host of other chloroorganics in the sewage sludge. The concentrations, of course, were in the percent range.)
Lombardo: FDA’s Chemical Contaminants Program TABLE1 INDUSTRIAL CHEMICAL RESIDUESFOUNDIN FOODS* Range, ppmt
Location
Chlorinated Benzenes
I
monochloro 1,4-dichloro 1,2-dichloro 1,3,5-trichloro 1,2,3-trichloro 1,2,4-trichloro 1,2,3,5-tetrachloro 1,2,4,5-tetrachloro 1,2,3,4-tetrachIoro pentachloro hexachloro
I
Tombigbee R. AL Ohio R. OH Niagara R. NY White Lake, MI Spring Creek, PA Bald Eagle Creek, PA Mississippi R. LA/MO
tr-6.7
0.1 1 0.07
(peanut oil) (peanut oil)
Chlorinated Benzvl Chlorides rnonochioro dichloro trichloro 3,4-dichloro Chlorinated Benzotrifluorides 4-chloro 3,4-dichloro 2.4-dichloro trichloro tetrachloro
0.3-2.0 tr-0.1 0.2-0.8
t t
Other Chlorinated Aromatics 4-chloronitro benzene 2-chloronitrobenzene 3,4-dichloronitrobenzene 2,3-dichloronitrobenzene tetrachloronitrobenzene pentachloronitrobenzene pentachloroaniline pentachlorophenyl methyl sulfide pentachloroanisole pen tachloroanisole pentachlorophenol octachlorostyrene
0.01-0.33 0.006-0.12 0.05 0.01 tr 0.03 0.26 0.08 tr-0.15 0.1 tr-0.02 0.02-0.1
Mississippi R. MO
I
Mississippi R. MO (peanut oil) Mississi pi R. MO
Q
Mississippi R. MO many rivers and lakes (peanut oil) Mississippi R. LA Lake Ontario, NY White Lake, MI
- Chlorinated Cycloaliphatics hexachloronorbornadiene heptachloronorbornene epoxy tetrachlorocyclopentene pentachlorocyclopentene hexachlorocyclopentene
0.03-16.2
1 t 1
Mississippi R. LA/MO White Lake, MI
4
White Lake, MI
675
Annals New York Academy of Sciences
676
TABLE1 (Continued) Range, ppmt
Location
Chlorinated Aliphatics hexachlorobutadiene
White Lake, MI Mississippi R. L A / M O Ohio R. O H
tr-4.6
hexachloroethane pentachloroethane pentachlorobutadtene Brominated Aromatics
0.13
%
RtOH
Ohio Ohio R. O H
-
polybrorninated biphenyls polybrominated biphenyls
Pine R. MI Ohio R. W.VA
tr-1.1
1,rl-dibromobenzene
tr
I ,2,4-tribromobenzene
0.05
I ,2,4,5-tetrabromobenzene monobromobiphen yl dibromobiphenyl
0.04 I
1
Pine R. MI
f
Pine R. MI
Triaryl Phosphates triphenyl curnylphenyl diphenyl nonylphenyl diphenyl isopropylphenyl diphenyl
0.06-0. I5
trixylenyl tricresyl 2-ethylhexyl diphenyl Aromatic Arnines
0.02-0.08 0.02-0.04 I .4
I-naphthylamine
0.01-0. I2
N-ethyl-N-phenyl benzylamine N-ethyl-N-(m-tolyl) benzylamine 3.3'-dichlorobenzidine
0.001-0. I 7 0.001-0.0 I
benzidine
2.5
0.13-0.41 0.16-0.50 0.1-1 .o
0.1-0.3
Wauke an Harbor, IL
1
Waukegan Harbor, 1L Saginaw R. MI Kishacoquillas Creek, PA Columbia R. W A / O R Columbia R. WA/OR (animal fat) Delaware R. D E Buffalo R. N Y Delaware R. D E Delaware R. D E Muskegon County, MI (waste water) (waste water)
tr, = Trace *In fish unless otherwise indicated. +Edible portion basis. $ N o t quantitated because o f lack of reference material at time of analysis.
E. Chlorinated alipharics. The chlorinated butadienes and ethanes are related to octachlorostyrene and hexachlorobenzene in that they are all by-products of chlorinated hydrocarbon manufacture. Hexachlorobutadiene (HCBD) is not made commercially, but is a major component of waste products derived from perchloroethylene production. HCBD has been frequently found as a contaminant of fish. Prompted by our findings of HCBD residues, FDA conducted a field surveillance program in 1975, in which five of our district laboratories collected food samples near perchloroethylene plants. Residues of HCBD were found in 8 of 9 samples of fresh water fish (0.01-1.2 ppm), 2 of 20 salt water fish (0.01-0.02 ppm), and 1 of 20 milk samples (< 1 ppm, fat basis). None was found in 15 egg and 19 leafy vegetable
Lombardo: FDA’s Chemical Contaminants Program
677
samples. FDA toxicologists concluded that the concentration present did not constitute a toxicologic hazard to the consumer. F. Brominated aromatics. In addition to the polybrominated biphenyls, low levels of several bromobenzenes have been detected in fish collected near a bromocarbon producer in Michigan. G . Phosphates. Our interest in these chemicals stemmed from the fact that they have replaced PCBs in some flame retardant plasticizer and functional fluid applications. Our first findings of residues in fish were made in Waukegan Harbor, IL. After learning that a manufacturing facility that formerly discharged large amounts of a PCB hydraulic fluid had replaced it with an aryl phosphate, we obtained fish samples from near the outfall. As shown in TABLE1, concentrations of the major components of the fluid totaled almost 1 ppm in some fish. Subsequent findings of aryl phosphate residues have been made near other user sites. H. Aromatic amines. These chemical intermediates have been found in fish near dyestuff producers. Although the concentrations are low, we have maintained interest in this class of compounds because of their carcinogenic potential. Among other chemicals considered and temporarily shelved are chlorinated paraffins and phthalate esters. Production of chlorinated paraffins is greater than 100 million pounds annually, but they do not appear to biomagnify to any appreciable extent. We have also been unable to detect these compounds in fish and sediment collected near manufacturing facilities. The phthalates are of course widespread, but after conducting a nationwide survey, FDA concluded that the concentrations present in foods are not high enough to constitute a toxicologic threat. We are continuing to investigate and search for other potential food contaminants. In addition to those already mentioned, we are studying lower chlorinated phenols and anisoles, volatile halocarbons (such as perchloroethylene, haloforms, carbon tetrachloride, etc.), chlorinated dibenzofurans, and aromatic nitrogen compounds. It is our hope that these activities will enable FDA to uncover contamination of foods by industrial chemicals early enough to take corrective action. At the very least, the information developed will help FDA to react quickly in emergency situations.
Ix.
SURVEILLANCE FOR
FUTUREENVIRONMENTAL CONTAMINANTS
FDA’S CHEMICAL CONTAMINANTS PROGRAM: THE SEARCH FOR THE UNRECOGNIZED POLLUTANT Pasquale Lombard0 Division of Chemical Technology Food and Drug Administration Washington, D.C. 20204
During the past decade, it has become increasingly evident that industrial chemicals can contaminate foods even though they are not intentionally used on agricultural products or processed foods. Extensive contamination of fish by mercury was revealed in 1969, and widespread pollution of the environment by polychlorinated biphenyls (PCBs) was uncovered at about the same time. Government regulatory agencies were caught by surprise. Much had to be learned about these chemicals, and in order to determine the extent to which foods were contaminated, it was necessary to gain familiarity with analytic methods suitable for their detection and quantification. Considerable time and effort went into standardizing and simplifying the methods so that results would be comparable, and analyses could be run routinely. To provide better preparation for future occurrences of this nature, FDA launched its Chemical Contaminants Program in 197 1. The program covers industrial chemicals, pesticides, and metals, and its principal objectives are: (1) to develop sufficient information to establish guidelines for recognized industrial chemical contaminants of foods; (2) to anticipate and search for as yet unrecognized contaminants; (3) to evaluate their hazards if found in foods; and (4) to take steps to eliminate or minimize the problem. The basic aims, of course, are to accumulate background information in a noncrisis atmosphere, provide FDA an early warning system, and enable the agency to react rapidly in “emergency” situations. Although the program also encompasses pesticides and metals, emphasis here will be placed on industrial chemicals. The prime responsibility for research on industrial chemicals lies with the Division of Chemical Technology of FDA’s Bureau of Foods. Fundamentally, our charge is to determine which industrial chemicals have the greatest potential to become food contaminants, what areas are most likely to be affected, and to check likely target foods. The main criteria used in the selection of industrial chemical types for study are the same as those used by most agencies concerned with the environment. They include volume of production, associated impurities or by-products, predicted environmental stability, pattern of use, oil-water partition coefficients, bioaccumulation potential, known toxicity, and means of disposal. Background information is gathered chiefly through industry and government contacts, trade journals, and the literature. One of the chief groups with which we exchange information is, of course, the Environmental Protection Agency (EPA). Among the classes of materials under investigation are flame retardants, plasticizers, electrical fluids, halogented solvents, various chemical intermediates, functional fluids, lubricating oil additives, replacements for PCBs, and chemicals present in sewage sludge and wastewaters. Once it is decided that particular chemicals or groups of chemicals should be looked into, we determine if our traditional pesticide methodology can adequately recover them from foods. If not, our laboratory attempts to develop the necessary means for the detection of these compounds. Reference compounds are essential for
67 3 0077-8923/79/032&0673 $01.75/0 0 1919, NYAS
674
Annals N e w York Academy of Sciences
this, and we have established a collection of some 500 different industrial chemicals for our use. (These materials are also made available to our field units, other government agencies and selected researchers on request.) With analytic methodology in hand, our usual approach is to obtain food samples from geographic locations thought likely to contain the potential contaminant. The vast majority of our samples are obtained through the cooperative efforts of other federal and state agencies, whose help has proved invaluable. Our prime indicator organism is the fresh water fish, as most problem contaminants eventually find their way into this segment of the human food chain. If we are successful in finding the suspect pollutant, our monitoring activities are expanded, up to and including nationwide surveys of various foods by our field laboratories. On the basis of the results, our toxicologists may then judge whether the chemical contaminant constitutes a hazard to the consuming public. Ultimately, regulatory limits may be set for the chemical or chemicals in question. As a result of our investigations, we have been able to detect some of the less commonly encountered industrial chemicals in foods. These are summarized in TABLE 1. Unless otherwise indicated, the findings have been made in fish. Since almost all the samples were from inland waters near manufacturer or user sites, the residues are not necessarily reflective of what the general public is exposed to. I will comment briefly on some of these findings. A. Chlorinated benzenes. Annual production is large, totaling well over 500 million pounds. As the table illustrates, residues of these compounds have been found in fish from many different geographic locations. The chlorobenzenes are used for a variety of purposes, including chemical intermediates, dye carriers, electrical fluids, solvents, and pesticides. The findings of tri- and tetrachlorobenzenes are not surprising, as these chemicals have been used for many years in combination with PCBs in transformers. Leakage of the transformers would provide direct entry into the environment. Hexachlorobenzene, of course, is now a widely recognized environmental contaminant. B. Chlorinated benzyl chlorides and benzotrifluorides. Thus far, we have found these chemical intermediates solely in fish from the lower Niagara River in New York. C. Other chlorinated aromatics. We have detected the chloronitrobenzenes in fish only recently, and we intend to collect samples near other manufacturing sites to determine if these compounds are more widespread in the environment. Pentachloroaniline and pentachlorophenyl methyl sulfide are associated with the pesticide pentachloronitrobenzene (PCNB). Pentachloroanisole is derived from the pesticide pentachlorophenol, and is frequently found as a residue in fish. Octachlorostyrene is a by-product of many chlorination processes, and we have detected this compound in fish from the two locations shown. D. Chlorinated cycloaliphatics. The chlorinated norbornene and norbornadiene compounds are precursors of the pesticide endrin, and have been found in Mississippi River fish below a manufacturing plant in Memphis, T N . Epoxy hexachloronorbornene is an apparent environmental conversion product of one or both of these compounds. The chlorocyclopentenes were found in fish near a plant manufacturing hexachlorocyclopentadiene (HCP), and are probably by-products. We have never detected HCP itself in fish, although the compound is an important intermediate for several pesticides and flame retardants. It has been concluded by us and others that H C P is environmentally unstable a t low concentrations. (We were involved to some extent in the Louisville, KY problem, where large amounts of still bottoms from H C P production were dumped into the sewer system. In this case, we had no problem detecting HCP, octachlorocyclopentene, and a host of other chloroorganics in the sewage sludge. The concentrations, of course, were in the percent range.)
Lombardo: FDA’s Chemical Contaminants Program TABLE1 INDUSTRIAL CHEMICAL RESIDUESFOUNDIN FOODS* Range, ppmt
Location
Chlorinated Benzenes
I
monochloro 1,4-dichloro 1,2-dichloro 1,3,5-trichloro 1,2,3-trichloro 1,2,4-trichloro 1,2,3,5-tetrachloro 1,2,4,5-tetrachloro 1,2,3,4-tetrachIoro pentachloro hexachloro
I
Tombigbee R. AL Ohio R. OH Niagara R. NY White Lake, MI Spring Creek, PA Bald Eagle Creek, PA Mississippi R. LA/MO
tr-6.7
0.1 1 0.07
(peanut oil) (peanut oil)
Chlorinated Benzvl Chlorides rnonochioro dichloro trichloro 3,4-dichloro Chlorinated Benzotrifluorides 4-chloro 3,4-dichloro 2.4-dichloro trichloro tetrachloro
0.3-2.0 tr-0.1 0.2-0.8
t t
Other Chlorinated Aromatics 4-chloronitro benzene 2-chloronitrobenzene 3,4-dichloronitrobenzene 2,3-dichloronitrobenzene tetrachloronitrobenzene pentachloronitrobenzene pentachloroaniline pentachlorophenyl methyl sulfide pentachloroanisole pen tachloroanisole pentachlorophenol octachlorostyrene
0.01-0.33 0.006-0.12 0.05 0.01 tr 0.03 0.26 0.08 tr-0.15 0.1 tr-0.02 0.02-0.1
Mississippi R. MO
I
Mississippi R. MO (peanut oil) Mississi pi R. MO
Q
Mississippi R. MO many rivers and lakes (peanut oil) Mississippi R. LA Lake Ontario, NY White Lake, MI
- Chlorinated Cycloaliphatics hexachloronorbornadiene heptachloronorbornene epoxy tetrachlorocyclopentene pentachlorocyclopentene hexachlorocyclopentene
0.03-16.2
1 t 1
Mississippi R. LA/MO White Lake, MI
4
White Lake, MI
675
Annals New York Academy of Sciences
676
TABLE1 (Continued) Range, ppmt
Location
Chlorinated Aliphatics hexachlorobutadiene
White Lake, MI Mississippi R. L A / M O Ohio R. O H
tr-4.6
hexachloroethane pentachloroethane pentachlorobutadtene Brominated Aromatics
0.13
%
RtOH
Ohio Ohio R. O H
-
polybrorninated biphenyls polybrominated biphenyls
Pine R. MI Ohio R. W.VA
tr-1.1
1,rl-dibromobenzene
tr
I ,2,4-tribromobenzene
0.05
I ,2,4,5-tetrabromobenzene monobromobiphen yl dibromobiphenyl
0.04 I
1
Pine R. MI
f
Pine R. MI
Triaryl Phosphates triphenyl curnylphenyl diphenyl nonylphenyl diphenyl isopropylphenyl diphenyl
0.06-0. I5
trixylenyl tricresyl 2-ethylhexyl diphenyl Aromatic Arnines
0.02-0.08 0.02-0.04 I .4
I-naphthylamine
0.01-0. I2
N-ethyl-N-phenyl benzylamine N-ethyl-N-(m-tolyl) benzylamine 3.3'-dichlorobenzidine
0.001-0. I 7 0.001-0.0 I
benzidine
2.5
0.13-0.41 0.16-0.50 0.1-1 .o
0.1-0.3
Wauke an Harbor, IL
1
Waukegan Harbor, 1L Saginaw R. MI Kishacoquillas Creek, PA Columbia R. W A / O R Columbia R. WA/OR (animal fat) Delaware R. D E Buffalo R. N Y Delaware R. D E Delaware R. D E Muskegon County, MI (waste water) (waste water)
tr, = Trace *In fish unless otherwise indicated. +Edible portion basis. $ N o t quantitated because o f lack of reference material at time of analysis.
E. Chlorinated alipharics. The chlorinated butadienes and ethanes are related to octachlorostyrene and hexachlorobenzene in that they are all by-products of chlorinated hydrocarbon manufacture. Hexachlorobutadiene (HCBD) is not made commercially, but is a major component of waste products derived from perchloroethylene production. HCBD has been frequently found as a contaminant of fish. Prompted by our findings of HCBD residues, FDA conducted a field surveillance program in 1975, in which five of our district laboratories collected food samples near perchloroethylene plants. Residues of HCBD were found in 8 of 9 samples of fresh water fish (0.01-1.2 ppm), 2 of 20 salt water fish (0.01-0.02 ppm), and 1 of 20 milk samples (< 1 ppm, fat basis). None was found in 15 egg and 19 leafy vegetable
Lombardo: FDA’s Chemical Contaminants Program
677
samples. FDA toxicologists concluded that the concentration present did not constitute a toxicologic hazard to the consumer. F. Brominated aromatics. In addition to the polybrominated biphenyls, low levels of several bromobenzenes have been detected in fish collected near a bromocarbon producer in Michigan. G . Phosphates. Our interest in these chemicals stemmed from the fact that they have replaced PCBs in some flame retardant plasticizer and functional fluid applications. Our first findings of residues in fish were made in Waukegan Harbor, IL. After learning that a manufacturing facility that formerly discharged large amounts of a PCB hydraulic fluid had replaced it with an aryl phosphate, we obtained fish samples from near the outfall. As shown in TABLE1, concentrations of the major components of the fluid totaled almost 1 ppm in some fish. Subsequent findings of aryl phosphate residues have been made near other user sites. H. Aromatic amines. These chemical intermediates have been found in fish near dyestuff producers. Although the concentrations are low, we have maintained interest in this class of compounds because of their carcinogenic potential. Among other chemicals considered and temporarily shelved are chlorinated paraffins and phthalate esters. Production of chlorinated paraffins is greater than 100 million pounds annually, but they do not appear to biomagnify to any appreciable extent. We have also been unable to detect these compounds in fish and sediment collected near manufacturing facilities. The phthalates are of course widespread, but after conducting a nationwide survey, FDA concluded that the concentrations present in foods are not high enough to constitute a toxicologic threat. We are continuing to investigate and search for other potential food contaminants. In addition to those already mentioned, we are studying lower chlorinated phenols and anisoles, volatile halocarbons (such as perchloroethylene, haloforms, carbon tetrachloride, etc.), chlorinated dibenzofurans, and aromatic nitrogen compounds. It is our hope that these activities will enable FDA to uncover contamination of foods by industrial chemicals early enough to take corrective action. At the very least, the information developed will help FDA to react quickly in emergency situations.
