Final Report Analysis of Laboratory Capacity to Support U. S. EPA Chemical Testing Program Initiatives Prepared by:

Economics, Policy, and Analysis Branch ( 7406M) Office of Pollution Prevention and Toxics U. S. Environmental Protection Agency 1200 Pennsylvania Avenue NW Washington, DC 20460 August 30, 2004 CONTRIBUTORS The EPA analyst responsible for this report was Lynne Blake Hedges. Analytical and draft preparation support was provided by Eastern Research Group, Inc. under subcontract to Abt Associates Inc. under EPA Contract No. 68 W 02 077. ii TABLE OF CONTENTS Page 1.0 INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2.0 DEMAND FOR CHEMICAL TESTING SERVICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 2.1 HPV Testing in the United States . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 2.2 HPV Testing in the European Union . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2.3 OECD/ ICCA HPV Testing Program. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 2.4 Comparison of U. S. and EU HPV Chemical Testing Programs . . . . . . . . . . . . . . 5 2.5 Impact of the HPV Challenge and REACH on Chemical Testing Demand . . . . . . 8 2.6 U. S. Testing for Endocrine Disruption Potential . . . . . . . . . . . . . . . . . . . . . . . . 11 3.0 SUPPLY OF CHEMICAL TESTING SERVICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 3.1 Contract Research Organizations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 3.2 Captive In House Testing Labs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 3.3 Other Sources of Testing Capacity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 4.0 CURRENT INDUSTRY ISSUES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 4.1 Issues Affecting Demand . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 4.2 Issues Affecting Supply . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 5.0 CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 6.0 REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 1 A second and related question is whether such capacity is available at a reasonable price. This question, however, was not explicitly addressed in this report.

1 1.0 INTRODUCTION Under the authority of the Toxic Substances Control Act ( TSCA), the U. S. Environmental Protection Agency ( EPA) is authorized to request from industry certain data on the human health and ecological effects of commercially produced chemicals, if the Agency determines such test data is necessary to assist it in assessing the risks from such chemicals. In addition to such regulatory driven activities, industry has agreed to collect and submit certain types of chemical testing data to EPA on a voluntary basis.

In its planning and decisionmaking with respect to both regulatory and voluntary chemical testing initiatives, EPA wishes to be cognizant of the effects of such programs on industry. One question that has generated significant interest is whether sufficient laboratory capacity is available to satisfy the demand for chemical testing generated by such programs. 1 The purpose of this document is to improve EPA's understanding of the capacity of the chemical testing industry to respond to current and future testing initiatives. The report summarizes information on the current and potential future capacity in the industry to perform certain kinds of chemical tests in the United States, as well as overseas. Because the testing industry operates internationally, the report focuses not just on U. S. testing initiatives, but those elsewhere that also affect the global chemical industry, in particular the proposed expansion to the testing program in the European Union ( see Section 2.2).

In this report, the term " chemical testing industry" applies broadly to any organization 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), whose primary line of business is analytical testing; in house testing laboratories maintained by chemical companies or others ( who may also do work for hire); as well as 2 laboratories maintained and operated by academic or other institutions. The primary focus in this report is on CROs, who are likely to undertake the majority of the testing covered by this report,

although Section 3 ( supply of testing services) contains a discussion of captive, in house labs as well.

This report was prepared using public information compiled for EPA about the chemical testing industry, discussions with EPA and other experts familiar with the industry, and information collected first hand from laboratories exhibiting at a major trade show in the spring of 2004.

2.0 DEMAND FOR CHEMICAL TESTING SERVICES Laboratories and industry observers contacted during the preparation of this report agreed that the primary driver for the chemical testing industry, presently at least, is the demand for testing in the biotechnology and pharmaceutical areas. Contracts with biotech and pharmaceutical firms to conduct product testing currently account for a majority of CRO and in house testing activity, and such contracts were deemed most critical to the economic success or failure of a laboratory ( Piccirillo 2003). As a general statement, therefore, the demand for testing generated by EPAmandated ( i. e., TSCA) programs, as well as voluntary EPA testing programs, does not dominate the industry.

It is important to note that activity levels in all testing areas can change, and some labs may be more dependent on some programs than other. To help understand trends in the marketplace, the sections below review several major chemical testing programs underway in the U. S., the EU, and other countries.

2.1 HPV Testing in the United States In the U. S., one of the primary EPA testing initiatives is the " High Production Volume ( HPV)

Challenge" chemical testing program. Under the HPV Challenge, EPA has invited industry to 3 voluntarily sponsor the collection of a basic set of test data for the 2,089 chemicals produced or imported into the U. S. at volumes equal to or in excess of one million pounds. The HPV Challenge was initiated in response to findings that basic hazard data was unavailable for a substantial number of HPV chemicals.

Under the program, initiated in 1998, any needed testing should be completed by 2004 and all data will be made available to the public by 2005 ( U. S. EPA 2000). Individual chemicals that remain unsponsored may be evaluated by EPA as candidates for test rules under Section 4 of TSCA.

The HPV Challenge uses a set of 15 testing endpoints defined by OECD's " Screening Information Data Set" ( SIDS). As conceived by the OECD, the " SIDS battery" of tests can be used by governments to conduct an initial assessment of the hazards and risks posed by HPV chemical substances, and prioritize HPV chemicals to identify those in need of more in depth testing and assessment. More information on the SIDS testing protocols is presented below in Section 2.4.

2.2 HPV Testing in the European Union The European Union ( EU) operates a testing program for both new chemicals and existing chemicals produced at high volume, defined in the EU as 1,000 metric tons or greater ( 2.2 million pounds) ( European Chemicals Bureau 2004; Safepharm Laboratories 2003). Currently, it maintains dossiers on approximately 10,400 existing chemicals ( European Chemicals Bureau 2004).

The EU's proposed Registration, Evaluation and Authorisation of Chemicals ( REACH) program would substantially expand the provisions of the existing chemicals program ( Liikanen and Wallstöm 2003; Miller 2003; Synthetic Organic Chemical Manufacturers Association 2003;

Squire & Sanders 2003). Under current draft guidelines, substances produced or imported in annual quantities of 1,000 metric tons ( 2.2 million pounds) or more would need to be tested 4 within three years; 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 tested within six years; and substances produced or imported at annual quantities of 1 to 100 tons ( 2,200 to 220,000 pounds) would need to be tested within 11 years. Because it extends coverage to lower volume chemicals, the REACH proposal encompasses far more chemicals than the U. S. HPV program  an estimated 20,000 chemicals compared with the 2,089 HPV chemicals in the U. S.

Table 1. Proposed EU Chemical Testing Program ( REACH)

Threshold volume Estimated Number of Chemicals Time Frame to Complete Testing Metric tons* Pounds 1,000 or greater 2.2 million or greater 1,799 + 1,061 intermediates within 3 years between 100 and 1,000 between 220,000 and 2.2 million 1,645 within 6 years between 10 and 100 between 22,000 and 220,000 3,466 within 11 years between 1 and 10 between 2.2 and 22,000 11,711 Total chemicals covered 19,682

* Metric tons manufactured or imported to the EU on an annual basis. Source: Risk & Policy Analysts 2003.

2.3 OECD/ ICCA HPV Testing Program In 1998, the International Council of Chemical Associations ( ICCA), representing the global chemistry industry, announced an effort to work with OECD to develop test data for 1,000 priority OECD HPV chemicals ( ICCA 2002). The program has a goal of completing SIDS testing and initial hazard assessments on these chemicals by the end of 2004. This program is based on a broad international collaboration of chemical manufacturers. Under the HPV Challenge, EPA is recognizing commitments made to complete testing under the ICCA initiative ( U. S. EPA 2004). 5 While the bulk of the research is originating in Germany, Japan, the U. K., and the U. S., 20 other nations are also participating, ( OECD 2004).

2.4 Comparison of U. S. and EU HPV Chemical Testing Programs EPA's HPV Challenge Program and the EU's Existing Chemical Program involve a similar set of tests ( U. S. EPA 2003c; European Chemicals Bureau 2003; Commission of the European Communities 2003; Piccirillo 2003). The EU REACH program, however, calls for several tiers of testing, with more intensive testing required for chemicals produced at relatively high volume and less intensive testing required for chemicals produced at relatively low volume. Table 2 below provides a comparison between these two programs. 6 Table 2. Comparison of HPV and REACH Testing Programs EPA HPV EU REACH Proposal   Tiered Testing Based on Annual Volume of Chemical Produced or Imported to the EU 1 to 10 metric tonnesa 10 to 100 metric tonnes 100 to 1,000 metric tonnes 1,000 metric tonnes or more " Limited Set"

( Described in Annex V) " Base Set"

( Described in Annex VI) " Base Set + " Level 1"

( Described in Annex VII) " Base Set" + " Level 1" + " Level 2"

( Described in Annex VIII)

Estimated number of chemical substances being sponsored 2,089 11,711 + 1,061 intermediatesb 3,466b 1,645b. It is expected that some of these will ultimately be exempted from Level 1 testing. 1,799b. It is expected that some of these will ultimately be exempted from Level 1 or Level 2 testing.

Tests performed Physical Chemical Data C Melting point C Boiling point C Density ( relative density)

C Vapour pressure C Partition coefficient (

noctanol water)

C Water solubility C pH value and pKa value C Oxidation reduction potential C Adsorption/ desorption to soild C Melting point C Boiling point C Relative density C Vapour pressure C Surface tension C Water solubility C Partition coefficient n octanol/ water C Flash point C Flammability C Explosive properties C Self ignition temperature C Oxidizing properties C Granulometry Same as in column to the left Tests described in the column to the left, plus:

C Stability in organic solvents and identity of relevant degradation products C Dissociation constant C Viscosity Same as in column to the left Toxicological Studies C Acute toxicity C Repeated dose toxicity C Developmental toxicity/

Teratogenicity C Experiences with human exposure C Skin irritation or skin corrosion C Eye irritation C Skin sensitization C Mutagenicity: In vitro gene mutation study in bacteria Tests described in the column to the left,

plus:

C Skin irritation; In vivo skin irritation C Eye irritation: In vivo eye irritation C Mutagenicity: In vitro cytogenicity study in mammalian cells; In vitro gene mutation study in mammalian cells C Acute toxicity: by oral route; by inhalation; by dermal route C Repeated dose toxicity: short term repeated dose toxicity study ( 28 days)

C Reproductive toxicity: screening for reproductive/ developmental toxicity;

developmental toxicity study C Toxicokinetics Tests described in the column to the left, plus:

C Repeated dose toxicity:

shortterm repeated dose toxicity study ( 28 days); sub chronic toxicity study ( 90 days)

C Reproductive toxicity:

developmental toxicity study ( additional); two generation reproductive toxicity study Tests described in the column to the left,

plus:

C Reproductive toxicity: two generation reproductive toxicity study ( additional) Table 2. Comparison of HPV and REACH Testing Programs EPA HPV EU REACH Proposal   Tiered Testing Based on Annual Volume of Chemical Produced or Imported to the EU 1 to 10 metric tonnesa 10 to 100 metric tonnes 100 to 1,000 metric tonnes 1,000 metric tonnes or more " Limited Set"

( Described in Annex V) " Base Set"

( Described in Annex VI) " Base Set + " Level 1"

( Described in Annex VII) " Base Set" + " Level 1" + " Level 2"

( Described in Annex VIII)

7 Environmental Fate and Pathways c C Photodegradation C Stability in water ( hydrolysis)

C Monitoring data ( environment)

C Transport and distribution between environmental compartments including estimated environmental concentrations and distribution pathways C Biodegradation C Degradation: biotic; abiotic C Fate and behavior in the environment:

adsorption/ desorption screening study C Degradation:

biotic( additional);

identification of degradation products C Fate and behavior in the environment: adsorption/

desorption ( additional);

bioconcentration in one aquatic species, preferably fish C Degradation: biotic( additional)

C Fate and behavior in the environment ( additional)

Ecotoxicological Studies C Acute/ prolonged toxicity to fish C Acute toxicity to aquatic invertebrates ( daphnia)

C Toxicity to aquatic plants e. g. algae C Chronic toxicity to aquatic invertebrates ( daphnia)

C Toxicity to terrestrial organisms C Avian dietary toxicity test C Avian reproduction test C Earthworms acute toxicity test C Terrestrial plants, growth test C Aquatic toxicity: Short term toxicity testing on Daphnia Tests described in the column to the left,

plus:

C Aquatic toxicity: Growth inhibition study on algae; Short term toxicity testing on fish; Activated sludge respiration inhibition testing ests described in the column to the left, plus:

C Aquatic toxicity: Long term toxicity testing on Daphnia;

Long term toxicity testing on fish C Effects on terrestrial organisms: Short term toxicity to earthworms; Effects on soil micro organisms; Short term toxicity to plants Tests described in the column to the left,

plus:

C Effects on terrestrial organisms:

Longterm toxicity to earthworms;

Longterm toxicity to soil invertebrates;

Long term toxicity to plants C Long term toxicity to sediment organisms C Long term or reproductive toxicity to birds Sources: US. EPA 2003c, Commission of the European Communities 2003, Risk & Policy Analysts 2003.

a Also required for isolated intermediates transported in quantities of greather than 1,000 tonnes per year bSee Risk & Policy Analysts 2003, p. 35 and 37. Figures do not include polymers.

c EU documentation lists these tests under the category of " Ecotoxicological Studies"

d This test may also be categorized under Environmental Fate and Pathways 2 It is important to note that the test plans reviewed represent only 38 percent of all HPV chemicals. For the remaining chemicals it is not known whether existing data or modeling results will satisfy the testing requirements to the same degree.

8 2.5 Impact of the HPV Challenge and REACH on Chemical Testing Demand Testing demand to satisfy data needs for the HPV Challenge has been lower than initially expected because many of the data gaps identified in EPA's HPV testing initiative have been filled using existing research, thereby avoiding the need for new testing. For example, Environmental Defense's " HPV Tracker" tool indicates that, based on test plans filed through July 2004, no further testing is planned for 460 of 1,338 chemicals ( 34.4 percent) ( Environmental Defense,

2004).

EPA's own analysis indicates the amount of new testing required may be even lower. Through August 2003, EPA had received and reviewed ( but not necessarily approved) test plans covering approximately 790 HPV chemicals. Each test plan addresses the 15 SIDS endpoints, thus the test plans reviewed address a total of 11,850 endpoints. The reviewed test plans suggest that approximately 6,800 endpoints, or 45 percent of the total, can be satisfied with existing data ( see Table 3). For another 50 percent, or 7,400 endpoints, data was submitted based on analogy,

structure activity relationship modeling, technical discussion, " read across," or computer and mathematical modeling. Sponsors plan to conduct actual new testing to fill data gaps for only the remaining 785 endpoints. This would represent just 6.5 percent of the endpoints required to fulfill the SIDS testing requirements for these 790 chemicals2 ( U. S. EPA 2004b). 9 Table 3. Summary of Test Requirements for 790 Sponsored HPV Chemicalsa, b Testing Status Chemical Properties Environmental Fate and Pathways Ecotoxicity Health Effects Totals Melting Point Boiling Point Vapor Pressure Partition Coefficient Water Solubility Photodegradation Biodegradation Stability in Water Transport/

Distribution Acute Fish Acute Invertebrates Acute Algae Terrestrial Toxicity Acute Toxicity (

oral,

dermal,

inhalation) Genetic Toxicity (

in vitro:

bacterial Genetic Toxicity (

in vivo) Repeated Dose Toxicity Reproductive Developmental Number of Chemicals Proposed for testing 25 38 15 73 89 9 60 32 5 47 57 68 1 7 37 29 47 70 76 785 Analogy, SAR, Estimation 290 299 372 444 365 583 343 414 634 363 405 450 8 232 358 418 389 501 477 7,345 Adequate existing data 325 385 320 242 307 122 361 141 80 344 292 234 0 532 383 252 330 185 205 5,040 Testing based on results of other category members 0 0 4 1 1 8 0 3 13 4 4 4 0 0 0 0 0 0 0 42 Reproductive and developmental testing will depend on results of repeat dose studies 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 5 3 9 Not applicable due to physical/ chemical properties 150 68 79 29 28 68 25 200 57 32 32 34 781 19 11 61 23 26 25 1,748 Not addressed in test plan 0 0 0 1 0 0 1 0 1 0 0 0 0 0 1 30 0 3 4 41 TOTAL 790 790 790 790 790 790 790 790 790 790 790 790 790 790 790 790 790 790 790 15,010 aBased on EPA's preliminary review of submitted test plans as of August 29, 2003.

bThe columns show 19 endpoints, however only 15 must be completed to fulfill the SIDS dossier. For example: the transport and distribution test is optional; submitters may complete the genetic toxicity requirement using either in vivo or in vitro methods; and submitters may complete either the repeated dose toxicity test or a combination of the reproductive and developmental toxicity testing. See U. S. EPA ( 2003c) for further details. 10 11 The EU's REACH program is still in draft proposal form and it will likely be several years before legislation is put in place to make it law. Nevertheless, the broader coverage of REACH compared with the HPV program makes it important to look at even now.

From the standpoint of generating demand for testing, the REACH program will likely exceed that of HPV for several reasons. To begin with, the number of chemicals covered is substantially greater ( approximately 20,000 for REACH versus 2,089 for HPV Challenge). The more significant fact, however, is likely to be differences in the availability of existing data for thousands of lower volume REACH chemicals. As noted above, U. S. experience shows that test data exists already for many HPV Challenge chemicals. But these were chemicals produced at levels equal to or in excess of one million pounds. The REACH program will extend to chemicals produced at levels as low as one metric ton ( 2,200 pounds) per year. For these low volume chemicals the likelihood of industry producing existing test data could be much lower because the low production volumes neither warrant such testing nor generate the profit margins needed to fund such testing.

The EU Commissioners who introduced REACH estimate that European testing facilities will only be able to provide 25 to 30 percent of the testing capacity required ( Liikanen and Wallstöm 2003, p. 17). They anticipate that testing demand generated by REACH may be met using " capacity from elsewhere in the world," and suggest the possibility that " the decision to establish REACH will lead to investment in additional testing capacity." It is reasonable to anticipate,

therefore, that REACH will significantly influence the world wide chemical testing market in the years to come.

One testing lab, which focuses on environmental toxicity testing, reports that some of its clients are already scheduling tests called for under draft REACH legislation, even though the legislation may not be made into law for several more years ( Hutchinson and Jaber 2004). These firms are concerned that there could be a temporary shortage of capacity for environmental toxicity testing immediately following the passage of REACH, particularly if the timing coincides with the 12 implementation of endocrine disruptor testing requirements.

2.6 U. S. Testing for Endocrine Disruption Potential Scientific evidence has been accumulating that suggests that environmental exposure to chemicals that mimic hormones ( endocrine disruptors) may cause adverse health effects in human and wildlife populations. In the U. S., Congress acted in response to this evidence in the1996 Food Quality Protection Act, which amended the Federal Food, Drug, and Cosmetic Act ( FFDCA) and directed EPA " to determine whether certain substances may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or such other effects as [ EPA]

may designate". When carrying out the program, the statute requires EPA to " provide for the testing of all pesticide chemicals." The statute also provides EPA with discretionary authority to " provide for the testing of any other substance that may have an effect that is cumulative to an effect of a pesticide chemical if the Administrator determines that a substantial population may be exposed to such a substance." In addition, section 1457 of the Safe Drinking Water Act provides EPA with discretionary authority to provide for testing, under the FFDCA 408( p) screening program, " of any other substances that may be found in sources of drinking water if the Administrator determines that a substantial population may be exposed to such substance."

EPA is currently planning on using a two tier system to test chemicals for endocrine disruption effects. Tier 1 screening is designed to detect chemical substances capable of interacting with the estrogen, androgen, and thyroid hormonal systems. Tier 2 testing is designed to determine whether a chemical may have an effect similar to that of naturally occurring hormones and to identify, characterize, and quantify those effects for estrogen, androgen, and thyroid hormones.

Tier 2 testing will be required for chemicals that are identified as potential endocrine disruptors by the Tier 1 screening battery. EPA is currently developing and validating a number of assays, the majority of which are being considered for the Tier 1 screening battery. The assays under consideration are described below. More information is available at http:// www. epa. gov/ scipoly/ oscpendo/ assayvalidation/ status. htm. 13 Table 4. Endocrine Disruptor Screening Assays Under Consideration Tier 1 Screening Aromatase Aromatase is an enzyme complex responsible for estrogen biosynthesis that converts androgens into estrodiol and estrone. The Aromatase assay focuses on this portion of the steroidogenic pathway to detect substances that inhibit aromatase activity.

Steroidogenesis The Steroidogenesis assay uses sliced testes from the rat to detect interference with any steps leading to the production of testosterone.

Estrogen Receptor ( ER) Binding Chemicals can affect the endocrine system by binding to hormone receptors to either mimic the action of the natural hormone or block access of the hormone to the site and thus block hormone controlled activity. The Estrogen Receptor Binding assay monitors chemical binding with an estrogen receptor.

Androgen Receptor ( AR) Binding The Androgen Receptor Binding assay monitors chemical binding with an androgen receptor.

Uterotrophic The uterotrophic assay involves the use of whole rats to detect the ability of a chemical to stimulate or inhibit estrogenic responses of the uterus ( measured through change in uterine weight).

Hershberger The Hershberger assay involves the use of whole rats to detect the ability of a chemical to stimulate or inhibit androgenic responses in secondary sex organs ( e. g., ventral prostate and seminal vesicle).

Pubertal Female The Pubertal Female assay involves the use of whole rats to screen for estrogenic and thyroid activity in females during sexual maturation. This assay examines abnormalities associated with sex organs and secondary sexual characteristics.

Pubertal Male The Pubertal Male assay involves the use of whole rats to screen for estrogenic and thyroid activity in males during sexual maturation. This assay examines abnormalities associated with sex organs and secondary sexual characteristics.

Amphibian Metamorphosis The Amphibian Metamorphosis assay involves the use of whole tadpoles to characterize dose response characteristics and adverse reproductive and developmental effects.

Fish Screen The Fish Screen assay screens for estrogenic and androgenic effects. The assay involves the use of whole fish to examine abnormalities associated with survival, reproductive behavior, secondary sex characteristics, and fecundity ( i. e., number of spawns, number of eggs/ spawn, fertility, and development of offspring). Table 4. Endocrine Disruptor Screening Assays Under Consideration 14 Tier 2 Screening Mammalian 2 Generation The Mammalian 2 Generation assay involves the use of whole rats to characterize dose response characteristics and adverse reproductive and developmental effects.

Avian 2 Generation The Avian 2 Generation assay involves the use of whole birds to characterize dose response characteristics and adverse reproductive and developmental effects.

Amphibian 2 Generation The Amphibian 2 Generation assay involves the use of whole frogs to characterize dose response characteristics and adverse reproductive and developmental effects.

Invertebrate Lifecycle The Invertebrate Lifecycle assay involves the use of whole mysid shrimp to characterize dose response characteristics and adverse reproductive and developmental effects.

Fish Lifecycle The Fish Lifecycle assay involves the use of whole fish to characterize dose response characteristics and adverse reproductive and developmental effects.

Tier to be determined In Utero through Lactation The In Utero through Lactation assay involves the use of whole rats to assess post natal development after in utero, lactational, and post lactational exposure.

Table 5 summarizes the assays under consideration. Some of the assays list multiple substrates ( such as rat cytosol, human placental, and human recombinant). Testing for an assay would only be required for a single substrate source, although there could be optional substrates for some assays. Some of these substrates may eventually be eliminated from consideration. 15 Table 5. Endocrine Disruptor Screening   Assays Under Consideration Assay and substrate Assay Description Tier 1 Screening Aromatase Rat Cytosol Human placental ( post delivery) Human Recombinant In vitro. Aromatase is a cytochrome P450 enzyme complex responsible for estrogen biosynthesis and converts androgens ( testosterone and androstenedione) into estrodiol and estrone. The purpose of this assay is to focus on this portion of the steroidogenic pathway to detect substances that inhibit aromatase activity.

Steroidogenesis Sliced rat testes Cell based H295R In vitro. Steroidogenesis detects interference in any steps leading to the production of testosterone.

Estrogen Receptor ( ER) Binding Rat uterine cytosol Human recombinant In vitro. One of the most basic ways chemicals affect the endocrine system is to bind to hormone receptors, to either mimic the action of the natural hormone or block access of the hormone to the site and thus block hormone controlled activity. This assay detects binding ( or gene expression that results from several steps including binding) to the estrogen receptor.

Androgen Receptor ( AR) Binding Rat prostate cytosol Human recombinant In vitro. Similar to Estrogen Receptor Binding above, but for androgen receptor binding.

Uterotrophic ( OECD) Rat ( whole): Detects ability of chemical to stimulate or inhibit estrogenic responses of the uterus ( i. e., increased uterus weight).

Hershberger ( OECD) Rat ( whole): Detects the ability of a chemical to stimulate or inhibit androgenic responses in secondary sex organs ( e. g., ventral prostate and seminal vesicle).

Pubertal female Rat ( whole): Screens for estrogenic and thyroid activity on females during sexual maturation. Examines abnormalities associated with sex organs and secondary sexual characteristics.

Pubertal male Rat ( whole): Screens for androgenic and thyroid activity in males during sexual maturation. Examines abnormalities associated with sex organs and secondary sexual characteristics.

Amphibian Metamorphosis Tadpoles ( whole): Characterizes dose response characteristics and adverse reproductive and developmental effects.

Fish Screen ( OECD) Fish ( whole): Screens for estrogenic and androgenic effects. Examines abnormalities associated with survival, reproductive behavior, secondary sex character and fecundity. Table 5. Endocrine Disruptor Screening   Assays Under Consideration Assay and substrate Assay Description 16 Tier 2 Screening Mammalian 2 generation Rat ( whole): Characterizes dose response, characteristics and adverse reproductive and developmental effects.

Avian 2 generation Bird ( whole): Characterizes dose response characteristics and adverse reproductive and developmental effects.

Amphibian 2 generation Frog ( whole): Characterizes dose response characteristics and adverse reproductive and developmental effects.

Invertebrate Lifecycle Mysid shrimp ( whole): Characterizes dose response characteristics and adverse reproductive and developmental effects.

Fish Lifecycle Fish ( whole): Characterizes dose response characteristics and adverse reproductive and developmental effects.

Tier to be determined In Utero through Lactation Rat ( whole): Assesses postnatal development after in utero, lactational and post lactational exposure ( F 1 ).

Assay Development and Validation The FFDCA required EPA to use " appropriate validated test systems and other scientifically relevant information" to determine whether substances have an endocrine effect. The science related to measuring and demonstrating endocrine disruption is relatively new and validated testing methods are still being developed. EPA is putting the assays through a process of development, pre validation, validation, and peer review.

Pre validation involves optimization and standardization of the protocol and the development of preliminary data on reproducibility within a single laboratory ( e. g, performance criteria).

Validation tests the transferability of the protocol to other laboratories, determines the reliability of the protocol, and further documents its relevance. Validation studies are conducted at several different laboratories using the same protocol. After testing is complete, EPA compares the interlaboratory results statistically to determine whether or not the protocol meets the criteria for 17 reliability . All EDSP methods must be peer reviewed before they are approved for regulatory use. The study results generated during protocol development, pre validation, and validation are combined into EDSP method specific documents. These documents then undergo an external peer review following Agency guidelines. Once the Agency has considered the results of the peer review and the regulatory procedures are made known, the Agency can begin requiring the ED testing using the optimized and validated protocols.

Number and Types of Chemicals Affected The number and types of chemicals that may be subject to testing for endocrine disrupting potential is uncertain. In its December 2002 request for comments on the screening program,

EPA proposed to follow the recommendations of a subcommittee of the EPA Science Advisory Board ( SAB) and the FIFRA Scientific Advisory Panel ( SAP) to initiate the Tier 1 screening program with a set of 50 to 100 chemicals and use the results to further refine the program. The notice further goes on to say:

EPA has stated its intention to consider a broad universe of chemicals as potential candidates for testing under the EDSP including pesticide chemicals, non pesticide commercial chemicals, mixtures, and environmental contaminants ( 63 FR 71542). However, for the first group of chemicals to be tested, EPA is intending to focus only on pesticide active ingredients and high production volume ( HPV) chemicals with some pesticidal inert uses ( i. e., the chemicals that are specifically mandated for testing under section 408( p) of FFDCA). The pesticide inerts to be considered are those with relatively large overall production volumes considering both pesticide and non pesticide uses. This approach will allow EPA to focus its initial endocrine screening efforts on a smaller and more manageable universe of chemicals that emphasizes early attention to the pesticide chemicals that Congress specifically mandated EPA to test for possible endocrine effects.

( 67 FR 79611; December 30, 2002)

Thus, in all likelihood the program will start small but could expand to include greater numbers and more types of chemicals, depending on the results of the initial screening. 3 Table A 1 identifies labs according to their capabilities in each of these areas. Tables A 2 through A 10 highlight each of the nine areas of testing. Table A 11 provides contact information for each of the 50 18 3.0 SUPPLY OF CHEMICAL TESTING SERVICES In this report, the analysis of chemical testing services supply is based primarily on expert knowledge of the testing industry and first hand discussions with laboratory representatives, as EPA has not found comprehensive information on the industry in published sources. The following sections review the contract research organization ( CRO) segment of the market and the in house, captive testing segment of the market, and other sources of testing services supply.

3.1 Contract Research Organizations To assist in assessing the number and geographic distribution of CROs capable of conducting the types of testing required under the programs identified above, an industry expert was consulted and dispatched to the annual meeting and exhibition of the Society of Toxicology ( SOT), which took place in Baltimore from March 21 to 25, 2004. This meeting, known as ToxExpo, is billed as the largest toxicology meeting and exhibit in the world, attracting some 6,000 attendees from industry, academia, and government and over 280 exhibitors from the U. S. and overseas ( SOT 2004). Based on a review of exhibitor lists from past SOT meetings, EPA judged that the 2004 meeting was likely to attract a majority of CROs with chemical testing capabilities of interest for this report ( Piccirillo 2003).

Prior to the conference, the consultant reviewed the list of 2004 exhibitors and identified those known or believed to participate in chemical testing. At the conference, the consultant visited the booths of 50 such CROs, picked up laboratory qualifications statements and other literature, and asked general questions about capabilities.

Following the conference, the consultant reviewed the materials and analyzed the capabilities of the labs based on the information collected. Appendix A shows these results in detail. 3 Each lab laboratories.

19 has been evaluated to determine its capabilities in nine areas of testing:

C Physical/ chemical characteristics C General toxicity  acute C General toxicity  repeated/ subchronic C General toxicity  teratogenicity/ developmental toxicology C General toxicity  reproductive/ reproduction C General toxicity  chromosomal aberation micronucleus C Aquatic toxicity  fish/ daphnia/ algae C Analytical chemistry C Environmental fate The results of the analysis are summarized in Table 6 below.

Table 6. Capability of Contract Research Organizations to Conduct Chemical Testing Type of Testing Number of Labs U. S. Non U. S. Total Physical/ chemical characteristics 6 9 15 General toxicity  acute 19 22 41 General toxicity  repeated/ subchronic 20 23 43 General toxicity  teratogenicity/ developmental toxicology 11 21 32 General toxicity  reproductive/ reproduction 11 20 31 General toxicity  chromosomal aberration micronucleus 8 18 26 Aquatic toxicity  fish/ daphnia/ algae 6 10 16 Analytical chemistry 20 18 38 Environmental fate 8 11 19 Total number of labs with testing capabilities 27 23 50 Source: Piccirillo 2004.

As shown, the number of U. S. based labs exhibiting at ToxExpo that were judged capable of 20 conducting the types of testing needed to provide HPV data ranges from as few as a half dozen to twenty, depending on the type of testing. Generally, an equal or greater number of labs outside the U. S. have similar capabilities. These include labs located in Brazil, Canada, Denmark,

England, Germany, India, Italy, Japan, Korea, Netherlands, and Switzerland ( see also Appendix A).

Currently, there is no single U. S. laboratory that can provide the full range of capabilities potentially required to fully test the safety of an industrial chemical ( Piccirillo 2004). A total of six non U. S. based labs were judged to be capable of conducting the full suite of testing, and an additional four were judged to be capable to conduct testing in all but one area. The mean number of capabilities ( out of a total of nine) is 5.2 when averaged among all 50 labs. For the 27 U. S. based labs, the mean number of capabilities is 4.0, while the mean number of capabilities for the 23 non U. S. based labs was 6.6. Thus, labs outside the U. S. on average provide a somewhat greater range of capabilities.

According to observers of the industry, CRO chemical testing laboratories are generally specialized into two groups  those that focus on mammalian toxicology and those that study toxicology in fish and/ or birds. Worldwide, there are only about 16 CROs in the field of aquatic toxicology and 11 in the field of avian toxicology ( Hutchinson and Jaber 2004).

In addition, there are approximately eight CROs qualified to conduct testing in genetic toxicology ( Piccirillo 2004). There are only three CROs in the United States that perform biodegradation tests, supplemented by a few small labs in Europe and a few major chemical manufacturers ( e. g.,

ExxonMobil) that conduct in house testing ( Hutchinson and Jaber 2004). Testing labs that can conduct physical chemical studies are more common and widespread; the necessary expertise is more available and the laboratory work can be conducted relatively quickly.

In addition to first hand data collected at ToxExpo, EPA reviewed a 2001 report from the U. K's Institute for Environment and Health which estimated there to be approximately 16 CROs in the 4 The report defined a " base set" as the following set of tests: mammalian acute oral toxicity, mammalian acute dermal irritation/ corrosion, mammalian acute eye irritation, mammalian skin sensitization, mammalian repeated dose 28 day oral toxicity, mammalian reproductive/ developmental toxicity screening, and acute toxicity in fish.

21 European Union ( EU) capable of performing chemical safety testing ( Institute for Environment and Health 2001). On average, each of these laboratories has the capacity to conduct a full " Base Set" of tests for 40 chemicals per year. 4 In light of the global, integrated structure of the chemical testing market, it is assumed that this throughput can be taken as generally representative for fullservice testing labs throughout the world.

3.2 Captive In House Testing Labs Observers of the testing market also note that chemical manufacturers themselves are providing some of the capacity for chemical testing through their in house laboratories ( Piccirillo 2004;

Muermann 2004; Ohne and Siddiqui 2004; Hutchinson and Jaber 2004). Industry observers were unable to compare the relative volume of testing work performed at CROs and at in house industrial laboratories, but agreed that a significant volume of testing is performed in house. The testing programs of Dow, Dupont, and ExxonMobil were mentioned as particularly noteworthy.

However, a number of factors restrict the extent to which chemical manufacturers can rely on their own testing facilities. For example, a Dow Corning representative stated that the company had no current in house capacity to conduct genetic toxicology testing ( Ohne and Siddiqui 2004).

Factors that play into in house testing allocations include available space, the particular expertise available in house, the relative cost of in house testing versus outsourcing, and the motivation to form testing consortia with other manufacturers. When several chemical manufacturers agree to form a consortium for the testing of a particular chemical, it is often most expedient for the consortium to use a CRO rather than the in house lab of any one member, due to concern over the appearance of conflict of interest ( Muermann 2004).

3.3 Other Sources of Testing Capacity 22 Additional sources of laboratory testing capacity may exist withing university departments or other research centers in the U. S. and around the world. While they may have capabilities to conduct some of the testing described in this report, such facilities are generally not set up to perform testing on a commercial scale. Although this report did not examine these kinds of facilities in detail, industry observers consider it unlikely that significant commercial testing capacity would be available from such sources ( e. g., Piccirillo 2003).

4.0 CURRENT INDUSTRY ISSUES As described in Section 2, recent demand for testing has in fact been beneath the expectations of CRO testing laboratories. Among the circumstances contributing to lower than expected testing demand has been the ability of industry to satisfy HPV Challenge data needs using existing data,

or computer modeling. As noted in Section 3, less than seven percent of 790 chemicals covered by HPV Challenge test plans reviewed by EPA were proposing new testing. This section discusses other issues identified that may be affecting both the demand for and supply of testing services.

4.1 Issues Affecting Demand As noted above, demand for HPV testing has been below expectations, but this may begin to change as the proposed expansion to the EU testing program gets underway. The EU REACH proposal would encompass many more chemicals, albeit while applying a tiered testing approach.

Until the testing demand driven by REACH begins to materialize, however, it appears that other drivers will dominate the market for chemical testing.

The primary " other" driver of testing demand is the pharmaceutical and biotech business. One major testing lab indicated that its non pharmaceutical market represents only six to eight percent of total sales ( Muermann 2004). Because of this reliance on pharmaceutical demand, changes in demand driven by other factors, such as EPA testing activity, are not likely to have great influence 23 on capacity decisions.

Another factor that has kept chemical testing demand in check has been the recent trend towards consolidation in the chemical and agri chemical industries, reducing the number of product lines that need to be tested. Several labs that reported downward trends in testing demand over the last two or three years attributed the change ( at least in part) to consolidations and mergers among major clients ( for example, the recent merger of Bayer and Aventis) ( Holbert 2003,

Hutchinson and Jaber 2004). These mergers have had several effects, including consolidation of product lines ( fewer new products means fewer new tests) and also greater reliance on in house testing capabilities.

Both chemical manufacturers and testing laboratories ( and regulatory agencies as well) have been under pressure from animal rights groups to minimize the amount of animal testing being conducted. In the case of upcoming testing under the EU REACH program, pressure from animal rights groups is likely to be even more intense ( Piccirillo 2003). One testing lab even reported that it had moved away from the entire field of mammalian toxicology because social pressure had moved its primary clients ( in the cosmetics industry) away from animal testing in the early 1990s ( Kim 2004).

ACC indicates that the need for new laboratory work in response to the HPV initiative is distributed fairly evenly across the fields of mammalian toxicology, environmental toxicology, and physical/ chemical properties. One possible exception is mammalian toxicology, where there is a somewhat greater need for new lab work in the field of reproductive testing ( proposed under REACH) and developmental testing ( included in HPV testing and proposed under REACH)

( Russell 2003).

Overall, while it is difficult to assess relative strength of demand for particular types of testing,

those areas of testing in which demand has been reported to be particularly strong ( relative to testing capacity) are: the testing of chemical toxicity via inhalation pathways, the testing of 24 reproductive toxicity, and the testing of biodegradation ( Piccirillo 2003).

4.2 Issues Affecting Supply The ability of laboratories to respond to changes in demand is of interest because EPA and others who propose new testing initiatives need to provide sufficient lead time for such testing to be completed. Preliminary interviews indicate the HPV testing initiative has produced significantly less new business for the chemical testing industry than was anticipated when the program was announced ( Picciorillo 2003; Holbert 2003; U. S. EPA 2004b). Industry observers call this the latest in a " pattern of disappointment" that has followed past EPA testing initiatives. This feeling of disappointment may contribute to future industry wariness to expand capacity in response to testing initiatives.

The ability of labs to expand capacity beyond what currently exists will depend on several factors,

such as equipment and buildings costs. Capacity to conduct the most sophisticated tests, such as those that assay developmental or neurotxicological effects may be far more difficult to scale up,

in comparison with more standardized testing such as acute toxicity ( Picirrillo 2003). Among the reasons cited are the lengthy and costly validation processes for these types of testing, and the limited availability of trained program managers and technicians. To validate tests in which experimenters make subtle observations ( about animal behavior or developmental morphology,

for example) each laboratory must conduct regular trials that demonstrate the consistency and accuracy of their staff's judgement. However, lab capacity to conduct screening level HPV tests ( i. e., the standard SIDS battery) is not limited by these validation issues  the issue is more relevant with respect to the advanced testing that HPV screening tests may prompt.

A particular bottleneck in testing capacity may exist in the area of inhalation testing, where the expense and expertise necessary to custom build the inhalation apparatus is a significant factor limiting expansion of capacity, particularly for new entrants into the field. One firm that conducts inhalation toxicity testing reports that, despite two rounds of capacity expansion, it is currently 25 running a four month backlog. Potential clients initially balk at accepting this delay in beginning work, until they discover that the firm's competitors have comparable backlogs ( Sved 2004). One reason why capacity is particularly restricted for inhalation testing of chemicals is that there is little pharmaceutical demand for such tests to encourage companies to invest in the necessary equipment ( Sved 2004, Hardy 2004). Even those prospective drugs which require inhalation toxicity testing ( e. g., nasal aerosols and powders) are generally tested using a different protocol ( snout only) from industrial chemicals ( whole body). Thus, the market for inhalation toxicology testing is unusually small and reliant upon regulatory programs to generate business demand.

There is a great deal of variability among tests in terms of the industry's ability to adjust capacity to meet demand ( Piccirillo 2003; Holbert 2003). Acute toxicity testing work may be scaled up relatively easily, but more complex testing such as two generation developmental toxicology studies may be limited by available space and staffing. Two generation developmental toxicology studies in particular present logistical difficulties because they typically require raising and housing over 1,000 animals ( Piccirillo 2004). Also, the initial investment to enter certain fields of testing may be prohibitive  for example, it is estimated to cost close to a million dollars ( in equipment and method validation) to enter the field of neurotoxicological testing. Similarly, testing of toxicity via inhalation pathways requires particularly expensive, specialized equipment ( Hardy 2004, Sved 2004).

One CRO laboratory, about 65,000 square feet in size, reports that it currently performs between 200 and 300 acute toxicity studies in a year but could easily double that volume if the demand were present ( Holbert 2003). One ecotoxicology laboratory reports that it could increase avian toxicology testing by 30 to 40 percent and double avian toxicology testing without experiencing any delays or capacity troubles. ( Hutschinson and Jaber, 2004). Conversely, labs involved in other fields of testing such as biodegradation tests, tests of reproductive toxicity, and toxicity tests involving inhaled chemicals are currently operating closer to current capacity ( Hutchinson and Jaber 2004; Hardy 2004, Sved 2004). 26 The availability of trained staff can also present a barrier to capacity expansion. Recruiting challenges vary considerably depending on geography and the particular skill sets required. For example, a central Ohio testing laboratory reports that the difficulty of finding suitable staff for its respiratory toxicology work places a significant constraint on testing capacity ( Sved 2004).

However, a Boston area testing laboratory reported few problems finding staff to fill its expanded facilities for general mammalian toxicology ( Dreckert 2004). Sometimes, the difficulty in finding suitable staff is overqualification rather than underqualification ( Newton 2004). While some positions are best filled by persons with bachelor's or master's degrees, others are best filled by persons with associate's degrees ( Newton 2004, Hutchnson and Jaber 2004).

Anticipation of increased demand from pharmaceutical companies subject to FDA regulation is the primary driver of business expansion among chemical testing labs. One chemical testing lab that provides acute, subchronic, and chronic toxicity testing reports that it is in the midst of a major expansion of its mammalian toxicology facilities ( Deckert 2004). The lab is also hopeful that the provisions of EU's REACH program will increase demand for its laboratory facilities.

Even though capacity adjustment may be relatively easier in some fields than in others, the chemical testing industry as a whole is hesitant to increase capacity in response to upsurges in demand. A representative of the American Chemistry Council emphasizes that there are strong barriers to the expansion of the overall capacity of the chemical testing industry ( Russell 2003).

He argues that the supply of chemical testing is fairly inelastic  recently, testing firms have been responding to increases in demand by raising prices rather than by expanding capacity. In addition,

the use of customized testing protocols will tend to restrict capacity, as only the most highly specialized labs are able to implement modified versions of standard testing protocols. Chemical testing labs are wary of over reacting to short term swings in demand from temporary regulatory initiatives. One chemical testing company explained that it deliberately cross trains its personnel in a variety of fields so that it can respond to localized swings in demand for particular tests without changing overall staffing levels ( Muermann 2004). 27 When new regulations increase demand for a particular kind of testing ( for example, FIFRA between 1989 and 1993), toxicological testing laboratories tend to respond by raising their prices and accumulating a backlog of assignments rather than expanding capacity ( Piccirillo 2004).

However, a lab with highly specialized expertise in inhalation testing reports that it is responding to increased demand by expanding its capacity ( Sved 2004). Capacity expansion notwithstanding,

two labs agreed that the need for reproductive toxicology studies of inhaled chemicals is likely to be a significant bottleneck and data gap for chemical testing in the near future ( Sved, 2004; Hardy 2004).

It is difficult to extrapolate from existing experience with the HPV Challenge to predict the effect of the EU's REACH program, particularly since the definite provisions of the REACH program will not be settled until at least 2005 ( Russell 2003; Cascone 2004; Dalton 2004). Even if the EU REACH program is passed as currently written, there remains significant uncertainty about how it will influence chemical policies in jurisdictions outside the EU.

Some labs have high hopes for future business to be generated by Tier 1 endocrine testing. A total of 16 labs have been involved in validating these Tier 1 endocrine tests. There remains significant uncertainty about what the final provisions of EPA's endocrine disruptor testing program will be ( Becker 2003; Silagi 2003). It is not known currently which tests will be validated for use in this program and what the proposed pace of testing will be. A representative from the American Chemistry Council pointed out that the pace of testing will need to be known before the question of capacity can be addressed ( Russell 2003).

Overall, based on contacts made for this report, the current economic condition of the chemical testing industry appears mixed. Some testing labs report slack demand, while others ( particularly those with a strong base of clients in pharmaceutical research and development) report excellent sales and ongoing facilities expansion ( Holbert 2003; Newton 2004; Deckert 2004; Hutchinson and Jaber 2004).

As a possible indicator of economic health of the chemical testing industry, EPA examined data 28 on trends in lab accreditation, specifically accreditation under the Association for the Assessment and Accreditation of Laboratory Animal Care ( AAALAC) standard. While AAALAC accreditation is not legally required, it is an important credential for any commercial lab engaged in tests involving animals. AALAC reports a relatively steady, 1 to 2 percent growth rate over the last decade in the accreditation of laboratories that use laboratory animals as subjects. ( AAALAC 2004). Unfortunately, more detailed data breaking out statistics for chemical testing labs ( versus other types of labs that use animals) were not available from AAALAC. There does not appear to be any other body that accredits chemical testing labs specifically. Although many such labs must adhere to principles of Good Laboratory Practice ( GLP), GLP compliance is audited directly by clients or consultants, not by any trade organization ( Muermann 2004).

One CRO reported that it noticed an inverse relationship between the economic health of its clients and the amount of business it receives from them. ( Sved 2004). The rationale proposed for this phenomenon is that economic troubles encourages businesses to invest in research and development, generate new products, and then submit the new products to the CRO for testing.

A final factor that may affect the relative availability of testing capacity to U. S. chemical manufacturers is the relative weakness of the dollar ( Muermann 2004). Chemical testing is a globalized market, in which a range of international clients seek the services of a global array of testing laboratories. When the dollar devalues against the euro, the substantial portion of the global testing market that is located in Europe becomes less accessible to U. S. firms. As a corollary, a weaker dollar also means that U. S. chemical companies are likely to face stiffer competition with European firms for the limited testing capacity available in the U. S. 29 5.0 CONCLUSIONS This report examines the global market for testing of industrial chemicals for evidence of effects on human health and the environment. Such testing information is required by governments to assist in evaluating the risks to humans and the environment from the manufacturing, processing,

transportation, distribution, use, and disposal of such chemicals. The demand for such testing is driven by government regulatory programs as well as voluntary programs. In the U. S., the primary drivers for such testing are programs authorized under the Toxic Substances Control Act ( TSCA), particularly TSCA Section 4, and voluntary programs such as the HPV Challenge, also administered by the U. S. Environmental Protection Agency ( U. S. EPA).

Because the chemicals industry is global in nature, the testing and evaluation programs in other parts of the world are also of interest. The primary non U. S. program examined in this report is the existing chemicals program of the European Union, in particular the proposed expansion of the existing chemicals testing program known as Registration, Evaluation and Authorisation of Chemicals, or REACH.

The report finds that, to date, the testing of chemicals for human and environmental effects driven by regulatory and voluntary programs such as those managed by EPA ( including the HPV Challenge) have not been the major driver for chemical testing demand overall. In fact, testing to satisfy pharmaceutical and biotechnology product introductions has tended to overshadow EPArelated testing. Numerous contract research organizations ( CROs) report that testing to support pharmaceutical and biotech product market introduction dominates their testing programs.

EPA's own analysis indicates that the HPV Challenge, while large in scope ( encompassing more than 2,000 high volume chemicals) has not generated the volume of new testing demand that was initially expected. To industry, this reinforces a pattern it has seen before: a tendency for regulatory programs to generate less demand for testing than initially promised. As a result,

numerous laboratories report taking a " wait and see" attitude to EPA programs. Much the same 30 position is taken towards REACH and towards other types of testing on the horizon, such as that for endocrine disruption potential. At this point, the ultimate impact on testing demand cannot be determined, and few labs are expanding capacity in anticipation of increased demand.

Based on EPA's analysis of the capabilities of labs exhibiting recently at one of the world's largest trade shows, there is substantial capability for conducting the types of testing required for HPV chemicals in both the U. S. and abroad. Of the 50 labs judged to have at least some capabilities for HPV types of testing, 27 were based in the U. S. and 23 were based outside the U. S.

The ability of such labs to expand capacity in response to increases in demand will depend on the type of testing. Standardized types of testing such as acute toxicity testing can be scaled up relatively quickly because the equipment needed to conduct such testing is widely available at modest cost and there is a substantial workforce trained in conducting such testing. For more specialized types of testing, expanding capacity can become much more complicated. Capacity to conduct sophisticated tests, such as those that assay developmental or neurotxicological effects,

may be far more difficult to scale up. Among the reasons cited are the lengthy and costly validation processes for these types of testing, and the limited availability of trained program managers and technicians.

One particular area where capacity appears notably constrained and difficult to expand is toxicity testing via inhalation routes. In this area, the expense and expertise necessary to custom build the inhalation apparatus is a significant factor limiting expansion of capacity, particularly for new entrants into the field. In addition, participants in this market note unlike other types of testing there is an absence of pharmaceutical demand in this area, making those firms more dependant on regulatory driven demand. 31 6.0 REFERENCES AAALAC. 2004. Personal Communication with Kathryn Bayne, Associate Director, Association for the Assessment and Accreditation of Laboratory Animal Care. January 21, 2004.

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Dalton, Matthew. 2004. Senators Seek Investigation of Toxics Law Shortfalls for Possible Legislative Overhaul. Inside Washington Publishers. January 9, 2004.

Deckert, Fred. 2004. Toxikon. Personal communication. March 22, 2004.

Environmental Defense. 2004. HPV Tracker. Online database. Available at: < http:// www. environmentaldefense. org/ documents/ 2724_ HPVTracker. xls>>. July 20, 2004.

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European Chemicals Bureau. 2004. Existing Chemicals Work Area Web Site ( IUCLID). < ecb. jrc. it/ existing chemicals>. Accessed January 13, 2004.

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Holbert, Mark. 2003. Personal communication with Vice president of Company Operations, Stillmeadow, Inc., September 17, 2003.

Hutchinson, Curl and Mark Jaber. 2004. Wildlife International. Personal communication. March 22 and 23, 2004.

ICCA, 2002. The ICCA HPV Chemicals Initiative. April 2002. < http:// www. iccachem org/ pdf/ icca006. pdf>. Accessed July 2004.

Institute for Environment and Health. 2001. Testing Requirements for Proposals Under the EC White Paper ` Strategy for a Future Chemicals Policy' ( IEH Web Report W6). Leicester, UK. July, 2001.

Kim, Dee. 2004. MB Research. Personal communication. March 22, 2004.

Liikanen, E. and Wallström, M. 2003. Chemicals Orientation Paper. April 27, 2003.

Miller, Henry I. 2003. EU over REACH. Canada National Post, Op Ed. September 4, 2003 Muermann, Carolyn. 2004. Huntingdon Laboratories. Personal communication. March 22, 2004.

Newton, Paul. 2004. MPI Research. Personal communication. March 22, 2004.

OECD 2004. OECD Integrated HPV Database ( Sponsored Chemicals). < http:// cs3 hq. oecd. org/ scripts/ hpv/>. Accessed January 13, 2004.

Ohne, Kris and Waheed Siddiqui. 2004. Dow Corning. Personal communication. March 22, 2004.

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Synthetic Organic Chemical Manufacturers Association. 2003. Comparative Analysis of the European Union's Proposed REACH System and the U. S. Toxic Substances Control Act. < www. socma. com/ pdffiles/ reach_ tsca. pdf>. June 13, 2003.

ten Brink et al., 2003. Patrick ten Brink, Claire Monkhouse, Christine Füll, and Astrid Ladefoged. Policy Brief for the EP Environment Committee, EP/ IV/ A/ 2003/ 09/ 01. Ad hoc Report on Chemicals: Comparative Analysis of REACH and Other International Approaches. Brief number 03/ 2003. November 10, 2003.

U. S. EPA. 2000. Voluntary Participation in the HPV Challenge Program. Chemical Right to Know Fact Sheet Series. EPA 745 F 98 002b. July 2000. < www. epa. gov/ chemrtk/ hpvvol2. pdf> Accessed July 2004.

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U. S. EPA. 2003c. SIDS Test Guidelines. < www. epa. gov/ chemrtk/ sidsappb. htm>. Accessed September 29, 2003.

U. S. EPA. 2004a. Summary Report. High Production Volume ( HPV) Challenge Program. January 16, 2004. < www. epa. gov/ chemrtk/ sumresp. html>. Accessed July 2004.

U. S. EPA 2004b. SECT4ICR_ 04_ FINAL. WK4. Spreadsheet prepared in support of the TSCA Section 4 Information Collection Request ( ICR): TSCA Existing Chemical Test Rules, 34 Consent Orders, Test Rule Exemptions, and Voluntary Test Data Submissions ( OMB No. 2070 0033; EPA ICR# 1139.) May 21, 2004. APPENDIX A CAPABILITIES OF U. S. AND FOREIGN CHEMICAL TESTING LABS EXHIBITING AT 2004 TOX EXPO BALTIMORE, MD A 1 Table A 1. Capabilities of 2004 ToxExpo Exhibitors to Conduct Chemical Testing, by Type of Testing No. Name of Lab Physical/

Chemical Characteristics General Toxicology Acute General Toxicology Repeated/

Subchronic General Toxicology Teratogenicity/

Developmental Toxicology General Toxicology Reproductive/

Reproduction Genetic Toxicology Chromsomal Aberation Micronucleus Aquatic Toxicology Fish/

Daphnid/

Algae Analytical Chemistry Environmental Fate Total number of labs 15 41 44 32 33 26 17 39 19 1 ABC Labs x x x x 2 Battelle x x x 3 Bioagri Pharma x x x x x 4 Bioanalytical Systems Inc. ( BASi) x x x x x 5 Biological Testing Centre ( BTC) x x x 6 Bio Reliance x x x x 7 Calvert Labs x x x x x x 8 Centre International de Toxicologie ( CIT) x x x x x x x 9 Centrel Toxicology Labs ( CTL) x x x x x x 10 Charles River Labs x x x x x 11 Covance x x x x x x x x 12 CTBR x x x x x x 13 Fraunhofer Institute of Toxicology x x x x x x 14 Huntingdon Life Sciences x x x x x x x x x 15 IITRI Research Institute x x x x x 16 INA Research x x x x x Table A 1. Capabilities of 2004 ToxExpo Exhibitors to Conduct Chemical Testing, by Type of Testing No. Name of Lab Physical/

Chemical Characteristics General Toxicology Acute General Toxicology Repeated/

Subchronic General Toxicology Teratogenicity/

Developmental Toxicology General Toxicology Reproductive/

Reproduction Genetic Toxicology Chromsomal Aberation Micronucleus Aquatic Toxicology Fish/

Daphnid/

Algae Analytical Chemistry Environmental Fate A 2 17 Intn'l Institute of Biotech. & Toxicology ( IIBAT) x x x x x x x x 18 Inveresk Research x x x x x x x x 19 ITRLaboratories Canada x x x 20 JAI Research Institute x x x x x x x x x 21 Korea Institute x x x x x x x x 22 LAB Research x x x x x x 23 MB Research x x x 24 Midwest Research x x x x 25 MPI Research x x x x x 26 Next Century x 27 Northview Biosciences x x x 28 No Tox x x x x x x x x x 29 Product Safety Labs x x x x 30 Provident Preclinical x x x x 31 Quintiles x x x x 32 Rallis Research Centre x x x x x x x x x 33 RCC x x x x x x x x x 34 Research Toxicology Centre ( RTC) x x x x x x x x 35 Ricerca Biosciences x x x 36 RTI International x x x Table A 1. Capabilities of 2004 ToxExpo Exhibitors to Conduct Chemical Testing, by Type of Testing No. Name of Lab Physical/

Chemical Characteristics General Toxicology Acute General Toxicology Repeated/

Subchronic General Toxicology Teratogenicity/

Developmental Toxicology General Toxicology Reproductive/

Reproduction Genetic Toxicology Chromsomal Aberation Micronucleus Aquatic Toxicology Fish/

Daphnid/

Algae Analytical Chemistry Environmental Fate A 3 37 Safe Pharm Labs x x x x x x x x x 38 Scan Tox x x 39 Sequani x x x x 40 Shin Nippon Research Labs ( SNBL) x x x x x x 41 Sitek Research Labs x x 42 Southern Research Institute x x x x 43 Springborn Smithers Labs x x 44 Stillmeadow Inc. x x x x x 45 TNO Pharma x x x x x x 46 Toxicology Research Labs x x x x 47 Toxikon x x x x x 48 T. R. Wilbury Labs x x x x 49 WIL Research Labs x x x x x x 50 Wildlife International x x x x A 4 Table A 2. Lab Capabilities   Physical/ Chemical Characteristics 1. Covance USA 2. Huntingdon Life Sciences UK 3. Intn'l Instiute of Biotech. & Toxicology ( IIBAT) India 4. Inveresk Research Scotland 5. JAI Research Institute India 6. Midwest Research Institute USA 7. NoTox Netherlands 8. Product Safety Labs USA 9. Rallis Research Centre India 10. RCC Switzerland 11. SafePharm Labs UK 12. Shin Nippon Research Labs ( SNBL) Japan 13. Stillmeadow Inc. USA 14. T. R. Wilbury Labs USA 15. Wildlife International USA A 5 Table A 3. Lab Capabilities   General Toxicology   Acute 1. Battelle USA 2. Bioagri Pharma Brazil 3. Bioananalytical Systems Inc. ( BASi) USA 4. Biological Testing Centre ( BTC) USA 5. BioReliance USA 6. Calvert Labs USA 7. Central Toxicology Labs ( CTL) UK 8. Centre International De Toxicologie ( CIT) France 9. Charles River Labs USA 10. Covance USA 11. CTBR Canada 12. Fraunhofer Institute of Toxicology Germany 13. Huntingdon Life Sciences UK 14. IITRI Research Institute USA 15. INA Research Japan 16. Intn'l Institute of Biotech. & Toxicology ( IIBAT) India 17. Inveresk Research Scotland 18. ITR Laboratories Canada Canada 19. JAI Research Institute India 20. Korea Institute Korea 21. LAB Research Canada 22. MB Research USA 23. Midwest Research USA 24. MPI Research USA 25. Northview Biosciences USA 26. NoTox Netherlands 27. Product Safety Labs USA 28. Provident Preclinical USA 29. Quintiles UK 30. Rallis Research Centre India 31. RCC Switzerland 32. Research Toxicology Centre ( RTC) Italy 33. Ricerca Biosciences USA 34. SafePharm Labs UK 35. Sequani UK 36. Shin Nippon Research Labs ( SNBL) Japan 37. Southern Research Institute USA 38. Stillmeadow Inc. USA 39. TNO Pharma Netherlands 40. Toxikon USA 41 WIL Research Labs USA A 6 Table A 4. Lab Capabilities   General Toxicology   Repeated/ Subchronic 1. Battelle USA 2. Bioagri Pharma Brazil 3. Bioanalytical Systems Inc. ( BASi) USA 4. Biological Testing Centre ( BTC) USA 5. BioReliance USA 6. Calvert Labs USA 7. Central International De Toxicologie ( CIT) France 8. Central Toxicology Labs ( CTL) UK 9. Charles River Labs USA 10. Covance USA 11. CTBR Canada 12. Fraunhofer Institute of Toxicology Germany 13. Huntingdon Life Sciences UK 14. IITRI Research Institute USA 15. INA Research Japan 16. Intn'l Institute of Biotech. & Toxicology ( IIBAT) India 17. Inveresk Research Scotland 18. ITR Laboratories Canada Canada 19. JAI Research Institute India 20 Korea Institute Korea 21 LAB Research Canada 22. MB Research USA 23. Midwest Research USA 24. MPI Research USA 25. Northview Biosciences USA 26. NoTox Netherlands 27. Product Safety Labs USA 28. Provident Preclinical USA 29. Quintiles UK 30. Rallis Research Centre India 31. RCC Switzerland 32. Research Toxicology Centre ( RTC) Italy 33 Ricerca Biosciences USA 34. SafePharm Labs UK 35. ScanTox Denmark 36. Sequani UK 37. Shin Nippon Research Labs ( SNBL) Japan 38. Southern Research Institute USA 39. Stillmeadow Laboratories USA 40. TNO Pharma Netherlands 41. Toxicology Research Labs USA 42. Toxikon USA 43. WIL Research Labs USA A 7 Table A 5. Lab Capabilities   General Toxicology   Teratogenicity & Developmental Toxicology 1. Bioagri Pharma Brazil 2. Bioanalytical Systems Inc. ( BASi) USA 3. Calvert Labs USA 4. Central Toxicology Labs ( CTL) UK 5. Centre International De Toxicologie ( CIT) France 6. Charles River Labs USA 7. Covance USA 8. CTBR Canada 9. Fraunhofer Institute of Toxicology Germany 10. Huntingdon Life Sciences Uk 11. IITRI Research Institute USA 12. INA Research Japan 13. Intn'l Institute of Biotech. & Toxicology ( IIBAT) India 14. Inveresk Research Scotland 15. JAI Research Institute India 16. Korea Institute Korea 17. LAB Research Canada 18. MPI Research USA 19. NoTox Netherlands 20. Provident Preclinical USA 21. Quintiles UK 22. Rallis Research Centre India 23. RCC Switzerland 24. Research Toxicology Centre ( RTC) Italy 25. RTI International USA 26. SafePharm Labs UK 27. Sequani UK 28. Shin Nippon Research Labs ( SNBL) Japan 29. Southern Research Institute USA 30. TNO Pharma Netherlands 31. Toxicology Research Labs USA 32. WIL Research Labs USA A 8 Table A 6. Lab Capabilities   General Toxicology   Reproductive / Reproduction 1. Bioagri Pharma Brazil 2. Bioanalytical Systems Inc. ( BASi) USA 3. Calvert Labs USA 4. Central Toxicology Labs ( CTL) Uk 5. Centre International De Toxicologie ( CIT) France 6. Charles River Labs USA 7. Covance USA 8. CTBR Canada 9. Fraunhofer Institute of Toxicology Germany 10. Huntingdon Life Sciences UK 11. IITRI Research Institute USA 12. INA Research Japan 13. Intn'l Institute of Biotech. & Toxicology ( IIBAT) India 14. Inveresk Research Scotland 15. JAI Research Institute India 16. Korea Institute Korea 17. LAB Research Canada 18. MPI Research USA 19. NoTox Netherlands 20. Provident Preclinical USA 21. Rallis Research Centre India 22. RCC Switzerland 23. Research Toxicology Centre ( RTC) Italy 24. RTI International USA 25. SafePharm Labs UK 26. Sequani UK 27. Shin Nippon Research Labs ( SNBL) Japan 28. Southern Research Institute USA 28. TNO Pharma Netherlands 30. Toxicology Research Labs USA 31. WIL Research Labs USA A 9 Table A 7. Lab Capabilities   Genetic Toxicology   Chromosomal Aberration / Micronucleus 1. Bioagri Pharma Brazil 2. BioReliance USA 3. Calvert Labs USA 4. Central Toxicology Labs ( CTL) UK 5. Centre International De Toxicologie ( CIT) France 6. Covance USA 7. CTBR Canada 8. Fraunhofer Institute of Toxicology Germany 9. Huntingdon Life Sciences UK 10. IITRI Research Institute USA 11. INA Research Japan 12. Intn'l Institute of Biotech. & Toxicology ( IIBAT) India 13. Inveresk Research Scotland 14. JAI Research Institute India 15. Korea Institute Korea 16. LAB Research Canada 17. Next Century USA 18. NoTox Netherlands 19. Rallis Research Centre India 20. RCC Switzerland 21. Research Toxicology Centre ( RTC) Italy 22. SafePharm Labs UK 23. Sitek Research LAbs USA 24. TNO Pharma Netherlands 25. Toxikon USA A 10 Table A 8. Lab Capabilities   Aquatic Toxicology   Fish / Daphnid / Algae 1. ABC USA 2. Huntingdon Life Sciences UK 3. Intn'l Institute of Biotech. & Toxicology ( IIBAT) India 4. JAI Research Institute India 5. Korea Institute Korea 6. NoTox Netherlands 7. Rallis Research Centre India 8. RCC Switzerland 9. Research Toxicology Centre ( RTC) Italy 10. SafePharm Labs UK 11. ScanTox Denmark 12. SpringbornSmithers Labs USA 13. Stillmeadow Inc. USA 14. Toxikon USA 15. T. R. Wilbury Labs USA 16. Wildlife International USA A 11 Table A 9. Lab Capabilities   Analytical Chemistry 1. ABC Labs USA 2. Bioanalytical Systems Inc. ( BASi) USA 3. Biological Testing Centre ( BTC) USA 4. BioReliance USA 5. Calvert Labs USA 6. Central Toxicology Labs ( CTL) UK 7. Centre International De Toxicologie ( CIT) France 8. Charles River Labs USA 9. Covance USA 10. CTBR Canada 11. Huntingdon Life Sciences UK 12. Intn'l Institute of Biotech. & Toxicology ( IIBAT) INdia 13. Inveresk Research Scotland 14. ITR Laboratories Canada Canada 15. JAI Research Institute India 16. Korea Institute Korea 17. LAB Research Canada 18. MB Research USA 19. Midwest Research USA 20. MPI Research USA 21. Northview Biosciences USA 22. NoTox Netherlands 23. Product Safety Labs USA 24. Quintiles UK 25. Rallis Research Centre India 26. RCC Switzerland 27. Research Toxicology Centre ( RTC) Italy 28. RTI International USA 29. SafePharm Labs UK 30. Shin Nippon Research Labs ( SNBL) Japan 31. Sitek Research Labs USA 32. SpringbornSmithers Labs USA 33. TNO Pharma Netherlands 34. Toxicology Research Labs USA 35. Toxikon USA 36. T. R. Wilbury Labs USA 37. WIL Research Labs USA 38. Wildlife International USA A 12 Table A 10. Lab Capabilities   Environmental Fate 1. ABC USA 2. Battelle USA 3. Centre International De Toxicologie ( CIT) France 4. Covance USA 5. Fraunhofer Institute of Toxicology Germany 6. Huntingdon Life Sciences UK 7. Inveresk Research Scotland 8. JAI Research Institute India 9. Korea Institute Korea 10. NoTox Netherlands 11. Rallis Research Centre India 12. RCC Switzerland 13. Research Toxicology Centre ( RTC) Italy 14. Ricerca Biosciences USA 15. SafePharm Labs UK 16. Stillmeadow Inc. USA 17. T. R. Wilbury Labs USA 18. WIL Research Labs USA 19. Wildlife International USA A 13 Table A 11. Lab Capabilities   Lab Contact Information No. Lab Name Address City State Country Internet 1 ABC Laboratories 7200 E. ABC Lane Columbia MO USA www. abclabs. com 2 Battelle 505 King Street Columbus OH USA www. battelle. org/ pharmaceutical 3 BioAgri Pharma Rodovia Rio Clara Piracicaba SP Brazil wwww. bioagriata. com. br 4 Bioanalytical Systems, Inc.

( BASi) 2701 Kent Avenue West Lafayette IN USA www. bioanalytical. com 5 Biological Testing Center (

BTC) 2525 McGAw Avenue Irvine CA USA www. biologicaltestcenter. com 6 BioReliance 14920 Broschart Road Rockville MD USA www. bioreliance. com 7 Calvert Labs 100 Discovery Drive Olyphant PA USA www. calvertlabs. com 8 Centre Internatioanle De Toxicologie ( CIT) 9700 Great Seneca Highway Rockville MD USA www. citox. com 9 Centrel Toxicology Labs ( CTL) Alderley Park Macclesfield Cheshire UK ann. evans@ syngenta. com 10 Charles River Labs 15 Worman's Mill Ct Frederick MD. USA www. criver. com 11 Covance 3301 Kinsman Blvd. Madison WI USA www. covance. com 12 CTBR 87 Sennville Rd. Sennville Quebec Canada www. ctbr. com 13 Fraunhofer Institute of Toxicology Nikolai Fuchs Str 1 Hanover Germany www. lifesciences. fraunhofer. de 14 Huntingdon Life Sciences Woolley Road Alconbury Cambridgeshi re England www. huntingdon. com 15 IITRI Research Institute 10 W. 35th St. chicago IL USA www. iitri. org/ lifesciences 16 INA Research Inc. 2148 188 Nishiminowas Ina Shi Nagano ken Japan www. ina research. co. jp 17 Intn'l Institute of Biotech. & Tox.

( IIBAT) Padappi 601 301 Tamil Nadu India fippat@ giasmd01. vsnl. net. in 18 Inveresk Research 11000 Weston Carey NC USA www. inveresk. com 19 ITR Laboratories Canada, Inc. 19601 Clark Graham Baie d'Urfe Montreal Canada www. itrlab. com 20 Jai Research Foundation P. O. Box 30 Valsad Gujarat India www. jrfchemtox. com 21 Korea Institute of Toxicology ( KIT) P. O. Box123 Yuseong Daejon Korea www. kitox. re. kr 22 Lab Research ( LAB) 445 Armand Frappier Blvd. Laval Quebec Canada www. preclin. com 23 MB Research Labs 1765 Wentz Rd. Spinnerstown PA USA www. mbresearch. com 24 Midwest Research Institute 425 Volker Blvd. Kansas City MO USA www. mriresearch. org Table A 11. Lab Capabilities   Lab Contact Information No. Lab Name Address City State Country Internet A 14 25 MPI Research 54943 North Main St. Mattawan MI USA www. mpiresearch. com 26 Next Century Inc. 3 Innovation Way Newark DE USA www. nextcenturyinc. com 27 Northview Biosciences 1880 Holste Rd. Northbrook IL USA www. northviewlabs. com 28 NoTox P. O. Box 3476 Hertogenbosch Netherland s www. notox. nl 29 Product Safety Labs ( PSL) 2394 Route 130 Dayton NJ USA www. productsafetylabs. com 30 Provident Preclinical Inc. 2003 Lower State Rd. Doylestown PA USA www. ppicro. com 31 Quintiles 10245 Hickman Mills Drive Kansas City MO USA www. quintiles. com 32 Rallis Research Centre Peenya Industrial Area Bangalore Karnataka India www. rallis. co. in 33 RCC Itingen Switzerlan d www. rcc. com 34 Research Toxicology Centre ( RTC) Via Tito Speri 12 Pomezia Rome Italy www. rtc. it 35 Ricerca Biosciences 7528 Auburn Rd. Concord OH USA www. ricerca. com 36 RTI International 3040 Cornwallis RD. Research Triangle Park NC USA www. rti. org 37 SafePharm Laboratories P. O. Box 45 Derby England UK www. safepharm. co. ik 38 ScanTox Hestehavevej Ejby Lille Skensved Denmark www. scantox. com 39 Sequani Bromyard Rd. Ledbury England UK www. sequani. com 40 Shin Nippon Biomedical Labs ( SNBL) 6605 Merril Creek Parkway Everett WA USA www. snblusa. com 41 Sitek Research Laboratories 15235 Shady Grove Rd. Rockville MD USA www. siteklabs. com 42 Southern Research Institute 2000 Ninth Avenue South Birmingham AL USA www. southernresearch. org 43 Springborn Smithers Laboratories 790 Main Street Wareham MA USA www. springbornsmithers. com 44 Stillmeadow Inc. 12852 Park One Drive Sugar Land TX USA www. stillmeadow. com 45 TNO Pharma Utrechtseweg 48 Ziest Netherland s www. pharma. tno. nl 46 Toxicology Research Laboratory University of Il. Chicago IL USA www. uic. edu/ labs/ tox 47 Toxikon 15 Wiggins Ave. Bedford MA USA www. toxikon. com 48 T. R. Wilbury Labs Inc. 40 Doaks Lane Marblehead MA USA ward@ trwilburylabs. com Table A 11. Lab Capabilities   Lab Contact Information No. Lab Name Address City State Country Internet A 15 49 WIL Research Labs. Inc. 1407 George Rd. Ashland OH USA www. wilresearch. com 50 Wildlife International Ltd. 8598 Commerce Drive Easton MD USA ecotox@ wildlifeinternational. com APPENDIX B EPA LIST OF LABORATORIES WITH CAPABILITIES IN ECOLOGICAL TESTING B 1 Table B 1. EPA/ OPPT List of Laboratories With Ecological Testing Capabilities No. Name of Laboratory Location Country 1 ABC Laboratories, Inc. Columbus, MO USA 2 Aqua Survey, Inc. Flemington, NJ USA 3 AquaTox Research, Inc. Syracuse, NY USA 4 AScI Corp/ AScI Duluth Environmental Testing Division Duluth, MN USA 5 Betz Laboratories, Inc. Trevose, PA USA 6 Biological Monitoring, Inc. ( BMI) Blacksburg, VA USA 7 Biomonitoring Services Laboratory Gulf Breeze, FL USA 8 Burlington Research, Inc. Burlington, NC USA 9 Carolina Ecotox, Inc. Durham, NC USA 10 Chem Nuclear Laboratory Services Greenville, SC USA 11 DOW Chemical Company, Environmental Toxicology and Chemistry Research Laboratory Midland, MI USA 12 EA Engineering, Science, and Technology, Inc., Hunt Valley/ Loveton Center, Aquatic Toxicology Laboratory Sparks, MD USA 13 Eastman Kodak Company, Environmental Science Section Rochester, NY USA 14 ENSR, Environmental Toxicology Services Division Woods Hole, MA USA 15 Environmental Science and Engineering Gainesville, FL USA 16 Enwright Environmental Consulting Laboratories, Inc. ( now Chem Nuclear Laboratory Services, Inc.) Greenville, SC USA 17 ETT Environmental, Inc. Greenville, SC USA 18 EXXON Biomedical Sciences, Inc., Environmental Toxicology Laboratory East Millstone, NJ USA 19 E. I. du Pont de Nemours and Co., Inc., Haskell Laboratory for Toxicology and Industrial Medicine Newark, DE USA 20 Grove Scientific Orlando, FL USA 21 Hazleton Wisconsin, Inc. Madison, WI USA 22 HydroLogic, Inc. Morrisville, NC USA 23 Laboratory Technology, Inc. Kenner, LA USA 24 Malcolm Pirnie, Inc. Tarrytown, NY USA 25 Mid State Associates, Inc. Baraboo, WI USA 26 Parametrix, Inc. Bellevue, WA USA 27 PETROLITE CORPORATION, Environmental Studies Group Webster Grove, MO USA 28 Research Triangle Institute ( RTI), Comparative & Environmental Toxicology, Center for Life Sciences & Toxicology Research Triangle Park, NC USA 29 Resource Analysts, Inc., EnviroSystems Division Hampton, NH USA 30 Ricerca, Inc. Painesville, OH USA 31 Robert J. Goldstein & Assoc., Inc. Raleigh, NC USA 32 SGS United States Testing Company, Inc. Fairfield, NJ USA 33 Shealy Environmental Services, Inc. Cayce, SC USA 34 Springborn Laboratories, Inc. Wareham, MA USA 35 Stonybrook Laboratories, Inc. Princeton, NJ USA 36 Swearingen Ecology Associates Columbia, SC USA 37 TAI Environmental Sciences, Inc. Mobile, AL USA 38 Toxikon Environmental Sciences Jupiter, FL USA 39 TRAC Laboratories, Inc. Denton, TX USA 40 T. R. Wilbury Laboratories, Inc. Marblehead, MA USA 41 Union Carbide Chemicals and Plastics Company, Inc. South Charleston, WV USA Table B 1. EPA/ OPPT List of Laboratories With Ecological Testing Capabilities No. Name of Laboratory Location Country B 2 42 Webb Technical Group, Inc. Raleigh, NC USA 43 Wildlife International, Ltd. Easton, MD USA 44 Beak Consultants Limited Brampton, Ontario Canada 45 Hazleton Europe North Yorkshire England 46 Huntingdon Research Center, Ltd. Cambridgeshire England 47 Huntington Life Sciences, Limited Suffolk England 48 ICI: Imperial Chemical Industries PLC, ICI Group Environmental Laboratory Devon England 49 Institute of Freshwater Ecology, The Windermere Laboratory Cumbria England 50 Life Science Research, Ltd. Suffolk England 51 SafePharm Laboratories Limited Derby England 52 Hazleton France Pontcharra Sur Turdine France 53 Pharmakon Europe L'Arbresle France 54 BASF Aktiengesellschaft, Department of Toxicology Ludwigshafen Germany 55 Battelle Europe Frankfurt Germany 56 Bayer AG, Crop Protection Research/ Environmental Research Leverkusen Germany 57 Dr. U. Noack Laboratory For Applied Biology Hildesheim Germany 58 Henkel KGaA Dusseldorft Germany 59 Hoechst Aktiengesellschaft, Pharma Research Toxicology and Pathology/ Pharma Development Central Toxicology Frankfurt Germany 60 Huls Aktiengesellschaft, Prufinstitut fur Biologie Marl Germany 61 IBR International BioResearch, Bioanalytical Centre Hannover Germany 62 Institut Fresenius Taunusstein Germany 63 Robdorf Germany 64 Stockhausen, Laboratory for Toxicology and Ecotoxicology Krefeld Germany 65 Istituto di Ricerche Biomedicine Giaasa ( Torino) Italy 66 Akzo Nobel Central Research Arnhem Netherlands 67 Akzo Research Laboratories Arnhem Arnhem Netherlands 68 RCC NOTOX B. V. Hertogenbosch Netherlands 69 TNO Institute of Environmental Sciences Delft Netherlands 70 Inveresk Research International, Elphinstone Research Center Tranet Scotland 71 CIBA GEIGY Limited, D& C Product Ecology Basel Switzerland 72 CIBA GEIGY, Inc., Product Safety Basel Switzerland 73 RCC Umweltchemie AG Itingen Switzerland Source: List maintained by Vince Nabholz, USEPA/ OPPTS/ HERD/ EEB ( 7403).