The endocrine disruptor screening program: How EPA plans to select an initial group of chemicals for...

On December 30,

2002, the United

States Environmen-

tal Protection

Agency (EPA) pub-

lished a notice re-

questing public

comment on its

planned approach

for selecting an ini-

tial group of chemi-

cals to be screened in the Agency’s Endocrine Dis-

ruptor Screening Program (EDSP).1

This article describes the EDSP and outlines

EPA’s proposed initial chemical selection process.

Background: Development of the EDSPEPA created the Endocrine Disruptor Screening

Program in response to a Congressional mandate

set out in the Federal Food, Drug, and Cosmetic Act

(FFDCA). A provision of the FFDCA enacted in

1996 directed the Agency to “develop a screening

program, using appropriate validated test systems

and other scientifically relevant information, to de-

termine whether certain substances may have an

effect in humans that is similar to an effect pro-

duced by a naturally

occurring estrogen,

or such other en-

docrine effect as the

[EPA] Administrator

may designate.”2

The FFDCA re-

quires EPA to “pro-

vide for the testing

of all pesticide

chemicals” and

gives EPA discretionary authority to “provide for

the testing of any other substance that may have

an effect that is cumulative to an effect of a pesti-

cide chemical if the Administrator determines

that a substantial population may be exposed to

such a substance.”

In addition, section 1457 of the Safe Drinking

Water Act (SWDA) gives EPA discretionary au-

thority to provide for testing, under the FFDCA

section 408(p) screening program, “of any other

substances that may be found in sources of drink-

Environmental Quality Management / Autumn 2003 / 43

© 2003 Wiley Periodicals, Inc.Published online in Wiley InterScience (www.interscience.wiley.com).DOI: 10.1002/tqem.10096

Kathleen Gibson

The Endocrine DisruptorScreening Program: HowEPA Plans to Select anInitial Group of Chemicalsfor Screening

EPA proposes a methodology for

choosing the first round of

chemicals to be screened under

the EDSP

Kathleen Gibson44 / Autumn 2003 / Environmental Quality Management

ing water if the Administrator determines that a

substantial population may be exposed to such

substance.”

EPA first described the proposed EDSP in the

Federal Register on August 11, 1998.3 The Agency

provided additional information on the program,

and solicited public comment, on December 28,

1998.4

EDSTAC Recommendations The specifics of the EDSP were based on the

recommendations of the Endocrine Disruptor

Screening and Testing Advisory Committee (ED-

STAC), an advisory group that was chartered

under the Federal Ad-

visory Committee Act.

EDSTAC’s members

represented a range of

affected stakeholders,

including the com-

mercial chemical and

pesticides industries,

federal and state agen-

cies, worker protection

and labor organizations, environmental and

public health groups, and research scientists. The

committee was asked to advise the Agency re-

garding:

• methods for chemical selection and priorities

for screening,

• a set of available, validated screening assays

for early application,

• ways to identify new and existing screening

assays and mechanisms for their validation,

• processes and criteria for deciding when addi-

tional tests beyond screening would be

needed and how to validate such tests, and

• processes for communicating to the public

about EDSTAC’s decisions and recommenda-

tions, and conveying the information devel-

oped during priority setting, screening, and

testing.

EDSTAC recommended that EPA’s program

address potential human and ecological effects;

examine effects on estrogen-, androgen-, and thy-

roid hormone-related processes; and include non-

pesticide chemicals, contaminants, and mixtures

in addition to pesticides.

A Tiered Approach Deciding which chemicals to test under the

EDSP, and in what order, was a major concern of

both EPA officials and EDSTAC members. The

universe of chemicals that may potentially act as

endocrine disruptors is extremely large—it is esti-

mated to number over 87,000—and includes not

only pesticides, but also commercial chemicals,

cosmetic ingredients, food additives, nutritional

supplements, and many chemical mixtures.

EPA clearly cannot hope to test all these sub-

stances. The Agency thus realized that a sound

methodology for prioritizing the review of chem-

icals was necessary in order to make the EDSP

work with reasonable efficiency.

Based on EDSTAC’s recommendations, EPA

developed a tiered approach for the EDSP. The

core elements of the approach are: Priority set-

ting, Tier 1 screening, and Tier 2 testing.

As used in the EDSP, the term “priority set-

ting” refers to determining which chemicals

should get priority in Tier 1 screening.

Tier 1 screening is envisioned as a battery of

screening assays that would identify substances

that have the potential to interact with the estro-

gen, androgen, and thyroid hormone systems.

Tier 2 testing would determine whether sub-

stances could cause endocrine effects mediated

by estrogen-, androgen-, and thyroid-related

processes. It would also seek to establish the

relationship between doses of an endocrine-ac-

Deciding which chemicals to testunder the EDSP, and in what order,was a major concern of both EPAofficials and EDSTAC members.

Environmental Quality Management / Autumn 2003 / 45The Endocrine Disruptor Screening Program

One recommendation of the SAB/SAP Sub-

committee was that EPA initiate the Tier 1 screen-

ing program with a set of 50 to 100 chemicals,

and then convene a panel of independent scien-

tists to review the screening data for the purpose

of evaluating and optimizing the Tier 1 screening

battery. EPA is proposing to adopt this SAB/SAP

recommendation in order to help further refine

the EDSP.

Implementing the EDSP EPA currently is implementing the EDSP in

three major parts. The Agency is:

• developing and

validating Tier 1

screening level as-

says, selecting the

appropriate screen-

ing assays for the

Tier 1 battery based

on the validation

data, and develop-

ing and validating Tier 2 tests;

• developing an approach for selecting an ini-

tial set of chemicals to go through Tier 1

screening; and

• developing the procedures the Agency will

use to require screening.

The December 30, 2002 notice dealt with the

second of these steps—that is, the development

of the approach that EPA will use to select the ini-

tial set of chemicals for Tier 1 screening.

Characteristics of Initial Chemicals To BeScreened

The December 2002 notice announced EPA’s

decision on how it proposes to select the first

group of chemicals to be screened under Tier 1 of

the EDSP.

tive substance administered in the test and any

effects.

Establishing Priority for Screening In December 1998, EPA proposed an approach

for establishing the priority of chemicals for Tier

1 screening.5

According to the Agency, the proposed ap-

proach reflected a concern that the quantity and

quality of exposure and effects information avail-

able about chemicals would be uneven. EPA

wanted to ensure that data-rich and data-poor

chemicals did not directly “compete” in the pri-

ority setting process, because such an approach

might lead to data-poor chemicals being ranked

low in priority simply because of lack of informa-

tion about them.

EPA characterized its recommendation as a

“compartment-based approach.” It was based on

exposure- and effects-related compartments,

even though the Agency recognized that effects

or toxicity data relevant to endocrine disruption

would be extremely limited for the majority of

chemicals.

To help compensate for the lack of relevant

toxicity data, EPA proposed conducting High

Throughput Priority Screening (HTPS) on all

non-pesticide active-ingredient chemicals with a

production volume in excess of 10,000 pounds

per year. EPA developed the Endocrine Disruptor

Priority Setting Database (EDPSD) to assist in as-

signing chemicals to compartments and setting

priorities.6

SAB/SAP RecommendationsA joint subcommittee of the EPA Science Ad-

visory Board (SAB) and the Federal Insecticide,

Fungicide, and Rodenticide Act (FIFRA) Scientific

Advisory Panel (SAP) also reviewed a set of scien-

tific issues related to the development of the

EDSP.

EPA developed the Endocrine Dis-ruptor Priority Setting Database

(EDPSD) to assist in assigningchemicals to compartments and

setting priorities.


As stated in the notice, EPA intends to focus

initially on pesticide active ingredients and

high production volume (HPV) chemicals with

some pesticidal inert uses. The pesticide inerts

to be considered are those with relatively large

overall production levels. According to EPA,

this approach will allow the Agency to focus on

a smaller and more manageable universe of

chemicals.

The proposed approach focuses on human ex-

posure-related factors, rather than on a combina-

tion of exposure- and effects-related factors. The

approach would exclude from Tier 1 screening

those chemicals for which the available effects in-

formation clearly

shows endocrine-me-

diated effects; such

chemicals would be

considered for pro-

posed Tier 2 tests,

mechanistic or special

studies, or hazard as-

sessment. EPA’s pro-

posal would also ex-

clude substances that the Agency anticipates have

low potential to cause endocrine disruption.

Although EPA’s general focus is on pesticide

active ingredients and inerts with relatively

greater potential for human exposure, the Agency

believes that the proposed approach will also

identify chemicals that have a high potential for

human exposure from non-pesticide uses, as well

as chemicals with widespread environmental ex-

posures to other organisms.

Selecting Chemicals for Tier 1 Screening: AnOverview

Based on the SAB/SAP review and recommen-

dations, EPA is proposing to select and screen ap-

proximately 50 to 100 chemicals drawn from pes-

ticide active ingredients and HPV chemicals with

some pesticidal inert uses (HPV/Inert chemicals).

The Agency hopes that this first round of

screening will help it further refine the EDSP. As

noted above, EPA intends to submit the data ob-

tained from the initial screenings to an inde-

pendent external panel of experts and request an

evaluation of potential program improvements.

Pesticide Active IngredientsEPA is proposing to use several databases to

identify pesticide active ingredients for screening

in the Tier 1 battery. These data focus on human

exposure by different pathways:

• consumption of food containing pesticide

residues,

• consumption of drinking water containing

pesticide residues,

• residential use of pesticide products, and

• occupational contact with pesticide-treated

surfaces.

For each of the pathways, EPA has identified

data it believes will help identify the active ingre-

dients likely to be among those having either rel-

atively more widespread or higher levels of

human exposure. The Agency proposes to assign

a higher priority for inclusion on the initial

screening list to chemicals that are likely to result

in human exposure via multiple pathways.

HPV/Inert Chemicals EPA is proposing to use a generally similar ap-

proach to identify HPV/Inert chemicals to be in-

cluded in the initial list for screening in the Tier

1 battery. However, EPA has less information on

exposures to HPV/Inert chemicals. For this rea-

son, the Agency has identified different data and

approaches for selecting an initial set of

HPV/Inert chemicals.

For HPV/Inert chemicals, EPA will focus on

several indicators of the potential for human ex-

posure, including production volume, specific

EPA is proposing to use severaldatabases to identify pesticide ac-tive ingredients for screening in theTier 1 battery.


In addition, the Agency plans to use exposure

data as the primary basis for chemical selection,

rather than using HTPS, Quantitative Structure

Activity Relationships (QSARs) or other hazard

data in conjunction with exposure data.7 The ini-

tial list of chemicals to be screened also would

not include mixtures. Moreover, the Agency does

not plan to accept public nominations of chemi-

cals for the initial list.

EPA is proposing to exclude from the initial

Tier 1 screening battery any chemicals that are no

longer produced or used in the United States. Al-

though these chemicals may have been detected

in the past, the discontinuation of their use and

manufacture means

that exposure to these

substances is likely to

be declining.

EPA notes further

that testing discontin-

ued substances would

present significant

practical difficulties.

For instance, the Agency would have difficulty

determining who would be required to conduct

the testing.

Selecting Pesticide Active IngredientsEPA is proposing to use several sets of criteria

for identifying pesticide active ingredients to be

given priority for screening. As noted above,

these criteria would focus on human exposure by

several different pathways: consumption of food

containing pesticide residues; consumption of

drinking water containing pesticide residues; res-

idential use of pesticide products; and occupa-

tional contact with pesticide-treated surfaces.

For each of these pathways, the Agency would

review existing databases to identify active ingre-

dients that are generally expected to be among

those having either widespread or high levels of

human exposure.

pathways of exposure, and presence in human

tissues. The Agency will review existing databases

to identify chemicals that are both pesticide in-

erts and HPV (defined as chemicals that are man-

ufactured or imported into the United States for

all uses in amounts equal to or greater than one

million pounds per year).

This first step will focus the initial Tier 1

screening on chemicals that have higher poten-

tial human exposure because of the large

amounts produced or imported.

EPA will also review existing data to identify

HPV/Inert chemicals that have been found to be

present in:

• human tissue,

• ecological tissues that have human food uses

(e.g., fish),

• drinking water, and

• indoor air.

Under this approach, an HPV/Inert chemical

that appears in monitoring data from one or

more of these media would have a higher priority

for testing than one that does not appear in mon-

itoring data from any media.

Comparison with General EDSP PrioritySetting

The proposed approach for selecting the ini-

tial list of chemicals to undergo Tier 1 screening

differs from the more general EDSP priority set-

ting approach. In particular, EPA plans to focus

chemical selection for this initial list on the sub-

set of chemicals that is subject to a statutory man-

date for screening (i.e., pesticide chemicals). As

noted, for the initial Tier 1 screening list, EPA pro-

poses to focus on pesticide active ingredients and

HPV chemicals that are used as pesticide inert in-

gredients—i.e., the chemicals that are specifically

mandated for testing under section 408(p) of the

FFDCA.

EPA is proposing to exclude fromthe initial Tier 1 screening battery

any chemicals that are no longerproduced or used in the United

States.


EPA has indicated that while its general focus

is on pesticide active ingredients with relatively

greater potential human exposure, this does not

mean that the list of active ingredients will not

contain substances that also have potentially

high levels of environmental exposure to ecolog-

ical receptors.

In practice, many pesticide active ingredients

that have a greater potential for human exposure

will also have a greater potential for exposure to

wildlife. For example, drinking water (one path-

way of human exposure) is also a pathway

through which aquatic life and many terrestrial

species are exposed.

Most of the data-

bases that EPA will

consider in evaluating

active ingredients for

exposure through

drinking water contain

monitoring data col-

lected on raw surface

water —i.e., at a point

before the water enters

a community water system. Thus, these monitor-

ing data show the levels of pesticide residues that

fish, amphibians, and other aquatic species will

encounter.

Similarly, when data show higher and more

widely distributed levels of pesticide residues in

food, EPA believes these results generally tend to re-

flect greater usage and persistence of the pesticide

on crops, and thus greater environmental loads.

Based on these considerations, EPA believes

that the approach proposed to evaluate pesticide

active ingredients, while focused on human ex-

posure, will also capture many active ingredients

with widespread environmental exposures.

The Food PathwayEPA proposes to identify the pesticide active

ingredients that are most frequently found as

residues on the top 20 foods that people

consume.

In order to identify these ingredients, the

Agency will first examine the most recent Con-

tinuing Survey of Food Intake by Individuals

(CSFII) to determine the mean amount of each

raw agricultural commodity consumed in the

general population.

The CSFII is a database derived from surveys

performed by the U.S. Department of Agriculture

(USDA). The most recent is based on a survey

conducted from 1994 through 1996, and supple-

mented with additional survey responses col-

lected in 1998.

In making its calculations, EPA converts the

reported food consumption for each survey re-

spondent into constituent raw agricultural com-

modities. For example, if a person reports having

eaten six ounces of beef stew, EPA would estimate

the amounts of each raw agricultural commodity

(including beef, carrots, potatoes, and other in-

gredients) used in making that quantity of beef

stew. The Agency would make similar conver-

sions for each of the different finished foods re-

ported in the CSFII.

EPA would then estimate the total amount of

each of the various raw agricultural commodities

eaten over the course of a day. This individual

food consumption database will provide the basis

for identifying the top 20 foods consumed, in

terms of mean daily consumption for the general

population.8

EPA would next characterize the pesticide

residue levels on these foods using information

collected by two federal agency monitoring pro-

grams: the USDA Pesticide Data Program (PDP),

and the Surveillance Monitoring Program con-

ducted by the U.S. Food and Drug Administra-

tion (FDA) Center for Food Safety and Applied

Nutrition.

PDP, which has been collecting pesticide

residue data since 1991, is designed to provide a

EPA proposes to identify the pesti-cide active ingredients that aremost frequently found as residueson the top 20 foods that peopleconsume.


Notwithstanding the limitations outlined

here, EPA believes that the approach it has cho-

sen is the most practicable.

The Water PathwayTo assess relative exposures to different pesti-

cides found in water, EPA would examine a num-

ber of different databases that contain the results

of programs that monitor surface and groundwa-

ter for pesticide residues. These databases contain

data collected by federal and state agencies, acad-

emicians, pesticide manufacturers, and others.

They include:

• EPA’s Pesticides in Ground Water Database

(PGWDB);11

• EPA’s chemical-spe-

cific monitoring

data;12

• monitoring data

collected by the

Water Quality Lab-

oratory at Heidel-

berg College in Tif-

fin, Ohio;13

• the U.S. Geological Survey (USGS)/EPA Reser-

voir Monitoring Study;14

• data from EPA’s Environmental Monitoring

and Assessment Program (EMAP);15

• the National Sediment Inventory (NSI);16

• the National Drinking Water Contaminant

Occurrence Database (NCOD);17

• National Stream Quality Accounting Network

(NASQAN) data;18 and

• National Water Quality Assessment (NAWQA)

data.19

The Agency notes that most of the monitor-

ing databases report results from samples of

“raw” (or untreated) water, rather than “finished”

drinking water treated by a drinking water facility

for use by its customers. Some treatment method-

representative database on the distribution of

pesticide residues in food as close as possible to

the actual time of consumption. The USDA fo-

cuses on foods consumed in large amounts by

children throughout the year. The PDP has col-

lected data on over 290 different pesticides and

50 different commodities.9

The FDA Surveillance Monitoring Program fo-

cuses on the pesticide residues found on food. It

is designed primarily to enforce the pesticide tol-

erances allowed on imported and domestic foods

shipped in interstate commerce.10

EPA proposes to use the PDP and FDA moni-

toring program databases to identify the pesticide

active ingredients that appear in the highest pro-

portion of samples, focusing on the 20 foods that

make up the largest part of the U.S. diet. Gener-

ally, the Agency would give higher weight to pes-

ticides that appear frequently on multiple foods.

In reviewing these data, EPA will take into ac-

count any risk-mitigation measures implemented

since residue levels were monitored.

Because of differences in how samples are col-

lected and handled under the PDP and FDA pro-

grams, EPA would rely on the PDP database when

both sources cover the same pesticides and com-

modities. The Agency would consider the FDA in-

formation as a supplement to the information de-

rived from the PDP database.

The Agency recognizes that its proposed ap-

proach would give higher priority to those pes-

ticides that are subject to routine monitoring in

either the PDP or the FDA program. Both pro-

grams rely on “multi-residue methods” that are

capable of detecting many different chemical

substances using a single analytical procedure.

Those chemicals that can only be detected using

specialized analytical methodology may not be

found, and thus would not be likely to be in-

cluded for consideration in the food pathway.

This limitation particularly applies to newer pes-

ticide active ingredients.

The Agency recognizes that its pro-posed approach would give higher

priority to those pesticides that aresubject to routine monitoring in ei-

ther the PDP or the FDA program.


ologies (such as flocculation, softening, filtration,

chlorination, or sedimentation) may potentially

remove or transform pesticide residues in source

water. Thus, residues found in samples from raw

water may not accurately reflect the exposure of

members of the public who are consuming fin-

ished water.

EPA has considered this issue, but has con-

cluded that conventional water treatment

processes in fact have little or no effect on the re-

moval of certain pesticides. Therefore, the Agency

regards the results of monitoring raw or ambient

water as an appropriate indicator of potential

human exposure.

The Residential-UsePathway

EPA proposes to

use information from

pesticide labels to indi-

cate which pesticides

could give rise to po-

tential human expo-

sure through their use.

The Agency would review its databases and

identify those active pesticide ingredients ap-

proved for residential use. Aside from products

approved only for limited exposure uses (such as

rodenticides applied in tamper-resistant bait

boxes), all pesticides currently registered for resi-

dential use would be identified as having a higher

priority with respect to the residential use path-

way.20

Occupational Exposure PathwaysIn assessing occupational exposure pathways,

EPA proposes to focus on exposures to pesticides

after their application. The Agency states that its

decision on this issue was based on available data

and current agricultural practices, which show

that the number of workers exposed after appli-

cation is greater than the number of workers ex-

posed through mixing, loading, and applying

pesticides.

The extent of the post-application exposure of

agricultural workers is affected by many factors.

Different activities involve varying levels of con-

tact with pesticide-treated surfaces, and therefore

can lead to different levels of exposure.

Exposure levels also depend on the amount of

pesticide residue available on a treated surface,

which in turn depend on the amount of pesticide

initially applied, how quickly the material de-

grades or is taken up by the plant, and how soon

after application the worker contacts the treated

surface.

Pesticides vary considerably in their applica-

tion rates, application timing, and environmental

fate. For this reason, the residue levels on treated

surfaces encountered by workers differ signifi-

cantly among pesticides and uses.

EPA proposes to rank pesticides based on their

potential for post-application exposure by agri-

cultural workers. According to the Agency, a rela-

tively recent database developed by the Agricul-

tural Reentry Task Force (ARTF) clearly indicates

that certain work activities in particular crops

lead to higher levels of exposure than other post-

application work activities. For example, harvest-

ing fruit in orchards or pruning vines in a grape

vineyard requires extensive contact with plant fo-

liage that is likely to contain pesticide residues.

The ARTF is a consortium of pesticide compa-

nies that formed a joint venture to develop data

for use in EPA assessments of worker risk. The

consortium conducted a series of carefully con-

trolled studies that measured the amount of pes-

ticide residue present on workers’ clothing after a

specific period of time working in a crop with

known amounts of pesticide residue on the crop

foliage.

The ARTF set of data is very extensive, and in-

cludes almost all crops where workers might

come into contact with pesticide-treated leaf sur-

Pesticides vary considerably intheir application rates, applicationtiming, and environmental fate.


In addition, EPA would review the available ef-

fects information to identify any chemical that

clearly shows an endocrine-mediated effect or per-

turbation; such chemicals would be considered for

proposed Tier 2 tests, mechanistic or special studies,

or hazard assessment. EPA also would identify sub-

stances that it anticipates would have a low poten-

tial for causing endocrine disruption. The Agency

would consider excluding the substances in both of

these categories from the first group of chemicals to

undergo Tier 1 screening.

Selecting HPV/Inert Chemicals EPA is proposing to use several sets of criteria

in order to identify the HPV/Inert chemicals that

should be given prior-

ity for screening in the

Tier 1 battery.

In general, the ap-

proach is similar to

that proposed for pes-

ticide active ingredi-

ents. The Agency will

focus on several indi-

cators of the potential for human exposure, in-

cluding production volume, specific pathways of

exposure, and presence in human tissues.

As is the case with pesticide active ingredi-

ents, this focus does not mean that the list will

contain no substances with high levels of expo-

sure to ecological receptors. Many of the

HPV/Inert chemicals that have a greater potential

for human exposure will also have a greater po-

tential for exposure to wildlife. EPA believes that

the approach proposed to evaluate pesticide

HPV/Inert chemicals, while focused on human

exposure, will also capture HPV/Inert chemicals

that have widespread environmental exposures.

The Agency has more extensive information

available for assessing exposure to pesticide active

ingredients than it has for HPV/Inert chemicals.

Similarly, it has more extensive information on the

faces. The ARTF studies permit the calculation of

a standardized “transfer coefficient” for particular

crops and activities. Activities that have higher

transfer coefficients should result in higher levels

of worker exposure, all other factors being equal.

EPA will review the ARTF’s transfer coefficient

studies to identify those work activities and crops

that have the highest potential for post-applica-

tion exposure. The Agency proposes to identify

approximately a dozen crops that have the high-

est transfer coefficients, and then identify the

pesticides that have the highest levels of use on

those crops.

EPA would estimate the total number of acre

treatments for each pesticide on all of the high-

coefficient crops, and then rank the pesticides on

the basis of the highest totals. The number of acre

treatments for each pesticide would be gathered

from a variety of public and private data sources,

including USDA’s National Agriculture Statistics

Service,21 California’s Department of Pesticide

Regulation, and Doane Marketing Research.

EPA believes that its proposal offers a feasible

approach for identifying pesticide active ingredi-

ents with the potential for either widespread or

high levels of exposure to workers after application.

Integration of Pathway PrioritiesApplying the criteria proposed for each of the

four pathways, the Agency plans to produce four

lists of candidate chemicals for potential screen-

ing in the endocrine disruptor Tier 1 battery.

Some pesticide active ingredients are expected to

appear on more than one pathway list. EPA

would assign higher priorities to chemicals ap-

pearing on multiple lists.

The Agency also proposes giving greater prior-

ity to chemicals that appear on the food pathway

list (which generally involve the most widespread

exposure), followed by those that appear on the

occupational pathway list (which generally in-

volve the highest per-capita levels of exposure).

EPA would estimate the total num-ber of acre treatments for each pes-ticide on all of the high-coefficientcrops, and then rank the pesticides

on the basis of the highest totals.


usage of active ingredients. For these reasons, the

databases available to evaluate potential human

exposure to the two classes of chemicals also differ.

EPA will review existing databases to identify

those HPV/Inert chemicals that are present in

human tissue, ecological tissues that have human

food uses, drinking

water, or indoor air. The

Agency will then set

priorities for these

chemicals based on the

number of exposure-

type databases in which

particular chemicals are

found.

EPA may also assign

a higher priority to those HPV/Inert chemicals that

appear in human tissues, as compared to those

that appear only in water, air, or ecological tissues.

As a final step, the Agency would review the

available effects information to identify any chem-

ical that clearly shows an endocrine-mediated ef-

fect or perturbation; these chemicals would be

considered for proposed Tier 2 tests, mechanistic

or special studies, or hazard assessment. EPA also

would identify substances that it anticipates would

have low potential to cause endocrine disruption.

The Agency would consider excluding substances

in both these categories from the first group of

chemicals to undergo Tier 1 screening.

Chemicals Found in Human TissuesEPA proposes to review several databases in

order to determine which HPV/Inert Chemicals

are found in human tissues. They include:

• the Third National Health and Nutrition Ex-

amination Survey (NHANES III),22

• the National Report on Human Exposure to

Environmental Chemicals,23

• the National Human Adipose Tissue Survey,24

and

• the Total Exposure Assessment Methodology

(TEAM) studies.25

Chemicals Found in Ecological Tissues withHuman Food Uses

EPA plans to review data sources to determine

which HPV/Inert chemicals have been detected

in non-human tissues, where the data are poten-

tially relevant to human ingestion exposure. The

data sources to be reviewed include:

• the NSI26 data on fish tissue and

• the National Fish Tissue Study.27

Chemicals Found in Drinking Water The Agency proposes to review the following

data sources in order to determine which

HPV/Inert chemicals have been detected in drink-

ing water or in potential sources of drinking water:

• the NCOD,28

• the National Human Exposure Assessment

Survey (NHEXAS),29

• water data from the TEAM studies,30

• NASQAN data,31 and

• NAWQA data.32

Chemicals Found in Indoor AirEPA plans to review the following data sources

to determine which HPV/Inert chemicals have

been detected in residential indoor air:

• literature published by EPA’s Office of Re-

search and Development

• the NHEXAS33

• relevant data from the TEAM studies.34

Integration of Pathway Priorities The Agency plans to produce four lists of can-

didate chemicals (one for each type of monitor-

ing data) for potential screening in the endocrine

disruptor Tier 1 battery.

EPA plans to review data sources todetermine which HPV/Inert chemi-cals have been detected in non-human tissues, where the data arepotentially relevant to human inges-tion exposure.


Notes

1. 67 Fed. Reg. 79611-79629 (December 30, 2002).

2. 21 U.S.C. 346a(p).

3. 63 Fed. Reg. 42852 (August 11, 1998).

4. 63 Fed. Reg. 71541 (December 28, 1998).

5. Id.

6. For more information on priority setting, see http://www.epa.gov/scipoly/oscpendo/prioritysetting/.

7. Recognizing the limitations on existing hazard data, EPAproposed the use of in vitro HTPS to assist in sorting and pri-ority setting. 63 Fed. Reg. 71541 (December 28, 1998).

8. The top 20 foods include the following raw agriculturalcommodities, in alphabetical order: apples, bananas, beef, car-rots, chicken, corn (field and sweet), eggs, grapes, lettuce,milk, oil, onions, oranges, pork, potatoes, rice, soybeans,sugar, tomatoes, and wheat.

9. Additional information on the PDP can be found athttp://www.ams.usda.gov/science/pdp/index.htm.

10. Additional information on the FDA monitoring programis available at http://www.cfsan.fda.gov/~dms/pesrpts.html.

11. The PGWDB was created to provide a more complete pic-ture of groundwater monitoring for pesticides in the UnitedStates.

12. Pesticide registrants have conducted, and submitted in-formation to the Agency on, targeted surface- and ground-water monitoring studies for approximately 50 pesticide ac-tive ingredients.

13. This laboratory monitors the impact of agricultural andurban land use on the water resources of the Midwest and theGreat Lakes regions. The laboratory has been studying pesti-cides since 1981. Further information on its research andmonitoring activities can be found at http://www.heidel-berg.edu/WQL/index.html.

14. The USGS/EPA Reservoir Monitoring study was a pilotmonitoring program initiated by USGS and EPA to provide in-formation on pesticide concentrations in drinking water andto assist in the implementation of the Food Quality ProtectionAct of 1996.

15. EMAP is an EPA research initiative designed to support thedevelopment of tools necessary to monitor and assess the sta-tus and trends of national ecological resources. Further infor-mation on EMAP can be found at http://www.epa.gov/emap/.

16. The Water Resources Development Act of 1992 directedEPA, in consultation with the National Oceanic and Atmos-pheric Administration and the U.S. Army Corps of Engineers,to conduct a national survey of data regarding the quality ofsediments in the United States. Further details on the NSIdatabase and the National Sediment Quality Survey, whichthe NSI was developed to support, can be found athttp://www.epa.gov/waterscience/cs/nsidbase.html andhttp://www.epa.gov/waterscience/cs/draft/survey.html.

17. The NCOD is a repository of drinking water quality data.Mandated by Congress in 1996 as part of the Safe DrinkingWater Act amendments, NCOD contains national contami-nant occurrence data on public water systems, as well as data

In selecting HPV/Inert chemicals to recom-

mend for screening, EPA would give higher pri-

ority to chemicals that appear in multiple types

of monitoring data. To the extent it becomes

necessary to establish priorities within the four

types of monitoring data, the Agency proposes

giving greater priority to HPV/Inerts that appear

in human biological monitoring data, followed

by those that appear in drinking water or indoor

air monitoring data, and finally those that ap-

pear in ecological monitoring data relevant to

human exposure.

EPA would review the available effects infor-

mation to identify any chemical for which the in-

formation clearly indicates an endocrine-medi-

ated result. Such chemicals would be considered

for proposed Tier 2 tests, mechanistic or special

studies, or hazard assessment.

Closing Comments On December 30, 2002, EPA published a no-

tice requesting public comment on its planned

approach for selecting an initial group of chemi-

cals to be screened under Tier 1 of the EDSP.

Comments were received by the Agency until

April 1, 2003. Information on public comments

was not available at the time of this writing in

mid-2003.

The December 2002 proposal dealt only with

the first group of chemicals to be screened under

Tier 1. EPA hopes to learn from the experience it

gains in screening this initial set of chemicals.

Based on this experience, and other knowledge

gained in connection with the ongoing develop-

ment of EDSP tools, the Agency anticipates that it

will modify its chemical selection process for sub-

sequent Tier 1 screening lists.

For Additional InformationFor additional information on endocrine dis-

ruptors and the EDSP, visit http://www.epa.gov/

oscpmont/oscpendo/resource.htm.


on ambient (source) water derived from the USGS NationalWater Information System. Further information on theNCOD can be found at http://www.epa.gov/safewater/data/ncodgateway.html.

18. The NASQAN, a monitoring and data-collection programconducted by the USGS, is designed to characterize raw sur-face water in large sub-basins of rivers, determine regionalsource areas for chemicals, and assess the effects of human in-fluences on observed concentrations and amounts of chemi-cals. Further details on the program can be found at http://water.usgs.gov/nasqan/.

19. In 1986, Congress appropriated funds for the USGS to usein designing and implementing a program to address ques-tions related to the status of, and long-term trends in, raw sur-face- and groundwater quality throughout the United Statesat the national, regional, and local levels. The USGS beganwith a NAWQA pilot in seven project areas, and fully imple-mented the program in 1991. Further information on theNAWQA program can be found at http://wwwga.usgs.gov/nawqa/main.nawqa.html.

20. EPA recognizes that registration of a pesticide for residen-tial use does not necessarily mean that it is widely used, orthat its use necessarily entails significant levels of human ex-posure. However, the Agency states that it does not have suf-ficient information to compare the extent of application ofdifferent active ingredients in residential uses.

21. For more than ten years, the USDA’s National Agricul-tural Statistics Service (NASS) has conducted annual surveysof pesticide use on a large number of crops, surveying thou-sands of agricultural producers in any given year. NASS con-ducts this use survey every year for a set of row crops. Moreinformation on NASS pesticide use data can be found athttp://www.pestmanagement.info/nass/.

22. NHANES III, which was conducted between 1988 and1994, involved 33,994 people throughout the United States.The survey was designed to develop nationally representa-

tive data on the health and nutritional status of the U.S.population.

23. The National Report on Human Exposure to Environmen-tal Chemicals is a project by the Centers for Disease Controland Prevention (CDC) that provides exposure information onpeople participating in an ongoing national survey of the gen-eral U.S. population.

24. The National Human Adipose Tissue Survey analyzeshuman adipose tissue specimens in order to monitor humanexposure to potentially toxic chemicals.

25. The TEAM studies were designed to develop methods formeasuring individual total exposure to toxic substances(through air, food, and water) and the resulting “body bur-den” of toxic and carcinogenic chemicals. Researchers seek toapply these methods within a probability-based samplingframework in order to estimate the exposures and body bur-dens of urban populations in several U.S. cities.

26. See note 16.

27. EPA is conducting a screening-level study to estimate thenational distribution of selected persistent, bioaccumulative,and toxic chemical residues in fish tissue from the lakes andreservoirs of the continental United States. More informationon the study can be found at http://www.epa.gov/water-science/fishstudy/results.htm.

28. See note 17.

29. EPA designed the NHEXAS program to address some of thelimitations of single-chemical and single-media exposureroute studies.

30. See note 25.

31. See note 18.

32. See note 19.

33. See note 29.

34. See note 25.

Kathleen Gibson is General Manager of the Environmental Strategies Corporation office in Somerset, New Jersey.

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