LABORATORY TESTING OF CHEMICALS FOR ENDOCRINE DISRUPTION 

POTENTIAL–ANALYSIS OF MARKET FACTORS 

October 14, 2009 

Final 

Economics and Policy Analysis Branch 

Economics, Exposure, and Technology Division 

Office of Pollution Prevention and Toxics 

U.S. Environmental Protection Agency 

Washington, D.C. 20460 
CONTRIBUTORS

The analyst responsible for completion of this report was Lynne Blake-Hedges. Analytical and draft 

preparation support was provided by Eastern Research Group, Inc. of Lexington, Massachusetts under 

EPA Contract No. EP-W-05-014. 
TABLE OF CONTENTS 

1.0 INTRODUCTION .........................................................................................................................1

1.1 BACKGROUND...............................................................................................................................2

1.1.1 EDSP Generated Demand for Endocrine Disruptor Testing Services.......................................3

2.0 SUPPLY OF ENDOCRINE DISRUPTOR TESTING SERVICES..........................................5

2.1 LABORATORIES CAPABLE OF TIER 1 SCREENING.........................................................................5

2.2 INDUSTRY CAPACITY FOR TIER 1 SCREENING..............................................................................7

2.3 POTENTIAL FOR ENTRY INTO THE MARKET/EXPANSION FOR ENDOCRINE DISRUPTOR TESTING 8

3.0 ISSUES THAT COULD IMPACT ENDOCRINE DISRUPTOR TESTING DEMAND AND 

SUPPLY........................................................................................................................................11

3.1 FOOD AND DRUG ADMINISTRATION REQUIREMENTS ................................................................11

3.2 EUROPEAN REQUIREMENTS........................................................................................................13

3.2.1 Registration, Evaluation, and Authorisation of Chemicals .....................................................13

3.2.2 Pesticide Restrictions ..............................................................................................................14

3.3 OTHER U.S. ENVIRONMENTAL PROTECTION AGENCY INITIATIVES...........................................14

3.3.3 Toxic Substances Control Act.................................................................................................14

3.3.4 Federal Insecticide, Fungicide, and Rodenticide Act..............................................................15

4.0 LABORATORY CAPACITY CONCLUSIONS.......................................................................16

5.0 COST ESTIMATES FOR CONDUCTING TIER 1 ASSAYS ................................................18

5.1 METHODOLOGY ..........................................................................................................................18

5.2 ASSAY COSTS .............................................................................................................................19

5.2.1 Assumptions............................................................................................................................19

5.2.2 Cost Data .................................................................................................................................20

5.2.3 Limitations ..............................................................................................................................22

5.3 ADDITIONAL COSTS....................................................................................................................22

5.3.4 Analytical Methods and Validation.........................................................................................23

5.3.5 Preliminary Analytical Work ..................................................................................................24

5.3.6 Additional Cost Summary .......................................................................................................24

5.3.7 Chemicals................................................................................................................................25

5.4 DISCOUNTS .................................................................................................................................25

5.5 COST SUMMARY .........................................................................................................................26

APPENDIX A LABORATORIES CAPABLE OF TIER 1 SCREENING...............................A-1

APPENDIX B EXAMPLE COST AND CAPACITY QUESTIONS........................................ B-1

APPENDIX C POTENTIAL CHEMICALS TO BE TESTED AS PART OF EDSP .............C-1
1.0 INTRODUCTION 

In recent years, some scientists have proposed that certain chemicals might be disrupting the endocrine 

system of humans and animal wildlife. A variety of chemicals have been found to disrupt the endocrine 

systems of animals in laboratory studies, and compelling evidence shows that endocrine systems of 

certain fish and wildlife have been affected by chemical contaminants, resulting in developmental and 

reproductive problems. The 1996 Food Quality Protection Act, which amended the Federal Food, Drug, 

and Cosmetic Act (FFDCA), directed the U.S. Environmental Protection Agency (EPA) to develop a 

screening and testing program, using appropriate validated test systems and other scientifically relevant 

information, to determine whether certain substances may have hormonal effects in humans. Also in 

1996, amendments to the Safe Drinking Water Act authorized EPA to screen substances that may be 

found in sources of drinking water for endocrine disruption potential. To meet its regulatory obligations, 

EPA initiated the Endocrine Disruptor Screening Program (EDSP) that developed a Tier 1 battery of in 

vitro and in vivo screening assays and Tier 2 in vivo tests to examine pesticide chemicals and 

environmental contaminants for their potential to affect the endocrine systems of humans and wildlife.1

Due to the potential number of chemicals requiring examination and number of screening and testing 

assays to be requested, EPA wishes to know whether sufficient laboratory capacity is available to satisfy 

the demand for chemical screening and testing requested by the EDSP. The purpose of this report is to 

provide a snapshot of the relevant laboratory capacity from a segment of the chemical testing industry in 

the United States, as well as overseas. This report provides neither comprehensive coverage of the entire 

industry nor does it represent a statistical sample of the industry. Rather, the intent is to provide insight 

into the testing industry’s likely response to the EDSP test orders and infer, based on limited industry 

contacts, whether sufficient capacity exists for complying with the test orders. 

Another purpose of this report is to provide updated cost estimates for the Tier 1 EDSP screening assays. 

In 2009, EPA provided the Office of Management and Budget (OMB) with estimates of the cost of Tier 1 

screening in support of an Information Collection Request (hereafter referred to as the ICR estimates).2

 In 

that submission EPA relied upon cost data from an industry-sponsored survey conducted by Applied 

Pharmacology and Toxicology, Inc. in 2003,3

 with the data updated to 2008 dollars and adjusted by EPA 

to reflect (a) Agency costs of having the validation tests conducted and (b) changes made to the Tier 1 

protocols. The protocols have completed validation and are now closer to what will be required under 

Tier 1 test orders. Since the ICR estimates were based upon the unvalidated and preliminary test 

protocols, EPA sought laboratory review of the most recent versions of the assay protocols and input on 

the costs of performing the tests. The cost information provided in this report is the result of consultations 

with a limited number of laboratories conducted during May and June 2009. 

In this report, the term “chemical testing industry” applies broadly to any organization, in the United 

States and abroad, that has the capability to use standard laboratory methods to determine the effects that 

a particular chemical may have on humans or the environment. These may include contract research 

organizations (CROs) conducting toxicology chemical testing; in-house testing laboratories operated by 

chemical companies or others (who may also do work for hire), as well as laboratories maintained and 

 

1

 Additional information about the development of the program can be located at www.epa.gov/endo. 2

 Attachment F to EPA ICR #2249.01 dated April 3, 2009. The Federal Register notice “Agency Information 

Collection Activities; Submission to OMB for Review and Approval; Comment Request; Tier 1 Screening of 

Certain Chemicals Under the Endocrine Disruptor Screening Program (EDSP); EPA ICR No. 2249.01” was 

published on April 15, 2009. 3

 Applied Pharmacology and Toxicology, Inc. Cost Estimate Survey: Endocrine Screening Assays. May 23, 2003. 

Available at http://www.apt-pharmatox.com/pdf/2003EDSP-CostReport.final.pdf 

1
operated by academic or other institutions. The majority of organizations contacted for and discussed in 

this report, however, are U.S.-based CROs. 

1.1 BACKGROUND

EPA developed a two-tiered approach to gather information needed to identify endocrine-active 

substances. Tier 1 screening uses a battery of assays to identify substances with the potential to interact 

with the estrogen, androgen, or thyroid hormone systems. Chemicals identified as having such potential 

following Tier 1 screening proceed to Tier 2. Tier 2 testing is intended to identify and establish a doseresponse relationship for any adverse effects that might result from the interactions identified through the 

Tier 1 assays. 

Section 408(p) of the FFDCA requires EPA to use validated test systems and other scientifically relevant 

information in the EDSP . Even though Tier 1 screening assays were developed and validated 

individually, EPA plans to use them in the context of a battery of complementary assays. An individual 

assay may serve to strengthen the weight of evidence in a determination4

 or provide coverage of 

mechanisms of actions not addressed by other assays in the battery. Table 1 displays the Tier 1 assays, all 

of which have completed the validation process.5

Table 1. EDSP Tier 1 Screening Assays Proposed by EPA 

Assay 

In vitro 

Rat uterine cytosol estrogen receptor binding (Rat ER binding) 

Rat prostate cytosol androgen receptor binding (Rat AR binding) 

Human placental or recombinant aromatase (Human aromatase) 

Human cell line (H295R) steroidogenesis (Human steroidogenesis) 

Human estrogen receptor-α transcriptional activation (Human ER transcriptional) 

In vivo rat tests 

Uterotrophic (rat) 

Hershberger (rat) 

Pubertal female (rat) 

Pubertal male (rat) 

In vivo tests of aquatic species

Amphibian metamorphosis (frog) 

Fish short-term reproduction 

Chemicals that go through Tier 1 screening and are found to have the potential to interact with the 

estrogen, androgen, or thyroid hormone systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on available data from Tier 1. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the test chemical and 

establish a quantitative relationship between dose and endocrine effect. Table 2 presents the Tier 2 assays, 

as well as their validation status as of June 2009. Since most of Tier 2 assays are still under development, 

the remainder of this report is focused on Tier 1 assays. 

 

4

 For example, EPA could determine that positive results in an ER binding assay, in conjunction with positive 

results in the uterotropic and pubertal female assays, provide a consistent signal for estrogenicity. 5

 Additional information about the assays can be located at www.epa.gov/endo/pubs/assayvalidation. 

2
Table 2. EDSP Tier 2 Testing Assays Proposed by EPA 

Assay Validation Status as of June 2009 

In vivo 

Amphibian development, reproduction Pre-validation in progress 

Avian 2-generation Validation in progress 

Fish lifecycle Pre-validation in progress 

Invertebrate lifecycle Pre-validation in progress 

Mammalian 2-generation reproductive 

toxicity test Validated 

1.1.1 EDSP Generated Demand for Endocrine Disruptor Testing Services 

The universe of chemicals identified as potential candidates for the EDSP include: 

 Pesticides; 

 Commercial chemicals; 

 Cosmetic ingredients; 

 Food additives; 

 Nutritional supplements; and 

 Certain mixtures. 

EPA proposed a strategy for prioritizing chemicals for initial chemical selection for Tier 1 screening in 

the Federal Register in December 2002.6

 The approach focused initially on pesticide-related chemicals 

that EPA is required to screen, including pesticide active ingredients and high production volume 

chemicals that are also inert pesticide chemicals. Upon review of comments received in response to the 

proposed approach, EPA published a final approach for the initial selection of chemicals in the Federal 

Register in September 2005 and a draft list of initial substances in June 2007.7, 8

 In April 2009, the 

Agency published the final list of 67 substances to undergo screening based upon exposure potential.9

This chemical list was included with EPA’s April 2009 submission to OMB for review of an ICR.10 The 

ICR describes the process for collecting Tier 1 screening data for the first group of chemicals. Based on 

the ICR, EPA estimates it will issue test orders to 390 manufacturers, importers, and pesticide registrants 

 

6

 EPA, “Endocrine Disruptor Screening Program, Proposed Chemical Selection Approach for Initial Round of 

Screening; Request for Comment,” Federal Register, December 30, 2002; Available at 

www.epa.gov/endo/pubs/12-02-frnotice.pdf. 7

 EPA, “Endocrine Disruptor Screening Program; Chemical Selection Approach for Initial Round of Screening,” 

Federal Register, September 27, 2005; Available at www.epa.gov/fedrgstr/EPA-TOX/2005/September/Day27/t19260.pdf. 8

 EPA, “Draft List of Initial Pesticide Active Ingredients and Pesticide Inerts to be Considered for Screening 

under the Federal Food, Drug, and Cosmetic Act,” Federal Register, June 18, 2007; Available at 

www.epa.gov/endo/pubs/draft_list_frn_061807.pdf. 9

 EPA, “Final List of Initial Pesticide Active Ingredients and Pesticide Inert Ingredients to be Screened under the 

Federal Food, Drug, and Cosmetic Act,” Federal Register, April 15, 2009; Available at 

http://www.epa.gov/endo/pubs/final_list_frn_041509.pdf 10 EPA, “Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment 

Request; Tier 1 Screening of Certain Chemicals Under the Endocrine Disruptor Screening Program (EDSP); 

EPA ICR No. 2249.01, OMB Control No. 2070–New,” Federal Register, April 15, 2009. Available at 

http://www.epa.gov/endo/pubs/icr_frn_041509.pdf. 

3
of the 67 chemicals. EPA expects most of the recipients to respond by selecting one of the three courses 

of action, described in the ICR, to comply with the order:11

1. Agree to individually generate new data; 

2. Participate in a consortium to generate new data; or 

3. Submit or cite existing data. 

Based on its experience with the pesticide registration program and testing requirements under the Toxic 

Substances Control Act, EPA assumes new testing will be undertaken largely by consortia representing 

manufacturers, importers, and pesticide registrants of individual chemicals or groups of chemicals to 

avoid duplication of effort and reduce costs. This expectation was shared by two CROs and one in-house 

laboratory likely to be asked to conduct testing, who were contacted for this report.12 An unknown 

number of test order recipients may already have conducted testing, and therefore, will submit existing 

data. Given the uncertainty about the extent of consortia-forming and the amount of test data that may 

already exist, this report assumes two scenarios regarding the volume of new test requests generated by 

the EDSP test orders. In its ICR documentation the Agency assumed only one set of data on average 

would be generated for the 67 chemicals. Since the focus of this report is on available laboratory capacity, 

EPA also explored a high volume scenario in which two sets of data, on average, would be generated per 

chemical, or a total of 134 data sets. While expected to be an overestimate, this assumption may mimic 

capacity demands placed on the laboratories for other testing that may use similar capabilities 

EPA anticipates requiring recipients of the test orders to follow this schedule: 

 90 days: submission of initial response describing how the company will respond to the test 

order; 

 12 months: submission of a progress report; and 

 24 months: final submission of data. 

Assuming that the EPA issues the test orders in the Fall of 2009, the majority of EDSP-generated Tier 1 

screening from the initial list of chemicals will occur in 2010 and 2011. 

Additional chemicals will be selected for screening in the future; however, EPA has not yet determined 

how it will prioritize the next set of chemicals.13 Therefore, further endocrine disruptor testing rounds are 

expected, but the likely timeline has not been determined. This report focuses on EDSP-related testing of 

the initial 67 chemicals over the 2010-2011 timeframe.

 

11 Personal communication with Molly Rodgers, Environmental Scientist, Eastern Research Group—Contractor 

supporting EDSP. April 6, 2009. 12 Personal communication with David Geter, Toxicology Specialist, Dow Chemical Company. May 14, 2009; 

personal communication with Kevin Causey, Manager, ILS. May 26, 2009; and personal communication with 

Jon Rhodes, Director of Chemical Services, ABC Laboratories. May 28, 2009. 13 In the U.S. House of Representatives’ version of the fiscal year 2010 appropriations bill for EPA (H.R. 2996), 

the Agency is required to publish within one year a second list of no less than 100 chemicals for EDSP 

screening that includes drinking water contaminants, such as halogenated organic chemicals, dioxins, flame 

retardants, plastics, pharmaceuticals, and personal care products. 

4
2.0 SUPPLY OF ENDOCRINE DISRUPTOR TESTING SERVICES 

Since a comprehensive list of laboratories capable of conducting endocrine disruptor testing is not readily 

available from the industry, one goal of this report is to identify a subset of those laboratories that may be 

capable of conducting the testing needed to support the EDSP data requirements. This section was 

prepared using published information about the chemical testing industry, discussions with EPA and other 

experts familiar with the industry, and information collected first hand from laboratories exhibiting at the 

Society of Toxicology’s ToxExpo in March of 2009 in Baltimore, Maryland. Additionally, laboratories 

interviewed for Section 5 regarding testing costs were asked about their capacity. 

The information provided here, including the list of laboratories provided in Appendix A, should not be 

construed as a comprehensive survey of the chemical testing industry. Data collection was limited by 

resources available and compliance with the Paperwork Reduction Act.14 This section, therefore, is 

designed to help EPA better understand the potential number of laboratories with these capabilities and 

their capacity for conducting EDSP Tier 1 screening. The section is broken into three subsections: 

1. Total number of laboratories with endocrine disruptor testing experience; 

2. Estimate of the number of tests that can be completed; and 

3. Discussion of factors in laboratories’ decision to expand or enter the endocrine disruptor 

testing market. 

2.1 LABORATORIES CAPABLE OF TIER 1 SCREENING

EPA has compiled a list of 32 laboratories believed to be capable of providing endocrine disruptor testing 

services (see Appendix A)15. Two of these are in-house laboratories that support testing for their 

corporate parent only, although one of them indicated a willingness to perform testing for third parties.16

Table 3 summarizes the testing capabilities of these laboratories by indicating the number of laboratories 

that are able to conduct each of the Tier 1 screening assays. The majority of laboratories specialize in 

certain categories of tests, with only 4 of the 32 able to cover the entire Tier 1 battery of assays, which 

consists of 11 separate screens. More than 70 percent of the laboratories can complete all four in vivo

rodent screens, and approximately half have capabilities to conduct the in vitro screens. 

 

The in vitro human aromatase and steroidogenesis assays and in vivo fish and amphibian assays are 

conducted by the fewest number of laboratories: 11, 11, 12, and 10, respectively. More detailed 

information on individual laboratories and their ability to perform endocrine disruptor testing is found in 

Appendix A. 

While EPA may accept test data conducted in developing countries under the provision that it meets 

EPA’s good laboratory practice (GLP) standards, two laboratories located in non-developed countries 

(i.e., Brazil, India) identified during discussions with ToxExpo exhibitors have not been included in the 

total capacity calculations in Table 4 further below. Additionally, none of the laboratories described 

14 The Paperwork Reduction Act prohibits federal agencies from making the same information request of more 

than nine non-federal entities without approval from OMB. 15 Reference to any specific commercial products, process, or service by trade name, trademark, manufacturer, or 

otherwise, does not constitute or imply its endorsement, recommendation, or favoring by the United States 

Government. 16 Dow Chemical Company only performs in-house testing, while Bayer CropScience indicated that they would be 

willing to perform testing for third parties. 

5
below as having the potential to enter the market are included in the total capacity reported in Tables 3 

and 4. 

Table 3. Count of Laboratories with Capabilities for Tier 1 Screening* 

Number of Laboratories 

Location 

Assays U.S. 

Other 

Developed 

Country 

NonDeveloped 

Country Total 

In vitro 

Rat ER binding 13 2 0 15 

Rat AR binding 13 2 0 15 

Human aromatase 10 1 0 11 

Human steroidogenesis 10 1 0 11 

Human ER transcriptional 12 2 0 14 

In vivo rodent tests

Uterotrophic (rat) 17 4 2 23 

Hershberger (rat) 17 4 2 23 

Pubertal female (rat) 17 4 2 23 

Pubertal male (rat) 17 4 2 23 

In vivo tests of aquatic species 

Amphibian metamorphosis 6 3 1 10 

Fish reproduction 7 4 1 12 

* Based on a subset of 32 laboratories believed to have endocrine disruptor testing capabilities (includes 

both in-house and CRO laboratories). Does not include laboratories who indicated they could potentially

conduct these tests. This table does not represent total industry capabilities. 

Eleven laboratories that do not currently perform endocrine disruptor testing suggested they could enter 

the endocrine disruptor testing market due to their experience in related areas.17 These laboratories 

already perform toxicology tests, including, in some cases, in vivo rodent or aquatic species testing, and 

thus are in good position in terms of trained personnel and equipment to perform these types of endocrine 

disruptor tests. Several laboratories suggested that it would take approximately one to three months to 

obtain the necessary animals, ensure they are prepared for the test, and train their employees on the 

protocol(s) before they could begin testing. Laboratories’ ability to adapt to demand is further examined 

in Section 2.3. 

In addition to the 11 laboratories discussed in the previous paragraph, EPA also identified two 

laboratories that previously offered in vitro rat endocrine disruptor testing services, but no longer do. WIL 

Research Laboratories participated in EPA’s validation of in vitro Tier 1 assays under the EDSP, but no 

longer performs this type of testing due to low demand. Another laboratory, Harlan Labs, indicated it had 

not received a test request in the past two years so had shifted resources to other business areas. Harlan 

indicated, however, that it could re-enter the endocrine disruptor testing market with three to six months 

of preparation if justified by an increase in testing demand. 

 

17 These laboratories are: Banyan Biomarkers, BASi, BioQual, Caliper Life Sciences, Center for Environmental 

and Human Toxicology (University of Florida, College of Veterinary Medecine), CorDynamics, Certichem, 

Irisys, Lifecyte, RADIL (University of Missouri), and Wuxi AppTech. 

6
2.2 INDUSTRY CAPACITY FOR TIER 1 SCREENING

In addition to understanding the number of the laboratories that offer toxicology testing services, the 

Agency is also interested in understanding whether these laboratories have the capacity to handle the 

additional testing demand that would be generated by the EDSP, over the timeframe envisioned for the 

program (see Section 1.1.1). Since the proposed in vitro screening assays can typically be performed in a 

matter of days and generally allow for the use of automated equipment, laboratories can handle a high 

throughput of samples and capacity is not expected to be a constraint. Two laboratories commented that 

they prefer running in vitro tests on multiple chemicals at a time as this minimizes the level of effort for 

each chemical since there are significant economies of scale in performing this work.18 Many small and 

large laboratories indicated they could perform “hundreds” or “thousands” of the in vitro endocrine 

disruptor assays each year.19 The minimum number of assays that could be completed in a single 

laboratory per year was estimated to be 10, and that was reported by a small laboratory associated with a 

University. Overall, given the nature of the testing and opportunities for automation, EPA feels confident 

that a majority of the laboratories could complete the five in vitro assays for 100 chemicals annually. As 

calculated in Table 4, even using a conservative estimate of 10 chemicals per laboratory per year, EPA 

believes that at least 110 chemicals could be tested. This is almost twice the number required under 

EPA’s high volume estimates (i.e., 134 data sets over a two year period is 67 chemicals each year). This 

analysis is primarily based on testing capacity identified in the United States, but also includes four 

laboratories located in other developed nations (i.e., Europe, Japan, Canada). 

Table 4. Estimated Annual Capacity for EDSP Tier 1 Assays 

Capacity (Tests 

Conducted Per 

Year) 

Total Annual 

Capacity** 

Annual Demand 

Under EDSP 

Assays 

Number of 

Labs* Low High Low High ICR High 

ER & AR binding (rat) 15 150 825 

ER transcriptional (human) 14 140 770 

Steroidogenesis and 

aromatase (human) 11 110 605 

In vivo rat assays 21 

10 100 

210 1,155 

In vivo amphibian 

metamorphosis 9 19 171 

In vivo fish reproduction 11 20 220 

34 67 

* The number of laboratories with capacity to conduct each type of testing is derived from Table 3, excluding 

laboratories located in developing countries. 

** EPA’s low estimate is obtained by multiplying the number of laboratories by the minimum number of tests that 

can be conducted per year, as reported by interviewees. The high estimate assumes half of the laboratories could 

conduct testing at the higher volume, and the other half perform the low estimate, which EPA believes to be 

conservative. It was beyond the scope of this report to conduct a detailed survey, but EPA expects the true capacity 

among these laboratories to lie between the low and high end points. For in vivo aquatic testing (amphibian 

metamorphosis and fish short-term reproduction) EPA multiplied the average capacity (based on data from more 

than half of the laboratories) by the number of laboratories with such capabilities.

 

18 Personal communication with David Geter, Toxicology Specialist, Dow Chemical Company. May 14, 2009; 

and personal communication with Alexander Lyubimov, Director, University of Illinois at Chicago, Toxicology 

Research Lab. June 9, 2009. 19 EPA identified laboratories as small if the parent company had less than 100 employees. 

7
Estimated capacities for the in vivo rat assays tended to range from 10 to 20 chemicals per year for 

smaller laboratories to sometimes in excess of 100 chemicals per year for larger laboratories. Again, if 

EPA assumes a conservative estimate of 10 chemicals per year can be completed per laboratory, current 

capacity would accommodate 210 chemicals for in vivo rat screening, compared to a high volume 

estimate of 67 chemicals to be tested annually under the EDSP. EPA believes the actual capacity for in 

vivo screening to be much larger than the low estimation, indicating that the incremental increase in 

testing demand generated by EDSP will be met with sufficient capacity. 

Historically, EPA has identified fewer laboratories with aquatic chemical testing capabilities.20 Given this 

concern, EPA collected detailed information about capacity from 7 of the 12 laboratories with capabilities 

for conducting one or two of the aquatic screening assays. The number of chemicals that could be tested 

among these laboratories ranged from a low of 4 to as many as 30 per year. No capacity differential was 

identified between small and large laboratories. One laboratory that performs the entire battery of Tier 1 

assays explained that these aquatic screens required significantly more time and resources compared with 

other endocrine disruptor assays that they conduct.21 The equipment involved, set-up costs, and time to 

expand capacity make it less attractive for laboratories to undertake this type of testing. The average 

annual capacity among these laboratories was 19 chemicals for the amphibian assay and 20 for the fish 

assay. As calculated in Table 4, even with the smaller number of laboratories capable of completing the 

aquatic in vivo testing, EPA believes capacity is sufficient.

EPA believes that sufficient capacity exists for endocrine disruptor testing of aquatic species based on the 

analysis done in Table 4; however, a few laboratories expressed concern that there is insufficient capacity. 

Three in vivo aquatic testing laboratories suggested EPA’s two year timeframe to complete the testing is 

not feasible.22, 23, 24 One of these laboratories suggested that EPA needs to account for a three to six 

month lag before industry would issue test requests because of time needed to coordinate consortia. 

Additionally this laboratory has noticed that companies often delay issuing test requests to benefit f

others’ experience with the new testing requirements. However, the major reason voiced by these 

laboratories is their assumption that only they and potentially one other laboratory have the capabilities to

perform this type of testing. Given that these three laboratories also reported lower average capacity (11 

chemicals per year compared to an average of 19 to 20 chemicals per year for all laboratories with these 

capabilities), their concern about capacity is understood. As seen in Tables 3 and 4, however, there 

additional capacity these laboratories may not be aware of, which can reconcile the difference of opinion

between these three laboratories an

rom 

is 

d EPA. 

 

2.3 POTENTIAL FOR ENTRY INTO THE MARKET/EXPANSION FOR ENDOCRINE DISRUPTOR 

TESTING

In developing this report, EPA also sought to better understand how laboratories will respond to testing 

demand precipitated by the EDSP. Laboratories interviewed for the report uniformly stated that the 

promise of demand alone would not lead them to increase capacity or expand into new areas. While no 

one laboratory could exactly define “sufficient” market demand that would cause them to consider 

20 Eastern Research Group, Analysis of Laboratory Capacity to Support U.S. EPA Chemical Testing Program 

Initiatives. U.S. EPA, Office of Pollution Prevention and Toxics, Economic Analysis and Policy Branch. EPA 

contract 68-W6-02-077. August 30, 2004. 21 Personal communication with David Geter, Toxicology Specialist at the Dow Chemical. May 14, 2009. 

22 Personal communication with David Palmer, Director of Business Services, Wildlife International, Ltd. May 21, 

2009. 23 Personal communication with Ron Biever, Chief Scientific Officer, Springborn Smithers. May 26, 2009. 24 Personal communication with Jon Rhodes, Director of Chemical Services, ABC. May 28, 2009. 

8
expansion, the common theme among laboratories is an observed backlog of several months in current 

testing demand, along with a strong forecast that the high demand would continue for several years. 

As indicated in Section 2.1, a number of exhibitors at ToxExpo who are not currently offering endocrine 

disruptor testing felt that their expertise would allow them to branch into this area. At the same time, they 

indicated that their business planning would require more than a few short-term requests to generate real 

interest in developing these capabilities. Many laboratories noted the importance of a multiple year 

contract with either a government agency, private industry, or a group of manufacturers. 

In general, laboratories report that they do not hire in anticipation of testing. Several noted their practice 

of accumulating “several months worth” of work in backlog before hiring, to avoid later layoffs if the 

demand increase turns out to be short lived. Laboratories also indicated that the depressed and volatile 

state of the current economy contributes to their sense of caution with respect to hiring. These statements 

are consistent with findings from 2004 when EPA queried laboratories about their capacity in anticipation 

of EPA’s High Production Volume (HPV) Challenge and the European Union’s Registration, Evaluation, 

Authorization and Restriction of Chemical substances (REACH) testing programs.25 While laboratories 

remarked on their ability to quickly move into new areas of testing, they also noted that entry into a new, 

albeit related, field would involve shifting of personnel and incremental costs, and that they would 

proceed with capacity expansion cautiously. 

Four laboratories that currently offer aquatic endocrine disruptor testing services discussed expansion 

specific to EPA’s EDSP. None of the laboratories indicated they would consider expansion based on the 

initial set of 67 chemicals. One laboratory described the first group of 67 chemicals as a “blip”, but if 

EPA rolled out a much larger list of chemicals to be tested, they would consider expansion.26 One other 

laboratory stated that they would look to expand capacity if EPA required supplemental rounds of testing 

of the magnitude of approximately 1,000 chemicals.27 A third laboratory echoed these sentiments stating 

they would look to double or triple capacity if EPA required expanded their testing requirement to a 

“much larger” list of chemicals.28The fourth laboratory indicated it would only expand if it secured a 

contract from a group of manufacturers.29 Previously, this laboratory had invested in equipment to 

increase capacity for work that had not materialized. 

Laboratories with endocrine disruptor testing experience discussed their company’s commitment to crosstraining employees to help with lulls that inevitably occur within a specific testing area. Many CROs 

indicated they intentionally hire employees with diverse skill sets and experience in order to increase their 

areas of expertise, allow for greater flexibility in the services they offer, and improve their ability to adapt 

to changing market conditions.30 One example cited was the recent hire of a Ph.D with expertise related 

to amphibians. This employee was selected to meet current demand for their services and strengthen th

laboratory’s knowledge of amphibian testing. Although not hired because of EPA’s EDSP Tier 1 

screening, the employee’s experience with amphibians had factored into their hiring decision. 

e 

 

25 Eastern Research Group, Analysis of Laboratory Capacity to Support U.S. EPA Chemical Testing Program 

Initiatives. Office of Pollution Prevention and Toxics. EPA contract 68-W6-02-077. August 30, 2004. 26 Personal communication with David Palmer, Director of Business Services, Wildlife International. May 21, 

2009. 27 Personal communication with Ron Biever, Chief Scientific Officer, Springborn. May 26, 2009. 

28 Personal communication with Doug Fort, Manager, Fort Environmental Labs. June 4, 2009. 

29 Personal communication with Irv Schultz, Manager, Battelle. June 8, 2009. 

30 Personal communication with Kevin Causey, Manager, ILS. March 17, 2009; personal communication with 

Robert Foster, Senior Scientific Advisor, NOTOX. March 17, 2009; personal communication with Timothy 

Ward, Regulatory Affairs Specialist, ABC Laboratories. March 17, 2009. 

9
Based on discussions with laboratories and given the prediction of sufficient capacity to conduct the 

initial round of Tier 1 assays, EPA concludes that laboratories are unlikely to expand their capacity or add 

new capabilities based on projected EDSP test data demand. 

10
3.0 ISSUES THAT COULD IMPACT ENDOCRINE DISRUPTOR 

TESTING DEMAND AND SUPPLY 

When considering the supply of laboratory capacity for conducting endocrine disruptor testing, it is also 

important to understand other issues that may impact industry capacity such as competing demand for its 

services or other market factors. This section reviews some of these factors to provide additional context 

to the information provided in Section 2. EPA believes that sufficient laboratory capacity should be 

available to meet the initial testing demand generated by the EDSP. That conclusion was based, however, 

on only the incremental demand represented by the EDSP, without consideration of other sources of 

industry demand. The following sections explore whether other testing initiatives including those of the 

U.S. Food and Drug Administration (FDA), EPA, and the European Union, could impact with industry’s 

ability to meet incremental EDSP testing demand. The section also explores how the recent economic 

decline has affected demand in these other areas. 

3.1 FOOD AND DRUG ADMINISTRATION REQUIREMENTS

CROs involved in toxicological testing reported that testing associated with FDA and other 

pharmaceutical-related requirements represents the largest share of their business base. As a result, 

decisions related to physical space, equipment, and human resources are strongly linked to FDA testing 

program requirements. Under the authority of the FFDCA, FDA requires toxicology testing of 

pharmaceuticals and food additives. Some of this testing is similar to that required under the EDSP or 

requires similar capabilities. Since laboratories generally indicated there were no concerns with expansion 

of Tier 1 in vitro testing capacity (see Section 2.2), this subsection considers the extent to which FDAdriven testing overlaps with in vivo Tier 1 assays. 

Commonly required in vivo tests by the FDA in the area of human pharmaceuticals include:31

 Toxicokinetics and pharmacokinetics in rodents and/or other species 

 Single-dose studies in rodents, and occasionally dogs and primates 

 Subacute (14-28 day), subchronic (90 day) and/or chronic (90+ day) studies in rodents, dogs, 

and occasionally primates 

 Reproduction segment I––fertility studies in rodents 

 Reproduction segment II––prenatal developmental toxicity in rodents and rabbits 

 Reproduction segment III––postnatal development in rodents 

 Mutagenicity and genotoxicity studies of at least two varieties 

 Carcinogenicity studies in rats and transgenic mice 

 Immunotoxicity in rodents 

 Triggered specialized studies (e.g., phototoxicity and pyrogenicity) 

While the vast majority of CROs with in vivo capabilities noted that they are currently operating below 

their capacity, several laboratories did note that pharmaceutical in vivo tests requiring rodents 

(particularly the chronic tests taking over 90 days) could potentially compete for personnel and space with 

endocrine disruptor in vivo rat screening assays. Many of the EDSP in vivo tests take at least 21 days to 

complete and require multiple tanks or cages per chemical. Nonetheless, because of large demand from 

the pharmaceutical sector for in vivo rodent testing, CROs capacity is large. As shown in Table 3, more 

than 70 percent of the laboratories that were identified through the development of this report offer in vivo

 

31 The Humane Society of the United States and Procter & Gamble, “FDA,” December 6, 2007. Available at: 

www.alttox.org/ttrc/us/regulatory-research-agencies/fda.html 

11
rodent testing services. Laboratories do not anticipate any capacity issues for conducting EDSP’s in vivo

rodent tests. 

When asked to identify any areas of EDSP testing that could present capacity or bottleneck issues in a 

hypothetical situation of increased demand generated from FDA, the most common areas cited were 

amphibian metamorphosis and fish short-term reproduction assays. One laboratory explained that the fish 

Early Life Stage (ELS) studies often required by FDA would directly compete with the fish short-term 

reproduction endocrine disruptor assay.32 The factors limiting capacity expansion to meet any increased 

demand are primarily related to equipment, particularly the diluters used in the testing. Facility space may 

also be a factor, but to a lesser extent. For context, the laboratory estimated that each additional fish 

endocrine disruptor assay would displace one and half ELS studies in terms of capacity. 

In light of the recent economic slowdown, laboratories are reporting a general decline in demand for 

testing from pharmaceutical and biotechnology companies. Among exhibitors at the ToxExpo, those that 

rely most heavily on FDA-driven testing requests described their situation using terms such as “barely 

afloat” or “taking it off the chin.” 

One laboratory whose workload has historically been evenly split between the pharmaceutical and 

chemical industry reported a major decline in demand from pharmaceutical clients. Demand from the 

chemical sector, on the other hand, has remained strong. As a result, this laboratory has shifted staff in the 

short term to accommodate more industrial chemical toxicology work. Doing so has been minimally 

disruptive as a result of their cross-training of employees and use of similar equipment and skill sets in 

both types of testing. Somewhat ironically, this same firm made a shift in the opposite direction seven 

years ago, when it faced a decline in chemical testing tied to consolidation in the chemical and agrichemical industries. In the present environment, they are seeing consolidation in the pharmaceutical and 

biotech markets in 2009, with many large pharmaceutical companies buying out biotech companies. This 

is leading to fewer testing requests because of a decline in new products being brought to market. 

A few laboratories noted that biotech and pharmaceutical companies have laid off employees to try to 

save money, which has led to more outsourcing of testing previously conducted in-house. According to 

market researchers at Frost and Sullivan, the greatest growth potential for CROs is in the early stage work 

for biotechnology and pharmaceutical development.33 This type of work includes toxicology studies that 

until recently had been conducted by in-house laboratories. The significance of this phenomenon could 

not be ascertained but some CROs described it as a trend that has temporarily helped counteract the loss 

in demand linked to the struggling economy. 

In conclusion, CROs that depend on testing requests from pharmaceutical and biotech companies have 

surplus testing capacity. Several of these laboratories expressed interest in better understanding the 

potential testing needs generated from the EDSP to help fill the decline in FDA-driven work, which 

utilizes similar equipment and trained personnel. Although the observation is based on anecdotal evidence 

from a small number of CROs, it may be indicative of some flexibility in the testing industry to adjust 

capabilities in response to changes in testing demand. 

 

32 Personal communication with Jon Rhodes, Director of Chemical Services, ABC Laboratories. May 28, 2009. 

33 Dubin, Cindy. “CRO Trends & Drivers,” Specialty Pharma, 9(4), April 2009. 

12
3.2 EUROPEAN REQUIREMENTS

3.2.1 Registration, Evaluation, and Authorisation of Chemicals 

In 2007, the European Union’s legislation to create the Registration, Evaluation, and Authorisation of 

Chemicals (REACH) program went into effect. REACH requires the registration of chemicals, including 

the submission of test data to demonstrate the registrant’s evaluation of the chemical’s risks. Under the 

program, substances produced or imported in annual quantities of 1,000 metric tons (2.2 million pounds) 

or more would need to be registered by November 30, 2010; substances produced or imported at annual 

quantities of 100 to 1,000 metric tons (220,000 to 2.2 million pounds) would need to be registered by 

May 31, 2013; and substances produced or imported at annual quantities of 1 to 100 tons (2,200 to 

220,000 pounds) would need to be registered by May 31, 2018.34

The testing requirements for chemicals under REACH vary based on the production volume of the 

chemical (i.e., less test data are required for lower production volume chemicals) and the suspected 

toxicity of the chemical.35 Some of the basic information requirements for REACH include: 

 Substance identity; 

 Physicochemical properties; 

 Mammalian toxicity; 

 Ecotoxicity; 

 Environmental fate, including abiotic and biotic degradation; and 

 Information on manufacture and use(s) as well as risk management measures. 

Much of the test data requested relies on the Organisation for Economic Cooperation and Development’s 

(OECD’s) Screening Information Data Set (SIDS) batteries. While REACH does not specifically require 

the same testing as the EDSP, several of the SIDS testing areas are similar to those in EDSP. Thus, there 

is potential for REACH testing to compete with endocrine disruptor testing in terms of laboratory space, 

equipment, and human resources. At the time of the ToxExpo (mid-March 2009), however, CROs stated 

that they had little or no testing scheduled related to REACH. Testing laboratories in Europe, as well as 

Asia, are uncertain about REACH’s impact on the market. None of the laboratories indicated that they 

have expanded in anticipation of REACH; however, a couple of European laboratories had been 

consulting with chemical companies about how to approach the REACH requirements. 

The expected workload to be generated by REACH varied dramatically from laboratory to laboratory. A 

few CROs expect chemical companies to complete the testing using in-house laboratories, form consortia 

to minimize duplicative efforts, or submit data that has already been generated. At the other end of the 

spectrum, one laboratory representative expressed concern that companies were procrastinating until the 

deadline and that demand would suddenly materialize as deadlines approach. Some believe or fear that 

affected companies will delay their testing to learn from the experiences of other companies on how to 

respond to the requirements. One laboratory in particular expressed concern about a possible influx of 

 

34 Any manufacturer or importer that did not pre-register a chemical with the European Chemical Agency prior to 

the 2008 deadline is required to submit the registration immediately if they wish to continue its manufacture or 

import. 35 Foster, Bob. “REACH Registration and Evaluation.” NOTOX BV. Presented at SOCMA Corporate Excellence 

Conference. May 18, 2008. 

13
testing requests in the second half of 2010 that would overwhelm European testing capacity, pushing 

overflow requests to Asia and the United States.36

A recent article written by a REACH consultant also expressed concern that CROs will become a 

bottleneck in meeting the REACH deadline.37 Using the environmental testing on pharmaceutical 

products created by the European Medicines Agency in 2007 as an example, the author stated that the 

required increase in laboratory capacity in Europe and the United States lagged by two years before it met 

the 10 percent increase in market demand for testing services. The primary reason cited for the delay was 

the time needed to put qualified staff in place. 

3.2.2 Pesticide Restrictions 

In January 2009, the European Parliament adopted a new regulation that will ban certain pesticides from 

use in food production unless industry provides test data demonstrating them as safe. Many of these 

pesticides have been identified as having the potential to disrupt the endocrine system.38 Although the 

regulation still requires approval from the Agriculture Council for formal endorsement by the member 

States, the regulation is expected to become effective in late 2010. Thus, industry may conduct endocrine 

disruptor testing for banned pesticides in order to allow their continued use. This new regulation has the 

potential to increase demand for endocrine disruptor testing services, however, the level of this demand is 

unknown. 

3.3 OTHER U.S. ENVIRONMENTAL PROTECTION AGENCY INITIATIVES

3.3.3 Toxic Substances Control Act 

Working under authorities and requirements of the Toxic Substances Control Act (TSCA), EPA gathers 

and reviews data, assesses risk, and regulates chemicals in commerce. Under Section 4 of TSCA, EPA 

can require companies to conduct testing on selected chemicals for which data are needed to evaluate 

potential health or environmental hazards. Over the last several years, the Agency has worked to ensure 

the availability of data on High Production Volume (HPV) chemicals by asking for manufacturers to 

commit voluntarily to provide testing information.39 TSCA initiatives, including the voluntary HPV 

Challenge, use the OECD’s SIDS batteries as the basic set of test data. The SIDS dossiers cover five main 

categories of data: general information (e.g., use patterns, volume), physical-chemical properties, 

environmental fate and transport, ecotoxity, and toxicity. Data to be summarized for human toxicity 

include studies assessing acute toxicity, subchronic toxicity, genotoxicity, and developmental and 

reproductive toxicity. 

The HPV Challenge Program led to the sponsoring of more than 2,200 HPV chemicals; however, most of 

the information from these sponsored chemicals came from data that companies already had, or was 

derived using structure-activity relationship (SAR) modeling to predict the characteristics of a compound 

 

36 Personal communication with K.S. Rao, Head of Corporate Development, Advinus Therapeutics. March 18, 

2009. 37 Erler, Steffen. Technical Director, Smithers REACH Services. “Dr Reach - Who are you?,” Chemical Watch, 

May 2009. Available at http://chemicalwatch.com/2223. 38 Pesticide Residues Committee, Summary Impact Assessment: Proposal for a Regulation of the European 

Parliament and of the Council Concerning the Placing of Plant Protection Products on the Market, January 

2009. Available at

www.pesticides.gov.uk/prc_home.asp?id=1980#authorisation_regulation_and_sustainable_use_directive 39 An HPV chemical is one that is produced or imported in the United States in quantities of 1 million pounds or 

more per year. 

14
based on its structural similarity to other compounds with existing data. The widespread use of existing 

data and SAR-based approaches to meet the HPV Challenge requirements resulted in substantially less 

new business for the chemical testing industry than was expected. 

Based on the low volume of new testing demand coming out of the HPV Challenge program and 

available capacity to perform testing in the industry, testing related to Section 4 rules and programs is not 

expected to compete with EPA’s endocrine disruptor testing initiative. One lasting impact of the 

industry’s experience with HPV, however, may be a reluctance to expand laboratory capacity to 

accommodate similar types of initiatives. A few of the CROs explained that the condition of the economy 

combined with the past disappointment with initiatives such as the HPV Challenge has led them to adopt 

a “wait and see” approach to any demand increase associated with new testing initiatives. 

3.3.4 Federal Insecticide, Fungicide, and Rodenticide Act 

EPA has authority to regulate pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act. 

Before registering a new pesticide or new use for a registered pesticide, EPA requires more than 100 

different scientific studies and tests from applicants in order to make a determination that proper use of 

the pesticide will cause no harm to human health and will pose no unreasonable risks to the 

environment.40 One CRO expects laboratories to be contracted for EDSP testing of agri-chemicals as a 

follow on to their work supporting the chemical’s initial registration.41

One laboratory suggested that the fish short-term reproduction assay required under the EDSP could 

compete for resources with any 260-day fish full lifecycle studies required by EPA for pesticide 

registration.42 Both tests require similar equipment, laboratory space, and personnel, but the fish full 

lifecycle test is equivalent to nearly ten fish EDSP assays in terms of resource intensity. Thus, if a 

laboratory received one or two unexpected requests to perform this test, it might not have capacity to 

perform the EDSP fish assay. According to the same laboratory, however, requests for fish full lifecycle 

studies are rare. 

 

40 Office of Pesticide Programs, “Regulating Pesticides,” U.S. EPA. June 9, 2009. Available at 

www.epa.gov/pesticides/regulating. 41 Personal communication with Kevin Causey, Manager, ILS. May 26, 2009 

42 Personal communication with Ron Biever, Chief Scientific Officer, Springborn Smithers. May 26, 2009. 

15
4.0 LABORATORY CAPACITY CONCLUSIONS 

This report presents the results of EPA’s efforts to analyze the chemical testing industry and evaluate its 

current capacity to conduct testing using EPA’s EDSP Tier 1 screening assays. Although part of this task 

involved efforts to identify specific laboratories, including international and domestic CROs, readers are 

cautioned that this report and its conclusions are based on information from only a subset of the industry. 

It was beyond the scope of this effort to conduct a comprehensive survey of all laboratories. 

Within these limits, EPA identified 32 laboratories that offer endocrine disruptor testing services and 

concluded that these laboratories represent sufficient capacity to complete the testing demand generated 

by the EDSP under EPA’s high volume scenario (i.e., two data sets are generated for each chemical). 

Since EPA believes that on average only one data set will be generated per chemical, this conclusion 

appears justified. 

Some areas of testing may be more constrained than others. While there is sufficient capacity to complete 

the in vivo fish and amphibian screens, there appears to be less excess capacity in these areas than in 

others required under the EDSP. Several laboratories that conduct this type of testing expressed concern 

about being able to complete the testing in a two-year window. These laboratories may underestimate 

U.S. capacity for in vivo fish and amphibian screening, identifying only four laboratories qualified to 

undertake the aquatic toxicology work compared with the numbers confirmed by EPA (i.e., seven 

laboratories for fish related testing and six laboratories for amphibians). Additionally, EPA has identified 

additional capacity for these tests in Canada and Europe. 

Some laboratories that provide toxicology testing to meet FDA requirements indicate that they could enter 

the market for endocrine testing with approximately three months preparation time. Those laboratories 

with the necessary equipment and staff, and who may have excess capacity due to reduced test requests 

from pharmaceutical clients, would be most likely to enter the market for EDSP testing. It is important to 

note, however, that these laboratories consistently expressed hesitation to undertake the costs of moving 

into a new field without a long term guarantee of work. 

Similarly, laboratories already providing endocrine disruptor testing services would expand only after 

sustaining a backlog of test requests for several months and concluding that the higher level of demand 

will continue. From discussions with laboratories, none indicated that entry of an initial 67 chemicals into 

the program would cause them to expand capacity to accommodate additional testing during the two year 

testing timeframe. Few laboratories engage in speculative expansion in anticipation of increased future 

testing driven by EPA or European chemical testing initiatives. Some of this reluctance may be a result of 

past experience waiting for EPA-driven testing demand that never materialized. Several aquatic 

toxicology laboratories did suggest, however, that if EPA required a larger number of chemicals to be 

screened under EDSP (which one laboratory suggested would need to be on the order of 1,000 chemicals) 

they would consider doubling or tripling their current capacity. 

EPA also investigated whether other chemical testing initiatives, such as the European Union’s REACH 

or forthcoming pesticide regulation, along with other EPA programs, could create any spike in demand 

for CRO testing services. One consultant has estimated there to be insufficient testing capacity in place to 

meet the 2010 REACH deadline. Based on discussions with CROs, however, EPA was unable to 

determine the impact of REACH on endocrine disruptor testing capacity. 

16
Potential new restrictions on pesticides in Europe may require industry to undertake endocrine disruptor 

testing to develop data to support exempting chemicals from the ban. The resulting volume of testing 

work, however, is unknown at this time. Overall, EPA believes there is sufficient capacity to 

accommodate additional testing needs assuming that a majority of the REACH-related demand would not 

compete with the specialized skills required of the EDSP assays. Further, the capacity totals presented in 

this report represent an unknown subset of all laboratories. In particular, EPA believes there is additional 

European capacity available that is not accounted for in this report. 

17
5.0 COST ESTIMATES FOR CONDUCTING TIER 1 ASSAYS 

5.1 METHODOLOGY

The number of laboratories that could be solicited for cost information was restricted by the Paperwork 

Reduction Act, which prohibits federal agencies from making the same information request of more than 

nine entities, and the project’s resource limitations. EPA felt its data quality objectives for the project 

could be met if the testing assays were divided into three different groups based upon the type of 

testing—Group A: in vitro, Group B: in vivo rat toxicology, and Group C: in vivo aquatic toxicology. 

EPA deemed the questions for each group of laboratories to be sufficiently different, which would allow 

up to nine laboratories in each group to be asked questions regarding the costs of testing for the particular 

protocols that the different groups would be able to conduct. The screening assays were divided into the 

three groups as shown in Table 5. The table identifies the version date of the protocol provided to the 

laboratories. 

Table 5. EDSP Tier 1 Screening Assays 

Protocol 

Version Provided to 

Laboratories 

Group A: In vitro tests 

Rat uterine cytosol estrogen receptor binding 

(Rat ER binding) 6/17/08 

Rat prostate cytosol androgen receptor binding 

(Rat AR binding) 8/29/08 

Human placental & recombinant aromatase 

(Human aromatase) 8/28/08 

Human cell line (H295R) steroidogenesis 

(Human steroidogenesis) 7/31/08 

Human estrogen receptor-α transcriptional 

activation (Human ER transcriptional) 6/5/08 

Group B: In vivo rat tests 

Uterotrophic 10/16/07 

Hershberger 9/2/08 

Pubertal female 2008, v.3 

Pubertal male 2008, v.3 

Group C: In vivo tests of aquatic species 

Amphibian metamorphosis 6/25/2008 

Fish short-term reproduction 

Undated, v. 1 

July 6, 2006 for 

histopathology guidelines 

18
Since a comprehensive list of laboratories capable of conducting endocrine disruptor testing is not readily 

available from the industry, EPA identified a 32 laboratories (both U.S. and foreign) believed to have the 

capabilities to perform testing in one or more of the groups of Tier 1 endocrine disruptor assays shown in 

Table 5. The identification process for these laboratories is described in Section 2. 

From the list of laboratories (provided in Appendix A), EPA randomly selected six to eight laboratories 

with capabilities in each testing area (Groups A, B, and C in Table 5). This process initially resulted in a 

total of 17 laboratories to be interviewed, with a handful of the larger laboratories asked to provide 

estimates for two different test groups. Of the original 17, four replacement laboratories were required to 

substitute for ones that either declined an interview, could not provide the information in the required 

timeframe, or provided cost estimates that did not meet EPA’s data quality objectives.43 Ultimately, 15 

laboratories contributed cost data. 

Laboratories that agreed to provide cost information were sent the most current version of each assay 

protocol for their group(s), a list of example questions (Appendix B), and the list of potential chemicals to 

initially be screened (Appendix C). EPA provided the laboratories sufficient time to familiarize 

themselves with this material prior to the interview. A majority of the interviews were conducted by 

phone though responses for some of the more common protocols, such as the in vivo rat assays, were 

collected via email. In order to ensure the integrity of the data, EPA investigated any potential outliers 

(i.e., cost was significantly higher or lower than other laboratory estimates). A follow-up discussion was 

held to determine the reasons for the potential discrepancy and to ensure that the cost estimates were not 

inadvertently including support work (e.g., pre-testing validation of dosing concentration, analytical 

chemistry) with the cost of the actual testing. Section 5.2 focuses on the actual cost of testing, followed 

Section 5.3’s discussion of ancillary costs such as method validation and analytical chemistry work. 

5.2 ASSAY COSTS

5.2.1 Assumptions 

EPA instructed the laboratories to provide estimates for performing the tests under GLP. During the 

interviews, three laboratories indicated that performing the tests under GLP would increase the price for 

conducting the test by 10 to 25 percent.44 The increased price is due to the higher level of effort required 

in the report writing and additional quality control measures that need to be undertaken. The estimates 

provided in this report are what laboratories expect to charge per assay if such requests were made by 

industry. Laboratories were asked to estimate the cost of the assay without including the price of methods 

development and any analytical work including method validation, preliminary analytical work, 

verification of dosing concentrations, and confirmation of the chemical’s identity and purity. These 

additional costs are discussed in Section 5.3. 

 

43 EPA’s primary determinant in deciding whether the cost information was deemed acceptable was the laboratory 

contact’s understanding of the protocol. For example, one laboratory admitted that they had conducted similar 

assays for FDA requirements, but their price was based on that work and they had not reviewed EPA’s 

protocols to determine how the price would differ. 44 Personal communication with David Geter, Toxicology Specialist, Dow Chemical Company. June 19, 2009; 

personal communication with Nikou Hessami, Toxicology Specialist, Molecular Diagnostics. June 6, 2009, and 

personal communication with Irv Schultz, Senior Scientist, Battelle. June 8, 2009. 

19
5.2.2 Cost Data 

Table 6 summarizes the cost data for the Tier 1 assays provided by the laboratories participating in this 

study. Some laboratories provided a range of costs while others provided a point estimate. For 

laboratories that provided a range (i.e., low and high cost), the mean of the high and low cost was taken to 

obtain a single averaged cost estimate for each assay. The in vitro rat and human ER transcriptional 

assays cost approximately $22,000 each. The human steroidogenesis is estimated to cost approximately 

$16,000 and the human aromatase test was priced at $28,000. As seen in the table, the range in the 

estimates provided is large. 

Table 6. Cost Estimates for EDSP Tier 1 Screening Assays 

Costs 

Assay Median Minimum Maximum 

# of 

Responses 

In vitro 

Rat ER binding $17,250 $7,000 $55,000 7 

Rat AR binding $17,250 $7,000 $55,000 7 

Human aromatase $25,000 $4,000 $60,000 6 

Human steroidogenesis $13,750 $4,500 $31,400 4 

Human ER transcriptional $15,000 $3,000 $55,000 6 

In vivo rat tests 

Uterotrophic $43,050 $9,500 $65,500 6 

Hershberger $47,400 $9,200 $72,000 6 

Pubertal female $87,100 $47,200 $152,500 6 

Pubertal male $93,500 $47,200 $160,000 6 

In vivo tests of aquatic species

Amphibian metamorphosis $80,597 $20,000 $97,700. 6 

Fish reproduction $92,500 $85,000 $137,650 7 

Total

All 11 assays $532,397

For the in vivo tests, the median of laboratories reported costs for conducting the rat uterotrophic and 

Hershberger assays were $43,050 and $47,400, respectively. The low and high cost estimates for these 

assays were approximately $9,000 to $72,000. The median cost for the rat pubertal in vivo assays were 

$87,100 (female) and $93,500 (male). The price variation between the low and high estimates for these 

assays was more than $100,000, with the low end at $47,000 and the high end at $160,000. The 

amphibian metamorphosis and fish short-term reproductive assay had median costs of approximately 

$80,597 and $92,500, respectively; however, this does not include the cost for setting up the delivery 

system, which is a one time cost applicable to both the amphibian and fish assay and is discussed in 

Section 5.3. 

Given the wide variation in the cost estimates, EPA plotted the individual laboratory estimates along with 

the median cost to better illustrate the data. These are shown in Figure 1 (in vitro assays) and Figure 2 (in 

vivo assays). The figures also plot the estimates provided by EPA in support of the EDSP ICR. With the 

exception the fish short-term reproduction assay, the ICR estimates are all within the range given by 

laboratories in this study. For most tests, there is a large disparity between the minimum and maximum 

estimates. A single laboratory provided the highest estimates for all in vitro tests and another provided all 

the lower bound estimates. The highest estimates for the in vivo testing are shared by two companies as 

are the lowest estimates. All of the laboratories with high and low estimates are familiar with ED testing 

20
either with EPA protocols or similar protocols. For this reason, EPA found no reason to exclude any 

estimates. 

Figure 1. Price Estimates for Five In Vitro EDSP Tier 1 Screening Assays 

In Vitro EDSP Assay Costs

$0

$10,000

$20,000

$30,000

$40,000

$50,000

$60,000

$70,000

(AR) binding-rat

prostate 

(ER) binding-rat

uterus

ER

Transcriptional

(human)

Steroidogenesis

(human)

Aromatase

(human)

 O = median of estimates

 = ICR estimate ($2008)

+ = individual lab estimate

21
 Figure 2. Price Estimates for Six In Vivo EDSP Tier 1 Screening Assays 

In Vivo EDSP Assay Costs

$0

$20,000

$40,000

$60,000

$80,000

$100,000

$120,000

$140,000

$160,000

$180,000

Uterotrophic

(rat) 

Hershberger

(rat) 

Pubertal female

(rat) 

Pubertal male

(rat)

Amphibian

Metamorphosis

Fish Short-Term

Reproduction

 O = median of estimates

 = ICR estimate ($2008)

+ = individual lab estimate

 

5.2.3 Limitations 

One of the limitations faced by EPA in collecting cost data using this approach was the varying 

knowledge of the laboratory contact about the assay protocols. Several laboratories had participated in the 

validation of the protocols and these laboratories tended to provide estimates at the higher end of the cost 

range. EPA believes these interviewees may be able to make more informed estimates based on what they 

had learned from their validation work. Many of the low-end estimates came from laboratories that 

demonstrated the capacity to perform the testing, but may have based their cost estimates on a quick read 

of the protocols or on their experience performing the assays with similar, but not identical, protocols.45

5.3 ADDITIONAL COSTS

As noted in Section 5.2, EPA requested that laboratories not include in their estimates any costs not 

directly related to the assays themselves. Costs for ancillary activities including method development and 

validation, verification of dosing concentrations, and confirmation of the chemical’s identity and purity, 

are not included in the cost estimates shown in Table 6. EPA found these additional costs to be highly 

dependent on the nature of the chemical being tested and more easily discussed in the context of the cost 

per chemical, separate from the cost of the assays themselves. The laboratories also had a more difficult 

time providing itemized estimates for these activities and the Agency collected fewer specific data points. 

45 The in vitro rat ER binding, steroidogenesis, and fish protocols are over 50 pages long with the other eight 

protocols ranging from 17 to 32 pages. 

22
5.3.4 Analytical Methods and Validation 

In conducting the cost interviews, EPA provided each laboratory with the most current version of protocol 

and informed them they would have to follow the protocol instead of developing their own method. Thus, 

method/protocol46 development was excluded as a relevant cost but EPA asked laboratories to discuss the 

ancillary costs they incur before conducting the test under GLP requirements, which have not been 

included in the cost estimates reported in the previous section. 

Laboratories conduct method validation to optimize method performance of a given assay with their 

personnel and equipment, and establish quality control limits. For many of the in vitro assays and in vivo

rat assays, this is accomplished by running the assay using a known chemical at a known dosage and 

comparing the laboratory’s results against results published in the assay protocols. For example, for the 

uterotrophic assay, a specified concentration of 17α-ethinyl estradiol can be used as a control substance to 

verify the proficiency of the laboratory with the assay. Laboratories excluded these costs in their 

estimated price of each assay because this “validation” is conducted every six months (as required in the 

uterotrophic protocol) or prior to routinely conducting the assay (as required in the in vitro ER binding rat 

protocol). Laboratories indicated that the cost of conducting validation would be spread over the volume 

of chemicals being tested and among similar tests, making it difficult for them to provide an exact cost 

per chemical. Although all the laboratories interviewed were asked about these costs, very few felt 

comfortable providing specific costs. 

In Vitro Assays 

One laboratory provided an average cost for validation as $8,000 for the complete set of the five in vitro

assays. They provided a range of $7,000 to $9,000, with the lower price representative of chemicals that 

had similar properties to one that was already validated, while the higher end of the range would be 

charged for chemicals that the laboratory is less familiar with. 

In Vivo Rat Assays 

One laboratory provided an average validation cost of $11,500 for the complete set of in vivo rat assays. 

This average is calculated from their low and high estimates of $8,000 to $15,000; the cost determination 

related to the chemical proprieties and the laboratory’s experience with the test substance. 

In Vivo Aquatic Assays 

Three laboratories provided validation costs for the aquatic assays. The protocol validation includes 

performing analysis of the test substance in water to verify that the delivery system is working and 

dispensing the chemical in water as prescribed in the protocol. The average cost was $7,333, with a low 

and high range of $5,000 to $10,000. This validation is a one-time cost per chemical as the same delivery 

system method can be used for both the amphibian and fish assays. One laboratory explained that the cost 

of validation is based on the equipment needed for validation.47 When a high-performance liquid 

chromatography (HPLC) is sufficient, the costs are at the lower end of the range; however, some 

validations are unsuccessful on HPLC and are redone on an HPLC with mass spectrometry which 

increases the laboratory’s costs. 

 

46 Laboratories used the terms protocol and method interchangeablely. 

47 Personal communication with John Aufderheide, Senior Toxicologist, ABC Laboratories. June 2, 2009. 

23
5.3.5 Preliminary Analytical Work 

In addition to validation costs, laboratories also indicated there is also preliminary analytical work that is 

not included in the assay costs presented in Table 6. This section describes this work and associated costs. 

Preliminary Solubility and Delivery Trials 

Prior to the protocol validation, laboratories conducting the fish and amphibian tests need to perform 

preliminary solubility and delivery trials. This work is necessary to understand how the chemical delivery 

system will function in water, and for these two aquatic species tests, this is part of verifying that the 

delivery system delivers the correct dosing concentration to the test subjects. Three laboratories provided 

estimates for this preliminary work. Each estimated that for a water soluble chemical it would cost $5,000 

per chemical. Chemicals with limited water solubility would be more expensive at an average of $15,000. 

Their estimates ranged from $5,000 to $20,000. This work is completed per chemical since the same 

delivery system is used in the amphibian and fish assays. Laboratories also noted that if they were 

creating delivery systems for chemicals with similar properties that the cost for additional chemicals 

would reduce to less than $5,000 each. 

Verification of Dosing Concentration 

Laboratories must, on a regular basis, verify that the dosage of chemicals used in these assays is 

consistent. Many laboratories make stock solutions of the chemical at a known concentration which can 

be used for delivery on multiple animals over a period of weeks, while other laboratories make smaller 

batches of stock solution, sometimes daily. Regardless of the method, laboratories must verify that they 

are administrating the correct dosage of chemical. Creation of the solutions and quality control 

verification of the dosing concentration could potentially be done for multiple assays at a time. Three 

laboratories estimated the average cost at $2,000 per chemical for the four in vivo rat assays with a low to 

high range of $1,000 to $2,500. A laboratory explained that much of this range arises from how many 

batches of varying concentrations are required by the protocol. For the in vivo amphibian and fish assay, 

the verification of the dosing concentration is completed as part of the delivery system step and is not 

presented as a separate cost. For in vitro assays, this cost was already included in the estimates of 

conducting the assays. 

Verification of the Chemical’s Identity and Purity 

Most of the laboratories interviewed expected that the manufacturer of the chemical would be responsible 

for verification of the chemical’s identity and purity. As part of GLP protocol the manufacturer typically 

submits a form verifying the identity and purity of the compound to the laboratory performing the testing. 

Several laboratories said that if a chemical provider did not verify the identity and purity of a compound, 

they would charge between $2,000 and $5,000 per chemical. This was based on estimates from three 

laboratories with an average one time cost of $3,500. This additional cost was not included in Table 7 

because contract laboratories stated they rarely are required to perform such testing. 

5.3.6 Additional Cost Summary 

The additional costs presented above in Section 5.3 are summarized in Table 7. This work is conducted 

on a per chemical basis. 

24
 Table 7. Summary Table of Additional Costs 

Additional Costs 

Method Validation 

Preliminary 

Analytical Work 

Assay Range Average Range Average 

Average Total 

Additional Costs 

In vitro 

Rat ER binding 

Rat AR binding 

Human aromatase 

Human steroidogenesis 

Human ER transcriptional 

$7,000 to 

$9,000 $8,000 Included in the cost of the assay (Table 6). $8,000 

In vivo rat tests 

Uterotrophic 

Hershberger 

Pubertal female 

Pubertal male 

$8,000 to 

$15,000 $11,500 $1,000 to $2,500a $2,000a $13,500 

In vivo tests of aquatic species

Amphibian 

Fish 

$5,000 to 

$10,000 $7,333 $5,000 to $20,000b $10,000c $17,333 

a

 For verification of dosing concentration 

b

 For preliminary solubility and delivery trial setup 

c The average for soluble compounds was $5,000 while less soluble compounds was $15,000. The mean of these 

two averages is $10,000. 

5.3.7 Chemicals 

Laboratories were asked to review the list of chemicals in Appendix C and discuss whether their test cost 

estimates would need to be adjusted for specific substances. The laboratories performing the fish and 

amphibian assays noted that the protocols require the development of special delivery systems for those 

chemicals that are not very water soluble (e.g., pyrethroids, phthalates, trifluran). Testing these less 

soluble chemicals would be at the high end costing about $15,000 to $20,000 (approximately $10,000 to 

$15,000 more than water soluble ones costing approximately $5,000). This is reflected in the range 

provided in Table 7. Laboratories also stated that chemicals with higher vapor pressures could also add 

complexity (i.e., cost) to the fish and amphibian assays. Several of the laboratories said that if the fish and 

amphibian protocols allowed for the use of other solvents (as is the case in the other nine protocols), the 

costs of conducting the test would be similar to that for water soluble chemicals; however, the cost 

savings could be partially or completely offset by the need to run a control test measuring the endocrine 

disrupting potential of the solvent. 

Laboratories indicated that the properties of the chemicals to be tested have less of an impact on cost for 

the in vitro assays and in vivo rat assays than the fish and amphibian assays. A couple of laboratories 

noted that the list contained chemicals that require the use of respirators during handling, which could 

increase the time to conduct the tests. The impact on the testing cost, however, would be minimal. 

5.4 DISCOUNTS

EPA asked laboratories if they would offer discounts to customers requesting the full suite of Tier 1 

assays or for customers requesting multiple chemicals be tested. Most laboratories indicated that 

discounts are offered to existing customers that request a large volume of work (e.g., $2.5 million). When 

25
asked for more specifics, however, most of the laboratories stated that these discounts are determined on a 

case-by-case basis and hesitated to quantify them. 

EPA found that laboratories performing in vivo assays, particularly the fish and amphibian tests, felt that 

discounts to attract customers are unnecessary given their expertise niche. They speculated that with the 

limited time frame likely required by the EDSP test orders, they will be working at capacity and have 

been in discussion already with existing clients. 48 However, a couple of laboratories said that they would 

consider discounts for customers with multiple chemicals with similar properties for the fish and 

amphibian assays since they could potentially use the same delivery system for each chemical for the 

assays (as described in Section 5.3), but again they hesitated to quantify these discounts. Other 

laboratories conducting in vivo tests reported that the labor intensive nature of the work with animals does 

not benefit from much economies of scale when multiple chemicals are tested. In general, EPA found that 

there would be little to no discounts passed on to customers for in vivo testing. 

EPA found that with the in vitro rat assays, in particular, laboratories could perform the tests at significant 

discounts when dealing with multiple chemical requests. One interviewee explained that both the ER and 

AR rat binding assays require a large amount of setup work (e.g., chemical acquisition, cytosol 

preparation, characterization by a saturation assay) much of which can be done once for multiple assays. 

This laboratory estimated that while the cost of performing these assays for one chemical might be 

$55,000 each, they would reduce their price to $13,200 per chemical if 20 or more chemicals were being 

tested. EPA spoke with another laboratory that provided cost estimates for all five in vitro tests (Group A 

in Table 5). They indicated that for an individual assay the per chemical cost when analyzing 10 

chemicals together was approximately 40 percent less than the per chemical cost of performing that assay 

with a single chemical. The laboratory explained that after performing the initial in vitro assays for one 

chemical, the level of effort required to perform subsequent chemicals is significantly less.49 A third 

laboratory explained how in contrast to the in vivo assays, the in vitro assays can be set up in a high 

throughput manner. Sets of three or more chemicals can easily be loaded into machines thus lowering the 

per chemical cost of the assay as more chemicals with similar properties are analyzed at once.50 A fourth 

laboratory did not provide a cost estimate for running the steroidogenesis test with one chemical as they 

typically only run the test using several chemicals at a time to minimize level of effort and cost. Their 

estimate was $15,000 to $21,500 on the basis of running 10 to 20 compounds. 

5.5 COST SUMMARY

This section summarizes the estimated cost for the suite of the 11 Tier 1 EDSP assays. For laboratories 

that provided a range (i.e., low and high cost), the mean of the high and low cost was taken to obtain a 

single averaged cost estimate. Altogether, the in vitro assays cost approximately $118,000 per chemical. 

The in vivo rat toxicology assays cost approximately $284,000 per chemical, while the two in vivo aquatic 

assays are estimated to be $193,000. The estimated total of performing all 11 assays including ancillary 

testing prep work is $595,698 as shown in Table 8. A majority of this estimate, $556,865 is the cost for 

conducting the assays, with an additional cost of $38,833 for the analytical work (e.g., method validation, 

dosing concentration). 

 

48 As discussion in Section 2, EPA identified the least number of laboratories capable of performing fish and 

amphibian tests. 49 Personal communication with Alexander Lyubimov, Director, University of Illinois at Chicago, Toxicology 

Research Labs. June 15, 2009 50 Personal communication with David Geter, Toxicology Specialist, Dow Chemical Company. June 19, 2009. 

26
27

Table 8. Summary Table of the Full Suite of Testing for One Chemical 

Costs 

Assay Assay Cost 

Method 

Validation 

Preliminary 

Analytical Work Subgroup Totals

In vitro 

Rat ER binding $21,729 

Rat AR binding $22,214 

Human aromatase $28,200 

Human steroidogenesis $15,850 

Human ER transcriptional $22,267 

$8,000 Already included $118,260 

In vivo rat tests 

Uterotrophic $37,867 

Hershberger $42,208 

Pubertal female $93,592 

Pubertal male $96,975 

$11,500 $2,000 $284,142 

In vivo tests of aquatic species

Amphibian $73,399 

Fish $102,564 $7,333 $10,000 $193,296 

Total 

All 11 assays $556,865 $26,833 $12,000 $595,698 

Table 8 was calculated with the assumption that laboratories would only be testing one chemical at a 

time; however, several laboratories stated that conducting multiple in vitro tests achieves economies of 

scale and they would charge significantly less (on the order of 40 to 50 percent less) when performing 

them in batches of 10 or more chemicals. This could potentially drop the subtotal of all five in vitro tests 

from approximately $118,000 to $65,000. 

Laboratories did not report any significant economies of scale with in vivo tests. Some laboratories 

indicated that some of the analytical work in preparing for these assays could be reduced if chemicals 

with similar properties are tested together; however, this is not likely to reduce the cost from the estimate 

in Table 8 by more than a few thousand dollars. 
APPENDIX A LABORATORIES CAPABLE OF TIER 1 SCREENING 

The information provided in this Appendix is primarily based on information collected from online research and from exhiToxExpo in March 2009. The tables are neither an industry directory nor a statistical sample of the entire chemical testing A-1 suggests laboratories that would be able to conduct endocrine disruptor tests. Table A-1. Laboratories Claiming to Have Capabilities to Perform EDSP Tier 1 Assays51

Name 

Corporate Headquarter Location Web site 

Rat uterine cytosol 

estrogen receptor 

binding 

Human 

recombinant 

estrogen receptor binding

Rat prostate 

cytosol androgen 

receptor binding

Human cell line 

steroidogenesis 

Human placental 

& recombinant 

aromatase 

Rat uterotrophic 

and hershberger 

ABC Laboratories USA www.abclabs.com Advinus Therapeutics Pvt. Ltd. 

India www.advinus.com X 

Battelle USA www.battelle.org/pharmaceutical X X X X X Bayer CropScience52 France www.bayercropscience.com X X X X X X BioAgri Pharma Brazil www.bioagri.com.br X Brixham Lab UK www.brixham-lab.com Calvert Labs USA www.calvertlabs.com X X X X X X Cantest Canada www.cantest.com 

51 Reference to any specific commercial products, process, or service by trade name, trademark, manufacturer, or otherwise, does not co

endorsement, recommendation, or favoring by the United States Government. 

52 They are an in-house laboratory, but they expressed willingness to do testing for third parties. 

A-1
Name 

Corporate 

Headquarter Location Web site 

Rat uterine cytosol 

estrogen receptor 

binding 

Human 

recombinant 

estrogen receptor 

binding

Rat prostate 

cytosol androgen 

receptor binding

Human cell line 

steroidogenesis 

Human placental 

& recombinant 

aromatase 

Rat uterotrophic 

and hershberger 

Ceetox USA www.ceetox.com X X X X X Charles River Labs USA www.criver.com X CIT France www.citox.com XDow Chemical Company53 USA www.dow.com X X X X X X Fort Environmental Laboratories 

USA www.fortlabs.com 

The Hamner USA www.thehamner.org X X X X X X Harlan Labs USA www.harlan.com X IITRI Research Institute USA www.iitri.org X X X X X X INA Research Japan www.ina-research.co.jp X Integrated Laboratory Systems, Inc. 

USA www.ILS-INC.com X X X X X X 

JRF International 

United Kingdom www.jrfonline.com 

MB Research Labs USA www.mbresearch.com X X X 

53 They conduct in-house testing only. 

A-2
A-3

Name 

Corporate Headquarter Location Web site 

Rat uterine cytosol 

estrogen receptor 

binding 

Human 

recombinant 

estrogen receptor 

binding

Rat prostate 

cytosol androgen 

receptor binding

Human cell line 

steroidogenesis 

Human placental 

& recombinant 

aromatase 

Rat uterotrophic 

and hershberger 

Midwest Research Institute (MRI) 

USA www.mriresearch.org X 

Molecular Diagnostic Services, Inc. 

USA www.mds-usa.com X X X X X X 

MPI Research USA www.mpiresearch.com X NOTOX The Netherlands www.notox.nl X X X X X X RTI International USA www.rti.org X X X X X X Singulex, Inc. USA ww.singulex.com X X X SNBL USA USA www.snblusa.com X X X X X Springborn Smithers Laboratories 

USA www.springbornsmithers.com 

Stillmeadow USA www.stillmeadow.com X University of IL at Chicago USA www.uic.edu/labs/tox X X X X X X WIL Research Labs. Inc. USA www.wilresearch.com X X X Wildlife International USA www.wildlifeinternational.com 
APPENDIX B EXAMPLE COST AND CAPACITY QUESTIONS 

Prior to conducting the interviews, EPA provided the laboratories with the following list of example 

questions for the interviews: 

1. EPA will require that the Endocrine Disruptor Screening Program (EDSP) studies be conducted in 

compliance with Good Laboratory Practices (GLPs). Are you familiar with EPA’s GLP requirements 

in 40 CFR part 160? Do you routinely follow these GLPs when conducting tests? If not, do you 

follow other GLPs? 

2. What would you estimate the average cost of conducting [insert test assay] will be? What 

assumptions have you made in making this estimate? 

3. Looking at the attached chemical list, are there certain chemicals that would cause you to adjust the 

cost estimate you provided in Question 2 higher or lower? Which ones, and why? 

4. For the attached chemical list, we are interested in understanding the analytical cost and range finding 

requirements, such as: 

a. Verification of the chemical’s identity and purity 

b. Verification of dosing concentrations 

Can you provide a cost estimate for methods development, sample preparation, and analysis for this 

type of testing (assuming these costs were not given as part of the answer to Question #1)? Please 

assume that the results for in vitro binding assays would be made available for in vivo tests. 

5. How would these cost estimates you provided in Question #4 change if the methods did not need to 

be developed (i.e., for an existing chemical)? 

6. How many of these tests would you be able to conduct in one year? 

7. Would there be any discounts to a customer requesting the full suite of Tier 1 assays? Or any other 

reason? If yes, please elaborate. 

8. Would there be any discounts to a customer requesting multiple chemicals to be tested? Or any other 

reason? If yes, please elaborate. 

B-1
APPENDIX C POTENTIAL CHEMICALS TO BE TESTED AS PART 

OF EDSP 

EPA published in the Federal Register on April 15, 2009 a list of initial pesticide active ingredients and 

pesticide inert ingredients the Agency will require to be screened as part of EDSP. Laboratories were 

asked to base their testing cost estimates on this list of chemicals. 

Table C-1: List of Chemicals Provided to Laboratories to Base Cost Estimates On 

Chemical Type or Description 

Acephate Organophosphate 

Chlorpyrifos Organophosphate 

Diazinon Organophosphate 

Dimethoate Organophosphate 

Disulfoton Organophosphate 

Ethoprop Organophosphate 

Glyphosate Organophosphate, but not 

representative 

Malathion organophosphate 

Methamidophos Organophosphate 

Methidathion Organophosphate 

Methyl parathion Organophosphate 

Phosmet Organophosphate 

Carbaryl Carbamate 

Carbofuran Carbomate 

Methomyl Carbamate 

Oxamyl Carbamate 

Bifenthrin Pyrethoids 

Cyfluthrin Pyrethorid 

Cypermethrin Pyrethroid 

Esfenvalerate Pyrethroid 

Permethrin Pyrethroid 

Resmethrin Pyrethroid 

Butyl benzyl Phthalate 

Captan Phthalate 

DCPA (or chlorthal–dimethyl) Phthalate 

Dibutyl phthalate Phthalate 

Diethyl phthalate Phthalate 

Dimethyl phthalate Phthalate 

Di–sec–octyl phthalate Phthalate 

Atrazine Triazine 

Metribuzin Triazine 

Simazine Triazine 

C-1
Chemical Type or Description 

Propiconazole Triazole 

Tebuconazole Triazole 

Myclobutanil Azole 

Triadimefon Azole 

Folpet Carboximide 

Gardona (cis–isomer) ( aka tetrachlorvinphos) Carboximide 

Benfluralin Dinitroaniline 

Trifluralin Dinitroaniline 

Dicofol Organochlorine 

Quintozene Organochlorine 

Abamectin Fermentation product of 

streptomyces avermitilis 

Acetone 

Carbamothioic acid, dipropyl–, S–ethyl ester 

Chlorothalonil Chloronitrile 

Dichlobenil Nitrile 

Endosulfan Chlorinated hydrocarbon 

Fenbutatin oxide 

Flutolanil Benzanilide 

Imidacloprid Chloro-nicotinyl 

Iprodione Dicarboximide 

Isophorone Unsaturated cyclic ketone 

Linuron Substituted urea 

Metalaxyl Benzxenoid 

Methyl ethyl ketone 

Metolachlor 

Norflurazon Pyridazinone 

o–Phenylphenol 

Piperonyl butoxide 

Propachlor Chloroacetanilide 

Propargite Organosulfite 

Propyzamide Benzamide 

Pyridine, 2-(1-methyl-2-(4-

phenoxyphenoxy)ethoxy) 

Toluene 

C-2