GAO

United States General Accounting Office

Report to Congressional Requesters

September 2000 CHILDREN AND

PESTICIDES

New Approach to

Considering Risk Is

Partly in Place

GAO/HEHS-00-175

Page 1 GAO/HEHS-00-175 Children and Pesticides

Contents

Letter 3

Appendixes Appendix I: Methodology 24

Appendix II: Three Pesticides Evaluated Under FQPA’s New

Requirements: Dicofol, Methomyl, and Phosmet 26

Appendix III: GAO Contact and Staff Acknowledgments 34

Tables Table 1: Key Pesticide Regulatory Requirements Added by FQPA 7

Table 2: Examples of Questions Considered in Safety Factor Reviews 11

Table 3: Safety Factor Decisions 13

Table 4: Results of Tolerance Reassessments Involving FQPA

Considerations 20

Figure Figure 1: Overview of Risk Assessment and Mitigation for Pesticide

Exposure 6

Abbreviations

EPA Environmental Protection Agency

FQPA Food Quality Protection Act of 1996

ILSI International Life Sciences Institute

OPP Office of Pesticide Programs
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United States General Accounting Office

Washington, D.C. 20548

Health, Education, and

Human Services Division

B-284334 Letr

September 11, 2000

The Honorable Edward M. Kennedy

The Honorable Barbara A. Mikulski

The Honorable Frank R. Lautenberg

The Honorable Jack Reed

United States Senate

Managing the risk of exposure to pesticides is important for all Americans,

but especially for children, whose developing systems can be more

susceptible to harm. The Food Quality Protection Act of 1996 (FQPA)

requires the Environmental Protection Agency (EPA), which regulates the

use of pesticides at the federal level, to reevaluate the amounts of pesticide

residues allowed on or in food—known as tolerances. EPA must ensure

that the tolerances are safe, that is, that there is a reasonable certainty that

no harm will result from exposure from all food and nonfood sources. In

doing so, unless another safety factor is determined to be appropriate, EPA

is required to apply an additional 10-fold safety factor in setting tolerances

to ensure the safety of foods for children. EPA is also required to ensure

that there is reasonable certainty that no harm will result to children

specifically from aggregate exposure to a pesticide from all sources (such

as lawn treatments, household uses, and drinking water, as well as food). In

addition, EPA must consider available information concerning the

combined or cumulative effects on children from groups of pesticides that

may act on the body in similar harmful ways. The law requires EPA to

consider all these factors in reassessing tolerances for pesticide residues in

foods, and in doing so, EPA must give priority to pesticides that appear to

pose the greatest risk to public health.

You asked us to examine how EPA is applying these requirements of the

FQPA. We focused our efforts on three questions:

• What approach has EPA developed for making decisions about applying

the new safety factor?

• What progress has been made in considering aggregate exposure and

cumulative effects?

• What progress has been made in reassessing tolerances for pesticide

residues?
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This report is based in part on a review of documents related to safety

factor determinations and pesticide risk assessments, as well as a review of

EPA’s database for tracking tolerance reassessments. We supplemented this

analysis with interviews at EPA, as well as with federal health agencies,

chemical industry and environmental groups, and outside experts. We did

not evaluate EPA’s regulatory decisions or the quality of the data behind

them. Appendix I provides further details on our methodology. We

performed our work from October 1999 through July 2000 in accordance

with generally accepted government auditing standards.

Results in Brief When FQPA became law in 1996, EPA immediately began efforts to

consider the additional safety factor for children, using available methods

and data in an interim approach that has evolved over time. An internal

committee now recommends whether to apply the additional safety factor

in pesticide reviews, based on data completeness and evidence of

increased susceptibility in children. Using this approach, EPA has made

decisions about applying the additional safety factor for 105 of the more

than 450 pesticides to be reassessed. It determined that an additional safety

factor was necessary in 49 cases and not necessary in the remaining 56

cases.

EPA also has interim procedures in place for considering aggregate

exposure, which incorporate available data on exposures from food,

drinking water, and residential uses. Data on nonfood exposures have been

lacking for most pesticides, however, and methods for estimating and

combining such exposures are still being developed. EPA has not yet begun

to consider cumulative effects in the regulatory process. It has determined

that one group of pesticides that is considered to be high-risk, called the

organophosphates, will need to be assessed for cumulative effects, but

methods for doing so are still under development. The potential effects of

considering aggregate exposure and cumulative effects are beginning to

emerge. On June 8, 2000, after applying the additional safety factor and

conducting an aggregate exposure assessment for chlorpyrifos (an

organophosphate sold as Dursban, and the most widely used household

pesticide in the United States), EPA announced a need to substantially

reduce children’s exposure to this pesticide by reducing its use on foods

frequently eaten by children and by eliminating nearly all household uses.

EPA has not completed aggregate exposure reviews for all 39

organophosphates individually, but when it does, a cumulative assessment

will be required for the group, which may identify the need for additional

changes.
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EPA has reported progress in reassessing existing tolerances for pesticide

residues on foods, but relatively few of these allowable limits have changed

as a result of considering FQPA’s new requirements. The act called for

reassessing one-third of all existing tolerances by August 1999—a goal EPA

met. We analyzed a somewhat larger group, those counted as reassessed

through April 2000. For about 47 percent of these tolerances, the

manufacturer agreed with EPA to eliminate the tolerances and withdraw

the pesticides from those uses (a pesticide has a separate tolerance for

each food crop it is used on), before the additional safety factor or

aggregate exposures were considered. In most of these cases the pesticide

was no longer being used on a particular food crop or the manufacturer

decided not to maintain the ability to use it on a particular food crop. Most

of the remaining reassessments in the group we analyzed resulted in no

change. In reassessing tolerances, EPA has given priority to high-risk

chemicals. Some high-risk pesticides have been reassessed. However, the

only tolerances counted as reassessed for the high-risk organophosphate

pesticides were ones that were canceled voluntarily, because the

organophosphates will require a cumulative assessment before existing

tolerances can be formally reassessed.

Background In essence, evaluating and managing the risk from exposure to pesticides

involve determining the maximum safe level of exposure to a pesticide and

assessing whether expected actual exposure is below this maximum level.1

Figure 1 shows how these two steps relate to each other. As long as the

expected exposure remains lower than the maximum safe exposure, the

risk created by use of the particular pesticide is within acceptable limits

and usually no action is required. However, once expected actual exposure

levels exceed the maximum safe amount, EPA must determine the best

ways to reduce exposure below the safe level to mitigate the risk. Many

possible risk mitigation actions may be applied, ranging from prohibiting

an agricultural or residential use of the pesticide to changing directions for

its use (such as spraying less often). These mitigation steps are intended to

reduce overall exposure from all sources, including exposure through

pesticide residues on foods.

1

The word “pesticide” is used broadly here to include insecticides, herbicides, fungicides,

rodenticides, and the like, which are designed to prevent, destroy, repel, or reduce pests.
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Figure 1: Overview of Risk Assessment and Mitigation for Pesticide Exposure

a

If this pesticide is part of a group that acts on the body in similar harmful ways, EPA must assess risk

based on cumulative effects, that is, the combined aggregate exposure for each pesticide in the group.

New Law Fundamentally

Changed How Risks Are

Assessed

FQPA made several fundamental changes in how EPA assesses and

manages pesticide exposure risks to humans.2 Under FQPA, EPA must

reevaluate existing tolerances for pesticide residues in foods within 10

years. In doing so, EPA is required to (1) apply an additional 10-fold safety

factor in setting tolerances to ensure the safety of foods for children, unless

reliable data support a different factor; (2) ensure that there is reasonable

certainty that no harm will result to children from aggregate exposure to a

pesticide from food, drinking water, and residential sources; and (3)

consider available information concerning the cumulative effects on

children of pesticides that act in a similar harmful way (known as a

common mechanism of toxicity). These FQPA requirements also apply in

Assessing maximum safe level of exposure for humans Determining how much exposure is likely to occur

Testing

(usually by

manufacturer)

determines

maximum

safe level in

animals

Under previous approach,

EPA would set acceptable

level for humans at 1/100

of safe level in animals

Under new approach,

additional safety factor

reduces acceptable level to

1/1,000 of safe level in animals

unless data indicate some

other level is appropriate for

children

Analytical methods

and data applied

 Computer

 models

 Field studies

 Survey data

 Other scientific

 literature 

Maximum

safe level of

exposure

that should

be allowed

from all

sources a

Expected

aggregate

exposure

from all 

sources

Generally, if expected aggregate exposure is 

less than maximum safe level of exposure, 

the risk is presumed to be acceptable.

Multiple sources

considered

 Food

 Water

 Home pesticides

 Lawn and garden

 pesticides

 Other nonjob

 sources

If expected aggregate exposure exceeds 

maximum safe exposure, mitigation 

steps must be taken to reduce exposure.

Possible actions include prohibiting use 

or changing directions for use. 

?

2

FQPA amended existing laws that are intended to protect the public from harmful

exposures to pesticides. The amended laws were primarily the Federal Insecticide,

Fungicide, and Rodenticide Act (7 U.S.C. 136 et seq.) and the Federal Food, Drug, and

Cosmetic Act (21 U.S.C. 301 et seq.).
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setting tolerances for new pesticides that are being registered and for new

uses of existing pesticides. In reassessing existing tolerances, EPA must

give priority to pesticides that appear to pose the greatest risk to public

health. Table 1 provides a brief overview of these requirements.

Table 1: Key Pesticide Regulatory Requirements Added by FQPA

Among the difficulties EPA has faced in implementing FQPA requirements

is the fact that the scientific knowledge necessary to accomplish some of

these new mandates did not exist in 1996. EPA’s pesticide regulatory

process has traditionally focused on exposures from food and considered

each pesticide separately. Under FQPA the agency has been required to

develop the methods and data to perform the new aggregate exposure and

cumulative effects assessments, which incorporate exposures from

Requirement Explanation

Applying an

additional safety

factor for

children

To account for differences in sensitivity between humans and test

animals, as well as differences in sensitivity among different people,

EPA routinely applies a safety factor for humans that sets the maximum

acceptable or safe level of exposure to a pesticide at 1/100 of the

maximum amount observed as safe in animals. The additional safety

factor for children generally reduces the safe level by another factor of

10, thereby lowering it to 1/1,000 of the amount for animals.

Considering

aggregate

exposure

Aggregate exposure is the exposure to a single pesticide that a person

would be likely to face from all sources, including food, drinking water,

and home and garden use of the pesticide. Before FQPA, EPA was

required only to assess exposure from food, although in practice the

agency sometimes considered other sources as well.

Considering

cumulative

effects

The cumulative effects of exposure are those that a person would be

likely to face from the combined aggregate exposures to several

pesticides that act on the body in similar harmful ways. Groups or

classes of pesticides that act in a similar way are said to have a

common mode of action or a common mechanism of toxicity. When

EPA determines that a group of pesticides has a common mechanism

of toxicity, it must consider the aggregate exposure from every pesticide

in the group.

Reassessing

tolerances

A tolerance is the maximum legal amount of a pesticide residue that is

allowed to remain on a food commodity that has been treated with the

pesticide. It is usually expressed in parts per million or parts per billion.

The allowed residue from the use of one pesticide on one specific crop,

such as apples or asparagus, represents one tolerance. Thus a single

pesticide may have many tolerances. FQPA requires EPA to reassess

all tolerances in effect prior to passage of the law in August 1996 (9,721

tolerances for more than 450 pesticides) to ensure that they are safe for

children.
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nonfood sources and the combined effects of entire classes of pesticides

that were previously considered individually.

The first class of pesticides to be affected by cumulative assessment under

FQPA will likely be the organophosphates. EPA has identified the

organophosphates as a class of pesticides requiring cumulative assessment

because they can impair nervous system function by inhibiting the enzyme

cholinesterase. The organophosphates are older pesticides, and EPA

considers some of them to be more hazardous (although not all older

pesticides are necessarily more hazardous). They are of special concern

because of their toxicity and widespread use both in agriculture and in

homes and gardens, according to the National Research Council’s 1993

report, Pesticides in the Diets of Infants and Children.

3 One of them is the

single most widely used household pesticide in the United States—

chlorpyrifos, which is sold under such names as Dursban and Lorsban.

EPA’s Office of Pesticide

Programs Has Main

Responsibility for

Implementation

EPA’s Office of Pesticide Programs (OPP) has the lead responsibility for

implementing the new FQPA requirements within its existing system of

pesticide regulation. This system includes registering or licensing new

pesticide products for use in the United States and reevaluating older

pesticides to ensure that they meet current health standards and that their

risks are adequately mitigated (a process required to reregister the

pesticide for continued use).4 Nearly 900 people organized into nine OPP

divisions carry out these activities. Two divisions have the main

responsibility for managing pesticide risk assessments: the Registration

Division (for assessing new chemicals and new uses of existing chemicals)

and the Special Review and Reregistration Division (for assessing most

3

National Research Council, Pesticides in the Diets of Infants and Children (Washington,

D.C.: National Academy Press, 1993), pp. 17, 245-46.

4

As directed by the 1988 amendments to the Federal Insecticide, Fungicide, and Rodenticide

Act, EPA has been conducting a comprehensive review of pesticides initially registered

before November 1, 1984, to determine their eligibility for reregistration.
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conventional chemical pesticides for reregistration and for reassessing

tolerances as required by FQPA).5

To help conduct these risk assessments, the two divisions use analyses

provided primarily by another division, the Health Effects Division.

Scientists in the division examine the substantial body of studies and data

reports that under regulation are required to be submitted by the pesticide’s

registrant (that is, the applicant for registration, usually the manufacturer),

along with other available data, to ensure the reliability of the studies,

assess the toxicity of the pesticide under review, and estimate the risks of

exposure. Sources of possible exposure that are considered include water

and residential contamination, in addition to the traditional focus on food

exposures. The risk assessments are subject to internal peer review by the

Health Effects Division staff.

Approach for Making

Safety Factor

Decisions Continues to

Evolve

Soon after FQPA became law in 1996, EPA began to include consideration

of the additional safety factor for children in its pesticide risk assessments,

as required. EPA developed interim guidelines for determining whether this

additional safety factor should be applied, and these procedures have

evolved over time.6 Under this approach, an internal review committee of

scientists, managers, and other experts within OPP—the FQPA Safety

Factor Committee—takes lead responsibility for recommending whether

the additional safety factor should be applied, with OPP management

making the final decisions. By March 2000, this committee had reviewed

and prepared safety factor recommendations for 150 pesticides, and OPP

management had made final safety factor decisions for 105 of them.

5

While OPP regulates all types of pesticides, we focused our review on the largest group, the

conventional pesticides, leaving aside antimicrobials and biopesticides. These other types of

pesticides are the responsibility of OPP’s Antimicrobial Division and Biopesticides and

Pollution Prevention Division, respectively. Those two divisions both assess and manage the

risks associated with chemicals under their purview. FQPA standards apply, and reassessed

tolerances for antimicrobials and biopesticides are counted in the EPA Tolerance

Reassessment Tracking System.

6

EPA’s interim guidelines are operating policies and procedures that the agency follows to

make the decisions required by FQPA, such as whether to apply the additional safety factor

for children, while the process of developing more complete, formal policies and

procedures continues. Decisions made under interim guidelines may be revisited, if

appropriate, as methods and data are improved and policies refined.
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Approach for Considering

Additional Safety Factor

Has Evolved Since 1996

EPA began to consider the additional safety factor in its pesticide reviews

and tolerance reassessments soon after FQPA was passed. By October

1996, EPA had drafted an initial version of its approach to applying the

additional safety factor, and by January 1997 it had issued a notice

providing detailed guidelines for manufacturers on how pesticide reviews

for registration and reregistration would proceed, taking the new FQPA

requirements into account.7 In March 1997, EPA published an

implementation plan for FQPA that addressed how it would consider the

additional safety factor for children. The implementation plan called for

applying the following approach:

• EPA would require the additional 10-fold safety factor for children if the

agency lacked complete and reliable data to assess pre- or postnatal

toxicity relating to infants and children or if the data indicated pre- or

postnatal effects of concern.

• If data were incomplete, an additional safety factor between 3 and 10

would be applied, with the size of the factor depending on how much

information was incomplete and the seriousness of any concerns about

effects.

• If data were sufficient to demonstrate no potential pre- or postnatal

effects of concern, no additional safety factor would be applied.

To make recommendations to OPP management about applying the safety

factor in individual pesticide risk assessments, OPP established a Safety

Factor Committee in February 1998.8 This internal peer review group is

composed of risk assessors (including toxicologists and exposure experts)

from OPP science divisions and risk managers (staff responsible for risk

mitigation activities) from the divisions that regulate most of the

7

Pesticide Registration Notice 97-1 stated that data requirements for pesticide registrations

and reregistrations would not be revised immediately to reflect the new FQPA requirements.

The notice included, however, a detailed outline of the additional data and studies that EPA

was requesting from registrants on a voluntary basis to support timely pesticide reviews

under FQPA.

8

EPA officials told us that, up to that time, two predecessor groups had conducted the

reviews. The first was the Reference Dose Committee in the Health Effects Division, which

was responsible for reviewing pesticide toxicity data at the time FQPA was passed. It

continued its reviews, including consideration of the new safety factor, until summer 1997,

when a new group was established for that purpose. This second group was the Hazard

Identification Assessment Review Committee, a committee that still reviews the toxicology

database for each pesticide to determine what adverse health effects the pesticide might

cause. This committee performed a limited number of reviews, based on toxicity data only.
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chemicals. The committee’s procedures call for systematically reviewing

both toxicology and exposure data for each chemical, focusing on two

overriding concerns: (1) uncertainties in the data used for the toxicology

and exposure assessments (data gaps) and (2) evidence of increased

susceptibilities in infants and children (the potential for pre- and postnatal

toxicity).9 Examples of the types of questions considered in these subject

areas are presented in table 2.

Table 2: Examples of Questions Considered in Safety Factor Reviews

Committee members are encouraged to apply scientific judgment as well as

qualitative and quantitative data in reaching consensus on whether to

apply, reduce, or remove the safety factor. The committee considers

9

According to an EPA official, the data studies that are most useful in assessing pre- and

postnatal toxicity are the prenatal developmental toxicity studies in rats and rabbits, the

two-generation reproductive toxicity study in rats, and, when available, the developmental

neurotoxicity study in rats. All of these studies are done using pregnant and young animals.

The first two studies are always required for assessing food use pesticides, and the third

study (the developmental neurotoxicity study) is conditionally required.

Subject area Questions

Toxicology Do we have adequate hazard (toxicity) studies to evaluate risk to infants

and children?

Do these studies show enhanced susceptibility in infants and children?

That is, do the effects in the young occur at doses that do not cause

effects in adults?

Food

exposure

What kinds of residue databases are available for each crop (for example,

field study data or monitoring data) and what are their sources?

Is information available on percentage of crop treated?

According to food consumption data, which crops contribute significantly

to the diet for adults? For infants and children?

Drinking water

exposure

Are models or monitoring data used to estimate drinking water exposure?

If models are used, what scenarios are used in the model, and what are

the resulting estimated environmental concentrations?

If monitoring data are used, what kinds of data were collected and under

what conditions (for example, from vulnerable areas at maximum label

rates)?

Residential

exposure

Is the compound used around the home in such a way that children and

infants may be exposed? What are the frequency and rate of application?

Are reliable biologically based exposure data or epidemiology data

available to support the results of the assessment (for example, incident

reports or Centers for Disease Control and Prevention biomonitoring

data)?
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written reports and oral presentations and seeks to reach a consensus in

each case on the FQPA safety factor it will recommend to OPP managers.10

As of March 2000 the committee had reviewed 150 pesticides and

submitted safety factor recommendations to OPP managers. In reviewing

the committee’s justifications for its recommendations, we found that

when the committee identified both toxicology data gaps and evidence of

increased susceptibility in children, the pesticides were most likely to

receive a recommendation for a 10-fold safety factor. When there was no

evidence of increased susceptibility, but incomplete data, a safety factor

was also recommended, but it was less than 10 when the data suggested

that a lower safety factor was sufficient. Pesticides with neither increased

susceptibility nor data gaps usually received a recommendation for no

additional safety factor.

While EPA has incorporated consideration of the new safety factor in its

pesticide reviews, it has continued efforts to refine its policies on applying

the safety factor. A formal policy document on the safety factor has been

developed (it is not a regulation), which discusses in detail the legal

framework, overall approach, and related toxicology and exposure issues.

It is much more extensive than the guidelines under which the Safety

Factor Committee has been operating, but is consistent with them. An EPA

official explained that the two documents serve somewhat different

purposes, with the policy document providing comprehensive discussion

of the issues and the operating procedures translating those policies into

practical guidelines. The safety factor policy document was released for

public comment in 1999. As of July 2000, an agency official told us that EPA

was still assessing the comments it had received, and the document had not

yet been issued in final form.

No Additional Safety Factor

Has Been Applied in Half of

Decisions

OPP senior managers make the final decisions about whether to apply the

additional safety factor for children, based on the Safety Factor

Committee’s recommendations and other considerations. As of the end of

March 2000, OPP had made safety factor decisions for 105 of the 150

pesticides the Safety Factor Committee had reviewed. OPP determined

that a safety factor to protect children, in addition to the routinely applied

10In the few cases in which the committee could not reach a consensus recommendation, a

memorandum was prepared to division directors for their decision. An example of this

situation is dicofol, a pesticide case described in app. II.
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100-fold safety factor, was necessary in 49 cases and that available

evidence was sufficient to show that an additional safety factor was not

required in 56 cases (see table 3). For the organophosphate pesticides, OPP

decided to apply the additional safety factor in 24 cases and not to apply it

in 15.

Table 3: Safety Factor Decisions

In most cases, OPP managers adopted the committee’s recommendations

for the level of safety factor to protect children, but in some cases they

increased those levels. In 19 of the 105 decisions, the factor was increased

(made more protective) to account for other types of uncertainties. OPP

officials said these uncertainties most often related to serious data gaps or

special concerns about the severity of a pesticide’s health effects. In 5

cases, OPP increased the combined safety and uncertainty factors to

greater than 10-fold.11

To provide an indication of whether EPA was following its procedures, we

selected three high-risk pesticides of different types (including one

organophosphate) that had gone through the safety factor review process

and asked a consultant with expertise in environmental toxicology to

review the process and results. These three examples are described in

appendix II. The consultant concluded that in all three cases EPA’s actions

were thorough and its conclusions reasonable.

Type of pesticide

OPP decision

Number

reviewed No additional factor 3-fold factor 10-fold factor

Factor greater than

10-fold

Organophosphates 39 15 12 10 2

All others 66 41 11 11 3

Total 105 56 23 21 5

Percentage of total 53% 22% 20% 5%

11OPP most often applied a higher safety factor when a risk assessment used a “lowestobserved-adverse-effect level” in animal studies as a threshold no-harm level, instead of the

preferred “no-observed-adverse-effect level,” and thus was less certain and protective.

Safety factors for one pesticide, for example, were increased by the FQPA 10-fold factor for

children and multiplied by an additional 10-fold factor for uncertainties.
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Procedures Are in

Place for Considering

Aggregate Exposure

but Not Cumulative

Effects

EPA has interim procedures in place for considering aggregate exposure in

its pesticide reviews and tolerance reassessments. These procedures

incorporate available data on exposures from drinking water and

residential uses, along with food exposures. Efforts are being made to

improve available data on nonfood exposures and the methods for

estimating combined exposures to individual pesticides from all sources.

Efforts to consider the cumulative effects of exposure to groups of similar

pesticides have not progressed as far as those for aggregate exposure. EPA

has adopted policies for identifying classes of pesticides that have a

common mechanism of toxicity, but methods for conducting cumulative

assessments for these classes of pesticides are still under development. As

a result, EPA has not yet considered cumulative effects in its pesticide risk

assessments. In the case of the organophosphates—and chlorpyrifos in

particular—the potential effects of aggregate exposure and cumulative

assessments, in terms of needed mitigation steps, are beginning to emerge.

Interim Procedures for

Aggregate Exposure

Assessments Are in Place

Although formal policy guidance for performing aggregate exposure

assessments has not yet been issued in final form, EPA has interim

procedures in place for considering aggregate exposure using available

data and methods.12 Traditionally, EPA has assessed the risk of food use

pesticides on the basis of estimated exposure from all foods containing

residues of the pesticide. Under FQPA, EPA must also take into account the

amount of exposure to each pesticide that is likely to occur from drinking

water and from uses in and around the home. Common residential uses

include lawn and gardening uses, pet applications, and roach and termite

treatments. Not all pesticides have residential uses, but for those that do,

adding those types of exposures to food and water exposures might push

the total beyond the maximum safe level of exposure, leading to a need for

mitigation steps and possible changes in tolerances.13

Because of its traditional focus on pesticide exposures from foods, EPA’s

data and methods for estimating food exposures are relatively highly

developed, but for most pesticides the agency has lacked the data and

12The latest draft of the policy guidance for performing aggregate exposure assessments,

dated October 1999, was being revised to respond to public comments for release in

summer 2000.

13In app. II, phosmet provides an example of a pesticide with residential uses of concern, in

this case as an insecticide for home and garden use and a flea dip treatment for dogs.
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methods to estimate nonfood exposures from drinking water and

residential uses. Moreover, EPA has lacked a method for combining

exposures from these sources to estimate aggregate exposure. While such

data and methods are being developed, the agency is using an interim

approach that relies on available data and conservative scientific

judgments to protect health; that is, in most cases the high-end estimates

for drinking water and residential exposures are added to the estimated

food exposure.

Estimating exposures from pesticides used in and around the home has

been a particular challenge for EPA. In a working paper on assessing these

residential exposures, EPA stated that it relies primarily on the scientific

literature and industry sources because it lacks data for most pesticides to

characterize exposures from nonfood sources. Many types of needed data

still are not available. For example, an official told us that results from an

effort initiated in 1995 to collect data on outdoor residential exposures

(mainly from lawn chemicals) are only now coming in, and other efforts to

collect data on indoor residential exposures and commercial pesticide

applications are still under way. Methods for using such data to estimate

residential exposures are being developed, which, when approved by EPA’s

Scientific Advisory Panel, will apply to both aggregate exposure and

cumulative assessments. EPA intends that ongoing development and

refinement will follow, as the agency gains experience with the methods.

Development of Methods to

Assess Cumulative Effects

Is Under Way

Developing ways to assess both aggregate exposure and cumulative effects

has been more difficult and time-consuming than EPA anticipated, but

developing approaches to cumulative effects assessment has proved

particularly difficult. Experts in toxicology, exposure assessment, and risk

assessment methodologies have indicated that the science necessary to

successfully factor in these types of exposures, especially for cumulative

effects, is a work in progress. Beginning in 1997, EPA contracted with the

International Life Sciences Institute (ILSI)14 to convene workshops that

EPA hoped would bring together representatives of industry and academia

and other interested parties to participate in developing the new exposure

assessment policies required under FQPA. An ILSI group worked on

14ILSI is a nonprofit worldwide foundation established in 1978 to advance the understanding

of scientific issues relating to nutrition, food safety, toxicology, risk assessment, and the

environment. Its Risk Science Institute, established in 1985, seeks to advance and improve

the scientific basis of risk assessment.
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aggregate exposure assessment methods in 1997 and 1998, and another

workshop reported on a framework for cumulative risk assessment in 1999.

Because of the complexity of the scientific issues involved, EPA has

included considerable review by experts both inside EPA (including staff

and advisory committees) and in the academic and research communities

in its development of ways to measure aggregate exposure and cumulative

effects. According to one EPA official, while this peer review likely

provided benefits, it also slowed the process. The review has come from

such groups as EPA’s Scientific Advisory Panel and the Tolerance

Reassessment Advisory Committee, which also have provided review of

policies related to other aspects of implementing FQPA.15 The Scientific

Advisory Panel, which has been the main source of ongoing peer review,

now meets about every 2 months for 4 to 5 days, the official told us. All

panel meetings are open to the public, industry, and environmental groups.

Obtaining review from the Tolerance Reassessment Advisory Committee

required substantial time and resources, according to the official, because

many background and policy documents had to be prepared.

To put cumulative assessment in place, EPA first needed methods to

identify groups of pesticides that act on the body in similar ways to cause

adverse health effects. A January 1999 document laid out the principles

EPA applies to determine if a group of pesticides acts through a common

mechanism of toxicity. Using these principles, EPA has identified the

organophosphates as one such group of pesticides because they

impairnervous system function by inhibiting the enzyme cholinesterase.16

The next step, developing the methods for actually conducting cumulative

assessments, has been more difficult and time-consuming, and the first

15The Scientific Advisory Panel is a scientific peer review group that advises EPA on major

issues. It has reviewed and commented on science policy issues and their related guidance

documents, including the policies and procedures for applying the safety factor and

methods for aggregate exposure and cumulative assessments. Panel members are mainly

from academia or other government agencies. The Tolerance Reassessment Advisory

Committee met from May 1998 through October 1999. It included representatives of the

pesticide industry, agricultural interests, and environmental groups who were convened by

EPA to identify key science policy issues affecting risk assessment. It was replaced by a new

group, the Committee to Advise on Reassessment and Transition, in June 2000.

16According to an EPA official, OPP has identified two other groups of pesticides that have a

common mechanism of toxicity and are candidates for cumulative risk assessment: the

cholinesterase-inhibiting carbamates and some of the chloroacetanilides.
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draft of the methodology was not released for public comment until June

2000.17

EPA has not yet conducted a cumulative assessment. In addition to the

need for an acceptable methodology, a cumulative assessment requires

aggregate exposure assessments for each of the individual pesticides in the

cumulative effects group. While aggregate exposure assessments are in

process for the 39 organophosphates, they are not all complete.

Nonetheless, EPA agency staff expect to present a pilot test of the

proposed cumulative assessment methodology to the Scientific Advisory

Panel in September 2000, using a case study of 25 organophosphate

pesticides (including 7 chemicals with residential uses and 2 with water

residues). The pesticides will not be named, to encourage focus on the

assessment process, but the data will be real and fairly complete.

Potential Effects of

Aggregate Exposure and

Cumulative Assessments

Beginning to Emerge

EPA currently lacks the methods to consider cumulative effects associated

with classes of pesticides that have a common mechanism of toxicity, such

as the organophosphates, but the potential effects of aggregate exposure

assessment can be seen in the example of chlorpyrifos (sold under such

names as Dursban and Lorsban), a major organophosphate pesticide that

has many food and residential uses. Chlorpyrifos is found in many insect

sprays and is the single most widely used household pesticide in the United

States. It is also used by many commercial growers. In this instance, EPA

has applied an additional 10-fold safety factor to protect children and has

assembled considerable data about aggregate risk from the many sources

of possible exposure to chlorpyrifos. At a technical briefing on June 8,

2000, EPA announced agreement with the pesticide’s manufacturer to

eliminate all home, lawn, and garden uses of the pesticide, to eliminate the

majority of termite control uses, and to significantly lower allowable

pesticide residues on several foods regularly eaten by children, such as

apples, grapes, and tomatoes. These mitigation steps are intended to

reduce expected aggregate exposure below the maximum safe level.

Whether actions similar to those for chlorpyrifos will result from

considering aggregate exposures to other less widely used

organophosphate pesticides is unknown. However, when EPA conducts a

cumulative assessment, combining aggregate exposures for all the

17The draft was released for public comment on June 29, 2000. Following the comment

period, EPA plans to revise the draft and publish it in final form, but no date has been set.
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pesticides in this group, additional mitigation steps may be necessary to

protect children’s health.

EPA Has Made Some

Progress in

Reassessing

Tolerances to Date

EPA has made some progress in reassessing existing tolerances, as

required by FQPA, but relatively few of these allowable limits for pesticide

residues have changed as a result of considering the law’s new

requirements. As of April 2000, EPA reported that it had reassessed nearly

3,500 tolerances for about 300 pesticides.18 However, nearly half of these

tolerance reassessments did not require consideration of the additional

safety factor for children or aggregate exposure, because the manufacturer

agreed with EPA to voluntarily eliminate the tolerances and withdraw the

pesticides from those uses. Most of the other reassessed tolerances were

unchanged. Although EPA has given priority to reassessing tolerances for

high-risk pesticides, reassessments for the high-risk organophosphate

pesticides cannot be completed until a cumulative assessment has been

done for the group.

EPA Reports That Nearly

3,500 Tolerances Have Been

Reassessed

FQPA requires EPA to reassess all food use tolerances that were in effect

prior to passage of the law in August 1996—9,721 tolerances—to ensure

that the maximum residue levels they allow reflect any changes that might

result from the act’s new protections. EPA must complete these tolerance

reassessments within 10 years of FQPA’s enactment on a specific schedule:

one-third by August 1999, two-thirds by August 2002, and the rest by August

2006.

According to EPA, 3,290 tolerances (34 percent of the total) had been

reassessed by August 1999, the date of its first deadline. EPA also

announced that 2,178 (66 percent) of those reassessed tolerances were for

pesticides in the highest risk group. By April 2000, when we conducted our

analysis, the number of tolerance reassessments stood at 3,471, or 36

percent of the total.

18EPA sets a tolerance for each use of a pesticide on a single food product; thus pesticides

applied to many types of food will have multiple tolerances. Some pesticides have more

than 100 tolerances.
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Nearly Half of Tolerances

Were Eliminated Voluntarily

Our analysis of the 3,471 tolerances that EPA counted as reassessed in

April 2000 showed that nearly half of them—1,638 tolerances, or 47

percent—did not involve consideration of the new FQPA requirements.

Most of these (1,257) were eliminated or canceled by EPA, with the

manufacturer’s agreement, before risk assessments for the associated

pesticides were completed.19 Tolerance reassessments considered to be

voluntary removals or cancellations generally fell into two categories:

• Tolerance no longer needed. When a particular use (for example, on

apples) has been removed from the list of registered uses for a pesticide,

a tolerance is no longer needed for that use. There were cases in which

tolerances for previously removed uses had not yet been canceled, and

if they were not needed for imported foods, EPA completed the

cancellation process.20

• Manufacturer withdraws support. Manufacturers may withdraw support

for certain tolerances for a variety of reasons. For example, they may

determine that the costs of continued registration of the pesticide for

that use—including the costs of additional testing and registration

fees—are not justified by market conditions. An EPA official told us that

in a number of these cases, risk concerns that the agency expressed

about the associated pesticide contributed to the manufacturer’s

decision to drop the tolerance.

Most Tolerance

Reassessments That

Considered FQPA

Requirements Were

Unchanged

Fifty-three percent of the tolerance reassessments (1,833) were based on

pesticide risk assessments that considered aggregate exposure and the

additional safety factor for children. Most of these tolerance

reassessments—1,421 tolerances, or 77.5 percent—resulted in no change

(see table 4). The remainder of the tolerances were revoked (eliminating

the use), lowered (allowing less residue), or raised (allowing more

residue).

19The remainder of the tolerances that were canceled in this way involved biological

pesticides regulated by another EPA division, inert ingredients and some other pesticides

exempted from FPQA’s requirements (for example, for not applying to food, such as use on

tobacco), and other special circumstances.

20An import tolerance is maintained for imported foods for which there is no U.S.

registration for the pesticide in question. FQPA applies the same standards to imports as it

does to other tolerances.
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Table 4: Results of Tolerance Reassessments Involving FQPA Considerations

EPA officials indicated that only a small percentage of tolerances were

lowered, even after the additional safety factor and aggregate exposures

were considered, because historically the agency has set tolerances

conservatively. As a result, they said, many tolerances were already at

levels that would pass FQPA’s more stringent requirements. Likewise, EPA

officials told us that their decisions to raise 175 tolerances (that is, to allow

an increased concentration of pesticide residue to remain on the food) do

not represent an unacceptable risk to children or the general population.

Instead, the raised tolerances reflect new data from additional studies or

field trials that allowed EPA to perform more refined analyses of pesticide

exposure and risk.

Tolerance Reassessments

for High-Risk

Organophosphates Have

Not Been Completed

FQPA required EPA to give priority to reassessing tolerances for high-risk

chemicals, and in August 1997 the agency published a Federal Register

notice21 that divided the pesticides with tolerances requiring reassessment

into three priority groups by level of risk. The highest priority group, Group

1, which EPA considers to be the highest risk, included the

organophosphates, probable cancer-causing chemicals, and other

pesticides of particular concern. This group accounts for the largest

proportion, about 57 percent, of all tolerances that need to be reassessed.22

Total reassessed

Tolerance decision

Kept same Revoked

Lowered (allows less

residue)

Raised (allows more

residue)

Number 1,833 1,421 98 139 175

Percentage 77.5% 5% 8% 9.5%

21Federal Register, vol. 62, no. 149, pp. 42020-30, Aug. 4, 1997.

22Group 1 (228 pesticides/5,546 tolerances), the highest-risk chemicals, includes the

organophosphates, carbamates, organochlorines, and probable carcinogens. Group 2 (93

pesticides/1,928 tolerances) includes the lower-risk possible carcinogens and all remaining

reregistration chemicals (those that were first registered before 1984). Group 3 (148

pesticides/2,247 tolerances) includes the remaining pre-FQPA pesticides with reregistration

eligibility decisions, the remaining post-1984 pesticides, biological pesticides, and the

remaining inerts.
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Of the 3,471 tolerances that EPA has counted as reassessed through April

2000, two-thirds (2,286, or 66 percent) were for pesticides in Group 1. This

represents reassessment of 41 percent of all tolerances for the high-risk

pesticides. Less than 30 percent (483 of 1,691) of tolerances for the highrisk organophosphate pesticides were counted as reassessed, and most of

these were canceled voluntarily. Even though safety factor decisions have

been made for 39 organophosphates and risk assessments including

aggregate exposure are in process, EPA has been unable to finalize the

pesticide risk assessments and their associated tolerance reassessments,

because the individual reviews must be combined in a cumulative

assessment for all of the organophosphates.

Conclusions FQPA brought substantial changes to EPA’s pesticide regulatory process,

and these changes are still works in progress. Some of the tools needed by

EPA to implement FQPA were not available when the law was enacted.

EPA set about developing the necessary procedures, methodologies, and

data almost immediately. The agency has adopted a series of interim

approaches while specifying, with the assistance of peer reviewers, more

refined permanent methods, which are now nearing completion. EPA has

made progress in reviewing pesticides and reassessing tolerances since

1996, but so far relatively few tolerances have changed as a result of

considering the new FQPA requirements. While it is too early to tell what

the future effects of FQPA may be, the next few years could bring

substantial changes, as the organophosphates and other groups of high-risk

pesticides are reconsidered in the light of their aggregate exposures and

cumulative effects. It appears that EPA’s recent decision on chlorpyrifos,

for example, will result in major changes in the uses of that pesticide that

are intended to protect people, and children in particular, from potentially

adverse health effects.

Agency Comments We provided a draft of this report for comment to EPA, which supplied

technical comments that we incorporated where appropriate.

We will send copies of this report to the Honorable Carol Browner, EPA

Administrator, appropriate congressional committees, and other interested

parties. We will also make copies available to others on request.
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Page 22 GAO/HEHS-00-175 Children and Pesticides

If you or your staffs have any questions about this report, please call me at

(202) 512-7119. Major contributors to this report are listed in appendix III.

Janet Heinrich

Associate Director, Health Financing

and Public Health Issues
Page 23 GAO/HEHS-00-175 Children and Pesticides
Page 24 GAO/HEHS-00-175 Children and Pesticides

Appendix I

Methodology ApApenednxidexiIs

To examine how EPA is making decisions about applying the new safety

factor for children, we obtained documentation for each FQPA safety

factor determination. This consisted of three documents: (1) a summary log

of recommendations made by the Safety Factor Committee as of March 21,

2000, with justifications for these recommendations, (2) a list of final

decisions made by OPP managers for regulatory purposes, and (3) a “Safety

Factor Report” dated March 22, 2000, which explains the differences

between the Safety Factor Committee recommendations and the final

safety factor decisions. We synthesized information from these lists with

other documentary evidence obtained from EPA, as well as information

from EPA’s Tolerance Reassessment Tracking System (discussed below), to

summarize the results of FQPA safety factor decisions made to date. In

addition, we obtained detailed documentation and support material for

three pesticides that were reviewed by the Safety Factor Committee and

asked a consultant with expertise in environmental toxicology, H.B.

Matthews, Ph.D., Society of Toxicology Congressional Fellow, to review

those cases in depth. We did this to provide specific examples of EPA

processes and their results and to determine whether EPA’s processes for

assigning FQPA safety factors seemed reasonable.

To determine what progress EPA has made in considering aggregate

exposure and cumulative effects, we obtained documents showing the

development of policies and procedures, including numerous interim

drafts, and interviewed EPA officials regarding the history behind the

development of these policies. We also held numerous discussions with

EPA officials to determine the extent to which EPA has assessed aggregate

exposure and cumulative effects in the pesticides reviewed since passage

of FQPA, and the schedule for the completion and implementation of the

policies. Information on EPA’s plans, schedule, and progress in reassessing

the group of organophosphate pesticides is available on the OPP Web site

at www.epa.gov/pesticides/op/status.htm.

Finally, to identify what progress has been made in reassessing tolerances,

we obtained EPA’s Tolerance Reassessment Tracking System database

current to April 11, 2000. EPA created this database to track the agency’s

progress in meeting the deadlines associated with FQPA’s requirement to

reassess all tolerances. The tracking system contains extensive information

on all permanent pesticide tolerances registered as of August 1996, as well

as data on each pesticide associated with the tolerances. In order to

examine the agency’s use of the FQPA safety factor in assessing risk for

each pesticide, we added to the database a field containing the specific

safety factor decisions for each chemical. Because most pesticides in the
Appendix I

Methodology

Page 25 GAO/HEHS-00-175 Children and Pesticides

tracking system have more than one tolerance, we associated each

pesticide’s safety factor with all tolerances for that chemical.

We used the tracking system to identify groups of tolerances and pesticides

with specific attributes by creating a series of database filters. For

example, by selecting for tolerances EPA counted as reassessed, which had

an FQPA safety factor decision, but were not reassessed administratively

through notices in the Federal Register,

1 we identified those tolerances that

were reassessed as the result of a complete pesticide risk assessment,

including an FQPA safety factor decision and consideration of aggregate

exposures. Similarly, we used various criteria to determine other attributes

of the tolerances EPA has counted as reassessed, such as pesticide type

(organophosphate, carbamate, organochlorine, and so on), risk priority

group (Group 1, 2, or 3), and the resulting tolerance reassessment actions

(raise, lower, same, or revoke).

1

EPA officials told us that the tolerances counted as reassessed administratively through

notices in the Federal Register were not the result of a full pesticide risk assessment and

hence were not affected by an FQPA safety factor decision.
Page 26 GAO/HEHS-00-175 Children and Pesticides

Appendix II

Three Pesticides Evaluated Under FQPA’s

New Requirements: Dicofol, Methomyl, and

Phosmet ApendxiI

We asked a consultant with expertise in environmental toxicology, H.B.

Matthews, Ph.D., Society of Toxicology Congressional Fellow, to help us

review three pesticide cases to provide detailed examples of how OPP

considers the new FQPA requirements in its pesticide risk assessments. In

these examples, we focused primarily on the work of the FQPA Safety

Factor Committee, but we considered other aspects of OPP’s review and

decision-making process as well.

We selected three pesticides for review, using the following criteria: the

pesticides selected must have received a final safety factor decision; must

have tolerances to be reassessed under FQPA; and must be high-risk Group

1 pesticides1 of different types, including an organophosphate; preferably

should have multiple uses (tolerances), including nonfood residential uses

requiring aggregate exposure assessment; and must be likely to affect

children through food and other exposures. The pesticides we selected

were dicofol, an organochlorine; methomyl, a carbamate; and phosmet, an

organophosphate.

We obtained documents to describe the OPP review process for these three

pesticides from the OPP officials who manage the FQPA Safety Factor

Committee. We provided these documents to our consultant for his review,

which focused on such basic questions as the following:

• As an overall conclusion, based on the input reports and committee

deliberations, does the Safety Factor Committee’s recommended safety

factor appear to be reasonable and reasonably well justified?

• Did the committee follow its own review criteria in a systematic way?

• Did the committee adequately justify its decisions on (1) data

completeness and reliability (data gaps) and (2) evidence of increased

susceptibility in children?

• How did the committee consider aggregate exposures?

• Was cumulative assessment addressed in any way?

Our expert reviewer prepared comments addressing these questions for

each of the pesticide examples, and in some cases provided additional

information and opinion based on his own knowledge and experience.

Those comments have been combined with a description of the pesticide

and a summary of its review history in the sections below.

1

Group 1 pesticides are those identified by EPA as the highest risk and whose tolerances

require priority reassessment under FQPA.
Appendix II

Three Pesticides Evaluated Under FQPA’s

New Requirements: Dicofol, Methomyl, and

Phosmet

Page 27 GAO/HEHS-00-175 Children and Pesticides

Dicofol

Description Dicofol is an organochlorine pesticide in EPA’s high-risk Group 1. It is used

primarily on cotton, apples, and citrus crops and has nonresidential uses on

lawns and ornamental shrubs (for example, it may be used by professional

applicators on golf courses and landscaping, but it may not be used by

homeowners). Dicofol was first registered as a pesticide in the United

States in 1957. There are 50 current food use tolerances registered for

dicofol, all of which have been reassessed under FQPA requirements.

FQPA Review History Dicofol was reviewed at one of the first meetings of the FQPA Safety Factor

Committee, on March 30, 1998. Information was excerpted from the

pesticide’s reregistration document, which was nearly “Toxicological

Considerations for FQPA Safety Factor Selection.”

The reregistration document’s “FQPA considerations” section presented

the following conclusions: (1) the data provided no indication of increased

sensitivity in young animals, but (2) a developmental neurotoxicity study

was required, but not available (a data gap), because dicofol is an

organochlorine, is structurally related to DDT (which is neurotoxic), and is

considered an endocrine disruptor. A safety factor of 3 was recommended.

The main concern in terms of exposure was for occupational users.

However, at that time there were two homeowner uses, and no data were

available to assess residential exposure. Because of this lack of data, the

reregistration document recommended that residential use of dicofol be

discontinued. The document stated that EPA did not have the methods or

the data to consider potential cumulative effects from dicofol and other

members of the organochlorine class of pesticides.

The Safety Factor Committee reviewed the information from the

reregistration document for dicofol in March 1998 but was unable to reach

a consensus decision because it was concerned that its recommendation

could set a precedent for other endocrine disruptors. After seeking

guidance from OPP division directors, the committee recommended a 3-

fold safety factor.

OPP managers accepted this recommendation, and the revised (July 2,

1998) and final (November 1998) dicofol reregistration documents issued

by EPA included the 3-fold FQPA safety factor. Reasons given were as
Appendix II

Three Pesticides Evaluated Under FQPA’s

New Requirements: Dicofol, Methomyl, and

Phosmet

Page 28 GAO/HEHS-00-175 Children and Pesticides

follows: (1) aggregate exposure concerns were reduced because the two

residential uses were dropped, (2) cumulative effects from dicofol and

other organochlorines could not be considered, (3) strong concerns

regarding occupational exposure remained, and (4) significant risk

mitigation actions were required, including voluntary cancellation of some

uses by the registrant. Eligibility for reregistration was contingent on the

results of a dermal toxicity study and a dislodgeable foliar residue study (to

be submitted).

Reviewer’s Comments Our reviewer noted that dicofol is an old pesticide, which is only

moderately toxic and not extremely persistent in the environment, with no

remaining residential uses. It raises concerns because of its structural

relation to DDT. Having considered the documents described above, he

reported that EPA’s review of dicofol was thorough, although this was one

of the first pesticides the Safety Factor Committee reviewed and its

procedures were not as explicit as they later became. In the reviewer’s

judgment, data for dicofol appeared to be complete, with the only identified

data gap being the need for a developmental neurotoxicity study; and the

decision that there was no evidence of increased susceptibility in children

was well justified. He concluded that EPA and the Safety Factor Committee

responded appropriately to FQPA requirements to consider aggregate

exposures for dicofol. EPA was not prepared to consider cumulative

effects at that time. The reviewer noted that because pesticides related to

dicofol have been removed from the market, cumulative effects from

dicofol and other organochlorines would be effectively limited.

Methomyl

Description Methomyl is a carbamate insecticide, also in EPA’s high-risk Group 1. It has

a wide variety of registered uses on field, vegetable, and orchard crops, turf

farms, livestock quarters, and commercial premises and refuse containers.

It was first registered in the United States in 1968. There are 80 current

food use tolerances for methomyl but no homeowner residential uses.

Ornamental and greenhouse uses were canceled voluntarily during the

course of the pesticide’s review in 1998. Tolerance reassessment under

FQPA has been completed.
Appendix II

Three Pesticides Evaluated Under FQPA’s

New Requirements: Dicofol, Methomyl, and

Phosmet

Page 29 GAO/HEHS-00-175 Children and Pesticides

FQPA Review History Methomyl was reviewed by the Safety Factor Committee on April 6, 1998.

The committee received a report from the internal toxicology review

committee (known as the Hazard Identification Assessment Review

Committee), along with a document known as the “FQPA Responses,”

which was prepared to address the committee’s specific questions in its

standard operating procedures.

The toxicology review committee’s report reviewed the toxicology

database, including a new study submitted by the registrant (21-day dermal

toxicity in rabbits). Data gaps were identified: acute and subchronic

neurotoxicity studies were required but not available. Consequently, data

on cholinesterase inhibition, behavioral effects, and nervous system effects

by the pesticide were missing. The neurotoxicity studies were required

because methomyl is a carbamate (a class of pesticides with known

neurotoxic effects) and neurotoxic effects from methomyl were seen in

dogs and rabbits. The requirement for a developmental neurotoxicity study

was noted as “reserved,” pending the results of the acute and subchronic

studies.

The Safety Factor Committee decided to recommend a 3-fold safety factor

for methomyl, based on (1) no indication of increased susceptibility in

children and (2) data gaps—specifically, the lack of acute and subchronic

neurotoxicity studies. The committee reviewed exposure data for food and

drinking water, but not for residential exposures because there were no

residential uses. Data quality was considered generally high, and realistic

assumptions (conservative models) were used.

The final reregistration document for methomyl, dated December 1998,

reflected the 3-fold FQPA safety factor decision. Because there were no

homeowner uses, the aggregate exposure assessment did not consider

residential exposures. However, because methomyl is produced when

another pesticide, thiodicarb, degrades, the aggregate risk assessment

considered methomyl residues from applications of both methomyl and

thiodicarb. The document also states: “The Agency does not have, at this

time, available data to determine whether methomyl has a common

mechanism of toxicity with other substances or how to include this

pesticide in a cumulative risk assessment. For the purposes of this

assessment, therefore, the Agency has not assumed that methomyl has a

common mechanism of toxicity with other substances.”
Appendix II

Three Pesticides Evaluated Under FQPA’s

New Requirements: Dicofol, Methomyl, and

Phosmet

Page 30 GAO/HEHS-00-175 Children and Pesticides

Reviewer’s Comments On the basis of his review of the EPA documents, our reviewer felt that a 3-

fold safety factor was appropriately conservative for methomyl. Input data

were provided to address the Safety Factor Committee’s review questions,

and the committee’s report indicated a thorough and careful review. That

report provided justification for reducing the 10-fold safety factor to 3-fold

by referring to sections of the source reports. Regarding the data gap for

acute and subchronic neurotoxicity studies in rats that was the reason for

the 3-fold safety factor, the reviewer noted that the gap did not seem to be a

pressing need, because similar data were available for two other species,

dogs and rabbits. His opinion was that if EPA had been willing to accept the

data for dogs and rabbits as an alternative to the rat data, the safety factor

might have been removed. The lack of a cumulative risk assessment in this

case was not likely a problem, the reviewer said, because of the short halflife of the chemical, meaning that it would dissipate rapidly.

Phosmet

Description Phosmet is a member of the largest class of insecticides, the

organophosphates. It is a broad-spectrum insecticide that causes systemic

toxicity by inhibiting cholinesterase, and there also have been concerns

about carcinogenicity. Phosmet is marketed for agricultural uses,

nonagricultural occupational uses, and homeowner uses to control pests,

including moths, beetles, weevils, lice, flies, fleas, and ticks. It is used on a

variety of fruit and vegetable crops (especially apples and peaches), tree

crops, nut trees, cotton, and ornamentals and in forestry. In addition,

phosmet is used for direct animal treatments on cattle, swine, and dogs

(flea and tick treatments). There are 43 current food use tolerances for

phosmet, of which 1 has been revoked voluntarily during the course of the

review. The remainder have yet to be reassessed, pending the required

cumulative assessment for the organophosphates.

FQPA Review History The Safety Factor Committee has reviewed phosmet twice since the law

passed in 1996. The first review was through what OPP calls its “OP

[Organophosphate] Marathon Meetings,” in which all of the

organophosphate pesticides, including phosmet, were reviewed together.

The Safety Factor Committee held its marathon meeting on June 15 and 16,

1998. In the case of phosmet, it concurred with the findings of the May 1998
Appendix II

Three Pesticides Evaluated Under FQPA’s

New Requirements: Dicofol, Methomyl, and

Phosmet

Page 31 GAO/HEHS-00-175 Children and Pesticides

toxicology review committee marathon meeting and recommended a 3-fold

FQPA safety factor, based on data gaps noted by the toxicology group.2

Specifically, the marathon meetings found that there was no evidence of

increased susceptibility to phosmet in young animals, but there were data

gaps for two types of neurotoxicity studies, and the requirement for a

developmental neurotoxicity study would depend on the results of those

other studies. Because no data were available to assess neurotoxicity,

cholinesterase inhibition, behavioral effects, or neuropathology for

phosmet, the 3-fold safety factor was recommended.

The second review of phosmet took place in summer 1999 after the

registrant submitted new data, including the acute and subchronic

neurotoxicity studies. On the basis of the results of these studies and

additional information from the registrant, the toxicology review

committee determined that the developmental neurotoxicity study was not

required. The Safety Factor Committee then concluded that there were no

remaining data gaps and no evidence of increased susceptibility. The

committee reported that adequate actual data, surrogate data, and/or

modeling outputs were available to satisfactorily assess dietary food and

residential exposures3 and to provide a screening level of drinking water

exposure assessment. Consequently, the committee recommended that the

FQPA safety factor be removed.4

OPP’s regulatory decision agreed with the Safety Factor Committee that no

additional FQPA safety factor was needed for phosmet, and the

reregistration document was revised to reflect the new data and decisions

2

There was also a separate toxicology review committee meeting on phosmet on September

4, 1997, as part of phosmet’s reregistration process. The discussion covered FQPA

requirements, such as data availability and data gaps—specifically, the need for a

developmental neurotoxicity study; possible endocrine disruption; and possible human

carcinogenic effects. The toxicology review committee recommended a 3-fold safety factor

at that time.

3

There were no chemical-specific data for phosmet to assess potential exposures to children

following outdoor residential applications. Therefore the draft Standard Operating

Procedures for Residential Exposure Assessments was used with surrogate data. This type

of analysis is intended to represent worst-case or screening-level assessments.

4

Phosmet’s potential for causing cancer in humans was also reassessed in 1999 through a

separate internal committee process. As a result, phosmet was classified in the category

“suggestive evidence of carcinogenicity, but not sufficient to assess human carcinogenic

potential.” This was consistent with the previous classification, and therefore no change

was needed in the risk assessment, which already took this level of cancer risk into account.
Appendix II

Three Pesticides Evaluated Under FQPA’s

New Requirements: Dicofol, Methomyl, and

Phosmet

Page 32 GAO/HEHS-00-175 Children and Pesticides

(see the version of October 7, 1999, and the February 9, 2000, public release

version). The risk assessment for phosmet concluded that (1) dietary food

and water risks are not a concern, even when combined, from either acute

or chronic exposure, (2) risks from residential exposure to treated dogs

and garden uses are a concern, especially for toddlers exposed to treated

dogs, and (3) there also are concerns for workers handling the pesticide

and regarding some ecological hazards (to birds, water, and honey bees).

This latest revised risk assessment describes the risks associated with use

of phosmet alone, and it may be revised again when EPA has conducted the

necessary cumulative assessment for the organophosphates.

Reviewer’s Comments Our reviewer concluded that through repeated reviews and reports, EPA’s

consideration of the data on phosmet has been very thorough. The Safety

Factor Committee reviews followed the standard operating procedures

systematically, and decisions on the completeness and reliability of the

data and the lack of data gaps were adequately justified. The committee’s

conclusion that there was no apparent developmental or reproductive

toxicity also was adequately justified and supported removal of the 10-fold

safety factor. Our reviewer stated that phosmet is rapidly metabolized and

degrades quickly under most environmental conditions; therefore it is

seldom detected in food or water, and exposures usually are very low. This

helps explain why aggregate exposure to phosmet is low. In our reviewer’s

opinion, calculated exposure of children resulting from contact with

treated dogs appeared to be conservative. Regarding the postponed

cumulative risk assessment, he noted: “Having worked on the problem of

cumulative risk assessment, I realize that issues relating to cumulative

risks present a very complex and controversial problem—a problem that is

not going to be easily solved. And the solution, when it comes, is not likely

to be to anybody’s complete satisfaction.”

Incidents of human poisoning from phosmet apparently are relatively

common, because our reviewer said that phosmet accounts for the largest

number of residential exposures to pesticides that result in treatment in a

health care facility. But he observed that these incidents are not an

indication of unusual toxicity as much as they are a result of incorrect use.

Almost all of the poisoning incidents resulted from failure to properly

dilute a concentrated formulation of phosmet for use as flea dip treatment

for dogs. Regarding the question of whether phosmet is likely to cause

cancer, our reviewer noted that the evidence is limited to reports of

increased incidences of tumors in mouse livers (which were marginally
Appendix II

Three Pesticides Evaluated Under FQPA’s

New Requirements: Dicofol, Methomyl, and

Phosmet

Page 33 GAO/HEHS-00-175 Children and Pesticides

statistically significant) and that there are differences of opinion as to the

relevance of increased mouse liver tumors to human health risks.
Page 34 GAO/HEHS-00-175 Children and Pesticides

Appendix III

GAO Contact and Staff Acknowledgments ApendxiI

GAO Contact Janet Heinrich, (202) 512-7119

Staff

Acknowledgments

The following staff made key contributions to this work: Ellen M. Smith,

Matthew W. Byer, Stanley G. Stenersen, and Katherine M. Iritani.

(101887) Letr
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