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 reg-
ulatory issues surrounding pesticide residues in food. Factors affecting the establishment of regu-
latory limits are discussed. Pesticides monitored by state and federal agencies are compiled and
the need for improvements in analytical techniques and enforcement procedures in govemmen-
tal 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 Re-
search 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 responsibil-
ity 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.
 PESTICIDES AND FOOD SAFETY 159

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 in-

herently biologically active substances deliberately introduced into the environment,
as opposed to some other environmental contaminants that are introduced uninten-
tionally. 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 infor-
mation or a permissible limit established for different media. The problem is compli-
cated 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 pre-
viously 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 pri-
mary health concern is related to acute exposure, which can lead to vomiting, diar-
rhea, lacrimation, bradycardia, blurred vision, and muscular involvements. Some
organophosphates can cause neurotoxicity, leading to protracted peripheral neuropa-
thy. In recent years, some have been suspected of being mutagenic and/or carci-
nogenic.
The concern regarding organochlorines is associated with long-term exposure be-
cause of their persistence in the environment, storage in body fat, and carcinogenicity
in test animals. Many of these compounds are strong inducers of microsomal en-
zymes and can interfere with metabolism of chemicals. They can also affect the ner-
vous system at high doses producing such symptoms as paresthesia, irritability, dizzi-
ness, tremors, and convulsions.
Controversial issues of potential teratogenicity and carcinogenicity revolve around
the chlorophenoxy herbicides. Other herbicides and fungicides include the nitrophe-
nolic and nitrocresolic compounds which owe their toxicity to an uncoupling of oxi-
dative 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 pres-

ent 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 con-
sumption. Livestock, poultry, and fish can be contaminated when their feed contain
an excessive amount of pesticide residue as a result of application or manufacturing
160 FAN AND JACKSON

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 trans-
port 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 physio-
logical 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 contam-
inated 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; Podre-
barac, 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. Depart-
ment 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 perform-
ing its exposure analyses in developing its Tolerance Assessment System (TAS) relat-
ing 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 consid-
ered to be more sensitive to the toxic effects of chemicals, including pesticides. Ge-
netic 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 vul-
nerability.
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-
 PESTICIDES AND FOOD SAFETY 161

term exposure. The insecticide parathion is relatively nonpersistent primarily be-

cause 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 hydrocar-
bons, 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 Pre-
sumption 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
162 FAN AND JACKSON

TABLE 1
PESTICIDESUNDERREGULATORYSCRUTINYAND/ORFOUNDINCONSUMERSURVEY

Found in
EPA” FDAb CDFAC CDHSd San Francisco CDHS
oncogenic residue residue residue produce tolerances
Pesticides pesticides screen screen screen survey’ evaluations

Acephate (Orthene) X X X
Acifluorten X
Alachlor (Lasso) X X X
Aldicarb (Temik) X X X X
Aldrin X X X X
Ametryn X
Amitraz (Baam) X
Anilazine (Dyrene) X X
Arsenic acid X
Asulam X
Atrazine (AAtrex) X X
Azinphos-ethyl (Ethyl
Guthion) X
Azinphos-methyl
(Guthion) X X X X
Benomyl (Benlate) X
Benefin (Balan) X X
Bensulide (Betasan) X
BHC (Benzahex) X X X
Bifenox (Modown) X
Biphenyl X
Bromoxynil (ester form
only) X
Bromoxynil octanoatc X
Bromopropylate (Acarol) X
Bromacil X
Calcium arsenate X
Captafol (Difolatan) X X X X
Captan X X X X X
Carbaryl (Sevin) X X X X
Carbofuran (Furadan) X X
Carbophenothion
(Trithion) X X X
Chinomethionat
(Morestan) X X
Chlorbenside X
Chlordane X X X
Chlorfenvinphos (Supona) X X
Chlordimeform X
Chlorobenzilate
(Acaraben) X X X
Chloroneb X
Chlorothalonil (Bravo) X X X X
Chloroxuron (Tenoran) X
Chlorpyrifos (Dursban) X X X X
Chlorthiophos X
CIPC X
Copper arsenate X
 PESTICIDES AND FOOD SAFETY 163

TABLE t-Continued

Found in
EPA‘= FDAb CDFA’ CDHSd San Francisco CDHS
oncogenic residue residue residue produce tolerances
Pesticides. pesticides screen screen screen survey e evaluation/

Coumaphos (Co-Ral) X
Crotoxyphos (Ciodrin) X
Cyanazine (Bladex) X X
Cyhexatin X
Cypermethrin (Ammo,
Cymbush) X
Cyromazine (Larvadex) X
2,4-D (Isopropyl ester) X X
DCNA (Botran)
DCPA (Da&al) X X X XX
Diallate X
DDT (DDE, DDD) X X X X
DEF X X X
Demeton (Systox) X
DemetonSsulfone X
Dialifor (Torak) X X X
Diazinon X X X X
Dichlobenil (Casoron) X
Dichlorvos (DDVP) X
Dichlone X X
Dicloran (DCNA, Botran) X X X
Diclofop methyl (Hoelon) X
Dicofol (Kelthane) X X X X X
Dicrotophos (Bidrin) X X
Dieldrin X X X X
Dimethoate (Cygon) X X X X8
Dioxathion (Delnav) X X
Diphenamid X
Disulfoton (Di-Syston) X X
X X
Endosulfan (Thiodan) X X X X
Endrin X X X Xg
EPN X X X
Ethalfluralin (Sonalan) X
Ethoprop (Mocap) X X X
Ethion X X X X
Ethylan (Perthane) X X
Ethylene oxide X
ETU (Ethylene thiourea) X
Fenamiphos (Nemacur) X X
Fenitrothion (Sumithion) X
Fensulfothion (Dasanit) X X X
Fenthion (Baytex) X X X
Fenvalerate (Pydrin) X
Fluchlorahn (Basalin) X
Folpet X X X X X
Fonophos (Dyfonate) X X
Fosetyl Al (Aliette) X
Glyphosate (Roundup) X
Heptachlor (and
heptachlor epoxide) X X X
164 FAN AND JACKSON

TABLE 1-Continued

Found in
EPA” FDAb CDFA’ CDHSd San Francisco CDHS
oncogenic residue residue residue produce tolerances
Pesticides pesticides screen screen screen surveye evaluation’

Iprodione (Rovral) X
Isofenphos (Oftanol) X
Leptophos (Phosvel) X
Lead arsenate X
Lindane X X X X
Linuron X X X
Malathion X X X X X
Maleic hydrazide X
Mancozeb (Dithane M-45) X
Maneb X
Mephosfolan (Cytrolane) X
Merphos (Folex)
Methamidophos (Monitor) X X
Methaneamonic Acid X
Methidathion (Supracide) X X X
Methiocarb (Mesurol) X
Methomyl (Lannate) X X X
Methoxychlor X
Methyl parathion X X
Methyl trithion X
Metiram X
Metolachlor (Dual) X
Metribuzin (Sencor) X X
Mevinphos (Phosdtin) X X X X X
Mirex X
Monocrotophos (Azodrin) X
Naled (Dibrom) X X
Nitrofen (TOK) X X X
Oryzalin (Surtlan) X
Ovex (Chlorfenson) X
Oxadiazon (Ronstar) X X X
Oxyfluorfen (Goal) X
Oxydemeton-methyl
(Meta-systox-R) X
Parathion X X X X
Paraquat (Gramoxone) X
Pendimethalin (Prowl) X
Pentachloronitrobenzene
(Quintozene, PCNB) X X X X
Permethrin X X
Phenthoate X
0-Phenylphenol X
Phorate (Thimet) X X X
Phosalone (Zolone) X X X
Phosmet (Imidan) X X X X
Phosphamidon
(Dimecron) X X X X
Phoxim X
Polychorinated biphenyls
(PCBs, Alachlors) X
Profenofos (Curacron) X
 PESTICIDES AND FOOD SAFETY 165

TABLE I-Continued

Found in
EPA” FDAb CDFA” CDHSd San Francisco CDHS
oncogenic residue residue residue produce tolerances
Pesticides pesticides screen screen screen survey e evaluation/

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

to unsafe levels of pesticide residues in food. Currently, federal legislation is being

introduced to strengthen the efficacy of the FDA’s program.

LAWS AND 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 bene-
fits 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 con-
sumers 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 contam-
inant 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
 PESTICIDES AND FOOD SAFETY 167

TABLE 2
KEY DATA ELEMENTS FOR TOLERANCE PETITIONS

1. Chemistry of the pesticide

2. Expected quantity of residues present in food based on field trials
3. Laboratory analytical procedures used for obtaining residue data
4. 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 theoreti-
cal 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 fumi-
gant for preemergence use and grain storage. It was originally thought to be suffi-
168 FAN AND JACKSON

Toxicology/pharmacology (FIFRA data requirement)

Data evaluation

Identification of endpoint of concern

NOEULOEL

I t Safety factor (dependent on quality of data)

ADI
(or risk reference dose)
+ Food consumption rate
t Sources of exposure

Permissible level in food

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

1. Governed by FDC Act, Section 408 1. Governed by FDC Act, Section 409
2. Tolerances based on field trials designed 2. Concentration after processing necessitates
to achieve the highest residue levels Section 409 tolerances and potentially
likely under normal agricultural triggers application of Delaney Clause
practice, before leaving farm gate 3. Risk-based general safety standard,
3. Risk-benefit 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-observed-
effect 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 carba-
mate pesticide. Its illegal use on watermelon led to the largest reported North Ameri-
can epidemic of food-borne pesticide poisoning (MMWR, 1986). Active surveillance
ascertained reports of 638 probable cases and 344 possible cases. Another 333 proba-
ble and 149 possible cases were reported from other western states and provinces of
Canada. Illness ranged from mild gastrointestinal upset to severe cholinergic poison-
ing. 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.
 PESTICIDES AND FOOD SAFETY 169

TABLE 3
SOME RECENT INCIDENTS OF CONCERN RELATING TO PESTICIDES IN FOOD
IN OR AFFECTING CALIFORNIA, 19842~~s~~~

Pesticide Food

Ethylene dibromide Grain, bakery products

Aldicarb Watermelon
DDT” Fish
Daminozide” Apples, processed apple products, other
Demeton-methyl Wine
S,S,STributylphosphorotrithioateD Chili peppers, other

’ Ongoing investigation.

(3) Demeton-methyl in wine, 1985. Demeton-methyl is an organophosphate pesti-

cide. 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 sev-
eral 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 pollu-
tion in the area.
(5) S,S,S-Tributylphosphorotrithioate in chili peppers, 1986. SXS-Tributylphos-
phorotrithioate (DEF), an organophosphate registered for use only on cotton, has
been found on chili peppers and other food crops. No action level has been estab-
lished for DEF. The major health concern with DEF is neurotoxicity. It also has
extensive toxicological data gaps precluding any adequate evaluation. The investiga-
tion 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 regu-
late 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 can-
not be removed by washing. Experimental data in the 1970s suggested that daminoz-
ide and its hydrolysis product, unsymmetric dimethylhydrazine (UDMH), are car-
 170 FAN AND JACKSON

TABLE 4

1. Acute oral, dermal, and inhalation studies

2. Chronic feeding studies on rodents and nonrodents
3. Oncogenicity studies on mice and rats
4. Two-generation reproduction study
5. Temtogenicity studies on rats and rabbits
6. 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 propor-
tionate intake of apples and processed apple products such as apple sauce and juice,
because processing concentrates UDMH. New carcinogenicity studies have been ini-
tiated 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 evalua-
tion of such tolerances is the availability of adequate toxicological data on the particu-
lar pesticide involved. The data requirements are governed by FIFRA (Table 4). Un-
fortunately, 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) re-
ported 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 in-
volved. Preliminary assessments of 124 of 600 active ingredients resulted in require-
ment of numerous studies by EPA from pesticide firms and imposed some restric-
tions 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 pesti-
cides are likely to be identified as oncogenic or potentially oncogenic, inviting regula-
tory 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 AND FOOD SAFETY 171

TABLE 5
PESTICIDES IDENTIFIED AS POTENTIALLY ONC~GENIC BY EPA

Active ingredient (common/trade name)

Acephate” (Orthene) Copper arsenate Lead arsenate Permethrin”

Acifluorfen (Blazer) Cypermethrin” Lindane (Ambush, Pounce)
Alachlor’ (Lasso) (Ammo, Cymbush) Linuron” (Lorox) Pronamide” (Kerb)
Amitraz (Baam) Cyromazine” Maleic hydrazide Sodium arsenate
Arsenic acid (Larvadex) Mancozeb“ Sodium arsenite
Asulam Daminozide (Alar) Maneb” Terbutryn”
Azinphos-methyl” Diallate Methanearsonic acid Tetrachlorvinphos
(Guthion) Diclofop methyl” Methomyl (Lannate) Thiodicarb (Larvin)
Benomyl” (Benlate) (Hoelon) Metiram” Thiophanate-methyl
Calcium arsenate Dicofol (Kelthane) Metolachlor” (Dual) Toxaphene
Captafol” (Difolatan) Ethalfluralin” O-Phenylphenol” Trifluralin (Treflan)
Captan” (Sonalan) Oryzalin” (Surflan) Zineb”
Chlordimeform” Ethylene oxide Oxadiazon” (Ronstar)
(Galecron) Folpet” Paraquat
Chlorobenzilate Fosetyl Al” (Aliette) (Gramoxone)
Chlorothalonil” Glyphosate’ Parathion”
(Bravo) (Roundup) PCNB

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 scien-
tific and technical uncertainties. Assumptions are made using a conservative ap-
proach 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 con-
sumer risks, but they provide an index of priorities by ranking pesticides for regula-
tory 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 TO THE NRC ( 1987)
ESTIMATED DIETARY ONC~GENIC RISKS

Pesticides Foods

Herbicide
Linuron” Tomatoes
Beef
Insecticide Potatoes
Permethrin” Oranges
Chlordimeform b Lettuce
Apples
Fungicide Peaches
Zineb b Pork
Captatol b Wheat
Captan b Soybeans
Maneb’ Beans
Mancozeb b carrots
Folpet b Chicken
ChlorothalonilC Corn (bran, grain)
Metiram b Grapes
Benomyl”
0-Phenylphenol’

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 to
the number of tolerances granted for crops.

MANAGING FOOD CONTAMINATION BY PESTICIDES AND

RECENT DEVELOPMENTS

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 num-
ber 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 expand-
ing 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 ade-
quacy 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 un-
dergoing 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 ani-
mals. 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 Fish-
ing 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 alter-
natives 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 initi-
ated, 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 Cali-
fornia laws which mandate the identification of toxicological data gaps for pesticides,
evaluation of pesticide tolerances for processed foods, and study of fish contamina-
tion. 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 pro-
cess. 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 per-
missible 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.

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174 FAN AND JACKSON

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