CHEMICAL TESTING INDUSTRY
PROFILE OF TOXICOLOGICAL TESTING
by
Samuel G. Unger
Daniel W. Francke
Stuart L. Fribush
Geneva S. Hammaker
Frank D. Lerman
Contract No. 68-01-6064
and
Task 7, Contract No. 68-01-6287
Project Officer
Sammy K. Ng
Economics and Technology Division
Office of Toxic Substances
Washington, D.C. 20460
OFFICE OF PESTICIDES AND TOXIC SUBSTANCES
U.S. ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
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DISCLAIMER
This report was prepared under contract to an agency of the United States
Government. Neither the United States Government nor any of its employees,
contractors, subcontractors, or their employees makes any warranty,
expressed or implied, or assumes any legal liability or responsibi1ity for
any third party's use or the results of such use of any information,
apparatus, product, or process disclosed in this report, or represents that
its use by such third party would not infringe on privately owned rights.
Publication of the data in this document does not signify that the contents
necessarily reflect the joint or separate views and policies of each
sponsoring agency. Mention of trade names or commercial products does not
constitute endorsement or recommendation for use.
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PREFACE
The attached document is a contractor's study done with the supervision and
review of the Office of Pesticides and Toxic Substances of the U.S.
Environmental Protection Agency. The purpose of the study is to establish
an economic profile of the chemical testing industry, emphasizing the
toxicological testing segment.
This report was submitted in fulfillment of Contract No. 68-01-6064 and
Task Order No. 7 of Contract No. 68-01-6287 by Development Planning and
Research Associates, Inc. and ICF Incorporated. Work was completed as of
October, 1981.
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CONTENTS
fMi
PREFACE iii
EXECUTIVE SUMMARY 1
I. INTRODUCTION 1-1
A. Background 1-1
B. Scope of the Analysis 1-2
C. General Approach 1-4
II. LITERATURE AND DATA REVIEW 11-1
A. Industry Structure and Organization II-l
B. Literature/Data Review I1-2
C. Data Sources and Limitations 11-4
III. THE TOXICOLOGICAL TESTING INDUSTRY AND SUPPLY OF
TESTING RESOURCES III-l
A. Profile of the Toxicological Testing Industry IX1-2
B. Testing Capabilities 111-12
D. Resource Supplies and Constraints 111-22
IV. DEMAND FOR TOXICOLOGICAL TESTING IV-1
A. Methodology of Demand Assessment IV-2
B. Demand for Pesticide Testing under FIFRA IV-3
C. Demand for Toxicological Testing Under TSCA IV-12
D. Demand for Toxicological Testing Under FFDCA IV-21
E. Commercial Demand for Testing not Directly Induced
by Regulation IV-43
F. Research Demand for Toxicological Testing IV-43
G. Summary: Demand for Resources Used in
Toxicological Testing IV-44
V. CONCEPTUAL SUPPLY-DEMAND MODEL DEVELOPMENT V-l
A. Analytical System V-2
B. Supply Module V-6
C. Demand Module V-7
D. An Accounting Subsystem V-8
E. An Economic Subsystem V-15
F. General Implementation Requirements V-20
G. Research Implications V-27
VI. REFERENCES VI-1
APPENDIX A - LISTING OF TOXICOLOGICAL TESTING LABORATORIES
APPENDIX B - TOXICOLOGY LABORATORY CONTACT FORM AND
TELEPHONE SURVEY INSTRUMENT
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CHEMICAL TESTING INDUSTRY: PROFILE OF TOXICOLOGICAL TESTING
EXECUTIVE SUMMARY
The Toxic Substances Control Act (TSCA) of 1976 requires that all chemical
substances which may present unreasonable risks to either health or the
environment shall be tested for their toxicological effects. Under Section
4 of TSCA, the Administrator of the Environmental Protection Agency (EPA)
is to promulgate rules for the obtaining of health and environmental
effects data and is to consider:
"...the reasonably foreseeable availability of the facilities
and personnel needed to perform the testing required under
the rule (Subsection 4b(l))."
That latter consideration provided the impetus for this chemical testing
industry study—the primary purpose of which is to assess the capacity and
resources of the toxicological testing industry in relation to the demands
made upon that industry with and without TSCA's additional testing
requirements.
The two main objectives of this study are: (1) to develop an economic
profile of the toxicological testing industry—its supply and demand
attributes, and (2) to prepare a list of laboratories that supply the
industry's services. Initially the study depended entirely upon secondary
data; however, when such were found to be inadequate, the study team
conducted a survey of the chemical testing industry's laboratories and
facilities to broaden that data base. Various data limitations are still
pronounced, and these are documented in industry and research literature
and noted in this report.
The study's economic profile analysis includes three major parts: (1) an
assessment of the toxicological testing industry and the availability of
its key testing resources, (2) the identification of aggregate regulatory
and nonregulatory resource demands (including non-testing resource uses),
and (3) the development of a resource-based supply-demand model. A listing
of confirmed toxicology laboratories was also prepared from a telephone
survey of laboratories (Appendix A).
Both existing and new chemical substances may require toxicological effects
testing under the provisions of TSCA. Although the precise magnitude of
the overall testing that will be required is unknown, the complexity of the
task is suggested by the fact that some 55,000 chemical substances are
currently on TSCA's inventory of chemical substances and additional
substances, many requiring testing, are regularly introduced by both
private and public developers.
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Although not all chemicals do or will require extensive testing, the
industry's anticipation of increased testing requirements has prompted the
rapid expansion of testing facilities in recent years. During this
expansion period, professional and technical personnel were in relatively
short supply. Current personnel numbers appear adequate relative to
present testing levels, however.
The review of available literature and secondary data sources provided a
basis for segmenting and characterizing, in general terms, the chemical
testing industry. Based upon this review, the chemical testing industry
was divided into three segments: biological, environmental, and product
chemistry. Due to the nature of tests included in each category, resource
competition between these segments appears minimal. Toxicological testing
encompasses both environmental and biological chemistry testing; however,
biological (animal) chemistry testing was the main focus of this study
because of TSCA's potential demands upon this specific industry's resources
and the probable constraints that will be posed.
Two previous studies (ICF, 1980; Enviro Control, 1980) of the chemical
testing industry provided the following observations that were
determinative within this present study:
« Professional manpower was a critical resource constraint to
testing supply.
• Laboratory space, capital, and equipment were potential resource
constraints.
t Testing laboratories, reporting widely varied price estimates for
tests, apparently compete on factors other than price.
Review of other sources (e.g., periodicals) supported the above
observations and provided additional evidence for the following:
• Testing capacity is potentially insufficient.
• Mutagenicity testing research may yield new methods for testing
and screening and, consequently, may favorably alter the
industry's potential to meet increased demand.
t The chemical testing industry includes four categories of
laboratories: independent, in-house (company), university and
government.
Data limitations were found for measuring both supply and demand. Supply
sources include various incomplete laboratory lists which, additionally, do
not generally provide information on facility capacity and capability.
Too, these sources are outdated and unverified. A few sources on manpower
were available. Some demand sources were available for characterizing
regulatory demand by Agency and Act, but little data on nonregulatory
(private) demand were found.
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Supply of Testing Resources
This study's assessment of the toxicological testing supply includes
descriptions of the industry and the major groups of its laboratories,
characterizes capacity utilization in the industry, and analyzes the
availability of industry resources.
The surveying of a screening list of potential toxicology laboratories
provided an estimate of 280 to 290 laboratories performing commercial
toxicological testing. (For the study's analytical purposes, a population
estimate of 285 was used.) These primarily included independent contract
laboratories and captive laboratories. Some university laboratories that
indicated the ability or desire to do commercial toxicological testing were
also included. (Other universities may also operate toxicology
laboratories, but these, because they are primarily used for teaching or
basic research, were excluded.) Other sources of testing
supply—government and foreign laboratories—were considered less
significant contributors to testing supply and outside the scope of this
report; therefore, they received only limited examination.
The survey also provided extensive and, heretofore, unavailable information
on toxicology laboratories. Some of the more general findings were that
• 34 percent of the laboratories were independents and 66 percent
were captives (including universities),
• the average business mix is approximately 58 percent contract
testing and 42 percent in-house testing although many
laboratories do only contract or only in-house testing,
• the average employment is 57 persons per laboratory and an
estimated 16,000 employees constitute the industry's total labor
force,
• the labor force is composed of 36 percent professionals, 45
percent technicians, 13 percent managers and administrators, and
6 percent other staff,
• measurable industry concentration exists but it is not enough to
restrict market entry or control key resources,
• current annual sales are about $650 million or $2.3 million per
laboratory, and
• the industry has an average testing space of 28,100 square feet
per laboratory.
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Toxicological testing can be divided into four general areas: mammalian,
in-vitro, environmental effects, and chemical fate testing. Most
toxicology laboratories will also perform product and analytical testing
(though the latter is generally not considered toxicological testing). The
incidence and estimated volume of testing in these six areas is shown in
Exhibit 1.
Mammalian testing, the largest general area of toxicological testing,
includes several specific types of tests: acute, subchronic, chronic,
reproduction, teratogenic, oncogenic, and histopathological. These may
also contain additional sub-types of tests. Acute testing is the most
common type of mammalian testing performed. The most commonly used mammals
for testing are small rodents (mice, rats, gerbils, hamsters), and they are
used in 97 percent of the mammalian laboratories with an average use or
inventory of 11,000 per laboratory.
In-vitro testing categorizes those biological tests which are conducted
outside the organism; environmental effects testing seeks to determine
toxic effects on an entire aquatic or terrestrial ecological community; and
chemical fate testing assesses the persistence or changes of a chemical
substance in the environment. All of these are important testing areas;
however, their testing volume is relatively law compared to that for
mammalian testing, their resource constraints are not considered serious,
and the impact of TSCA regulation on them will not be as great or as direct
as it will be on mammalian testing.
The supply of toxicological testing is dependent on the industry's
capacity. Currently, excess capacity exists in all major testing areas,
and surveyed laboratories indicated they could perform about 20 percent
more testing. That margin indicates an industry utilization rate of 80 to
85 percent--the result of recent declines in demand from that which was
anticipated during the mid-and late-1970's.
The key resources used in supplying testing services are professional and
technical manpower, animals, equipment, supplies, laboratory space, and
capital. Currently, capital and professional manpower are the most
constraining resources on industry expansion. Capital is understandably a
cyclical constraint; however, the constraint imposed by a shortage of
professional personnel can be of long term because of the lengthy period
required for professional preparation. The availability of other resources
is not as critical to expansion according to laboratory officials.
Demand for Toxicological Testing
The study characterizes toxicological testing demand both by alternative
sources and by their key resource requirements. The study estimated
regulatory, nonregulatory (commercial), research, and aggregate demand for
toxicological testing and its key resources. Non-testing demand was found
to compete significantly for manpower resources (particularly veterinary
pathologists); however, the non-testing demand for other toxicological
resources was not found to cause resource constraints.
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Exhibit 1. Estimated number of U.S. toxicology laboratories and their volume of
testing (dollars) by testing area, 1981
Toxicology Volume of testing
Testing area laboratories Total testing Toxicological testing 1J
(*)
(No.)
<*)
($ mil.)
(%)
($mi1.)
Mammalian
63
180
38
250
56
250
In-vitro
51
150
12
80
18
80
Environmental effects
51
150
13
80
18
80
Chemical fate
48
140
7
40
9
40
Product and analytical
(toxic and nori-toxic testing)
81
230
30
200
NA
NA
TOTAL
100
650
100
450
JJ Excludes product and analytical testing which may or may not be related to toxicological testing.
NA = Not Applicable
Source: Francke, 1981.
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The study's primary methodological concern in estimating demand was to
include all sources of demand; thus, for this analysis, demand was divided
into three components—regulatory (derived from a particular agency or
act), nonrsgulatory (private, commercial), and research.
Regulatory demand was defined as all testing required by the federal
government under TSCA, FIFRA (Federal Insecticide, Fungicide, and
Rodenticide Act), and FFDCA (Federal Food, Drug and Cosmetic Act).
Although direct data are not available to estimate such regulatory demand
definitively, the following observations indicate the general magnitude of
the task.
FIFRA requires health and safety testing in the registration of pesticides.
In addition to overseeing new pesticide registration, EPA is required to
reregister all currently registered pesticides—some 1,400 active
ingredients and some 38,000 formulations. EPA will eventually review
existing toxicological data on each pesticide to determine the testing
requirements for reregistration. EPA estimated the testing demand for
nineteen acute, subchronic and chronic tests under FIFRA for both new
active ingredients and formulations and for those which will be
reregistered, and estimated as well as the number of pesticides which will
require such testing. There are a number of uncertainties associated with
these estimates: uncertainty exists concerning the number of pesticides
which will be affected or the rate at which EPA will require such testing.
Estimates suggest that FIFRA's annual testing demand requires over 4,000
tests each for the categories of acute dermal and oral tests; over 3,000
each for acute inhalation, primary eye, and dermal irritation tests; 2,000
dermal sensitization tests; and fewer than twenty each for acute
neurotoxicity, subchronic (oral, dermal, inhalation and neurotoxicity),
chronic (feeding, oncogenicity, teratogenicity, reproduction and
mutagenicity), and metabolism tests.
The study considered TSCA testing demand as required under the TSCA's
Section 4 (the testing of existing chemicals as recommended by the
Interagency Testing Committee (ITC)) and the TSCA's Section 5 (the testing
associated with new chemicals). The study's projections of the number of
chemicals, the types of tests, and the aggregate test demand under Section
4 requirements were based on EPA's first proposed test rules for seven
chemicals or categories in 1980. Section 5 annual testing was projected on
the basis of the test data presented in premanufacturing notices (PMN's) in
1980. Section 4 will require an annual volume of sixty tests each for the
test categories of oncogenicity, mutagenicity, teratogencity and chronic
effects; forty-five reproduction tests will be required. Approximately 200
tests each for the categories of acute oral, primary dermal, and eye
irritation; approximately one hundred Ames and acute dermal, forty-eight
dermal sensitization, thirty-one acute inhalation and sixty-five other
tests may be done for new chemicals. (These estimates are dependent on
several factors, i.e., EPA regulatory schedules and anticipated new
chemical introductions by private industry).
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FFDCA requires manufacturers to document the safety of human and animal
drugs, food additives, and cosmetics. Historical data exist for the
testing of human drugs, and based on these data, the number and kind of
tests and chemicals tested annually were derived. An estimated 3,000 acute
oral tests will be required, as well as 300-600 subchronic oral tests;
130-180 each for acute dermal, inhalation, and dermal irritation tests; 86
primary eye irritation tests; and fewer than 50 dermal sensitization,
subchronic oral 12-month, ophthalmic, and vaginal-rectal application tests.
Animal drug registration requirements initiate an approval procedure
similar to that for human drugs. Except for teratology tests
(approximately 164), fewer than 100 acute toxicity, skin or eye irritation,
subacute, chronic and multigenerational reproduction tests will be
generated annually under animal drug approval requirements.
Food additive testing, in addition to abiding by the above germane
requirements, is responsive to FDA guidelines. The number of 1980
additives, by type, submitted for approval, combined with the tests
required for each type yielded this study's estimate of the toxicological
testing for additives: acute oral toxicity tests—184; lifetime feeding
studies, short-term feeding studies, and multi-generational reproduction
feeding studies~141; and subchronic feeding studies--73.
Both research demand and commercial (private) demand, the latter considered
substantial, also contribute to total annual toxicological demand.
Research demand is difficult to estimate, but government sponsored research
includes that generated by the $69 million budgeted for the National
Toxicology Program in FY 1980.
In summary, TSCA, FIFRA and FFDCA demand, and nonregulatory demand, must be
aggregated and categorized into specific resource requirements. Estimates
of the resources consumed by each test are necessary to this conversion of
demand into resource units. Such estimates were available for some tests,
and this study estimated the aggregate demand for one resource—board-
certified veterinary pathologists: 475 veterinary pathologists, of a total
of 486 available in 1980, could be utilized by combined TSCA, FIFRA and
FFDCA toxicology testing demand.
Conceptual Supply-Demand Model Development
In its concluding chapter, this study also presents a conceptual supply-
demand model of the chemical testing industry (toxicological testing only)
and illustrates its implementation with a specific example. The
formulation of the model indicated that substantially more quantitative
supply, capacity, and demand data are needed to effectively implement the
proposed model.
The concluding chapter presents, then, a general analytical system for
characterizing the economic profile of the chemical testing industry.
Besides including traditional supply and demand modules in the economic
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system, the system outlines three related modules that are needed for a
dynamic analytic model: capacity, growth, and price-profit response. Only
the capacity module is developed in detail in conjunction with the supply
and demand modules.
The supply and demand modules of the model are explicitly defined for the
toxicological testing industry. Both supply and demand are expressed in
common resource units, i.e., key resources that are potentially constraints
over the industry. Because the toxicological testing industry is
essentially a service industry, the capacity (and supply) of the industry's
laboratories should be determined by their capabilities and resources
rather than by any pre-defined unit of testing. Additionally, to reflect
the unique characteristics of the industry's multiple supply sources (e.g.,
independent and captive laboratories) and multiple demand sources (e.g.,
regulatory agencies and Acts and other), the model, as presented,
incorporates two separate, but linked, subsystems: an accounting subsystem
and an economic subsystem. The accounting subsystem is designed to track
resource-specific components of the model and to establish accounting-type
conditions. The economic subsystem focuses on economic conditions and
constraints as reflected through simulated supply and demand functions and
optimization criteria.
Overall the proposed model is presented as a mathematically programmable,
simulation system, i.e., one that is effectively a multi-equation system.
The model discussion concludes with a summary of the research implications
of this study's conceptual model development and the data needs for
implementing the model. Much of the needed supply-related data for the
model are obtainable from this study's toxicology laboratory survey or
proposed extensions of it which would add resource-specific and
growth-related data. The needed demand data are also partially developed
in this study, although a much larger research effort is necessary to
adequately characterize toxicological testing demand for existing and newly
developed chemicals. Each chemical substance tested may require various
toxicological tests with differing protocols that involve many testing
resources.
While a modeling approach appears technically feasible, it will require
substantial additional research. In the near future, periodic surveys may
be adequate to characterize changes in the toxicological testing segment of
the chemical testing industry. From these, the industry's changing
capacity and utilization can be estimated; the reasonably foreseeable
availability of resources to perform additional toxicological testing can
also be estimated. Projecting the expected level of aggregate testing
demand arising from both private and regulatory sources will be the major
remaining analytical issue.
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I. INTRODUCTION
A. Background
Section 4 of the Toxic Substances Control Act (TSCA) authorizes the
Administrator of the Environmental Protection Agency (EPA) to develop
health and environmental effects data on chemical substances which may
present unreasonable risks to either health or the environment. In
promulgating such rules, the Administrator is required, under Subsection
4(b) (1), to also consider:
"... the reasonably foreseeable availability of the
facilities and personnel needed to perform the testing
required under the rule."
For the Administrator to forward the development of the regulations and
guidelines required, the available capacity of the chemical testing
industry to perform the tests required within reasonable time limits must
be determined.
The potential magnitude of TSCA testing efforts is indicated by the fact
that there are 55,000 chemicals on the TSCA inventory of chemical
substances. Although not all chemicals will be subject to Section 4
testing requirements, the volume of testing potentially required by TSCA
poses questions concerning the adequacy of the existing capacity of the
chemical testing industry.
Other chemicals are also likely to be tested because of TSCA, and the
testing requirements are expected to increase in terms of the types,
numbers, complexity and duration of tests. Other regulatory programs
requiring comparable testing may result in yet additional testing demands;
consequently, to be most accurate, TSCA-related testing demands should be
assessed within this broader demand framework.
As the chemical toxicological testing industry has expanded to meet these
anticipated demands upon its resources, two consequential factors have
become clear. In the first instance, predicted demand increases have not
been fully realized; hence, the industry has but partially expanded. And
in the second instance, though apparently most supply resources appear
adequate to demand, capital constraints and a shortage of qualified
professional and technical personnel limits the industry's present
capabilities and capacities.
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Based on an examination of chemical testing literature, the industry can be
grouped into three major categories: (1) biological chemistry testing, (2)
environmental chemistry testing, and (3) product chemistry testing (See:
Exhibit 1-1). For the most part, toxicology testing encompasses the first
two categories of chemical testing, biological and environmental.
8iological chemistry testing--a major focus of this study—can also be
further categorized into acute, subchronic and chronic testing.
Acute toxicity studies are used to evaluate the short-term effects of a
given chemical or drug and they provide the basis for later, more
comprehensive tests. The simplest acute toxicity test is an LD50 test, one
which determines the dose that would be lethal to 50 percent of a
representative target animal population.
Subchronic toxicity studies provide data on the toxic effects of a chemical
and determine the dose level and time required for these effects to be
produced. Dosing duration is generally between thirty to ninety days,
periods during which time clinical, biochemical and pathological
evaluations are initiated. Subchronic studies aid in discerning the
potential toxic effects of repeated chemical dosages.
Chronic toxicity studies are generally performed for periods varying from
six months to the lifetime of the test animal. These studies assess the
long-term reproductive, genetic, teratogenic, oncogenic, and carcinogenic
effects of long-term exposure to a chemical. The state of the art is such
that no one comprehensive test adequately evaluates all potential mutagenic
effects. Consequently, most laboratories conduct a series of in vitro
(outside living organism) and in vivo (inside living organism) studies.
B. Scope of the Analysis
The two main objectives of the study were:
• to develop an economic profile of the chemical testing industry,
and
• to prepare a comprehensive listing of chemical testing
laboratories.
To forward these objectives, the study considered industry data to provide
the following information and to include it within this report.
The availability of testing services and the adequacy of the chemical
testing industry to meet regulatory-related demands were examined. In
particular, the supply of key resources—manpower, space, animals,
equipment, supplies and capital—required to conduct quality testing
were assessed via a survey. Particular emphasis was given to the
biological chemistry testing segment. The industry's possible
constraints on growth were also examined.
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Exhibit 1-1. Major segments of the chemical testing Industry and associated types of tests. 1/
Biological (Animal) Chemistry
Acute Testing
Acute oral toxicity
Acute dermal toxicity
Acute inhalation toxicity
Primary eye irritation
Primary dermal irritation
Dermal sensitization
Acute delayed neurotoxicity
In vitro genetics
Subchronic Testing
Subchronic oral dosing
Subchronic 21-day dermal toxicity
Subchronic 90-day dermal toxicity
Subchronic Inhalation toxicity
Subchronic neurotoxicity
In vivo genetics
Teratogenic
One generation reproduction
Chronic Testing
Chronic feeding study
Oncogenicity studies
Teratogenicity studies
Long-term reproduction studies
Carcinogenicity studies
Multigeneration genetic studies
Multlgeneratlon genetic reproduction
Environmental Chemistry
Physio - chemical Degradation 2J
Chemical transformation: hydrolysis
Chemical degradation: oxidation
Photochemical transformation in water
Metabolism
Aerobic soil
Anaerobic soil
Anaerobic aquatic
Microbes on chemicals
Chemicals on microbes
Activated sludge
Mobility
Leaching
Volatility
Adsorption
Water dispersal
F1eid Dissipation
Soil
Water
Ecosystem
Ecological Effects 3/
Cellulose decomposition
Nitrogen transformation
Sulfur transformation
Microbial effects tests
Plant effects tests
Animal effects tests
Algal inhibition test
Lemna inhibition test
Seed germination and early growth
Accumulation
Special Chemistry
Product Chemistry
General Physical/Chemical Properties
Water solubility
Vapor pressure
Adsorption
Boiling/melting/sublimation points
Density/specific gravity
Dissociation constant
Flaninabil ity/explodabil ity
Particle size
pH measurement
Chemical incompatibility
Vapor phase UV spectrum for halocarbons
Ultraviolet and visible absorption spectra
in aqueous solution
1/ Preliminary. Additional tests may be applicable within each segment.
2/ Includes product chemistry types of testing.
3/ Includes biological chemistry types of testing, e.g., animal effects.
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The total demand for chemical testing services—regulatory,
non-regulatory and research—and the incremental demand for testing
generated by Section 4 TSCA were assessed. In addition to these
demands, the non-testing demand for testing resources was estimated in
order to fully characterize the market for toxicological testing.
•Finally, a conceptual supply-demand model of the chemical testing
industry was constructed to provide a predictive tool for assessing
future industry trends when the required detailed data become
available.
A list of laboratories capable of performing the type of testing
required under Section 4 TSCA was compiled from information assembled
in the course of the survey. This listing, an integral part of the
chemical testing supply section of the study, is included in
Appendix A.
C. General Approach
Initially, literature and data reviews were conducted. The resultant
toxicology testing information is summarized in Chapter II of this report
and provided selected material for subsequent chapters on supply and
demand.
The study's literature review also identified data shortages characteristic
of chemical testing supply and demand. Chemical testing supply was
partially characterized in this study by a number of lists of
laboratories/facilities which conduct toxicology testing and by a partial
documentation of key personnel resources, i.e., certified pathologists,
toxicologists, and technicians. However, the laboratory data sources used
for such characterization were found to be inadequate in several respects:
they were often out-of-date, non-descriptive, and usually limited to the
laboratory name and address (often incomplete). Accessible chemical
testing demand data sources primarily reflect direct government demand.
Private testing demand and the distinction between government-induced and
voluntary testing demand were not found in existing data and hence, these
demands could not be assessed independently, from information in current
1iterature.
The industry structure was defined and characterized from secondary sources
and discussions with industry representatives, and telephone survey
interviews of laboratories. From the survey of toxicology testing
laboratories, the testing capabilities, capacity and utilization of
capacity were assessed. The survey also helped identify and evaluate
resource constraints. The toxicology testing industry and supply
characteristics are discussed in Chapter III. The list of chemical testing
laboratories, included in Appendix A, contains independent commercial
laboratories, captive laboratories and selected private research and
university laboratories.
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In Chapter IV, the sources of industry demand are evaluated. These include
U.S. government regulatory agencies and research institutes, private
industry, private foundations, and universities. Although much of the
demand for toxicological testing is directly or indirectly generated by
federal regulations, data from written records and information supplied by
regulatory agencies' personnel indicate that the amount of testing demand
generated by regulation, in a particular year, is extremely difficult to
estimate. Specifically, short delays in issuing regulations and budgetary
fluctuations result in actual demand volumes that can differ enormously
from predictions made six months before. Demand projections, therefore,
must be made by examining the projected development of the regulatory
programs over the next several years, rather than by examining plans for a
single year.
In order to characterize fully the market for toxicological testing, the
non-regulatory generated demands for testing resources must not be
neglected. This study's information gathered from professional
associations permitted an estimate of these and, finally, the existence of
a non-testing demand for toxicology testing resources is acknowledged, no
estimates were made of its magnitude.
Chapter V presents and discusses a conceptual supply-demand model of the
industry within a systems analysis framework. This model is resource based
and is segmented by testing categories. Although the complete supply-
demand data required for implementing the model and for using the model for
predictive purposes are not available, its conceptual developments are
documented so that later model implementation may be more readily
accomplished when data are sufficient. The research implications of the
study, the data needs, and the possible methods of acquiring such data are
summarized, also.
The list of toxicology laboratories is presented in Appendix A. The survey
instrument designed and utilized to obtain more detailed toxicology
laboratory information is included as Appendix B.
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II. LITERATURE AND DATA REVIEW
Thorough analysis of the chemical testing industry requires that the
economic characteristics of the industry and its markets be determined.
To provide the framework for that characterization and to identify the
data available for assessing the industry's baseline supply and demand for
chemical testing services, this study initially reviewed germane literature
and industry data sources.
A. Industry Structure and Organization
After assessing existing documents, journal articles, industry profiles and
after consulting with industry and academic personnel, this study's
researchers divided the chemical testing industry into three segments:
• Biological chemistry (mammalian, in-vitro, fish and wildlife)
t Environmental chemistry
• Product chemistry
Furthermore, each of these three segments was subdivided according to the
types of tests each performs (See: Exhibit 1-1). (These test
subcategories will be discussed later in terms of their required
resources.)
The rationale for dividing the market into three segments reflects both
academic principles and industrial procedures. Biological (animal)
chemistry testing encompasses a series of related tests. Specific tests
are classified by genre (acute, subchronic, and chronic) rather than by
target animal; consequently, an acute toxicity to fish test will be listed
as a biological test and not a fish or wildlife test because it is
categorically an acute toxicity test that incidentally uses fish as its
target species.
Environmental chemistry testing includes physio-chemical degradation
analysis, field dissipation assessment, and various ecological effects
analyses. Resource competition between environmental chemistry and
biological chemistry appears minimal due to the contrasting nature of
the differing professional personnel, test procedures, and testing
equipment required to conduct the various tests in each test category.
Such separation makes market segmentation both applicable and desirable for
the purposes of the present industry economic analysis.
II-l
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Product chemistry is that category which focuses on determining general
physical and chemical properties (e.g., vapor pressure and absorption). A
wide variety of analytical laboratories can perform these tests and their
personnel and other resource requirements appear to compete but minimally
with the two other categories. The economic characteristics of the product
chemistry industry, then, may also be assessed separately. Additionally,
product chemistry is not conceptually included among those technologies
more directly involved with health and environmental effects testing—
although TSCA may require such testing data.
The primary focus of this study is on the biological chemistry segment of
the chemical testing industry. Expected to have the most critical
personnel and other resource constraints, this segment is that which will
be most affected by the expected testing requirements of Section 4 of TSCA.
B. Literature/Data Review
Because chemical testing capacity has only recently become an important
underlying issue in the development of federal policy on the regulation of
chemicals, relevant literature is sparse. The literature reviewed for the
present study consists of several periodical articles and two recently
completed reports for EPA. This literature is briefly summarized below.
1. Profile of the Chemical Safety Testing Industry: An Assessment of
Pesticide Testing Capacity (May 1980)
This profile study, completed by ICF for the EPA's Office of Pesticide
Programs, addresses the ability of the chemical testing industry to meet
those demands stemming from the generic approach to pesticide registration.
The approach used in the study was:
• to determine those segments of the market in which constraints to
supply do or potentially exist, and
• to compare total projected demand with total projected supply for
those segments with supply constraints.
Because the chemical testing industry is not well documented, the profile
employed data gathered from a variety of sources including:
• personal and telephone contacts with representatives of
government, trade associations, and laboratories,
§ available documented sources (See: "References" at the end of
this report), and
• a written questionnaire completed by fifteen laboratories.
11-2
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Within the limits of the information obtained, the ICF's profile made
implicit the following observations and implications that are consequential
to the present study:
Observation 1 - The supply of high-quality animal testing is constrained
primarily by the supply of veterinary pathologists and, to a lesser extent,
by the supply of toxicologists. Other resources, such as laboratory space,
capital, and equipment, are also potential short-term constraints.
Implication: The availability of adequately trained professional manpower
is clearly an important determinant of the supply of toxicological testing
services and should be a major focus of supply assessment.
Observation 2 - Large variations in reported testing prices for reasonably
well defined protocols suggest that testing laboratories compete on factors
other than price.
Implications: Because this is a market for services rather than commodity
goods, decision modeling based solely on price will not adequately reflect
market behavior.
Observation 3 - Current research in genetic toxicology may result in
significant breakthroughs in testing technology, breakthroughs that
potentially change the testing resources currently necessary to meet
toxicological testing demand.
Implications: A supply-demand model must be so designed with sufficient
flexibility that it can accommodate changes in testing technology.
2. Cost Analysis Methodology and Protocol Estimates: TSCA Health Standards
and FIFRA Guidelines (April 1980, draft report to EPA)
Enviro Control Incorporated and Borriston Laboratories completed this draft
report for the Office of Regulatory Analysis (currently Regulatory Impacts
Branch) of EPA's Office of Toxic Substances. The study developed a
methodology for estimating the cost of health effects testing protocols.
Pricing determinations applicable to protocols for several acute,
subchronic, chronic and mutagenic tests were made directly by Borriston
Laboratories and by a limited survey (less than 10 contacts) of other
testing laboratories. Results indicated that price estimates for a well
defined protocol can vary by as much as plus or minus 50 percent from the
average.
In providing price estimates, Borriston characterized each protocol in
terms of the component resources it utilized. If these resources'
breakdowns are sufficiently validated, they can serve as useful inputs to
the implementation of an industry supply model. Because the survey showed
broad ranges for price data, the report is a further indication that the
industry competes on factors other than price. A supply model design,
therefore, should separate the industry's physical resources and
requirements from its associated cost and price data in determining the
industry's supply-demand specifications.
11-3
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3. Other Literature
A variety of other literature sources such as toxicology laboratory
directories, technical and industrial journals, and various federal
publications provided evidence of the following concerning the chemical
toxicological testing industry.
• Capacity—There is a potential shortage of overall health
and environmental effects testing capacity. (Anon., 1980a;
Murray, 1978; West, 1979.)
• Manpower—There is a shortage of qualified professional personnel
underlying the industry's potential capacity shortage. (Abelson,
1978; Anon., 1978b; Keller, 1979; Maugh, 1978; Murray, 1978.)
• New Technology—Mutagenicity testing is a growing area of
toxicological testing and has the potential to redefine the
market for such testing. (Anon., 1980b; Haworth, 1979; Maugh,
1979.)
• Qua!ity--Testing firm reputation and other non-price factors are
important for both facilities and personnel. (Anon., 1980a;
Keller, 1979; Murray, 1978; West, 1979.)
• Laboratory Classification - Chemical testing laboratories can be
classified into three general groups:
Commercial
independent
captive
University
Government
The present study so classifies the industry in order to analyze its
sources of chemical testing resources and to identify and compile a list of
chemical testing laboratories.
C. Data Sources and Limitations
Historically, the chemical testing industry has not been well documented as
an economic sector; consequently, no regular statistical reports exist on
the structure and performance of any segment of this industry. This
section of this report does, however, briefly summarizes a number of data
sources that are germane to estimating industry resource supply and
industry demand.
11-4
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1. Data Sources: Supply
Relevant supply data include partial information on laboratories,
personnel, and other resources. Several lists of selected laboratories are
available, as shown in Exhibit 11-1. With some exceptions, these lists
present problems to the researcher.
t Most are not compiled or updated regularly; rather, they are
one-time efforts (except those of the American Council of
Independent Laboratories).
• They do not sufficiently describe the testing services offered
(except those of the Society of Toxicology).
• The resources that affect supply capacity are not well
documented.
• The validity of descriptive information, when provided, is
unknown.
Nevertheless, these lists provided the foundation for a master list of
laboratories which provide chemical testing services. This preliminary
list was used initially as a source of contacts for a telephone survey of
laboratories conducted to identify their services and characteristics.
(Francke, 1981.)
A few documented data sources are available which discuss the industry's
professional manpower. The American College of Veterinary Pathology
publishes data on the number and the activities of board-certified
veterinary pathologists, but few other data are available. Information on
other pathologists (M.D., Ph.D., D.O., D.D., other D.V.M.) may exist from
other trade associations; however, the extent to which these other
pathologists would be considered "qualified" under the final TSCA testing
guidelines is unclear. The National Institute of Environmental Health
Services (NIEHS) has proposed a study germane to toxicological manpower
needs. The study will develop a taxonomy that will classify toxicologists
and toxicology training programs and will be instrumental in projecting the
supply of future toxicologists. In addition, some certifying organizations
exist for technicians (histology technicians and animal handling
technicians). These organizations could provide basic information about
the supply of such technicians.
Information on the supply of other resources, such as animals and
equipment, must be obtained directly from suppliers.
2. Data Sources: Demand
The present study also assessed to the extent possible both government-
related and private demand. The former includes both regulatory and direct
research demands; private demand includes that industry testing for product
development and evaluation which is not directly attributed to regulation.
(Private research includes also, the demands made upon university and
foundation research efforts.)
11-5
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Exhibit. ll-l. Partial source listing of testing laboratories, chemical testing Industry study
1. EPA, Office of Pesticide Programs, June 1977.
List of 381 laboratories which was cited as a source of data in
support of a registration application for pesticides, 1947-77. List
also notes how many times each lab was cited as a source.
2. Food and Drug Administration (List of laboratories that have per-
formed work submitted to the FDA), June 1979.
This list of about 500 labs contains information about the type of
laboratory (government, sponsor, contract, or university) and the
Bureau within FDA where data were submitted, June 30, 1979.
3. American Council of Independent Laboratories, Inc., Directory 1978.
About 200 member laboratories give descriptions of their service in
this directory which is indexed by geographical location and type
of service performed. Host of these laboratories offer nrimarily
analytical chemistry arid chemical engineering services rather than
toxicological testing.
4. Society of Toxicology, Toxicology Laboratory Survey, March 1976.
This booklet on about 130 laboratories is based on a mailed survey
^ of all members of the Society of Toxicology. Information on each
i lab Includes the type of tests performed, in-house capabilities and
^ personnel, experience with types of compounds, and whether lab does
contract work.
5. Chemical Times arid Trends, "Testing Laboratory Directory", Oct. 1979.
About 120 laboratories that perform toxicological testing are listed
In this issue of the Journal of the Chemical Specialties Manufacturers
Association. Addresses, phone numbers, names of contracts are pro-
vided and whether the laboratory Is currently accepting contracts.
6. Tox-Tips (Toxicology Testing 1n Progress), National Library of
MiJicine, December 1979.
This monthly bulletin prints an index of institutions and investiga-
tors In its quarterly issues for all studies participating in the
project.
7. Mutagenicity Testing Laboratories in the U1S. Compiled by Dr. Michael
D. Shelby, Office of the Associate Director for Genetics, National
Institute of Environmental Health Sciences, November 1979.
This booklet contains names and addresses of 43 laboratories that
perform mutagenicity tests and lists the specific tests available
or under development at each laboratory. Also indexed by geographical
location and type of test.
8. "Report of the Subcommittee on Inhalation toxicology of the Department
of Health Education and Welfare Committee to Coordinate Toxicology
and Related Programs", Raymond E. Shapiro, Executive Secretary, Journal
of Environmental Pathology and Toxicology, 1:353-381, November 1977.
Contains a list of lb academic Institutions, 16 government facilities
and 39 private labs that perform inhalation toxicology testing. De-
scribes present facilities in each lab, studies being done, capacity,
and future plans.
9. National Association of Life Science Industries, Membership list,
May 1978.
List of 21 members of NALSI and names of laboratory representatives .
to the association.
10. American Society for Testing & Materials. Directory of Testing
Laboratories. 1975.
Approximately 90 of the 439 laboratories In this directory are listed
as having toxicological capabilities. All are equipped to undertake
testing on a fee basis. Specific tests, staff, capacity and experience
are not recorded.
11. Analytical Chemistry, "Laboratory Guide Issue", August 1979.
This annual guide Includes an alphabetical list of analytical and
research services.
12. fhoinas Register of American Manufacturers, 1980
Numerous listings of laboratories are presented in "environmental",
"experimental" and "research and testing" categories. Besides
address and phone numbers, Thomas includes a very brief Indication of
type of service, a classification by "approximate minimum tangible
assets", and, for some laboratories, either an advertisement or
reproduction of the company catalog.
13. OHEW, Toxicology Research Projects Directory.
This monthly directory of projects classified by toxic agent, research
orientation and areas of environmental concern Includes a subject in-
dex and a performing organization Index (cumulated annually). The
sponsoring and performing agencies both Include a variety of govern-
ment and non-government institutions.
14. Industrial Research Laboratories of the United States, 1977 Bowker
15th Ed.
Most of these research facilities are owned and operated by industrial
firms, foundation-supported facilities and university labs Independent
of university control. In addition to addresses and phone numbers, the-
directory includes names of principal executives, number of professional
staff, a fairly specific statement of research and development activity
and whether facilities are available for non-company projects. Over
120 laboratories are listed as conducting toxicological testing.
Source: Compiled by ICF Incorporated and Development Planning and Research Associates, Inc.
-------
There is little documented information available which can be used to
readily and accurately determine the demand for chemical testing. The
following programs (other than TSCA) appear significant in their effect on
creating industry demand.
• Federal Insecticide Fungicide and Rodenticide Act (FIFRA)
¦ Food and Drug Act (FDA)
• National Institute of Environmental Health Services (NIEHS)
• National Institute for Occupational Safety and Health (NIOSH)
• National Cancer Institute (NCI)
This study's efforts to identify demand data did result in the following
general observations concerning the characteristics and availability of
demand data sources.
Estimates of the testing demand generated by government-related programs
are usually subjective ones made by appropriate government personnel.
However, they are often reluctant to have their appraisals used for
analytical purposes.
The estimates on testing consequent to government-supported research are
more objective. Most research agencies maintain documented plans for and
lists of on-going projects which can be used to estimate this component of
demand. Such documentation exists for NIOSH, NCI and for the National
Toxicology Program in general. EPA and FDA research-generated
demands are generally documented. Finally, some developmental work with
new chemicals subject to pre-manufacturing regulation under Section 5 of
TSCA can be documented.
Private (non-statutory responsive) demand both in general and specifically
for product development and evaluation were neither found nor identified.
Existing data do not clearly distinguish between regulatory-induced demand
and voluntary demand. In developing this study's baseline demand, such a
distinction, however, is not necessary, for both regulation-induced and
voluntary testing should be included and aggregate resource demand
identified. The relevant information required for an assessment of TSCA
induced changes in the baseline demand are (1) the classes of chemicals for
which testing is required, (2) the types of tests that may be required, and
(3) the probability of the tests being performed. Impact and sensitivity
analyses could show how future patterns of regulation or research could
change the baseline demand.
11-7
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III. THE TOXICOLOGICAL TESTING INDUSTRY AND SUPPLY
OF TESTING RESOURCES
The toxicological testing industry's supply is clearly dependent upon the
availability of its critical resources: manpower, laboratory space,
animals, equipment and capital. Skilled toxicologists capable of designing
and performing studies, especially those in biological testing, are
critical to the industry. Pathologists are needed, as well, to examine
tissues consequent to those studies. Laboratory space, a potentially
constraining resource, is critical to the industry for it is one in which
varied tests and studies must be conducted concurrently and in distinctly
separate testing areas and individual animal rooms. Laboratory animals,
especially those resulting from unique breeding and specific species
requirements, are a potential constraint of long-term significance. Highly
automated, precision equipment is required so that varied, reliable, and
reproducible test data may be obtained by the industry. Finally, industry
capital availability is significant, so that the necessary quality and
quantity of such critical resources can be maintained.
This chapter assesses the supply of toxicological testing and the
industry's ability to meet the demands exercised by public and private
entities. Much of the information presented reflects that of a recent
survey (Francke, 1981) of the chemical testing industry, a survey which
identified toxicology testing laboratories and their characteristics and
capabilities. This survey's data are supplemented by information from
other research literature, industry publications, and from contacts with
industry technical and administrative personnel.
The chapter is organized in four parts:
A. Profile of the toxicological testing industry—a background
discussion of the industry which includes its number of firms,
employment, sales, concentration and other general
characteristics.
B. Testing capabilities - a discussion of the toxicology testing
performed by laboratories.
C. Capacity and utilization - a discussion of the industry's
capacity and ability to increase testing.
D. Resources supply and constraints - a discussion of the adequacy
of the industry's professional manpower, test animals, laboratory
space, capital, and other critical resources.
III-l
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A. Profile of the Toxicological Testing Industry
The former Division of Chemistry of the United States Department of
Agriculture conducted toxicity testing as early as 1880; however, not until
passage of the 1938 amendments to the Federal Food, Drug, and Cosmetic Act
of 1906 did government regulation begin to generate substantial toxicology
testing. Prior to these amendments, small-scale, in-house testing was
carried out by some of the chemical and pharmaceutical producers. The 1938
amendments required producers to submit proof of the safety and
effectiveness of their products prior to marketing. Although this
legislation did not include specific testing requirements, its effect was
to initiate testing on a large-scale basis and prepare the way for the
growth in independent laboratories and the expansion of in-house facilities
which occurred during the 1970's. (Anon. 1980c; Veraska, 1980.)
1. Number of Laboratories
Toxicology testing has recently become a major business in the United
States. Much of the industry's growth was in response to the demand
stemming from such federal statutes as the Toxic Substances Control Act
(TSCA) of 1976, and the amendments to the Federal Insecticide, Fungicide
and Rodenticide Act (FIFRA). Although the Resource Conservation and
Recovery Act (RCRA) and the Clean Water Act (CWA) do not specifically
require testing, their provisions also furthered the growth of testing. As
now written, these and similar laws will continue to generate demand for
toxicology testing, and the industry should sustain long-term growth.
While toxicology testing is a major industry, its relative newness has
prevented the development of a comprehensive information base from which to
profile it. This limitation has been alleviated significantly by a recent
survey which contacted about 800 laboratories to determine if they qualify
as toxicological testing laboratories. _1/ The survey identified 272
laboratories that perform toxicological testing, and of these, 242
cooperated and responded to the complete survey while 30 did not. 2/
The survey depended on public listings and referrals for its initial
screening list of 800 chemical laboratories. The various public listings
used spanned the last six years, and none was comprehensive. These
limitations plus the time constraints and some refusals prevented complete
industry coverage, as intended, and the end result was a large sample
survey.
Ij The survey was done as a supplement to this present analytic report of
the toxicology industry and was carried out jointly for the
Environmental Protection Agency by Development Planning and Research
Associates of Manhattan, Kansas, the Center for Public Affairs of the
University of Kansas, and ICF Incorporated of Washington, D.C. The
survey, approved by the Office of Management and Budget (0MB No.
2000-0141), constitutes Appendix B of the present study.
2/ A listing of all laboratories which indicated they performed
toxicological testing is included in Appendix A.
111-2
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Nevertheless, its coverage is extensive and the 242 responding firms are a
significant proportion of the estimated 280 to 290 existing toxicology
testing laboratories. This report, then, uses an industry population
estimate of 285 toxicology laboratories for its descriptive and analytic
characterizations of the industry.
2. Employment
The survey responses of the toxicology laboratory personnel indicated that
the industry employed an average of 57 employees per laboratory in 1980 or
a total of slightly more than 16,000 (57 x 285 firms). The relative
distribution of this employment among professionals, technicians, managers
and administrators, and other staff is:
Percent of employees Number If
Professionals 36 5,800
Technicians 45 7,200
Management & Administrative 13 2,000
Other Staff 6 1,000
Total TCCT 16,000
Large variations exist among laboratories regarding employment, with sizes
ranging from five or fewer employees to over five hundred. Overall,
the following distribution by size is estimated:
Number of employees
per laboratory
1-10
11-50
51-100
101 or more
Percent of
laboratories
28
48
13
11
lM
3. Laboratory Space
Laboratory space is another critical resource affecting the industry's
capacity for toxicological testing. Test conditions can require extensive
animal cage space as well as inhalation chambers that are especially
dependent upon restricted, specialized areas.
The surveyed toxicology laboratories contained an average of 28,100 square
feet. Again, substantial variation exists within the industry--many small
laboratories contain fewer than 5,000 square feet and the very large, over
100,000 square feet. The distribution of laboratories by general size
categories is:
1/ Estimated to nearest two significant digits.
111-3
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Square feet of laboratory space
Percent of
laboratories
5,000 or less
6,000 to 20,000
21,000 or more
40
31
29
lTHT
Much of this space is apparently new, for considerable laboratory space
expansion has occurred in recent years. A review of industry literature
and conversations with industry officials provide the following examples of
new expansion in laboratories.
t Mobay and Stauffer recently completed 60,000 square foot animal
test facilities. (Chemical Marketing Reporter (CMR),
11/05/79, p. 16; Chemical Week, 1/23/80, p. 38.)
• In 1978, Goodyear Tire and Rubber Company added a $100,000
testing laboratory to its existing research facilities in order
to investigate whether new tire industry chemicals are
hazardous to human health. (Chemical Marketing Reporter,
9/11/78, p. 32.)
• In April, 1980, ICI Americas, Inc. applied for a $43.5
million industrial revenue bond issue to finance a proposed
expansion of the company's biological research center at
Goldsboro, NC. (Wall Street Journal, 4/4/80, p. 19.)
• In January, 1980, Dow Chemical Company was in the process
of adding 28,000 square feet to its toxicology testing lab-
oratory at Midland, MI. The company has expanded this
facility five times since its founding and it now employs
sixty scientists. (Chemical Week, 1/23/80, p. 38.)
• Shell completed a 60,000 square foot toxicological testing
laboratory at its Houston research complex during 1979 (Chemical
Week, 1/23/80, p. 38.)
• During 1980, Allied, Monsanto and DuPont's Haskell Laboratories
proposed additions to or were expanding their toxicology testing
laboratories that had been completed just a few years previously.
(Chemical Week, 1/23/80, p. 38; CMR, 10/9/78, p. 50; J. Commerce,
9/17/79, p. 50.)
- In April, 1979, Allied completed a $1.4 million, 17,000
square foot animal laboratory. Another 25,000 square foot
laboratory has been requested from the Board.
- Monsanto plans to add to its 47,000 square foot, $12 million
toxicology testing laboratory that was dedicated in the fall
of 1978. Until completion of the present facility, Monsanto
111-4
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had used independent laboratories to do safety testing, but
according to a company spokesman, the company's research needs
"outstripped the capabilities of these outside laboratories."
- Haskell Laboratories completed a 70 percent expansion in 1976
and is now adding an $8 million facility which will further
expand capacity by 30 percent.
• The Chemical Industry Institute of Toxicology completed a $10
million testing and research laboratory in Research Triangle
Park, NC (CMR, 1/3/77, p. 7 and 6/20/77, p. 20.)
• In 1978, Medtronics, Inc. of Minneapolis, the world's largest
manufacturer of cardiac pacers, opened an in-house toxicology
laboratory for testing the chemical industry's products. The
firm has extensive experience in testing its own products.
(Chemical Week, 2/20/79, p. 48.)
• Syracuse Research Corporation completed an aquatic toxicology
laboratory in 1979 to help the chemical industry meet new federal
testing requirements. (Chemical Week, 2/28/79, p. 48.)
• Biospherics, Inc. of Rockville, MD, expanded its laboratory
which monitors the effects of potentially toxic chemicals,
pesticides, and drugs on aquatic animals and plants.
(Environmental Science and Technology, 9/79, p. 1182.)
• Jacobs Engineering Group established a 12,000 square foot
analytical laboratory at Pasadena, CA, in 1978. (Environmental
Science and Technology, 8/79, p. 1089.)
• Litton Bionetics opened an 88,000 square foot laboratory in
Rockville, MD, in 1978 to perform biological safety evaluation.
(Graham, 1980.)
• International Research and Development Corporation completed a
100,000 square foot facility during the latter half of its 1978
fiscal year. (SEC, 1979) This addition, not fully utilized at
the end of fiscal year 1979, has been contributing to the firm's
increased costs and lower profits during the past few years.
• Hazleton Laboratories plan to begin work in the near future on a
$10 million laboratory in Sterling, VA, where the company
currently has a 103,000 square foot laboratory. (Rowe, 1981.)
4. Financial characteristics
Limited data are available on the financial characteristics of the
toxicology laboratory industry. Three major factors contribute to this
condition:
III-5
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• The toxicology testing industry is but one segment of the
chemical testing industry, and it has not been traditionally
identified uniquely enough to have its financial characteristics
reported separately.
• The toxicology testing industry is relatively young and dynamic,
and historical data bases have not been established.
• Many laboratories are relatively small, private operations for
which public information is not available.
Because of these conditions, information on financial character)'sties are
restricted to general estimates of industry revenue or volume of business
and a small sample of data on service fees. No significant data were found
on costs, operating margins, and capital structure.
The survey did not request information concerning the responding firms'
specific financial characteristics. Such information is not critical to
the assessment of testing capabilities, and traditionally it is an area in
which low and unreliable response rates are experienced. However, a
combination of the survey information and company financial reports and
brochures does yield acceptable estimates of revenues. Specifically, a
small sample of company brochures and reports shows that laboratories
generate average annual revenues of $40,700 per employee. Applying this
revenue factor to an industry employment level of 16,000 employees results
in estimated industry annual revenues of $650 million or an average of $2.3
million per laboratory for 1981. This estimate approximates that quoted in
a 1980 New York Times article which indicated that chemical testing by
commercial laboratories had become a $500 million a year business.
(DeWitt, 1980.)
Historical estimates on revenues are unavailable from the survey or
published sources, but significant growth occurred through the 1970's, a
growth primarily attributed to a perceived increased demand in response to
environmental regulations and product liability related testing. In the
last six to eighteen months that growth has slowed. If, however, such
slowdown is due to the weakness in the nation's general economy and to
uncertainty about key regulatory decisions that may be made regarding
environmental issues (DeWitt, 1980; Veraska, 1980), such a slowdown may be
temporary rather than a reflection of industry potential.
Company brochures and reports also provided a small sample of data on
service fees for certain types of tests, primarily in the area of in-vitro
and acute mammalian testing. These tests are relatively standard tests
with more simple protocols and lower costs compared to chronic tests or
environmental tests. As shown below, however, there is still a wide
variation in service fees charged for comparable tests. The variation may
reflect differences in testing quality, costs and cost accounting,
marketing strategy, protocols and staffing.
111-6
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Type of tests Range for service
(sample size) fees 1981 ($)
IN-VITRO
Ames mutagenicity-plate and pre-incubation,
duplicate (6) 375 - 1,200
Mouse lymphoma (4) 3,600 - 6,500
DNA repair - E. Coli polymerase assay (3) 300 - 575
Chromosome aberration (2) 3,500 - 4,000
Drosophila mutagenicity (2) 10,800 - 12,500
IN-VIVO
Chromosome aberration-bone
Rat (2) 13,500
Mouse (2) 10,000 - 10,800
ACUTE MAMMALIAN TESTS
Oral-screening or single dose (8) 85 - 610
Oral - LD50 determination (6) 430 - 3,100
Dermal-screening or single dose (5) 240 - 1,100
Dermal - LD50 determination (4) 700 - 5,750
Primary eye irritation (6) 175 - 990
Primary dermal irritation (5) 205 - 660
Pyrogen-three rabbit-negative (5) 45 - 75
While these data are indicative of general price levels, they are
insufficient in providing detailed information on average prices, price
trends and relationships between testing supply and prices.
5. Concentration
Concentration in the toxicology testing industry can be estimated on the
basis of the survey data related to employment by extrapolating that data
through two measures of concentration: (1) a traditional concentration
table which shows concentration ratios for sets of firms and (2) the more
comprehensive "lorenz curve." The latter measure shows, as a continuous
function, the percentage of total industry employment level accounted for
by the fractions of all firms ranked in order of size.
The following table shows employment concentration ratios for various sets
of laboratories from the 235 firms that provided employment data.
Size of laboratories by Percent of
employment (n = 235) employment
Largest 4 (2% of sample) 17
Largest 8 (3%) 28
Largest 20 (9%) 48
Largest 50 (21%) 71
Smallest 100 (43%) 6
Smallest 200 (85%) 38
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While these data do not include all laboratories, most of the largest are
included and the small laboratories that are excluded represent a small
percentage of total employment. Thus, these estimated concentration ratios
are good estimators of actual levels (with but a small upward bias). The
ratios indicate that the top four firms account for less than 20 percent of
total employment. They could control slightly more of the industry's sales
or testing (traditional measures of concentration) if these larger
laboratories were to generate more sales or perform more tests per employee
than do small firms. Large-firm market power, however, is still not
expected to be dominant. Generally, 4-firm ratios in U.S. industries will
range from less than five percent to over 90 percent with a ratio of less
than 30 percent being considered relatively low.
Using the sample data and employing similar procedures of matching percent
of firms ordered by size with percent of employment represented by these
firms, a more comprehensive Lorenz curve can be developed to indicate
concentration in the toxicology testing industry. The results of this
procedure appear in Exhibit 111-1. For example, the data indicate that the
smallest 40 percent of the firms accounts for only 6 percent of the total
employment—approximately 900 employees. This includes 114 firms employing
14 persons or fewer per laboratory. Moreover, the largest 20 percent of
the firms (the 80 percent figure on horizontal axis) employs 69 percent of
the employees of the industry (100% - 31%) or an estimated 10,350 persons.
These are represented by firms employing 65 or more persons per laboratory.
In sumnary, employment data indicate that the toxicology testing industry
exhibits a measurable amount of concentration, but the level is not high
enough to restrict market competition or to allow individual firm control
of key resources. Market power should also continue to be dispersed, for
this is a growth industry which provides a relatively homogeneous,
undifferentiated service with somewhat low capital requirements. Such
characteristics traditionally stimulate competition and firm entry into an
industry.
6. Type of Ownership
The ownership of toxicology laboratories providing commercial testing
services is traditionally divided into two categories: captive (in-house)
laboratories and independent (contract) laboratories. If The latter are
independently owned and operated and perform work for various clients only
on a contract or bid basis.
Independent laboratories are organized either for profit or not-for-profit.
Major not-for-profit laboratories include Battel!e-Columbus Laboratories
and Battelle-Pacific Northwest, Midwest Research Institute, and Stanford
1/ Other laboratory types which contribute to testing supply, but which do
so less significantly than do contract or captive laboratories are
discussed in Section 9~, Other Laboratories.
II1-8
-------
16,000
100 n
- 12,800
80 -
c
-------
Research Institute (SRI International); certain university laboratories
would also be included here. Industry sources usually refer to the
following five firms (presented in alphabetical order) as those among the
leaders of the for-profit laboratories:
• Bio/dynamics, Inc.
• Hazleton Laboratories of America, Inc.
• International Research and Development Corporation (IRDC)
• Litton Bionetics, Inc.
• Raltech Scientific Services
Captive laboratories, divisions or subsidiaries of firms, perform in-house
testing for their companies. Importantly, however, some also perform
contract testing, a practice which reduces the importance that ownership
characteristics may play in determining a laboratories' testing
capabilities. The survey data indicate that captive laboratories perform a
sizeable amount of contract work.
Nonetheless, about 34 percent (about 100 laboratories) of all toxicology
laboratories are classified as independent, contract firms. The remaining
180 to 190 laboratories are owned and controlled by parent firms and
perform work both in-house and on a contract basis.
7. Type of Business
The aggregate industry work, categorized as in-house or contract testing,
is divided into about 58 percent contract and 42 percent in-house. An
individual laboratory's work mix will, however, vary extensively from this
industry mean:
Type of Business % of Laboratories
In-house (100% in-house) 24
Primarily in-house (71-99% in-house) 12
Combined (30-70% in-house) 11
Primarily contract (71-99% contract) 19
Contract (100% contract) 34
100
While no data exist from which to estimate overall industry trends,
industry literature suggests an increasing contract business. This
primarily reflects:
• the lack of in-house facilities,
• the strain placed on existing in-house capacity by long-term
studies, and
• the belief of some companies that regulators favor data from
unbiased outsiders who have no self-interest in the chemical
being tested.
Industry sources suggest, as well, that much expansion has taken place in
captive laboratories. Several reasons are given among which are (1) better
quality control, (2) improved scheduling, and (3) cost savings.
111-10
-------
8. Important Qualitative Factors
Two qualitative factors are important to an understanding of the chemical
testing industry: the quality of testing and the potential breakthroughs
in testing methods.
Toxicological testing is a service industry and, as is true of other
service industries, its quality considerations play an extremely important
role. Indeed, these quality considerations are consequential, non-price
determinants when a prospective customer chooses a particular laboratory.
This importance is emphasized, also, by various measures that have been
taken since the industry has shown evidence of uneven testing quality. In
answer to this, for instance, EPA has proposed Good Laboratory Practices
and Testing Guidelines. Other recent quality control efforts have also
been instituted: The Toxicology Laboratory Accreditation Board has been
established to accredit laboratories; the American Board of Toxicology now
certifies toxicologists; and the Food and Drug Administration promulgates
and enforces the Good Laboratory Practices standards. The apparent
dilution of testing resources has raised the potential for a decline in the
industry's quality of testing.
The second important qualitative factor is that the industry's potential
for significant breakthroughs in testing methods could markedly alter the
mix of its critical resources. The reality of today's testing methods for
chronic effects, for instance, is that such tests take three or more years
to complete, cost hundreds of thousands of dollars, and can still be
inconclusive in terms of estimating human risk, particularly at
low-exposure levels.
A need clearly exists for quicker, less expensive, and more reliable
testing methods for both oncogenic and non-oncogenic effects. Much
research has been conducted in this area, particularly using in-vitro
methods to screen for mutagenic and carcinogenic effects. (Bates, 1977;
Dagani, 1980; Freed, 1979; U.S.H.E.W., 1979.) While some of this research
has been promising and some disappointing, a significant breakthrough would
change testing methods and would have the potential to consequentially
redefine the market for toxicological testing and change the required mix
of underlying resources.
9. Other Laboratories
The foregoing analysis concentrated on laboratories which are capable of
providing commercial toxicology testing services. These included
independent contract laboratories (profit and non-profit), captive
laboratories, and selected university laboratories. Three additional
classifications of chemical testing laboratories are part of the supply of
the industry's chemical testing service: other university, government, and
foreign laboratories. These sources, which were not included in the survey
or in the foregoing analysis of supply, are briefly discussed below.
III-ll
-------
University laboratories are evidently becoming increasingly interested in
providing contract testing services. Because some are included on
toxicology testing lists and are seeking commercial testing work, a
selected number of university laboratories were included in this study of
the toxicology testing industry. Others also operate toxicology
laboratories; they, however, are used for basic research and teaching and
would not be available to perform testing in response to government
regulations. These laboratories may, however, still play an important role
in determining the supply of chemical testing services, for they too
compete with contract and captive laboratories for critical resources.
Government facilities can be considered as part of the chemical testing
supply since considerable toxicological testing is conducted by the federal
government itself; however, these facilities are restricted to addressing
only governmental toxicological testing demands. For this reason, then,
government toxicological testing facilities were not assessed as part of
the chemical industry's testing supply. One significance of the government
sector is its competition for testing resources - particularly
toxicologists and pathologists.
Foreign laboratories operate on both contract and captive bases in many
European countries, Japan, and Canada and compete, to some extent, with
U.S. contract laboratories. (Hazleton 10K report, (SEC, 1980a.) In
addition to their foreign based laboratories, multinational chemical and
pharmaceutical companies do use U.S. laboratories and, hence, utilize a
part of the chemical testing supply available to U.S. firms. The capacity
and utilization of such multinational firms are less well documented than
are U.S. facilities; thus, these laboratories were considered beyond the
scope and resources of this study.
B- Testing Capabilities
1. General Areas of Testing
Toxicology testing laboratories perform health and environmental testing in
four general areas that are potentially required under TSCA regulations
(44 FR 16240—16292). These are:
• Mammalian (Animal) Testing
• In-Vitro Testing
§ Environmental Effects Testing
• Chemical Fate Testing
Most laboratories are also capable of performing general product and
analytical testing which may or may not be related to health and
environmental testing.
The laboratory resource survey which was formative in presenting the
industry profile of the preceding section also provided information on the
extent of testing in the above four major test areas. As shown in
111-12
-------
Exhibit III-2, 63 percent of the toxicology laboratories are currently
performing mammalian testing. Mammalian testing accounts for 38 percent of
the testing revenues generated by toxicology laboratories which is
equivalent to total annual revenues of $250 million. While about one-half
of the laboratories perform in-vitro, environmental effects and chemical
fate testing, each area represents but a small portion of all industry
testing volume: mammalian testing represents an average of 38 percent of
the volume; the other three toxicology testing areas represent only 7 to 13
percent of the industry's testing.
Most of the laboratories, 81 percent, also perform standard analytical and
product testing; however, such testing is much less resource intensive and,
thus, generates a smaller share of testing revenues than mammalian testing,
30 percent versus 28 percent. Thus, while about 28 percent more
laboratories provide analytical and product testing than mammalian testing
(a component of biological testing), the former generates 20 percent less
testing revenues than mammalian testing. Product and analytical testing
may also serve as a management tool, for those areas can be more easily
expanded or reduced depending upon the level of utilization in the health
and environmental testing areas.
Within the four major health and environmental testing areas, many specific
types of tests exist and provide a further understanding of the
capabilities of the testing industry. These are discussed in detail in the
following sections according to their general test areas.
2. Mammalian Testing
Mammalian testing is that component of biological testing which utilizes
the highest order vertebrates in its testing procedures. [For this study,
it is equivalent to "animal testing" for it does include a limited use of
poultry (non-mammalians)]. Mammalian testing capabilities can be
categorized by (1) the types of tests it performs and (2) the types of
mammals (animals) it utilizes. While these categories are not entirely
separate, they are convenient and logical measures with which to address
industry capability and resource issues.
a. Types of tests
The general category of mammalian (animal) testing includes seven testing
types:
(1) acute
(2) subchronic
(3) chronic
(4) reproductive
(5) teratogenic
(6) oncogenic
(7) histopathological
III-13
-------
Exhibit 111-2. Estimated number of U.S. toxicology laboratories and their volume of
testing (dollars) by testing area, 1981
Toxicology Volume of testing
Testing area laboratories Total testing" Toxicological testing 1_/
(X)
(No.)
(*)
($ mil.)
(%)
($mil.)
Mammalian
63
180
38
250
56
250
In-vitro
51
150
12
80
18
80
Environmental effects
51
150
13
80
18
80
Chemical fate
48
140
7
40
9
40
Product and analytical
(toxic and non-toxic testing)
81
230
30
200
NA
NA
TOTAL
100
650
100
450
\j Excludes product and analytical testing which may or may not be related to toxicological testing.
NA = Not Applicable
Source: Francke, 1981.
-------
In addition, within the acute, subchn
several major sub-types of tests can <
Acute
• acute oral toxicity
• acute dermal toxicity
• acute inhalation toxicity
i primary eye irritation
t primary dermal irritation
• dermal sensitization
• acute delayed neurotoxicity
ic, and chronic types listed above,
so be identified:
Subchronic
• oral dosing
• 90-day dermal toxicity
• inhalation toxicity
• neurotoxicity
Chronic
• oral
• dermal
• inhalation
• parenteral
To completely assess the ability of the commercial testing industry to
perform its present and potentially required testing, the capability of the
laboratories that conduct these specific sub-types of mammalian testing
must be known. For example, almost 94 percent {about 170) of laboratories
performing mammalian testing offer acute oral toxicity testing. In
contrast, only 55 percent (or 100) of the mammalian testing laboratories
conduct the more resource-consuming acute inhalation toxicity tests and a
comparatively low 51 percent perform delayed neurotoxicity tests. In the
remaining areas of acute testing, over 80 percent of the mammalian testing
laboratories (over half of all toxicology laboratories) perform the tests.
Exhibit III-3 summarizes the specific mammalian testing capability of the
surveyed laboratories.
Further review of Exhibit 111-3 indicates that fewer laboratories perform
inhalation toxicity and neurotoxicity tests, be they acute, subchronic or
chronic than perform the other sub-types of tests. This is attributable to
the extensive capital required to secure the needed specialized equipment
and laboratory space and to the relatively limited numbers of personnel
available to perform the more sophisticated protocols required in these
areas. There may also be relatively less demand for inhalation and
neurologic tests as they may be delayed until the less complex oral and
dermal tests have been performed.
This analysis is limited as only the number of laboratories performing the
specific tests is known. Not known is the capacity for each specific type
of test for laboratories and the industry and no direct data are available
to estimate current or future demand for these types of tests. The
implications are, however, that a simple count may underestimate capacity
in some areas as cross-tabulations show that about 75 percent of the firms
employing over 100 persons provide acute and subchronic inhalation testing
111-15
-------
Exhibit III-3. Percent and number of laboratories performing specific types of mammalian tests, 1981
Percent of
toxicology
laboratories
performing tests
Estimated
number of
toxicology
laboratories
Category or
subcategory of
mammalian testing
Percent of mammalian
testing laboratories
performing test
MAMMALIAN TESTING
1. ACUTE
Oral Toxicity
Dermal Toxicity
Inhalation Toxicity
Primary Eye Irritation
Primary Dermal Irritation
Dermal Sensitization
Delayed Neurotoxicity
2. SUB CHRONIC
Oral Dosing
90-day Dermal Toxicity
Inhalation Toxicity
Neurotoxicity
3. CHRONIC
Oral
Dermal
Inhalation
Parenteral
4. REPRODUCTION
5. TERATOGENIC
6. ONCOGENIC
7. HISTOPATHOLOGIC
100
94
87
55
82
87
83
51
83
74
42
46
74
66
36
64
63
64
63
70
63
60
55
35
52
55
52
32
52
47
27
29
47
42
23
40
40
40
40
44
180
170
160
100
150
160
150
90
150
130
80
80
130
120
60
110
110
110
110
130
Source: Francke, 1981.
-------
where as only 15 to 30 percent of firms employing 10 persons or less
provide these tests. Thus, although no estimate can be derived, actual
testing resources or supply could be relatively abundant . Furthermore, if
demand for inhalation or neurotoxicity tests is relatively low, then such
test capabilities may be adequate.
b. Animals used
Small rodents are the most commonly used animals for toxicity testing. An
estimated 97 percent of the laboratories performing mammalian tests use
such small rodents as mice, rats, hamsters and gerbils, and an average
laboratory requires an on-going inventory of about 11,000 rodents.
Rabbits, the next most frequently used animals, are utilized by 95 percent
of the mammalian testing laboratories, and facilities' average inventory is
about 230. The incidence of the use of these and the other animals and
average number in use and inventory per laboratory are shown below.
Average number
of animals
Percent of matronal i an in use and
Test Animal laboratories using animal inventory
Small rodents (mice, rats,
hamsters, gerbils) 97 11,000
Rabbits 95 232
Guinea Pigs (large rodents) 91 180
Dogs 63 186
Cats 50 28
Primates 37 257
Poultry 43 148
Large Domestic Animals (e.g. cows) 29 52
These data provide an estimate of the animal resources normally in use in
mammalian testing laboratories. For example, these data indicate that the
industry will normally maintain about 1.9 million rodents either in tests
or inventory at any given time. The normal maintenance levels for other
animals would be 40,000 for rabbits, 29,000 for guinea pigs, 31,000 for
dogs, 3,000 for cats, 17,000 for primates, 11,000 for poultry and 3,000
for large domestic animals.
3. In-Vitro Testing
In-vitro testing is that form of biological testing in which the test is
conducted outside of an organism (as opposed to in-vivo, or
"within-the-organism" testing). The major types of specific in-vitro tests
are:
• tests for detecting gene mutations (e.g. Ames test,
mouse-lymphoma assay)
• tests for detecting chromosomal aberrations (e.g. cytogenetics,
dominant lethal assay)
II1-17
-------
• tests for detecting primary DNA damage (e.g. DNA repair,
unscheduled DNA synthesis)
• tests of physiological parameters (e.g. biochemical, cytology)
A summary of the frequency of specific in-vitro testing in the toxicology
testing industry is shown in Exhibit III-4. The number of laboratories
performing each specific test is between 75 and 105 laboratories out of a
total of 150 in-vitro laboratories and 285 commercial toxicology
laboratories.
4. Environmental Effects Testing
Environmental effects testing is conducted to determine the toxic effects
of chemicals on entire aquatic or terrestrial ecological communities. It
differs from mammalian and in-vitro testing which are conducted
specifically to assess the toxicity of chemicals to humans. About 150
toxicology laboratories perform environmental effects tests. The two major
categories of environmental effects tests performed by toxicology
laboratories are: (1) terrestrial testing and (2) aquatic testing. .
Of the laboratories offering environmental effects testing, 27 percent (40
laboratories) perform only terrestrial testing, 33 percent (50
laboratories) perform aquatic testing and 40 percent (60 laboratories)
perform both. (Francke, 1981.)
5. Chemical Fate Testing
Chemical fate testing determines the chemical persistence of a compound and
indicates that chemical's ability to retain its physical, chemical, and
functional characteristics in the environment through which it is
transported and distributed (44 FR 16240-16292). Chemical fate testing is
provided by an estimated 140 laboratories and involves two major types of
studies:
• laboratory studies (e.g. hydrolysis, photo-degeneration, soil
metabolism)
• field studies (e.g. field dissipation, bioaccumulation)
These two types of tests are carried out by the industry in the following
proportions. Laboratory studies only are conducted by 36 percent (50
laboratories) of the chemical fate testing laboratories; 13 percent (20
laboratories) perform only field studies and 51 percent (70 laboratories)
of the chemical fate laboratories perform both. (Francke, 1981.)
C. Capacity and Utilization
The foregoing review of the general nature and testing capabilities of the
toxicology industry (Sections A and B) has provided necessary, but
insufficient information for determining the ability of the industry to
II1-18
-------
Exhibit III-4. Laboratories capable of performing specific in-vitro tests, 1981.
In-vitro tests
Percent of laboratories
providing
in-vitro testing
Percent of
all toxicology
laboratories
Estimated
number of
laboratories
Of
f'o
%
No.
Detecting Gene Mutation
67
35
100
Detecting Chromosomal Abberations
52
27
80
Detecting Primary DNA Damage
50
26
75
Physiological Parameters
71
37
105
ALL TYPES
100
51
150
Source: Francke, 1981.
-------
perform additional testing in response to TSCA or other government
regulations. The determination requires an evaluation of the industry's
capacity and its level of utilization.
1. Laboratories with Excess Capacity by Type of Test
The toxicology testing industry currently exhibits excess capacity in all
areas of general testing, y Surveyed laboratories indicated that 73
percent of the mammalian testing laboratories have additional capacity. In
addition, 78 percent of the in-vitro laboratories; 84 percent of the
environmental effects laboratories, and 75 percent of the chemical fate
laboratories have excess testing capacity. These survey responses are
consistent with industry literature which indicates recent rapid industry
expansion and probable excess capacities (Veraska, 1980.)
2. Amount of Excess Capacity
Surveyed laboratory representatives who indicated excess capacity were also
asked to specify the extent of that excess. Specifically, for each general
testing area, they were asked if they had 1-10 percent, 10-20 percent,
20-30 percent, or over 30 percent excess capacity. Of those with excess
capacity, 41 to 54 percent indicated 30 percent or more excess capacity,
depending upon the testing area considered.
Exhibit II1-5 summarizes the industry's overall excess capacity levels by
test area. Depending upon the test areas considered, laboratories can
perform between 18 and 22 percent more testing. Given these levels,
industry utilization would appear to be about 80 to 85 percent. Many
laboratories operate at less than 75 percent utilization.
Analysis was also done to determine if the level of excess capacity varied
according to size of 1aboratories. Crosstabulation and chi-square tests
indicate that an insignificant relationship exists between the
employment size of laboratories and their level of excess capacity. Large
firms, then, are just as likely to have excess capacity as are small firms.
Unfortunately (for regulatory planners), the current disequilibrium between
test demand and capacity cannot be expected to exist indefinitely, and only
extensive analysis can determine the industry's critical future capacity
levels. {This issue receives more detailed attention in Chapter V:
"Conceptual Supply-Demand Model Development.")
1/ "Excess capacity" as used here refers to the industry's ability to
perform additional work. Ho "unit" of excess capacity is established.
"Utilization" is simply the ratio of current operating level (indexed
at 100) to the sum of operating level plus excess capacity. If excess
capacity is 20 percent, then utilization would be 100/(100+20) or 83
percent.
111-20
-------
Exhibit 111-5. Summary of excess testing capacity for
general areas of testing
Excess
GENERAL AREAS OF TESTING Laboratories capacity in area
Excess Capacity No. (%)
MAMMALIAN TESTING
No excess capacity
1 - 101 (51) 1/
10 - 201 (15%) 1/
20 - 30% (25%) 1/
Over 30% (35%) 1/
Total
IN-VITRO TESTING
No excess capacity
1 - 10%
10 - 20%
20 - 30%
Over 301
Total
ENVIRONMENTAL EFFECTS TESTING
No excess capacity
1 - 10%
10 - 20%
20 - 30%
Over 301
Total
CHEMICAL FATE TESTING
No excess capacity
1 - 10%
10 - 20%
20 - 30%
Over 30%
Total
27
12
15
15
31
TO
23
12
13
11
41
iro
16
10
20
9
45
25
13
18
11
33
m
50
20
30
30
50
BIT 2/
30
20
20
20
60
T5J 2/
20
15
30
15
70
TOT If
35
20
25
15
45
"PO 2/
1
2
4
11
If
0
1
2
3
14
W
0
1
3
2
16
12*
0
1
3
3
12
19
1/ Assumed group mean used for all general areas of testing.
2J Estimated total number of laboratories in industry by category, 1981,
Source: Francke, 1981.
111-21
-------
D. Resource Supplies and Constraints
The potential supply of toxicology testing for regulatory actions is a
function of the availability of the industry's critical resources: its
professionals, animals, equipment, supplies, laboratory space, and capital.
1. Resource Supplies
a. Professionals
The underlying professional manpower resources, including pathologists,
toxicologists, and veterinarians, are critical determinants of the
industry's capacity to conduct toxicology testing. This study section
briefly describes the characteristics and availability of industry
professionals.
(1) Pathologists. Patho1ogists--both general and veterinary
pathologists--are primarily responsible for the examination of animal
tissue as a means of determining the toxicological effects of the chemical
substances that are under study.
A number of pathologists are board-certified members of the American
College of Veterinary Pathologists whose training and education, prior to
eligibility for certification, spans eleven to thirteen years and includes
college, veterinary school, and five years of professional experience.
Exhibit III-6 indicates the employment placement of the 486 board-certified
veterinary pathologists who were registered members of the ACVP in 1980.
{ACVP, 1981.) One hundred ten (23 percent) of the members were employed by
industry (their specific employing organizations were not identified by the
ACVP registry data) and, according to toxicological industry personnel, an
unspecified, increasing number of the categorized university and government
veterinary personnel are also employed by the industry laboratories on a
part-time basis. Industry personnel indicate, also, that toxicological
laboratories also employ other veterinary pathologists who are fully
professional, or "board eligible" for certification but not
"board-certified."
Clearly, the toxicological industry's supply of pathologists is not limited
to veterinary pathologists alone. Indeed, other pathologists now examine
animal tissues within the industry. In its January, 1978, report, the
American College of Veterinary Pathology estimated that in addition to a
probable 100-200 non-registered veterinary pathologists (many with Ph.D.'s)
working in drug and toxicity testing programs, approximately 500-600
non-registered non-veterinary pathologists were also so employed.
Doubtless, then, the industry does and can continue to address its need for
veterinary pathology services by seeking supporting personnel. Although
some industry personnel view with mixed attitudes the use of "other"
pathologists, such professionals do work in the industry. Too,
technicians can be used for such tasks as slide screening to supplement the
work of the veterinary pathologists (although, this too receives mixed
reviews).
Ill-22
-------
Exhibit III-6. Distribution of board-certified veterinary
pathologists by employment sector
Sector Number Percent
UNIVERSITY
Teaching
91
19
Research
79
16
Other
19
4
Total
189
39
INDUSTRY
Research
91
19
Other
19
4
Total
110
23
GOVERNMENT
Federal
23
5
State, local, international
32
7
Total
55
12
FOREIGN (outside U.S.)
40
8
PRIVATE PRACTICE
29
6
RETIRED
17
3
OTHER
9
2
UNKNOWN If
37
7
Grand Total
486
100
If Membership list data insufficient to identify employer.
Source: 1980 American Veterinary Medical Association Directory.
II1-23
-------
(2) Toxicologists. As Exhibit II1-7 shows, the Society of Toxicology
(SOT)membership registry indicates a possible total of 1,103 toxicologists
in 1980. Universities employed the greatest number of SOT members--313 or
28 percent, closely followed by private industry which employed 300 SOT
members or 27 percent. The remaining members were employed by government
(14 percent), firms outside the U.S. (10 percent), commercial testing
laboratories (7 percent), and other institutions, including hospitals,
trade associations, and private foundations (3 percent). Five percent of
the members were retired. (Employment type could not be identified for six
percent of the society members.) A workshop held in April, 1978, sponsored
by NIEHS, the Chemical Industry Institute of Toxicology (CIIT), EPA, and
the Conservation Foundation, reported that SOT membership represented about
20 percent of professionals working in the field of toxicology and
estimated the supply of toxicologists at about 5,000 professionals. The
workshop further estimated that an additional 1,000 professional
toxicologists were needed to meet immediate demand. (Gusman, 1978.)
The Society of Toxicology initiated the formation of the American Board of
Toxicology, Inc. -- a certifying board for general toxicologists. As of
August, 1980, 373 persons had sat for the qualifying examination and 216
had passed. In addition, certifying boards for toxicologists exist in
highly specialized areas such as veterinary toxicology, medical toxicology,
and clinical toxicology. NIEHS is currently developing a taxonomy to
classify toxicologists and their training programs and to project the
supply to toxicologists into the coming year.
The degree of lateral mobility in toxicology and related disciplines is
generally high. One report estimates that "additional toxicologists can be
trained from other biological sciences in 2-3 years." (Weig, 1980.)
(3) Veterinarians. The proposed TSCA testing guidelines require that test
animals' care and welfare be the responsibility of a veterinarian who is
certified or eligible for certification by the American College of
Laboratory Animal Medicine (ACLAM) and who has at least two years of
experience, (The experience requirements for ACLAM eligibility include
four years beyond the veterinary degree.) There are between 280 and 290
members of ACLAM, but the number of other eligible veterinarians is
unknown. Whether or not a shortage of animal care veterinarians occurs as
TSCA is implemented will depend on the additional number of available
ACLAM-eligible (but not certified) veterinarians, and, more generally, on
the overall supply of veterinarians.
In 1979, there were over 33,000 veterinarians in the U.S. (including those
inactive or retired) of which 30,706 were members of the American
Veterinary Medical Association. (Anon., 1980e.) As shown in Exhibit
III-8, almost 80 percent of the association membership was in private
practice in 1979, and only 12 percent was listed under the category of
"other, including veterinary services."
II1-24
-------
Exhibit 111-7. Distribution of Society of Toxicology members
among employment sectors
Sector
Number
Percent
Universities
313
28
Private Industry
300
27
Government (all levels)
155
14
Foreign (outside U.S.)
105
10
Commercial Testing Laboratories
75
7
Retired
58
5
Other Institutions 1/
34
3
Unknown 2/
53
6
Total
1,103
100
_1/ Includes hospitals, private foundations, and trade associations.
2/ Membership list data insufficient to identify employer.
Source: Society of Toxicology - Membership List 1980.
111-25
-------
Exhibit III-8. Type of employment of members of the
American Veterinary Medical Association
Type of employment
Estimated
number
Percent
Private Practice
26,100
79
Large animals
2,300
7
Small animals
12,200
37
Mixed
11,600
35
Other Practice
Regulatory veterinary medicine
1,000
3
Veterinary public health
300
1
Military veterinary services
300
1
Other, including laboratory services
4,000
12
Retired, not in practice, or status not reported
1,300
4
Total
33,000
100
Source: Unpublished data from American Veterinary Medical Association,
Schaumburg, IL, 1980.
111-26
-------
In the past two decades, the annual number of veterinary school graduates
has more than doubled, from 824 in 1961 to 1,712 in 1979. (Anon., 1980 e);
however, the evidence of a shortage of veterinarians does exist. In a
recent survey of academic veterinary science departments, 35 percent
reported a perceived critical veterinarian supply shortage (NRC, 1978.)
b. Capital
Capital availability is of obvious significance. It will frequently
determine the adequacy of other critical resources; it is critical, also,
for expanding laboratory testing capabilities and maintaining an
organization's operations during periods of reduced demand or unusually
sharp competition. Unlike that for professionals and other testing
resources (i.e., animals and laboratory equipment), the capital resource
availability for the toxicological industry is dependant upon competition
with other industries as each makes demands upon the nation's general
capital resources. This condition, too, determines the industry's capital
resource availability. It should be noted, however, that capital is always
available; its relative availability is reflected in capital's price-
interest rates.
c. Other resources
Other resources that may affect the capacity for toxicological testing
include space, animals, and equipment.
(1) Availability of space. Because many toxicological studies required
their own animal rooms, laboratory space was a potentially constraining
resource when testing demand increased during the mid- and late-1970's.
For this reason, and because chemical companies have been increasing their
in-house capacity and new firms have entered the industry, much expansion
in laboratory facilities occurred in recent years. This has reduced the
concern about the availability of this resource for the near future. (See
Section A-3.)
(2) Availability of laboratory animals. According to the Animal Resources
Division and Veterinary Resources Branch of NIH, no serious problem exists
for the availability of conventional laboratory animals other than
primates. A senior staff veterinarian for the Division of Veterinary
Services, Department of Agriculture, agreed that the supply and demand
balance for test animals is fairly equal; he did caution, however, that
specific animals are, at times, in short supply.
A shortage can occur for a variety of reasons. At times, a laboratory's
otherwise stable and adequate test animal inventory can be decimated or
made unacceptable for testing by the outbreak of a disease or the failure
of laboratory security. Sudden testing trends can call for an unusually
high and an immediately unanswerable demand for particular animals or
species. State and local legislation can result and, in some areas has
resulted, in laboratories being restricted in their procurement of "random
source" animals (i.e., cats and dogs received from pounds) for testing
111-27
-------
purposes. And, too, the availability of non-human primates can be
constricted and, at times, become a problem of long-term shortage by the
passage of statutes in the U.S. and in their country of origin that place
these animals in "threatened" or "endangered" species categories.
The apparent supply and demand balance for test animals, despite the large
increases in testing in recent years, is due to the large number of
commercial breeders of laboratory animals and to the practice of research
organizations breeding their own animals. An official at the Department of
Agriculture reports that between 180 to 200 companies are licensed under
the Animal Welfare Act of 1966 to sell animals for research purposes. In
addition, this figure does not include those facilities breeding only rats
and mice (currently not required to register with the Department of
Agriculture). Preliminary assessment by the Department, however, indicates
that approximately fifty breeders of rats and mice also supply laboratory
needs.
(3) Avai 1 abi 1 it.y of equipment. The equipment needed for toxicological
testing has become increasingly specialized, with computer-based
information systems now being used in both the in-life and pathology phases
of testing. Although testing laboratories are now confronted with a wide
array of equipment of varying levels of sophistication, no evidence has
uncovered suggesting that equipment availability is a constraint to growth.
Equipment decisions are normally made through standard capital budgeting
processes.
2. Resource Constraints
a. Critical Expansion Factors
During the survey conducted for the present study, laboratory officials
were asked to rate the importance of various resources in constraining
expansion of toxicology testing in the U.S. Specifically, they were asked
to rate factors on a scale from one to seven (one is "not critical" and
seven is "very critical"). Out of the six major resource areas listed
above and in Exhibit 111-9, the availability of capital was rated the most
critical constraint to expansion with an average rating of 5.0 and,
furthermore, 31 percent rated it "very critical." Availability of
laboratory space and professionals were a distant second at 3.9 and 3.8,
respectively, and only 11 to 12 percent of the respondents listed these as
"very critical" for expansion. Animals, equipment, and supplies were
generally not considered to be critical constraints.
Further analysis was done to determine which types of professionals—
toxicologists, veterinary pathologists, and pathologists--were the more
critical manpower constraint. In cases where professionals were a critical
constraint (rated 4 or over), toxicologists were rated as the most critical
constraint, followed by veterinary pathologists, and then pathologists.
The average rating for each class of professional was as follows.
111-28
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Exhibit 111-9. Summary of the critical nature of the availability of resources
to industry expansion
Critical nature of availability
Availability of: Not critical Critical -Very critical Average
1 2 3 4 5 6 7 value
(percent)
Professionals
17
14
15
13
19
11
11
3.8
Animals
46
23
16
6
4
1
3
2.1
Equipment
40
22
18
7
4
3
4
2.4
Supplies
47
23
12
7
5
3
3
2.2
Laboratory Space
18
9
17
13
17
13
12
3.9
Capital
9
5
8
12
17
18
31
5.0
Source: Francke, 1981.
-------
Toxicologists...
Vet. Pathologist
Pathologists
5.34 (1 = not critical, 7 = very critical)
5.06
4.23
An analysis of variance statistical test indicated these means were
significantly different at the 95 percent confidence level.
Note again that these specific manpower constraints were rated only when
the overall manpower constraint was rated 4 or higher; thus, the above
means would be biased upward if compared to the other resource constraints,
and they are, therefore, not comparable.
Finally, the survey results may understate the critical nature of
professional manpower resources. A combination of three conditions suggest
this. First, the timing of the survey may have caused capital availability
to be overrated as interest rates are at a near term high, and a survey
taken during lower interest rates could show relatively higher concern for
manpower resources. Second, current demand for testing and manpower
resources appears to be significantly below the supply of testing
capabilities and the current concern for manpower resources to expand
testing is relatively low. Third, the responses reflect individuals'
judgements relative to their own individual firms and not the industry as a
whole; an individual firm through salary and work incentives can attract
new professionals from another firm much faster than the industry can
attract new professional entrants. Industry analysts have also suggested
that manpower could be a serious constraint in upcoming years as
significant lead time is required for training. In summary, this implies
professional manpower resources may deserve close monitoring and additional
study.
b. Most Constraining Resources
To further clarify questions of constraint to industry supply expansion,
laboratory representatives were asked to identify the most critical
constraint to expansion. The results were consistent with the prior
analysis and showed capital to be the most critical resource. The relative
frequency that various resources were named as most critical is shown as
follows.
Constraining Resources
Percent of representatives
naming most critical
Professional s
Animals
Equipment
Supplies
Laboratory Space
Capital
Other.
Total
19
1
1
0
10
46
23
m
II1-30
-------
Note that the open-ended "other" was the category with the second greatest
frequency as "most critical". This "catch-all" constraint category
reflected such concerns as:
• government regulations
• demand/market/competition factors
• shortage of non-professional personnel
t public antipathy toward animal testing
These are not significant resource constraints per se, but they indicate
that, in addition to the general resource needs of the industry, market
perception and business climate are strong concerns for those laboratories
considering future expansion. 1/
1/ More detailed survey data and analysis on this and other topics are
available in this study's supplemental report: Toxicology Laboratory
Testing Industry—A Survey Analysis, prepared for EPA by Daniel W.
Francke, et al, Development Planning and Research Associates, Inc.,
November yggTT
111-31
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IV. DEMAND FOR TOXICOLOGICAl TESTING
The demand for toxicological testing stems from several sources. Testing,
for both research and commercial purposes, is conducted fay governments,
universities, other research institutes, and the private sector
laboratories. The commercial testing which is conducted by the private
sector is divided into testing that is either directly or indirectly
induced by regulation, a distinction necessarily vague since it depends
upon the intent, not always discernible, of those ordering the tests. For
this demand study, testing is considered directly induced by regulation if
it is reported to the government in connection with regulatory activities
under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the
Toxic Substances Control Act (TSCA), or the Federal Food, Drug and Cosmetic
Act (FFDCA). Examples of indirectly induced testing includes tests
motivated by the Resource Conservation and Recovery Act, the Clean Water
Act, and the Clean Air Act as no testing is specified by these acts.
In this chapter are estimates of the annual demand for testing that can be
expected over the next several years. Section A outlines a methodology for
estimating demand. Sections B through D estimate the demand for
toxicological testing which is directly generated by FIFRA, TSCA, and
FFDCA. These sections describe the regulatory processes and their required
tests, and estimate the number of chemicals passing through these
regulatory processes. This information is combined to produce an estimate
of the total amount of testing demand induced by statutory regulations.
Section E includes a discussion of the commercial demand for testing not
directly induced by regulation. Research demand for toxicological testing
is discussed in Section F, Section G summarizes the chapter and
aggregates, to the extent possible, the direct and indirectly induced
demands.
In order to completely characterize the demand side of the toxicological
testing market, both the non-testing demand for the resources used in
testing as well as the testing demands themselves must be determined.
Toxicological testing requires several different resources: laboratory
space, animals, equipment and supplies, support personnel, technicians, and
professionals. At any time, the availability of each of these resources
for use in toxicological testing is limited by other, non-testing demands
on those resources. Such non-testing demand is not, however, equally
consequential for all resources. Some resources, such as toxicologists and
certain types of equipment, are so specialized that toxicological testing
constitutes virtually the entire demand for that resource. For other
resources (e.g., secretaries, computer programmers) testing demand
constitutes but an insignificant proportion of the total demand for such
IV-1
-------
resources. A previous study of toxico"logical testing (ICF, 1980), on the
other hand, found the availability of professional manpower—toxicologists,
veterinarians, and veterinary pathologists— to be a major constraint to
growth in testing capacity. (The markets for professional manpower were
analyzed in the preceding chapter on the supply of toxicological testing
resources. Therefore, the demand for professional manpower is not
discussed further in this chapter.)
A. Methodology of Demand Assessment
The primary requirement for a satisfactory methodology is that it include
al1 sources of testing demand, for the exclusion of any significant source
of demand could seriously bias the estimate of the balance between supply
and demand. As an aid to ensuring that all sources of demand were covered,
testing demand was divided into three components:
• regulatory demand,
• commercial, nonregulatory demand, and
• research demand.
The regulatory demand for toxicological tests is primarily generated by
three federal laws under which chemicals are regulated: TSCA and FIFRA,
both administered by the U.S. Environmental Protection Agency, and FFDCA,
administered by the Food and Drug Administration. Although all
commercially marketed chemicals are covered under one of these three laws,
not all such testing need be reported to the applicable regulatory
agencies: tests must be reported only (1) when a chemical is initially
approved or (2) when testing is specifically required by the agency. Firms
may do further tests for their own purposes on existing chemicals, and
firms may conduct tests of new chemicals which, for one reason or another,
are not introduced commercially. For instance, during their research and
development stage, potential new products may be discarded for a variety of
reasons including unfavorable test results. In either case, what is of
importance is that the magnitude of this commercial, nonregulatory demand
cannot be assessed merely by looking at these chemicals submitted for
government approval. In addition to the testing demand directly induced by
regulations under TSCA, FIFRA, and FFDCA, and other testing demanded by
industry, toxicological testing is also done in the course of scientific
research by universities, governments, and other research organizations.
The estimates of demand for toxicological testing employed in this study
stem from a variety of sources. Regulatory demand was derived from records
on new chemical introductions kept by the primary regulatory agencies, EPA
and FDA. Commercial, nonregulatory demand was estimated from conversations
with industry personnel, from research on chemical innovation research, and
from public sources. Research demand was estimated from public documents
and from conversations with members of research organizations.
IV-2
-------
The estimates made in this chapter are intended to project the average
annual amount of toxicological testing that will be required over the next
several years. An estimate based upon long-term experience is more stable
than one based upon the testing demand for a single year. In spite of any
estimate's accuracy, however, budget restrictions, the state of the
economy, changes in the discretionary authority of the regulatory agencies,
and the growth and altering circumstances of chemical firms can cause
relatively large, short-term variations in testing demand.
B. Demand for Pesticide Testing under FIFRA
This section provides the estimated average annual demand for pesticide
testing required by FIFRA regulations over the next several years. It does
not include that which may be carried out for other purposes: pesticide
manufacturers, for instance, may conduct a substantial amount of pesticide
testing not connected with FIFRA requirements. The demand for testing
which will not be directly induced by FIFRA is discussed in Section E.
The section describes (1) the FIFRA regulatory process, including the
recently implemented data call-in program, and (2) the FIFRA requirements
for the toxicological testing of pesticides under FIFRA. The section then
estimates the numbers of pesticides that are expected to enter the
regulatory process during the next several years. Finally, the section, by
combining data on the types of tests required and the number of pesticides
to be regulated, includes estimates of the demand for toxicological testing
under FIFRA.
1. The Regulatory Process
Regulation of pesticides under FIFRA has been in effect since 1947, and
under EPA's jurisdiction since 1970. Before being sold, each new active
ingredient and formulation containing that active ingredient must be
registered with EPA. During that registration process, health, safety and
efficacy studies are reviewed by the Agency before registration is
permitted. Currently some 38,000 pesticides are registered with EPA, of
which about 1,400 are active ingredients and the remainder formulations of
those ingredients. The 1972 amendments to FIFRA directed EPA to "publish
guidelines specifying the kinds of information which will be required to
support the registration of a pesticide" and to reregister all currently
registered pesticides. (FIFRA, 1972.) To fulfill this mandate, EPA issues
guidelines which present the specific tests appropriate for health and
safety studies, the suggested protocols for running the tests, and the
descriptions of the data needed to support registration. The toxicological
testing guidelines which describe the specific tests needed for product
registration and the protocols for conducting those tests were proposed in
1978 (EPA, 1978). Their final versions were to be issued in 1981.
IV-3
-------
In addition to developing such guidelines for toxicological and other types
of testing, EPA is designing standards for the entire registration process.
Under the registration standards system (also known as the "generic
standards system"), EPA intends to develop registration standards which
cover those pesticide products which contain the same active ingredient.
Each standard will be of two parts: one will cover an active ingredient
and its manufacturing-use products 1/, and one part will cover all end-use
products (formulations) which contaTn that active ingredient. Each part
will, in turn, contain four components:
t a statement of the agency's regulatory position defining the
acceptable uses of a pesticide and establishing restrictions on
the composition of products,
« a statement of the rationale for that position,
• an assessment of all data reviewed by the Agency, including an
assessment of the costs and benefits consequent to the use of
that pesticide, and
t a listing of the tolerances for those pesticides which leave
residues in food or feed (under authority of FFDCA rather than
FIFRA).
Data are on agency file for those products which are currently registered.
But, for two reasons, these data are not likely to be adequate for
reregistrati on. EPA now requires more data than it did when many products
were first registered, and the data that are available frequently reflect
studies now regarded as fundamentally inadequate or otherwise unacceptable
for product use in currently registered pesticides (Chemical Regulation
Reporter (CRR) 1980a). Since many studies take several years to complete,
a commensurate time may be necessary to issue complete standards for these
pesticides. Rather than delaying .issuance of any standard for these
pesticides, EPA will issue interim standards which address those issues for
which insufficient data exist, list the studies which must still be
performed, and establish a timetable for their performance.
For those currently registered pesticides for which standard development
has not yet begun--those based on the 598 active ingredients on the
registration standards list--EPA has implemented a data call-in program.
The goals of this program are to identify the data that will be needed for
the preparation of a registration standard and to ensure that pesticide
manufacturers begin the required testing. The data call-in program
concentrates on studies that take more than six months to complete:
oncogenicity, teratogenicity, reproduction, and chronic effects. Further
testing requirements, primarily short-term ones, will be determined for
each pesticide at the time EPA begins developing an applicable registration
standard.
1/ Manufacturing-use products are products intended for end use
as pesticides only after reformulation or packaging.
IV-4
-------
Under the data call-in program, EPA will evaluate the data already on file
with the Agency to determine if they are sufficient to support registra-
tion. When they are not, EPA will provide each registrant of the pesticide
with a notification which includes:
• the long-term toxicology data requirements for that chemical,
• that portion of the data requirements which is not currently
available, and
• the rejection criteria which define minimally acceptable protocol
and methodology requirements for existing studies.
After receiving the notice, the registrant will have ninety days to
demonstrate that either appropriate steps are being taken to secure the
required data (including replacing those data which do not meet the
rejection criteria) or that procedures have been implemented for reaching
agreement with other registrants concerning joint data development. The
registrant will have to satisfy the requirements either by submitting new
or citing existing data and certifying the acceptability of that data when
judged against the rejection criteria or by agreeing to conduct new
studies. Unless such procedures are instituted, EPA can suspend the
product's registration. The agency's call-in process includes EPA's review
of all proposed test protocols and schedules that are submitted by the
registrant. Following the agency's and registrant's agreement on schedules
and protocols, the call-in process will be completed. After the completion
of the call-in process, the agency will continue to monitor the progress of
the studies until they are completed. Registrants are given four years
from the date of the notice to provide all necessary data. (CRR 1980b and
1981a.)
2. Requirements for Toxicoloqical Testing
EPA published an Economic Impact Analysis of its testing guidelines in
September, 1978 (EPA, 1978b.) which contained the Agency's estimates of the
costs of the proposed testing requirements and the estimated numbers of
tests that would have to be performed for new and currently registered
pesticides. This section reviews that analysis and updates the estimates
in the light of recent events and data. Exhibit IV-1 shows these revised
estimates.
The specific requirements for the testing of each new or currently
registered pesticide are based on that product's intended use and its
probable environmental exposure. For example, pesticides that remain as
residues in food or that otherwise involve repeated human exposure require
tests that evaluate its hazard to humans and animals. However, this is the
theoretical basis for EPA's testing guidelines and the Agency's estimates
of testing demand could not be based solely on such a basis. Instead, EPA
extrapolated historical data to estimate the number of pesticides that
would require various kinds of tests. (EPA, 1978b.) For example, when
extrapolated, the application volumes from 1971-1978 suggested that
-------
Exhibit IV-1. EPA estimates of the proportion of pesticide active
ingredients and formulations requiring a given toxicological test
EPA's estimate Estimated percent of
of percent of registered products with
new products acceptable data of this
requiring test \j type on file with EPA 2/
Active Formu- Active Formu-
ingred- lated ingred- lated
Test name ients products ients products
-Percent
1.,. Acute Oral Toxicity
98
99
1-10
1-10
2. Acute Dermal Toxicity
98
99
1-10
1-10
3. Acute Inhalation Toxicity
15
75
0
0
4. Primary Eye Irritation
99
99
75
75
5. Primary Dermal Irritation
99
99
75
75
6. Dermal Sensitization
100
50
0
0
7. Acute Delayed Neuro-
toxicity
7
N/A
80
N/A
8. Subchronic Oral Dosing
24
N/A
99
N/A
9. 21-Day Dermal Toxicity 3/
21
N/A
10
N/A
10. 90-Day Dermal Toxicity T/
1
N/A
0
N/A
11. Subchronic Inhalation
Toxicity
11
N/A
0
N/A
12. Subchronic Neurotoxicity
1
N/A
0
N/A
13. Chronic Feeding
24
N/A
50
N/A
14. Oncogenicity
31
N/A
approx. 50%
in N/A
rat studies
5%
in mouse studies
15. Teratogenicity
33
N/A
50
N/A
16. Reproduction
33
N/A
50
N/A
17. Mutagenicity
33
N/A
0
N/A
18. Metabolism--Single Dose
34
N/A
45
N/A
19. Metabolism—Multiple Dose
24
N/A
35
N/A
\J EPA, "Proposed Guidelines, Economic Impact Analysis," 43, Federal
Register, Sepbember 6, 1978, Tables 2.3, 5, 6, 8, 10, 11, 13, and 14,
and p. 39647.
lj Estimated by EPA staff, registration division, in early 1980; communi-
cated to ICF by Gary Ballard, OPP. Estimates for chronic feeding,
oncogenicity, and reproduction updated after conversations with Gary
Ballard and William Burnham in January 1981.
3/ Under the Guidelines, these two tests may be required of formulations
on a case-by-case basis, but EPA did not estimate the proportion of
formulations which would require these tests.
NA = Data not available.
IV—6
-------
approximately fifteen new applications for the registration of active
ingredients would be received (or approved) in a given year in the 1980's.
(EPA, 1978b.) Furthermore, each of these fifteen new active ingredients
would require product chemistry testing, and a smaller proportion
individual tests for environmental, fish and wildlife, and human and
domestic animal hazard evaluations. The estimated proportions of
individual tests needed were based on the experience of use patterns,
chemical classes, and exposure routes of currently registered products.
For currently registered products, EPA assumed that approximately 5-10
percent of the necessary data would be available in its files. (Ballard,
1980.) (For human and domestic animal hazard testing, EPA estimated
separate proportions for each individual test.) Finally, for many
formulations, both new and currently registered, the Agency believed
testing requirements would be less extensive and made separate estimates.
EPA's estimates assumed that new active ingredients and their formulations
would follow the same use and exposure patterns as do the currently
registered pesticides; therefore, the Agency imposed new product data
requirements that reflected past registration data needs. (EPA, 1978b.)
The Agency's assumption, however, may not be valid, because of the changing
economics of the pesticide industry and the increasing costs for testing.
For example, as testing requirements become more stringent, and, hence,
more costly, pesticides for use on minor crops may become economically
infeasible. Thus, EPA's assumptions about the use distribution of future
pesticides may not be accurate. At the moment, however, the point is
essentially one of caution, for no definitive data exist which would
authoritatively amend EPA's estimates. The present study continues to
employ EPA's assumptions.
Current information suggests, too, that EPA's estimates of the tests to be
performed on currently registered pesticide may be incorrect. EPA
originally assumed that relatively high percentages of currently registered
products would have acceptable data on file from long-term studies—chronic
feeding, oncogenicity, teratogenicity, and reproduction. However, the
Agency's Scientific Advisory Panel has argued that under EPA's rejection
criteria, nearly all older chronic effects studies would have to be redone.
(CRR, 1980c.) Although Agency pesticide program officials suggest that the
Scientific Advisory Panel's concern may be overstated, the rejection
criteria are still being modified, and even when in final form, will still
be subject to interpretation by EPA. Because of this uncertainty and
because the data call-in program is just beginning, it is too early to tell
how the criteria will be applied. It does appear, however, that previous
estimates of the suitability of existing data from chronic studies were
optimistic. (Ballard, Burnham, 1980.)
3. Number of Pesticides to be Regulated
Exhibit IV-2 shows the estimated number of newly registered and
reregistered products to be tested in the early 1980's. As noted below,
these estimates are highly uncertain.
IV-7
-------
Exhibit IV-2. Estimates of the annual number of pesticides
undergoing tests
I. New Products
a. active ingredients
b. formulated products
15 1/
3,000 2/
II. Currently Registered Products
a. active ingredients
b. formulated products
1,750
50
1/ The average annual number of new active ingredients applying for
registration, FY 1971-FY 1980.
2/ The average annual number of new formulations applying for
registration FY 1971-FY 1980.
Source: Registration Division, Office of Pesticide Programs, EPA.
IV-8
-------
In its economic impact analysis, EPA estimated that fifteen new, active
ingredients and 3,000 new formulations would be introduced each year in the
early 1980's~the average annual numbers of new active ingredients and
formulations for which registration was sought during the period FY 1971-FY
1978. Data from FY 1979 and FY 1980 do not change this estimate. 1/
The situation for the reregistration of currently registered pesticides is
somewhat more complex. EPA originally hoped that 50 standards and 100
early notifications of future standard development could be issued each
year (EPA, 1978b). Assuming the tests begin upon receipt of early
notification, then about 75 active ingredients would be undergoing tests
annually. The experience of the early 1980's registration standards
program, however, suggests that EPA's estimate of 100 early notifications
and 50 standards per year was optimistic. In February 1980, the Agency
estimated that in 1980, 10-20 standards would be issued and in 1981, 20-40
standards. (CRR, 1980d.) EPA actually managed to complete but six
standards in FY 1980 and by the end of June, 1981, added four and was close
to completing six additional standards. (CRR, 1980b, 1981b.) Starting in
1983, the Agency hopes to complete 35 standards a year. (CRR, 1980k.)
Although the delay of standard-setting decreases the number of pesticides
per year for which tests are done, the data call-in program works to
increase that number. EPA hopes to complete the call-in program (i.e., the
establishment of testing schedules) by early 1982 (CRR, 1980b.); however,
the Agency does believe that four years or 1984 is a more realistic
estimate of the time required for completion. (Werdig, 1981.) A four-year
schedule for completing the data call-in program would result in about 135
completions per year. Because registrants are given four years from the
date of the notice to provide the missing data, a four-year schedule for
completing the data call-in program could result in that testing taking
an eight-year period for completion. Assuming that all testing associated
with the 55 active ingredients not covered by the call-in program (those
for which registration standard development has already begun) is also
completed over this eight-year period, the reregistration process will
generate testing on about 75 active ingredients per year in the 1980's.
However, testing may not proceed this quickly. Registrants can request
delays in testing schedules for legitimate reasons, including the lack of
testing capacity. (Werdig, 1981.) The Agency is well aware that TSCA
testing may strain testing capacity, and is prepared to be flexible in
approving necessary testing schedule delays. (CRR, 1980b). Although that
flexibility is beneficial to producers and consumers of pesticides, it does
complicate efforts to estimate the volume of testing demand. The data
1/ In FY 1979, registration was sought for 17 active ingredients and 378
formulated products. In FY 1980, the figures were 9 and 1,571. The low
number of formulated products for which registration was sought is
regarded as an aberration by EPA, one caused by changes in internal pro-
cedures. It is expected that registration will be sought for over 5,000
formulated products in FY 1981. (Ballard, 1980.)
IV—9
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call-in program and the actual standard-setting process are assumed to
generate testing on about 50 chemicals per year during the early 1980's.
That estimate is highly uncertain.
The present study assumed a mean of 49 formulations for each currently
registered active ingredient to calculate the annual testing demand for the
pesticide products. Although EPA provided no estimate of formulations in
its economic impact statement, the ten registration standards issued thus
far have an average of 49 formulations. 1J
Finally, in its 1978 Economic Impact Analysis, EPA assumed that products
representing 10 percent of the total sales volume of active ingredients
would not be economically viable under the guidelines for registering
products and would be withdrawn by their manufacturers. (EPA, 1978b.)
Because high volume products are the more likely to be reregistered, the
assumption argues that fewer than 90 percent of the products would be
reregistered. In fact, for the first ten standards, registrants responded
to protect their registrations for about 72 percent of the 159 product
registrations affected. (CRR 1981c.) This study, therefore, assumed that,
on the average, tests will be conducted on 35 formulated products (72
percent of 49) for each active ingredient.
4. Demand for Toxicological Testing
In summary, then, Exhibit IV-3 combines all the information in Exhibits
IV-1 and IV-2 to predict the number of each type of toxicological test that
would be conducted per year in the early 1980's under the assumptions given
above. For example, Exhibit IV-1 shows that 33 percent of active
ingredients require teratogenicity tests annually; thus, about 5
teratogenicity tests will be conducted on new active ingredients. The
table also indicates that about 33 percent of the 50 currently registered
pesticides also require teratogenicity tests; however, since about 50
percent of these products are assumed to have acceptable data already on
file with EPA, only 16 percent'of the 50 currently registered pesticides
would require new teratogenicity tests. Because none of the active
ingredients for which registration standards have been developed have been
totally withdrawn by their manufacturers, it is assumed that no active
ingredients will be withdrawn. However, as stated above, only about 72
percent of the formulated products covered by the first ten registration
standards were protected by their registrants.
\J Of the ten products for which registration standards have been issued,
one (deet) has 239 products, another (dichlone) has 68, and the rest
have between 17 and 35. As would be expected, the sample variance is
quite high. Therefore, the use of the estimates mean number of
formulated products—49 — is logical but conjectured.
IV-10
-------
Exhibit IV-3. Pesticide-related testing demand: Estimated
annual number of human and domestic animal hazard tests
Number of tests by application type
New Currently registered
active
Formu-
Active
Formu-
ingred-
lated
ingred-
lated
Test name
ients
products
idents
products
Totals
1.
Acute Oral Toxicity
15
2,970
44
1,123
4,152
2.
Acute Dermal Toxicity
15
2,970
44
1,123
4,152
3.
Acute Inhalation
Toxicity
2
2,250
8
945
3,205
4.
Primary Eye Irritation
15
2,970
13
312
3,310
5.
Primary Dermal
Irritation
15
2,970
13
312
3,310
6.
Dermal Sensitization
15
1,500
50
630
2,175
7.
Acute Delayed Neuro-
toxicity
1
0
1
0
2
8.
Subchronic Oral Dosing
4
0
0
0
4
9.
21-Day Dermal Toxicity
3
2/
9
1/
12 ¦
10.
90-Day Dermal Toxicity
0
1/
1
1/
i :
11.
Subchronic Inhalation
Toxicity
2
0
6
0
8
12.
Subchronic Neurotoxicity 0
0
1
0
1
13.
Chronic Feeding
4
0
6
0
10
14.
Oncogenicity
5
0
12
0
17
15.
Teratogenicity
5
0
8
0
13
16.
Reproduction
5
0
8
0
13
17.
Mutagenicity
5
0
16
0
21
18.
Metabolism—Single Dose 5
0
9
0
14
19.
Metabol ism—Multiple
4
0
8
0
12
Dose
1/ Under the Guidelines, these two tests may be required of formulations on
a case-by-case basis, but EPA did not estimate the proportion of
formulations which may require these tests.
2] Under the Guidelines, these two tests may be required of formulations
on a case-by-case basis, but EPA did not estimate the proportion of
formulations which would require these tests.
Entries in this table were arithmetically derived from Exhibits IV-1 and
IV-2 and are rounded to the nearest unit.
IVrll
-------
Finally (and as a further example of the present study's estimate
rationale) of the 1,750 formulated products covered by the regulation
standard and data call-in program each year, 99 percent (1,732) would
require primary eye irritation tests. Of these, 25 percent (433) would not
have acceptable data on file with EPA, and, of these, 72 percent (312)
would be defended by their manufacturers. Therefore, based on these
assumptions, 312 primary eye irritation tests would be required for
formulated products covered by registration standards and the data call-in
program in the early 1980s. Where Exhibit IV-1 gives a range of figures,
the higher number was chosen.
C. Demand for Toxicological Testing Under TSCA
Under TSCA, EPA is given the authority to regulate all chemical substances
and mixtures not regulated under FFDCA, FIFRA, or the Atomic Energy Act.
Toxicological testing may result from regulations promulgated under two
different sections of TSCA. Under Section 4, EPA can require the testing
of any chemical substance or mixture for which there are insufficient data
to determine whether the chemical substance or mixture presents an
unreasonable risk of injury to health or the environment. Under Section 5,
any firm seeking to manufacture a new chemical substance or to use an
existing chemical substance in a significantly different way must submit a
notice of its intentions to EPA. If EPA finds a reasonable basis to
conclude that production or use of the chemical will present an
unreasonable risk of injury to health or the environment or that the data
are insufficient to determine whether such an unreasonable risk exists, the
Agency can prohibit or limit the manufacture and use of the substance.
Although no testing is required per se under Section 5, testing may be
generated if firms feel that it is useful in avoiding restrictive EPA
action against production and use of the substance.
This section of the present study estimates the testing demands expected as
a result of Sections 4 and 5 of TSCA. Because the regulation of chemicals
under TSCA is relatively recent, few historical data on which to base
projections exist. The actions that have been taken under each of the two
sections are discussed below, the factors which might produce future
changes in the implementation of the law are evaluated, and the resultant
information is then used to estimate the testing demand incident to TSCA.
1. Section 4 Testing
Although testing can be required .for any substance which meets the
requirements of Section 4, under Section 4(e) the agency is required to
give priority consideration to a list of chemicals developed by the
Interagency Testing Committee (ITC). This list is to be updated at least
every six months by the Committee, and within twelve months after a
chemical is added to the list, EPA must either initiate a rulemaking to
require testing or publish in the Federal Register its reasons for not
doing so. Since its initial report in October, 1977, the ITC has presented
IV-12
-------
seven additional lists to EPA, recommending a total of 46 chemicals or
categories of chemicals for a variety of tests. By law, the list can
contain no more than 50 chemicals or categories of chemicals at any one
time.
In July, 1980, EPA proposed its first test rule covering substances on the
ITC list. At that time, EPA proposed that chloromethane be tested for
oncogenicity and structural teratogenicity and that a representative sample
of the chlorinated benzenes be tested for oncogenicity, structural
teratogenicity, reproductive effects, and subchronic effects. Although the
ITC had recommended doing so, EPA did not require that chloromethane be
tested for acute toxicity. The Agency deferred decisions on whether to
require chloromethane to be tested for neurotoxicity, behavioral
teratogenicity, and mutagenicity, and whether to require the chlorinated
benzenes to be tested for neurotoxicity, behavioral teratogenicity,
mutagenicity, and metabolic effects. At the same time, EPA decided not to
require health effects testing for acrylamide, another substance on the ITC
list. (CRR, 198Ge; EPA, 1980.) These decision actions are shown in
Exhibit IV-4.
In June, 1981, EPA proposed test rules for three more chemicals from the
ITC list: dichloromethane, nitrobenzene, and 1,1,1-trichloroethane. EPA
proposed that dichloromethane be tested for acute dermal sensitization and
reproductive effects, that nitrobenzene be tested for structural
teratogenicity and behavioral effects, and that 1,1,1-trichloroethane be
tested for structural teratogenicity. In addition, EPA will perform the
initial mutagenicity test itself, because although it believes that
sequenced testing would be appropriate, no criteria for progressing from
initial testing to higher level testing are available. EPA will propose
higher tier tests if needed based on an analysis of lower tier results.
(EPA, 1981.)
a. Requirements for toxicological testing
Information on the types of tests to be required under Section 4 is not
limited to the actions already taken by TSCA. The ITC's testing
recommendations provide information on the tests that EPA might require for
chemicals which have not yet been acted upon by EPA. As shown in Exhibit
IV-5, oncogenicity, mutagenicity, teratogenicity, and other chronic effects
testing are recommended for more than two-thirds of the 46 chemical
substances and categories on the eight ITC lists. If these reconmendations
were adopted by EPA, testing demand estimates could be drawn from the ITC
lists. As shown in Exhibit IV-6, EPA accepted 10 of 28 of the ITC's
recommendations. In the case of acrylamide, however, EPA concluded that a
consistent neurotoxic effect is demonstrated at a sufficiently low level
that further testing is not necessary. Any restrictions which would
significantly limit neurotoxic effects would, therefore, also provide
significant protection from other health effects. In addition, Dow has
assured EPA that it plans to conduct oncogenicity tests. (CRR, 1980f.)
IV-13
-------
Exhibit 1V-4. Section 4 test rules, acrylamlde, chloromethanes, chlorinated benzenes, nltrobenzenes and
1,1,1-trichloroethane
Gnco- Muta- Structural Reproductive
genicity genicity Teratogenicity effects
Subchronic/
chronic Acute Neuro- Behavioral Metabo-
toxiclty toxicity toxicity teratogenicity lism
Acrylamlde
Chloromethane
Oichloromethane - M/
Mono- and Dichlorinated
Benzenes:
Morioch I oroben2 ene
o-Dlchlorobenzene
p-Dichlorobenzene
Nitrobenzene
Tri-, Tetra-, and Penta-
Chlorlnated Benzenes:
1,2,4-trichlorobenzene
1,2,4,5 tetrachlorobenzene
Pentachlorobenzene
1,1,1-trichloroethane
Total
D
D
D
x 1/
D
D
D
* y
3
0
D
D
0
0
D
1/ To be performed by EPA.
D = Decision to propose testing deferred
x = Testing proposed.
Source: EPA, "Chlorontethane and Chlorinated Benzenes Proposed Test Rule; Amendment to Proposed Health Effects Standards," 45 Federal
Register, p. 48524, July 18, 1980; Chemical Regulation Reporter, July II, 1980, p. 355.
-------
Exhibit IV-5. ITC testing recommendations
Test
Number of items for
which test is recommended
Percentage of total
number of items
on ITC list 1/
Oncogenicity
35
76
Mutagenicity
34
74
Teratogenicity
36
78
Other Chronic Effects 2/
32
70
Reproduction 2/
6
13
Developmental Effects
1
2
1/ An item can be a chemical or a category of chemicals. There are 46
items on the first seven ITC lists.
2J Reproduction is often included explicitly among other chronic effects
by the ITC, and it may be included implicitly in other cases. In only
four cases is it mentioned separately.
Source: Reports of the Interagency Testing Committee.
IV-15
-------
Exhibit IV-6. Comparison of ITC testing recommendations ana
EPA test rules
Chemical substance Onco- Muta- Terato- Chronic
or category genicity genicity genicity effects
Acrylamide
ITC Recommendation x x x N
EPA Test Rule N _1/ N N N
Chloromethane
ITC Secoranendatlon x x x x
EPA Test Rule x D :< N
Di chloromethane
ITC .Recommendation x x x x
EPA Test Rule N 2 / N 3/ N N 3/
Mono- and Oi-chlorinated
Benzenes
ITC Secommendation x x x x
EPA Test Rule N 0 x x
Nitrooenzene
ITC Recomnendation x x N N
EPA Test Rule N If N 3/ x N V
Tri, Tetra-, and Penta-
chlorinated Benzenes
ITC Recommendation x x x x
EPA Test Rule x 0 x x
1,1,1-Tricnlorethane
ITC Recommendation x x x x
EPA Test Rule N 2/ N 3/ x N 3/
'if One of the reasons that EPA cited for not requiring tasting for
acrylamide was that Dow plans to conduct oncogenicity testing of the
chemical.
2f EPA will do the initial mutagenicity testing itself, out may propose
other tests later.
3/ EPA stated that the oncogenicity testing of these substances being per-
formed by the National Cancer Institute should be sufficient for EPA's
needs for these tests. Therefore, no additional testing was proposed.
D = Oecision to propose testing deferred,
x = Testing proposed.
?l - Testing not sroposed.
Source: Exhibit IV-4 and reports of the Interagency Testing Conmittee.
IV-16
-------
For dichloromethane, nitrobenzene, and 1,1,1-trichloroethane, EPA is not
proposing further testing because the National Cancer Institute is
conducting tests sufficient for EPA's purposes. EPA will conduct the
initial mutagenicity tests itself (EPA, 1981).
b. Number of chemicals to be regulated
The estimate of the number of chemicals expected to undergo Section 4
testing is even more uncertain than the estimate of the types of tests that
are expected under Section 4. In May 1979, EPA was sued by the Natural
Resources Defense Council (NRDC) for failing either to develop test rules
or to decide not to require testing for chemicals on the ITC list. In
December 1980, EPA proposed a testing schedule found acceptable by the
NRDC. Under this schedule, EPA must develop test rules or decide not to
require additional testing for chemicals on ITC1s first six lists within
the next three years. Under this schedule, EPA would issue test rules for
eight chemical substances from the ITC lists during the rest of 1981, and
thirteen each during 1982 and 1983. (CRR, 1981d; 1980g.) Assuming that
EPA does, indeed, meet the court-imposed schedule, and assuming that EPA
takes action on all chemicals added to the list during the three years
of the statutory deadline, the Agency would have to take action on about
twenty-two to twenty-four chemicals or groups of chemicals per year (if, of
course, ITC continues its past schedule). In an affidavit filed during the
course of the NRDC suit, EPA estimated that it can develop test rules for
fifteen to twenty chemicals per year. (CRR, 1980h.) Therefore, unless EPA
devotes more resources to the development of test rules than is planned, or
unless the ITC adds fewer chemicals to the list over the next few years
than it previously has added, three years from now the Agency will still be
behind schedule in promulgating testing requirements.
Any attempt to estimate the number of chemicals to be tested under Section
4 is further complicated by the fact that the individual items on the ITC
list are both individual chemicals and categories of chemicals. Of the 46
items on the seven ITC lists, 27 consist of a single chemical substance and
the other 29 items contain as many as 100 chemicals. JJ This means that it
cannot be assumed that taking action on 20 ITC items a year would result in
a maximum of 20 of each type of test. This can be seen by examining
Exhibit IV-4: only five ITC categories are included for structural
teratogenicity tests, but eight chemicals will eventually require the
tests.
However, one cannot assume that if a test is required for that category, it
will be required for all chemicals (or even all commercially important
chemicals) in that category. This can be seen by examining the chlorinated
1/ Some of the categories are "open" -- they contain a potentially
immense number of chemicals. For these categories, the approximate
number of chemicals currently in use, or with relatively important
uses, was estimated.
IV—17
-------
benzenes, for which test rules have already been proposed. Chlorinated
benzenes make up two items on the ITC list, and together they consist of
eleven distinct chemical substances. But testing is required for only six
of those eleven (and, further, not all the tests are required for each of
the six). In general, EPA does not believe that each member of a
structurally related category need be tested. Instead, a representative
sample can be selected that will enable EPA to evaluate the entire
category. (EPA, 1980.)
c. Demand for toxicoloqical testing
To estimate the number of tests to be generated by Section 4 test rules,
this study assumed that EPA will take action on 20 items from the ITC list
each year. It further assumed that the following four tests will be
required of about two-thirds of those 20 items: oncogenicity,
mutagenicity, teratogenicity, and chronic effects. This assumption is a
product of the observation that the ITC recommended these tests somewhat
more than two-thirds of the time, and in the test rules issued thus far,
EPA has recommended testing to a somewhat lesser degree than the ITC had
recommended. (See Exhibit IV-6.)
In addition, this study assumed that testing for reproductive effects will
be required in about half of the cases. Even though reproduction tests are
specifically mentioned as a separate category for only 6 of the 46 items,
reproduction is specifically mentioned as a chronic effect that should be
examined in 6 other cases, and it is probably incorporated implicitly under
chronic effects in many other cases. It is worth noting that EPA requires
testing for reproductive effects among both categories of chlorinated
benzenes on the list, even though such tests were not mentioned
specifically by the ITC.
On the basis of the above assumptions, this study estimated the number of
chemicals to be tested from among those 20 items. The relative composition
of those 20 items is assumed to be the same as the relative composition of
the 46 items named on the list thus far, that is, their number of single
chemicals, number of chemical categories, and number of chemicals in the
chemical categories will be similar. The number of chemicals in each
category on the list was obtained for all "closed" categories. (An
estimate of the number of chemicals currently in commercial production, or
with relatively important uses, was used for all "open" categories.) As
stated above, EPA does not intend to require tests on all chemicals in a
category—tests on a "representative sample" will be sufficient. About
half the chemicals were tested among the chlorinated benzenes, the only two
categories for which test rules have been issued thus far. It is assumed
that this policy will be continued for all categories which have a
relatively small number of members, i.e., a dozen or fewer—the two
chlorinated benzenes categories had four and seven members—and that for
the larger categories, testing will affect about one-fourth of their
chemicals. Under these assumptions, EPA should require testing on about 89
chemicals per year under Section 4. The estimated number of tests is shown
in Exhibit IV-7.
IV-18
-------
Exhibit IV-7. Estimated toxicological tests per year
required under Section 4 of TSCA
Test
Number
Oncogenicity
60
Mutagenicity
60
Teratogenicity
60
Chronic Effects
60
Reproduction
45
Source: Exhibits IV-4, IV-5 and IV-6.
Exhibit IV-8. Toxicological testing on chemicals submitted
to EPA under Section 5 of TSCA,
1980
Test
Number
Acute oral toxicity
123
Primary Dermal Irritation
110
Primary Eye Irritation
109
Dermal Sensitization
28
Ames
52
Acute Dermal Toxocity
57
Acute Inhalation Toxicity
18
Other
38
Source: ICF analysis of Section 5 notices submitted to EPA, 1981.
IV-19
-------
2. Section 5 Testing
Under Section 5 of TSCA, no EPA tests are required for approval of a new
chemical. If, however, insufficient information exists to permit a
reasoned evaluation of the health and environmental effects of a chemical
substance, EPA may restrict the production and use of that chemical.
Manufacturers, consequently, in the course of their developing and
submitting new chemicals for approval, may perform toxicological tests in
order to avoid restrictive actions. A survey of the public file of 383
Section 5 notices received by EPA during calendar year 1980 revealed that
535 tests were performed on the chemicals submitted (Exhibit IV-8).
Since the number of new chemicals actually submitted to EPA is roughly the
number expected by the Agency, a way to estimate future Section 5 testing
could be to simply accept EPA projections. However, before making such an
assumption, two issues should be considered:
• Are the chemicals introduced in 1980 representative
of those expected to be introduced in tne future? In early
1980, Section 5 notices were filed more slowly than they were
in the latter part of 1980, and the increase in submissions
continued during the first half of 1981. In the first half of
1980, 153 Section 5 notices were filed, and in the second half,
230 were filed. Two explanations are reasonable. Manufacturers
may have delayed submitting notices until they had a clearer idea
of how the program would work. Or manufacturers may have
inventoried substances still undergoing development in order to
avoid the premanufacturing review process. (CRR, 1980i.) If the
latter were true, then more new chemicals can be expected in
future years as this effect is reduced. The number of chemicals
introduced also depends on the standards set by EPA for the
approval of Section 5 notices. The higher the standards, the
less likely that firms will submit new chemicals for approval.
The types of chemicals introduced in 1980 may be different than
will be the types of chemicals introduced in future years. TSCA
intends to direct chemical innovation away from the more to the
less environmentally hazardous chemicals. To the extent that
this goals is eventually realized and it results in less needed
testing, the amount of testing should decline. However, this
effect may be counterbalanced by other factors, as discussed
below.
• Are the types of tests conducted on new chemicals introduced this
.year representative of the types of tests that will be conducted
in years to come? As stated above, a move toward safer chemicals
would probably result in fewer new tests and higher standards of
approval would probably reduce the total number of chemicals
introduced. However, such higher standards of approval would
also increase the amount of testing done on new chemicals because
IV-20
-------
firms producing them would seek to do a better job of convincing
EPA of their chemicals safety. Thus it is not clear, a priori,
whether the number of tests will increase or decrease. At
present, guidelines exist to indicate what tests will be done on
new chemicals. Under the Carter Administration, EPA did publish
testing guidelines calling for the tests in the OECD premarket
data set (Exhibit IV-9) to be performed on new chemicals
submitted to EPA under Section 5. But more recently, the Reagan
Administration blocked a decision by the OECD to make the use of
that data set binding upon all member countries. (CRR, 1981e,
1981f, 1981g.)
Because the premanufacture notification program is still evolving,
estimates of future testing must be uncertain. Program operations thus far
suggest that the amount of future testing will be similar to that of 1980;
however, 660 Section 5 notices received in the first half of 1981, rather
than the 383 submitted during 1980, have resulted in demand for 922 tests
arising from Section 5 notices over a recent 18 month period which is
equivalent to a rate of 615 tests per year (Exhibit IV-10). It is worth
noting that an error in estimating Section 5 testing demand will be less
serious than an error in estimating testing demand from other sources.
Section 5 tests are almost always acute tests, and those utilize fewer
testing resources than do those done under Section 4 and FIFRA.
0. Demand for Toxicological Testing Under FFDCA
The Food and Drug Administration requires toxicological testing under
several different regulatory programs. The Bureau of Drugs must approve
all human drugs before they can be marketed; the Bureau of Veterinary
Medicine must approve all new animal drugs; and the Bureau of Foods becomes
involved if a drug is to be used on animals sold for consumption. All food
additives and problem cosmetics are regulated by the Bureau of Foods. In
this section, the demand for toxicological testing from human and animal
drugs, and food additives and cosmetics is estimated.
1. Human Drugs
The government has exercised some authority over human drugs since the Pure
Food and Drug Act of 1908 prohibited the sale of misbranded and adulterated
foods and drugs. The Federal Food, Drug and Cosmetic Act of 1938 placed
further responsibility on drug manufacturers by requiring them to prove
the safety of drugs before marketing. Under its provisions, the
manufacturer was required to file a New Drug Application (NDA) which
included data in support of its product; however, if the FDA failed to take
action within sixty days, the drug could be marketed.
The Drug Amendments of 1962 (21 U.S.C. 355} and their subsequent
regulations substantially increased FDA authority over new drugs by
requiring the manufacturer to file a Notice of Claimed Investigational
IV-21
-------
Exhibit IV-9. Toxicological tests in OECD minimum
premarketing data set
Acute Oral Toxicity
Acute Dermal Toxicity
Acute Inhalation Toxicity
Dermal Irritation
Dermal Sensitization
Eye Irritation
Repeated Dose Toxicity, 14-28 days
Gene Mutation
Chromosome Aberration
Source: Chemical Regulation Reporter, January 16, 1981, p. 1297.
Exhibit IV-10. Estimated toxicological testing under Section 5 of TSCA
Test Number
Acute Oral Toxicity 212
Primary Dermal Irritation 190
Primary Eye Irritation 188
Dermal Sensitization 48
Ames 90
Acute Dermal Toxicity 98
Acute Inhalation Toxicity 31
Other 65
IV-22
-------
Exemption (IND) with the FDA before the drug could be used in human testing
(21 CFR 312). In addition, new drugs had to be proved effective as well as
safe. (Although drugs approved between 1930 and 1962 were not required to
prove safety and efficacy under the new amendments, the FDA could withdraw
approval if it received evidence to the contrary.) The obligation to prove
efficacy and safety has resulted in an increase in the amount of testing.
To insure quality testing, the FDA has proposed minimum standards for good
laboratory practices (FDA, 1978). When an NDA is filed, the manufacturer
must state that tests were carried out according to these practices or
explain any differences. In addition, FDA testing guidelines are available
to aid the manufacturer in designing drug development test protocols
(Bureau of Drugs). Unlike the "good laboratory practices," however, these
guidelines are not formal regulations and as new techniques develop, the
guidelines may change.
Determining such standard procedures for drug testing is difficult for two
reasons: first, much variation exists in the use and activity of the
drugs. The type of testing required depends on the mode of entry of the
drug, the target population, the length of treatment, and the relationship
of the drug to those already in use. Second, the results of previous tests
may or may not suggest what the future course of testing should be. For
instance, if a drug shows ambiguous results in early tests, more testing
may be required to clarify these. A drug which is pharmacologically
similar to other known drugs and whose preliminary tests show no
complications might progress through the testing process much faster than
one which is unique. Thus, the testing program must be tailored to the
individual drug. To clarify such problems, the manufacturer may contact
the FDA to discuss the program as testing progresses.
Human drugs go through three phases of testing: the discovery, the
development, and the clinical phases. (Hansen, 1979.) These are shown in
Exhibit IV-11. The discovery phase includes the drug's basic chemical
research—compound synthesis, early pharmacological studies, and research
on physiopathological processes. If this early research results in a new
chemical entity which shows promise, the company will move to the
development phase and begin animal toxicity testing. The early research on
the drug is done without formal outside review, and not until the drug is
to be tested in humans, does it becomes part of the FDA public record.
Thus, no formal record exists for the drugs that begin testing and are
dropped before the drug enters the regulatory system. Since the testing
can be quite expensive, the company must weigh the costs against the
expected return at each stage in the research and development process.
In order to begin clinically testing the drug on humans, the company must
file a Notice of Claimed Investigational Exemption for a New Drug (IND) (21
CFR 130). At this time, the company must file its unique in-house
production information. The IND must, also, include the protocols for the
planned chemical investigation. If the proper short term animal testing
was performed and the results show no significant or adverse findings, the
IND is granted.
IV-23
-------
Exhibit IV-11. Phases of testing of human drugs
IND Filed 1/
NDA Filed 2/
Di sco very
Phase
Development
Phase
CIinical
Phase
> NDA
Approval
Further Testing
May Be Required
Marketing
1/ Notice of Claimed Investigational Exemption for a New Drug.
2/ New Drug Application.
Source: R. W. Hansen, "The Pharmaceutical Develoment Process: Estimates of Development Costs and
Time and the Effects of Proposed Regulatory Changes," in Issues in Pharmaceutical
Economics, R. I. Chien, ed. (Lexington, MA., D.C. Heath and Company, 1979.
-------
There are three phases to clinical testing:
Phase I - drug application to healthy human volunteers, to test
human toxicity and absorption
Phase II - drug application to human patients to test therapeutic
value 'and side effects
Phase III - drug application to extensive groups of human patients to
test for the drug's less common side effects.
At the same time that clinical testing is being conducted, the
pharmaceutical company may also initiate long-term animal testing in
preparation for marketing its product. If at the end of the clinical
testing the company decides to market the drug, it must file a New Drug
Application (NDA) with the FDA. The FDA reviews the results of all testing
and may request additional tests. Only after the drug passes the FDA tests
for efficacy and safety does FDA grant marketing approval for the drug.
a. Requirements for toxicologies! testing
The specific toxicological tests which each drug must undergo depend upon
its intended use. In its guidelines, the FDA divides drugs into the
following categories according to their method of entry to the body:
Oral or parenteral
Inhalation
Dermal
Ophthalmic
Vaginal or rectal
Combination
The type of tests for chronic toxicity required for each of these
categories is listed in Exhibit IV-12. All of the drugs require acute
tests in at least one species, and those drugs which will be administered
orally or parenterally require acute testing in three or four species.
This testing takes place before an IND is filed. Certain sub-chronic and
chronic tests must be completed, also, before human testing can begin. For
instance, before an oral drug can be administered to healthy humans for a
period of several days up to two weeks (Phase I), it must be tested in two
species for two weeks. For the drug to enter Phase II of clinical testing,
it must be tested in two species for up to four weeks. Generally, drugs
that are expected to be administered to the human patient for longer
duration require longer periods of animal testing.
b. Number of chemicals to be regulated
The data for IND applications since the 1962 Amendments went into effect in
1963 are shown in Exhibit IV-13. No significant trend in IND applications
is apparent—some variation from year to year does exist. The distribution
of types of drugs on IND applications for 1979, a typical year, is shown in
Exhibit IV-14. Most drugs are oral or parenteral--65 percent of the total.
Drugs to be applied dermally follow with 17 percent, while drugs
administered by inhalation, ophthalmic or vaginal or rectal application
make up a combined total of 18 percent.
IV-25
-------
Exhibit IV-12. Summary of tests required for human drugs
4
_ Subchronic and chronic tests
2 3 To be completed
1 Duration of human Acute toxicity before human
Drug cdtcgorjf administration tests (oral) Required testing phase:
Oral or Parental Several Days 3-4 species. 1 non rodent 2 species; 2 weeks I
Up to 2 Weeks " 2 species; 2 weeks I
M 2 species; up to 4 weeks II
" 2 species; up to 3 months (1 nonrodent) III
Up to 3 Months " 2 species; 4 weeks I
" 2 species; 3 months (1 nonrodent) III
" 2 species; up to 6 months NDA
6 Months " 2 species; 3 months (1 nonrodent) I
to Unlimited " 2 species; 6 months or longer (1 nonrodent) III
" 2 species; 12 months (nonrodent)
18 months (rodent) NDA
inhalation 2 species 4 species; 5 days (3 hours/day by 1
(General Anesthetics) - notice to be administered
clinlcally
Dermal Single Application 2 species, 1 non-rodent 1 species; single 24-hour exposure I
followed by 2-week
observation
Single or Short-tenii " 1 species; 20-day repeated exposure 11
Application (intact and abraded skin)
Short-term Application " As above NDA
Unlimited Application " As above, but intact skin study
extended up to 6 months
Ophthalmic Single Application 1 or 2 species ' I species; 3 weeks daily applications, I
Multiple Application 11 as in clinical use
1 species; duration commensurate with NDA
period of drug administration
Vaginal or Rectal Single Application 1 or 2 species 2 species; duration and number of 1
Multiple Application " applications determined by
proposed use
Source: Synopsis of "General Guidelines for Animal Toxicity Studies," FDA.
-------
Exhibit IV-13. Annual number of IND's 1/ and NDA's 2/ filed
Original IND's Original NDA's
Year submitted submitted NDA's approved
1963
1,066
192
71
1964
875
160
70
1965
761
221
50
1966
715
216
50
1967
671
128
74
1968
859
108
56
1969
956
60
39
1970
1,127
87
53
1971
923
256
68
1972
902
272
42
1973
822
149
77
1974
802
129
95
1975
876
137
68
1976
885
127
101
1977
925
124
63
1978
925
121
86
1979
940
182
94
Average
884
157
68
Average 1963-1967
818
183
63
Average 1969-1973
946
165
56
Average 1975-1979
910
138
82
1/ Notice of claimed investigational exemption for a new drug.
2/ New drug application.
Source: Stanley A. Stringer, Bureau of Drugs, Food and Drug
Administration.
IV-27
-------
Exhibit IV-14. Distribution of IND's by category, 1979
Category
Number
Percent of total
Oral/Parenteral
624
65
Inhalation
73
8
Dermal
161
17
Ophthalmic
86
9
Vaginal/Rectal
12
1
Combination
0
0
TOTAL
956 1/
100
1/ In 1979, 940 IND drug applications were received and some of these
drugs were included in more than one testing category.
Source: Stanley A. Stringer, Bureau of Drugs, Food and Drug
Administration.
II1-28
-------
If it is assumed that the future distribution of drugs among the categories
will be similar to that of the past, the number of each type of test
required by the IND's introduced in a particular year can be predicted.
Since the IND is filed in order to begin clinical testing, then all IND
drugs go through the animal testing required to reach Phase I. The tests
required to reach Phase I are given in Exhibit IV-15. Ninety percent of
the IND drugs never get past Phase I because (1) they produce no effective
pharmacological activity in humans, (2) they have undesirable side effects,
or (3) the testing program studied biological processes in humans rather
than sought to develop a marketable drug. (Anon., 1978c.)
Unless the risks turn out to be greater than anticipated or commercial
problems develop, NDA's will eventually be filed on the drugs entering
Phase II. (Hansen, 1979.) Thus, the NDA's submitted will reflect the
number of drugs that pass through human testing. In addition to the human
tests, these drugs will go through the animal testing outlined in Exhibit
IV-16.
c. Demand for toxicological testing
Since the number of drugs whose manufacturers have filed IND's and NDA's is
known, the number of tests required for FDA approval of these types of
applications can be calculated. Although data on the distribution for the
NDA's are not known, the distribution should be similar to that of the
IND's. Based on this distribution, Exhibit IV-17 shows the estimated
number of drugs with IND's and NDA's in 1979. Combining the testing data
from Exhibits IV-15 and' IV-16 and the numerical data from Exhibit IV-17
results in the total number of tests shown in Exhibit IV-18.
2. Animal Drugs
The government also regulates animal drugs under the FFDCA. The approval
process for animal drugs was formerly complicated by the fact that a drug
could be regulated as a "new drug," an "antibiotic," or a "food additive,"
depending upon its intended use. Since the primary purpose of these
regulations was to control products that would be used directly by humans,
they did not specifically address the protection of target animals and
their indirect effect on humans. The Animal Drug Amendments of 1968
drew together all of the sections of the FFDCA which concern animal drugs.
In addition, the drugs which are used in food animals are subject to the
regulations covering food additives.
A new animal drug is regarded as unsafe until it is approved by the FDA,
and until it is approved, it is illegal for the drug to be marketed in
interstate commerce. In order for the drug to be approved, the FDA must
find that the drug is safe and effective for its intended use. The FDA
evaluates testing results which are submitted in a New Animal Drug
Application (NADA).
As with human drugs, it is difficult to describe a definitive set of
testing protocols, since later phases of testing depend upon earlier
results. Exhibit IV-19 outlines the general sequence of testing. The
IV-29
-------
Exhibit IV-15. Animal tests required for IND )J application for human drugs
Drug
type
Duration of
human administration
Oral
Acute tests
Dermal
Primary eye
Oral
-{number of tests)
Subchronic tests
Inhalation
Dermal
Vaginal/
Rectal application
Oral/parenteral
Inhalation
Dermal
Ophthalmic
Vaginal/rectal
Several days
Two weeks
Three months
Six months
All dosages
Single dose
Single or short term
Short term
Unlimited
Single
Multiple
Single
Multiple
3-4*
3-4*
3-4*
3-4*
2*
2*
2*
2*
1-2
1-2
1-2
1-2
2*-two wks.
2*-fotir wks.
2*-four wks.
2*-three mos.
* = One nonrodent test required
1/ Notice of claimed investigational exemption for a new drug.
Source: Adapted from, "Guidelines for Preliminary Toxicity Testing of Investigational Drugs for Human Use." Bureau of Drugs, Food and
Drug Administration.
-------
Exhibit IV-16. Tests required for NDA \J for human drugs
ORAL/FARENIERAI. DRUGS
Duration of human
administration
Several days
2 weeks
3 weeks
6 months
Acute oral
3-4* 2/
3-4*
3-4*
3-4*
INHALATION {GENERAL ANESTHETICS)
All dosages
DERMAL
Duration of human
administration
Single application
Single or short term
Short term
Unlimited
OPHTHALMIC
Duration of human
administration
Single
Multiple
VAGINAL/RECTAL
Duration ol human
application
Single application
Multiple application
Acute
oral
2*
2*
?*
2*
2 wks
2
Acute
oral
1-2*
1-2*
4 wks
or
Acute oral
Acute
dermal
1
1
I
1
Acute oral
1-2
1-2
Subchronic oral dose
3 BIOS
6 mos
2*
2*
or
12 mos
2*
18 mos
Subchronic inhalation
Subchronic
dermal
Primary eye
irritation
1
1
Dermal
sensitization
1
1
1
1
Subchronic
application 3 weeks
1
1 3/
Vaginal or rectal
1/ New drug application. This Includes the tests required for IND applications.
7/ Numbers refer to number of species in which tests are required.
1/ May be longer, depending on the expected duration of the treatment.
7 = indicates that testing in one nonrodent required.
Source: Adapted from, "Guidelines for Preclinical Toxicity Testing of Investigational Drugs for Human Use." Bureau of Drugs, Food and Drug
Administration.
-------
Exhibit IV-17. Number of human drugs in each phase (1979).
Category £/
IND
applications
IND-NDA 2/
NDA 3/
Oral
524
90
Several days
(156)
133
(23)
up to 2 weeks
(156)
133
(23)
up to 3 months
(156)
134
(22)
6 months to unlimited
(156)
134
(22)
Inhalation
73
62
11
Dermal
161
23
Single application
(41)
35
(6)
Single or short-term
application
(40)
34
(6)
Short-term application
(40)
34
(6)
Unlimited application
(40)
35
(5)
Ophthalmic
86
13
Single application
(43)
36
(7)
Multiple application
(43)
37
(6)
Vaginal or rectal
12
1
Single application
(6)
5
(1)
Multiple application
(6)
6
(0)
1/ Investigational new drug.
2/ New drug application.
3/ We have assumed that the distribution of NDA among the different
categories is similar to the distribution of IND applications.
A/ The distribution of applications among the different categories was
not available. We have assumed that the drtig applications are dis-
tributed equally among the categories.
Source: Adapted from Exhibit IV-14.
IV-32
-------
Exhibit IV-18. Estimated total number of animal tests required
for approval of human drugs
Acute oral toxicity
rodent
nonrodent
1,861-2,677
913
Acute dermal toxicity
184
Acute inhalation toxicity
168
Primary eye irritation
86
Primary dermal irritation
137
Dermal sensitization
23
Subchronic oral
2 wks rodent
nonrodent
202
156
4 wks rodent
nonrodent
335
335
3 mos rodent
nonrodent
178
178
6 mos
12 mos rodent
nonrodent
22
22
18 mos
0
Subchronic ophthalmic application
50
Subchronic vaginal or rectal
application
rodent
nonrodent
11
11
Source: Exhibits IV-16 and IV-17.
IV-33
-------
Exhibit IV-19. Phases of testing of animal drugs
INAD filed 1/
DISCOVERY
PHASE
DEVELOPMENT T
PHASE
NADA filed 2/
CLINICAL ?
" PHASE
NADA
APPROVAL
MARKETING
J[/ Claimed investigational exemption for a new animal drug.
2/ New animal drug application.
-------
animal drugs go through the same first two phases of testing as do human
drugs: the discovery phase—the drug's basic chemical research—and the
development phase, which includes toxicological and efficacy testing on
laboratory animals. If a manufacturer decides that the drug looks
promising after this early animal testing, the company will apply for a
Claimed Investigational Exemption for a New Animal Drug (INAD). This is
necessary for two reasons: it allows the drug's distribution for clinical
research, and it allows the drug to be used on food animals—meat, dairy or
poultry. For instance, if a company is developing a drug to be
administered in cattle feed, it must test that drug on cattle, and in order
for these cattle to be slaughtered for food, the drug must be listed with
the FDA as being exempt from the requirements for approval. To insure
human safety, the FDA examines the resultant toxicological data and may
assign a requirement for a withdrawal period—a time before slaughter
during which the drug cannot be administered.
The types of tests required for a new animal drug (NAD) are listed in
Exhibit IV-20, and the number of investigational new animal drugs and new
animal drug applications approved in the years 1978 to 1980 are shown in
Exhibit IV-21. This study could not determine how many applications were
not approved. Although the testing of each drug is performed on an ad hoc
basis, an upper limit for the numbers of tests can be set by assuming that
each drug which has an INAD filed goes through the full range of animal
toxicity tests:
(1) acute toxicity studies in mice and rats or
skin and eye irritation studies,
(2) teratology studies in two rodent species,
(3) subacute or chronic study in mice, rats, and dogs,
(4) multigeneration reproduction study in rats, and
(5) sub-acute toxicity in target species.
The upper limit for the number of animal tests required for animal drugs is
shown in Exhibit IV-22. No basis exists for estimating how many of the
drugs require further carcinogenic studies, reproduction studies, or
chronic studies. The requirements for these depend on previous test
results.
3. Food Additives and Cosmetics
Though the FFDCA of 1938 prohibited the use of unsafe substances in food,
it was the federal government's responsibility to prove that a substance
was poisonous or otherwise deleterious. The burden of proof was shifted to
the food processors with the Food Additive Amendment of 1958 which decreed
that processors must demonstrate that a food additive is safe before it can
be used. Under the Amendment a food additive is defined as "any
substance... which may reasonably... be expected to... (become) a component
IV-35
-------
Exhibit IV-20. Tests required for animal drugs
1. Discovery phase - Research to identify potential of chemical.
2. Dose efficacy studies
dose-range efficacy studies
controlled efficacy studies
efficacy and field use experiments in three locations
3. Environmental impact analysis
plant/fish toxicity
stability of residues in environment
4. Acute toxicity studies in mice and rats \J
5. Skin and eye irritation studies \j
6. Teratology studies in two rodent species *
7. Subacute/chronic study in mice, rats and dogs *
8. Multigeneration reproduction study in rats *
9. Subacute toxicity in target species *
10. Trace drug and metabolites in different organs - target species
radioactive study
nonradioactive study
11. The following depend on threshold assessment:
carcinogenic study in mice
reproduction through weaning
12 month necropsy
24 month survival
30 month survival
6 month chronic study in dogs
\j Assume that each drug was tested for either one or the other of these
tests.
* Toxicity tests which were used in developing Exhibit IV-21.
Source: "Impact of Government Regulations on Development of Chemicals Used
in Animal Production," Council for Agricultural Science and
Technology Report No. 85, October 1980.
IV-36
-------
Exhibit IV-21. Annual number of INAD's _!/ and NADA's 2/ approved
Original
Original
Year
INAD's filed
NADA's filed
FY 1978
71
141
FY 1979
104
131
FY 1980
71
116
Yearly average
82
129
1/ Investigational new animal drug.
2/ New animal drug application.
Source: Homer R. Ransdell, Chief, Case Guidance Branch, Division of
Compliance, Bureau of Veterinary Medicine, Food and Drug
Administration.
IV-37
-------
Exhibit IV-22. Total number of animal tests required
for approval of animal drugs 1/
Acute toxicity test 2/
Mice 61
Rats 61
Skin or eye irritation test 2/ 21
Teratology tests 164
Subacute/chronic tests
Mi ce 82
Rats 82
Dogs 82
Hultigenerational reproduction test in rats 82
Subacute toxicity test in target species 82
Carcinogenic study in mice 3/
Reproduction through weaning- 3/
6-month chronic study in dogs 3/
\j This is the upper limit of tests required; we assume that each animal
drug for which an 1NAD is filed has gone through all of these tests.
Based on average annual number of INADs filed, 1978-1980.
2/ We have assumed that the same percent (26%) of drugs is used for skin
and eye tests in both humans and animals.
y No basis for estimate.
Source: Exhibits IV-20 and IV-21.
IV-38
-------
or affect the characteristics of a food. (21 CFR 570.3e.) Additives can be
direct or indirect. Direct additives are added to the food to perform some
function (i.e., stabilizing, preserving, improving appearance). Indirect
additives are those substances which are introduced as a by-product of some
process, such as their migration from packaging material. A third group of
substances was exempted from the requirement of proof of safety—those
generally recognized as safe (GRAS) after a long term of use. These
latter additives are currently under review by the Bureau of Foods, which
plans to require testing of those GRAS additives found to be suspect. The
GRAS testing requirements will not go into effect until 1983. (Morgenroth,
1981.) Substances added for color purposes only were not covered until the
1958 act, and the Color Additive Amendment of 1960 requires that color
additives be demonstrated safe for their intended use. Twenty-three color
additives which had been provisionally approved are currently in testing.
The testing had been expected to be complete by 1981, but the deadlines
have been extended over the next two years. (New York Times, 11/4/80.)
As do those manufacturing human and animal drugs, the manufacturers of food
additives consult with FDA toxicologists to determine testing requirements
and acceptable protocols. (Kokoski, 1975.) Exhibit IV-23 shows the
testing and protocol guidelines which are currently in use. Unless
otherwise noted, the tests will be required for each additive and other
tests are required if preliminary tests indicate a need. Teratogenicity
tests, for instance, may not be required for a direct food additive unless
the multigenerational reproduction study shows that the additive has
affected the offspring of rats exposed to the substance. In other cases,
the number of required tests increases with the expected amounts of
exposure; hence, because indirect food additives with virtually no
migration evidence would normally not appear in high concentration in food,
they would require only acute oral testing. On the other hand, a direct
food additive which could be expected to accumulate in the body in larger
amounts, undergoes acute, subchronic, and multigenerational studies.
Exhibit IV-24 estimates the number of additives for which data are
submitted to the FDA for approval. Combining these data with the testing
required for each type of additive, yields the total number of each type of
test required as is shown in Exhibit IV-25.
4. Summary: Demand for Toxicoloqical Testing Under FFDCA
Under the FFDCA provisions, the FDA requires pre-marketing testing for
human drugs, animal drugs and food additives. This study section
summarizes the tests required for these three groups of drugs. The largest
demand for testing is for human drugs, which must undergo both animal and
extensive clinical testing before approval of the new drug application
(NDA). There has been an annual average of 157 NDA's filed and 68 approved
since 1962. Animal drugs also undergo both animal and clinical testing
before approval, and an average of 129 new animal drug were approved each
year between 1977 and 1980. Testing for food additives depends on the
expected fate of the additive. Direct food additives undergo a full range
of animal tests, as do indirect food additives which have extensive
IV-39
-------
Exhibit IV-23. Tests required for approval of food additives
Indirect food additive
Direct food
additive
Virtually nil
Migration 1/
Negligible Significant
Color additive
Ingested Topical
Sutures
Acute oral toxicity - rodent
Acute oral toxicity - nonrodent
Subchronic feeding study (90-day) - rodent
Subchronic feeding study (90-day) - rat
Subchronic feeding study (90-day) - nonrodent
Lifetime feeding study (ca 2-year) - rodent
with in-utero exposure
Lifetime feeding study (ca 2-year) - rodent,
for carcinogenesis
Short-terni feeding study (ca 6 nto. to 1 yr.) -
nonrodent
Multigeneration reproduction feeding study
rodent
Teratology study
Mutagenicity screen
Dermal irritation/percutaneous toxicity - rabbit
Acute eye irritation (Draize test)
Ocular toxicity (repeat eye instillation) - rabbit
Lifetime skin painting (ca 2-years) - mouse
Implantation studies -
***
***
A * *
***
X
**~
X
X
X
X
*
**
**
X
**
X
a. lifetime - rate for non-absorbable sutures
b. short-term - for absorable sutures
c. ocular - for ophthalnic sutures
Sensitization studies - guinea pig
Sensitization studies - humans
Metabolism studies
Skin penetration studies
Sj Food additive Migration!
Virtually nil = 0.05 ppm
Negligible or insifnifleant » 0.05 ppm.
X = required.
* = if indicated by available information.
** =* suggested.
*** = if needed as preliminary to further study.
**** = jf usecj eyC, area.
Source: C. H. Kokoski and M. R. Gittes, "Toxlcologlcal Testing Under Varying Food and Color Additive Situations," Distributed by Bureau of Foods,
FDA.
-------
Exhibit IV-24. Annual number of additives applications
for approval 1/
Type of additive Number
Direct additives 94
Indirect additives 294
no migration (less than 0.05 ppm) 184
negligible migration (more than 0.05 ppm) 73
significant migration 37
Color additive
ingested 10
topical 0
sutures 0
\j 1980 data.
Source: Dr. Victor Morgenroth, Bureau of Foods, Food and Drug
Administration.
IV-41
-------
Exhibit IV-2S.
Total numbers of tests performed for
food additive approval 1/
Test
Number
Acute oral toxicity - rodent
Acute oral toxicity - nonrodent
Subchronic feeding study (90-day) - rodent
with in-utero exposure
Subchronic feeding study (90-day) rat
Subchronic feeding study (90-day) nonrodent
Lifetime feeding study (ca 2-year) - rodent
with in-utero exposure for carcinogensis
and chronic toxicity
Lifetime feeding study (ca 2-year) - rodent,
for carcinogenesis
Short-term feeding study (ca 6 mo. to 1 year) -
nonrodent
Multigeneration reproduction feeding study
(3 generation, 2 1itters/generation, with
teratology phase) - rodent
Teratology study
Mutagenicity screen
Dermal irritation/percutaneous toxicity
ca 1 to 3 months) - rabbit
Acute eye irritation (Draize test)
Ocular toxicity (repeat eye instillation) - rabbit
Lifetime skin painting (ca 2-years) - mouse, for
carcinogenesis
Implantation studies -
a. lifetime - rate for non-absorbable sutures
b. short-term - for absorbable sutures
c. ocular - for ophthalmic sutures
Sensitization studies - humans (repeat patch test:
Draize type test) with photosensitization test
Metabolism studies
Skin penetration studies
184
U
73
II
73
141
141
141
141
2/
V
0
0
0
0
2/
u
1/ Based on 1980 data. Tests which are "suggested" rather than "required"
are not included.
2/ No basis for estimate.
Source: Exhibits IV-23, IV-24.
IV-42
-------
migration characteristics or color additives which are ingested. Food
additives which show little migration and color additives which are used
topically are screened, but they do not undergo extensive animal testing
unless the results of early tests indicate a problem.
E. Commercial Demand for Testing not Directly induced by Regulation
The demand for toxicological testing directly stemming from FIFRA, T5CA,
and FFDCA requirements does not include all of the testing done for
commercial purposes. In addition to the tests reported to the government
under these and other laws, firms may do additional tests on existing
chemicals for their own purposes (e.g., their concern over product
liability). Furthermore, firms may conduct tests of new chemicals which,
for one reason or another, are never introduced commercially.
Clearly trade journals and chemical industry personnel indicate that the
amount of such testing appear to be substantial (CRR, 1981b, 1980.), but
inadequate data are available for estimating the extent of such testing.
F. Research Demand for Toxicological Testing
Because of the multiple sources of research activity and the funding of
that activity, research demand is more difficult to estimate than testing
demand associated with the regulation of commercial chemical production.
Toxicological research is carried out at a large number of installations.
In addition, the funding for toxicological research comes from a
substantial variety of research foundations and government agencies. In
this section of the present study, estimates are presented for research
demand only from the Department of Health and Human Services (HHS).
Although toxicology-related research is sponsored by other federal
agencies, the HHS funds are estimated to be at least equal to, and probably
significantly greater than, the funds provided by all other federal
agencies combined. (HEW, 1979.) However, analysts are unable to estimate
the research demand for that toxicological testing funded by other sources.
Another difference between this study's estimates of regulatory demand and
research demand is the difference in the way that the estimates are
presented. In the previous three sections, of the demand estimates for
each type of test were made; however, such information cannot be obtained
for research demand. Instead, this study uses that which is available--the
amount spent on research.
To facilitate a comparison between the results in earlier sections and
those in this section, the research demand is expressed both in dollar
amounts and in the numbers of oncogenicity tests that those dollar amounts
would buy. The assumed relationship between those dollars and the
oncogenic tests is taken from a recent survey of testing costs which found
the average cost of oncogenic tests to be $655,000. (Enviro Control,
1980.) However, that figure has been increased by a 10 percent inflation
IV-43
-------
margin to give a final figure of $720,000 per oncogenic test. This
conversion provides a rough basis of comparison between the results here
and the results in earlier sections.
The activities covered in this section include more than just basic
research -- test method development and that testing conducted or paid for
by government agencies are also included. The testing demand discussed in
this section includes demand from EPA and FDA, agencies which were also
covered in previous sections. The difference between the demands covered
in this section and those covered in previous sections, however, is that in
previous sections, that testing demand was generated by firms in response
to regulations and in this section, only nonregulatory sources of demand
are considered.
The National Toxicology Program (NTP) was formed by the Department of
Health, Education and Welfare (HEW, now HHS) in 1978 to coordinate the
toxicological activities of HHS agencies. Not all agencies in HHS
participate in the program nor is all toxicological research in those
agencies under the auspices of the National Toxicology Program. The four
NTP agencies - Food and Drug Administration, National Cancer Institute,
National Institute for Occupational Health and Safety, and the National
Institute for Environmental Health Sciences -- originally planned to spend
$219 million in FY 1980 of which $69 million was to be under the auspices
of the National Toxicology Program. Other HHS agencies were to spend an
additional $43 million in FY 1980. Of the total of $262 million, $114
million was to be spent on basic research, $124 million on testing, and $24
million on method development (HEW, 1979). The $262 million total is equal
to the resources needed to conduct about 400 oncogenicity tests. A full
range of tests are conducted by HHS agencies, but the emphasis is on
oncogenicity, mutagenicity, teratogenicity, reproduction and chronic
effects.
G. Summary: Demand for Resources Used in Toxicological Testing
This chapter provided estimates of the demand testing generated directly by
FIFRA, TSCA and FFDCA. Commercial demand for testing not directly induced
by regulation and research demand were also briefly discussed (good
estimates were not obtained for either of the two latter areas). This
final section, translates demand for tests into demand for the resources
used in testing. The availability of the different resources used in
testing may vary markedly from one resource to another; therefore, in order
to completely characterize the demand side of the market, it is necessary
to discuss the demand for the resources used in testing.
Exhibit IV-26 displays the resources required for several different types
of toxicological tests as they are described in TSCA and FIFRA testing
protocols. The estimates, developed from a separate study, are based on
information obtained from testing laboratories, federal contractors,
manufacturing companies that contract similar studies, personnel placement
firms, industry trade associations and the contractor's own experience in
the field. (Enviro Control, 1980.)
IV-44
-------
Exhibit IV-26. Resources required for toxicological testing per type of test
Acute Acute Acute
Personnel oral dermal inhalation
(Hours) toxicity toxicity- toxicity
Primary Primary Acute Subchronic
eye Dermal Dermal delayed oral dosing
irritation irritation sensitization neurotoxicity T IT III
Subchronic
Inhalation Subchronic
toxicity neurotoxicity
Study Director
I
1
1
1
1
2
2
96
52
148
52
9
Veterinarian
16
8
24
8
Compound Prepa-
1
I
8
1
1
11
1
96
52
148
90
48
ration Technician
Senior Technician
10
14
24
1
1
41.5
17
328.5
208.5
537
482
50
Animal Technician
10
14
24
7
4
41.5
17
328.5
208.5
537
482
50
Animal Caretaker
13
19
16
8
5
30.6
26
1032
227
1259
127
100
Clinical Lab
46.33
33.10
79.43
16.55
Supervisor
Clinical Lab
138.97
99.26
238.23
49.63
Technician
Necropsy Supervisor
7
8
7.5
13.13
54
34
88
10
18.75
Necropsy Technician
21
24
22.5
39.39
162
102
264
30
56.25
Histology Supervisor
.88
1.64
1.66
35.52
32.26
67.78
16.57
7.45
Histology Technician
3.54
6.54
6.64
148.02
111.62
259.64
66.27
29.86
Board-Certified
7
10
12.19
16.88
163.50
114
277.50
57.50
35.63
Pathologist
Report Writing
20
24
44
35
25
Supervisor
Report Writer
20
20
32
8
8
32
40
300
320
620
350
150
Computer Programmer
48
26
74
30
40
Computer Coder
48
26
74
30
40
Report Typists
8
10
20
4
4
16
20
200
300
500
200
50
General Secretary
1
1
1
1
1
48
26
74
26
5
Quality Assurance
1
1
8
1
1
8
8
70
52
122
80
40
Inspector
Animals (Number)
Rats
48
60
192
192
96
Mice
Rabbits
40
11
8
Dogs
58
58
Chickens
36
72
Guinea Piys
24
Source: Enviro Control, Incorporated, Cost Analysis Methodology and Protocol Estimates: TSCA Health Standards and FIFRA Guidelines, April 1930.
Continued
-------
Exhibit IV-26. (continued)
Personnel (Hours)
Teratogenic health
effects
I 11 III
Reproductive
effects
General
metabolism
I
Oncoqenic effects
II III
1
I
Chronic toxicity
It III
Study Director
24
24
48
62
208
208
416
240
208
448
Veterinarian
25
25
50
60
60
120
Compound Preparations
12
16
28
60
416
41b
832
480
384
864
Technician
Senior technician
324
291
615
850
676
3142
1984
5126
3724
1011
4735
Animal Technician
324
291
615
850
386
3142
1984
5126
3724
1011
4735
Animal Caretaker
75
70.5
145.5
817.5
304
3765
1500
5265
4325
3889
8214
Clinical Lab Supervisor
8.78
8.78
17.56
52.96
39.22
92.68
Clinical Lab Technician
26.33
26.33
52.66
158.82
119.2
277.94
Necropsy Supervisor
30
27
57
33
5
100
80
180
116
54
170
Necropsy Technician
90
81
171
99
15
300
672
972
348
162
510
Histology Supervisor
76.74
183.12
168
351.12
252.88
48
300.88
Histology Technician
306.94
732.48
672
1404.48
1011.52
192
1203.52
Board-Certified Pathologist
30
27
57
109.74
625
605
1230
841
100
941
Report Writing Supervisor
10
10
20
50
50
50
100
100
50
150
Report Writing
100
80
180
400
750
750
1500
1000
750
1/50
Computer Programmer
24
24
48
120
96
96
192
160
96
256
Computer Coder
24
24
48
120
96
96
192
160
96
256
Report Typist
50
30
80
150
160
450
450
900
750
450
1200
General Secretary
12
12
24
31
20
104
104
208
120
96
216
Quality Assurance Inspector
48
48
96
80
16
224
224
448
254
230
484
Animals (Number)
Rats
144
144
168
480
480
560
560
Mice
480
480
Rabbits
85
85
Dogs
58
58
Chickens
Guinea Pigs
Source: Enviro Control, Incorporated, Cost Analysis Methodology and Protocol Estimates: TSCA Health Standards and F1FRA Guidelines, April 1980.
Continued
-------
Exhibit IV-26 (continued)
Combined chronic effects
Personnel (Hours) 1 II III IV
Study Director 240
Veterinarian 60
Compound Preparation Technician 480
Senior Technician 3724
Animal Technician 3724
Animal Caretaker 4325
Clinical Lab Supervisor 52.96
Clinical Lab Technician 158.82
Necropsy Supervisor 116
Necropsy lechnician 348
Histology Supervisor 252.88
Histology Technician 1011.52
Board-Certified Pathologist 841
Report Writing Supervisor 100
Report Writing 1000
Computer Programmer 160
Computer Coder 160
Report Typist 750
General Secretary 120
Quality Assurance Inspector 254
Animals (Number)
Rats 560
Mice
Rabbits
Dogs
Chickens
Guinea Pigs
208 208 656
60 25 145
384 416 1280
1011 2506 7241
1011 2506 7241
3889 1969 10183
39.72 61.78 154.46
119.12 185.29 463.23
54 69.6 239.6
162 208.8 718.8
48 232 532.88
192 928 2131.52
100 794.6 1734.6
50 50 200
750 750 2500
96 96 352
96 96 352
450 450 1650
96 104 320
230 230 714
560
556 556
58 58
Source: Fnviro Control, Incorporated, Cost Analysis Methodology and Protocol Estimates: TSCA Health Standards and F1FRA Guidelines, April 1980.
-------
To illustrate how these data on resources required for toxicological
testing can be used to characterize the market for individual resources,
the number of Board-Certified Veterinary Pathologists required to conduct
the tests directly induced by FIFRA, TSCA and FFDCA was calculated. These
estimates, inherently containing a great deal of variance, are
extrapolations produced by the application of assumptions to information on
current testing levels, which are themselves highly uncertain. The
estimates of the resources required for each test are also uncertain; the
authors of a cited study suggest that a variance range of +50 percent might
be appropriate (Enviro Control, 1980). Particularly uncertain are the
estimates for the resources required by FFDCA tests, for the estimates of
the numbers of required tests are most uncertain for FFDCA. In addition, the
protocols in Exhibit IV-26 are EPA protocols rather than FDA protocols.
They may not apply to tests done under FFDCA.
The estimates of the demand for Board-Certified Veterinary Pathologists
from testing directly induced by FIFRA, TSCA and FFDCA are shown in Exhibit
IV-27. The total demand of 475 Board-Certified Veterinary Pathologists is
only slightly less than the total number, 486, of Board-Certified
Veterinary Pathologists in 1980 shown in Exhibit 111-6. But the demand
data do not include the demand from research,other commercial testing,
teaching, and government.
Testing demands like those described in this chapter may lead to severe
constraints on the availability of Board-Certified Veterinary Pathologists.
However, several factors may reduce the shortage suggested by these
figures. As discussed previously, there are about 700 other pathologists
working in drug and toxicity testing programs. Many of these may be
Board-eligible or be substitutable for Board-Certified Veterinary
Pathologists. Technicians may also be substituted for some tasks.
IV-48
-------
Exhibit IV-27. Esimated demand for board-certified veterinary
pathologists from FIFRA, TSCA and FFDCA
Number of board-certified
veterinary pathologists required
FIFRA
72
TSCA
Section 4
69
Section 5
2
FFDCA
Human drugs
117
Animal drugs
82
Food additives
133
TOTAL
475
Source: Exhibits IV-3, IV-7, IV-10, IV-18, IV-22, IV-25 and IV-26.
IV-49
-------
V. CONCEPTUAL SUPPLY-DEMAND MODEL DEVELOPMENT
The U.S. chemical testing industry provides numerous and complex
toxicological testing services. From its early emphasis on foods, drugs
and cosmetics chemical testing, the industry has evolved into one that
tests chemical substances of all types, including pesticides, other
commercial chemicals, and industrial intermediates.
Various types of laboratories comprise this industry and have contributed
to its expanded capacity and testing capabi1ity—independent, captive
(company), university, and government (see Chapter III). International
chemical testing capabilities and laboratory capacities have grown
similarly in the recent past. Collectively, these various sources or types
of laboratories "supply" the toxicological testing services that are
required by need and regulation.
Conversely, numerous and varied chemical developers "demand" toxicological
testing services (see Chapter IV). Such testing includes both regulatory
and nonregulatory demands. Government regulations, e.g., FFDCA, FIFRA,
TSCA, and others, have increased the general level and complexity of
toxicological testing, although many chemical companies had previously
initiated comprehensive toxicological testing on a nonregulatory basis.
Basic research programs often involve toxicological testing of a
nonregulatory nature. Regardless of whether these sources of demand are or
are not regulation-induced, they compositely reflect the aggregate demand
for the chemical testing industry's services.
While the perspective is simplified, it is instructive to characterize the
chemical testing industry in terms of its aggregate "supply" and "demand."
Various economic relationships are theoretically assessable in aggregate
terms although the magnitude and composition of the industry's testing
services have and will continue to change over time. These basic supply
and demand constructs will be developed initially and then integrated
within a common analytical system. As explained in this chapter, the
ability to represent both supply and demand in a common system is based on
the delineation of underlying key resources of the toxicological testing
"service" industry. Other modeling approaches are possible, although no
others are developed in this study.
The principal objective of this chapter is to formulate a supply-demand
model of the toxicological testing industry that can be used to measure
regulation-induced economic impacts on the industry. With such a model,
analysts can more readily simulate and project industry decisions and
market behavior that can occur under alternative regulatory programs, such
as TSCA, or under alternate economic conditions.
V-l
-------
The preceding chapters of this study have described the baseline supply and"
demand conditions of the chemical testing industry, i.e., toxicology
testing services, based on secondary data sources and this study's survey
data. However, substantially more development is required to
quantitatively define and assess the industry's traditional economic supply
and demand relationships and, also, to statistically model industry
behavior.
A complication of the chemical testing industry is that a broad range of
toxicological tests, requiring both basic and specialized resources, may be
performed by laboratories (suppliers of testing services). Hence, the
"supply" of services cannot be readily quantified as a simple economic
function of the "price" of tests. On the demand-side, an equally complex
problem exists because the actual tests required or demanded will vary
among the chemicals to be tested which, in turn, will differ through time
as chemical product requirements change and chemical innovations are made.
This chapter presents a traditional economic supply-demand model of the
chemical testing industry. It first presents an overall analytical system
within which the industry's supply and demand constructs are defined. It
then develops the supply and demand modules of that proposed analytical
system. Third, it formulates a supply-demand model that has both
accounting and economic subsystems. Finally, the chapter defines the
model's general implementation requirements.
A. Analytical System
Exhibit V-1 depicts a conceptual analytical system that characterizes an
economic profile of the chemical testing industry by segment and,
theoretically, in the aggregate. In addition to showing the industry's
conceptual supply and demand modules, the exhibit indicates the
relationship between the industry's laboratory capacity from which
its resources are drawn (stock concept) in order to generate current period
supply (flow concept). This supply function concept (quantity of services
offered at alternative price levels) can be reasonably expressed only in
relation to capacity constraints that are currently applicable.
The indicated capacity module can be defined for a specified time period,
t, although changes in capacity are possible within the "dynamic" testing
service industry. Such changes, whether positive or negative, are
conceptually represented by a growth module. Various economic forces will
influence management decisions to expand or contract laboratory capacities
and capabilities.
Major inputs into the growth module are the price and profit conditions
reflected by short-term, supply-demand interrelationships. Such
conditions, both in macroeconomic (industry) and microeconomic (firm)
terms, are conceptually depicted in Exhibit V-l as a price/profit response
module. Such an analytical module is generally required to assess the
dynamic aspects of the testing industry. (Static economic relationships
V-2
-------
Exii ib t V-l. i'roposec anaiyt ca system, c iem ea test ng :muscry stuciy ..j
Capacity
Module, t
Requirements
Resources
Stock
Growth *
Module, t
Demand
Module, t
Flow
Flow
Pri ce/Profit
Response
Module *
Capacity *
Module, t+1
J/ Components of the system to be applied to each major type of testing.
* These indicated modules are outside the scope of study, but they are essential elements of the overall
system when viewed as a dynamic vs. a static system.
-------
will be understood as a fixed period within a dynamic modeling framework;
hence, the analytical system depicted includes basic linkages required for
a dynamic, iterative analysis.)
Two other vital components in the proposed analytical system are: (1) the
resources component of the supply model that is concurrently linked to the
capacity and growth modules, and (2) the requirements component of the
demand module. An essential condition of the analysis is to express units
of testing supply and demand on a common basis and this appears to require
that supply-resources and demand-requirements components be specified in
comparable terms, e.g., personnel man-hours (by skill level), space,
equipment hours (by type), animals, etc. Through the use of testing
protocols or other estimating procedures, test demands must be converted
into these basic requirements. Supplies of such resources can then "flow"
from the capacity module. Generally, however, only those resources and
requirements that are most limited or constraining need to be incorporated
within the overall model.
A model design concept that expresses capacity, supply, and demand modules
in common "units" is critical. Such units are the resources provided by
suppliers of testing services and required by regulatory agencies to
satisfy their testing rules. With this design concept, analysts ascertain
whether sufficient resources are generally available to meet any specified
set of test demands.
In general terms, this model should incorporate the following conditions:
Condition 1. Available capacity, C, during a given period t, must be
greater than or equal to the supply, S, of testing
services performed. Both C and S are expressed as
functions of common resources R^, where k denotes all
applicable or key resources. That is,
ctist
where
Ct = ft (Rl* R2' 4 *
St = 9t ^Rl' R2' "" 'V
R.
0
Condition 2.
Realized demand, D, for testing services during a given
period, t, should equal supply, S, given Condition 1.
D is also expressed as a function of common resources,
R^. That is,
°t- st
where
3t ht (Rl' R21
R|, J • • •)
V-4
-------
Condition 3. Specified capacities, supplies, and demands from
alternate sources are to be aggregated (unless
"submarkets" are uniquely defined for which separate
analyses are then applicable). For example, C., S. ,
and are sets that will be aggregated as follows:
Ct = Clt + C2t + + Cit +
St = Slt + S2t +
+ Sit +
Dt = Dlt + D2t
+ Djt +
where
Ct and St components and S^, are matched sets,
and
D^. components D^, are distinct.
The above general conditions, which are detailed subsequently, must be
satisfied within an operational system. One known operational approach is
to specify a multi-equation model within a mathematical programming system.
In a block-matrix context, the following equation-condition system is
applicable:
Right
Hand
Vectors Side
C(X1) S(f2) D(X3) (b)
Capacity, C
Supply, S
C/S
Demand, D
S/D
A11
i
A22 !
i
A31
A32
i
I A
i 43
b4
A A
52 | 53
V-5
-------
where
(b^ = capacities)
(fc>2 = supplies)
(t>3 = excess capacity)
("5^ = demands)
= supp1y-demand=0)
A52X2+A53X3
= 0
The purpose of this equation system is to establish whether a "feasible"
(vs. optimal) capacity, supply and demand set of conditions can be met.
These capacity, supply and demand conditions determine whether the
specified demand can be supplied (regardless of price) from available
capacity. A subsequent equation system is needed to establish other
supply-demand conditions and economic relationships.
Further specifications of the proposed model are presented in Sections D,
E, and F. However, the supply and the demand modules of the overall model
are first described in greater detail to introduce additional factors that
should to be assessed.
The chemical testing industry is a service industry with a range of testing
capabilities that may be utilized with limited flexibility in the short
term. Specific toxicological tests generally require laboratory facilities
that provide space, specialized equipment, uniquely trained personnel and
other special resources (e.g., test animals and chemicals). To a degree,
the maximum available supply of testing services is dependent on the mix of
specific tests demanded because variable amounts of different key resources
may be required. The concept of determining the most limiting special
resource for any set of test demands can be employed to resolve this type
of conflict, i.e., the "supply" is defined in terms of the most likely
limiting resources during a given period of time, yet only one type will
generally be the constraining, or key, resource for a given period of
analysis.
Empirically, there are distinguishable supply sources of testing services:
(1) independent laboratories, (2) captive laboratories, (3) university
laboratories, (4) government laboratories, and (5) foreign laboratories.
An element of concern to the analysis is that each source is not uniformly
able to conduct specific chemical tests for commercial, private sector
products. For example, government laboratories may be restricted from
conducting product development-related testing. University laboratories
may provide only limited and variable testing services. Foreign
laboratories may be viewed as a competitive supply source or an auxiliary
source if "excess demand" for testing arises. (In general, foreign
laboratories' supply of resources are not assessed further in this study.)
B. Supply Module
V-6
-------
Each of these sources has distinctive capacity (resource availability) and
supply (resource use) characteristics. It is recommended that the capacity
and supply modules of the model reflect each source separately as well as
in the aggregate. In doing so, all sources' capacity and supply,
individually and collectively, should be specified in common resource
units.
Although each source's capacity and supply may be separately represented,
another element of concern is that no provision has been made to identify
from which supply source subsequent demands will be met. In other words,
only an aggregate supply-demand interface is anticipated without the
ability to uniquely link a given testing demand to a specific source of
supply, S,. Via network analysis principles, one can establish node-link
conditions to assure that certain supply sources are utilized, if
applicable. However, further study is required to determine whether such
specifications are needed.
Another issue to resolve is that resource capacities from alternate sources
may not be fully additive if they are not transferable or mobile. For
example, excess personnel at one source (e.g., captive laboratory) may not
be utilizable at another source (e.g. independent laboratory) should this
resource be limiting at the latter source. Some physical resources, such
as laboratory space, are not mobile; the mobility assumption would be very
limiting in this case. However, unless otherwise developed, testing
resources are presumed to be transferable within the system.
Aggregate toxicological testing demand can also be shown to stem from a
variety of sources including both regulatory and nonregulatory testing.
Within the regulatory category, the primary basis for organizing demand
requirements is by Congressional or Executive agency act or by other
regulatory authority. Thereafter, estimates must be made of the types of
testing required and the specific amounts of testing to be conducted.
For example, the following Agencies and Acts provide a basis for
categorizing testing demands, each of which can be modeled as a separate
demand source:
C. Demand Module
Agency
Act
EPA
• TSCA
• FIFRA
• Other
FDA
• FFDCA
t FHSA
OSHA
CPSC
• OSHA
• CPSA
USDA
• FAWA
V-7
-------
Within each agency or act category, the types of testing required must be
thoroughly assessed and test demands estimated (see Chapter IV).
Furthermore, such demands need to be broken down into specific resource
requirements within the demand module. Generally, the following hierarchy
of testing requirements must be determined:
1. Chemical(s) to be tested
2. Specific tests (acute-subchronic-chronic)
3. Protocols (or estimated protocols)
4. Resource requirements (all modeled resources)
The latter resource requirements for all chemical substances and tests will
represent the testing demand for each major source (agency or act).
Exhibits IV-25 and IV-26 sunmarize the total number of tests for three
sources--TSCA, FIFRA, FFDCA and the resources required for specified tests
and protocols. These data, while preliminary, form a basis for modeling
chemical testing demand.
The sum of all such regulatory demands (sum of all resource requirements)
will represent the aggregate regulatory demand. Nonregulatory demands by
both government and the private sector must also be determined and added to
the regulatory requirements to determine total testing demand.
Nonregulatory testing demand is not well documented on an industry-wide
basis; however, much of the previously "voluntary" toxicological testing
may now be mandatory. Hence, the remaining nonregulatory testing may
be comparatively minor. Even so, more effort is required to ascertain the
sources and levels of testing (and the associated resource requirements) of
nonregulatory demand. A component of this demand may be foreign testing
demand that utilizes U.S. testing services.
As briefly indicated, all testing demands ultimately must be expressed in
terms of their resource requirements. This will permit assessing the
supply-demand resource balances and the utilization analysis of available
capacities of resources from all sources.
An unresolved issue is the timing of testing demands and the associated
resource requirements during a given period of analysis, e.g., year.
Short-term testing requirements can be aggregated directly; however,
long-term testing requirements must be allocated among the periods impacted
with carry-over provisions for resource requirements that affect subsequent
periods. Thus, "carry-in" requirements should also be assessed as well as
any new testing demands.
D. An Accounting Subsystem
An accounting subsystem within the overall model is proposed to provide
built-in capabilities for tracking resource-specific components of each of
the analytical system's modules. As previously described, the capacity (C)
and supply (S) modules are both expected to be source-dependent
V-8
-------
(independent laboratories, captive laboratories, etc.) as well as
resource-specific. The demand (D) module is also source-dependent (TSCA,
FIFRA, etc.) and resource-specific.
The purposes of an accounting subsystem include establishing
resource-specific capacities of all supplying sources, simulating the flow
of resources from the capacity module into the supply module, estimating
resource-specific requirements by all sources of testing demand in the
demand module, and equating resource-specific demand with supply subject to
resource availabilities. In addition, these general accounting
requirements will be subject to concurrent economic subsystem conditions
which are described in Section E (although many of the proposed accounting
features of the overall model are largely independent of subsequent
economic specifications and constraints).
A more thorough specification of the capacity, supply and demand modules'
variables and relationships follow. In particular, the accounting-type
requirements of the overall model are shown.
Capacity, C, is characterized as the set (omitting subscript, t, for time
which is implicit):
C - {Cj j ^2' ***' ^•j' •*•'
where
C = total capacity
C. = capacity of source i for all applicable i
also,
Ci = VRir Ri2' ' Rik'
where
R.^ = resource k from source i for all applicable k
f.. = functional relationship, general.
Toxicology laboratories comprising a given source i may alter their
available resource levels under varying economic conditions. However, a
static, beginning-of-the-period inventory-type measure of capacity is
proposed, so that, also:
S s ^ii» Ri2' Rik' "'1
where
C". = fixed, resource-specif ic capacity of source i for all
applicable i
V-9
-------
R., = the sum of all source i laboratories' available resource k (at
1 the beginning of period t).
For this reason, capacity is said to be a stock concept (although the
proposed growth module in Exhibit V-l allows additions or deletions to be
made to capacity). Also, capacity is a multi-variable concept because any
number of resources, k, may be included, As noted, however, the major
concern is to model critical or key resources, any one of which may be the
constraining ("capacity-limiting") factor under alternate demand (or
resource mix) conditions.
Another description of capacity, C, in this study's context, is that the
resource values, R-^, represent the maximum values available from all
applicable laboratories for each source i. (These are fixed values for a
given period of analysis, t). All sources realized capacity may be further
aggregated as follows:
Cr = llRn, ZRi2, ..., sl?ik, ...]
where
Cr = realized total capacity for all sources i
zR., = sum of all source i's resource capacities for all applicable
i resources, k.
Supply, S, has general characteristics similar to capacity, C. However,
the supply of toxicological services is operationally quite distinct.
Supply, S, is also characterized as a set:
S - (S^, s2j ...» s¦, ...}
where
S = total supply
S. = supply of source i for all applicable i
1 (Note: and S. are matched components for source i)
Also,
Si = MRil' Ri2> Rik'
where
R., = resource k from source i for all applicable k
1 K
g.. = functional relationship, general.
V-10
-------
The function, , is conceptually complex and it represents the actual
utilization of resources for conducting toxicological tests during a given
period. This function does not explain how the supply is to be determined,
rather it simply denotes that the supply of toxicological testing services
consists of a collection of key resources from each source i. Differing
combinations of resources may be supplied from each source (although no
procedure is proposed herein to estimate each source's realized supply).
An important accounting property, however, is that the aggregate supply, S,
is presumed to be the sum of all utilized resources, k, across all sources
i. In general notation the aggregate supply, S, is:
S = g(ss.)
= g[2gi(Rn, Ri2, Rik, ...)]
where
ES.J = sum of all S- (unspecified summation procedure)
g = functional relationship, general.
This general notation can be made more specific if there exists a unique
"solution". For example, if supply equals demand during a given period,
then a point on the general supply function, g, implicitly exists. Also,
specific points on each source's supply function, g., exists. Thus, for
such a case, the realized supply, S., can be defined in terms of the
resources actually utilized. The aggregate realized supply, across all
sources i, is defined as follows:
S = SR^j •••» •••]
where
Sr = realized supply (a specific value of the g supply function)
ZR., = sum of resources, k, utilized by all sources, i.
i 1K
r r
This supply estimate, S , is in the same form as the capacity estimate, C ,
above. Hence, the model condition that capacity be greater than or equal
to supply can be assessed on a resource-specific basis.
The accounting requirements of the demand module are similar to the supply
module in the aggregate because realized demand (resources required) must
equal realized supply (resources provided) in "equilibrium"—an accounting
condition. This condition will apply for each of the modeled resources.
V-ll
-------
Testing demand in economic terms is naturally expressed as a function of
the tests that will be conducted on various chemicals under differing
economic conditions. However, the following resource-specific demand
equations are presented from an accounting subsystem perspective. These
specifications, or definitions, are consistent with the economic subsystem
although the economic rationale for them is indirect as is explained in the
following pages of this section.
Demand, D, is the set:
D = 1D|, D£, ..., Dj> •••}
where
D = total demand
D; = demand from source j for all applicable j.
J
Also,
°j
= hj(Rj3.» Rj2' "•» Rjk'
where
= resource k required by demand source j for all applicable k
h. = functional relationship, general.
' jRjk'
V-12
-------
where
D = realized demand, (a specific value of the h demand function)
2R.. = sum of all source j's resource k requirements for all
j J applicable k
In summary, these definitions of capacity, supply and demand will form an
accounting subsystem framework where, ultimately, realized supply, Sr, will
be equated with realized demand, Dr, subject to the condition that supply
does not exceed the specified capacity, Cr, of any key resource.
Sr = Dr (Equilibrium condition, applicable for all specified
resources)
such that
Sr <_ Cr (Capacity constraint)
A more elaborate specification of the demand resource requirements is
needed in the model to track the toxicological testing demand process which
is, generally, as follows:
Chemical Tests -»¦ Protocols + Resource Requirements
As described in Chapter IV, a series of tests will usually be conducted for
a given chemical—perhaps both regulatory and nonregulatory tests depending
upon corporate and regulatory toxicological testing policies. Although
specified tests may not be conducted in precisely the same manner for
different chemicals, testing protocols are being developed or may be
estimated for representative cases. Such estimated protocols are essential
for simulating the demand, i.e., the resource requirements for various
tests. Again, only major or critical resources such as pathologists,
toxicologists, specified equipment, space, etc. may need to be simulated.
Non-major resources such as laboratory supplies are presumed to be
available in the quantities required and need not be (yet could be)
embedded in the accounting subsystem.
A demand module accounting procedure is proposed as follows. Define a set
of all possible tests, T, that may be used to assess the set of all
expected chemical materials, M. (Either set may be expanded as required).
That is, let
{T1' T2' T3' Tm'
- , ..., , ... /
T
and
M
V-13
-------
where
= set of all tests possible
= specific test m of set T
M = set of all materials expected
1 n,
m
M = specific material n of set M.
Each test, Tm> is to have a specified and unique protocol, P , which
minimally defines the level (see Exhibit IV-26) of all potentially critical
resources that are required to perform the test. These resource
requirements are denoted as follows:
Pm = ^lm1 ^2m' ' *km' '' ^
where
Pm = protocol or resources required for test Tm
= estimated amount of resource k required to perform protocol P .
Because each test, T^, has a unique protocol, P , only the numbers of each
test demanded by each source j is necessary to derive the associated and
required toxicological testing resources. In particular, for each chemical
material, M^, all applicable tests must be determined by demand source, D^.
The number of each test required is summed for all chemical materials from
that demand source. For example, the resource requirements of D. can be
J
indirectly expressed as the ordered set, N, of the number of each test
required (or estimated):
(Nji, N-2, , N. , ...)
"j v ji' ' jnr
where
N- = estimated total number of tests, or testing demand, from
^ demand source j
N. = the number of test T required by demand source j.
jiti m n J
As indicated above, since each test, T , has a unique protocol, P , this
total demand for source can now be converted into specific resource
requirements. Further, the aggregate demand, D, from all sources can be
derived by summing their tests (2N. ) and their associated resource
requirements. j ^
V-14
-------
A general procedure for incorporating these more detailed demand level
resource requirements in the accounting subsystem of the model is outlined
further in Section F. At this general development stage, the primary focus
is on aggregate capacity, supply and demand conditions that must be
satisfied according to economic expectations.
The following section discusses the economic subsystem of the overall
model, including linkages to the accounting subsystem which will ensure
that the resource specific conditions defined above will be satisfied along
with subsequent economic conditions and objectives.
E. An Economic Subsystem
The preceding accounting subsystem provides one method for aggregating
chemical testing resource units that are either supplied or demanded. This
aggregation process can be completed for numerous supply sources (types of
laboratories) and demand sources (agencies, acts and other). However, such
an accounting procedure does not recogni-ze the extremely variable economic
conditions that affect both supply formation and demand generation
processes. Ultimately, an economic subsystem is needed to simulate supply
relationships by source and in the aggregate, and to simulate demand
relationships by source and in the aggregate. As presented in Exhibit V-l,
above, dynamic supply (capacity) and demand conditions are also relevant
and can be introduced via the growth and the price-profit response modules
of the proposed analytical system. Initially, however, static economic
relationships should be developed in more detail.
Although simplified, theoretical toxicological testing supply, capacity and
demand relationships may be depicted as shown in Exhibit V-2. For a given
period, t, the supply, S^, is shown to increase as a function of price up
to a maximum quantity (capacity). Demand, 0^, is also a function of price
but with a negative slope depicting higher quantities of testing with lower
prices. A short-run equilibrium price-quantity point, (Pq, Qq), is shown
where the realized supply is also less than the capacity—a necessary
condition.
A problem arises in interpreting "quantity" in this framework because
various resources used in differing combinations for a variety of chemicals
and tests are implied by the demand for (and supply of) toxicological
tests. In practice, one can explicitly define all of the resources
required to achieve the quantity, Qq, but each alternate level Q might
represent a different combination of resources. No problem exists in
characterizing resource requirements, per se, so long as no limiting
resource exists. Even then, the most limiting resource will determine the
capacity to supply testing services, i.e., Qc in Exhibit V-2.
The aggregate supply function depicted in Exhibit V-2 stems from alternate
sources (e.g., independent, captive). Conceptually, the supply function
for each source should first be estimated and then these functions summed
V-15
-------
Exhibit V-2. Hypothetical chemical testing industry supply
(and capacity) and demand functions for a given period, t
Price
P
0
Quanti ty
(Capacity)
V—16
-------
to simulate the aggregate chemical testing supply (and capacity). Also,
each source's supply is theoretically the sum of the marginal cost curves
for all firms in the industry segment. In practice, analysts typically
evaluate only representative types and sizes of firms and then estimate
intermediate and aggregate relationships from these cases. Major
additional research is needed, however, to estimate the aggregate chemical
testing industry supply by this method, i.e., from the micro (firm)-level
to the aggregate level.
In the absence of such detailed supply estimates by source, only a grossly
simplified aggregate supply estimate, such as portrayed in Exhibit V-2, is
possible. For purposes of this conceptual discussion, the ability to
estimate an aggregate supply (and capacity) function is presumed to exist.
The aggregate demand function depicted in Exhibit V-2 also represents
multiple sources (e.g., agency, act and other). In theory, each source's
demand function should be separately estimated and then all demand
functions summed to simulate the aggregate-demand function as shown. This
study partially estimated the quantity of testing required by selected
agencies and acts as described in Chapter IV. The estimated number of
tests required were not functionally related to the prospective prices of
tests, however, and much additional research is needed to establish
functional relationships for all sources of demand. Toxicological testing
demand is derived from the prospective demand for the chemical products
being developed as well as the cost of testing. Hence, this demand
estimation process is complex. Again, in order to continue this conceptual
discussion, the ability to estimate an aggregate demand function is
presumed to exist.
At this stage, no attempt is made to characterize the mix of tests or
resources that might be reflected by one-unit of the "quantity" of testing
demand (and supply). However, given some unit of measurement (discussed
further below), both the demand for and the supply of toxicological testing
services should be defined as step-functions in a multi-equation model
system where the economic subsystem can then be linked to the previous
accounting subsystem. For example, the demand function could be expressed
in terms of equal increments of demand (quantity of services) that are
sought, but at consistently lower prices. The supply function could be
expressed in terms of equal increments of supply (quantity of services)
that are available only at increasingly higher prices (and until a
constraining resource is encountered).
On the demand side, an initial procedure might be to simulate the
completion of all testing requirements that are independently forecast by
source of demand. Tests could be performed at "unit prices" (reflecting
near minimum average total costs per test for representative laboratories
or bid prices for tests per the protocol for each test. Implicitly, this
demand function would be perfectly inelastic. If all tests can be feasibly
conducted (without any resource capacity constraints), market prices may be
near the estimated "unit prices". However, should resource constraints
V-17
-------
appear via the simulation (and excess demand appears in satisfying all
accounting conditions) then adjustments in the supply and demand function
should be made to forecast an equilibrium price and quantity.
The supply and demand functions should be estimated from both theoretical
and empirical information. Previous market behavior data can aid in
estimating whether wide price-cost margins arise during periods of
shortages of toxicological capacity or whether cost subsidization occurs
during periods of apparent surplus capacity. Also, microeconomic analysis
of model firms can be conducted to estimate likely firm behavior based on
economic theory. Numerous qualitative as well as quantitative factors
influence firm decisions and aggregate market behavior.
In sum, these economic considerations should augment the accounting
subsystem conditions as described in Section D. Procedures are needed to
incorporate into the overall model those applicable supply response and
demand behavior conditions while maintaining the previously described
accounting subsystem conditions.
The above general analytical approach can be readily implemented using
available mathematical programming and network analysis techniques.
However, additional theoretical and empirical research is necessary before
reasonably accurate supply and demand prices can be associated with the
proposed equal increments of the "quantity of services".
Two additional model development concepts are critical: (1) specifying an
objective function for predicting supply-demand behavior, and (2)
simulating likely behavior in the chemical testing industry over a limited
price-quantity range. First, to implement the model, some type of decision
algorithm or objective function is required to predict behavioral
responses. For example, in Exhibit V-2, one can readily infer that the
point (Pn, Qn) is an equilibrium point where demanders' "willingness to
pay" equals suppliers' prices, and the suppliers' capacity is not exceeded.
But such functions, are unknown, a priori. This same equilibrium point
might be simulated in a different manner, however. One approach is to
specify an objective function that "adds" incremental units of testing
demand (quantity of services), at minimum cost, so long as the demand price
is greater than or equal to the supply price—and the supply capacity is
not exceeded. A mathematical programming system can readily simulate such
a solution.
The second concept involves a concentration of research effort within a
pertinent range around the expected equilibrium point in the simulations.
Again referring to Exhibit V-2, analysts will seldom be highly interested
in supply or demand levels and prices that are very distant from the
equilibrium values. This does not preclude the assessment of a wide range
of quantities or prices that may be caused by major shifts in supply
demand. Rather, the analysis should generally concentrate on "finding"
initial equilibrium values and then assessing likely deviations therefrom
due to changes in economic conditions.
V-18
-------
An earlier suggestion for estimating an initial solution (after which a
range of supply-demand price and quantity values might be assessed) was to
presume the demand function is perfectly inelastic (vertical in Exhibit
V-2). This would facilitate determining whether projected demands could be
met with available resources (less than or equal to capacity). In such a
simulation, a step-function supply relationship, with rising costs for
additional increments of supply, could be used. The primary purpose for
such a simulation would be to find an approximate equilibrium value and
establish a range of prices and quantities over which more accurately
specified demand and supply step-functions could be modeled and assessed.
Since various implementation approaches are possible, no exact procedure is
proposed. However, the following economic subsystem conditions and
constraints are essential:
1. Simulate a supply function. A step-function approach is proposed
where increments of supply are "available" at increasingly higher
prices (up to the capacity constraint as defined in the
accounting subsystem). Ideally, the aggregate supply will be
estimated from more detailed analysis of each supply source.
2. Simulate a demand function. Aggregate testing demand from all
sources might also be simulated using a step-function approach.
In this case, increments of demand are added but at consistently
lower prices (willingness to pay). Characteristics of each
demand source (market) should be known in developing such an
aggregate demand.
3. Specify an objective function (decision algorithm). A common
objective function in a mathematical programming system is to
satisfy requirements (demand) at minimum cost (price) while also
meeting other conditions/constraints. The minimum cost of
incremental resources is reflected in the supply function. In
this model, the proposed objective function is to maximize the
sum of the differences between the demand price, P^, and the
supply cost, Cs, over all levels of testing demand and supply
(i.e. maximize the sum of consumer's and producer's surplus).
4. Other conditions. The suggested step-function approach (both
supply and demand) requires that the last increment of supply be
added so long as the "demand price" (associated with a
corresponding increment of demand) is greater than or equal to
the "supply price". This economic condition must be incorporated
in the model. An illustration of this type of constraint is
included in Section F.
These economic subsystem constraints and conditions are suggested to apply
in the aggregate, i.e., for all supply sources and for all demand sources.
Unique supply and demand functions for each applicable source are desired
and they can be summed to derive aggregate relationships. Also, model
linkages among specific supply and demand sources can be developed if
applicable. These conditions are not illustrated, however.
V-19
-------
F. General Implementation Requirements
While this study's scope of work does not include implementing the proposed
conceptual model, several methodological steps are suggested below. As
described above, the conceptual model development presumes that source-
dependent demands and supplies can be estimated and aggregated. Such
estimates will be difficult to obtain. A further complication is that some
common unit of testing service ("quantity") is required for each source
separately and in the aggregate. This requirement is generally too strict
in an overall sense, but if a "near-equilibrium" solution could be
simulated, then the same "mix of resources" could serve as a proxy unit of
supply and demand, e.g., a unit might be one veterinary pathologist plus
the average amount of'space, equipment, animals, etc. associated with this
resource. Step-function changes in supply and demand could be simulated
thereafter. Prospective shifts in demand induced by TSCA might then be
characterized in this unit of analysis and evaluated.
Another basic approach, after simulating a baseline, short-term equilibrium
is to forecast TSCA-related incremental demand and to determine whether
such testing demand (required resources via protocols) can be supplied from
the remaining resource capacities, regardless of their supply source. This
approach would focus on the accounting subsystem conditions, however, and
not reflect probable "price" increases because of shifts along the
industry's supply function.
This latter approach is similar to presuming that the aggregate supply
function is perfectly elastic (up to the first constraining resource level)
and the demand function is perfectly inelastic as depicted in Exhibit V-3.
In this graph an assumed initial equilibrium "price" and "quantity" level,
(p0*, Qq*)> is defined, but no further price effect will occur until
the capacity of the most limiting resource is reached. Then, price is
indeterminant. In contrast, the with-TSCA demand shift, D^, is expected to
result in a new equilibrium higher price, Pi, and quantity, Qi, between Qn*
and Qj*, as depicted.
The conditions set-forth in the accounting subsystem section above are
effectively represented by the solid-line demand and supply functions in
Exhibit V-3, i.e., the perfectly elastic supply and the perfectly inelastic
demand assumptions.
The primary goal of the economic subsystem is to more closely reflect
actual supply-demand conditions either in the aggregate or by source of
supply and demand. This goal should be accomplished while maintaining the
accounting subsystem conditions. Hence, at least some degree of
improvement in estimating price levels and quantity levels of testing is
expected.
An illustration of the previously described accounting and economic
subsystems' conditions within a mathematical programming framework is shown
in Exhibit V-4. This illustration is simplified by limiting the number of
V-20
-------
Exhibit V-3. Potential chemical testing industry supply and demand functions,
accounting vs. economic concepts
*6
••si'
°0
—
/ *D1(with TSCA)
l
l
I
1
1
I
1
S0
•
I
I
1
1
I
l
1 "D.
I
1
1
t
1
1
1
1
1 1
Q0* Qj_' Qj* Qc Quantity
(Capacity)
[Note: Sj' and D^' represent theoretically expected supply and demand
functions—see Exhibit V-2. Expected equilibrium equals (, Q^) versus
(P0*. Q]*) w1'i:'1 incremental TSCA demand to D^.]
V-21
-------
Exhibit V-4. Preliminary matrix specification of a Mathematical programing i*odel of the chemical testing industry
Activity
cr
Capacity
C2 C
ir
It
01
Demand
i>? n
Resources required
Tr_a_.-T_
Condition
irtipacHy
CI R1
B2
C2 Rl
R2
C R1
R2
2. Supply"
R1 R? Rl R2 Rl R2 R1 R2 Rl R2 R1 R2 T1 T2 Tl T2 T1 T2 R1 R2 Rl R2 Rl R2
Excess
demand Supply Demand
aSlaST" aBT~aIFZ dl- Right Hand
Rl R2 (cl) (r.2) (pi) (p2) tion Side
Step Functions 1/
Supply Demand Con-
1 -1
-1
1
51
52
1
Rl
R2
Rl
R2
S Rl
R2
3. CapacTIy/Stipply
C/S Rl
_R2
4. DewanJ
01 T1
12
D2 T1
T2
D Tl
12
5. Resources (lest Protocolsj 27
-1
-1
-1
-1
-1 -1
Tl
12
T
Rl
R2
Rl
R2
Rl
R2
IS!
-l
-1
-1
l
-I -l
-l -l
(1) 3/
- Rll
« Rl2
= R21
- J?22
= 0
« 0
> 0
> 0
> 0
> 0
st 0
- 0
> 0
Nil
N12
N21
N22
0
0
- 0
= 0
« 0
- 0
= 0
= 0
6. Suppiy/Demand (Equality)
S/0 Rl
R2
1
1
-1
-1
i
II 1
© o
1
i ;
7. Step functions
S(R1) S (Supply)
I
-1 -1
- 0
AS!
1
< AS1
aS2
1
< aS2
U(lil) 0 (Demand)
1
-1-1 - 0
Al)l
1 < AD1
AD2
1 < AD2
17 The supply function costs, c , per Interval, ASs and the demand function prices, pd, per Interval, may be used Tn the model's objective
function to maximize the sum of the differences between tlie demand prices and the supply costs, i.e., continue testing, subject to model
conditions so long as f>() > c , i.e. max I (pj
but a specified mix of resources could be modeled.
c;) over all intervals. Ihese functions are expressed here in terms of a single resource, R^
2/ lest protocals are to be expressed in units of each potentially constraining resource. Only two general resources, R, and R,,, are shown for
illustration.
y Excess demand is a slack activity always > 0 that would enter the solution only if the capacity of one or more resources was exceeded. This
specification allows the problem to be soTved but the solution Is Invalid as will be known by the Excess Demand column solution of the model.
Ihe amount of excess demand far each resource will be denoted.
-------
supply and demand sources to two each. Also, only two tests with two
resources are incorporated within the model. Actual implementation of such
a system could be readily expanded to simulate numerous sources, tests and
resources, as applicable.
As a guide to interpreting the activities and conditions of the matrix
formulation of the model, the following definitions will apply (based on
preceding descriptions of variables):
Capacity
• C = {Cj, c2>
where
C = total capacity (maximum available resources) from all
applicable sources i
C. = capacity of source i, i = 1, 2.
• ^or a sPecific Period of time, t.)
where
C. = specified resource capacities for source i (for all
applicable resources k)
"R.. = maximum available amount of resource k from source i,
1K k = 1, 2.
Supply
• S (S^, S2>
where
S = total supply of testing resources
S.j = supply of testing resources from source i, i = 1, 2.
• Sr = [SR^, ZR-^] (To 136 determined with the model)
where
Sr = realized supply of testing resources for all applicable
sources i, i = 1, 2.
£R
ik = sum of each resource k utilized by all sources i,
k = 1, 2.
V-23
-------
Demand
• D = {D,, D2>
where
D = total demand for testing resources
D. = demand for testing resources from source j, j = 1, 2.
yt
• D = [ z R j j, z R j 2 li (To be determined with the model)
where
Dr = realized demand for testing resources for all applicable
sources j, j = 1, 2
2R-, = sum of each resource k required by each demand source j,
j JK k = 1, 2.
Tests (and Protocols)
• t = av t2>
where
T = the set of all possible tests that may be demanded by all
demand sources j, j = 1, 2.
Tm = test m of the set, m = 1, 2.
• may be conducted and specified any number of times on any
applicable chemical material by all applicable demand sources.
However, a unique and specified protocol, P , will determine the
amount of resources required. That is, P^ = [R-^m> where
^km ls amount 0^ resource k required to conduct the test, T .
In particular, for this example, h [a^, b^] and P^ = [agj b^].
• Nj = (Nj j, N.g) (To be input into the model)
where
N. = estimated total number of tests, or testing demand, from
J all applicable demand sources j, j = 1, 2.
N. = the number of test T required by demand source j,
m = 1, 2. m
V-24
-------
Resources
• Resource requirements to meet a given demand by source (and in
the aggregate) can be calculated with the preceding variables.
For example, for demand source j, the total resource requirements
are estimated as follows:
(1) Test I: Njj x R^ = R^ requirement
Njl x R21 = Rj2 re<^u"' reraent
(2) Test 2: Nj2 x R12 = Rjl recluirement
x R^2 = Rj2 re
-------
Given these definitions, the following accounting and economic subsystem
conditions are embedded in the proposed model.
1. Capacity—the maximum available resources from each source are
specified as right hand side (RHS) values, i.e., R.,. Also,
1 K
these resources are accumulated for all sources, i.e.,
ER.,, for each k.
i 1K
2. Supply—each source's supply of resources must be greater than or
equal to zero (RHS condition). These resources are aggregated,
i.e., sR^, for each k. Two linkages are also involved:
capacity-supply, and supply-demand equality as described below.
3. Capacity-Suppl,y--the condition in which capacity is greater than
or equal to the supply (of each resource) is specified, i.e.,
4. Demand—demand is characterized as the number, N-m, of each test,
T , that is projected to be required by each demand source j.
These requirements are specified as RHS values. Also, the total
number of each test required by all demand sources is
accumulated. (A less than or equal RHS condition denotes that
all tests may not be conducted subject to the objective
function economic criteria discussed below.)
5. Resources (Test Protocols)--each test has a specific amount of
each major resource that is required to complete the test per a
test protocol. For example, P^ = [a^, b^] and P2 = [a^, b2J.
These resource coefficients are specified for each test as column
vectors in Exhibit V-4. The amount of each resource required for
all tests is aggregated within the system, e.g., a, and a2 relate
to R^ and b^ and b2 relate to R2.
6. Supply-Demand Equality—a necessary accounting condition is that
supply equal demand, i.e., all resources required (demanded) must
be obtained from the capacity of resources available (supplied).
This condition can be met unless the capacity of any one resource
is exceeded, i.e., excess demand. A mathematical programming
convention is to allow for this occurrence by introducing a slack
activity which denotes a "problem", but which allows the
supply-demand equality condition to be technically satisfied.
7. Excess Demand—as indicated in 6, slack activities for each
resource, Rj and R2, are incorporated in the model. Should
either of these column vectors, or both, enter the final
programming solution, then an excess demand for the resource(s)
exist. The amount of excess demand will be determined.
V-26
-------
8. Step Functions—both the supply and the demand estimates can be
programmed as incremental, step functions. As defined above,
Supply S = (&S^ + AS^) and Demand D = (aD^ + AD^). Also, supply
costs, c , and demand prices, p^, are specified for each
increment. The amounts of testing supply and demand (each
expressed in terms of R^ only) are specified as RHS values and
conditioned to be less than or equal to the specified amounts.
This condition does not require that all increments be supplied
or demanded (subject to the objective function of the problem).
9. Objective Function—an ultimate goal of this type of model is to
simulate industry behavior. While much further development is
required, an initial simulation, using the objective function of
a mathematical programming system, is to maximize the sum (p^ -
c ) over all increments of demand and supply. In this situation,
if the supply cost, c$, increases (or the demand price, p^,
decreases) and is greater than p^, then all tests would not be
conducted because of economic conditions. The solution obtained
would, in economic terms, maximize the sum of consumer's and
producer's surplus.
A much more elaborate price-profit response module is preferred
when simulating industry behavior. However, the type of model
proposed can be effective in characterizing and assessing
aggregate industry behavior.
G. Research Implications
The implementation of a comprehensive supply-demand model of the
toxicological testing industry, will require substantially more industry
data than are presently available. More detailed supply data (resources)
are required to implement the proposed model and an extension of the
toxicology laboratory survey (see Chapter III) is recommended as a
practical means for estimating resource capacities, testing capabilities,
and related economic characteristics of the toxicological testing industry.
More detailed demand data (chemicals, tests and their resource
requirements) are also required to implement the proposed model. As
discussed earlier in this report (see Chapter IV), anticipated testing
demands are much more difficult to estimate. Regulatory agencies can
require that certain types of chemicals be tested for their toxicological
effects, but the number of chemicals that will actually be introduced by
chemical developers is generally unknown. Simple trend extrapolations of
past testing (concerning the number of chemicals introduced and the profile
of tests required or actually conducted) are perhaps useful, but not
explanatory. Overall, a much greater research effort is necessary to
improve toxicological testing demand estimates and to incorporate such
estimates in the proposed model.
V-27
-------
More specific implications of this research are discussed below.
1. Supply and Capacity
Two sources of testing supply provide the majority of the capacity for
commercial toxicological testing—independent laboratories and captive
(company) laboratories. These sources need to be better documented in
terms of their toxicological testing capabilities and capacities, i.e., key
resources. This study's laboratory survey (see Appendix B) provided some
of the needed information but more detailed data are preferred.
Data obtained via the survey allow analysts to broadly estimate the total
industry testing capacity, the current utilization of that capacity
for present regulatory and non-regulatory demands, and, thus, the potential
capacity available for use in testing chemicals under Section 4 of TSCA.
The information obtained from the survey also provides for a general
economic assessment of the present industry. Problems remain, however, in
in translating the information into a resource-specific form useful for the
model. These data are useful in assessing the industry for a particular
point in time, but changes occurring over the short and longer term need to
be estimated if the model is to be an accurate tool for regulatory
officials. The survey information is most helpful in developing the
accounting subsystem of the model and in determinating the industry's
present supply (and capacity) in terms of testing capabilities and
resources. A more extensive survey of the industry's toxicology
laboratories could provide detailed supply and capacity data for the model.
Two other chemical testing sources are university and government
laboratories. These supply sources provide limited commercial testing
services, which should be modeled, but more importantly, they compete for
personnel and other key resources. Hence, for both reasons, the capacities
and capabilities of these sources need further study. Foreign
laboratories, as well, are potential suppliers of chemical testing
services; their potential supply source capability and capacity should be
assessed in greater detail.
2. Demand
A major effort was made in this study to estimate both regulatory and
nonregulatory toxicological testing demand as discussed in Chapter IV.
Many assumptions and estimates were necessary to forecast expected testing
levels (chemicals, tests, protocols, and resources). Improved forecasts
are needed and possible, but only with much additional research.
Regulatory agencies such as FDA and EPA have extensive data bases that
might be analyzed further to estimate testing demands.
Chemical developers (companies) conduct many toxicological tests either for
research (before regulatory testing) or for nonregulatory reasons. These
testing demands were not well documented with available data, and a better
analysis of such testing demands is needed. The timing of research and
V-28
-------
nonregulatory testing is apparently affected substantially by competing
regulatory requirements. This type of industry behavior needs to be better
understood. Modeling efforts, especially the dynamic aspects of
toxicological testing, should be tailored accordingly to better estimate
continuing or multi-period testing demands for each period of analysis.
Uncertainties of the timing of regulations and their protocols also
contribute to irregular demand levels.
3. Prices and Other Factors
Prices for toxicological tests are a difficult to assess. Wide variability
exists in quoted prices for similar tests. Part of this variability stems
from differences in test protocols, but quality and other factors (e.g.,
ability to provide legal representation) apparently affect prices markedly.
If traditional supply-demand economic models are to be used successfully,
further studies need to be made of price-profit mechanisms within the
industry.
The toxicological testing segment of the chemical testing industry has
experienced rapid changes in the recent past, e.g., 1976-1981. Both
independent and captive laboratories have been built and existing
facilities have been expanded. In general, economic conditions in the
industry have been unstable—largely because of uncertainties surrounding
regulatory programs, including TSCA, FIFRA, and FFDCA. While these recent
changes complicate economic analyses--with or without a model—they also
exemplify the need to develop a better understanding of the chemical
testing industry.
In conclusion, this study represents an initial effort to establish an
economic profile of the toxicological testing segment of the chemical
testing industry. The supply and demand characteristics of the industry
are documented to the extent possible based upon secondary data and this
study's relatively brief telephone survey of toxicology laboratories.
Additionally, the study developed a supply-demand model capable of being
implemented. Many research tasks remain before a comprehensive economic
profile is established and an economic supply-demand model of the industry
can be implemented, but these tasks are realistically attainable. Provided
that a model is not implemented in the near future, a survey of toxicology
laboratories, like the one conducted successfully for this study, might be
repeated periodically. Such a survey documents the status of this dynamic
industry and periodic surveys would disclose important economic
characteristics regarding the availability and adequacy of toxicological
testing services in the U.S.
V-29
-------
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January 23, 1980a, page 38.
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Abelson, Philip H. "Regulation of the Chemical Industry," Science, Volume
202, November 3, 1978, page 473.
American Association for Accreditation of Laboratory Animal Care Report,
Volume 8, December 31, 1979, pages 5-6.
American College of Veterinary Pathologists (ACVP), 1981 information
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Ballard, G., Office of Pesticide Programs, EPA. Personal communication,
1980.
Bureau of Drugs, Food and Drug Administration. "Guidelines for Preclinical
Toxicity Testing of Investigational Drugs for Human Use."
VI-1
-------
Burnham, W. Office of Pesticide Programs, EPA. Personal communication,
1980.
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d. February 1, p. 1655 d. January 23, p. 1324
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f. July 11 f. January 30, p. 1389
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i. October 3, p. 842
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k. November 21, p. 1083
Chemical Week, McGraw Hill Book Company, 1221 Avenue of the Americas, New
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Chemistry and Industry, April 15, 1978, pages 256-259.
Code of Federal Regulations, Title 21, Parts 130, 312, 570.
Council for Agricultural Science and Technology, "Impact of Government
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Dagani, R. "Mutagenicity Testing Laboratories a Growing Business,"
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Department of Health and Human Services (HHS), Public Health Service,
National Survey of Laboratory Animal Facilities and Resources, FY 1978,
1980, page 26.
Department of Health, Education and Welfare (HEW), Review of Current PHEW
Research Related to Toxicology, Washington, D.C., 1979, pages 6, 9-11.
DeWitt, K. "A Company that Thrives on Regulation," New York Times,
December 7, 1980, pages F-9.
Domingaez, George S. "What TOSCA Means for the CP I." Chemical Engineering,
Volume 85, April 24, 1978, pages 76-82.
Drug Amendments, U.S. Code, Vol. 21 (1962).
VI-2
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Enviro Control, Inc., Cost Analysis Methodology and Protocol Estimates:
TSCA Health Standards and FIFRA Guide!ines, April, 1980.
Environmental Protection Agency (EPA), "Proposed Guidelines for Registering
Pesticides in the United States, Subpart F, Hazard Evaluation: Humans and
Domestic Animals," Federal Register, Volume 43, August 22, 1978a, page
37366.
EPA, "Chloromethane and Chlorinated Benzenes Proposed Test Rule; Amendment
to Proposed Health Effects Standards," Federal Register, Volume 45, July
18, 1980, pages 48524, 48531-2.
EPA, "Dichloromethane, Netrobenzene, and 1,1,1-Trichloroethane; Proposed
Test Rule," Federal Register, Vol. 46, June 5, 1981, p. 30300.
EPA, "Guidance for Premanufacture Testing: Discussion of Policy Issues,
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March 16, 1979, pages 16240-16292.
EPA, "Proposed Guidelines, Economic Impact Analysis", Federal Register
Volume 43, September 6, 1978(b), pages 39644, 39656-30647, 396777
Federal Council for Science Technology. Intergovernmental Use of Federal
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Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), P.L. 95-516,
Section 3c2, as amended October 21, 1972.
Food and Drug Administration (FDA), "Nonclinical Laboratory Studies Good
Laboratory Practice Regulations," Federal Register, December 22, 1978, page
60012.
Fowler, E. M. "Careers: A Growing Need for ToxicologistsAmerican
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Glatz, B. A. "Short-Term Bioassays for Environmental Mutagens and
Carcinogens," American Water Works Association Journal, Volume 71, July
1979, pages 396-402.
Graham, C. N., "Litton Bionetics Identifies Dangerous Chemical Compounds,"
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Gusman, S. Training Scientists for Future Toxic Substances Problems,
Workshop Report, Sponsored by the Conservation Foundation, April, 1978.
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Hansen, R. W. "The Pharmaceutical Development Process: Estimates of
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Keller, John. "Toxicology 1979: Some Perspectives," Chemical Times and
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Kokoski, C. J., and H. R. Gittes, "Toxicological Testing Under Varying Food
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April 1979, pages 26-30.
VI-5
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APPENDIX A
LISTING OF TOXICOLOGICAL
TESTING LABORATORIES
A-l
-------
APPENDIX A
LISTING OF TOXICOLOGICAL TESTING LABORATORIES
The following listing contains 272 laboratories that have indicated
toxicological testing capabilities. The list stems from a telephone survey
of a screening list containing 800 potential toxicology laboratories and
represents the laboratory's own designation as a toxicology laboratory.
The screening list was compiled primarily from numerous directories and
lists of laboratories; these sources are identified on the next page.
Other laboratories for the screening list were obtained from trade journals
and magazines and from referrals by surveyed laboratories.
The study and screening list was oriented toward laboratories providing
commercial testing, either in-house or contract, and thus some university
(teaching and research) laboratories and government laboratories were
excluded. Due to a lack of information and study constraints, foreign
laboratories also were excluded.
The final listing is not comprehensive even for commercial testing
laboratories, as several factors prevented reaching this goal. Directories
and listings were somewhat out-dated and none was comprehensive. During
the survey, time was not sufficient to thoroughly investigate potential
laboratories not answering telephones or with telephone numbers no longer
in service (these laboratories were assumed to be out-of-business). Most
new laboratories were included only through referrals and some probably
were not identified. Still it is the study team's judgment that the list
provides excellent coverage of the industry and only about 10 to 20
laboratories exclusions are estimated, bringing the total number of
laboratories providing commercial toxicological testing to about 280 to 290
or, for analytical purposes, an estimated 285.
The listing contains the following types of laboratory information (unless
unavailable):
• Name
• Address
§ Contact Person (survey respondent)
• Phone
While the survey provided additional information on most of the
laboratories, this information was not included to avoid individual
laboratory concerns about confidentiality of the survey.
A-2
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SOURCES OF LABORATORY LISTS
ACIL/80 The American Council of Independent Laboratories, Inc.
Directory, 1980
ACLG/80 Analytical Chemistry Lab Guide, 1979-80, Aug. 1979, Vol. 51,
No. 10. Published by the American Chemical Society
APHIS/80 Department of Agriculture, Animal and Plant Health Inspection
Service, Animal Welfare; List of Registered Research Facil-
ities, FEDERAL REGISTER, Vol. 45, No. 54, Mar. 18, 1980,
17523-17548
ASTM/75 American Society for Testing and Materials, Directory of
Testing Laboratories, 1975
CTT/79 Chemical Times & Trends, 1979 Directory of Toxicology Testing
Laboratories
CTT/80 Chemical Times & Trends, 1980 Directory of Toxicology Testing
Laboratories
EPA/77 EPA/OPP list of 381 companies submitting pesticide registra-
tion test data, 1977
FDA/79 FDA list, 6/30/1979
FSQS/80 USDA, Food Safety and Quality Service list of recognized
laboratories, 1980
GLPP/79 1979 list of laboratories inspected under the Good
Laboratories Practice Program
GLPP/80 1980 list of laboratories inspected under the Good
Laboratories Practice Program
IRL/77 Industrial Research Laboratories of the United States, 1977
Bowker 15th Ed.
MTL/79 National Institute of Environmental Health Sciences, Research
Triangle Park, N.C., Mutagenicity Testing Laboratories in the
U.S., 1979
NALSI/78 National Association of Life Science Industries Membership
List, 1978
PHE/80 Pesticide Handbook - Entoma, 1979-80, Entomological Society of
America
SOT/76 Society of Toxicology, Toxicology Laboratory Survey, Mar. 1980
TR/1980 Thomas Register, 1980. New York: Thomas Publishing Co.
A-3
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TOXICOLOGY TESTING LABORATORIES
— ALPHABETICAL LISTING
1 aaSOTT LABORATORIES
i4Co sheaicArt ln.
.N.CHICAGO
IL 40054
PHONE: 312/937-5763
CONTACT: OR. KESTERSON
2 AER-AQUA LA30RATORIE S INC.
P G BOX 18615
HOUSTON
TX 77023
3 ALLERGAN PhARMACEUTICALS/HERBERT LABORATORIES
2525 OUPCNT OR.
IRVINE CA 52713
4 ALLIED ANALYTICAL ANC RESEARCH LABORATORIES
3031 GLENF I ELD
CALLAS TX 75224
5 ALLIED CHEMICAL CORP./CHEMICAL RESEARCH CENTER
? C BOX 1D57R
*OfiR ISTCHN iN J 07960
6 ALLIED LABORATORIES. L TO.
7011 HIGGINS AVE.
CHICAGO IL 606 56
PHONE: 713/923-4365
CCNTACT:
PHCNE: 714/752—7400
CONTACT: FRANK KILLEY
PHCNE: 214/33 7-39 S6
CONTACTS MORRIS WELLES
PHONE: 201/455-20 CO
CONTACT: OR. RE IN HOLD
PHONE: 312/631-15 53
CCNTACT: DR. IRVlhG OCMSKY
7 AMERICAN BACTERIOLOGICAL 6 CHEMICAL RESEARCH CORP.
3437 SOUTHEAST 24Th AVE.
3A INESVILLE FL 32601
PHONE: 904/372-0436
CONTACT: MR. B. BCRCEAUX
fi AMERICAN CYANAMIC
CUAC KERSRIDGc RO.
WEST WINDSOR
NJ
PHONE: 609/799-0400
CONTACT: CR. OEEMS
9 AMERICAN C-tiNAMlC CO. LECERLE LABORATORIES
N. 1ICDL£TCW.\| SO.
PEARL 3IVER NY 10965
PHONE: 914/735-5000
CCNTACT: OR. JCHN NOBLE
10 AMERICAN HEALTH FCUNOATICN NAYLOR DANA INSTITUTE
CANA 3D.
VALHALLA NY 10595
11 AMERICAN HOSPITAL SUPPLY CORP. EDWARDS LABORATORIES DIV.
17221 RED HILL AVE.
Santa ana CA 927 05
12 AMERICAN HOSPITAL SUPPLY CORP. ."1CGAW LABORATORIES DlV.
2525 flCGAW AVE.
IRVINE CA 926 50
13 AMERICAN STANDARDS TESTING BUREAU, INC.
AO WATER ST.
NY NY 100 04
PHCNE: 914/592-2600
CONTACT: DR. SHIMACI
PHCNE: 714/557-89 10
CCNTACT: JOANNE FARLEY
PHCNE: 714/7S4—2000
CONTACT: DR. ASH8R0CK
PHONE: 212/943—3156
CONTACT:
A-4
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TOXICOLOGY TESTING LABORATORIES — ALPHABETICAL LISTING
14 AMCCO CHEMICAL CORP.
200 E. RANCCLPH DR.
Cri IC AGO
IL 60601
PHGNE: 312/356-5991
CONTACT: DR. GARVIN
15 AMR 3 I CLOG ICAL RESEARCH
690 SOUTH CLINTGN
TRENTON
NJ C86II
PHONE: 6O9/695-77C0
CONTACT: DR. S. MARGOLIN
16 AWAY CORP ./RESEARCH £ DEVELOPMENT OIV.
7575 c. FULTON RO.
AOA MI 493 55
PHONE: 616/676-6279
CONTACT: SUE USHER
17 ANALYTIC ANO BIOLOGICAL LABORATORIES INC.
10754 PCRC HO.
GARDEN CITY HI 48135
PHONE: 313/422—74 74
CONTACT: F. MCLAUGHLIN
13 ANALYTICAL 3I0-CHE." ISTRY LABORATORIES INC.
P Q BOX 1097
COLUMBIA HO 65201
PHONE: 314/474-8579
CONTACT: MR. LYLE JCHNSON
19 ANALYTICAL CENTER INC.
P 0 30* 15635 6001 CLIhTCN DR.
HOUSTCN
TX 770 20
PHONE: 713/676-0141
CONTACT: 6. SEASE
2C ANALYTICAL RESEARCH LABORATORIES INC.
160 TAYLOR ST.
MONROVIA
CA 91016
PHONE: 213/357-3247
CONTACT: RAYMOND JAY
21 APPLIED BIOLOGICAL SCIENCES LABORATORIES INC.
6320 SAN FERNANDO RC.
GLENCALc CA 91201
PHONE: 213/242-6944
CONTACT: OR. J. 8. ClCHAELSCN
22 APPL IEC RESEARCH LA3CRATCR IES OF FLORIDA INC.
650 PALM AVE.
HlALEAh FL 23010
PHONE: 305/245-3660
CONTACT: OR. STEViAR T
23 ACUALA8S INC.
2221 HANCOCK OR.
AUSTIN
TX 78756
PHONE: 512/453—35C3
CONTACT: M. EDGAR
24 ARGUS RESEARCH LABORATORIES
2025 RIDGE RO.
PERKASIE
PA 18944
PHONE: 215/ 25 7- 27 41
CONTACT: MR. ALLEN hOBERMAN
25 ARMOUR RESEARCH LABORATORY
15101 N. SCOTTSDALE RC.
SCGTTSOALt
A I 85260
PHGNE: 602/991-3000
CONTACT: HELEN NCRTA-ROCT
26 ARTHUR 0. LITTLE INC.
ACORN PARK
CAMBRIDGE
MA 02140
PHONE: 617/864-5770
CONTACT: DR. ANDESSGN
A-5
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TCXICCLQGY TESTING LABORATORIES — ALPHABETICAL LISTING
27 ASSOCIATED WATER AND AIR RESOURCES ENGINEERS INC.
2907 12TH AVE. S.
NASHVILLE TN 27204
PHONES 615/383-45ei
CONTACT: MR. RICK OAV IS
28 AYERST LABORATORIES, INC.
64 MAPLE ST.
ROUSES POINT
NY 129 79
PHCNE: 518/297-66U
CONTACT:
29 8.f. GCCORICH CHEMICAL CC.
61C0 OAK TR5H 8LV0.
CL6VELAN0
GH 44131
PHCNE: 21 6/ 27 "3-26
-------
TCXICCLQGY TESTING LABORATORIES
— ALPHABET ICAL LISTING
40 810-SAFETY RESEARCH LABORATORIES
*1 IK A NO 3RGA0 STREETS
8RANCHVILLE
41 BIO-TECHNICS LABORATORIES INC.
1133 CRENSHAW dLVD.
LOS ANGELES
,\J Q7826
CA S0Q19
FHCNE: 201/948-54S4
CONTACT: MR. RGSENFELO
PHCNE: 213/933-59SI
CONTACT! MICHAEL SPEC TOR
42 81C/0YNAMICS INC. TOX ICOLQGICAL RESOURCES
SETTLERS SO.
EAST M ILLSTC/N6 NJ 088 73
43 3IGASSAV 5YSTEHS CORP.
225 WILDWGCD.
«G3URM
4-4 BIOSCIENCE RESEARCH
CITY OF INQLSTRY
45 SICS EASCH INC.
P 0 30X 35=3
PHILAOELPHIA
46 3ICSPHfiflIC S INC.
4923 WYACCNCA RD .
ROCKV(LLE
4? Bicrr ICS RESEARCH CORP. INC.
P G BCX 36333
HOUSTON
43 30RR1STGN RESEARCH IA8GRATGRY
5050 SEECH PLACE
TEMPLE HILLS
45 8RIST0L LA80RA TOR IES
THOMPSON RO. 3 3 BOX 6 5?
SYRACUSE
MA 01801
CA
PA 19101
MQ 208 52
TX 77036
MO 200 31
NY 132 01
50 BRISTOL-MEYERS RESEARCH C DEVELOPMENT LABORATORY
1350 LI3ERTY AVE.
HILLSUS NJ 07207
PHONE! 201/873-25 50
CONTACT: GARY 3EMKE
PHONE: 617/661-6883
CONTACTS OAVE JCHKSCN
PHCNE: 213/961-2110
CONTACT:
PHCNE: 215/848-4AS9
CONTACT: OR. KARL GABRIEL
PHONE: 301/770— 77 CO
CCNTACT: DR. LARRY MERRICXS
PHCNE: 7X3/789-9020
CONTACT:
PHONE: 301/899-35 36
CONTACT: OR. HELMLTh
PHONE: 315/432-20C0
CCNTACT: OR. HAOISSCO
PHONE: 201/926- 6 7 56
CONTACT: OR. V. CCTTY
51 BUFFALO TESTING LABORATORIES INC.
902 KENHORE AVE.
BUFFALO
ISY 14216
52 BURROUGHS WELLCLME CO. TOXICOLOGY £ EXPERIMENTAL. LAS
CCRNHAltIS RD.
RESEARCH TRIANGLE PARK NC 27709
PHONE: 716/873-22Q2
CONTACT: MR. KRIS
PHONE: 919/54.1-9090
CONTACT: A. W. MACKLIN
A-7
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TOXICOLOGY TESTING LA80RATORIES —
ALPHABETICAL listing
53 BUSHY RUN RESEARCH CENT6P
R. 0. 4 MELLON RC.
EXPORT
PA 15632
PHONE: 412/32 7—1020
CONTACT: OR. FRANK
54 CANNON LABORATORIES
P C 30X 362?
REAOING
55 CAPSULE LAacaA TORIES
340 SI8LSY MEMORIAL HWY.
ST. PAUL
PA 19605
MN 55118
PHONE: 215/375-4536
CONTACT: MR. PARKE
PHCNE: 612/457-4526
CONTACT: CLARENCE JCHNSGN
56 CARTER WALLACE INC. WALLACE LABORATORIES
HALF ACRE RD.
CRAN8URY NJ
085 12
PHONE: 609/635—60CQ
CONTACT: OR. JAMES MCGSE
57 CDC RESEARCH INC.
RT. 63 2 P C 80 X 359
CLARKS SUBMIT
PA 184U
PHONE: 717/586-11Q6
CONTACT: DR. LARSCH
58 CHEMICAL INDUSTRY INST IT LTE OF TOXICOLOGY
P 0 SOX 12137
RESEARCH TRIANGLE PARK NC
277 09
PHCNE: 919/541-2070
contact: or. mm
59 CHEMICAL SERVICE LABORATORY INC.
P G BOX 22C 3408 INDUSTRIAL PKWY.
JEPF6RSCNV ILLS
IN 47130
PHONE: 312/282-13 59
CONTACT: MR. E.V. EIQER
60 CHEMtE RESEARCH AND MANUFACTURING CO. INC.
160 CCNCORO OR.
CA SSEL36RRY
61 CHEVRON RESEARCH CO.
576 STANflARC AVE. SC. 5201
RICHMOND
PL 32707
CA S43 02
PHCNE: 305/331-4519
CONTACT:
PHCNE: 415/237-44 11
CONTACT:
62 CI6A-GEIGY CCRP.
556 MORRIS AVE.
SUKM IT
NJ C7901
PHONEi 201/277—50CO
CONTACT: OR. 01 ENER
i3 CIEA-GEIGY CORP. AGRICULTURE OIV,
410 SWING 30.
GREENSaCRC
64 CLINICAL RESEARCH ASSOC.
50 MAOISGN AVE.
NY
NC 27409
NY 10010
PHONE: 919/292-71 CO
CONTACT: OR. STEVENS
PHONE: 212/685-8789
CONTACT:
65 C0LGAT6-P AL.MOL IVE CO.
909 RIVER RC.
PISCA T AWAY
NJ 08854
PHCNE: 201/463-1212
CONTACT: OR. GENc HLD SON
A-8
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TOXICOLOGY TESTING LA30RA TGRIES — ALPHABETICAL LISTING
66 COMMONWEALTH LABORATORY INC.
2209 E. BROAO ST.
RICHMOND
VA 23223
6 7 CONTRACTORS ANO ENGINEERS SERVICES INC.
606 N. JOHN ST. P a BOX 762
GOLOSBCRO NX 275 30
68 CONTROLS FCR cAiV IRONMENTAL POLLUTION INC.
1925 RCSINA
SANTA FE
69 D. W. RYCXMAN ANO ASSOCIATES
P G SOX 27310
ST. LOUIS
7G DALLAS LAECRATCRIES
13 23 WALL
DALLAS
71 OAWSCN RESEARCH CORP.
P C BOX 30666
OR LANOC
72 DETROIT TESTING LABORATORY
3720 NCRTH6N0
GAK PASK.
73 CIAGNCSTIC CATA INC.
513 LOGUc AVE.
MOUNTAIN VIEW
Nf 375 02
MO 63141
TX 75215
FL 32862
Ml 48237
CA 94043
74 OIAMGND SHAMROCK CGRP. T.R. EVANS RESEARCJi CENTER
P G BOX 348 CHIO RT. 44 £ AU3URN RC.
PAINESVILLE OH 44077
75 DIVERSIFIED LABORATORIES INC.
FAIRFAX CIRCLE 3LOG. 3251 OLO LEE HWY.
FA IRJ-A X
VA 22030
76 COW CHEMICAL CO. PATHOLOGY-TOXICOLOGY DEPT.
P C 3GX 63511
INOIANAPOLIS IN 46263
77 CO* CHEMICAL CC. RESEARCH S DEVELOPMENT USA
1303 3LOG. 147)
CtCLANC MI 45640
75 DOW CHEMICAL CG. TEXAS OIV. RESEARCH S DEVELOPMENT
FREE PC RT TX 77541
PHONE: 304/648-33 53
CONTACT: MR. R. h4WKINS
PHONE: 919/735-73=5
CONTACT: SHERRY GfiACY
PHCNE: 505/982-9841
CONTACT: jlH MUELLER
PHCNE: 314/569—
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TCXICCLCGY TESTING LABORATORIES — ALP HA8ET ICAL LISTING
7<3 wO'n CCPNING CORP.
SOUTH SAG I iN AM RO.
*tOLANC
MI 48640
30 CRACKETT S ESEARCH £ DEVELOPMENT LABORATORY
5020 SPRING GRCVE AVE.
CINCINNATI CH 452 32
SI CUPCNT HASKELL LA3CHATCRY FOR TOXICOLOGY £ INOUS. MEC[CINE
ELXTC.N RO.
N6V.ARK DE 19? U
32 EASTHAN KCCAK. CO.
KGGAK. PARK
RGCHESTER
HEALTH.SAFETY £ HUMAN FACTORS LABORATORY
NY 14650
83 ECXRICh, PETER . £ SONS INC.
1025 OSAGE ST.
FORT WAYNE
34 eONAWOCD LieCRATCRIES
48 20 OLD SPANISH TRAIL
HOUSTON
5 5 EG £ G MA SON RESEARCH INSTITUTE
57 UNICfl ST.
fiGPC ESTER
IN 46802
TX 7702X
HA 01608
86 SG£G 8ICNCMICS AQUATIC TOXICOLOGY LA80RATGRY
790 MAIN ST.
WAREHAW Mi 02571
87 EG£S BIGNOMICS MARINE RESEARCH LABORATORY
SOX 1002 Rl. 6
PENSACCLA FL 32507
38 £G£G MASON RESEARCH INSTITUTE
1530 E. JEFFERSON ST.
PUCKVILLE MO 203 52
6S ELARS eiORESEARCh LABORATORY
225 COMMERCE DR.
FORT CCLLIKi CO 80521
90 ELI LILLY £ CO.
9 c aox 6X3 740 S. ALA8APA
INDIANAPOLIS IN 462 06
91 €H LILLY S CO. ELANCO PRODUCTS 01V.
GREENFIELD IN 46140
PHCNE.* 5X7/496-5047
CONTACT: MR. CHUCX GRCH
PHONE: 513/632-lfCO
CONTACT; MR. DAVE PERKINS
PHONE: 302/366-5264
CONTACT: S. MCXIIS ICK
PHCNE: 716/722-2716
CONTACT: C. J. TERHAAR
PHCNE: 219/481-2034
CONTACT: OR. DRAUCT
PHONE: 713/747—7271
CONTACT: MRS. ALICE PERRY
PHCNE: 617/ 79 I—0<5 31
CONTACT: V. RC8ESTS
PHONE: 617/295-2550
CONTACT: 8CB FOSTER
PHCNE: 904/492-0515
CONTACT: MR. ROO PARR IS
PHGNE: 301/770-44CO
CONTACT: OR. STEVE HA WORTH
PHONE: 303/221-2050
CGNTACT: DR. 3ECK
PHONE: 317/261-2000
CONTACT: HAROLD VtATH
PHCNE: 317/462-8306
CONTACT: OR. AMUfiCSEN
A-10
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TOXICOLOGY TESTING LABORATORIES
— ALPHABETICAL LISTING
52 5NOC LABORATORIES
IOQO STE'hART AVE .
GARDEN CITY
NY 11533
PHONE: 516/832-3148
CCNTACT: DR. RGSEPT CLARK
93 ENERGY RESOURCES CO. INC.
185 ALEWIFE 8RC0K PKHY
CAM8RICGS
MA 02138
PHQNEs 617/661-2111
CONTACTS OR. PETER SOUW
<54 ENVIRO PACT INC.
SI 5 W. 13TH
HI aleah
PL 33010
PHGNE: 305/885-1869
CONTACT: MR. MURPKY
55 ENVIRC-MED LABORATORIES INC.
414 w. CALIFORNIA
RLSTCN
LA 712T0
PHGNE: 318/255-0040
CCNTACT:
96 ENVIRO-MED LASORATOR IES INC.
1874 DALLAS OR.
8ATCN SOUGH
LA 70806
PHCNE: 504/928-0232
CONTACT: OR. R. FLCLRKOY
97 ENVIRONMENTAL CONSULTANTS INC.
1531 HOSIER RD.
SUFFOLK
VA 234- 34
PHONE: 804/ 53 "3—2321
CONTACT: KATHY GINGHER
58 ENVIRONMENTAL PROTECT ICN SYSTEMS INC.
P C BOX 20382 106 UPTON OR.
JACKSCN
MO 39209
PHONE: 601/922—8242
CONTACT: OR. C0R8 IN MCGRIFF
55 ESA LABORATORIES
43 WIGGINS AVE.
8E0FCRD
MS 0173O
PHGNE: 617/275-0100
CONTACT: DR. GRIFFIN
100 EXXON CORP. RESEARCH ANO ENVIRONMENTAL HEALTH OIV.
P C SCX 235
5. HILLSTGNE NJ 088 73
PHCNE: 201/873-6GC0
CONTACT: GERARD F. EGAN
101 FMC CO PP./CHEMICAL OEPT./CORPORATE TOXICOLOGY DEPT.
? C 30X 8
PRINCETON N4 CS540
PHCNE: 609/452-23 CO
CONTACT: OR. FLETCHER
102 FOOD A.NC CRUG RESEARCH L.A8CRAT0RIES
P 0 30X 107 RT. 17C
ViAVERLY
NY 14892
PHCNE: 607/565-2531
CONTACT:
103 FOOD AND ORUG RESEARCH LA8GRAT0RIES INC.
60 EVERGREEN PLACE
EAST ORANGE NJ 07018
PHONE: 201/67 7-9500
CONTACT: MR. HOWAFO FEINM AN
L04 FOREMOST—MCKEESON INC. MCKEESON LA60RATORIES
424 GRASMEPE AVE.
FAIRFIELD CT 06430
PHCNE: 203/259-1661
CONTACT:
A-11
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TQX ICOLOGY TESTING LABORATORIES — ALPHABET I CAL LISTING
LOS FRANKLIN LABORATCR IES DIV./DENVER LABORATORY
4238 YORK
DENVER CC 80216
PHONE: 303/625-6626
CONTACT: QAVE SHEETS
106 FREDERICK CANCER RESEARCH CENTER
P C BOX 3
FT. DETRICK MO 21701
LG7 GENERAL .MOTORS RESEARCH LABORATORIES
WARREN MI 43090
108 GENEX CORP.
6110 EXECUTIVE 3LVD. SUITE 1090
ROCKVILLE MO 208 52
ICS GHT LAEORA TORIES OF IMPERIAL VALLEY INC.
106 S. EIGHTH ST.
3RAWLEY CA <322 27
PHONE: 301/66 3-8000
CONTACT: DR. SERRANO
PHCNE: 313/57 5-30S8
CONTACT: J. VOSTAL
PHCNE: 301/770-0650
CONTACT: MRS. A. MEYERS
PHONE: 714/34-4-25 22
CONTACT: LINDA CCNNAtoAY
110 GIBRALTAR 3IOLOGICAL LA8CRATCRIE S
23 JUST RO.
FAIRFI ELD
NO 07066
PHCNE: 201/227-68 S2
CONTACT: DR. HERBERT PRINCE
111 GILBERT ASSOCIATES INC. LABORATORY SERVICES
30 NC8LS ST. P 0 8CX 1490
READING PA 19602
112 GILLETTE CC.
1413 RESEARCH QLVD.
SOCXVILLS
113 COLO KIST RESEARCH CENTER
2230 INDUSTRIAL 8LV0.
USHCNIA
114 GOOCYEAR TIR= a SU8BER CC.
1144 E. .MARKET ST.
AKRCN
MO 208 50
GA 300 58
CH 4A3 16
PHONE: 215/775-2600
CONTACT: MR. BOB IAPGS
PHONE: 617/268-3200
CONTACT: LOU OIPASQULE
PHONE: 404/482—7466
CONTACT: OR. JOHN ESKEN
PHCNE: 216/796-7445
CONTACT: MR. C. 3CULMAN
115 GULF SCIENCE AND TECHNOLOGY CO. LIFE SCIENCES LABORATORIES
F C 3CX 3240
PITTSBURGH PA 15230
PHONE: 412/665-60 CO
CONTACT: DR. HAROLD MCFARLANC
116 GULF SOUTH RESEARCH INSTITUTE
P 0 BOX 1177
Nc* IBERIA LA 70126
U? HAHNEMANN ."SOICAL COLLEGE S HOSPITAL
230 H. SRCAO ST.
PHILADELPHIA PA 19102
PHCNE: 318/365-2411
CONTACT: Oft. BILL GREER
PHONE: 215/4*8-6227
CONTACT: DP.. CALESNiCK
A-12
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TCXICCLOGY TESTING LAEQRATuRlES — ALPHA8ET ICAL LI STING
ua HAUCWEUL LABORATORIES PRODUCT investigations INC.
151 e. TENTH AVE.
CCNSHOHOCKEN Pi 19428
119 HAZLETCN IA8CR ATGRI£S
9200 LEESdURG TURNPIKE
VIENNA VA 22130
12c miu-tcp research
HWY. 126
Ml AH IV U..LC GH 45147
121 hOLLISTER-STIER LA3QRAT0RIES
30X 3145 TERMINAL ANNEX
SPOKANE MA 39220
122 HOWARD UNIVERSITY MECICAL SCHOOL/OEPT. OF PHARMACOLOGY
WASHINGTON DC 200 59
PHCNE! 215/825-8210
CONTACT: DR. SHELANSKI
PHCNE: 703/893-54CO
CONTACT: MR. LEc GARDEN
PHCNE: 513/831-3114
CONTACT: OAVIO CCMNE
PHCNE: 509/489-5656
CONTACT: DON CLARIDGE
PHCNE: 202/636-6311
CONTACT: OR. WILL I At* WEST
123 ICI AMERICAS BIOMEDICAL RESEARCH DEPT.
NEW MURPHY SO. L CONCORD PK.
WILMINGTON
OE 193 97
PHONE: 302/575-8C21
CONTACT: OR. KLAUS HUBSEN
124 IMS AMERICA LTD. ENVIRONMENTAL RESCURCES GRCUP
MAPLE AVE. £ BUTLER ? IKE
AMBLER PA 19002
125 INCEPENOENT EQUIPMENT CC3P./RECQN SYSTEMS INC.
51 FIFTH ST. P 0 30X 842
SGM6RV ILLE NJ 088 76
PHONE: 215/643-0400
CONTACT: AURORA ChANG
PHCNE: 201/685-0442
CONTACT: MR. TORO
126 INCUSTRIAL LA3CRATCR IES
3001 CULLEK ST.
FORT WCRTH
127 INCUSTRIAL LA8CRATGRIES CO., THE
1450 E. 62NC AVE.
OENVER
TX 76107
CO 302 16
PHONE: 317/332-22 59
CONTACT: MR. RANQY CAHOGN
PHCNE: 303/287-S6 S1
CGNTACT: MR. PAUL OChS
128 INHALATION TCXICCLOGY RESEARCH INSTITUTE
P C BOX 5390
AL8UGUERQUE NM 87115
PHCNE: 505/264-6825
CONTACT: OR. R. MCCLELLAN
129 INSTITUTE FOR MEDICAL RESEARCH
CQPEViCCO ANC CAVIS STREETS
CAMOEN
130 INSTITUTE FOR RESEARCH INC.
83 30 *£STGL£N DR.
HOUSTON
08103
TX 77063
PHCNE: 609/966-7377
CONTACT: OR. L. CCR IELL
PHCNE: 713/783-84C0
CONTACT: MR. PHILLIP THOMAS
A-13
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TOXICCLCGY testing LABORATCRIPS — ALPHABETICAL listing
121 INTERNATIONAL MINEflALS £ CHEMICAL CORP.
1331 S. FIRST ST.
TERRE HAUTE
IMC TECHI*ICAL CENTER
IN 47303
122 INTERNATIONAL RESEARCH £ DEVELOPMENT CCRP.
500 N. MAIN ST.
PA TT AWAN MI 490Tl
133 INTER* RESEARCH CORP.
2201 21 ST ST.
LAWRENCE
134 INVER6SK RESEARCH INTERNATIONAL/K. J,
K. STREET N* SLUE 334
WASHINGTON
135 J6FPERSCN PROFESSIONAL SERVICES
P C BOX 3357
LITTLE ROCK
KS 66044
O'CCNNOR ASSOC.
OC 20005
AR
136 JOHNSON C. JOHNSON BABY PROOUCTS LABORATORY
GRANOVIEW RC.
SX ILL.MAN NJ 08553
137 jCNESt SDMCNOS S ASSOCIATES
730 N. WALEC RC.
GAINESVILLE
13 6 JRB ASSOCIATES INC.
3400 WESTP ARK CR.
k;lean
FL 32601
VA 22101
139 KANSAS STATE UNI V./COMPARATIVE TCXICCLCGY LABORATORIES
SCHCCL OF VETERINARY MEDICINE
MANHATTAN
140 KEM—TECH LABORATORIES
16550 HIGHLAND RC.
8ATCN RCUGc
141 KENQALL CC. RESEARCH CENTER
411 LAKE ZURICH RO.
EARR INGTON
142 LAflO RA TOR Y RESEARCH ENTERPRISES
6321 S. SIXTH ST.
KALAMAZOO
143 LANCASTER LABORATORIES I.NC.
5424 3LCHANAN TRAIL EAST ? 0 BOX 467
WAYNESBORO
KS 66506
LA 70209
IL 60010
HI 49001
Pi 172 68
PHONE: 812/232-0121
CONTACT: MS. JESSIE W IL BUR
PHONE: 616/668-3326
CONTACT: OR. GOLC6NTHAL
PHCNE: 916/341-17C0
CONTACT:
PHCNE: 202/638-2652
CONTACT: MR. K.J. O'CONNOR
PHONE: 501/374—12 S6
CONTACT: SHIRLEY LOUIS
PHONE: 201/874-1461
CONTACT: MR. MIKE CfcECKAWSKI
PHONE: 904/377-5321
CONTACT:
PHONE: 703/821-46 CO
CONTACT: MR. MIKE rlGGIN-S
PHONE: 913/532-5679
CONTACT: OR. FREC CEHf»E
PHCNE: 504/293-8650
CONTACT: MR. ARTIfELEE
PHONE: 312/381-0370
CONTACT: OR. MILLER
PHONE: 616/37 5—04 £2
CONTACT: OR. J. MEHRING
PHONE: 717/762-9127
CONTACT: MR. HOfcASO HCLZNAN
A-14
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'• v'_nr.Y testing laboratories — alphabetical listing
LAUCKS TESTING LABORATORIES INC.
1033 WESTERN AVE.
SEATTLE
*A 98104
PHONE: 20 2/622—C717
CONTACT: J. M. CkENS
LAW & CO. Of WlLiMINGTCN
P C BOX 62 9
kILMINGTGN
NC 28401
PHGNE: 919/76 2-7022
CONTACT:
LS2ERC0 LABORATORIES
123 HAkTHCRNG ST.
5T. RCSELLt PARK
NJ 07204
PHCNE: 201/245-1933
CONTACT: OR. I. LEV6NSTEIh
U7 LEE PHARMACEUT ICALS
1444 SANTA ANITA AVE.
SOUTH EL MONTE
CA 91733
PHONE: 213/442—3141
CONTACT: OR. DIANE TIcGLER
146 LEVER 8RCTI-ERS TCX ICCLCGY SECTION
45 RIVES RO.
EOGEV.ATER
NJ 070 20
PHONE: 201/943— 71CC
CONTACT: MR. A. 3ATJ-6NSTEIN
149 Lf 5 CORP. ENVIRONMENTAL ANALYSIS LA8CRATCRIES
2030 nRIGHT AVE.
R ICHMQNO CA 94304
PHCNE: 415/235-2633
CONTACT: DICK GERCIS
LITRCM LA8CRATOR ICS LTD,
1351 MOUNT HOPE AVE.
ROCHESTER
NY 14620
PHCNE: 716/275-4CC8
CONTACT: DR. ANDREW TC*£TSKO
151 LITTCN 8ICNETICS INC.
55 16 NICHOLSON L.N.
KENSINGTON
HO 20795
RHONE: 301/881-56 CO
CONTACT: OR. ROBE ST WEIR
152 "ALCCM PIRN IE INC.
2 CORPORATE PARK OR.
WHITE PLAINS
NY 10602
PHONE: 914/694-2100
CONTACT! JANE HUGl-ES
.53 MASSACHUSETTS INSTITUTE OF TECHNOLOGY/NUTRITION S FOOD SCI.
E 18 - 666
CAMBRIDGE *A 02139
PHONE: 617/253-6220
CONTACT: OR. TILLY
154 MCNEIL PHARMACEUTICALS
SPRINGHOUS E
PA 147 74
PHONE: 215/62 3—50CO
CONTACT: OR. MILLER
155 MECICAL COLLEGE OF V IRGIN IA/OEPT. OF PHARMACOLOGY
KCV/VCL/HSD 80 X 76 2
RICHMCNO VA 23298
PHONE: 804/736-0229
CONTACT: OR. J. 8CRZELLECA
156 MEOTP.ONICS INC.
30 55—T CLO HWY a
Mt.\NEAPGLI S
MN 554 18
PHONE: 612/574-4000
CONTACT:
A-15
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TESTING LABORATORIES — ALPHABET!CAL LISTING
157 MEI-CHARLTCN INC.
2233 SV. CANYON RO.
PORTLAND
153 MELOY LA80BATORIES
6715 ELECTBCNIC OR.
SPRlNGFIELO
OR 97201
VA 22151
PHONE: 503/22 3-96 43
CONTACT: MR. DON VALLEY
PHONE: 703/354-26 CO
CONTACT: MR. GRAY
159 MERRELL NATIONAL LA80RATCRIES/CINCINNATI LABORATORY
XIQ S. AMITY RO.
CINCINNATI GH 45215
PHONE: 513/943-9111
CONTACT:
160 METRO-SERVICES LABORATORY
235 E. 3URNETT AVE.
LOUISVILLE
KY 402 08
PHCNE: 502/635-5463
CONTACT: MR. COOPER
161 "ICRC3 ICLOGICAL ANC 3lCCi-EHlCAL ASSAY LA80RAT0RIES INC.
? 0 30* 946 1
HOUSTON TX 77004
PHCNE: 713/92 3—27C1
CONTACT: MR. HERMAN KS5SE
162 MICRC8I3LCGICAL ASSOCIATES
5221 RIVER RO.
BETHESCA
163 MICECC
42C CHIPEWA SUITE 230
SALT LAKE CITY
164 MICWEST 5ESEARCH INSTITUTE
425 VOLKER 3LV0.
KANSAS CITY
MC 20116
UT 84108
MO 64110
PHONE: 301/654-34CO
CONTACT: ANDY LCS IKCFf
PHCNE: 301/582-3136
CONTACT: OR. GERPY NELSCN
PHCNE: 316/753-7600
CONTACT: MR. J. KCi»ALSKI
165 .*UES LABORATOfiIES INC. CONSUMER PRODUCTS 0IV.
1127 MYRTLE ST.
ELKHART IN 46514
166 M03AY CHEMICAL CORP. RESEARCH CENTER
STIL'aELL KS 66085
167 MOBIL RESEARCH £ DEVELOPMENT
150 E. 42NC ST.
¦NY NY 10017
163 PONSANTO ENVIRONMENTAL HEALTH LABORATORY
645 S. NSVi STSAC AVE.
ST. LOUIS MO 63110
169 MONSANTO RESEARCH CORP. CAYTON LABORATORY
1515 NICHOLAS SO.
CAYTCN CH 45407
PHONE: 219/264—3111
CONTACT: OR. R- HARTNAGLE
PHCNE: 913/681-2451
CONTACT: OR. a. SCHPOE06R
PHCNE*. 212/983-4242
CONTACT:
PHCNE: 314/694-7*42
CONTACT: OR. FOLK
PHONE: 513/263-34 il
CONTACT: WILLIAM C. RC3S
A-16
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TCXICCLGGY TESTING LABORATORIES
ALPHABETICAL LI STING
170 fOTE HARINE LABORATORY INC.
1600 CITY ISLAND PARK
SARASOTA FL 3357T
171 MOUNT CESERT ISLANC 31CLCGICAL LABORATORY
SALS BURY COVE ME 046 73
172 TOUT RE Y £ ASSOCIATES INC.
2612 E. 46 TH ST. S.
TULSA GK 74145
113 NATIONAL MEOICAL SERVICES INC.
2300 STRATFCRO AVE.
WILLOW GROVE aA 19090
174 NATIONAL TECHNICAL SYSTEMS TESTING OIV.
1*31 PC7RERC AVE.
SOUTH EL MCNTE CA 51731
17 5 NEii ENGLANC RESEARCH ISC.
IS SAGAMORE RO.
WORCESTER HA C1605
176 NORTH AMERICAN SCIENCE ASSOCIATES
2261 TRflCY RO.
NORTHWCCO Qh 43605
177 NORTHROP SERVICES INC.
P 0 30X 12313
RESEARCH TRIANGLE PARK NC 22T09
173 NORTHROP SERVICES INC.
P 0 90X 3427
LITT IS ROCK AR 72201
1?9 NUTRITION INTERNATIONAL INC./PROCUCT SAFETY LASORATQRIES
725 CRANBERRY RO.
E. BRUNSWICK NJ 08816
PHCNE: 813/388-4441
CONTACT:
PHONE: 207/288—36C5
CONTACT: MR. GGRMLcY
PHONEJ 405/348-23*1
CONTACT:
PHONE: 215/657-4900
CONTACT: DR. RIEQERS
PHONE: 213/44.4-9511
CONTACT: OR. PAUL
PHONE s 617/752-0346
CONTACT: MR. G. CAMCUGIS
PHONE: 419/666-94f5
CONTACT:
PHONE: 919/549-0651
CONTACT: DR. T. GRAN
PHONE: 501/376-3036
CONTACT: DR. ROBERT E. L£A
PHQNS: 201/545— 17C4
CCNTACT: MR. R. ShAPISO
18C 0 A LA80RATCRIES INC.
1437 SADLIER CP. WEST CR.
INClANAPOLIS
131 CMAHA CHEMICAL S ENVIRONMENTAL TESTING
29 17 DOUGLAS ST.
O.MAhA
132 OMNI RESEARCH INC.
4800 RALENEL 4VE
BALTIMORE
IN 462 39
VE 68131
MC 21210
PHONE: 317/353—S 7i1
CONTACT: OR. WILLIAM CAT6SS
PHONE: 402/341-5181
CONTACT: MR. J. BAILIE
PHONE: 301/46 7-J 1 12
CONTACT: MR. XATZ
A-17
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TCXICCLGGY TESTING LABORATORIES
— ALPHABETICAL LISTING
l<>3 CREGCN STATE U.NIV./OAK CREEK LA80RATCR IES OF BIOLOGY
CORVALLIS CS S7331
184 CRMCNT DRUG £ CHEMICAL CC., INC. PANSAY DIV.
16600 NV» 54TH AVE.
PC AM I FL 330 14
PHCNE: 503/754-35C3
CONTACT: MR. L. ClRTIS
PHONE: 800/327-5345
CONTACT:
135 CRT HO PHARMACEUTICAL CORP.
RT. 202
RARITAN
NJ 03869
136 CRTHQ RESEARCH INSTITUTE OF MEDICAL SCIENCES
RT. 202
RARITAN N«; 08869
PHONE: 201/524—04C0
CONTACT: OR. NCGUIRE
PHCNE: 201/524-2733
CONTACT:
167 CXFORO CHEMCAL CIV.
P C 80X 30202
ATLANTA GA 30341
lee PACE LABORATORY
3121 -N ICOllST AVE. S.
MINNEAPOLIS MN 554-08
189 PARAMETRIX INC.
13C20 NCRTHRUP *AY SUITE 3
3ELLEVUE WA 98QQ5
L9C PAPKS-CAVIS PHARMACEUTICAL RESEARCH OIV.
23CQ PHTMCUTH RO.
ANN AReGR HI 48106
1S1 PASAT RESEARCH ASSOC IAT1CN INC.
6045 BARFIELO RO. SUITS 100
ATLANTA GA 20323
192 PATTISCN'S LASQRATORIES INC.
211 5. MONfiCS ST.
HARLINGEN TX 785 50
193 PCR INC.
P G 3C* 1466
GAINESVILLE FL 22602
194 PFIZER INC. CENTRAL RESEARCH
EASTERN PGINT 3D.
GRGTCN CT C6340
IS5 PFIZER INC. CHEMICALS CIV.
235 E. 42N0 ST.
hY NY 100 17
PHONg: 404/452—11 CO
CONTACT: MR. J. FALLER
PHONE: 612/824-26 75
CONTACT: MR. G'CC!\NCR
PHCN6: 206/455-2550
CONTACT: DR. OON fcHlTECANP
PHONE: 313/S94-35C0
CONTACT: OR. S. M. KRLTZ
PHONE: 404/256— C410
CCNTACT: DR. RAYMCNG HART
PHGNE: 512/423-2196
CONTACT: KENNETH HALEAS
PHCNE: 904/376-0246
CONTACT: DR. OALS WARAER
PHCNE: 20 3 / 44-5- 5611
CONTACT: OR. THECDORE KING
PHONE: 212/547-7712
CONTACT: DR. 80UChARD
A-18
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TCXtCCLOGY TESTING LA80RAT0RI£S
ALPHABETICAL LISTING
196 PHARMACHEM CORP.
719 STEFKC SO. ? a ecx 1035
8EThL£h£M
197 PHARMAKON LABQRATORIES
WAVERLY
I <58 PHAfiM ( -CHEM TESTING
17 50 L W. OLVAN Oft.
TINLEY PARK
15? PHYSIQLCGICAL RESEARCH LA8 ORATORY
15C0 NORThCALE 3LV0-
NNEAPQLI S
200 PITMAN—MOORE INC.
P C BCX 344
WASHINGTON CROSSING
201 PRINCETON TESTING LABORATORY
P 0 30X 31C8
PRINCETON
202 PROCTOR 5 C-AM3LE
301 E. SIXTh ST.
CINCINNATI
203 PURDUE UNIV./OEPT. CP PHARMACOLOGY ANO
W. LAFAYETTE
204 RALSTON PURINA CENTRAL RESEARCH LA8S S
CH6CXE F80A EC SC.
ST, LGLIS
205 RAISTCN PURtNA R6SEARO- PARM
RT. 2
CRAY SUMMIT
206 SALTECH SCIENTIFIC SERVICES
3QX 7543 3301 KINSHAN BLVO.
MACISCN
207 RANOCLPH u ASSOC. INC.
8901 N. INCUSTRIAL RC.
PEORIA
209 RECKEN LABORATORIES INC.
14721 CALIFA ST.
VAN NUYS
PA 18018
PA 18471
IL 604 77
»N 55433
NJ 08560
NJ C3540
OH 45202
TCXICOLCGY
IN 47907
RESEARCH SERVICES
MC 63183
MO 63039
Wl 53701
IL 61615
CA 91401
PHONE: 215/86 7-46 54
CONTACT:
PHCNE: 717/586-24U
CONTACTS R1 CHAR0 MATTHEWS
PHONE: 312/534-2261
CONTACT: P. FANCS^LI
PHCNE: 612/574-4901
CONTACTi OR. OEfcMS ELLSBURY
PHCNE: 609/737-37 CO
CONTACT:
PHCNE: 609/452—9050
CONTACT: DR. MIHI SCHAAF
PHCNE: 513/56 2—11 CO
CONTACT: MR. G. £. ViENUER
PHONE: 317/494-34 20
CONTACT: DR. RGG6P KAICKEL
PHONE: 314/982-01tl
CONTACT:
PHONE: 314/982—1CCQ
CONTACT:
PHONE: 608/241-44 71
CONTACT: MR. ROBEfT FIShBECX
PHCNE: 309/691-5044
CONTACT: MR. KIRK SHETLAND
PHONE: 213/992-27 CO
CONTACT:
A-19
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TGX ICCLC3Y TESTING LABORATORIES
— ALPHABETICAL LISTING
209 REEO. JAMES R. , £ AS SGCIAT5S INC.
313 FORREST OR.
NEWPORT NE*S
V A 23606
PHONE: 804/599-67?0
CCNTACT: OR. JA«6$ PEED
210 REYLCN RESEARCH CENTER INC.
945 ZEP5GA AVE.
3RCNX
NY 104 73
PHCNE: 212/824-90 CO
CCNTACT: OR. EARL 9RALER
211 RISKS, CARROLL, DULLER S ASSOCIATES
P 0 80X 130
H3PK INS
MN 55343
PHCNE: 612/935-6SC1
CONTACT: OUANE NELSON
212 SOHH £ HAAS CO.
P Q 30 X 13183
PHILAGELPhIA
PA 19116
PHONE: 215/592—316i
CONTACT: OR. A. IGNAT0WSK1
213 SAFETY SPECIALISTS INC.
3284F EDWARC AVE.
SANTA CLARA
CA S50 50
PHONE: 40 8/S38-1111
CCNTACT: T. C. NCELE
214 SALK INSTITUTE FOR BIOLOGICAL STUOIES
10010 N. rCSREY PINES RO.
LA JCLLA
CA 92037
PHCNE: 714/543-4100
CCNTACT: OR. GERARG SPAhN
215 SANDERS MECICal RESEARCH FOUNDATION INC.
33 SE 3R0 ST.
3CCA RATON FL 33432
PHCNE: 305/392-Q9C0
CCNTACT: OR. SANDERS
216 SANOOZ. PHARMACEUTICALS, PRECLINICAL SAFETY ASSESSMENT DEPT.
RT. 10
HANCVER
217 SCHERING-PLCUGH CORP.
RT. 94
LAFAYETTE
NJ C7936
NJ 078 48
PHONE: 201/386-6309
CONTACT: OR. STCLL
PHCNE: 201/931-2GCQ
CONTACT: DR. EDWARD SCHWARTZ
218 SCIENTIFIC ASSOCIATES INC.
6200 S. L i NC8ERGH 8LVC.
ST. LOLIS
«0 63123
PHCNE: 314/48 7-6 776
CONTACT: OR. R086RT MCULTCN
219 SCOTT, DW [ GhT C., RESEARCH CENTER
SCD1 ISLAWN RO.
¦MARY SV ILL c
CH 4 3040
PHCNE: 513/644-0011
CONTACT:
220 SEARLE, G.C., ANC CO- SEARLE LABORATORIES
P C 30X 5110
SKCXI5 IL 60680
PHGNE: 312/982—7C CO
CONTACT: DR. PCCL
221 SEAWAY INDLSTRIAL LABORATORIES INC.
542-544 CC.NXcY & JACXSCN ST.
HAWMCNO
IN 463 24
PHONE: 219/932-1770
CONTACT: MR. CIChCN
A-20
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TCX ICOLOGY TESTING LASGRATORIES — ALPHABETICAL LISTING
222 SECUOIA ANALYT ICAL LA8CRAT0RY
2549 HIDDLEFIELD RO.
R6CWGQC C ITY
CA 94063
PHCNE: 415/364-S222
CONTACT:
223 SERCO SANITARY ENGINEERING LABORATORIES INC.
1931 W. COUNTY RD. C-2
ROSE VI LLC *N 55113
PHONE: 612/636-7173
CONTACT: MR. RICK 0C8H.
224 SHARPS ASSOCIATES
76 7-3 CCNCCRC AVE.
CAMSRIOGc
MA 02138
PHONE: 617/354-2800
CONTACT:
225 SHELL LABORATORIES
HOUSTON
TX
PHCNE: 713/241-6161
CONTACT: DON STEVENSON
226 SKINNER I SHERMAN LA30RAT0RI6S INC.
300 SECOND AVE.
WALrHArt
HA 022 54
PHCNE: 617/890-7200
CONTACT: MR. HAL OALiELL
227 SMITH KLINE ANC FRENCH LABORATORIES
1500 SPRING SARDEN ST.
PHILAOEIPHU
PA 19101
PHONE: 215/354—4fl CC
CONTACT: OR. KALMAN T. SZA8C
22 8 SMITH KLINE ANIMAL HEALTH RESEARCH CENTER
1600 P AOL I
WESTCHESTER PA 19101
PHONE: 215/854—40CO
CONTACT:
229 SMITH KLINE CLINICAL LABORATORY
343 WINTER ST.
waltha y
MA 02154
PHCNE: 617/890—6161
CCNT ACT:
SOUTH .MOUNTAIN LABORATORIES
380 LACKAWANNA PL.
SOUTH GRANGE
NJ 07079
PHONE: 201/762-00 *5
CONTACT: MR. MARGIEPI
231 SOUTHERN RESEARCH INST IT UTE/K.ETTER ING MEYER LABORATORY
20C0 NINTH AVE. S.
91RMINGHAM AL 35205
PHONE'- 205/323-6592
CONTACT: ROBERT HEEKS
232
SOUTHWEST FCUNCATICN FCR RESEARCH ANO EDUCATION
P C 80X 28147
SAN ANTCNIC
TX 782 84
PHONE: 512/674-14 10
CONTACT: IRVING G6LLER
233 SOUTHWEST RESEARCH INSTITUTE
P 0 3CX 23 510
SAN ANTCNIC
TX 782 84
PHONE: 512/684-5111
CONTACT: OR. JQHSSCS
234 SOUTHWESTERN LABORATORIES
P C 80X 8768 222 CAVALCACE
HOUSTON
TX 77009
PHCNE: 713/692-9151
CONTACT: MR. 81LL CCLE
A-21
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TOXICOLOGY TESTING LABORATORIES — ALPHABETICAL LISTING
225 SPRINGSORN CROLP/SPR ING3CRN LA80RAT0RIES
TEN SPRING30RN CENTER
SPR! fcG SCRN CT 060 82
PHGNE: 203/74 9-63 71
CONTACT:
236 SPRINGBQRfi INSTITUTE PGR 5IORESEARCH INC.
553 N. BROACWAY ST.
SP6NC5RVILLE CH 45887
PHONE: 419/647-4156
CONTACT: JON C- FULFS
237 SQUI63, E.R. AND SONS
GcCRGES RD.
NEW BRUNSnICK
NJ 08902
PHGNE: 609/921-4000
CONTACT: DR. P. SIBLEY
232 SRI-INTERNATIONAL
333 RA VENSWGOD AVE.
MENLC PARK
CA 94025
PHGNE: 415/859—3GC0
CONTACT: OAVID JCNES
23S STAUFFER CHEMICAL CC.
1200 SOUTH 47TH ST.
RICHMOND
CA "54304
PHONE: 415/233-9361
CCNTACT: OR. TGM CASTLES
240 STERLING kINTHRGP RESEARCH INSTITUTE
COLUMBIA TFK.
RENSSELAER
241 STIEFSL LA30RATORIES/A.C.
ST. 145
CAK HILL
NY 12144
STIEFEL RESEARCH INSTITUTE INC.
NY 12460
PHGNE: 518/445-8100
CONTACT: OR. DRCEECX
PHCNE: 513/239-6903
CONTACT:
242 ST ILLMEAOCw INC.
<5525 TCWN PARK OR.
HOLS TON
TX 77036
243 SYRACUSE RESEARCH CORP. CHEMICAL HAZARD ASSESSMENT CENTER
f.ERR ILL Lh.
SYRACUSE
244 TECHNAM IMC.
2405 3CND ST.
PARK FCREST SCLTH
NY 12310
IL 60466
PHCNE: 713/776-8828
CONTACT:
PHONE: 315/425-5122
CONTACT: JOE SANTCDCNAOG
PHONE: 312/534-1779
CONTACT:
245 T6RRALA8
3535 VIA TSSftA
SALT LAKE CITY
246 THERMO ELECTION CORP.
101 FIRST AVE.
WALT HAM
UT 84115
MA C2154
24 7 THGRNTCN LA80RATCRI6S ANALYTICAL ANC CONSULTING CHEMISTS
1145 E. CASS ST.
TAMPA FL 33601
PHCNE: 801/2fa2-CO'?4
CONTACT:
PHCNE: 617/890-S7C0
CGNTACT: WING YL
PHCNE: 813/223-S7C2
CONTACT: VANCE PEARSON
A-22
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TCXICCLCGY TESTING LABORATORIES — ALPHABETICAL LISTING
248 TOX MONITOR LABORA TORY INC.
33 W. CHICAGO 4VS.
CAK PARK
249 TOXICITY RESEARCH LABORATORY
510 t*. H4CKLEY
MU SKEGCN
IL 60302
MI 49444
PHCNE: 312/345-6970
CONTACT: MR. LQCXE
PHCNE: 616/ 733—25 64
CONTACT: OR. OEAN
TOXICGN
3213 ^CNTEREY BLVO.
8ATCN PCUGE
LA 708 14
PHONE: 504/925—5C 12
CONTACT: MR. CRCliCh
TOXIGENICS INC.
1300 E. PERSHING RO.
DECATUR
IL 625 26
PHONE: 217/875-3920
CONTACT: OR. PAGE
252
TPS INC.
P C SOX 333
MOLNT V6RNCN
IN 476 20
PHCNE: 812/985—5900
CONTACT: DR. JAMES BGTTA
253 TRC £NV IRONHEN TAL CONSULTANTS INC.
125 SILAS OEANE HWY.
"HEThERS?11 cLC
CT 06109
PHCNE: 203/563-1431
CONTACT: MR. GORCCN BROCKMAfv
254 TRI-TECH LABORATORIES INC.
PEACH CT. OFFICE SLOG.
3REN TMCCO
253 TROJAN LABORATCR IE S
118 N. FIFTH
M0NTS8ELLG
TN 370 27
Zi 90640
PHONE: 615/373—4555
CONTACT: GARNETT CANT2LER
PHCNE: 213/721-9 5 74
CONTACT:
256 U.S. TESTING CO., THE
1415 PARK -4VE.
HQBCKEN
NJ 07070
PHCNE: 201/792-2400
CONTACT: MR. OROZCCWSKI
257 ULTRA SYSTEMS INC. CHEMICAL £ MATERIALS RESEARCH DEPT.
2400 MICHELSGN DR.
IRVINE CA S2715
PHCNE: 714/752-75C0
CONTACT:
25S UN I LAB RESEARCH
2800 SEVENTH ST.
BERKELEY
CA 94710
PHCNE: 415/548-64-4C
CONTACT: MSLANIS 6ALTE2GRI
259 UNIV. OF CINCINNATI/KETTERING LABORATORY
3223 ECEN AVE.
CINCINNATI CH 45267
PHCNE: 513/872-5709
Contact: sernaro salt z.man
260 UNIVERSITY LABORATORIES
31Q N. 2ND AVE.
HIGHLAND PARX
N J C79 04
PHCME: 201/246—1146
CONTACT: OR. EUGENE BERNSTEIN
A-23
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TOXICOLOGY TESTING LABORATORIES — ALPHA8ETICAL LISTING
261 UNIVERSITY OF KANSAS MEDICAL CENTER/CEPT. CF PHARMACOLOGY
KANSAS CITY ,
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APPENDIX B
TOXICOLOGY LABORATORY CONTACT FORM
AND
TELEPHONE SURVEY INSTRUMENT
B-l
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LABORATORY CONTACT FORM
Initial Contact
Hello, my name is from the University of Kansas Center for
Public Affairs. We are doing a survey for the U.S. Environmental
Protection Agency to gather information about the availability of chemical
testing services, and the types of tests provided by laboratories.
Does your toxicology laboratory test chemicals for environmental or health
effects?
Yes No
I.IF YES, PROCEED WITH INTERVIEW
IF NO, THANK RESPONDENT AND PUT IN "NOT APPLICABLE" FOLDER
Who would be the best person to provide information regarding these issues?
Name:
Is ("Name") in? Yes No
ilF YES, PROCEED WITH INTERVIEW
1IF NO, ASK WHEN S/HE'LL BE BACK AND MAKE APPOINTMENT ON CALLBACK RECORD
Contact with Actual Respondent
[REPEAT flftST PARAGRAPH "hELlO, MY NAME IS . . CONTINUE WITH:,'
Information collected will be used to develop a list of toxicology
laboratories for EPA. This will improve the understanding of chemical
testing laboratories which will be helpful in assessing testing
availability. Your laboratory was chosen because it appeared on , a
publicly available list. Your responses are completely confidential and
your cooperation is of course, voluntary. First of all, . . .
[PROCEED WITH INTERVIEW, QUESTION H
IF RESPONDENT DOES NOT HAVE TIME FOR A 15 - 20 MINUTE INTERVIEW, MAKE
ARRANGEMENTS TO CALL BACK ON THE COVER SHEET. DON'T ASK IF THEY HAVE TIME,
THEY WILL TELL YOU IF THEY DON'T
B-2
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Part II.
•PA Toxicology Laooratory Survey
0MB Apnrova! No. 2000-0141
A. 3ENERAL
I. In which of the following areas does your laboratory currently
perform chemical tasting: (circle response)
Area '
Nlanmalian Testing'
In-Vitro Testing
Environmental Effects Testing
Chemical Fate Testing
Product and Analytical Testing
(* See questions 8.1, C.l, etc.
Q.I
Perform
Yes No
2
2
2
2
2
(Q.A.2) Total Vol.
0.2
Percent
of
Vol ume
100%
2. »(hat percent of your total laooratory testing volune (Dollars)
is in each of the areas designated above (Q.A.I)?
3. What percent of your total laboratory testing —•
(a) Is on contract?
(b) is in-house (captive)?
Percent%
100%
4. Approximately how many total persons, on the average, did your
laboratory employ in 1980?
(Include professionals~6oxicologists> pathologists—,
technicians, management and acministrative, and other
staff)
Total Persons
3. Approximately how many of these employees were—¦
Professionals?
Technicians?
Management 4 Administrative?
Other Staff?
Check Total
(Sea A.4.)
5. Also, as a general measure, flow many square-feet of toxicology laboratory
space do you have at this facility?
Square feet
7. (If the answer to Mammalian Testing in Question A.I is no, then ask:) Addition
Oo you plan to add Mammalian Testing capability within the Yes No
next 1-2 years?
1 2
If "yes'1, 30 to Question 8.4 and 3.S
B-3
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B. MAMMALIAN TEST1SG (If Performed—Saa Q.A.I)
1. which of tne following specific types of Mammalian Testing can be performed
currently (with available resources) in your laboratory — (circle response)
(a) Acute Testing
Acute oral toxicity
Acute dermal toxicity
Acute Innalatlon toxicity
Primary eye irritation
?ri!nary dermal irritation
Dermal sensitization
Acuta delayed neurotoxicity
(b) Subchronic Testing
Subchronic oral dosing
Subchronic SO-day dermal toxicity
Subchronic inhalation toxicity
Subchronic neurotoxicity
(c) Chronic Testing
Chronic—oral )
)
Chronic—dermal ' )
) (Route/Technique)
Chronic—innalatlon)
)
Chronic—parenteral )
(d) Reproduction (e.g., 3 generation)
(e) Teratogenic
(f) Oncogenic
(g) Histopatholoqy
On) Other (Name)
2. Does your laboratory have the capacity to da additional oa«roa.lian testing?
(Annual rate, as compared to 1980)
(If yes): About what percent mare testing could be performed?
MOl.
11-201
21-30%
More than 30S
Current Capability
ves No
1 2
1 2
1 2
1 2
1 2
1 2
.1 2
1 2
1 2
1 2
1 2
1 2
1 2.
1 2
1 2
1 2
1 2
1 2
1 2
1 2
1 2
Additional Capacity
yes Mo
1 2
Parcent Range
1
2
3
4
B-4
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(a) Which of the following test animals'are you capable of using
currently in your laboratory?
"est Animal 'species)
Rodents (mice, rats, hamsters, gerbils
Rabbits
Guinea Pigs
Dogs
Cats
Primates
Poultry
Large Oomestic Animals
Animals Used
Ves
(b) For each test animal used, how many would you norma11y have
at your laboratory both in tests and in inventory? (Ave. No. above)
(c) Also, for each test animal used, what is the maximum ntanoer
that you could keep in tests or in inventory? (Max. No. above)
(d) Are any of the test animals named above, or others, in short
supply?
(If yes) which ones?
No
2
2
2
2
2
2
Ave. No.
at Lab
Max. No.
Possible
Short Supply
Yes No Jon' t Know
A number of general factors have been cited in publications as factors
that could constrain the expansion of toxicology testing in the U.S.
From the perspective of your laooratory how critical are each of the
fallowing factors on a scale of 1 to 7 where 1 is not critical and 7
is very critical.
Factor
3ati nq
Not Very
Critical < > Critical
1 2
(a) No. of Available Professionals
If (a) is rated 4 to 7, also rate the following:
4 5 5
12 3 4 5 6 7
» Toxicologists 1 2 3 4 5 5 7
• Veterinary Pathologists 1 2 3 4 5 5 7
• Pathologists 1 2 3 4 5 S 7
(b)
Availability af Animals
> 2
3
4
S
S
7
(c)
Availability af Equipment
T 2
3
4
5
a
7
(d)
Availability of Supplies
1 2
3
4
5
6
7
(e)
Availability of Laboratory Space
1 2
3
4
5
S
7
(f)
Availability of Capital
1 2
3
4
5
6
7
(g)
Other (specify)
1 2
3
4
5
6
7
1 2
3
4
5
6
7
Vih1ch of these 'actors is the most critical constraint to the expansion
of your toxicological testing capacity? Most Critical Factor
is concludes our questions on Mammalian Testing.
B-5
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C. IN-VITRO TESTING {If Performed—See q.A.1)
1. whieft of the following In-mro tests can 3e performed currently
(with available resources} in your laboratory—
"ests
(a) Tests for Detecting Sene Mutations
(e.g., Ames Test, .Mouse Lymphoma Assay)
(b) Tests for Cetectlng Chromosomal Aberrations
(e.g., Cytogenetics, Sominant Lethal Assay)
(c) Tests for Cetectinq Primary ONA Oamaoe
(e.g., ONA Repair, Unscheduled DMA Synthes 1 s)
(d) Tests of Physiological Parameters
(e.g.. Biochemical, Cytolagy)
Current Capability
Yes No
1 2
1 2
1 2
2. Ooes your laboratory have the capacity to do additional In-V1tro testing?
(If yes): About what Dercent more testing could be performed.
1-1 OS
11-20X
21-302
More than 30S
Additional Capacity
Yes No
1 2
Percent 3ange
1
2
3
4
0. ENVIRONMENTAL EFFECTS TESTING (If Perforned—See q.A.1}
1. Is your laboratory currently capable of performing—
(a) terrestrial testing?
(b) aquatic testing?
2. Does your laboratory have the capacity to do additional
environmental effects testing?
!tf yes): About what percent more testing can be performed.
1-10*
11-201
21-301
More than 30J!
Current Capacity
Yes No
Additional Capacity
Yes No
1 2
Percent Range
1
Z
3
4
B-6
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CHEMICAL FATE TESTIN
'If Performed—See.
.1)
Which of the following types ofcnemical fate
studies can be performed currently—
2.
(a) laboratory studies (e.g. hydrolysis,
photodegradation, son metabolista)
Cb) field studies (e.g. field dissipation,
bioaccumulation)
Does your laboratory have the capacity to do additional ehemical
fata testing?
(If yes):.About wnat percent -ore testing could be performed.
1 -JO*
11-202
21 - 308
More than 30S
Current Capability
Yes II o
1 2
Additional Capacity
Yes Ho
1 2
Percent Range
1
2
3
4
SOURCES OF DEMAND FOR TESTING (OPTIONAL—OMIT IF TIME IS LIMITED)
1. Approximately what percent of your laboratory's tasting 1s performed
in response to the foilowing:
EPA - Toxic Substances Control Act (T3CA)
tPA - Federal Insecticide, Fungicide and Rodenticlde Act (FIFRA)
EPA - Resource Conservation and Recovery Act (RCRA)
Food and Drug Administration (FDA)
National Institute for Environmental Health Science (NIEHS)
National Cancer Institute (NCI)
Consumer Products Safety Commission (CPSCJ
Occupational Safety and Health Act (OSHA)
OTHER:
Percent
That concludes the specific questions. Would you please send us a orochurei annual report, ar any other information
which you have readily available, which describes the types of services performed by your laboratory? In addition,
could you identify any new-testing laboratories af which you are aware?
Thank you for your cooperation.
B-7
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5 5*
iwJ-UKi DOCUMENTATION ,i._report no. 2.
PAGE
3, Recipient's Accession No.
Title and Subtitle
Chemical Testing Industry: .Profile of Toxicological Testing
5. Reoort Date
October 1981
6.
/ AuthorsSamuei q. Unger (DPRA), Daniel W. Francke (DPRA), Stuart L.
Fribush (ICF). Geneva S. Hammaker (DPRA). Frank D. Lerman (ICF)
8. Performing Organization Rapt. No.
i
9. Performing Organization Name and Address
Development Planning & Research ICF Incorporated
Assoc., Inc. (DPRA) 1850 K Street
P.O. Box 727 Washington, D.C. 20006
Manhattan, KS 66502
10. Proieet/Task/Work Unit No. \
1
11. ContractfCl or Grant(G) No.
to 68-01-6064 '
w 68-01-6287 - Task
¦ Order 7
12. Sponsoring Organization Name and Address
Office of Pesticides and Toxic Substances
U.S. Environmental Protection Agency
401 M Street, S.W.
Washington, D.C. 20460
13. Type of Report 4 Period Covered
Final Report
14.
IS. Supplementary Notes
EPA Project Officer: Sammy K. Ng
i
Abstract (Limit: 200 words)
The study assists the EPA in evaluating the foreseeable availability of the facilities and
personnel needed to perform the toxicological testing required under the Toxic Substances
nnfro] Act. The study profiles the toxicological testing industry which is estimated
: to contain 285 commercial toxicology laboratories with average employment of 57 per
i laboratory and average laboratory space, 28,000 sq. ft. Annual revenues for the industry
i are estimated at $650 million or $2.3 million per laboratory and market competition is high
jwith no individual firm or small group of firms controlling key resources. The current
| supply of testing resources is adequate with industry utilization at about 80 to 85 percent,
j Capital and professional manpower are key resources. Demand for testing and testing
resources should be strong and arises from regulatory sources including TSCA, FIFRA and
FFDCA and non-regulatory sources. Finally, a conceptual supply/demand model shows it is
possible to simulate and assess the potential economic impacts of regulatory changes as
well as changes in prices, availability of resources and industry structure, but data and
resource requirements to implement such a model would be substantial.
17. Document Analysis a. ©.script™ toxicology, laboratories, testing resources, pathologists,
veterinarians, mammalian testing, in-vitro testing, environmental effects testing, chemical
fate testing, environmental & health testing, supply-demand model, economic analysis,
mathematical programming, Toxic Substances Control Act (TSCA), Federal Fungicide,
Insecticide & Rodenticide Act (FIFRA), Federal Food Drug & Cosmetics Act (FFDCA)
b. ldenttfie«/Ope«-Ended Terms
c. COSAT1 Field/Group
IS. Availability Statement
19. Security Class (This Reoort)
21. No. of ?ages
Release Unlimited
Unclassified
20. Security C'ass (This Page)
22- Price
Unclassified
(Se* ANSI—Z39.I8) See Instructions on Reverse OPTIONAL FORM 272
(formerly NTJ^33)
Oesartment of Commerce
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