The Delaney Clause: The Dilemma of Regulating Health Risk for Pesticide Residues

Donna U. Vogt
Analyst in Life Sciences
Science Policy Research Division
92-800 SPR
November 9, 1992

SUMMARY

Under the authority of the Federal Food, Drug, and Cosmetic Act (FFDCA), the Environmental Protection Agency (EPA) is responsible for establishing tolerances for pesticide residues in or on foods and feeds. Tolerances are legal limits to the amount of pesticide residues that can be found on a raw agricultural commodity at the farm gate or in a processed food. The FFDCA has two sections, 408 and 409, which set up different and inconsistent criteria for setting tolerances for pesticide residues in foods.

Section 408, which applies to raw agricultural commodities, mandates a cost-benefit approach that balances the risks associated with the use of a pesticide against the benefits of using it in the food supply. Section 409, which applies only to processed foods, includes the Delaney Clause that prohibits a food additive, including pesticides, found to induce cancer in humans or animals. The Delaney Clause requires EPA to consider only a pesticide's risk and not to consider any offsetting benefits. It mandates a "zero risk" standard, implying that no food additive is likely to offer benefits sufficient to outweigh any risk of cancer.

In practice, EPA decided to regulate all pesticide residues using criteria known as "negligible risk" (used synonymously with the term de minimis) and ignore the criteria for setting tolerances in section 409 which requires "zero risk." EPA followed this policy in large part because negligible risk allows for residues that have a lifetime cancer risk of one in one million whereas the "zero risk" criteria creates severe problems from both a scientific and public health standpoint. EPA's negligible risk policy explicitly accepts small health risks in return for certain benefits. However, this policy was challenged in the courts and in July 1992 was overturned.

EPA assesses the dietary risk of pesticide residues by comparing the level of residues that are found on raw agricultural commodities and processed foods with health effect data to see if this level is acceptable. These assessments require certain types of data: residue chemistry data, dietary exposure data, and toxicological data.

The proposals and debates over food safety in the 102nd Congress focused on four issues. First, several Members felt that there should be no change in the Delaney Clause. Second, all the bills proposed that section 408 be used to set tolerances for all pesticide residues and that "negligible risk" to be used as the standard for acceptable risk. However, negligible risk was defined differently under the various proposals. A third approach would have changed the manner in which risk is used for establishing tolerances. Under this approach, EPA would use data on the actual residues left on food to assess risks rather than estimating the risks from laboratory tests. A fourth approach would promote a recent EPA initiative known as the Safer Pesticide Policy.

TABLE OF CONTENTS

INTRODUCTION
POLICY FRAMEWORK FOR PESTICIDE-RESIDUE REGULATION: IMPLICATIONS OF THE DELANEY CLAUSE
-- Sections 408 and 409
-- Contrast of Risk/Benefit versus Risk Alone
-- Delaney Clause
-- Use of De Minimis
-- National Academy of Sciences Report
-- Policy Debate
OVERVIEW OF THE TOLERANCE-SETTING PROCESS
-- Residue Chemistry Data
-- Dietary Exposure Calculations
-- Toxicology Data
-- Tolerance Decision: A Comparison
-- Criticisms of the Tolerance-Setting System
-- -- Choice of Models
-- -- Scientific Estimates Are Not Devoid of Values
-- -- Knowledge about Cancer-Causing Agents
-- -- Dietary Exposure Estimates
CONGRESSIONAL APPROACHES FOR CHANGING THE TOLERANCE-SETTING PROCESS
-- Do Nothing-Leave Delaney Clause Alone
-- Changing Statutory Authority to Include Negligible Risk
-- Use of Anticipated Residues for Reducing Exposure
-- Estimates Safer Pesticide Policy
CONCLUSION

APPENDIX. Glossary

THE DELANEY CLAUSE: THE DILEMMA OF REGULATING HEALTH RISK FOR PESTICIDE RESIDUES

INTRODUCTION

The Environmental Protection Agency (EPA) regulates pesticide residues in or on both raw agricultural commodities and processed foods under sections 408 and 409 of the Federal Food, Drug, and Cosmetic Act (FFDCA). Under these provisions, EPA sets legal limits, or tolerances, on the amount of pesticide residues allowed on foods, but EPA is caught in a dilemma because the two sections lay out inconsistent criteria for setting tolerances. To disentangle itself from these inconsistencies, EPA decided to regulate pesticide residues using criteria known as "negligible risk" and ignore the criteria for setting tolerances in section 409 (containing the Delaney Clause), which requires "zero risk." EPA followed this policy in large part because the "zero risk" criteria created severe problems from both a scientific and public health standpoint. This policy was challenged in the courts and in July 1992 was overturned. Currently, EPA, with the Administration, is considering three actions: 1) whether to appeal this lower court decision to the Supreme Court; 2) whether it will appeal to the 103rd Congress to change the statute to remove the inconsistent criteria for setting tolerances; and/or 3) how to apply zero risk if forced to.

Under section 408 of the FFDCA, EPA determines appropriate tolerance levels for pesticide residues in or on raw agricultural commodities by considering both the potential adverse health effects of residues and the value of pesticide uses. This cost-benefit approach, therefore, balances the risks associated with the use of a pesticide against the benefits of using it in the food supply. For pesticides found to be carcinogenic, EPA uses a "negligible risk" standard, or a lifetime cancer risk of one in one million, or 1 x 10-6, that an individual will experience cancer from daily exposure (over a 70-year lifetime) to a carcinogenic pesticide. EPA departs from "negligible risk" to allow somewhat higher risks when benefits are judged significant. Pesticides are beneficial to health by controlling disease and damage to foods caused by bacteria, fungi, and insects. The law reads that EPA must consider "the need for an adequate, wholesome, and economical food supply" when it establishes tolerances.

Section 409 of the FFDCA, which applies only to processed foods, includes the Delaney Clause that prohibits food additives, including pesticides, found to induce cancer in humans or animals. (1) The Delaney Clause requires EPA to consider only a pesticide's risk and not to consider any offsetting benefits. It mandates a "zero risk" standard, implying that no food additive is likely to offer benefits sufficient to outweigh any risk of cancer. In practice, EPA has adopted "negligible risk" (used synonymously with the term de minimis) as the criteria for establishing section 409 food additive regulations for carcinogenic pesticides.

In July 1992, the U.S. Ninth Circuit Court of California declared that EPA's use of de minimis or "negligible risk" for establishing tolerances for carcinogenic pesticides was invalid. EPA, therefore, must revamp its system for setting tolerances on pesticides shown to be carcinogenic. Since the Court's decision, EPA has identified about 30 pesticide compounds and 80 pesticide uses which would require revisions of their section 409 food additive tolerances. EPA officials see this number rising as they receive data regarding pesticides' carcinogenicity in its ongoing reregistration and tolerance reassessment programs. (2)

The challenge for EPA is to balance the estimates and judgments about risk of all pesticide residues in food to arrive at a consistent regulatory system that will protect the public health. To find levels of acceptable risk, scientists have developed a process known as risk assessment. Risk assessment is defined as the measurement of the probability and severity of adverse effects or harm to human and/or animal health. (3) Risk assessment is used to quantify the potential adverse effects of pesticides. Assessments of dietary risks from pesticide residues depend on data from many sources: field studies that show what pesticides are used and the levels of residues that can be expected to occur, the estimates of food people eat, and toxicological data which assess the potential for adverse health effects from specific pesticides.

Some consumers are concerned that foods they consume contain unsafe levels of pesticide residues. Such concerns have put Congress under pressure to change the statutory authority for the pesticide residue regulatory system and establish a system that will minimize the dietary risks of all pesticides, but will allow the use of pesticides for an adequate and wholesome food supply. Members of the 102nd Congress considered four major proposals to change the current system. (4) None, however, passed either House. However, it is likely that Members will be called upon to consider similar proposals in the 103rd Congress.

This report examines the current system for the regulation of pesticide residues in foods. (5) It looks at the current policy framework and explains the Delaney Clause's "zero risk" mandate in the FFDCA. It then briefly tells about EPA's regulatory process for setting tolerances and summarizes criticisms of this process. The report concludes with four approaches and issues that were considered in 102nd Congress for changing the current regulatory system.

POLICY FRAMEWORK FOR PESTICIDE-RESIDUE REGULATION: IMPLICATIONS OF THE DELANEY CLAUSE

The Federal regulatory system for ensuring food safety is based largely on setting tolerances for contaminants, particularly pesticide residues. The major food safety law, the FFDCA, authorizes the regulation of pesticide residues in or on foods. The major statute mandating all other regulations for pesticides is the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). It requires the registration of all pesticides prior to their use. In the pesticide registration process manufacturers must submit data on the residues that may remain in or on food or feed crops, which show that the pesticide use will conform with criteria laid out in the FFDCA. The FFDCA has several sections that govern these regulatory policies for pesticide residues. The two most important sections are sections 408 and 409. The two set up different criteria for managing the risk caused by pesticide residues in foods.

Sections 408 and 409

Section 408 classifies all pesticide residues in or on raw agricultural commodities as adulterants, unless the pesticide has an established tolerance or an exemption. Section 408 requires that tolerances be established by experts qualified by scientific training and experience to evaluate the safety of pesticide chemicals to the extent necessary to protect the public health. The law also requires that in setting 408 tolerances the EPA Administrator consider: (1) the necessity for the production of an adequate, wholesome, and economical food supply; (2) the ways in which the consumer may be affected by the same pesticide chemical, or by other related substances that are poisonous or deleterious; and (3) that the substance also be useful or benefit the food supply.

Section 409 authorizes a separate system to regulate pesticide residues in certain processed foods. It applies when a pesticide chemical is used directly or indirectly during processing or is used to treat a processed food. It also applies when pesticides used on raw agricultural commodities concentrate during processing and surpass the level set by the section 408 tolerance. Section 409 requires manufacturers of food additives to pretest substances that would be added to foods and to submit a petition to EPA for approval prior to marketing the product. This pre-market approval system for food additives means that Government regulators examine the risks of an additive before approving its use. The Act states that food additives are "unsafe" and thus unlawful, unless the Federal Government issues regulations specifying the conditions for the food additive's use.

The majority of tolerances are established for pesticides under section 408 and are set to cover the maximum use of the pesticide. A much smaller number of tolerances are set under section 409. EPA policy has been to reject registrations and tolerances under section 408 for any pesticide use if the pesticide concentrates during processing. EPA does this because theoretically a residue can be at its maximum amount or tolerance level and if it concentrates it will surpass the section 408 tolerance level and thereby cause adulteration in the food. This policy ensures that farmers who use a registered pesticide in accordance with its labeling will produce food that complies with both sections of the FFDCA. (6) Any other approach carries the risk that the lawful use of the pesticide by the farmer will result in food that contains illegally high residues, making the food adulterated and subject to seizure.

Contrast of Risk/Benefit versus Risk Alone

Section 408 recognizes that pesticides confer both benefits and risks and stipulates that tolerances be set balancing two criteria: 1) protection of the public health, and 2) benefits of the pesticide use to produce an adequate, wholesome, and economical food supply. (7) The manufacturer or registration-seeker has the burden of providing data to meet these criteria. Section 409, on the other hand, carries with it the requirement that the tolerance must be set considering only the risk of the pesticide residue and not considering the potential benefits of the use of the pesticides.

Delaney Clause

Section 409 also contains the Delaney Clause. It forbids the establishment of a tolerance if the food additive is "found to induce cancer when ingested by man or animal, or if found, after tests which are appropriate for the evaluation of the safety of food additives to induce cancer in man or animal." This clause means that no amount of a cancer-causing (carcinogenic) additive ("zero-tolerance" provision) may be present in food, no matter how small a risk that substance might pose. The "zero-risk" standard does not permit the incorporation of any new analytical methods developed by science, which increasingly are able to assess the risk and potency of carcinogens. Such residues may represent extremely low or negligible cancer risks. A paradox is created. Although the Delaney Clause was intended to protect public health, it may instead bar registrations of pesticides that may actually pose less risk than other pesticides on the market. The "zero-risk" standards of the Delaney Clause makes carcinogenic additives illegal, without regard to other characteristics of product use, such as other health risks or benefits.

Use of De Minimis

In establishing regulations to govern pesticide residues found in foods, under both section 408 and 409, EPA uses a de minimis approach. The de minimis approach derives from case law holding that an administrative agency (in this case EPA) has the inherent authority to avoid applying the terms of a statute literally when to do so would yield pointless results. To use de minimis two conditions are necessary: 1) the problem that would be addressed by a regulation must be trivial in fact so that no real benefit would result from regulation based on the letter of the law; and 2) the legislative design must allow the agency to use a de minimis approach. (9)

National Academy of Sciences Report

In 1987, with EPA's support, the National Research Council (NRC) of the National Academy of Sciences (NAS) published a report entitled, "Regulating Pesticides in Foods: The Delaney Paradox.'' (10) This report recommended that all pesticide residues in food, whether marketed in raw or processed form, or governed by old or new tolerances, should be regulated on the basis of consistent standards. One of the four theoretical scenarios (scenario 3) considered showed what would happen if "all tolerances would be revoked for a pesticide on a crop when the combined estimated cancer risk from the residues of that pesticide on both the raw and processed forms of a crop exceeds 1 in 1 million or 1 x 10 (-6)." The NRC called this one in one million case a "negligible risk." The NRC found that a negligible risk standard for carcinogens in food, applied consistently to all pesticides and to all forms of food, could dramatically reduce total dietary exposure to oncogenic pesticides with modest reduction of benefits. (Oncogenic means the causing of tumors, benign or cancerous, in a living tissue.) In fact, the committee found that, "if consistently applied, a negligible risk standard applied to raw and processed foods (assuming no consideration of benefits) could lead to the elimination of 98 percent of the existing dietary risk from exposure to the 28 pesticides comprising the NRC's estimate of dietary oncogenic risk." The NRC committee recommended that EPA regulate carcinogenic residues using an across-the-board negligible risk standard. The NRC also recommended that EPA be given more flexibility in responding to scientific advances.

Policy Debate

On October 19, 1988, EPA published in the Federal Register a notice which stated that:

EPA's position will be that the section 409's so-called Delaney Clause--which, read literally, purports to bar absolutely the issuance of a food additive regulation for a food additive that has been found to induce cancer in test animals--is subject to a de minimis exception where the human dietary risk from residues of the pesticide is at most negligible. "

This notice declares that, from then on, EPA would use a de minimis approach, which they equated with "negligible risk," to set tolerances for carcinogens. In the Federal Register notice, EPA defined negligible risk to be one chance in a million (1 x 10 (-6)) that an individual will experience cancer from daily exposure (over a 70-year lifetime) to a carcinogenic pesticide.

It is helpful to keep the risk estimates provided by quantitative risk assessments in perspective. For example, assume that a community with a population of 1 million persons is exposed to a pesticide which poses a lifetime cancer risk of 1 in 1 million. Mortality statistics show that over a lifetime approximately one in four persons will die of cancer. That means, excluding any cancer risk from the pesticide, the hypothetical community will experience 250,000 cancer deaths over a 70-year time frame. The additional cancer risk from exposure to the pesticide may increase the cancer deaths over that time [from 250,000] to 250,001. However, there may be no increase at all. (12)

In November 1989, President Bush announced his Food Safety Plan, which proposed a more flexible definition of risk be used as the standard by which all tolerances should be set. (13) The President's plan proposed to eliminate the use of the Delaney Clause for pesticide-residue tolerances, which would eliminate the dichotomy in the current system between carcinogenic pesticides and non-carcinogenic pesticides. It would define risk so that in the regulations, suspected risk for potential carcinogens would be in the range of one in one million (1 x 10 (-6)) to one part per one hundred thousand (1 x 10 (-6) or one in 100,000) or smaller, based on lifetime exposure using standard risk assessment procedures. The quantitative standard for tolerances would be set as a range in the law to allow the decision on risk to be left to the judgment of EPA based on the quality of the database and the certainty of the risk assessment.

A May 1989 petition from several environmental and consumer groups requested the revocation of food additive regulations governing seven carcinogenic chemicals. EPA responded on April 25, 1990, in the Federal Register, claiming that it refused to revoke the regulations because the chemicals posed a measurable de minimis risk of causing cancer. (14) The consumer groups filed their objections with EPA and, in response, on February 25, 1991, EPA issued its final order saying that it would use the de minimis interpretation to grant section 409 tolerances.

The petitioners sought the courts to review EPA's final order permitting four of the pesticides as food additives, although they were carcinogenic, alleging that EPA had violated the provisions of the Delaney Clause. (The petitioners did not protest approval for three of the original seven pesticide food additives.) Prior to 1988, EPA had permitted use of the four pesticides as food additives because at the time they were first registered, there was no evidence that they were carcinogenic. At some later point, EPA found these pesticides were carcinogens, but refused to revoke earlier regulations saying that the chemicals posed a measurable de minimis risk of causing cancer.

On July 8, 1992, the U.S. Court of Appeals for the Ninth Circuit (in the case of Kathleen A. Les, et al. v. William K. Reilly, Administrator of EPA) decided that the language of the Delaney Clause, its history and purpose, all reflect that Congress intended to prohibit EPA from setting regulations allowing the use of any food additive that is a carcinogen, regardless of the degree of risk involved. Therefore, the court held that EPA's de minimis interpretation of the language of section 409 was unlawful, barring EPA from using the concept of de minimis or negligible risk. In August 1992, the Justice Department petitioned for a rehearing of the court decision. On September 25, 1992, the petition for a rehearing was denied. On October 1, 1992, the Justice Department filed for a stay of the mandate to stop the use of the de minimis policy and to allow 90 days for the Government to decide whether it wanted to appeal to the Supreme Court. (15) on October 8, 1992, the stay was granted. EPA must decide by December 24, 1992, whether to appeal the decision to the Supreme Court.

In the meantime EPA has begun to plan how it will implement this decision. EPA is concerned that the number of pesticide uses subject to revocation is likely to increase considerably. In the Justice Department's petition to the Ninth Circuit Court in California, it stated that EPA had identified approximately 65 pesticide uses, which have or which would now require section 409 food-additive tolerances. All of these show some evidence of carcinogenicity. EPA officials are considering whether to make pesticide-use label changes, expiration dates on the tolerances of concern, and removal of only the section 409 food and feed tolerances, or whether to revoke all the associated section 408 tolerances and perhaps cancel the FIFRA registrations for any food uses that might lead to illegal residues.

Other concerned interest groups are participating in this process for revising tolerances. The National Agricultural Chemicals Association (NACA) filed with the Ninth Circuit Court as a respondent-intervenor. NACA argues that the court ignored the established judicial principle regarding an administrative agency's right to use de minimis in applying a statute. Also, five industry groups petitioned EPA to abandon its longstanding policy of not establishing a 408 tolerance if the pesticide cannot meet the 409 tolerance criteria. The petition claims that EPA's policy unlawfully incorporates the Delaney Clause of section 409 into criteria for tolerances laid out in section 408. (16)

Because of the inconsistencies in regulating pesticide residues, many policy makers and regulators are working together to legislate one policy that would be consistent for both raw agricultural commodities and processed foods. Numerous proposals before Congress in the last five years have tried to resolve these issues. It is probable that with the court decision of July 1992, as well as support from consumer, industry, and the Administration, the 103rd Congress will consider legislation to set a consistent policy direction.

OVERVIEW OF THE TOLERANCE-SETTING PROCESS

EPA assesses the dietary risk of pesticide residues by comparing the level of residues that are found on raw agricultural commodities and processed foods with health effect data to see if this level is acceptable. These assessments require certain types of data: residue chemistry data, dietary exposure data, and toxicological data. The assessments also differ if the pesticide is a carcinogen.

Residue Chemistry Data

These data, submitted by pesticide manufacturers, along with their petition for a registration and tolerances for specific pesticide/food combinations, show how the plant or animal breaks down the pesticides and what happens to the pesticide during processing. Any products of the metabolism of the pesticide, "degradation" products and/or metabolites, that may be significantly toxic, are considered to be residues of the pesticide for which tolerances are to be set. Some residue data are obtained from field tests where pesticides are used according to proposed label directions and under conditions designed to produce maximum residues. Field trials are done in several geographical areas where the pesticide will be used. (17)

Along with residue chemistry data, manufacturers recommend a method for analyzing/testing for that specific pesticide residue. EPA validates each new analytical method proposed to ensure that the procedures used to enforce the tolerance by FDA USDA, and State agencies will work. EPA tries to find tests that will yield data on several pesticides simultaneously, i.e., in multi-residue tests. Critics have complained that multi-residue analytical methods used by FDA and USDA can test for no more than half of the currently known pesticides. (l8)

Dietary Exposure Calculations

To judge the acceptable level of risk, EPA must also look at how much people eat of certain foods. The FDA's Total Diet Study Program, using information derived from market basket studies, shelf studies, and cooked food diet sampling, provides EPA with information about the dietary habits of various age, sex, or cultural groups. These data are used to characterize exposure based on the relationship between food items sampled and groups (geographic, ethnic, demographic) studied, and relationships between concentrations in uncooked versus prepared food. Information on the consumption of pesticide residues in foods is derived from a 1977-78 Nationwide Food Consumption Survey (NFCS) conducted by the Human Nutrition Information Service (HNIS), an agency of the U.S. Department of Agriculture. The survey covers the diets of the overall U.S. population, as well as a number of subgroups, including several different ethnic groups, regional populations, and age groups such as infants and children under 7 years. (19)

EPA then combines residue chemistry data with consumption data to estimate exposure using its Dietary Risk Evaluation System (DRES). A short-hand method of expressing what DRES does is to say:

Exposure = Residue x Food Consumption.

The DRES estimates of dietary exposure are expressed in milligrams per kilogram of body weight per day (mg/kg body weight/day). (20) For example, a typical U.S. citizen consumes 0.1 gram of grapejuice/kilogram of body weight/day, but only 13 percent of the population actually consume grape juice on a given day, and when they do, they consume it at an average rate of 0.7 grams/kg of body weight/day. The value of 0.1 g/kg/d may be used for estimates of chronic exposures done by DRES, whereas the value of 0.7 g/kg/d might be used to determine acute exposures. (21)

For each pesticide, EPA adds all the exposure estimates from all the pesticide/commodity combinations. This summation yields a number called the theoretical maximum residue contribution, or TMRC. The TMRC represents the "worst-case" exposure, for it greatly overestimates dietary exposure. It assumes that the crops were 100 percent treated with the pesticide and that they contain 100 percent tolerance level residues at the time of harvest. Actual residues are much lower. However, the TMRC serves as an upper limit on exposure which is easily calculated and which can identify any potential dietary concern quickly.

Toxicology Data

Toxicology data attempt to predict the relationship between the dose consumed and the intensity of a potential adverse effect in humans. Sponsors gather data from bioassays or tests on laboratory animals (mostly rats, mice, and dogs), which are fed different amounts of a pesticide to measure the effects from continuous ingestion of specific doses of a pesticide throughout a lifetime. (22) These data are evaluated to determine if they are relevant to humans and if harmful effects are either acute or chronic. The required toxicology studies calculate the pesticide's potential for causing adverse health effects, such as carcinogenicity, developmental toxicity, reproductive effects, mutagenicity, and structural chromosomal aberration and other genotoxic effects. (23)

In each of the required tests, EPA identifies a No-Observed-Effect-Level or NOEL. (24) A NOEL is the highest dose level of pesticide (consumed in the daily diet per unit of body weight) at which no adverse effect was observed.

For non-carcinogenic pesticides EPA then calculates a reference dose by dividing the NOEL by a safety factor (typically 100). The safety factor of 100 is derived from assuming that humans are 10 times as sensitive as the most sensitive animal tested, and that some humans are 10 times as sensitive as the least susceptible human.

For carcinogenic pesticides EPA determines a quantitative estimate of a pesticide's carcinogenic potency, called a "Q*" (or Q star). To calculate a "Q*," EPA uses evidence of cancer incidence in lifetime chronic animal feeding studies. EPA also assumes: 1) that human health effects would correspond to health effects observed in animals; and 2) that there is a linear dose-response relationship at low doses, so that the mathematical models used to extrapolate from high dose to low dose correctly predict the odds that the chemical will cause cancer in humans. This means that any dose above zero engenders some level of risk. To allow for these uncertainties, the odds are expressed with a 95 percent confidence level. This means that from animal data, usually based on three dose levels, the maximum dose-effect relationship is calculated. Then another slope, called the Q*, is calculated. This Q* is generally the upper 95 percent confidence interval, which is interpreted to mean that the probability is 0.95 that the actual value is not greater than this estimate (see figure 1).

EPA then multiplies the Q* by the exposure estimate to calculate the probability of additional cancers (additional to the current statistic of one in four people having cancer in their lifetime) occurring in the human population following a lifetime of exposure at the level calculated in the chronic exposure analysis.

For example, if the Q* for a chemical was calculated as 0.0045 (mg/kg/day) (-1) and the exposure estimate was 0.00055 mg/kg/day, the resulting product would estimate the probability of additional cancers in the population following a lifetime of exposure. In this example this probability would be the product of 0.0045 x 0.00055 or 2.5 x 10 (-6), meaning that the use of the chemical would result in an additional 2.5 cases of cancer for every million people [or 1 in 400,000] in the population who were exposed to 0.00055 mg/kg/day of the chemical over 70 year lifetimes. (25)

The risk is equal to Q* times exposure. The result of this example, 2.5 x 10 (-6), is above 1 x 10 (-6) or the amount that EPA has declared de minimis. Therefore. this chemical would not get a tolerance for use on a specific food that had this residue, if it is a carcinogen. However, if the manufacturer could lower the exposure ten times to 0.000055, the result would be a Q* of 0.25 x 10 (-6), an acceptable level of risk under the current de minimis policy. Exposure to risks below this level is considered insignificant. (26) Actual cancer potency may be considerably lower or even zero. (27)

MAXIMUM TOLERATED DOSE CONTROVERSY

One of the major controversies among scientists who test for Q* and other carcinogenic indicators is the use of the maximum tolerated dose (MTD) in animal bioassays. The use of the MTD is required by the EPA in their regulations regarding toxicological testings. One scientist claimed that:

Animal cancer tests are conducted at near-toxic doses (the maximum tolerated dose (MTD)) of the test chemical, for long periods of time, which can cause chronic mitogenesis (increased cell division). Chronic dosing at the MTD can be thought of as a chronic wounding, which is known to be both a promoter of carcinogenesis in animals and a risk factor for cancer in humans. Thus, a high percentage of all chemicals might be expected to be carcinogenic at chronic, near-toxic doses, and this is exactly what is found. About half of all chemicals tested chronically at the MTD are carcinogens. (a)

However, others disagree with the idea that using the MTD would naturally cause "chronic wounding" stating that science has recently shown that the carcinogenic process has at least three qualitatively distinct phases: initiation, promotion, and progression. (b) And in defense of the use of rodent bioassays and the MTD to test pesticide chemicals, another scientist claimed that "when adequately tested, virtually all of the specific chemicals known to be carcinogenic in humans are also positive in the rodent bioassays, and sometimes even at comparable doses and with similar organ specificity." (c)

a. Ames, Bruce N. and Lois Swirsky Gold. Too Many Rodent Carcinogens: Mitogenesis Increases Mutagenesis. Science. v. 249. Aug. 31, 1990. p. 970-971.

b. Catherine A. Picut and George A. Parker. Use of Biological Thresholds to Reinterpret the Delaney Clause: A Proposal for Minimizing Cancer Risk. Food and Drug Law Journal. v. 47, no. 1. 1992. p. 107-129.

c. Weinstein, Bernard. Mitogenesis Is Only One Factor in Carcinogenesis. Science v.251. Jan. 25, 1991. p. 387-388.

Tolerance Decision: A Comparison

After evaluating all the submitted data, the challenge for EPA is to balance the estimates and judgments about the dietary risk of a particular pesticide. EPA then sets a tolerance for a specific pesticide food combination that will protect the public health and convince consumers that the food supply is safe. To find the level of acceptable risk, EPA compares the level of residues found and the amount of estimated exposure to the residue with health effect data. In other words, EPA takes the TMRC and compares it to the RfD for non-carcinogens and the Q* for carcinogens. If TMRC is less than the RfD, EPA will establish a tolerance. If the Q* is below 1 x 10 (-6), EPA will establish a tolerance. If the TMRC is greater, EPA has two choices: it can deny the petition for a tolerance, or it can ask for different data. EPA has used actual residue data instead of the TMRC at times. EPA can also ask the pesticide manufacturers to reconfigure the use of the pesticide to reduce residues.

Criticisms of the Tolerance-Setting System

EPA has been criticized for many of its decisions regarding tolerances. The decisions are based on risk assessment and the choice of mathematical models used becomes important to the tolerance-setting process. These risk assessments and estimates are also not devoid of values. Science has begun to understand better (not completely) the mechanisms of a few cancer causing agents, as well as more accurately assess dietary exposure to pesticides in foods.

Choice of Models

Scientists are concerned whether the safety factors, the accumulation of all the uncertainty factors, have properly accounted for any risk so that tolerances protect public health without excessive margins of error. Uncertainty factors are scientific judgments concerning the type and quality of the data. In analyzing toxicological data for tolerances, scientists use mathematical models to predict the extent to which effects on animals will be similar to those on humans. In fact, the estimation of cancer risks can be affected by the choice of mathematical models. These models use numerous default assumptions and may have high levels of uncertainty.

Also, scientists understand that some humans are predisposed to being susceptible to some chemicals and not others. Scientists assume that a substance that causes a response at a high dose will cause a similar response at a low dose, yet it is still unknown what all the metabolic and other biological differences are between laboratory test animals' and humans' responses to chemical exposures. Extrapolating from animals to humans includes uncertainty, yet most scientists assert that rodent bioassays are critical in determining whether a chemical can cause cancer at some dose. (28)

Scientific Estimates Are Not Devoid of Values

As in the choice of models, scientists must make many assumptions when they estimate risk because of gaps in data and knowledge. Many of these assumptions contain subjective elements and are chosen with individual biases:

That a scientist makes the choices does not render the judgments devoid of policy implications. Scientists differ in their opinions of the validity of various options, even if they are not consciously choosing to be more or less conservative. In considering whether to use data from the most sensitive experimental animals for risk assessment, a scientist may be influenced by the species, strains, and gender of the animals tested, the characteristics of the tumor, and the conditions of the experiment. A scientist's weighing of these variables may not easily be expressed explicitly, and the result is a mixture of fact experience (often called intuition), and personal values that cannot be disentangled easily. As a result, the choice made may be perceived by the scientist as based primarily on informed scientific judgment. From a regulatory official's point of view, the same choice may appear to be a value decision as to how conservative regulatory policy should be, given the lack of a decisive empirical basis for choice.... Furthermore, a desire to err on the side of overprotection of public health by increasing the estimate of risk could lead an assessor to choose the most conservative assumptions throughout the process for components on which science does not indicate a preferred choice. (29)

Knowledge About Cancer-Causing Agents

Although much is still unknown, scientists now know a great deal more about the process of cancer. Cancer is a complex multistage development process and cancer-causing substances can be dissimilar. For example, some carcinogens participate in either initiating tumors and/or promoting or progressing cancerous tumors; they are classified as either primary or secondary carcinogens. (30) Consequently, risk assessments differ dramatically among carcinogens. However, the tolerance-setting process must comply with the statute. It contains the Delaney Clause, which makes no distinction between various pesticide hazards with its blanket "zero risk" mandate for carcinogens.

Dietary Exposure Estimates

It is difficult to know just what levels of residue people actually consume. Each person's diet differs and no scientist can estimate precisely how much of a particular pesticide residue remains on or in a food. There is a large contrast between the amounts of pesticides that are allowed under the tolerance (using the "worst-case" scenario) and the amount that is found at the dinner tabled Figure 2 shows the difference between the legal limit of the tolerance and dinner table residues. It also shows the factors which reduce residue levels in or on foods. Over time, pesticides usually dissipate and are reduced through peeling, juicing, cooking, and refining. However, processing may cause residues or their metabolites to concentrate and thereby could cause a health risk. On these occasions, EPA weighs whether a tolerance should be established.

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insert FIGURE 2 here

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Source: Mr. Ed Zager, Chief, Residue Chemistry Branch, Health Effects Division, Office of Pesticide Programs, Environmental Protection Agency. March 2, 1990. Modified by Congressional Research Service.

CONGRESSIONAL APPROACHES FOR CHANGING THE TOLERANCE-SETTING PROCESS

Various Members of Congress responded to the 1987 National Academy of Sciences (NAS) report entitled, "Regulating Pesticides in Foods: The Delaney Paradox," with proposals to change the statutory authority for setting tolerances. (32) The proposals and debates over food safety in the 102nd Congress focused on four approaches to changed. First, several Members felt that there should be no change in the Delaney Clause. Second, all the bills proposed that section 408 be used to set tolerances for all pesticide residues and that "negligible risk" be used as the standard for acceptable risk. However. negligible risk was defined differently under the various proposals. A third approach would have changed the manner in which risk is used for establishing tolerances. Under this approach, EPA would use data on the actual residues left on food to assess risks. A fourth approach would promote a recent EPA policy initiative on the use of safer pesticides, encourage the use of genetically engineered pesticides, and encourage the stockpiling of pesticides needed for public health concerns.

Do Nothing-Leave Delaney Clause Alone

Even after 30 years of scientific effort, much is still unknown about the etiology of cancer. Consequently, many support the current regulatory system. Their thinking reflects a concern that if one in four U.S. citizens will have cancer, there is no reason to expose people to more cancer-causing substances.

Changing Statutory Authority to Include Negligible Risk

The legislative proposals in the 102nd Congress would have moved the whole authority for setting tolerances and assessing risk to section 408 of the FFDCA with its risk/benefit mandate. Three proposals in the 102nd Congress and the Administration's Food Safety Plan of November 1989 recommended the use of negligible risk to be the standard by which all tolerances would be set. However, they all define "negligible risk" differently. The Administration's Plan defines "negligible risk" to be a level adequate to protect the public health and the environment. It would use "negligible risk" to institute a single protective standard for all foods. EPA would be permitted to use its best judgment in determining "negligible risk" and setting tolerances.

The Kennedy-Waxman proposal (S. 1074/H.R. 2342) would have defined negligible risk to mean that any dietary exposure to the residue should be reasonably certain to cause no harm to human health. It defined risk for threshold (non-carcinogenic) and non-threshold (carcinogenic) pesticides. For pesticides with threshold health effects, a tolerance could be set if a level can be identified which considered the residue's toxic effects; the validity, completeness, and reliability of the data about the residue; and the sensitivities of various population subgroups to the chemical pesticide. It defined the margin of safety to be used in the testing of pesticides. It required that human exposure per unit of body measurement to the residue be at least 100 times smaller than the NOEL and if human data were available, be at least 10 times smaller than the NOEL in humans.

S. 1074/H.R. 2342 also stated that for pesticide chemical residues with non-threshold (carcinogenic) health effects, a tolerance could be established if EPA finds that such a level:

will not cause or contribute in individuals exposed to such pesticide chemical residue a lifetime risk of an adverse human health effect which occurs at a rate of one in a million or a risk of an adverse human health effect which occurs at a rate of one in a million divided by 70 for any single year of exposure during the first 5 years of an exposed person, using conservative risk models.

It also stated that the tolerance be established in a manner that leaves the pesticide residue at the lowest reasonable level required to allow the accomplishment of the physical or technical effect for which the use of the pesticide is intended. In processed foods, the tolerance level should be set at the lowest level that occurs if such pesticide residue is removed to the extent possible in accordance with good manufacturing practices (GMP). GMP are generally accepted practices for the food industry that provide food producers and handlers with guidance in interpreting the phrase "unsanitary conditions" in the regulations.

Others, notably supporters of the revised and reported Bruce/Bliley Bill (H.R. 3216) and the Rose Bill (H.R. 3742), would define negligible risk as:

the level of dietary exposure to the pesticide residue in foods which is at a level that would present no material increase in lifetime risk of developing cancer, as determined by the (EPA) Administrator, calculated using generally accepted scientific methods and based on lifetime exposure. (34)

The EPA supports this proposal for it allows them the flexibility to decide the level of risk they judge acceptable in setting tolerance levels.

EPA may appeal to the Supreme Court the decision by the U.S. Court of Appeals for the Ninth Circuit against the use of de minimis and one in one million (1 x 10 (-6)). EPA would like to see the authority for regulating pesticide residues removed from section 409 with its Delaney Clause. It would also like to be given the authority to use a more flexible "negligible risk" policy to guide tolerance setting. (35)

Critics of this approach remain unconvinced that such a policy would protect the public health. Sidney Wolfe, the Director of Public Citizen's Health Research Group, identified why so many people still support the Delaney Clause. (36) Dr. Wolfe stated that animal studies on chemicals can only determine whether a chemical causes cancer in animals. He said that it is possible that humans are orders of magnitude more or less sensitive than animals to certain chemicals. Dr. Wolfe reasons that until we know more about the effects of chemicals in humans, the maintenance of Delaney is important because it prevents cancer-causing pesticides to enter the food supply, while at the same time it gives EPA the flexibility to decide whether animal studies are or are not done properly and whether the chemical would have other side effects.

Use of Anticipated Residues for Reducing Exposure Estimates

Currently, when EPA estimates risk to establish tolerances, it assumes it is overestimating the residues that may be found, for EPA scientists always use the "worst-case" scenarios when collecting residue chemistry data from field trials, as well as toxicology and consumption data, and other information. Tolerances are set to accommodate the maximum amount of pesticide use.

In assessing risk to the public health from pesticide residues, some think that using data collected from food consumed and not from bioassay tests in laboratories would allow risk managers the opportunity to assess the actual risks from exposure and do a better job of establishing tolerances. In fact, currently, if actual use data are available, EPA now uses these data because FIFRA gives them this authority. The Kennedy-Waxman bills (S. 1074/H.R. 2342), proposed the use of actual data to lower tolerance levels and better reflect actual residues found on foods.

The method of assessing risk from actual residues and setting tolerances from these data is known as setting an anticipated residue limit (ARL). It would use two types of data to establish a range rather than a single tolerance number: 1) it would measure levels of residues actually left on the plants at the farm gate; and 2) it would measure levels of residues in foods immediately after being processed. Because of many extenuating circumstances under which food crops are grown and processed, a range of numbers covering closer proximity to actual use may allow the legal limits to be reduced.

Whatever levels were established, they would reflect the lower residues that turn up at the farm gate rather than schemes that now use theoretical maximums or the TMRC (see page 10). EPA could set an ARL as a legal limit which could be tested to ensure the health and safety of consumers.

How would this work? Suppose a spaghetti sauce manufacturer buys tomato sauce from a Texas firm and from a Florida firm. Suppose further both use pesticide X which has a tolerance set at 2 parts per million. The manufacturer can produce residue data showing that although there are different growing conditions in Florida and Texas, in both States the farmers can effectively use agricultural practices that leave residues of only 1 part per million. EPA could set an ARL for pesticide X with a range about 0.5 to 1 part per million and the calculated estimate of risk is lessened.

Proponents of the ARL want the numbers in the risk assessment process to more closely match the amount of residue actually found in or on foods. Such a system would reward the producers who cut back on pesticide chemical use and perhaps use alternative pest management techniques. The benefits of this approach would be that it would lower the calculated risk from pesticide residues. In addition, FDA could enforce food tolerances in the same way it now does for both domestically produced and imported foods by testing shipments.

Critics, particularly producers who have more flexibility under the current system, claim that it would be prohibitively expensive to get data for actual residues on all food products. When producing conditions warrant the heavy use of a pesticide, the current tolerance system allows for higher levels of residues without jeopardizing public health. In particular, imported foods may be at a disadvantage because their growing system may require different uses of pesticides leaving higher levels of residues that may not be harmful to human health. Some claim it could be a very protectionistic proposal for it could prevent the freer flow of trade and would not necessarily be comparable to the Codex Alimentarius Commission system (of which the United States is a member), which seeks greater international harmonization of pesticide residue standards.

Safer Pesticide Policy

On July 20, 1992, EPA published a notice in the Federal Register on "Incentives for Development and Registration of Reduced Risk Pesticides." (37) The purpose of the notice (known as the Safer Pesticide Policy) was to solicit comments on potential policies that would give economic incentives for the development of pesticides that present lower risks to public health and the environment. EPA also wants to encourage integrated pest management (IPM) programs and apply the incentives that they now use for microbial and biochemical pesticides to conventional pesticides. These microbial and biochemical pesticides may present lower overall risk and are typically substances found in nature. They are effective in smaller amounts than more conventional chemicals, but may require increased applications.

In the future, this "safer pesticide policy" may incorporate genetically-engineered pesticides which could lower the overall risk of pesticides from drift and inadvertent contamination, as well as minimize the need for large amounts of toxic chemicals. For example, Monsanto scientists cloned a delta-entoxin gene called Bacillus thuringiensis (BT). Early in 1992, Monsanto was granted an experimental use permit to use transposable elements in field testing to install it in the chromosomes of a microbe that colonizes the surface of cotton plant roots. (38) In its host, the gene product retains its toxicity to protect the plant from the lepidopterean species. BT is a natural pesticide and had been registered as a biologic; it received an exemption from the tolerance requirement because it is not toxic to humans or mammals. Now, Monsanto has bioengineered BT. If and when Monsanto petitions EPA for a registration for its genetically engineered product, it may be exempt from the tolerance requirement. (39) The natural product is not toxic to humans, and there is almost no risk of the toxin spreading to the soil or groundwater. (40)

For tolerances on these new products, EPA officials will likely follow FDA's example on registering bioengineered plants. (41) EPA will likely set out criteria in the Federal Register, which will let the producer or manufacturer decide whether the product is Generally Recognized As Safe (GRAS). If the risk associated with the product has been changed, it is likely that EPA will require pre-market approval. However, if the risk associated with the product is similar to that of traditional breeding, it is unlikely that EPA will require a tolerance.

The impact of a safer pesticide policy on the current tolerance setting process is not clear. Given the somewhat mixed reaction to FDA's policy towards bioengineered foods in June 1992, it is possible that bioengineered pesticides may also receive some negative consumer response. However, not everyone would be a critic. If the expedited process had additional resources, it would streamline the registration process for newer and safer pesticides, including bioengineered pesticides. There is support among some farmers for this new policy for they claim a strong need for a variety of different alternative pesticides so that pest strains do not build up immunities. A whole host of new and perhaps targeted pesticide products could assist farmers. The stated goal of this policy is to lower risk from pesticides, and it is in the tolerance-setting process that much of the risk of pesticides on human health is assessed.

There is also support among the public health community for a safer pesticide policy. A recent study by the Institute of Medicine, Emerging Infections: Microbial Threats to Health in the United States, lists some concerns about the diminishing supply of effective pesticides for controlling vector-borne diseases. Because of the expense of gathering required safety data, some pesticide chemical manufacturers have chosen not to register or reregister their pesticides. The report states that the new registration requirements have limited the circumstances under which some products may be applied. The result is that:

many pesticides that might have been used to control emerging vector-borne diseases are either no longer registered or not available in sufficient quantity....The committee recommends that the EPA develop and implement alternative, expedited procedures for the licensing of pesticides for use in vector-borne infectious disease emergencies. These procedures would include a means for stockpiling designated pesticides for such use. (42)

CONCLUSION

The 103rd Congress will likely revisit the issues surrounding sections 408 and 409 of FFDCA, which set the policy for regulating pesticide residues in foods. There is growing support for new congressional proposals which address how to improve the assessment of risk because current statutory inconsistencies have not allowed EPA to keep up with science. In addition, support for statutory changes has also come from the Bush Administration, with the EPA clearly stating that it wants a single, protective risk standard which would apply to all pesticide residues in food. As pesticide manufacturers develop newer pesticides to keep up with changing growing conditions, they are looking towards the Congress and the Clinton Administration to set a consistent policy towards registration. In addition, consumer concerns about residues in foods remain high. Some consumers and public health officials want to see any risks from residues be balanced with the benefits of an adequate and wholesome food supply and which protect against vector-borne infectious diseases. Others object to any level of risks from residues regardless of the benefits. However, the "zero risk" requirement of the Delaney Clause in section 409 has become scientifically unmanageable.

APPENDIX. Glossary

Source: Compiled by the Congressional Research Service.

Endnotes

1. The Delaney Clause, added to the FFDCA in 1958, provides "that no additive shall be deemed to be safe if it is found to induce cancer when ingested by man or animal, or if it is found, after tests which are appropriate for the evaluation of the safety of food additives, to induce cancer in man or animals...Section 409 (21 U.S.C. 348 (c)(3)(A)), the Food Additives Amendment of 1958.
2. Motions for Stay Filed on Delaney Clause Court Decision. Pesticide & Toxic Chemical News. Oct. 7, 1992. p. 3-4.
3. Lowrance, William W. Of Acceptable Risk: Science and the Determination of Safety. Los Altos, CA. William Kaufmann, Inc. 1976. p.8.
4. U.S. Library of Congress. Congressional Research Service. Proposed Changes to Policies Governing Pesticide Residues in Foods. Report No. 92-179 SPR, by Donna U. Vogt. Washington, 1992.
5. This report does not discuss the monitoring of foods for compliance with the tolerances set by EPA. The agencies responsible for this enforcement are the Food and Drug Administration (FDA), under the Secretary of the Department of Health and Human Services (DHHS), and the U.S. Department of Agriculture (USDA). The FDA enforces tolerances for all foods except meat, poultry, and egg products, which USDA enforces.
6. EPA's "concentration policy" has developed in the last ten years. Prior to that time, EPA did not require extensive testing for pesticide residue concentration in processed foods. Currently, EPA scientists have a greater ability to detect residues in a larger variety of foods.
7. Rodgers, William H., Jr. Environmental Law: Pesticides and Toxic Substances. v. 3. St. Paul, Minn., West Publishing Co., 1988. p. 274-278.
8. The Delaney Clause stands in contrast with other environmental statutes. None of the other major statutes such as FIFRA, the Toxic Substances Control Act, and the Clean Air Act, have risk-only criteria and "zero-risk" like Delaney at the same time.
9. U.S. Environmental Protection Agency. Regulation of Pesticides in Food: Addressing the Delaney Paradox Policy Statement. Federal Register. v. 53, no. 202. Oct. 19, 1988. p. 41107.
10. This paragraph contains excerpts from National Research Council. Board on Agriculture. Committee on Scientific and Regulatory Issues Underlying Pesticide Use Patterns and Agricultural Innovation . Regulating Pesticides in Foods: The Delaney Paradox. Washington, D.C. National Academy Press, 1987.
11. U.S. Environmental Protection Agency. Regulation of Pesticides in Food: Addressing the Delaney Paradox Policy Statement. Federal Register. v. 53, no. 202. Oct. 19, 1988. p. 41104.
12. ---- Section 409 Food Additive Regulations; Order Responding to Objections to EPA's Response to Petition Requesting Revocation of Food Additive Regulations. Final Order. Federal Register. v. 56, no. 37. Feb. 25, 1991. p. 7755.
13. U.S. Library of Congress. Congressional Research Service. Proposed Changes to Policies Governing Pesticide Residues in Foods. Report No. 92-179 SPR, by Donna U Vogt. Washington, 1992.
14. U.S. Environmental Protection Agency. Section 409 Tolerances: Response to Petition Requesting Revocation of Food Additive Regulations. Federal Register. v. 55, no. 80. Apr. 25, 1990. p. 17560.
15. The motion concluded that "There is no substantial harm to the other parties in this litigation or to the public at large by staying issuance of the mandate for a short time. The added lifetime risks of contracting cancer from the food tolerances at issue in this case range from approximately 1 in 10,000,000 people to 2 in 100,000,000,000 (or 1 cancer every 15,000 years). Admittedly, the risks at issue in this case are truly de minimis and no meaningful or concrete harm can come from a 90-day stay of issuance of the court's mandate." Motions for Stay Filed on Delaney Clause Court Decision. Pesticide & Toxic Chemical News. Oct.. 7, 1992. p. 3.
16. Pesticide & Toxic Chemical News. EPA Petitioned to Not Revoke Section 408 Tolerances. Sept. 16, 1992. p. 11.
17. Amendments to FIFRA in the 1990 farm bill eliminated the need for field residue data for a minor use pesticide from geographic areas where the pesticide will not be used.
18. U.S. Congress. Office of Technology Assessment. Pesticide Residues in Food: Technologies for Detection. Chapter 8. Summary and Options. OTA-F-398. Washington, U.S. Govt. Print. Off. Oct. 1988. p. 87.
19. EPA decided not to use routinely the more recent 1987-88 survey in its dietary exposure calculations because it had serious concerns about the survey's validity for estimating consumption patterns for certain important subpopulations (such as infants and children). These concerns were reported by a General Accounting Office (GAO ) study which has criticized the 1987-88 NFCS saying that it under-represents certain subgroups that may be exposed to multiple concentrations of pesticide residues in foods. U.S. General Accounting Office. Pesticides: Food Consumption Data of Little Value to Estimate Some Exposures. GAP/RCED 91-125. May 22, 1991. A second GAO report concluded that the 1987-88 NFCS may not be representative of the U.S. population because of the survey's low response rate and discrepancies in the data collection. U.S. General Accounting Office. Nutrition Monitoring: Mismanagement of Nutrition Survey Has Resulted in Questionable Data. GAO RCED 91-117. July 1991.
20. Conversation with David Kimbell, Environmental Protection Specialist, Policy and Special Projects Staff, Office of Pesticide Programs. Environmental Protection Agency. June 25, 1992. (703) 305-7102.
21. J.R. Tomerlin and R. Engler. Estimation of Dietary exposure to pesticides using the Dietary Risk Evaluation System, In B.G. Tweedy, H.J. Dishburger, L.G. Ballantine, J. McCarthy (eds). Pesticide Residues and Food Safety: A Harvest of Viewpoints. American Chemical Society, Washington, D.C. p.192-201.
22. U.S. General Accounting Office. Guidelines Needed for EPA's Tolerance Assessments of Pesticide Residues in Food. Statement of Richard L. Hembra, Director. Environmental Protection Issues. Resources, Community, and Economic Development Division. Before the House Subcommittee on Health and the Environment, Committee on Energy and Commerce. May 17, 1989. p. 15. Also see GAO/RCED 86-125. Pesticides: EPA's Formidable Task to Assess and Regulate Their Risks. Apr. 1986. p. 123.
23. Telephone conversation with Marguerite L. Leng. Leng Associates specializes in pesticide registration and international regulatory affairs. 1714 Sylvan Lane, Midland, Michigan 48640-2538 (517) 832-2624.
24. The NOEL is used by toxicologists more often than the no-observed-adverse-effect-level or NOAEL because they would not like to make a distinction between any adverse health effect in the animal and any observable effect. At EPA any effect is presumed to be adverse.
25. Tomerlin, J. Robert and Christine F. Chaisson. Food Safety: What Your Mother Didn't Tell You. Proceedings of the 43rd Annual Reciprocal Meat Conference at Mississippi State University, Mississippi. v. 43. June 10-13, 1990.
26. EPA and FDA play active roles in interagency efforts to work out better risk assessment practices. Officials of both agencies attend meetings of the CRAM, the Committee on Risk Assessment Methodology of the National Academy of Sciences. This Committee is examining the fundamental assumptions underlying the quantitative risk assessment of carcinogens. Another interagency effort resulted in a uniform scaling procedure to assess cancer risk in the inter-species extrapolation among animals and between animals and humans in assessing carcinogenic risk. A third effort is being made to adopt a common default method of extrapolating cancer bioassay using the same mathematical model.
27. Levine, Tina E. Special Assistant to the Director, Registration Division, Office of Pesticide Programs, U.S. Environmental Protection Agency. Remarks entitled, Assessment and Communication of Risks from Pesticide Residues in Food. Food and Drug Law Institute. Nov. 7, 1990. p. 3.
28. Cogliano, Vincent James, W. Farland, P.Preuss, J. Wiltse, L. Rhomberg, C. Chen, M. Mass, S. Nosnow, P. White. Carcinogens and Human Health: Part 3. Science. v. 251. Feb. 8, 1991. p. 606-607.
29. Committee on the Institutional Means for Assessment of Risks to Public Health, Commission on Life Sciences, National Research Council. Risk Assessment in the Federal Government: Managing the Process. National Academy Press, Washington, D.C. 1983. p. 36-37.
30. Upton, Arthur C. Are There Thresholds for Carcinogenesis? The Thorny Problem of Low-level Exposure. Living in a Chemical World. Annals of the New York Academy of Sciences. v. 534. June 30, 1988. p. 863-884.
31. U.S. Environmental Protection Agency. Statement of Linda J. Fisher, Assistant Administrator for Prevention, Pesticides, and Toxic Substances before the Subcommittee on Environment, Energy, and Natural Resources, House Committee on Government Operations. July 23, 1992.
32. National Research Council. Board on Agriculture. Committee on Scientific and Regulatory Issues Underlying Pesticide Use Patterns and Agricultural Innovation. Regulating Pesticides in Foods: The Delaney Paradox. Washington, D.C. National Academy Press, 1987.
33. U.S. Library of Congress. Congressional Research Service. Proposed Changes to Policies Governing Pesticide Residues in Foods. Report 92-179 SPR, by Donna U. Vogt. Washington, 1992.
34. Committee Print of H.R. 3742 showing the amendment adopted by the Subcommittee on Department Operations, Research, and Foreign Agriculture on May 19, 1992. p. 143.
35. Telephone conversation with John Fleuchaus, Office of the General Council, EPA. (202) 260-7218.
36. Wolfe, Sidney. Has Delaney Outlived Its Time? Commentary. The Washington Times. Aug. 9 1992. p. B4.
37. U.S. Environmental Protection Agency. Incentives for Development and Registration of Reduced Risk Pesticides. Federal Register. v. 57, no. 139. July 20, 1992. p. 32140- 32145.
38. U.S. Congress. Office of Technology Assessment. New Developments in Biotechnology. 3: Field-testing Engineered Organisms Genetic and Ecological Issues. OTA-BA-350. Washington, U.S. Govt. Print. Off. May 1988.
39. Telephone conversation with Russ Snyder, Monsanto. October 29, 1992. (202) 783-2460.
40. Telephone conversation with Patricia Roberts, Lawyer, Environmental Protection Agency. August 24, 1992. (202) 260-7505.
41. Telephone conversation with Mary Jane Angello, lawyer. Environmental Protection Agency. Sept, 3, 1992. (202) 260-7523. Also see CRS Report 92-553 SPR, Foods and Biotechnology: FDA Policy on Foods Derived from New Plant Varieties. July 9, 1992.
42. Lederberg, Joshua, Robert E. Shope, and Stanley C. Oaks, Jr., eds. Emerging Infections: Microbial Threats to Health in the United States. Committee on Emerging Microbial Threats to Health. Division of Health Sciences Policy. Division of International Health. Institute of Medicine. Washington, D.C. National Academy Press. 1992. p. 164.