Pesticides and food safety

Pesticides and food safety

REGULATORY TOXICOLOGY AND PHARMACOLOGY 9,158-l 74 (1989) Pesticides and Food Safety ANNA M. FAN' AND RICHARD J. JACKSON Hazard Evaluation Sect...

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REGULATORY

TOXICOLOGY

AND

PHARMACOLOGY

9,158-l 74 (1989)

Pesticides and Food Safety ANNA

M. FAN' AND RICHARD

J. JACKSON

Hazard Evaluation Section, California Department of Health Services, 2151 Berkeley Way, Berkeley, California 94704

Received February 23,1988

This report reviews recent developments regarding the environmental, toxicological, and regulatory issues surrounding pesticide residues in food. Factors affecting the establishment of regulatory limits are discussed. Pesticides monitored by state and federal agencies are compiled and the need for improvements in analytical techniques and enforcement procedures in govemmental monitoring programs is pointed out. Specific incidents of concern related to pesticides in food including EDB in grain and grain products, aldicarb in watermelon, demeton-methyl in wine, DDT in fish, &S,Stributylphosphorotrithioate in chili peppers, and daminozide in apples and processed apple products are described. The National Academy of Science’s study on the Environmental Protection Agency’s (EPA) method for setting tolerances for pesticide residues is discussed, especially the dietary cancer risk estimates from pesticides and the inconsistencies in regulating oncogenic pesticides in raw and processed foods existing under the Delaney Clause. The EPA’s Tolerance Assessment System is identified to improve the quality of the tolerance establishment process. New California laws to ensure food safety include mandated activities in identifying the toxicological data gaps for pesticides and evaluating pesticide tolerances. Already initiated, tighter regulatory activities at both the federal and the state levels are expected to improve scientific information development, regulatory decisions, and public health protection. 0 1989 Academic Press, Inc.

INTRODUCTION The recent findings of the study by the Board on Agriculture of the National Research Council (NRC, 1987) which studied the Environmental Protection Agency’s (EPA) methods for setting tolerances for pesticide residues in food have brought to national attention a concern for the adequacy of the existing pesticide tolerances for public health protection. In California, the Department of Food and Agriculture (CDFA) has responsibilities in regulating pesticide registration and use in the State, but the State Department of Health Services (CDHS) is charged with the responsibility for public health protection relating to pesticide use. For years, we at the CDHS have been evaluating toxicological data for pesticides registered and used or proposed for use in the State, performing risk assessments for pesticide residues found in dietary ’ To whom correspondence should be addressed. 158 0273-2300/89$3.00 Copyright 0 1989 by Academic Press, Inc. All rights of repmduction in any form reserved.

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AND

FOOD

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SAFETY

items, and recently, assessing the adequacy of pesticide tolerances for processed foods as required by legislative mandate. The NRC report confirms our concern and the need to examine issues pertinent to pesticide and food safety. This report reviews and discusses recent developments regarding the environmental, toxicological, and regulatory issues surrounding pesticide residues in food. ENVIRONMENTAL

CONTAMINATION

BY PESTICIDES

Pesticide contamination is a unique toxicologic concern because pesticides are inherently biologically active substances deliberately introduced into the environment, as opposed to some other environmental contaminants that are introduced unintentionally. Pesticide use may result in undesirable residues in various media such as food, drinking water, and air. Not all the pesticides in use have adequate health information or a permissible limit established for different media. The problem is complicated when the pesticide involved ( 1) may have toxic properties for which sufficient quantitative information is not available, (2) may be detected but it has been previously generally assumed that it was volatile or would degrade and would leave no detectable residues, (3) may be detected but for which a permissible limit does not exist, (4) may be present at higher than the permissible level, or (5) may be associated with a combination of two or more of the above conditions. The organophosphates and carbamates are cholinesterase inhibitors whose primary health concern is related to acute exposure, which can lead to vomiting, diarrhea, lacrimation, bradycardia, blurred vision, and muscular involvements. Some organophosphates can cause neurotoxicity, leading to protracted peripheral neuropathy. In recent years, some have been suspected of being mutagenic and/or carcinogenic. The concern regarding organochlorines is associated with long-term exposure because of their persistence in the environment, storage in body fat, and carcinogenicity in test animals. Many of these compounds are strong inducers of microsomal enzymes and can interfere with metabolism of chemicals. They can also affect the nervous system at high doses producing such symptoms as paresthesia, irritability, dizziness, tremors, and convulsions. Controversial issues of potential teratogenicity and carcinogenicity revolve around the chlorophenoxy herbicides. Other herbicides and fungicides include the nitrophenolic and nitrocresolic compounds which owe their toxicity to an uncoupling of oxidative phosphorylation. The dithiocarbamates and thiocarbamates include many herbicides and fungicides. Fumigants cause central nervous system depression and some are carcinogenic in test animals and can produce adverse reproductive effects. PESTICIDE

RESIDUES

IN FOOD

Sources A pesticide in or on food becomes an environmental contaminant when it is present in food for which the application or use of the substance has not been approved, or when the residue in food is at a level higher than that permitted for human consumption. Livestock, poultry, and fish can be contaminated when their feed contain an excessive amount of pesticide residue as a result of application or manufacturing

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of pesticides occurring in the vicinity, or when residues are transported through the environment or accidentally mixed into feed. Undesirable residues may remain in or on agricultural products due to plant uptake, slow degradation, low volatility, wind drift from nearby fields, or illegal or excessive applications of pesticides. Improperly fumigated or cleaned railroad cars, trucks, ships, or storage buildings used for transport and storage of human food and animal feed are also sources of contamination (OTA, 1979).

Factors Afecting Regulatory Limits The seriousness of the occurrence of a pesticide contaminant in food is affected by several factors which are considered in establishing regulatory limits for pesticides in food. These include toxicity, residue level, food consumption rate, individual physiological vulnerability, and environmental persistence and alteration. Toxicity. The adverse health effects that may result from exposure to a pesticide contaminant in food depend on the inherent toxic properties of the chemical (i.e., ability to do harm), the severity of the effects (e.g., reversible vs irreversible effects), and the potency of the chemical (i.e., incremental dose leading to a relative increase in a toxic response). Residue level. The dose received by an individual who consumes pesticide contaminated food is a function of the residue level and the amount of food consumed. Residue levels are monitored in processed and unprocessed foods by both state and federal agencies. Such monitoring is used to enforce legal tolerance limits (CFR, 1983) or to provide a screening system for early warning by the agencies. They are also used to monitor the diet of infants, toddlers, and adults, as in the total diet study conducted by the Food and Drug Administration (FDA), in which market baskets containing items comprising the diet of the different age groups are collected and analyzed for residues of pesticides and other chemicals (Pennington, 1983; Podrebarac, 1984). Food consumption rate. The consumption rate of any single food item can vary with consumer age and geographical location, and among individuals of a given pop ulation. Several dietary or food consumption surveys have been conducted in the United States such as the Nationwide Food Consumption Survey of the U.S. Department of Agriculture (USDA) and the Health and Nutrition Examination Survey (HANES) of the National Center for Health Statistics (NCHS), providing in various reports and on data tapes information on the amount of intake of various food types by family, age, sex, and geographic location. The EPA used to apply food factors developed for the estimation of dietary intake of individual food items as portion of the total diet, but has adopted the more recent USDA consumption data in performing its exposure analyses in developing its Tolerance Assessment System (TAS) relating to pesticide residues in food (EPA, 1986). Physiological vulnerability of individual. Certain subgroups ofthe population, such as young children, pregnant women, the sick, and the elderly, are generally considered to be more sensitive to the toxic effects of chemicals, including pesticides. Genetic factors such as enzyme deficiencies that result in decreased capability of an individual to metabolize or detoxify a chemical may also affect the individual’s vulnerability. Environmental persistence.Pesticides such as some of the organochlorines (e.g., DDT) are persistent in the environment and thus create a concern for low-level, long-

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161

term exposure. The insecticide parathion is relatively nonpersistent primarily because it is chemically unstable, especially in aqueous solutions. Environmental alteration. The disappearance of pesticide residues in their original form at a given location may mean actual degradation of the hazardous chemical, translocation for bioconcentration into some ecosystem, or conversion into more dangerous chemicals. Residues in food are mostly in the form of environmentally altered chemicals. For example, DDE, dieldrin, and heptachlor expoxide are derived from the original insecticides DDT, aldrin, and heptachlor in the environment. PESTICIDE

MONITORING

OF FOOD

Food monitoring protects consumers by triggering seizures of contaminated food, determining short-term and long-term trends in pesticide residue levels in food, and identifying illegal pesticide applications. Table 1 shows the pesticides monitored by different regulatory agencies. At the federal level, the FDA analyzes samples of animal feeds, fruits, vegetables, grain, eggs, milk, processed dairy products, and seafood. The USDA analyzes meat and poultry products. At the state level, in California, the CDFA monitors unprocessed food crops for pesticides. The Food and Drug Laboratory of the CDHS routinely screens for 67 pesticides in processed foods collected by the Food and Drug Branch (FDB) through monitoring and other inspection activities. These included 33 chlorinated hydrocarbons, 29 organophosphates, and 5 carbamates. Current monitoring is designed to attempt to keep pesticide residues in food from exceeding prescribed limits, called tolerances or action levels. Little effort is made to detect and identify substances in the food supply for which no prescribed limits exist. The EPA uses the Special Review procedure (formerly referred to as Rebuttable Presumption against Registration, or RPAR) to evaluate unsafe pesticide residue levels in food with or without existing tolerance levels. The FDB of CDHS collects and analyzes samples of food for pesticide residues when there is any suggestion or reason to believe that the food may be contaminated. Public and governmental concern has been expressed over the adequacy of the residue monitoring programs. The National Resources Defense Council (NRDC), a public-interest environmental group, conducted a survey of fresh produce sold in San Francisco markets for pesticide residues and found 44% of 71 fruit and vegetable samples contained 19 different pesticides (Mott and Broad, 1984). Forty-two percent of the produce with detectable pesticide residues contained residues of more than one pesticide. The majority of the pesticides detected were found at concentrations below the EPA tolerances. The NRDC also pointed out weaknesses in the availability of health effects data, monitoring activities, analytical methods, and enforcement efforts. In a review of FDA’s activities to protect the public from exposure to illegal pesticide residues in the domestic food supply, the U.S. General Accounting Office (GAO, 1986a) found that FDA’s monitoring program spot-checks a very small amount (probably less than 1%) of the domestic food supply, that it does not regularly test for a number of pesticides that can be used or may be present in food, and that it does not prevent the marketing of most food that it finds to contain illegal residues. Another NRDC review of data on FDA’s import monitoring program reported that imported foods had twice as many food quality violations as did domestically grown items and only a small fraction of the total imported food shipments were inspected

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TABLE 1 PESTICIDESUNDERREGULATORYSCRUTINYAND/ORFOUNDINCONSUMERSURVEY

Pesticides Acephate (Orthene) Acifluorten Alachlor (Lasso) Aldicarb (Temik) Aldrin Ametryn Amitraz (Baam) Anilazine (Dyrene) Arsenic acid Asulam Atrazine (AAtrex) Azinphos-ethyl (Ethyl Guthion) Azinphos-methyl (Guthion) Benomyl (Benlate) Benefin (Balan) Bensulide (Betasan) BHC (Benzahex) Bifenox (Modown) Biphenyl Bromoxynil (ester form only) Bromoxynil octanoatc Bromopropylate (Acarol) Bromacil Calcium arsenate Captafol (Difolatan) Captan Carbaryl (Sevin) Carbofuran (Furadan) Carbophenothion (Trithion) Chinomethionat (Morestan) Chlorbenside Chlordane Chlorfenvinphos (Supona) Chlordimeform Chlorobenzilate (Acaraben) Chloroneb Chlorothalonil (Bravo) Chloroxuron (Tenoran) Chlorpyrifos (Dursban) Chlorthiophos CIPC Copper arsenate

EPA” oncogenic pesticides

FDAb residue screen

X X X

X

X X

CDFAC residue screen

CDHSd residue screen

Found in San Francisco produce survey’

CDHS tolerances evaluations

X X X X

X X X

X

X

X

X X

X X X X

X X X X

X X X

X

X

X

X

X X

X

X X X X X X X X X

X X X

X X X X

X X X

X

X

X

X X X X

X X X

X

X X X X X

X

X X

X X X

X X X

X X

X X

X

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AND FOOD SAFETY

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TABLE t-Continued

Pesticides. Coumaphos (Co-Ral) Crotoxyphos (Ciodrin) Cyanazine (Bladex) Cyhexatin Cypermethrin (Ammo, Cymbush) Cyromazine (Larvadex) 2,4-D (Isopropyl ester) DCNA (Botran) DCPA (Da&al) Diallate DDT (DDE, DDD) DEF Demeton (Systox) DemetonSsulfone Dialifor (Torak) Diazinon Dichlobenil (Casoron) Dichlorvos (DDVP) Dichlone Dicloran (DCNA, Botran) Diclofop methyl (Hoelon) Dicofol (Kelthane) Dicrotophos (Bidrin) Dieldrin Dimethoate (Cygon) Dioxathion (Delnav) Diphenamid Disulfoton (Di-Syston) Endosulfan (Thiodan) Endrin EPN Ethalfluralin (Sonalan) Ethoprop (Mocap) Ethion Ethylan (Perthane) Ethylene oxide ETU (Ethylene thiourea) Fenamiphos (Nemacur) Fenitrothion (Sumithion) Fensulfothion (Dasanit) Fenthion (Baytex) Fenvalerate (Pydrin) Fluchlorahn (Basalin) Folpet Fonophos (Dyfonate) Fosetyl Al (Aliette) Glyphosate (Roundup) Heptachlor (and heptachlor epoxide)

EPA‘= oncogenic pesticides

FDAb residue screen

CDFA’ residue screen

CDHSd residue screen

Found in San Francisco produce survey e

X X X

CDHS tolerances evaluation/

X X

X X X

X

X

X

X

XX

X X

X X X

X X

X

X X X

X X

X X

X X

X X X X X

X

X

X X X

X X8

X X X X X

X X X X X

X X X

X X X

X

X X X

X

X X X X

X X X X X X X X

X Xg

X X

X X

X X X X X X

X X X

X X X

X X X X

X

X X

X

X

X X

X

X

164

FAN AND JACKSON TABLE 1-Continued

Pesticides Iprodione (Rovral) Isofenphos (Oftanol) Leptophos (Phosvel) Lead arsenate Lindane Linuron Malathion Maleic hydrazide Mancozeb (Dithane M-45) Maneb Mephosfolan (Cytrolane) Merphos (Folex) Methamidophos (Monitor) Methaneamonic Acid Methidathion (Supracide) Methiocarb (Mesurol) Methomyl (Lannate) Methoxychlor Methyl parathion Methyl trithion Metiram Metolachlor (Dual) Metribuzin (Sencor) Mevinphos (Phosdtin) Mirex Monocrotophos (Azodrin) Naled (Dibrom) Nitrofen (TOK) Oryzalin (Surtlan) Ovex (Chlorfenson) Oxadiazon (Ronstar) Oxyfluorfen (Goal) Oxydemeton-methyl (Meta-systox-R) Parathion Paraquat (Gramoxone) Pendimethalin (Prowl) Pentachloronitrobenzene (Quintozene, PCNB) Permethrin Phenthoate 0-Phenylphenol Phorate (Thimet) Phosalone (Zolone) Phosmet (Imidan) Phosphamidon (Dimecron) Phoxim Polychorinated biphenyls (PCBs, Alachlors) Profenofos (Curacron)

EPA” oncogenic pesticides

FDAb residue screen

CDFA’ residue screen

CDHSd residue screen

Found in San Francisco produce surveye

CDHS tolerances evaluation’

X

X

X X X X X X

X X X

X X X

X X

X X X X X

X

X X X

X X X

X X X X X

X

X X X X X X X X

X X

X

X X

X

X

X

X X X X

X

X X

X X

X

X

X

X X X

X X X X X X X X X

X

X

X X X

X X X

X

X

X

X

X X

PESTICIDES TABLE

Pesticides Profluralin (Tolban) Prometryn Pronamide (Kerb) Propanil (Stam) Propargite (Omite) Propetamphos (Safrotin) Propham Propoxur (Baygon) Pyrazophos Ronnel Simazine Sonalan (Ethalfluralin) Sodium arsenate Sodium arsenite Sulfallate (Vegadex) Sulfur Sulprofos (Bolstar) Terbacil (Sinbar) Terbutryn Tetrachlovinphos (Gardona) Tetradifon (Tedion) Thiabendazole Thiobencarb (Bolero) Thiodicarb (La&n) Thionazin (Zinophos) Thiophanate-methyl Toxaphene (Attac) Triadimefon (Bayleton) Triazophos (Hostathion) Trichlorfon (Dylox) Trifluralin (Treflan) Vinclozolin (Ronilan) Zineb

165

AND FOOD SAFETY I-Continued

EPA” oncogenic pesticides

FDAb residue screen

X

X X

CDFA” residue screen

CDHSd residue screen

Found in San Francisco produce survey e

CDHS tolerances evaluation/

X X X

X

X X X X X X X

X X

X X

X X X X X

X

X X X X

X X X

X X

X X

X X X X

X

X

X

X X

X

X X

X

X

X X X X

X

X

a Environmental Protection Agency (NRC, 1987). b Food and Drug Administration (Luke et al., 1975, 1981; FDA Pesticides Analytical Manual (PAM)1,232.4). PAM- 1,232.4 contains >2OO pesticides, includingthose (> 100) that can be recovered by the Luke ef al. procedures. A total of about 600 pesticides are monitored by the FDA, some upon special requests. ’ California Department of Food and Agriculture (CDFA, 1987). Additional ones are monitored upon special requests. d California Department of Health Services. Additional ones are monitored upon special requests. e Mott and Broad ( 1984). ‘California Department of Health Services (Fan et al., 1987a). Possible 309 candidates. g Found in one commodity for which no tolerance exists although tolerances are established for other commodities.

for pesticide contamination (Hearne, 1984). The GAO and NRDC reports point to the need for improvements in analytical techniques and enforcement procedures in governmental residue monitoring programs in order to prevent consumer exposure

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to unsafe levels of pesticide residues in food. Currently, federal legislation introduced to strengthen the efficacy of the FDA’s program. LAWS

AND

is being

REGULATIONS

The Federal Food, Drug, and CosmeticsAct The Federal Food, Drug, and Cosmetic Act (FDC Act) prohibits the introduction of adulterated food into interstate commerce (NRC, 1987). The FDC Act allows the FDA to establish tolerances for toxic substances where occurrence in food cannot be avoided. Section 408 of the FDC Act explicitly recognizes that pesticides confer benefits and risks and that both should be taken into account in setting new commodity tolerances. Section 409 governs pesticide residues that concentrate in processed food above the level authorized to be present in or on their parent raw commodities. Such residues must be proven safe, defined as a reasonable certainty that no harm to consumers will result when the additive is put to its intended use. It does not authorize the consideration of benefits, and it contains the Delaney Clause which prohibits the approval of a food additive that has been found to induce cancer in humans or when fed to animals. Section 409 of the FDC Act provides the FDA the general authority to regulate the addition of substances to food (NRC, 1987). Pesticides in processed foods remain food additives, defined as “any substance the intended use of which results or may reasonably be expected to result . . . in its becoming a component of food,” and are subject to the premarket approval requirement of Section 409. Although FDA has primary responsibility for implementing Section 409, the EPA has been delegated responsibility for pesticides that are food additives. When Section 409 was adopted, residues that are present in a processed food at levels no higher than sanctioned on the raw agricultural commodity were exempted from food additive regulation. Such residues remain subject to the risk-benefit standard of Section 408 and elude the Delaney Clause. This inconsistency applied to raw and processed foods has created confusions.

Tolerance Levels and Action Levels The establishment of tolerance levels is a regulatory procedure employed to control pesticide contamination in food. A formal tolerance is the legal limit specifying the amount of a pesticide residue that can be present in or on food sold in interstate commerce. An action level is an administrative guideline about the level of a contaminant in food to which consumers may safely be exposed and is used for enforcement purposes. The setting of a tolerance level also considers economics and feasibility, and the procedure of establishing a tolerance is a lengthy one. The action level is determined for use often, but not always, as an interim guidance level before there is sufficient time or data to permit establishment of a formal tolerance. An action level is revoked when a regulation establishes a tolerance for the same substance and use. The EPA establishes tolerance levels for pesticides in raw or unprocessed foods (CFR, 1983). The FDA adopts the EPA tolerance levels for unprocessed foods for use on both processed and unprocessed foods. When an EPA tolerance level for a food

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TABLE 2 KEY DATA ELEMENTS

FOR TOLERANCE

PETITIONS

1. 2. 3. 4.

Chemistry of the pesticide Expected quantity of residues present in food based on field trials Laboratory analytical procedures used for obtaining residue data Residues in animal feed derived from crop by-products or from forages and resulting residues, if any, in meat, milk, poultry, fish, and eggs 5. Toxicity data on parent compound and any major impurities, degradation products, or metabolites

item is nonexistent, then the FDA tolerance level for that pesticide in the specific food item is zero, unless FDA has established an action level as a permissible limit. The data requirements for tolerance petitions (Table 2) are similar to those needed to support registration under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) (FR, 1984). One of the most difficult technical challenges is the gathering and interpretation of residue chemistry data, which generally require extrapolation from data on a limited number of field trials. The tolerance level or action level for a pesticide in or on a food item is generally set by the establishing an acceptable daily intake (ADI), based on the identification of a no-observed-effect level (NOEL) for the adverse health effect of concern derived from animal or human toxicological data, and application of an uncertainty factor (Fig. 1). It takes into consideration the consumption rate of the food and other foods which have a tolerance level for the same chemical. The factors involved may vary depending upon the availability and quality of the needed information. When a pesticide tolerance is set for a crop, the entire crop is not necessarily treated with that pesticide and cannot be presumed to carry a residue. However, the theoretical maximum residue contribution (TMRC) from all crops should not exceed the AD1 (currently referred to as the risk reference dose [RrD] by EPA in some cases) in order for the tolerances to be health protective. FOOD

CONTAMINATION

INCIDENTS

In 1986,0.48% of 460 1 commodity samples in California had residues exceeding the tolerance levels, 12.8% of the samples contained residues within tolerance levels, 1.43% had residues of pesticides for which tolerance was not established, and 85.29% had no residue detected (CDFA, 1986). FDA monitoring between 1979 and 1985 found that 2.9% of 67,500 samples contained illegal residues. During the same period, the FDA found 6.1% of 33,690 imported food samples to contain illegal residues. Often, such food contamination has both health and economic impacts.

Specific Pesticide-RelatedIncidents of Concern Several incidents of particular concern in relation to the presence of pesticides in food occurring in or affecting California within the last few years include the following (Table 3):

(1) Ethylene dibromide (EDB) in grain and bakery products, 1984. EDB is a fumigant for preemergence

use and grain storage. It was originally

thought to be suffi-

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FAN AND JACKSON Toxicology/pharmacology Data evaluation

(FIFRA data requirement)

Identification of endpoint of concern NOEULOEL

I

t

Safety factor (dependent on quality of data)

ADI (or risk reference dose) + t

Food consumption rate Sources of exposure

Permissible level in food / \ c- Economics \ , t- Technical feasibility 1’ Action level Tolerance level (Legal authority) (Interim guideline) / \ \ 1’ \ Processed Raw

1. Governed by FDC Act, Section 408 2. Tolerances based on field trials designed to achieve the highest residue levels likely under normal agricultural practice, before leaving farm gate 3. Risk-benefit standard

1. Governed by FDC Act, Section 409 2. Concentration after processing necessitates Section 409 tolerances and potentially triggers application of Delaney Clause 3. Risk-based general safety standard, reinforced by Delaney Clause

FIG. 1. Procedures for developing pesticide tolerances/action levels in or on foods. FIFRA = Federal Insecticide, Fungicide, and Rodenticide Act; NOEL/LOEL = no-observed-effect level/lowest-observedeffect level; AD1 = acceptable daily intake; FDC Act = Food, Drug, and Cosmetic Act.

ciently volatile that it would not leave a residue, and, therefore, a tolerance level was not established. EDB produces carcinogenic and adverse reproductive effects in laboratory animals. After being found nationwide in grain and bakery products at levels leading to estimated high cancer risks for consumers, it was banned for use with a phase-out period of 2 to 3 years. During the phase-out period, the EPA set tolerances of 30- 150 ppb for different types of food items. These were adopted by California with the exception that the State set a zero tolerance level for EDB in baby foods. (2) Aldicarb in watermelon, 1985. Aldicarb is an extremely toxic systemic carbamate pesticide. Its illegal use on watermelon led to the largest reported North American epidemic of food-borne pesticide poisoning (MMWR, 1986). Active surveillance ascertained reports of 638 probable cases and 344 possible cases. Another 333 probable and 149 possible cases were reported from other western states and provinces of Canada. Illness ranged from mild gastrointestinal upset to severe cholinergic poisoning. Levels in the melons that caused illness ranged from 0.07 to 3 ppm of aldicarb sulfoxide. The epidemic ceased after melons in distribution chains were destroyed, an embargo was imposed, and an inspection program was instituted.

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AND FOOD SAFETY TABLE 3

SOME RECENT

INCIDENTS OF CONCERN RELATING TO PESTICIDES IN OR AFFECTING CALIFORNIA, 19842~~s~~~

Pesticide Ethylene dibromide Aldicarb DDT” Daminozide” Demeton-methyl S,S,STributylphosphorotrithioateD

IN FOOD

Food Grain, bakery products Watermelon Fish Apples, processed apple products, other Wine Chili peppers, other

’ Ongoing investigation.

(3) Demeton-methyl in wine, 1985. Demeton-methyl is an organophosphate pesticide. It has a tolerance level established for grapes but not for wine. No action level has been set. It was found in some wines from a single producer apparently as a result of early harvest of the grapes. The levels found were evaluated not to be harmful to the wine consumer. The evaluation of the incident led to the identification of the need for more information on multiple sources of exposure, and for reevaluation of the acceptable daily intake for the chemical. (4) DDT in fish, 1985. The findings on DDT in ocean fish in Southern California are an example of the long-term implications of using persistent pesticides. For several years, a local DDT manufacturer had used the sanitary sewer for discharge of some of its industrial waste which contained DDT. A few million pounds of DDT were deposited on the ocean bottom around the sewage outfall. This waste discharge was halted many years ago but recent analyses of fish from this area have shown elevated levels of DDT (to over 1 ppm) in the edible flesh. In addition, some DDT was also dumped into the ocean by use of ocean dumping barges but the exact location is not known. Evidence indicates that the DDT levels are decreasing over time, but the levels found raise a health concern because DDT is considered a potential human carcinogen. The FDA action level of 5 ppm for DDT in fish was set long ago and did not consider the carcinogenic risk associated with DDT exposure. A study by the California Department of Health Services has been initiated to study marine pollution in the area. (5) S,S,S-Tributylphosphorotrithioate in chili peppers, 1986. SXS-Tributylphosphorotrithioate (DEF), an organophosphate registered for use only on cotton, has been found on chili peppers and other food crops. No action level has been established for DEF. The major health concern with DEF is neurotoxicity. It also has extensive toxicological data gaps precluding any adequate evaluation. The investigation is still ongoing. (6) Daminozide (Alar) in apples and processed apple products, 198%present. Daminozide is a systemic plant-growth regulator, used extensively on apples to regulate ripening, increase firmness, and impart a more red color. It is used to a lesser degree on other fruits and vegetables such as peanuts, cherries, peaches, pears, plums, tomatoes, brussels sprouts, and cantaloupes. Daminozide penetrates crops and cannot be removed by washing. Experimental data in the 1970s suggested that daminozide and its hydrolysis product, unsymmetric dimethylhydrazine (UDMH), are car-

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FAN AND JACKSON TABLE 4

1. 2. 3. 4. 5. 6.

Acute oral, dermal, and inhalation studies Chronic feeding studies on rodents and nonrodents Oncogenicity studies on mice and rats Two-generation reproduction study Temtogenicity studies on rats and rabbits Mutagenicity studies (gene mutation, structural chromosome aberration, other studies of effectson genetic material) 7. Delayed neurotoxicity studies on chickens (for cholinesterase inhibitors) 8. Plant and animal metabolism studies

cinogens in animals but the studies were subsequently identified to have serious flaws. Populations of concern are infants and young children who consume a high proportionate intake of apples and processed apple products such as apple sauce and juice, because processing concentrates UDMH. New carcinogenicity studies have been initiated by the manufacturer as requested by EPA. EPA is reviewing the data prior to a decision on the registration status of the pesticide and has meanwhile lowered the tolerance level on apples and processed apple products, while revoking the tolerances for some other commodities (Fan et al., 1987b). TOXICOLOGICAL

CONSIDERATIONS

A critical factor in the development of pesticide tolerances in food and the evaluation of such tolerances is the availability of adequate toxicological data on the particular pesticide involved. The data requirements are governed by FIFRA (Table 4). Unfortunately, few pesticides have the complete data as required under the act. Many pesticide tolerances were established a long time ago based on old or inadequate data, or data from tests that do not meet current standards. The U.S. GAO (1986b) reported that at the current pace, EPA’s reassessment and reregistration efforts would extend into the 21st century due to the magnitude and complexity of the tasks involved. Preliminary assessments of 124 of 600 active ingredients resulted in requirement of numerous studies by EPA from pesticide firms and imposed some restrictions on about 60% of the active ingredients. In the light of the deficiencies in the toxicological data bases, recent law (Senate Bill 950, Birth Defects Prevention Act) in California requires the identification and filling of data gaps for pesticides registered in the state. A data call-in program has been initiated. This should expedite the development of toxicological data needed for the evaluation of the pesticides found in our food supply. The EPA has also initiated programs to expand the data base on the toxicological properties of pesticides and the tendency of individual pesticides to concentrate in processed foods. When tested in accordance with current standards, many older pesticides are likely to be identified as oncogenic or potentially oncogenic, inviting regulatory action, and can become subject to the Delaney Clause if they concentrate in processed food. Concern for the safety of the food supply is reflected in the recent NRC report Regulating Pesticide Residues in Food (1987). Commissioned by EPA, NRC esti-

PESTICIDES

171

AND FOOD SAFETY TABLE 5

PESTICIDES IDENTIFIED

AS POTENTIALLY

ONC~GENIC

Active ingredient (common/trade Acephate” (Orthene) Acifluorfen (Blazer) Alachlor’ (Lasso) Amitraz (Baam) Arsenic acid Asulam Azinphos-methyl” (Guthion) Benomyl” (Benlate) Calcium arsenate Captafol” (Difolatan) Captan” Chlordimeform” (Galecron) Chlorobenzilate Chlorothalonil” (Bravo)

Copper arsenate Cypermethrin” (Ammo, Cymbush) Cyromazine” (Larvadex) Daminozide (Alar) Diallate Diclofop methyl” (Hoelon) Dicofol (Kelthane) Ethalfluralin” (Sonalan) Ethylene oxide Folpet” Fosetyl Al” (Aliette) Glyphosate’ (Roundup)

BY EPA

name)

Lead arsenate Lindane Linuron” (Lorox) Maleic hydrazide Mancozeb“ Maneb” Methanearsonic acid Methomyl (Lannate) Metiram” Metolachlor” (Dual) O-Phenylphenol” Oryzalin” (Surflan) Oxadiazon” (Ronstar) Paraquat (Gramoxone) Parathion” PCNB

Permethrin” (Ambush, Pounce) Pronamide” (Kerb) Sodium arsenate Sodium arsenite Terbutryn” Tetrachlorvinphos Thiodicarb (Larvin) Thiophanate-methyl Toxaphene Trifluralin (Treflan) Zineb”

a Compounds for which risk estimates were performed by NRC (1987).

mated the potential dietary oncogenic risks associated with 28 pesticides selected from 53 determined or suspected by the EPA to be oncogenic (Table 5). Nearly 80% of the estimated risks (from all 178 food uses of the 28 compounds that comprise the committee’s risk estimates) is attributable to residues of 10 pesticides on only 15 different foods (Table 6). The methods used in the estimation involved many scientific and technical uncertainties. Assumptions are made using a conservative approach which minimizes the chance of underestimating risks. In particular, the risk estimate for each pesticide was based on the worst-case assumptions that all the food crops contained the pesticide at the tolerance level, and that all food crops are treated with the pesticide. Actual residue data are likely to show that the risks are lower than those estimated. Therefore, these risk estimates should not be construed as true consumer risks, but they provide an index of priorities by ranking pesticides for regulatory attentions. The aim of examining health risks associated with pesticides in food is to provide a safe food supply but at the same time not to deprive the public of an adequate and wholesome food supply. Amidst all the issues considered by the regulating agencies is the need to evaluate the risk and benefits associated with pesticide uses. At the present time rules and standards applied to raw foods are different from those used for processed foods, a situation that leads to illogical results. Based on the report of the NRC, the analyses of alternate ways to regulate residues of oncogenic pesticides in food suggest that when raw and processed foods are subject to a consistent risk standard ( 1Oe6), the greatest progress toward risk reduction could be attained. When compared to the old method, a consistently applied negligible risk standard for each crop, combined with the processed forms, with no consideration of benefits, could eliminate most existing dietary oncogenic risk while allowing continued use of-and benefits from-certain low-risk compounds. This approach would provide an en-

172

FAN AND JACKSON TABLE 6 MAJOR

F%TICIDES AND FOODS CONTRIBUTING ESTIMATED DIETARY ONC~GENIC

Pesticides Herbicide Linuron” Insecticide Permethrin” Chlordimeform b Fungicide Zineb b Captatol b Captan b Maneb’ Mancozeb b Folpet b ChlorothalonilC Metiram b Benomyl” 0-Phenylphenol’

TO THE NRC RISKS

( 1987)

Foods Tomatoes Beef Potatoes Oranges Lettuce Apples Peaches Pork Wheat Soybeans Beans carrots Chicken Corn (bran, grain) Grapes

a EPA group C carcinogen (limited evidence of carcinogenicity in the absence of human data). b EPA group B2 carcinogen (sufficient evidence of carcinogenicity from animal studies, with inadequate or no epidemiologic data). ’ Has not been classified by EPA.

forcement tool for regulatory purposes. The risk, however, would be proportional the number of tolerances granted for crops. MANAGING

FOOD CONTAMINATION BY PESTICIDES RECENT DEVELOPMENTS

to

AND

The management of food contamination situations is affected by the complexity of the food system, the rapidity with which food is moved through the system, the time involved in the generation and dissemination of scientific information on the toxicological and chemical properties of the pesticide, the amount and type of food involved, and the contaminant level. Determinations have to be made regarding the immediate and long-term health hazards posed by the presence of the residues in food, be it raw agricultural commodities or processed foods. Decisions have to be made about whether or not an embargo or recall is necessary to prevent consumer exposure, or to permit further distribution. The situation is complicated by the number of agencies that may be involved-the EPA, FDA, and USDA at the federal level and departments of health and of agriculture at the state level. The CDHS is expanding its activities in assessing tolerance levels for pesticides in food. New bills are being introduced to examine imported foods. Recent legislation (Assembly Bill 2848, State Department of Health Services: pesticides) mandates the CDHS to evaluate the adequacy of tolerances for public health protection (Fan et al., 1987a) and over 300

PESTICIDES

AND FOOD SAFETY

173

pesticides have been identified as potential candidates for evaluation. Chemicals undergoing evaluation are shown in Table 1. The implications on pesticides in food resulting from the passage of the Safe Drinking Water and Toxic Enforcement Act of 1986 (Proposition 65) are yet to be determined. Another emerging issue is the pesticide contamination of sport fish and game animals. The Hazard Evaluation Section of CDHS which evaluates pesticide residues in raw agricultural crops and processed foods also conducts risk assessments of pesticide residues in fish and game. The section evaluates the public health implications of findings and issues health advisories when the data warrant public warnings (Fan et al., 1988). A new law (Assembly Bill 3505, Regulations) requires that such advisories issued by the CDHS be published in the Department of Fish and Game’s Sport Fishing Regulations. SUMMARY

AND

DISCUSSION

The NRC study examines the EPA’s tolerance establishment process, provides an index of priorities by ranking pesticides for regulatory attention, and discusses alternatives to control and eliminate most dietary oncogenic risks from pesticides. The calculated oncogenic risks should not be interpreted to represent actual consumer risks from certain pesticides on food crops, but the findings support our concern in the existing inconsistencies in regulating oncogenic pesticides in raw and processed foods and in the potential oncogenic risks presented by some pesticides. Already initiated, tighter regulatory activities at both the federal and the state levels are expected to improve scientific information development, regulatory decisions, and public health protection. The increasing concern regarding chemical contamination of food has led to California laws which mandate the identification of toxicological data gaps for pesticides, evaluation of pesticide tolerances for processed foods, and study of fish contamination. These are just the first steps of a long procedure needed to ensure fully the safety of our food supply. The recently developed Tolerance Assessment System at EPA is a forward step in improving the quality of the pesticide tolerance establishment process. A large but indefinite number of environmental contaminants still have no health-based acceptable levels in food items. When these contaminants are found in food, including pesticides for which no tolerances have been established or for which the tolerances or action levels are outdated, the Hazard Evaluation Section of the California Department of Health Services is responsible for establishing interim permissible levels. Enforcement activities are carried out by the Food and Drug Branch, interacting with the Department of Food and Agriculture on related issues, when agricultural commodities and processed foods are involved. Upcoming issues that will require close attention would be residues in processed food and pesticide intake in the young (infant and children) population- Government and industry officials and interested parties should be informed of the pesticide-related activities at both the state and the federal levels to ensure adequate safety standards in food, and local health officials should be particularly aware of the existing state reporting system for pesticide-associated illness. REFERENCES California Department of Food and Agriculture (CDFA) ( 1986). I986 Summary Residue Result Report by Origin. CDFA, Sacramento, CA.

174

FAN AND JACKSON

California Department of Food and Agriculture (CDFA) (1987). Multi-residue pesticide screens. CDFA, Division of Inspection Services, Chemical Laboratory Services Branch, Pesticide Residue Program, Sacramento, CA. Code of Federal Regulations (CFR) (1983). CFR Title 40. Environmental Protection Agency (EPA) ( 1986). Tolerance Assessment System. Hazard Evaluation Division, Toxicology Branch, EPA, Washington, DC. FAN, A. M., BANKOWSICA, Y., KNAAK, J. B., STRATTON, J. W., AND JACKSON, R. J. (1987a). Assessment of pesticide tolerances for processed foods for public health protection. Amer. CON. Toxicol. 6,560. FAN, A. M., JACKSON, R. J., AND AMES, R. A. (1987b). Daminozide: Toxicology, public health and food safety.Amer. CON. Toxicol. 6,557. FAN, A. M., POLLOCK, J. A., AND JACKSON, R. J. (I 988). A California program for evaluation of chemical contamination of fish. “1988 Annual Meeting of the Society of Toxicology, Dallas, Texas, February 1619, 1988.” Federal Register (FR) (1984). Data Requirements for Pesticide Registration. Fed. Regist. 49, 42,85642,905. General Accounting Office (GAO, 1986a). Pesticides. Need to Enhance FDA’s Ability to Protect the Public from IilegaI Residues. U.S. GAO, Report to Congressional Requesters, Washington, DC. General Accounting Office (GAO) ( 1986b). Pesticides. EPA ‘s Formidable Task to Assess and Regulate Their Risks. U.S. GAO, Report to Congressional Requesters, Washington, DC. HEARNE, S. A. (1984). Harvest of Unknowns. Pesticide Contamination in Imported Foods. National Resources Defense Council, Inc., New York. LUKE, M. A., FROBERG, J. E., DOOSE, G. M., AND MASUMOTO, H. T. (198 1). Improved multiresidue gas chromatographic determination of organophosphorous, organonitrogen, and organohalogen pesticides in produce, using flame photometric and electrolytic conductivity detectors. J. Assoc. Ofl Anal. Chem. 64,1187-1195. LUKE, M. A., FROBERG, J. E., AND MASUMOTO, H. T. (1975). Extraction and cleanup of organochlorine, organophosphate, organonitrogen, and hydrocarbon pesticides in produce for determination by gasliquid chromatography. .I Assoc. OjZ Anal. Chem. 58, 1020-1026. Morbidity and Mortality Weekly Report (MMWR) (1986). Aldicarb Food Poisoningfrom Contaminated Melons-California, Vol. 35, p. 254. MOTT, L., AND BROAD, M. (1984). Pesticides in Food. National Resources Defense Council, Inc., San Francisco, CA. National Research Council (NRC) (1987). Regulating Pesticides in Food. The Delaney Paradox Committee on Scientific Regulatory Issues Underlying Pesticide Use Patterns and Agricultural Innovation. Board on Agricultura, National Research Council. Office of Technology Assessment (OTA) (1979). Environmental Contaminants in Food. OTA, Congress of the United States, Washington, DC. PENNINGTON, J. A. T. (1983). Revision of the total diet study. J. Amer. Diet. Assoc. 82,166-173. PODREBARAC, D. S. ( 1984). Pesticide, metal, and other chemical residues in adult total diet samples. (XIV). October 1977September 1978. J. Assoc. Ofl Anal. Chem. 67,176- 185.