vvEPA
united States
Environmental Protection
Agency
Office of Pesticides
and Toxic Substances
Washington, DC 20460
EPA-560/2-81-004
May 1981
Toxic Substances
Economic Impact
Analysis:
Dicholoromethane,
1,1,1- Trichloroethane
and Nitrobenzene
Support Document
Proposed Test Rule
Section 4
Toxic Substances
Control Act
-------
EPA 560/4-81-004
May, I 981
ECONOMIC IMPACT ANALYSIS OF PROPOSED
TEST RULE FOR DICHLOROMETHANE
I, 1, 1-'rRICHLOROETHANE,
AND NITROBENZENE
by
Rao Tadavarthy
Joanne Collins
David Mayo
Barrett Riordan
Contract No. 68-01-5864
Project Officers
Sammy K. Ng
Peter Kimm
ECONOMICS & T"ECHNOLOGY DIVISION
OFFICE OF TOXIC SUBSTANCES
WASHINGTON, D.C. 20460
U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF PESTICIDES AND TOXIC SUBSTANCES
WASHINGTON, D.C. 20460
-------
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 analyze the potential economic impact
on manufacturers complying with proposed testing rules. These
proposed rules were prepared by the EPA Office of Pesticides and
Toxic Substances to implement Section 4 of the Toxic Substances
Control Act.
This report vIas submitted in fulfillment of Task Order
Number 5 of Contract Number 68-01-5864, by MATHTECH, Inc. Work
was completed as of May 1981.
This report is being released and circulated at
approximately the same time as publication in the Federal
Register of a proposed health and environmental effects test rule
under Section 4 of TSCA. The study is not an official EPA
publication. It will be considered along \vi th any comments
received by EPA before or during the proposed rulemaking
proceedings in establishing final regulations. Prior to final
promulgation of these test rules, the accompanying study shall
have standing i~ an EPA proceeding or court proceeding only to
the extent that it represGnts the views of the contractor who
performed the study. It cannot be cited, referenced, or
represented in any such proceedings as a statement of EPA's views
regarding the subject industry or the economic impact of the
regulation.
-------
1.
1.1.
1. 2.
1.2.1.
1.2.2.
1. 3.
1.3.1.
1.3.2.
1.3.3.
1. 4.
2.
2.1.
2.1.1.
2.1.2.
2.1.3.
2.1.4.
2.1.5.
2.2.
2.2.1.
2.2.2.
2.2.3.
2.2.4.
2.2.5.
2.2.6.
TABLE
OF CONTENTS
EXECUTIVE
SUMMARY.
......................... ...
Introduction.. .............
................
Objectives
and Methodology...
..............
Level
Economic Analysis.
........
......
I
Level
Economic
Impact Analysis.
......
II
Conclusions. . . . . . . .
....................... .
Dichloromethane.
...................... ..
1, 1, l-Trichloroethane.
..................
Nitrobenzene....
... ........ ........ .....
Limits
of Analysis.
. ....... ................
DICHLOROMETHANE.............
..................
Industry
Characteristics.
..................
Production
and Trade..
..................
Producers.. ........
.. ....... ............
Production
Process.
..... ......... .......
Uses. . . . . . . .
........................... .
Substitutes.
. .......... ..... ......... ...
Potential
for Economic
Impact.
.............
Direct Testing
Costs.
...................
Demand
Sensitivity.. .
...................
Cost
Characteristics.
...................
Industry
Structure................
......
Market Expectations.
....................
Conclusions.........
............... .....
i
Page
1-1
1-1
1-1
1-2
1-3
1-3
1-3
1-4
1-5
1-5
2-1
2-1
2-1
2-3
2-6
2-10
2-13
2-17
2-17
2-19
2-20
2-20
2-21
2-21
-------
3.
3.1.
3.1.1.
3.1.4.
3.1.3.
3.1.4.
3.2.
3.2.1.
3.2.2.
3.2.3.
3.2.4.
3.2.5.
3.2.6.
4.
4.1.
4.1.1.
4.1.2.
4.1.3.
4.1.4.
4.1.5.
4.2.
4.2.1.
4.2.2.
4.2.3.
TABLE OF CONTENTS
(continued)
l,l,I-TRICHLOROETHANE.......
. . . . . . . ,. . . . . . . . . .
Industry Characteristics.
.................
Production and Trade..
.................
Producers..........
....................
Production Process.
....................
Uses. . . . . . . . . . . . . . . . . . . . . . .
............
Potential
for Economic
............
Impact.
Direct Testing Costs.
..................
Demand Sensitivity...
..................
Cost Characteristics.
..................
Industry Structure..
...................
Market Expectations.
...................
Conclusions.
.. .........................
NITROBENZENE......
..........
.................
Industry Characteristics.
.................
Production and Trade..
.................
Producers..........
....................
Production Process.
....................
Uses. . . . . . . . . . . . .
.............. ..... ...
Projected Growth.
..........
............
Potential
for Economic
Impact.
............
Direct Testing Costs.
..................
Demand Sensitivity..
...................
Market Expectations.
...................
ii
Page
3-1
3-1
3-1
3-5
3-7
3-9
3-16
3-17
3-17
3-20
3-20
3-21
3-22
4-1
4~1
4-1
4-4
4-6
4-9
4-17
4-20
4-20
4-22
4-23
-------
4.2.4.
4.2.5.
4.2.6.
APPENDIX A:
APPENDIX B:
TABLE OF CONTENTS (continued)
Cost Characteristics..................
Industry Structure....................
Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . .
Economic Impact Methodology
Direct Cost Estimates
iii
Page
4-24
4-25
4-26
-------
Table 2-1:
Table 2-2:
Table 2-3:
Table 2-4:
Table 2-5:
Table 3-1:
Table 3-2:
Table 3-3:
Table 3-4:
Table 3-5:
Table 3-6:
Table 3-7:
Table 4-1:
Table 4-2:
Table 4-3:
Table 4-4:
LIST OF TABLES
Page
Production and Unit Sales Value
for Dichloromethane..................... 2-2
U.S. Imports and Exports of
Dichloromethane. . . . . . . . . . . . . . . . . . . . . . . .. 2-4
Dichloromethane Producers, Capacities,
Process Used and Other Chloromethane
Products Produced....................... 2-5
End-Use Demand Pattern for
Dichloromethane.........................
2-11
Estimated Test Costs,
Dichloromethane.........................
2-18
Production and Unit Sales Value
for l,l,l-Trichloroethane............... 3-2
United States Exports of l,l,l-Trichlo-
roethane by Quantity and Value by
Country of Destination ................. 3-4
l,l,l-Trichloroethane Producing
Companies, Plant Locations, and
Capacities. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 3-6
Key to Names, Abbreviations, and
Formulas for Chemicals Shown in
Figures 3-1 and 3-2.....................
3-11
Process
Chemical Reactions................
3-12
End Use Demand Pattern for
1,1, I-Trichloroethane. ..................
3-14
Estimated Test Costs:
1,1, I-Trichloroethane...................
3-18
Nitrobenzene Production................... 4-2
Imports of Nitrobenzene and Aniline....... 4-4
Manufacturers of Nitrobenzene by
Company and Location.................... 4-5
Estimated Test Costs, Nitrobenzene........ 4-21
iv
-------
Figure 2-1:
Figure 3-1:
Figure 3-2:
Figure 4-1:
Figure 4-2:
Figure 4-3:
Figure 4-4:
Figure 4-5:
Figure 4-6:
Figure 4-7:
LIST OF FIGURES
Manufacturing Process for
Chloromethanes. . . . . . . . . . . . . . . . . . . . . . .
Flowsheet for Chlorocarbons
Manufacture. ...........~..............
Flowsheet for Manufacture of
1, 1, l-Trichloroethane. ................
Scheme for Nitrobenzene
Ma n u fa c t u r e. . . . . . . . . . . . . . . . . . . . . . . . . . .
Uses
of Nitrobenzene......... ...........
Uses
of Aniline.........................
Consumption Pattern for
Polyurethane Foams 1978...............
Alternative Manufacturing Routes
to Ani 1 ine. . . . . . . . . . . . . . . . . . . . . . . . . . . .
End-Use Substitutes Originating
From Benzene.. . . . . . . . . . . . . . . . . . . . . . . . .
U.S. Nitrobenzene Production,
1970-1979. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
v
Page
2-9
3-8
3-10
4-8
4-10
4-11
4-13
4-14
4-18
4-19
-------
CHAPTER 1
EXECUTIVE SUMMARY
1.1.
Introduction
One of the major focuses of the Toxic Substance Control
Act (TSCA, 15 USC 2601) is to determine the toxic effects of
existing and potential substances.
In order to implement
this objective, sets of testing requirements are being de-
veloped on a case by case basis.
Section 4(b) (1) of TSCA
instructs the EPA Administrator to consider the relative
costs of various test protocols and methodologies which may
be required.
In general, the Act places an emphasis on con-
sidering the economic impacts of actions taken, as well as
the environmental and social impacts.
This report presents the
results of an economic impact analysis of proposed testing
requirements for three chemicals:
dichloromethane, l,l,l-tri-
chloroethane, and nitrobenzene.
The purpose of this study is to determine when signif-
icant economic impacts may occur as a result of particular
testing regulations and to estimate the magnitude of these
impacts.
Although benefits to society, such as a reduction
of disease incidence, may result from the testing of chemical
substances, this study deals only with the economic effects
associated with imposing testing regulations.
1.2.
Objectives and Methodology
In order to determine the economic impact of testing
requirements,
a two-level impact analysis scheme has been
1-1
-------
devised.
The overall objectives of these analyses are (1)
to determine whether there is any significant potential
for adverse economic impact resulting from testing regula-
tions: and (2) where the possibility of an adverse impact
exists,
to estimate the magnitude of the economic impact.
Level I economic impact analysis is concerned with the first
objective, whereas Level II deals with in-depth analysis of
impacts.
The general approach to analyzing economic impacts
is outlined in the following paragraphs and is discussed
in detail in Appendix A.
1 . 2 . 1 .
Level I Economic Analysis
Level I analysis involves determining whether the poten-
tial for adverse impact exists.
As such, it investigates
those market characteristics which indicate the likelihood
of economic impacts due to the regulation.
The market
characteristics investigated in Level I analysis include:
(1) demand sensitivity,
(2) cost characteristics (3)
industry structure, and (4) market expectations.
The information concerning these factors must be readily
developed, so that all substances recommended for EPA con-
sideration by the Interagency Testing Committee, or selected
by EPA for possible testing, can be subjected to Level I
analysis.
In light of this, the variables examined to
determine the potential for impact must be conservative in
nature.
That is, we wish to minimize the probability of
1-2
-------
falsely rejecting a chemical substance for Level II analysis;
i.e., a
Level II analysis should be conducted if there is
any possibility of adverse economic impact.
1.2.2.
Level II Economic Impact Analysis
For those chemical substances where the Level I analys~s
indicates a significant potential for adverse economic
impQcts, a comprehensive economic impact analysis is con-
ducted.
At this level an in-depth investigation concerning
the market characteristics is undertaken and estimates of
the important variables are made.
The direct cost of the
test requirements is integrated with these estimates in order
to determine the magnitude of the economic impacts.
1. 3.
Conclusions
1.3.1.
Dichloromethane
As described above and discussed in Appendix A, a set
of four market attributes are investigated in order to
determine the potential impact of testing requirements.
The results of these investigations indicate that the
potential for significant adverse economic impacts on the
dichloromethane industry is low.
This conclusion is based upon the following considera-
tions:
First, demand for dichloromethane appears to be
relatively insensitive to changes in price.
That
is, an
1-3
-------
increase in price is expected to result in a proportionately
smaller decrease in the quantity demanded, particularly over
the range of additional per unit cost (i.e., up to .03 cents
per lb. or .15 percent of prices).
The major market for
dichloromethane is in paint removal, where it is the most
effective product.
In addition, the market for dichloro-
methane is expected to grow, particularly in aerosol and
urethane foam blowing uses.
Thus, the demand for dichloro-
methane is expected to increase.
Although one company owns 48 percent of the total
production capacity, even the smallest firms produce sig-
nificant quantities of dichloromethane.
The production
.
equipment is relatively flexible, indicating the possibility
of adjusting production levels.
This suggests a competitive
market situation and no individual firm can be singled out
as particularly susceptible to adverse impacts resulting
from testing costs.
1.3.2.
l,l,l-Trichloroethane
l,l,l-Trichloroethane is a major solvent with a pro-
duction volume of over 700 million pounds per year.
It is
used primarily in cold metal cleaning and vapor degreasing.
From an analysis of the four market characteristics dis-
cussed above, it appears that the potential for significant
adverse impacts on the l,l,l-trichloroethane industry is
small.
1-4
-------
The major factor supporting this conclusion is the fact
that on a per unit basis the additional cost imposed as a
result of testing requirements is relatively insignificant,
ranging up to .01 cents per lb.
(or .07 percent of price).
This additional cost is particularly small in light of the
relative insensitivity of demand to price changes and the
moderate, but stable, growth predicted for l,l,l-trichloro-
ethane.
1.3.3.
Nitrobenzene
Nitrobenzene is a commercially important aromatic inter-
mediate, used almost exclusively as a feedstock for aniline,
and subsequently, polyurethanes.
Production of nitrobenzene
is growing at a very rapid rate and the impact of testing costs
on the industry is expected to be minimal.
The market for nitrobenzene is very strong, with new
uses being developed and the current end-use markets ex-
panding rapidly.
These two factors should insure continued
growth for nitrobenzene, even after test requirements are
imposed.
This is further supported by the fact that the
test costs are extremely small on a per unit basis (up to
.02 cents per lb.).
In addition, none of the producers
of nitrobenzene appears to be in a relatively vulnerable
position with respect to test costs.
1. 4.
Limits of Analysis
Analysis, such as described here, is invariably an un-
certain instrument.
For this reason, a "worst case"
1-5
-------
approach has been developed.
The objective is to never over-
look a situation where substantial adverse economic impact may
arise as a result of regulatory action.
The overall approach used in this report to analyze pot en-
tial economic effects is that of partial equilibrium analysis.
This approach considers all factors not directly accounted for
in the analysis (such as the total demand on testing facilities)
to be held constant.
It does not attempt to assess the "ripple"
effects of an action throughout the entire economy, but rather
concentrates on that part of the chemical industry directly im-
pacted, along with any upstream or downstream industries
significantly affected.
1-6
-------
CHAPTER 2
DICHLOROMETHANE
2 .1.
Industry Characteristics
Dichloromethane (methylene chloride) is a major
chlorinated solvent.
Its primary uses are as a solvent in
paint removers, as a propellant in aerosol mixtures, and for
metal vapor degreasing.
Production of dichloromethane (DCM)
has grown at a rapid annual rate, exceeding ten percent
overall since 1962, but leveling off in recent years.
A
combination of relatively low price and desirable chemical
properties make it very competitive in each of its major
markets.
2 . 1 .1.
production and Trade
production volume, sales volume and unit sales value for
DCM from 1962 to 1979 are presented in Table 2-1.
Domestic
production of DCM grew at an average annual rate of 12.8
percent between 1962 and 1974.
In 1975, production dropped
by over 18 percent and the growth rate has slowed during the
subsequent four years (1976-1979) to an average of 5.7 per-
cent per year.
A large portion of production is sold on the merchant
market (86 percent in 1978).
Thus, the unit sales value can
be considered a good indicator of annual average price.
The
unit sales value is derived from the value of large quantities
sold on contract and small quantities sold on the spot market.
2-1
-------
TABLE 2-1: PRODUCTION AND UNIT SALES
VALUE FOR DICHLORO~mTHANE
Production Unit Sales
Year Volume Value
Million 1bs. $/lb.
1962 143.8 0.09
1963 148.0 0.09
1964 179.6 0.09
1965 210.8 0.09
1966 267.2 0.10
1967 262.3 0.09
1968 302.6 0.08
1969 366.0 0.08
1970 402.2 0.08
1971 401.2 0.07
1972 471.3 0.07
1973 520.2 0.08
1974 608.8 0.13
1975 497.1 0.16
1976 537.7 I 0.17
1977 477.9 0.18
1978 570.1 0.23
1979 633.2 0.20
SOURCE:
Synthetic Organic Chemicals
(USITC-SQC 1962-1980).
2-2
-------
During the early 1970s, the average price was 7 to 8 cents per
pound.
Between 1973 and 1975, it doubled to 16 cents per pound,
due to a general increase in the price of petrochemicals.
In
1978 it rose to 23 cents per pound, but felL back to 20 cents
in 1979.
Imports of DCM have increased considerably since 1970.
However, they are currently small relative to domestic produc-
tion, representing about seven percent of production in 1979.
Exports, on the other hand, have remained fairly constant over
the past decade (although they dropped by a third in 1978,
they returned to more normal levels in 1979).
Exports re-
presented about 15 percent of domestic production in 1979, and
are expected to remain fairly steady in the future.
The volume
of DCM imports and exports since 1970 is shown in Table 2-2.
2.1.2.
Producers
Five companies produce DCM in the United States.
These
companies, their plant locations,
capacities,
and production
processes are shown in Table 2-3.
The other chloromethane
products produced by these companies are also indicated in
the table.
All producers except Vulcan Materials (at both
plant locations--Geismar, Louisiana and Wichita, Kansas)
also produce chloromethane.
In addition, all producers of
DCM also produce trichloromethane (chloroform).
Annual
capacities listed for DCM are very flexible and may be adjusted
according to demand for specific chloromethane end products,
since the same plant generally produces other chloromethane
products.
2-3
-------
TABLE 2-2: U. S. IMPORTS AND EXPORTS
OF DICHLOROMETH~~E
Year
Imports
(million 1bs.
Exports
(million 1bs. )
1970
1971
1972
1973
1974
1975
1976
1977
1978 i
1979 ;
I
9.5
7.8
11.1
42.3
12.3
12.1
42.1
60.9
61.0
42.9
85.5
86.9
103.6
114.2
101.4
97.0
84.2
97.4
62.2
92.5
SOURCES: Foreign Trade Reports (BOe-Imports, 1971-1980,
BOC-Exports, 1971-1980).
2-4
-------
TABLE 2-3
DICHLOROMETHANE PRODUCERS, ~APACITIES, PROCESS USED
AND OTHER CHLOROMETHANE PRODUCTS PRODUCED
rv
I
U1
Dichloromethane
Company Plant Location Capacity b Other Products Process
1978 1979 CH3Clc CHCl~ CCle
- 4
1\11 ied Chemical Corp. Houndsville, wv 50 50 Hydrochlorination of methanol fol-
Specialty Chemicals I I I lowed by thermal chlorination of
Division chloromethane
Diamond Shamrock Corp. Belle, wv 110 110
Industrial Chemicals
and Plastics Unit, I .; I
Electro Chemicals
Division
Dow Chemical U.S.A. Freeport, TXa 200 190 I I I Direct thermal chlorination of
methane
Plaquemine, LA 190 210 Hydrochlorination of methanol foI-
I I I lowed by thermal chlorination of
chloromethane
Stauffer Chemical Co. Louisville, KY 60 60
Industrial Chemical .; .; I
Division
vulcan Materials Co. Geismar, LA 80 80 I I
Chemicals Division
Wichita, KA 130 130- I I
TOTAL 820 830
-
SOUrtCZS; Directory of Chemical Producers
(SRI 1978), Chemical Marketing Reporter (~~ 1979).
aDow is increasing capacity at their Freeport, TX plant by an undisclosed amount in 1981.
bcapacities are very flexible for chloromethanes and may be adjusted according to demand for
cCII)Cl Chloromethane (Hethyl Chloride)
dClICl) Trichloromethane (Chloroform)
eCC14 Tetrachloromethane (Carbon Tetrachloride)
specific end-products.
-------
Total industry capacity has been stable since 1978 at more
than 800 million pounds per year.
Capacity utilization in
1979 was about 73 percent, which is considered about average.
Because of expected growth, discussed below, the largest pro-
ducer, Dow Chemical, is planning a capacity addition at its
Texas plant for 1981 (CMR 1979).
2.1.3.
Production Process
Dich1oromethane (DCM) is produced industrially in the
United States by two methods (Kirk-Othmer 1979, McKetta 1979):
o
Direct thermal chlorination of methane:
o
Hydroch1orination of methanol followed by the
thermal chlorination of chloromethane.
Since DCM hydrolyzes with water to produce toxic phosgene
and chlorine, the commercial product is usually stabilized
against hydrolysis by incorporating small amounts of phenols
or amines.
(1) Direct Thermal Chlorination of Methane.
The substitu-
tion of chlorine for hydrogen atoms in a hydrocarbon is an
important commercial chlorination process.
Chlorine is
activ~ted for the substitution reaction by either thermal or
photochemical means.
Thermal chlorination is inexpensive
and less sensitive to inhibition than the photochemical
process.
Chlorination of methane yields all four possible chlorin-
ated derivatives:
chloromethane (methyl chloride:
CH3Cl),
dich1oromethane (methylene chloride:
CH2C12), trichloromethane
2-6
-------
(chloroform:
CHC13), and tetrachloromethane (carbon tetra-
chloride:
CC14) .
Temperature and raw material flow rates
are therefore critical in producing the particular chloro-
methane desired.
The reactions are:
CH4
+
2C12
. CH2C12
=
2HCl
(CH3Cl,
I
CHLORO-
METHANE
CHC13' CC14)
I
TETRACHLORO-
METHANE
METHANE
CHLORINE
DICHLORO-
METHANE
HYDROGEN
CHLORIDE
TRICHLORO-
METHANE
In this method, excess methane is reacted directly with
chlorine at a temperature of approximately 485°-510°C.
As
explained above, this process produces several co-products.
The reactor effluent also contains unreacted methane and hydro-
gen chloride which are usually separated from the chloromethanes
by scrubbing.
The methane, freed from acid by water scrubbing,
is recycled to the chlorinator.
The chloromethane, which
contains the DCM and its co-products, passes to a sequence
of fractionating columns after washing, alkali scrubbing,
and drying.
( 2) Hydrochlorination of Methanol. In this method of
manufacturing, OCM is produced by first reacting methanol
and hydrogen chloride with the aid of a catalyst to form
chloromethane.
This reaction is generally carried out in
the vapor phase where methanol and hydrogen chloride are
continuously mixed in approximately equimolecular ratios and
passed through a preheater.
The gas mixture is then passed
2-7
-------
through a catalytic converter at about atmospheric pressure
and a temperature of about 350°C.
The chloromethane produced is then fed to reactors similar
to those used in the methane process, where it is combined
with chlorine to produce DCM, trichloromethane (chloroform),
and tetrachloromethane (carbon tetrachloride).
Condensers
collect and purify the hot reaction gases leaving the converte~
in a manner similar to that described for the methane process.
Dichloromethane can also be produced in the liquid phase
at 100 - 150°C by refluxing and distilling an aqueous mixture
containing methanol, hydrogen chloride, and zinc chloride.
This method is not as widely used (Kirk-Othmer 1979).
The
reactions are:
CH30H
METHANOL
+
HCl
, CH3Cl
+
H20
HYDROGEN
CHLORIDE
CHLORO-
METHANE
WATER
, CH2C12
I
DICHLORO-
METHANE
+ HCl
I
HYDROGEN
CHLORIDE
(CHC13,
I
TRICHLORO-
METHANE
CH3.Cl
CHLOHO
METHANE
+
C12
+
CC14)
I
TETRACHLORO-
METHANE
CHLORINE
.
Manufacturing processes for chloromethanes are shown in Figure 2-1.
Dichloromethane can also be produced by the reduction of
higher chloromethanes (trichloromethane, tetrachloromethane),
but such methods have not achieved industrial significance.
Seventy-seven percent of United States DCM capacity is
based on the hydrochlorination of methanol, while the remaining
2-8
-------
FIGURE 2-1~UFACTURING PROCESS FOR
CHLOROME THANE S
CH)OH
HCI
Al20)
Cl2
HEAT
CH4
KEY:
CH4
CH)OH
CH)Cl
CH2Cl2
CHCl)
CCl4
Cl2
HCl
Al203
j
CH3Cl
CH2Cl2
~
CHCl3
~
CCl4 [
Methane
Methanol
Chloromethane (Methyl Chloride)
Dichloromethane (Methlyene Chloride)
Trichloromethane (Chloroform)
Tetrachloromethane (Carbon Tetrachloride)
Chlorine
Hydrochloric Acid
Aluminum Oxide
SOURCE: Kirk-Othmer Encyclopedia of Chemical
Technology, Third Edition (Kirk-Othmer 1979).
2-9
-------
23 percent is based on the direct chlorination of methane.
There are several factors that favor the production of DCM
from chloromethane derived from methanol and chlorine over
the direct chlorination of methane.
First of all, methane
chlorination requires a very high purity methane feedstock,
prepared by very expensive cryogenic distillation of natural
gas.
Another factor in favor of a hydrochlorination route to
chloromethane is that there is no byproduct hydrogen chloride,
whereas when methane is chlorinated, one-half the total
chlorine feedstock goes to hydrogen chloride (HC1).
HCl can
be a serious problem unless the plant is located near a
market returning chlorine values for HC1.
When DCM is the
principal end product, combining the hydrochlorination
route with a thermal chlorination unit practically eliminates
the by-product HC1, since it is recycled back to hydrochlori-
nation of methanol and produces chloromethane.
2.1.4.
Uses
The end-use demand pattern for DCM is shown in Table 2-4.
Dichloromethane is used in many applications as a solvent.
The single most important application of DCM is in paint
removal--both industrial and retail--which accounted for 34
percent of domestic consumption in 1979 (CMR 1979).
When
used in paint stripping, DCM is usually blended with other
chemicals to maximize its effectiveness against specific
coatings.
Typical additives include alcohols,
acids,
,
amines
2-10
-------
TABLE 2-4:
END-USE DEMAND PATTERN FOR
DICHLOROMETHANE*
End Use
Percent
Total
Demand
Paint remover
34%
Aerosol Component
25%
Metal Degreasing
21%
Urethane Foam Blowing Agent
11%
Other
9%
SOURCE:
Chemical Marketing Reporter, (CMR 1979).
*Note:
15 percent of domestic production is expofted.
This amount is not included in the end-use
pattern.
or ammonium hydroxide, detergents, and paraffin wax.
For
industrial paint removal, DCM offers the advantage of not
attacking aluminum, unlike alkaline paint removers.
In
household formulations, nonflammability and low acute.toxicity
have helped it to dominate this market (SRI 1977).
The second most important application of DCM is as a
vapor pressure depressant and solvent in aerosol mixtures.
This end use accounted for 25 percent of domestic consumption
in 1979.
Growth in the aerosols sector has been enhanced by
the demise of chlorofluorocarbons as propellants.
Replacement
of fluorocarbons will continue to provide better than average
growth (CMR 1979).
2-11
-------
The third most important application of DCM is as a
solvent for vapor degreasing of metal parts.
This end use
accounted for 21 percent of domestic consumption in 1979
(CMR 1979).
Dichloromethane growth in this market is expected
to be lower than the overall rate in the degreasing market.
DCM is also used as a blowing agent for polyurethane
foam.
DCM has gained a large share of this market due to
the demise of chlorofluorocarbon blowing agents.
This appli-
cation accounted for 11 percent of domestic consumption in
1979.
Producers are very optimistic about blowing agent
demand (CMR 1979).
Other solvent applications of DCM are (ADL 1975, Kirk-
Othmer 1979, McKetta 1979, Radian 1979, TSCA-ITC 1978):
solvent for the decaffeination of coffee,
hops, edible fats, cocoa, and butter7
spices,
solvent to wash cellulose acetate in photographic
film manufacturing7
as an ingredient blended with other chlorinated
hydrocarbons for use as a cleaner in the metal
industrY7
solvent carrier for the manufacture of insecticide
and herbicide chemicals 7
process solvent in the manufacuture of steroids
antibiotics, vitamins, and to a lesser extent
as a solvent in the coating of tablets7
solvent for oils, ink dyes, waxes, and sterilizing
agents7
solvent in manufacturing of synthetic fibers such
as rayon and PVC.
Nonsolvent applications of DCM are:
formulated products containing DCM in adhesives7
2-12
-------
as an ingredient blended with other chemical
compounds in quick drying coatings~
low pressure refrigerants, air conditioning
installations, and as a low temperature heat
transfer medium~
in the manufacture of polycarbonate plastic from
bisphenol and phosgene~
in the manufacture of photoresist (Kirk-Othmer 1979)
coatings (ie. coatings applied to photoreactive polymers
to alter or inhibit this reaction);
as a component of fire extinguishing compositions~
as a chemical intermediate for the manufacture of
dyes, perfumes, chlorobromoethane, and hexamethylene-
tetramine.
2.1.5.
Substitutes
In this section we discuss substitutes for DCM in three
major uses:
paint removal, aerosol propellant and vapor de-
greasing.
(1) Substitutes for DCM as a Paint Remover.
There are
two broad types of paint removers:
the solvent type and the
chemical type, which is usually alkaline in nature.
(a) Solvent Type Paint Removers.
The most popular
solvent type of paint and varnish remover contains a primary
solvent, a cosolvent,
an activator, a thickener, an evapora-
tion retarder, a corrosion inhibitor, wetting agents, and
emulsifiers (Chandler 1971, Kirk-Othmer 1967, Martens 1968).
A number of factors must be considered in formulating a
solvent-type paint remover.
All of the desirable features
may not be realized in one product, but the goals are rapidity
of action,
correct viscosity, nontoxicity,
rinseability,
2-13
-------
non-corrosiveness,
and package stability (Martens 1968).
Since the active ingredient is the solvent, most attention
is paid to its selection.
Solvent-type paint removers may
be subdivided into the following three classes (Kirk-Othmer 1967):
1.
Paint removers based on chlorinated hydro-
ca'rbon sol vents;
2.
Paint removers consisting of mixtures of
solvents other than chlorinated hydrocarbon
solvents;
3.
Paint removers based on aqueous solutions or
dispersions of phenols and/or organic acids and
other compounds.
By far the most popular solvent-type paint remover is DCM;
it is practically nonflammable, the least acutely toxic, and
the most efficient of the chlorinated hydrocarbons (Martens 1968,
SRI 1977).
The most important chlorinated hydrocarbon sOlvent-type
paint removers in terms of solvency are shown below relative to DCM:
Solvent Solvency Rating
Dichloromethane 100
Chloroform 69
Ethylene Dichloride 45
Trichloroethylene 36
Monochlorobenzene 36
Because of their low cost, strippers based on solvents
other than chlorinated hydrocarbons are still used for removing
oleoresinous and less resistant finishes.
They are of the
lacquer-type solvents, such as benzene, and contain cosolvents
such as methanol and ketone.
Paint removers based on phenols
and the chloroacetic acids are highly active chemicals which
2-14
-------
are useful in certain specific functions.
Specific materials
that are commercially available at low cost are cresylic
acid (mixed cresols) and a crude mixture of mono-, di-, and
trichloroacetic acids (Chandler 1971, Kirk-Othmer 1967).
(b) Chemical-Type Paint Removers.
A boiling solution
of caustic soda, at a concentration of a few pounds per
gallon, is effective and inexpensive, and is often used for
general stripping of industrial paints.
Suitable additives
such as surfactants,
and activators are added to the caustic
soda to increase stripping rates.
Other chemical-type paint
removers are potassium hydroxide and lime (Kirk-Othmer 1967,
Martens 1968).
(2) Substitutes for DCM as an Aerosol Propellant.
Growth
in the aerosols sector for DCM has been spurred by the demise
of liquefied chlorofluorohydrocarbon propellants such as:
o
Trichlorofluoromethane (Propellant 11);
o
Dichlorodifluoromethane (Propellant 12)~
o
l,2-Dichloro-l,l,2,2-tetrafluoroethane
(Propellant 114).
Fluorohydrocarbons not containing chlorine (i.e., 1,1-
difluororethane (Propellant 152a)) are not implicated in the
ozone controversy (Chandler 1971, Kirk-Othmer 1978).
Other
liquified propellants which are used widely and discussed in
the literature are chlorinated hydrocarbons and hydrocarbons
(Herzka 1966, Kirk-Othmer 1978).
In most cases, blends are
used to produce the best combination of solubility, pressure,
2-15
-------
safety and cost.
Compressed gas propellants which are not
liquefied in conventional aerosol containers are also used.
Chloroethane, chloromethane, DCM, 1, 1, I-trichloroethane,
and vinyl chloride are all chlorinated hydrocarbons with
potential for propellant
use.
The last three compounds,
however, possess too Iowa vapor pressure by themselves, but
may be used as solvents, cosolvents, or pressure reducers in
blends with other propellants (Herzka 1966).
Propane, n-butane, and isobutane are in the hydrocarbon
propellant range.
These can be blended with each other or
with the halocarbons to produce the vapor pressures required
to atomize aerosol products.
The principal objection to light
hydrocarbons in aerosol formulations is flammability, although
it does not preclude their use.
with knowledge of these prop-
erties and with the necessary precautions, one can handle
hydrocarbons quite safely in transportation, storage filling
operations, and consumer use (Herzka 1966).
The compressed gas propellants, carbon dioxide (C02),
nitrous oxide (N20), and nitrogen (N2) are nontoxic, nonfiam-
mable, low in cost, and (except for N20) very inert.
Nitrous
oxide and carbon dioxide are considered to be the more soluble
of the compressed gases, and have long been used in the food
aerosol field.
The future of the compressed gas propellants
is as promising as, if not more promising than, the other
propellant groups because of their extreme versatility and low
cost.
2-16
-------
(3) Substitutes for DCM in Vapor Degreasing.
DCM used
for the vapor degreasing of metal parts is in competition
with trichloroethylene (TCE), perchloroethylene (PCE), and
l,l,l-trichloroethane (l,l,l-TCEA).
DCM, which has the lowest
boiling point of the four solvents, is used for cleaning
thermal switches, thermometers,. and other temperature sensi-
tive parts.
Because of its high solvent power, it is used
to remove tough paint residues and hard to dissolve resins.
Most vapor degreasing operations can be performed with any
of the four solvents, so the choice is based primarily on
performance characteristics, environmental considerations
and safety-
DCM generally lies at the higher end of the
cost range.
2.2.
Potential for Economic Impact
An analysis of the market characteristics for DCM leads
to the conclusion that the potential for adverse economic
effects due to the proposed testing requirements is low.
2.2.1.
Direct Testing Costs
The direct testing costs estimated for dichloromethane
are based on the tests recommended in the Proposed Test
Rule.
The estimated cost ranges, as shown in Table 2-5, are
purposely wide, reflecting the uncertainty about the test
parameters specified in the test rule.
In order to compare test costs with production and price
levels, the total costs must be annualized.
This is done
using a cost of capital of 25 percent over a period of 15
2-17
-------
TABLE 2-5: ESTI~ATED TEST COSTS~l
DI CHLOROMETH.A.NE
Test
Estimated Cost
Health Effects
Dermal sensitization
Reproductive effects
Subchronic cardivascular toxicity
1,950 - 5~800
135,000 - 406,000
46,000 - 138,100
Environmental Effects
Early life stage toxicity, fathead minnow
Early life stage toxicity. rainbow trout
Early life stage toxicity. sheepshead minnow
Daphnid life cycle, flow through
Mysid life cycle
5 day dietary toxicity, mallard
5 day dietary toxicity, quail
Avian reproduction, mallard
Avian reproduction, quail
Early seedling growth
Plant uptake and translocation
Bioconcentration, fish
5,700 -
7.200 -
5,700 -
2.000 -
1,650 -
1,400 -
1,000 -
12,100 -
10,300 -
1,200 -
1,000 -
4,150 -
17,000
21,500
17,000
6 ,100
4,950
4,200
3,000
36,200
30,800
16,000
25,000
12,400
Tota 1
1Source:
Borriston Labs, Inc. estimates.
protocol estimates.
See Appendix B for specific
2-18
$182,950 - 549~900
$ 53.400 - 194.150
$236,350 - 744,050
-------
years (capital recovery factor =. 25912)
(DuPont 1980).
The
annualized cost range is $61,250 - $192,800 per year.
Based on 1979 production, this represents .01-.03 cents per
pound, or approximately .05-.15 percent of the 1979 price.
2 . 2 . 2 .
Demand Sensitivity
The sensitivity of demand to changes in price affects
the ability of firms to pass on increases in manufacturing
costs.
This, in turn, determines the overall change in produc-
tion caused by an increase in costs and may suggest instances
in which a firm will cease production of this product.
The demand for DCM is believed to be relatively insen-
sitive to price increases.
In its major market (paint removal),
it is the most effective product.
As discussed above, many
other paint removal products are available, however DCM has the
highest relative solvent power.
For this reason it can be
used to remove any paint product and may be the only product to
meet specific requirements in certain applications.
Because
of these properties, the demand for DCM as a paint remover
should be relatively insensitive to price changes.
This is
particularly the case with respect to the small per unit
cost increases expected as a result of testing.
In the other major markets (aerosols and vapor degreasing)
demand may be more sensitive to price increases, due to the
existence of substitute products.
However, DCM has been
replacing some fluorocarbons (especially Fluorocarbon 11) and
2-19
-------
is expected to continue to do so, based on specific desirable
properties.
2 . 2 . 3 .
Cost Characteristics
The primary cost characteristic of DCM production relevant
to the potential impact of testing is the fact that each DCM
manufacturer also produces chloromethane and other chlorinated
methane products.
The equipment utilized is sufficiently
flexible that production can be shifted among the alternative
products at minimal cost.
As a result, producers can poten-
tially adjust production levels of DCM internally without
major impacts.
However,
it should be noted that several of
these other products are also being considered for testing
under TSCA (e.g., chloromethane).
2.2.4.
Industry Structure
Of the five companies that produce DCM, the largest owns
about 48 percent of total capacity and the two smallest own
about six percent each.
Although this range is rather large,
even the smaller firms produce significant quantities of
DCM.
For example, if the smallest firm operates at three-
fourths capacity, its annual production is over 35 million
pounds per year.
In addition, this firm (Allied Chemical)
produces a wide range of other chemicals, including all
of the other chlorinated methane products.
Because of
the flexibility of production equipment discussed above,
production adjustment and/or market entry should preclude
2-20
-------
noncompetitive behavior and above-normal profits in the
industry.
Thus, the firms are believed to operate in a
competitive atmosphere.
2.2.5.
Market Expectations
According to market analysts, the production of DCM is
expected to grow at an overall annual rate of 6.5 percent
through 1983 (CMR 1979).
Most growth should occur in the
aerosols market, where DCM will continue to replace fluoro-
carbons.
In addition, OCM should gain a larger market share
in the rapidly growing market for urethane foam blowing agents.
Demand for DCM in its major market (paint removal) is expected
to remain steady.
The combination of these factors leads to
an optimistic outlook for DCM over the next decade.
2.2.6.
Conclusions
The impact of the proposed testing requirements on the
dichloromethane industry should be small for two reasons.
First, the incremental cost of testing on a per pound basis
is estimated to be very small (up to .03 cents per lb.).
In
addition, demand for OCM in its major markets appears to be
relatively insensitive to changes in price.
Thus it is
possible that such a small cost increase could be passed on
by the producers.
The market outlook for DCM is relatively
strong and it appears that none of the producers would be
particularly adversely impacted by the increased cost.
For
these reasons, the potential for economic impact appears to
be low and no Level II economic impact analysis is recommended.
2-21
-------
REFERENCES - CHAPTER 2
~rL. 1975. Arthur D. Little, Inc. Shamel RE, et al. Preliminary economic
impact assessment of ~ussible regulatory action to control atmospheric
emissions for selected halocarbons. Washin~ton, DC: U.S. Environmental
Protection Agency, Office of Air Quality Planning and Standards. EPA Report
No. 450/3-75-073 (PB-247 115).
BOC-Imports. 1979-1980. Bureau of the Census. Foreign Trade Reports.
FT-135. United States Imports, Schedule A, Commodity Groupings. Commodity
by Country. Washington, DC: U.S. Department of Commerce.
BOC-Exports. 1971-1980. Bureau of the Census. Foreign Trade Reports.
FT-410, United States Exports, Schedule B, 1970-1977. Schedule E, 1978-1980
Commodity by Country. Quantity and Value, Current and Cumulative.
Washington, DC: U.S. Department of Commerce.
Chandler RH. 1971. Paint removers (bibliographies in paint technology,
no. 16. U.S. Patent Office.
CMR. 1979. Chemical profile: methylene chloride.
Reporter. August 6, 1979.
DuPont. 1980. Comments to chloromethane and chlorinated benzenes. Docket
Nos. 80T-125 and 80T-126. Washington, D.C: U.S. Environmental Protection
.Agency. October 31, 1980.
In:
Chemical Marketing
Herzka A. 1966. International Encyclopedia of Pressurized Packaging.
Herzka A, ed. New York: Pergamon Press.
Kirk-Othmer. 1967. Paint and varnish removers. In: Kirk-Othmer
Encyclopedia of Chemical Technology. 2nd ed., Vol. 14, New York:
Wiley-Interscience, pp. 485-490.
Kirk-Othmer. 1978. Kowan A, Flynn JB. Aerosols. In: Kirk-Othmer
Encyclopedia of Chemical Technology, 3rd ed., Vol. 1. New York:
Wiley-Interscience, pp. 582-597.
Kirk-Othmer 1979. Archer WL. Chlorocarbons and chlorohydrocarbons. In:
Kirk-Othmer Encyclepedia of Chemical Technology, 3rd ed. Vol. 3, New York,
Wiley-Interscience pp. 668-676, 686-693.
Martens C. 1968. Technology of Paints, Varnishes and Lacquers.
ed. New York: Reinhold Book Corporation.
Martens C,
McKetta JJ. 1979. Encyclopedia of Chemical Processing and Design, Vol. 8.
McKetta JJ, ed. The Netherlands: Harper and Row, pp. 214-270.
NAS. 1978. Chloroform. carbon tetrachloride. and other halomethanes:
an environmental assessment. Washington, DC: National Acac1emy of
Sciences, National Research Council.
Radian.
1979.
Lee BB, et al.
Organic solvent use study. Washington, DC:
2-22
-------
u.s. Environmental Protection Agency, Office of Toxic Substances.
No. 560/12-79-002.
EPA Report
SRI. 1977. SRI International. A study of industrial data on candidate
chemicals for testing. Washington, DC: U.S. Environmental Protection
Agency. Office of Toxic Substances. EPA Report No. 560/5-77-006 (PB-274 264).
SRI. 1978. SRI International.
States. Menlo Park, CA.
Directory of Chemical Producers, United
TSCA-ITC. 1978. TSCA Interagency Testing Committee. Second report of the
TSCA Interagency Testing Committee to the Administrator, Environmental
Protection Agency. Washington, DC: U.S. Enironmental Protection Agency.
EPA Report No. 560/10-78-002 (PB-285 439).
USITC-SOC. 1973. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales, 1971.
Washington, DC: Government Printing Office. USITC pub. 614.
USITC-SOC. 1974. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales, 1972.
Washington, DC: Government Printing Office. USITC pub. 681.
USITC-SOC. 1975. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales, 1973.
Washington, DC: Government Printing Office. USITC pub. 728.
USITC-SOC. 1976. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales, 1974.
Washington. DC: Government Printing Office. USITC pub. 776.
USITC-SOC. 1977a. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales, 1975.
Washington, DC: Government Printing Office. USITC pub. 804.
USITC-SOC. 1977b. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales, 1976.
Washington, DC: Government Printing Office. USITC pub. 833.
USITC-SOC. 1978. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales, 1977.
Washington, DC: Government Printing Office. USITC pub. 920.
USITC-SOC. 1979. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales, 1978.
Washington, DC: Government Printing Office. USITC pub. 1001.
USITC-SOC. 1980. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales, 1979.
Washington, DC: Government Printing Office. USITC pub. 1099.
2-23
-------
CHAPTER 3
1, 1, I-TRICHLOROETHANE
3.1.
Industry Characteristics
l,l,l-Trichloroethane (l,l,l-TCEA) is a major solvent
used in such applications as cold metal cleaning and vapor
degreasing.
Production has been growing at a rapid rate and
currently exceeds 700 million pounds per year.
Although the
growth rate has declined recently, the market for l,l,l-TCEA
is expected to continue to be relatively strong in the future.
3 . 1 .1.
Production and Trade
Production volume,
sales volume, and unit sales value
for l,l,l-trichloroethane from 1970 to the present are shown
in Table 3-1.
Production has increased from 366.6 million
pounds in 1970 to 716 million pounds in 1979.
The annual
production growth rate of 7.6 percent for l,l,l-TCEA is
above the growth rate for other chlorinated solvents, al-
though it has slowed considerably in recent years.
The rapid growth of l,l,l-TCEA during the early 1970s
was caused by the replacement 'of some trichloroethylene (TCE)
with l,l,l-TCEA.
Much of this replacement occurred in recogni-
tion of potential environmental and health problems with TCE.
Because of the high cost of emission control systems for TCE,
metal cleaning firms in particular have turned to l,l,l-TCEA
which does not need expensive controls.
In locations where
air quality has not been a problem, the change from TCE to
1, 1, I-TCEA has been slower (C&EN 1979b).
3-1
-------
TABLE 3-1: PRODUCTION AND UNIT SALES
VALUE FOR l,l,l-TRICHLOROETHANE
I
Year I Production Unit Sales
I Volume Values
I (Million Ibs.) $/lb.
I
I
1970 I 366.3 $0.10
I
1971 I 374.6 0.09
I
1972 I 440.7 0.09
I
1973 I 548.4 0.09
I
1974 I 591.6 0.13
I
1975 I 458.7 0.17
I
1976 I 631. 2 0.19
I
1977 I 634.8 0.20
I
1978 I 644.5 0.21
I
1979 I 716.3 0.15
I
SOURCE:
Synthetic Organic Chemicals, (USITC-SOC 1971-1980).
3-2
-------
Recent forecasts predict l,l,l-TCEA growth at a reduced
rate in the near term, although some analysts predict large
new markets in the long run.
The consensus forecast is that
domestic demand for l,l,l-TCEA will grow at about a two
percent annual rate (CMR 1979).
Although the growth rate has declined, new production
capacity for l,l,l-TCEA has come onstream.
Annual oper-
ating capacity grew from 690 million pounds in 1978 to about
975 million pounds in 1979 (CMR 1979, SRI 1978-1980).
As a
result,
industry capacity utilization fell from 93 percent
in 1978 to 73 percent in 1979.
During 1979, additional
capacity has been added so that total industry capacity in
1980 is about 1.3 billion pounds per year.
If production
remains relatively steady, industry capacity utilization for
1980 will be just over 50 percent (C&EN 1979b).
Data for imports of l,l,l-TCEA are not available, but
current imports are believed to be negligible due to falling
capacity utilization of U.S. producers (C&EN 1979b).
Imports in the past appear to have been important in times
when capacity utilization has been high.
Data for exports of l,l,l-TCEA are not available prior
to 1978.
In 1978, 39.7 million pounds of l,l,l-TCEA were ex-
ported and in 1979, 59.6 million pounds (BOC-Exports 1979, 1980).
A breakdown of U.S. volume and value of l,l,l-TCEA exports by
country of destination for 1978 and 1979 is shown in Table
3-2.
It is unlikely that the large volume of 1979 U.S.
3-3
-------
w
I
J::o
TABLE 3-2:
UNITED STATES EXPOHTS OF l,l,l-TRI-
CHLOROETHANE, BY QUANTITY AND VALUE
BY COUNTRY OF DESTINATION
Country 1, 1, I-Trichloroethane
of 1978 1979
Destination Quantity Value Quantity Value
(million Ibs.) ($ thousands) (million 1 bs.) ($ thousandE')
Canada 0.97 237.0 3.92 1,520.0
Mexico 1.0 234.0 2.51 765.0
Venezuela 0.43 110.0 1. 61 449.0
Brazil 7.86 1,048.0 6.27 621. 0
Argentina 0.42 82.0 1.17 280.0
United Kingdom 0.66 136.0 0.88 65.0
France 0.67 87.0 --- ---
Federal Republic of Germany 1.11 100.0 2.21 156.0
Singapore 10.78 2,102.0 5.96 1,035.0
Japan 3.99 677.0 3.20 526.0
Australia 10. 97 1,770.0 13.47 2,694.0
Bahamas --- --- 0.14 69.0
Chile --- --- 0.25 75.0
Netherlands --- --- 16.0 2,383.0
Belgium --- --- 0.04 101.0
Philippine Republic --- --- 0.05 84.0
China (Taiwan) --- --- 0.22 79.0
Other Countries 0.84 317.0 1. 67 378.0
TOTAL 39.7 $6,900.0 59.57 $11,280.0
SOURCE: Foreign Trade Reports (BOC-Exports 1978-1979).
-------
exports (8 percent of production) will be repeated in
1980 as l,l,l-TCEA production facilities have recently been
constructed in foreign countries (C&EN 1979b).
Production of l,l,l-TCEA is largely for sales on the
merchant market (as opposed to captive use) and sales in 1978
(631 million lbs.) accounted for about 98 percent of produc-
tion.
Because the majority of production is sold on the
merchant market, unit sales value can be considered a
reliable indicator of average yearly price.
The sales vol-
ume includes both large quantities sold on contract and
small quantities sold on the spot market.
Unit sales value
was about 9.0 cents per pound during 1971-73.
From 1973 to
1976 the average value rose significantly to 19 cents per
pound due to the increase in the price of petroleum based
feedstocks.
The current price is around 15 cents per pound.
3.1.2.
Producers
U.s. producers of l,l,l-TCEA, their plant locations,
capacities, and the production process (CMR 1979, SRI 1978-
1980) used are shown in Table 3-3.
l,l,l-TCEA is currently
produced in the United States by the Dow Chemical, PPG
Industries,
and Vulcan Materials.
Forty-six percent of
industrial capacity (Dow Chemical) is based on the hydro-
chlorination of the un isolated vinyl chloride monomer
(VCM) derived from ethylene dichloride (EDC); thirty-three
percent (pPG Industries) is based on the hydrochlorination
of the unisolated vinylidene chloride monomer (VdCM) also
3-5
-------
TABLE 3- 3 :
l,l,l-TRICHLOROETHANE PRODUCING COMPANIES,
PLANT LOCATIONS, AND CAPACITIES (million Ibs.)
w
I
0)
Company Plant 1975a 1978b 1979c Process
Location
Dow Chemical Company, Freeport, 450 450 450 Hydrochlorination of vinyl
U. S . A.l TX chloride derived from ethylene
dichloride
--.
PPG Industries, Inc. Lake Cha1Jles, 175 175 3252 Hydrochlorination of vinylidene
Chemicals Group LA chloride derived from ethylene
Chemicals Division dichloride
Vulcan Materials Co. Geismar, LA 65 65 2003 Direct chlorination of ethane
Chemicals Division
Ethyl Corporation 4 Baton Rouge, 50 Hydrochlorination of vinyl
--- ---
LA chloride derived from ethylene
dichloride
TOTAL 740 690 975
lDoW has 300 million lbs. ?er year of viable capacity in facilities at Plaquemine. LA. Com-
pleted in 1978. the unit was never brought onstream.
2Capacity does not include an older, 175 million- lbs. -per-year unit which is on standby
and may be cannibalized.
3Vulcan Materials Company has started up 200 tons per day unit at Geismar, LA. Total capa-
city at Geismar is now 300 tons per day.
4Ethyl Corporation closed its plant in 1976 in order to concentrate on its la~ger involvement
in trichloroethylene and perchloroethylene.
Sources: al975 Directory of Chemical Producers, U.S.A.,
bl978 Directory of Chemical Producers, U.S.A.,
cChemical Marketing Reporter,
(SRI 1976).
(SRI 1979).
(CMR 1979).
-------
derived from EDC.
The balance of the capacity (Vulcan
Materials) is based on the direct chlorination of ethane rather
than EDC.
Even though the growth rate has slowed, additional pro-
duction capacity for 1, 1, I-TCEA has recently come onstream
at plants of the three U.S. producers:
Dow Chemical, PPG
Industries, and Vulcan Materials.
In 1978, Dow completed
a 300-million-pounds-per-year plant at Plaquemine, LA, but
the unit was never brought onstream (CMR 1979).
PPG has
added a 325-million-pounds-per-year plant at Lake Charles, LA.
The capacity there does not include an older, 175-million-
pounds-per-year unit which is on standby.
Vulcan Materials
started up a 135-million-pounds-per-year unit at Geismar,
LA in 1979, bringing total capacity at Geismar to 200 million
pounds per year (C&EN 1980).
Ethyl Corporation closed its
plant in 1976 in order to concentrate on its larger involve-
ment in trichloroethylene (TCE) and perchloroethylene (PCE)
(CMR 1979).
3 .1. 3 .
Production Processes
Figure 3-1 describes the manufacture of l,l,l-TCEA and
other chlorinated hydrocarbons from various raw materials
(ADL 1975).
As discussed above, most l,l,l-TCEA is produced
by hydrochlorination of either unisolated VCM or VdCM.
Both
of these materials are derived from EDC.
The third process,
in which ethane is chlorinated directly to l,l,l-TCEA, does
3-7
-------
FIGURF. 3-1:FLOWSHEET FOR CHLOROCARBONS
MANUFACTURE
REF
GASE
ETHANE
!
PROPANE
!
ACETYLENE
INERY J I
S
I
E AND ..... ETHYLENE
ANE "
-
ETHYL CHLORIDE
TANE
ISOLATED VCM~
Y LIQUID . EDC -.. -'ISOLATED VdCM~
STOCKS
UNISOLATED VCM
-
RINE UNISOLATED VdCM
~
> 1, 1 , 1-TCEA
> PCE
> PCE
> TCE
ETHAN
PROP
n-BU
W
I
co
HEAV
FEED
> PVC RESIN
> COPOLYMER RESINS
> PVdC RESIN
> COPOLYMER RESINS
> 1, I, 1-TCEA
CHLO
> 1, 1 , 1-TCEA
> PCE
> TCEA
> EA
> LEAD SCAVENGER
> EXPORTS AND OTHERS
-------
not involve EDC.
The flowsheet for the manufacture of 1,1,1-
TCEA and other chlorinated hydrocarbons is shown in Figure 3-2
(Considine 1974, Kirk-Othmer 1979, McKetta 1979).
A key to
names, abbreviations, and formulae for chemicals shown in
Figures 3-1 and 3-2 is presented in Table 3-4.
In the most frequently used process, VCM, obtained from
EDC, is hydrochlorinated to l,l-dichloroethane which is then
thermally or photochemically chlorinated to produce l,l,l-TCEA
(Equations la and Ib in Table 3-5).
It is believed that this
process is used by Dow Chemical at Freeport, Texas.
Another
process is based on the reaction of chlorine with EDC, dehydro-
chlorinated to VdCM, which is again rehydroclorinated to
yield l,l,l-TCEA (Equations 2a, 2b, and 2c in Table 3-5).
It
is believed this process is used by PPG Industries at the
Lake Charles, Louisiana plant to produce VdCM as an inter-
mediate material not only for the production of l,l,l-TCEA,
but also for the product of VdCM resin and other copolymers.
In a process of less importance, l,l,l-TCEA is produced
by chlorinating ethane to l,l-dichloroethane, which is then
reacted with C12 in a thermal chlorination to produce 1,1,1-
TCEA (see Equations 3 and Ib in Table 3-5).
It is believed
this process is used by Vulcan Materials at Geismar,
Louisiana.
3.1.4.
Uses
l,l,l-TCEA is widely used in cold metal cleaning and
vapor degreasing operations because of its margin of workplace
3-9
-------
FIGURE 3-2:FLOWSHEET FOR MANUFACTURE
OF l,l,I-TRICHLOROETHANE
w
I
.......
o
E D C
5
1 I I, 2-TCEA
KEY:
EDC = ETHYLENE DICHLORIDE
VCM = VINYL CHLORIDE MONOMER
DCE = DICHLOROETHANE
TCE = TRICHLOROETHANE
VdCM = VINYLIDENE CHLORIDE MONOMER
MANUFACTURING
Route },2,3,4
Route 5,6,7,4
Route 8,9,3,4
ROUTE:
followed by Dow Chemical
followed by PPG Industries.
followed by Vulcan Materials.
ISOLATED
VCM
1
UNISOLATED VCM
POLYVINYL
CHLORIDE
HOMOPOLYMER
RESIN
COPOLYMER
RESINS
2
l,l-DCE
3
~-TCEA
1
I
I
I
i
I
I
I
I
I
I
I
I
I
,
------------- --------------~
UNISOLATED VdCM
VdCM
CPOLYVINYLIDENE CHLORIDE
HOMOPOLYMER RESINS
ISOLATED
VdCM
oCOPOLYMER RESINS
8 ETHANE
9 CHLORINE
4
END
USES
-------
TABLE 3- 4 :
KEY TO NAMES, ABBREVIATIONS,
AND FORMULAS FOR CHEMICALS SHOWN
IN FIGURES 3-1 and 3-2
Name
Abbreviation
Formula
Ethane
Propane
Acetylene
n- Butane
Chlorine
Ethylene
Ethyl Chloride
Ethylene Dichloride
l,l,l-Trichloroethane
Perchloroethylene
Trichloroethylene
Vinyl Chloride
Monomer
Polyvinyl Chloride
Resin
Vinlyidene Chloride
Monomer
polyvinylidene
Chloride Resin
Ethyleneamines
C2H6
C3Ha
HC=CH
EDC
C4HIO
C12
H2C:CH2
C2HSCl
CICH2CH2Cl
CIHC:CC12
C12C:CC12
CHCl:CC12
l,l,l-TCEA
PCE
TCE
VCM
H2C:CHCl
PVC
(-H2CCHCl-)x
VdCM
:12C:CC12
PvdC
(-H CCCI -)
2 2 x
EA
3-11
-------
la.
2a.
TABLE 3-5: PP.OCESS CHEr.nCAL RElI.CTIONS
CH2:CHCl + HCl
(VINYL
CHLORIDE
MONOMER)
(HYDROGEN
CHLORIDE)
lb.
CH3 CHC12
+
C12
) CH3CC13 + HCl
(l,l-DICHLORO
ETHANE)
(CHLORINE)
ClCH2CH2Cl + C12
(ETHYLENE
DICHLORIDE)
(CHLORINE)
2b.
ClCH2CHC12
-HCl
)CH2 : CC12
(1, 1, 2-TRICHLOROETHANE)
CH2:CC12 + HCl
)CH3CHC12
C12 vapor
pLlasEO
u.v.
(l,l-DICHLORO-
ETHANE)
( 1 , 1, I-TRI-
CHLOROETHANE)
)ClCH2CHC12 + HCl
(1,1,2 -TRI
CHLOROETHANE)
;cH3CC13 + HCl
(l,l,l-TRI- (HYDROGEN
CHLOROETHANE) CHLORIDE)
(HYDROGEN CHLORIDE)
(HYDROGEN
CHLORIDE)
(VINYLIDENE CHLORIDE MONOMER)
)CH3CC13
2c.
(VINYLIDENE
CHLORIDE
MONOMER)
(HYDROGEN
CHLORIDE)
3.
C2H6
(ETHANE)
2 C12
(CHLORINE)
+
(1,1, I-TRICHLOROETHANE)
X::H3CHC12
(l,l-DICHLORO
ETHANE)
3-12
+
2HCl
(HYDROGEN
CHLORIDE)
-------
safety over the other three halogenated solvents (TCE, PCE
and DCM)~
Additional advantages include optimum solvancy
and a good evaporation rate.
As shown in Table 3-6, the major uses of l,l,l-TCEA in
cold metal cleaning and vapor degreasing operations consumed
approximately 75 percent of 1978 domestic production (CMR 1979).
l,l,l-TCEA use in cold metal cleaning and vapor degreasing
is in direct competition with trichloroethylene (TCE),
perchloroethylene (PCE), and other solvents.
Inhibited
(stabilized) grades of l,l,l-TCEA are used in hundreds of
different industrial cleaning applications.
Direct solvent
uses include cold and vapor degreasing, metal cleaning for
electrical equipment, motors, electronic components and in-
struments, missile warheads, paint masks, photographic film,
printed circuit boards, as well as cleaning various metal
and plastic components during manufacture (Kirk-Othmer 1979).
Other halogenated solvents such as dichloromethane
(methylene dichloride) and trichlorotrifluoroethane (F-113)
are also used in metal cleaning.
Most industry sources have
discontinued the use of dichloromethane except in specialty
applications such as cleaning some polymers, paints and
paintlike films from electrical parts (ADL 1979).
l,l,l-TCEA
has competed with F-113 in high priority cleaning applications
such as missile components, high vacuum equipment, and semi-
conductor devices, and may compete with other fluorocarbons in some
applications.
Final resolution of the fluorocarbon controversy
3-13
-------
TABLE 3-6:
END-USE DEMAND PATTERN FOR
l,l,l-TRICHLOROETHANE
End Use
Percent of Total
Demand
Cold Cleaning
50%
Vapor Degreasing
25
Adhesives
8
Aerosols
7
Export
5
Coatings
2
Miscellaneous
3
SOURCE:
Chemical Marketing Reporter (CMR 1979).
3-14
-------
may create additional market opportunities for l,l,l-TCEA.
However, there is some concern that widespread use of l,l,l-TCEA
could pose as great a potential hazard to the ozone layer as
fluorocarbons (C&EN 1979a).
Since l,l,l-TCEA does not exhibit a number of the per-
formance characteristics of TCE, it has not been able to
replace TCE uniformly in all markets.
As a result, 1,1,1-
TCEA production is not expected to expand greatly over the
next few years.
with the majority of recent forecasts showing reduced
long run growth for l,l,l-TCEA, efforts are underway to expand
its present uses and to find large-volume new uses.
Most
of the development work has focused on the displacement of
volatile and other flammable materials in adhesives, with
the aim of using l,l,l-TCEA in place of other hydrocarbon
solvents.
This application accounted for eight percent of 1978
domestic consumption (CMR 1979) and is a promising growth area.
The same trend can also spread to aerosols (deodorants and
anti-perspirants) and coating formulations.
These uses
accounted for nine percent of 1978 consumption.
However,
gains for l,l,l-TCEA at the expense of other solvents, such
as aromatics, so far have been small at least in adhesives
and coatings which may indicate that l,l,l-TCEA use should
expand little in these areas (C&EN 1979b).
Other applications for l,l,l-TCEA (Radian 1979) include
uses as a solvent in:
3-15
-------
Drain cleaners
8hoe polishes
Fabric spot remover
Pesticides
Printing inks
Textile sizing
Pharmaceutical manufacturing
Miscellaneous applications for l,l,l-TCEA include use as a
coolant in metal cutting oils and as a carrier for lubricants.
The addition of 20 to 30 percent l,l,l-TCEA to metal cutting
fluids significantly increases tool life and/or cutting speeds
in difficult drilling and tapping operations (Kirk-Othmer
1979) .
The use of l,l,l-TCEA to supplement or replace present
aqueous textile processing and finishing techniques is another
possible future application (Kirk-Othmer 1979).
These misce1-
1aneous applications accounted for three percent of 1978
U.8.
production.
3.2.
Potential for Economic Impact
An analysis of the four market characteristics (demand
sensitivity, cost, industry structure, and market expec-
tations) indicates that the potential for adverse impacts
as a result of proposed testing requirements for l,l,l-trich1oro-
ethane is small.
3-16
-------
3.2.1.
Direct Testing Costs
The direct costs of the tests recommended for l,l,l-TCEA
are presented in Table 3-7.
The total cost of the recommended
tests ranges from $86,425 to $292,375.
This range is pur-
posely wide, reflecting the uncertainty about the specific
nature of the test protocols.
Annualizing the total cost estimate at a 25 percent cost
of capital for 15 years (capital recovery factor = .25912)
(DuPont 1980) gives a range of $22,400 to $75,760 per year.
This represents .003-.01 cents per pound, based on the 1979
production level, or .02-.07 percent of the 1979 average price.
3.2.2.
Demand Sensitivity
As discussed in Section 3.1.4., the major market for
l,l,l-TCEA is in solvent applications.
Cold metal cleaning
and vapor degreasing uses comprise about 75
percent of
total consumption.
In these uses, l,l,l-TCEA competes pri-
marily with other halogenated solvents.
The major substitutes
for l,l,l-TCEA include perchloroethylene, trichloroethylene,
and dichloromethane.
Although the first two of these have
lower unit prices (the price of the latter is slightly higher
than that for l,l,l-TCEA), l,l,l-TCEA competes well with
these solvents, based on other properties.
The relatively low boiling point, lower consumption per
use and non-flammability of l,l,l-TCEA allow its use in many
3-17
-------
TABLE 3-7: ESTIMATED TEST COSTS,1
1,1,I-TRICHLOROETHANE
Tests
Health Effects
Teratogenicity, rat
Teratogenicity, mouse
Environmental Effects
Estimated Cost
$ 20,500 - 61,000
18,000 - 54,500
Acute toxicity, flow through, rainbow trout
Early life stage toxicity, fathead minnow
Early life stage toxicity, rainbow trout
Early life stage toxicity, sheepshead minnow
Daphnid life cycle, flow-through
Mvsid life cycle
Avian chronic toxicity (reproduction),
Avian chronic toxicity (reproduction).
Early seedling growth
Seed germination and root elongation
Plant uptake and translocation
1
Source:
Borriston Labs, Inc. estimates.
protocol estimates.
3-18
375 -
5,700 -
7,200 -
5,700
2,000 -
1,650 -
mallard 12,100 -
qu ail I 0 , 300 -
1,200 -
700 -
1,000 -
1,125
17,000
21,500
17,000
6,100
4,950
36,200
30,800
16,000
1,200
25,000
To ta 1
$ 38,500 - 115,500
$ 47,925 - 176,875
$ 86,425 - 292,375
See Appendix B for specific
-------
general, as well as more specific, applications.
Because of
its lower vapor loss and lower boiling point, l,l,l-TCEA has
a lower consumption rate and requires less energy than use
of perchloroethylene and trichloroethylene.
In addition to
this, less sophisticated recycling equipment is required
to contain the vapors.
For these reasons l,l,l-TCEA is able
to compete with the other lower priced solvents in general
applications.
In more specialized solvent applications l,l,l-TCEA
competes with the fluorocarbons, especially trichlorotri-
fluoromethane (F-113).
These uses include cleaning circuit
boards, electronic components and electric motors.
In these
uses l,l,l-TCEA competes extremely well, due to the much
higher prices for fluorocarbons (e.g., the price for trichloro-
trifluoromethane is more than three times that for l,l,l-TCEA).
In the specialized markets, demand for l,l,l-TCEA is
not expected to be sensitive to changes in price.
However,
in the general solvents market an increase in price could
significantly affect demand.
In this market a combination
of general properties and cost effectiveness makes l,l,l-TCEA
preferred over other solvents and even a relatively small
change in price could eliminate this advantage.
In addition,
because of overcapacity, producers may not be willing to
raise the price of l,l,l-TCEA by a significant amount.
How-
ever,
because the maximum increase in per unit cost is small
(.03 cents or .2 percent of price), no significant impacts are
expected, even for this specialized market.
3-19
-------
3 . 2 .3.
Cost Characteristics
On the supply side, the raw materials costs for each of
the solvents discussed in the previous section are posi-
tively correlated with each other.
This is due to the fact
that, as shown in Figure 3-1, each of these solvents is derived
from a petroleum (or natural gas) based product and chlorine.
Thus, as oil prices rise, the cost of producing each solvent
will also
rise.
Processes which use natural gas should be less
affected, since natural gas prices have been rising more
slowly than petroleum prices and are expected to continue
to do so in the future.
For these reasons, the cost of
producing l,l,l-TCEA should place it at neither a comparative
advantage nor disadvantage.
From the small number of firms and the fact that raw
materials constitute a significant portion of production
costs, we can infer that the industry supply curve is posi-
tively sloped.
This implies that the producers would not be
able to pass a
cost
increase fully on to consumers (unless
the demand functio~ is totally unresponsive to price).
3.2.4.
Industry Structure
That only three firms produce l,l,l-TCEA would normally
imply an oligopolistic market structure; however, the existence
of close substitutes may preclude oligopolistic behaviour.
In an oligopoly market each firm faces a somewhat downward
sloping demand curve and is able to influence the market
price by its actions.
However, as has been shown above,
in
3-20
-------
the major solvent market several good substitutes compete
with l,l,l-TCEA.
Thus, the industry itself may face a very
flat demand curve and oligopolistic behavior would be ruled
out.
Thus, we do not expect that above-normal profits,
which would enable the firms to absorb the additional costs
of testing, are earned in this industry-
The nature of the production process and the firms in
the industry, however, indicate that the impact would probably
be very small.
The equipment required for the production of
l,l,l-TCEA is similar to that used for producing a variety
of chlorinated hydrocarbons, including polyvinyl chloride
(PVC)
and other solvents.
Thus, producers may be able to
shift the equipment and personnel to alternative products,
if the burden of testing costs rendered the l,l,l-TCEA pro-
cess unprofitable.
since each firm in the industry produces a range of
solvents or PVC at the location where l,l,l-TCEA is
manufactured, this conclusion is further supported.
In
fact, one former producer (Ethyl Corporation) shifted its
resources in 1976 from l,l,l-TCEA to other solvents, most
notably perchloroethylene and trichloroethyelene.
Thus, even
if the competitive situation forced the producers to cease
l,l,l-TCEA production, the impact should be minor.
However,
this is very unlikely to occur as a result of the testing re-
quirements.
3-21
-------
3.2.5.
Market Expectations
As discussed above, the market for l,l,l-TCEA grew at an
annual rate of more than seven percent during the late 1970s.
According to market estimates, this growth rate will drop to
about two percent for the first half of the 1980s (CMR 1979).
Although this rate is well below those formerly experienced,
it is possible that current efforts to secure new large-
volume uses could raise this considerably-
In addition, more
restrictions on the other major solvents, especially the
fluorocarbons, could allow l,l,l-TCEA to achieve previously
expected growth rates.
In summary, the market for l,l,l-TCEA
should grow steadily for the next decade at an annual rate
of at least two percent.
3.2.6.
Conclusions
bespite the potential demand sensitivity to price in-
creases,
the impact of testing requirements on the l,l,l-TCEA
industry is expected to be minor.
The primary factor which
supports this conclusion is that the per unit increase in
costs will be relatively insignificant (up to .03 cents).
In addition, industry growth is expected to be modest but
stable for the next decade.
Although excess capacity cur-
rently exists among the producers, none of the thfee producers
is expected to leave the market.
Each of the companies is
large and produces numerous related products.
If higher
prices result in a decrease in the quantity demanded, each
of the firms should be able to shift resources to other
3-22
-------
products with a minimum of disruption.
Thus, the effects on
the industry. firms and employment should be small.
In summary. impacts of a proposed testing requirement
for l,l,ltrichloroethane should not be significant and a
Level II analysis is not recommended.
3-23
-------
REFERENCES - CHAPTER 3
ADL. 1975. Arthur D. Little, Inc. Shamel RE, et ale Preliminary economic
impact assessment of possible regulatory action to control atmospheric
emissions for selected halocarbons. Washington. DC: U.S. Environmental
Protection Agency, Office of Air Quality Planning and Standards. EPA Report
No. 450/3-75-073 (PB-247 115).
ADL. 1979. Arthur D. Little, Inc. Preliminary evaluation of the economic
positions of selected chemicals. Draft Report. Washington, DC: U.S.
Environmental Protection Agency, Office of Pesticides and Toxic Substances.
Contract no. 68-01-4717. Task 2.
BOC-Imports. 1979. Bureau of the Census. Foreign Trade Reports, FT-135,
United States Imports. Schedule A, Commodity Groupings. Commodity
by Country. Washington, DC: U.S. Department of Commerce.
BOC-Exports. 1980. Bureau of the Census. Foreign Trade Reports. FT-410,
United States Exports, Schedule E, Commodity by Country, Quantity and Value,
Current and Cumulative. Washington. DC: U.S. Department of Commerce.
C&EN. 1979a. Methyl chloroform may harm ozone layer.
News. p.16. March 5. 1979.
In:
Chern. & Eng.
C&EN.
p.13.
C&EN.
News.
1979b. Key chemicals: 1,1,1-trichloroethane.
October 29. 1979.
1980. Checkoff-new plants: 1,1,1-trichloroethane.
p.16. January 14, 1980.
In:
Chern. & Eng. News.
In:
Chern. & Eng.
CMR. 1979. Chemical Profile: 1,1,1-trichloroethane.
Marketing Reporter. p.9. December 10, 1979.
In:
Chemical
Considine DM.
-285.
1974.
Chemical Processing Technology Encyclopedia, pp. 282
DuPont. 1980. Comments to chloromethane and chlorinated benzenes. Docket
Nos. 80T-125 and 80T-126. Washington, D.C: U.S. Environmental Protection
Agency. October 31, 1980.
Hawley GG. 1977. Condensed Chemical Dictionary, 9th ed.
Van Nostrand Reinhold.
New York:
Kirk-Othmer. 1971. Gage JC. Chlorocarbons and chlorohydrocarbons. In:
Kirk-Othmer Encyclopedia of Chemical Technology, 2nd ed., Vol. 5. New
York: Wiley-Interscience, pp. 154-187.
Kirk-Othmer. 1979. Archer WL. Chlorocarbons and chlorohydrocarbons. In:
Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Vol. 5. New York:
Wiley-Interscience, pp. 668-676, 728-731.
McKetta JJ.
1979.
Encyclopedia of Chemical Processing and Design, Vol. 8.
3-24
-------
McKetta JJ, ed.
The Netherlands:
Harper and Row, pp. 214-270.
Radian. 1979. Lee BB, et al. Organic solvent use study. Washington, DC:
U.S. Environmental Protection Agency, Office of Toxic Substances. EPA
Report No. 560/12-79-002.
SRI. 1976,1978-1980. SRI International.
United States. Menlo Park, CA.
TSCA-ITC. 1978. TSCA Interagency Testing Committee. Second report
of the TSCA Interagency Testing Committee to the Administrator
Environmental Protection Agency- Washington, DC: U.S. Enviro~mental
Protection Agency. EPA Report No. 560/10-78-002 (PB-285 439).
Directory of Chemical Producers,
USITC-SOC. 1972. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales, 1970.
Washington, DC: Government Printing Office. USITC pub. 479.
USITC-SOC. 1973. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales, 1971.
Washington, DC: Government Printing Office. USITC pub. 614.
USITC-SOC. 1974. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales, 1972.
Washington. DC: Government Printing Office. USITC pub. 681.
USITC-SOC. 1975. U.S. International Trade Commission. Synthetic
organic chemicals. United States production and sales. 1973.
Washington, DC: Government Printing Office. USITC pub. 728.
USITC-SOC. 1976. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales, 1974.
Washington, DC: Government Printing Office. USITC pub. 776.
USITC-SOC. 1977a. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales. 1975.
Washington, DC: Government Printing Office. USITC pub. 804.
USITC-SOC. 1977b. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales, 1976.
Washington. D~: Government Printing Office. USITC pub. 833.
USITC-SOC. 1978. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales. 1977.
Washington, DC: Government Printing Office. USITC pub. 920.
USITC-SOC. 1979. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales, 1978.
Washington, DC: Government Printing Office. USITC pub. 1001.
USITC-SOC. 1980. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales. 1979.
Washington, DC: Government Printing Office. USITC pub. 1099.
3-25
-------
CHAPTER 4
NITROBENZENE
4.1.
Industry Characteristics
Nitrobenzene is an important commercial aromatic de-
rived from benzene and used extensively as a feedstock for
aniline.
A very small percentage of nitrobenzene production
is used for the manufacture of benzidine, quinoline, and
azobenzene,
and as a solvent in chemical and petroleum refin-
ing processes.
The production of nitrobenzene has increased
significantly since 1975 due to the increased use of aniline-
derived isocyanates in polyurethane manufacture.
4.1.1.
production and Trade
According to the u.s. International Trade Commission,
the u.s. commercial production of nitrobenzene was 575.5
million pounds in 1978, an increase of four percent over 1977
(USITC-SOC 1979).
In 1979 nitrobenzene production increased
significantly to 952.4 million lbs.
(USITC-SOC 1980).
A large
portion of this increase is believed to be due to the start of
production at new facilities belonging to Rubicon at Geismar,
Louisiana.
Production and unit sales values for the years
1970 through 1979 are listed in Table 4-1.
Production of nitrobenzene is primarily used captively
and the quantity sold on the merchant market is a small per-
centage of total volume.
In spite of this, the per unit sales
value is the best indicator of the actual price of nitrobenzene.
4-1
-------
TABLE 4-1:
NITROBENZENE PRODUCTION
Year
1970
1971
1972
1973
1974
1975
1976
1977
1978
1979
I
I production
I Volume
I (Million lbs.)
I
I
I 560
I
I 444.9
I
I 551. 2
I
I 308.7
I
I 506.6
I
I 414.3
I
I 409.0
I
I 552.3
I
I 575.5
I
I 952.4
I
Unit Sales
Values
$/lb.
$0.07
0.06
0.14
0.23
0.22
0.21
0.24
Source:
Synthetic Organic Chemicals (USITC-SOC 1971-1980).
Although the unit sales value has increased from below ten
cents per pound in the early 1970s, recently the unit sales
value has fluctuated between 21 and 24 cents.
The 1979
unit sales value for nitrobenzene is 24 cents per pound.
According to the Chemical Marketing Reporter, domestic
consumption (demand) of nitrobenzene was 820 million pounds
in 1978 based on aniline production (CMR 1979b).
Since im-
ports of nitrobenzene are not a significant factor (1-2
tenths of a percent of domestic production), there appears
to be a discrepancy between this 820 million figure and the
4-2
-------
domestic production figure of 575.5 million, reported by the
International Trade Commission.
The most likely explanation
is that the addition of up-dated production proc~sses aimed
at increased capacity produce nitrobenzene of such purity
that it does not require isolation and measurement prior to
aniline production.
It is believed that the unisolated
quantity of nitrobenzene may not have been reported to the
International Trade Commission in 1978 and prior years,
although the aniline subsequently produced was.
An alterna-
tive possibility is that a portion of the total aniline
production is derived from a raw material other than nitro-
benzene (i.e., phenol or chlorobenzene); however, no published
information to support this viewpoint has been found.
Exports of nitrobenzene are not reported separately.
Imports amounted to 88,890 pounds in 1978 (USITC-IBC 1979).
This quantity is insignificant co~pared to the 575.5 million
pounds of nitrobenzene produced in the United States the same year.
Aniline is the main derivative of nitrobenzene and
could be produced overseas and imported if the nitrobenzene
production costs became prohibitive in the United States.
Imports in 1974 were 20 million pounds and 13 million pounds
in 1975, corresponding respectively to four and three percent
of domestic production for 1974 and 1975 (USITC-IBC 1976-1977).
There have been, however, no imports of aniline reported during
1976-1978 and imports were only 43,000 pounds in 1979.
Thus,
domestic aniline needs have been primarily supplied by U.S.
4-3
-------
aniline producers in recent years.
Imports for nitrobenzene
and aniline for the years 1974 through 1979 are listed in
Table 4-2.
TABLE 4-2: IMPORTS OF NITROBENZENE AND ANILINE
Nitrobenzene Aniline
Year Ibs. Ibs.
1974 None 20,068,901
1975 88,184 13,002,832
1976 None
1977 None
1978 82,890 None
1979 43,298
Source:
Imports of Benzenoid Chemicals (USITC-IBC
1976-1979).
4.1.2.
Producers
In 1979, there were five companies manufacturing
nitrobenzene at seven locations (see Table 4-3).
The total
nameplate capacity for these producers was over 1.6 billion
pounds per year.
The largest three of these producers own
78 percent of the total production capacity.
Each manufac-
turer of nitrobenzene also produces aniline and almost all
of the nitrobenzene produced is used captively-
Nitrobenzene plants are found in several major petro-
chemical complexes.
These are located in New Jersey, West
4-4
-------
TABLE 4-3: MANUFACTURERS OF NITROBENZENE BY COMPANY AND LOCATION
1979
Company
Location
Nameplate
Capacity
Million Ibs./Year
American Cyanamid Company
Bound Brook, NJ
Willow Island, WV
105
75
E.I. dupont de Nemours & Company
Beaumont, TX
Gibbstown, NJ
350
240
*'"
I
lJl
First Chemical Corporation
(Subsidiary of First Missis-
sippi Corporation)
pascagoula, MS
335
Mobay Chemical Corporation
(Owned by Bayer A.G.)
New Martinsville, WV
190
Rubicon Chemicals
(Owned by Imperical Chemical
Industries Ltd., and
Uniroyal, Inc.)
Geismar, LA
380
TOr;:'l'.L
1(,75
SOURCES:
Chemical Marketing Reporter (CMR 1979), Directory of Chemical
Producers (SRI 1980), Synthetic Organic Chemicals (USITC-SOC
1980) .
-------
Virginia, Texas, Louisiana and Mississippi, with production
capacity evenly distributed among these states.
Several of
the manufacturers are planning, or have und.er construction,
major expansions of their facilities to meet projected demand
for nitrobenzene and/or aniline by urethane producers.
4.1.3.
Production Process
Nitrobenzene is produced by the exothermic nitration
of benzene with fuming nitric acid in the presence of sulfuric
acid catalyst at 50-65°C.
o 50-65°C "ON02
+ 1 HN03 + H20 + Heat
Sulfuric
Benzene Nitric Acid Nitrobenzene
Acid
All of the processes which have been designed are based upon
this reaction.
They include a batch process, the Schmid-
Meissner Biazzi process, a continuous procesg using tubular
reactors, the Bofors Nobel Chematur's (Sweden) continuous
process, &nd the Chemetrics Industries continuous process.
Each of the processes includes a means to ensure thorough
mixing of the acids and the benzene, removal of the heat
produced during the reaction, and elimination or reduction
of by-products (complex nitrated benzenes).
Also, each of
the designs provides for recycle or purification of spent
sulfuric acid.
(Kirk-Othmer 1967, 1978a, 1978b, Habeistroh
1974, Hancock 1975).
4-6
-------
It is believed that all current manufacturers use tubular
reactors or one of the newer continuous process pump reactor
systems (Kirk-Othmer 1967, 1978a, Habeistroh 1974).
The
development of the reactors has gone from a single large
iron-steel stirred reactor, to multiple stirred reactors, to
tubular heat-exchanger type reactors, and finally, to pumps.
The newer processes are safer hecause small quantities of
benzene and nitric acid are reacted, and therefore, explosive
amounts of di- and tri-nitrobenzene are not formed (Kirk-Othmer
1967, 1978a, Habeistroh 1974).
Also, the newer processes
reduce energy costs and produce sulfuric acid pure enough
for sale or recycle while providing high (97-99 percent)
yields of nitrobenzene.
A general scheme of the reaction
process is presented in Figure 4-1.
A new process for ~ontinuous nitrobenzene manufacture
which eliminates the need for reactor cooling, and also re-
duces by 80 percent the amount of energy required for acid
reconcentration, has been described by Chemetrics Inter-
national (Chern Eng 1979).
The process has been in use since
June 1979 at a 120 million-pounds-per-year nitrobenzene
facility operated by American Cyanamid.
In addition, Rubicon
Chemicals at Geismar, Louisiana is starting up a 380 million-
pounds-per-year nitrobenzene plant in 1979 using the process
under license from Chemetrics (Chern Eng 1979).
4-7
-------
FIGURE 4-1;
SCHE~lli FOR NITROBENZENE MAnUFACTURE
BATCH OR CONTINUOUS PROCESS
Crude
Nitrobenzene
To Aniline Production
Refined
Nitrobenzene
Benzene
Acid
S
e
Wash
still
p
a
Nitrator
r
a
(Wa ter +
Sodium Carbonate)
Technical Grade
Nitrobenzene
t
~
I
00
Mixed
Nitric
and
Sulfuric
Acids
o
r
Spent Acid
to
Recovery and Recycle
Wastes
RAW MATERIAL REQUIREMENTS NEEDED TO PRODUCE
ONE TON OF NITROBENZENE:
Benzene
Sulfuric Acid
Nitric Acid
Water
Sodium Carbonate
1,300 lbs.
1,442 Ibs.
1,060 lbs.
218 lbs
20 lbs.
EQUIPMENT REQUIREMENTS:
Process requires a stirred and cooled reactor.
Sources: Faith, Keyes and Clark's Industrial Chemicals (1965), p. 541; and
Organic Chemical Processes as reprinted from Hydrocarbon Processing and
Refining.
-------
4.1.4.
Uses
Nitrobenzene is used primarily for the manufacture of
aniline.
In fact, 97.5 percent of all nitrobenzene production
is used in this manner.
In turn, 40-50 percent of all aniline
produced is used for the manufacture of MDI (p,p'-methylene
diphenyl diisocyanate) which is then used to manufacture
flexible and rigid polyurethane foams, elastomers, adhesives,
and fibers (CMR 1979b).
Although the vast majority of nitrobenzene is used in
aniline production, it is also used in several other pro-
cesses.
Nitrobenzene has excellent solvent properties and,
therefore, finds use as a solvent in such applications as
Friedel-Crafts reactions to hold aluminum chloride catalysts
in solution,
in petroleum refining, and in the manufacture
of cellulose ethers and acetate.
These solvent uses account
for about two percent of the nitrobenzene market (CMR 1979b).
A very small amount of nitrobenzene is used for the synthesis
of azobenzene, benzidine and quinoline, which are intermediates
for the manufacture of dyes and pharmaceuticals (CMR 1979b).
In the past, nitrobenzene has also been used as a flavor-
ing (artificial oil of bitter almonds or oil of mirbane), as
a perfume for soaps, and a solvent for shoe dyes.
Because
of the toxic nature of nitrobenzenes, and the fact that
nitrobenzene vapors are absorbed through the skin, these uses
are now prohibited in most countries (Noller 1951).
The uses of nitrobenzene and aniline are diagrammed in
Figures 4-2 and 4-3, respectively.
The numerous uses for
4-9
-------
II»
I
I-'
a
FIGURE 4-2;USES OF NITROBENZENE
*
97.5% >A . 1 .
nl lnc
Fuming HN03
+
H2301+
Benzene 9Nitrobenzen~'
50-65°C
o
ON02
>Solvent
*
2 5g,
. 0 >
Organic
>Synthesis
(Very Small %)
>(See Figure 3)
Solvent Petroleum Refining
of Organic Compounds
1%
Friedel-Crafts Reaction
(Anhydrous Aluminum Chloride)
Cellulose Ethers
1%
Process for Esterification
of Cellulose Acetate
Benzidine ~
NH2 NH2
Quinoline 00 N
o-N-N-o
Azobenzene
*percentages from Chemical Marketing Reporter
(CMR 1979b)
-------
FIGURE 4-3.
USES
Insulation
OF ANILINE E,OUSing
-fi9id_- Automobiles
Foam ~rucks
Isocyanates, ~rethanes----+Polyurethane lexible----Insulation
primarily MDI" Foam
----1AntitOXidants lastomers
Rubber Chemicals Antidegradeants -cutomObile
Vulcanization Accelerators Industry
(Thiazoles, Mercaptors, Ben?othialoles)
ther
--1HerbiCides
Fungicides
Agriculture t' 'd
Insec lei es
Animal Repellants
40%
35%
7%
.J::>
I
I-'
I-'
Aniline- --iRust Inhibitor
[Gasoline Additives Antiknock Compounds
Carburetor Deicing Compounds
f-2
-1Antifreeze
Corrosion Inhibitors
Boiler Water Feed
---isweetners
Pharmaceuticals Acetanilide
Analgesics
[~"'''i"'
) Quinolirle
A~benzene
---1QUJnones
Photochemicals
l1ydroquinones
4%
6%
Dyes
6%
"MDI=l,l'-methylene bis (4-Jsocyanatobenzene) also named p,p'-methylene-diphenyl-diisocyanate.
SOURCES: ~hemical Origins (Blackford 1977), Chemical Marketing Reporter (CMR 1980)
-------
aniline are presented because such a large percentage of
nitrobenzene goes to aniline production.
The largest use
for aniline is in the manufacture of polyurethanes.
Figure
4-4 shows the consumption pattern for polyurethane foams.
Although flexible and rigid foams constitute the majority of
polyurethane products, the elastomers and other ,uses have
been increasing and in 1979 amounted to 16 percent of all
polyurethanes production (C&EN 1979a).
There are no direct substitutes for nitrobenzene in
organic synthesis.
However, for the production of aniline
(where nitrobenzene finds 97.5 percent of its use), there
are other processes using other raw materials.
The major
alternative routes are shown in Figure 4-5.
Thus, mono-
chlorobenzene and phenol may be considered potential sub-
stitutes for nitrobenzene in the manufacture of aniline.
Although each of these processes has been used comuercially
in the past, it is believed that all current aniline produc-
tion is derived from nitrobenzene.
The choice of a particular raw material for manufacture
of aniline quite often depends upon the availability of in-
expensive feedstocks or energy and the company's knowledge
of the technologies associated with a particular process.
This may be the case in the recent decision by US Steel to
build a 200 million-pounds-per-year facility for aniline pro-
duction at its Haverhill, Ohio, plant (CMR 1980b).
USS Chemical
(a division of United States Steel) has phenol available on site
4-12
-------
FIGURE 4--4: CONSUMPTION PATTERN FOR POLYURETHANE FOAMS 1978
F1exibl
Foa
'of:>.
I
I-'
W
Polyurethane
Foams
840,000 Ibs.
Rigid
Foam
SOURCE:
14%* Bedding
37%
e 72% 10%
m
30%
9%
-
47%
6%
28% 19%
9%
9%
10%
Furniture
Rug Underlay
Transportation
Other
Building Insulation
Furniture
Household & Commercial Refrigeration
Industrial Insulation
Transportation
Other
Modern Plastics, (Mod Plast 1979).
*Due to rounding, percentages do not add to 100%.
-------
N02
aN03
Cl
o
NH3
Pro
/CH3
lene 0 C!l.CII'
Cumene
)
NH2
o
o
BENZENE
Monochlorobenzene
COAL TAR
Figure 4-5: Alternative Manufacturing
Routes to Aniline
All possible processes have not been included.
may be manufactured by other processes.
4-14
-------
and ammonia available from other US Steel facilities (SRI
1980).
The new aniline plant will use the Halcon Process
(reaction of phenol with ammonia) and is expected to start
production in 1982.
Rubicon has announced plans to produce
aniline using the older Bechamp process (C&EN 1980).
Recently, ARca Chemical announced a new process for the
manufacture of PMDI (a polyisocyanate) from nitrobenzene which
by-passes the production of aniline (CMR 1978, 1979b, C&EN
1978b).
The new process is attractive because chlorine,
used in other isocyanate processes, is not required and
energy costs are reduced.
While this development may reduce
the demand for aniline, the demand for nitrobenzene will not
be affected.
Even so, some restructuring of firms in the
marketplace may occur if ARca Chemical becomes a nitrobenzene
producer (CMR 1978).
There are numerous substitutes for end-products derived
from aniline.
For example, polystyrene foams, urea-formalde-
hyde foams, fibre glass, and felt are all possible substitutes
for polyurethanes in insulating applications.
Polyurethanes
made from toluene diisocyanates substitute for polyurethanes
made from methylene diphenyl isocyanates.
In automobiles and
housing construction, phenolic resins and various adhesives
are substitutes for polyurethane adhesives and elastomers.
Steel has been replaced by polyurethanes for automobile bumpers
but could, theoretically, again substitute for polyurethanes.
4-15
-------
The second largest end use for aniline is for rubber
processing chemicals, such as mercaptobenzothiazole, a rubber
vulcanization accelerator derived from aniline.
In 1978,
thiazole derivatives (mercaptobenzothiazole is a member of this
group of chemicals) accounted for over 90 percent of the
vulcanization accelerator production (USITC-SOC 1979).
Also included in the category of rubber chemicals are
antioxidants which may be further classified as amino compounds
or phenolic compounds.
Here, aldehyde- and acetone-amine
reaction products, phenolic compounds (bisphenols, styrenated,
alkylated, etc.), and phosphites may be considered substitutes
for p-phenylenediamines, chemicals which are derived from
aniline.
Acyclic chemicals such as thiurams, zanthates,
sulfides, and dithiocarbamate derivatives also are substitutes
for aniline derivatives as rubber processing chemicals.
Some substitutes for aniline, the primary derivative fr0m
nitrobenzene, include alkyl amines, halogenated aromatic amines,
and dinitrotoluene, which may be used in the manufacture of
chemicals for use in dyes, TOI (toluene diisocyanate), poly-
urethanes, rubber chemicals, and pesticides.
In the majority
of their applications, polyurethanes face competition from
other thermoset plastics which include styrene, polyesters,
polyethylene, and polypropylene.
Many of the potential substitutes for nitrobenzene are
also derived from benzene.
Therefore, they, or chemical
intermediates derived from them, are likely to be considered
4-16
-------
for toxicological testing.
Some of these relationships are
diagrammed in Figure 4-6.
4.1.5.
Projected Growth
As discussed above, almost all nitrobenzene is used
to produce aniline.
The major market for aniline is for
MDI (methylene diphenyl isocyanate), a derivative which,
in
turn, is used for manufacture of urethane resins, particularly
high resilience urethane foams and elastomers used as insula-
tion in building and transportation industries.
The second
most important market for aniline is rubber chemicals (OSHA 1977).
Nitrobenzene production has grown at an annual rate of
8.1 percent since 1968.
However, examination of the historic
production data, as listed in Table 4-1, supports the con ten-
tion that production may be closely tied either to the avail-
ability of benzene feedstock or production of consumer end-
products.
Nitrobenzene production dropped by 44 percent
from 1972 to 1973, and 18 percent from 1974 to 1975.
Each
of these declines appears to be related to decreases in
benzene production associated with the supply interruption
of petroleum (see Figure 4-7).
In each case, automobile and
housing markets also declined; these are among the primary
markets for derivatives of aniline such as polyurethanes
and rubber processing chemicals.
Thus, the market for nitro-
benzene appears to be strongly affected by general business
conditions.
4-17
-------
FIGURE 4-6: END USE SUBSTITUTES ORIGINATING FROM BENZENE
Polystyrene
Ethylbenzene ~ Styrene
Acrylonitrile-Butadiene Styrene Resins
ABS
Other Styrene Resins
~ Cyclohexanol~ Cyclohexanone---+ Adipic Acid--'Ca1?rolactam~Nylons
Phenol
Phenolic Resins
~
I
I-'
co
Benzen
Chlorobenzene ~ Aniline ~ MOl ~
~ PMOI ~ Polyurethane
Nitrobenzene ~Arco's New Process ~
Toluene diisocyante (TOI) goes into manufacture of a different type of polyurethane.
Since much of the benzene is produced from toluene, toluene becomes a factor in the
supplies of benzene and also a factor in manufacture of TOI, an intermediate in the
production of polyurethanes.
-------
million
lbs
1000
900
800
700
600
500
400
300
FIGURE 4-7:
U.S. NITROBENZENE PRODUCTION
1970-1979
70
72
73
74 75
77
78
71
79
Year
Source:
U.S. Synthetic Organic Chemicals
(USITC, 1971-1980)
4-19
-------
The demand for aniline is expected to grow at seven
to nine percent per year through 1985, primarily due to an
anticipated increase in demand for PMPI of 10 to 12 percent
per year.
Other markets for aniline are also expected to grow,
but at a slower rate of 1.6 to 5 percent per year.
The current
recession and slow-down in construction and transportation
industries may also affect the overall growth of the urethane
market for 1980 and 1981; however, the future for urethane de-
mand (and,
in turn,
aniline and nitrobenzene) looks relatively
bright (Mod Plast 1979).
4.2.
Potential for Economic Impact
Since the vast majority of all nitrobenzene is used
in aniline production, the quantity of aniline produced and
the alternative process by which it can be manufactured are
the most important factors affecting nitrobenzene production.
Factors affecting the demand for nitrobenzene will be dis-
cussed following the direct costs section and the alternative
processes will be dealt with in the cost characteristics
section.
Overall, the potential for significant economic
impacts appears to be small, especially in light of the low
per unit cost imposed (i.e.,
.01-.02 cents per lb.).
4.2.1.
Direct Testing Costs
The direct testing costs estimated for nitrobenzene are
presented in Table 4-4.
The ranges of cost presented are
purposely wide, reflecting the uncertainty about the test
4-20
-------
TABLE 4-4: ESTIMATED TEST COSTS, 1
NITROBENZENE
Test
Health Effects
Teratogenicity, rat
Teratogenicity. mouse
Reproductive effects
Estimated Cost
$ 20,500 - 61,000
18,000 - 54,500
135,000 - 406,000
Environmental Effects
Acute toxicity static or flow-through,
rainbow trout
Early life stage toxicity, fathead minnow
Early life stage toxicity, rainbow trout
Early life stage toxicity, sheepshead minnow
Daphnid life cycle, renewal or flow through
Mysid life cycle
5 day dietary toxicity, mallard
5 day dietary toxicity, quail
Avian reproduction, mallard
Avian reproduction, quail
Early seedling growth
Seed germination and root elongation
Plant uptake and translocation
Soil thin-layer chromatography
675 -
5,700 -
7,200 -
5,700 -
2,000 -
1,650 -
1,400 -
1,000 -
12,100 -
10,300 -
1,200 -
700 -
1,000 -
175 -
$173,500 - 521,500
2,075
17,000
21,500
17 ,000
6 ,100
4,950
4,200
3,000
36,200
30,800
16,000
1,200
25,000
1,000
Tota 1
1
Sou ree :
$ 50,800 - 186,025
$224,300 - 707,525
Borriston Labs, Inc. estimates.
protocol estimates.
See Appendix B for specific
4-21
-------
parameters to be specified in the test protocols.
For purposes of this analysis, the costs are presented in
annualized terms.
To do this a capitalization period of fifteen
years and a cost of capital of 25 percent, recommended by one
of the producers (DuPont 1980), is used.
These assumptions
will be revised if additional information suggests more appro-
priate values.
The annualized cost range is $58,120 - $183,350
per year.
Based on the 1979 level of production, this repre-
sents .01-.02 cents per pound (.03-.08 percent of 1979 price),
an extremely small amount.
4.2.2.
Demand Sensitivity
The demand for nitrobenzene is a derived demand, based
on the demand for aniline.
In turn, over 75 percent of the
aniline production is used as an intermediate in the manu-
facture of polyurethane foams and in rubber vulcanization or
formulation.
Thus, the demand for these products will most
significantly affect nitrobenzene demand.
As discussed above, aniline can be produced by a variety
of processes.
Therefore, the raw materials that form the
basis of each process can be considered substitutes to nitro-
benzene in the production of aniline.
These include mono-
chlorobenzene and phenol.
The comparative costs of each
process will be discussed in the next section.
Without
knowing these costs, it is not possible to determine how
changes in the demand for aniline will affect nitrobenzene
production.
4-22
-------
since the largest use for aniline is in the production
of polyurethanes, the demand for aniline is strongly related
to the market for polyurethanes.
In this process, aniline is
used in the manufacture of MDI and the majority of the latter
is used to produce rigid urethane and polyurethane foams.
Although other polyurethanes exist (based on other isocyanates)
these mayor may not substitute for MDI-based polyurethanes
in specific applications.
As shown in Figure 4-4, about 72
percent of polyurethanes are of the flexible foam type, while
the remainder are of the rigid foam variety.
Many materials can substitute for the MDI/aniline based
polyurethanes.
The major substitutes are other foams (e.g.,
polystyrene, urea-formaldehyde or other polyurethanes),
fiber glass, other plastic products and construction materials.
Although significant substitution possibilities may exist
among these and the aniline-derived polyurethanes, expected
growth in the polyurethane markets indicates that the demand
for aniline may continue to be strong.
4.2.3.
Market Expectations
The market outlook for the major end products which
incorporate nitrobenzene appears to be very good.
The market
for flexible and rigid plastic foams is expected to grow at
a very rapid rate.
The polyurethanes are expected to share
in this growth and the growth rate for these (and MDI) should
range around 10-12 percent per year through 1985 (CMR 1979b,
C&EN 1978a, 1980, Mod Plast 1979).
4-23
-------
Although aniline demand may not rise as rapidly if use
of the new ARCa process increases, the demand for nitro-
benzene should still be tied to MDI production.
The growth
rate for nitrobenzene may be affected by increased use of tne
phenol to aniline process.
However, in general the market
for nitrobenzene should be relatively strong, growing at about
8.5 percent per year (CMR 1979b, C&EN 1978a).
4.2.4.
Cost Characteristics
The primary cost characteristic of concern for this
analysis is the cost structure for producing aniline via the
various processes described above.
If the cost of producing
aniline from nitrobenzene increases, this may cause a shift
in the production of aniline away from this process.
Two factors indicate that the nitrobenzene process may
be the most cost effective manner in which to produce aniline.
First, the fact that all known production is currently based
on this process indicates that it may be more competitive
than other processes.
In addition, a preliminary analysis
indicates that the per unit raw materials cost is lower for
the nitrobenzene process than for the phenol process.
Although these factors indicate that the nitrobenzene
process is more cost effective in general, this may not
necessarily be the case for individual firms facing different
transportation costs and sources of feedstocks.
For example,
as mentioned earlier, USS Chemical is expected to begin pro-
ducing aniline via the phenol and ammonia process in 1982.
4-24
-------
USS Chemical already produces phenol at the same site and
has ammonia available from US Steel nearby.
This indicates
that other processes may be cost effective, based on other
factors, such as the availability of raw materials.
In
general, each of the aniline processes utilizes raw materials
based on benzene, as shown in Figure 4-5.
Thus we expect
that the prices of these feedstocks will be most affected by
changes in benzene prices and will be positively correlated
with each other.
For this reason the nitrobenzene-to-aniline
process should continue to be cost competitive.
Two recent developments strengthen the position of nitro-
benzene in the market.
As mentioned in the previous section,
a new process utilizing nitrobenzene to produce aniline has
been developed.
This process reduces energy requirements
and makes the nitrobenzene based production of aniline even
more cost effective.
In addition to this, a process has
been discovered in which MDI is produced directly from nitro-
benzene.
This process would reduce the captial equipment re-
quired and most likely reduce the cost of producing the major
aniline-derived product.
This should again improve the position
of nitrobenzene in the market.
4.2.5.
Industry Structure
Although only five firms produce nitrobenzene and the
largest two own more than half of the total capacity, the
industry is believed to operate in a competitive environment.
This is because the overall market for chemical intermediates
4-25
-------
used in plastic foams is very competitive.
For example, the
producers may not be able to influence nitrobenzene prices
because substitute processes exist for producing aniline.
Also, aniline is used in producing MDI-based polyurethanes
which compete with other isocyanate-based polyurethanes, as
well as other materials.
Thus, it is felt that nitrobenzene
producers are not in a position to significantly influence
the market or realize above-normal profits.
On the other hand,
the smallest producers each own over ten percent of the
total capacity and are not expected to be at a competitive
disadvantage.
For these reasons, no firm in the industry is
expected to be more affected than any other.
4.2.6.
Conclusions
Overall the market for nitrobenzene seems to be strong
and none of the manufacturers appears to be significantly
susceptible to the impacts of the proposed testing rule for
nitrobenzene.
Since new processes are being developed
which use nitrobenzene as an input, demand should continue
to grow.
In addition, the major end-use markets for products
derived from nitrobenzene also appear to be expanding.
In
combination these two factors should guarantee continued
market growth for nitrobenzene.
Although increased costs
of production, due to testing requirements, may reduce
this growth potential somewhat, they are not expected to
This is especially
true considering the fact that the per unit cost increase is
result in a decrease in nitrobenzene demand.
4-26
-------
very small (up to .02 cents per lb.).
Based on a review of
the production processes, no firm is expected to be placed
at a comparative disadvantage because of testing costs.
Each
of the plants is large (at least 75 million pounds per year
capacity) and the total number of firms is small.
Thus,
none of the companies is expected to bear an inordinate share
of the test cost burden.
In summary,
the impacts of a testing requirement for
nitrobenzene should not be significant and a Level II analysis
is not recommended.
4-27
-------
REFERENCES - CHAPTER 4
Blackford J. 1977.
International.
Chemical Origins.
Menlo Park, CA: SRI
BOC-Imports. 1978a. Bureau of the Census. Foreign Trade Reports, FT-135,
United States Imports, Schedule A, Commodity Groupings. Commodity
by Country. Washington, DC: U.S. Department of Commerce.
BOC-Exports. 1978b. Bureau of the Census. Foreign Trade Reports, FT-410,
United States Exports, Schedule E, Commodity by Country, Quantity and Value,
Current and Cumulative. Washington, DC: U.S. Department of Commerce.
CASIS. 1979a. Chemical Abstracts Service Information Systems.
Analine pricing U.S. In: Chemical Industry Notes,Vol. 8, no. 19,
p.11. Abstract no. 17416c.
CASIS. 1979b. Chemical Abstracts Service Information Systems.
pricing U.S. In: Vol. 8, no. 21, p.5. Abstract no. 19330u.
Aniline
CASIS. 1979c.
Industry Notes.
Chemical Abstracts Service Information Systems.
Vol. 8, no. 32, p.3.
Chemical
CASIS. 1979d. Chemical Abstracts Service Information Systems. Nitrobenzene
pricing U.S. In: Chemical Industry Notes, Vol. 8, no. 41, p.10 Abstract no.
38827c.
CASIS. 197ge.
pricing U.S.
no. 38827c.
Chemical Abstracts Service Information Systems-. Nitrobenzene
In: Chemical Industry Notes, Vol. 8, no. 41. p.lO. Abstract
CASIS. 1979f.
pricing U.S.
no. 39754p.
CASIS. 1979g. Chemical Abstracts Service Information Systems. Nitrobenzene
pricing U.S. In: Chemical Industry Notes, Vol. 8, no. 43, p.14.
Abstract no. 40743r. p.27. July 2, 1979.
Chemical Abstracts Service Information Systems. Aniline
In: Chemical Industry Notes, Vol. 8, no. 42. p.10. Abstract
C&EN. 1978a. Isocyanate growth put at 8% worldwide.
September 11, 1978.
In:
Chern. & Eng. News.
C&EN.
News.
1978b.
p.22.
Nitration process for aromatic's developed.
November 20, 1978.
In:
Chem. & Eng.
C&EN. 1979a. World polyurethane use heads for 7 billion lbs.
Eng. News. p.12. October 15, 1979.
In:
Chem. &
C&EN. 1.979b. Key chemicals: benzene.
November 19, 1979.
In:
Chem. & Eng. News.
p.20.
C &E N .
1980.
Isocyanates.
In:
Chem. & Eng. News.
p.l1.
February 4, 1980.
4-28
-------
Chern Eng.
1979.
Chemical Engineering.
p. 27. July 2, 1979.
CEP.
In:
1979. Sherwin HB. Developments in aromatics derivatives technology.
Chemical Engineering Progress, p.26. November 1979.
CMR. 1978. Aniline market awaits impact of ARCO isocyanate process.
Chemical Marketing Reporter. pp. 3,11. July 17. 1978.
CMR. 1979a. Benzene prices climb again while toluene remains tight.
Chemical Marketing Reporter. p.ll. June 11, 1979.
In:
In:
CMR. 1979b. Chemical profile:
Reporter. September 3, 1979.
CMR. 1979c. Chemical profile:
November 26, 1979.
nitrobenzene.
In:
Chemical Marketing
~1D I.
In:
Chemical Marketing Reporter.
p.9.
CMR. 1980a. Benzene prices depressed by slack derivative demand.
Chemical Marketing Reporter. pp. 7, 13, & 15. May 26, 1980.
In:
CMR. 1980b. USS sets aniline for its Haverhill site.
Marketing Reporter. p.3. June 2, 1980.
In:
Chemical
Chern Week. 1978. Markets: Is benzene losing to gas tanks? In:
Chemical Week. p.15. July 26, 1978.
DuPont. 1980. Comments to chloromethane and chlorinated benzene. Docket
Nos. 80T-125 and 80T-126. Washington, D.C: U.S. Environmental Protection
Agency. October 31, 1980.
Habeistroh W, Collins D. 1974. Synthetic organic chemicals.
J, ed. Reigel's Handbook of Industrial Chemistry. New York.
In:
Kent
Hancock EG. 1975. Benzene and its Individual Derivatives.
New York: John Wiley & Sons.
Hancock EG, ed.
Hawley GG. 1977. Condensed Chemical Dictionary. 9th ed.
Van Nostrand Reinhold.
New York:
Kirk-Othmer. 1967. Matsuguma HJ. Nitrobenzene and nitrotoluenes.
Kirk-Othmer Encyclopedia of Chemical Technology. 2nd ed., Vol. 13.
York: Wiley-Interscience, pp. 834-839.
Kirk-Othmer. 1978a. Northcott J. Aniline and its derivatives. In: Kirk-
Othmer Encyclopedia of Chemical Technology. 3rd ed., Vol. 2. New York:
Wiley-Interscience, pp. 309-321.
In:
New
Kirk-Othmer. 1978b. Purcell WP. Benzene. In: Kirk-Othmer Encyclopedia of
Chemical Technology, 3rd ed., Vol. 3. New York: Wiley-Interscience.
p.749.
McGraw-Hill.
1977 .
Abright LW, Shreve RN.
Nitration.
In:
Encyclopedia
4-29
-------
of Science and Technology. Vol. 9.
New York:
McGraw-Hill, pp. 120-121.
McKetta JJ. 1972. Petroleum organic chemicals. In: Chemical Technology:
An Encyclopedia Treatment, Vol. 4. The Netherlands: Harper and Row, pp.
517-518.
Mod Plast.
p.57.
Noller CR. 1951.
Saunders Company.
1979.
Polyurethane foams.
In:
Modern Plastics, January 1979.
Chemistry of Organic Compounds.
Philadelphia, PA: W.B.
OSHA. 1977. Occupational Safety and Health Administration. Economic impact
statement: benzene, Vols. 1 & 2. Washington, DC: U.S. Department of
Labor.
PROMT. 1979. Cyclic intermediate.
OH: Pedicast, p.131.
In:
PROMT, Vol. 71, No.4. Cleveland,
Settig M. 1962. Organic Chemical Processes.
The Noyes Press, Incorporated.
Pearl River, NY:
SRI. 1980. SRI International.
States, 1980. Menlo Park, CA.
USITC-IBC. 1976. U.S. International Trade Commission. Imports of
benzenoid chemicals and products, 1974. Washington, DC: USITC pub 762.
Directory of Chemical Producers, United
USITC-IBC. 1977a. U.S. International Trade Commission. Imports of
benzenoid chemicals and products, 1975. Washington, DC: USITC pub. 806.
USITC-IBC. 1977b. U.S. International Trade Commission. Imports of
benzenoid chemicals and products, 1976. Washington, DC: USITC pub. 828.
USITC-IBC. 1978. U.S. International Trade Commission. Imports of
benzenoid chemicals and products, 1977. Washington, DC: USITC pub. 900.
USITC-IBC. 1979. U.S. International Trade Commission. Imports of
benzenoid chemicals and products, 1978. Washington, DC: USITC pub. 990.
USITC-SOC. 1973. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales, 1971.
W~shington, DC: Government Printing Office. USITC pub. 614.
USITC-SOC. 1974. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales, 1972.
Washington, DC: Government Printing Office. USITC pub. 681.
USITC-SOC. 1975. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales, 1973.
Washington, DC: Government Printing Office. USITC pub. 728.
USITC-SOC.
1976.
U.S. International Trade Commission.
Synthetic
4-30
-------
organic chemicals, United States production and sales, 1974.
Washington, DC: Government Printing Office. USITC pub. 776.
USITC-SOC. 1977a. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales, 1975.
Washington, DC: Government Printing Office. USITC pub. 804.
USITC-SOC. 1977b. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales, 1976.
Washington, DC: Government Printing Office. USITC pub. 833.
USITC-SOC. 1978. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales, 1977.
Washington, DC: Government Printing Office. USITC pub. 920.
USITC-SOC. 1979. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales, 1978.
Washington, DC: Government Printing Office. USITC pub. 1001.
USITC-SOC. 1980. U.S. International Trade Commission. Synthetic
organic chemicals, United States production and sales, 1979.
Washington, DC: Government Printing Office. USITC pub. 1099.
4-31
-------
APPENDIX A
ECONOMIC IMPACT METHODOLOGY
-------
APPENDIX A
ECONOMIC IMPACT METHODOLOGY
A.l
Introduction
In keeping with the overall objectives of the Toxic
Substances Control Act, EPA intends to analyze the econom1c
impact of p=oposed Section 4 test rules.
The objectives
of these analyses are (1) to determine if there exists a
potential for significant adverse economic impact as a
result of imposition of a test rule, either at the level
of the
firm,
the industry, or the economy as a whole;
(2)
to determine if that impact potential will actually be
realized through imposition of a specific test rule; and
(3) to estimate the magnitude of the potential economic
impact.
The analytical methodology adopted to satisfy these
objectives reflects the hierarchial nature of the ohjectives.
Initially all chemicals and chemical groups subjected to
testing requirements are examined to determine the potential
for adverse economic impact.
Those found to possess a
significant potential are further examined to determine the
extent to which specific rules will cause this potential to
requirements
Ultimately those deemed sensitive to testing
(i.e., high testing costs and vulnerable market
be realized.
characteristics) are examined in detail in order to quantify
the full range of economic impacts that may be associated
wi th the rule.
A-l
-------
The methodology for determining impact potential for
all chemicals is termed, "Level I Analysis."
The in-depth
analysis of economic impacts for chemicals targeted during
the initial procedure is termed, "Level II Analysis."
The
following sections outline these methodologies in more
detail.
A.2
Level I Economic Impact Analysis
As described above, Level I analysis acts as a filter
to allow those chemical substances potentially adversely
impacted to be differentiated from others.
This is deter-
mined by the incidence of testing costs and the existence
of certain market characteristics.
The market characteris-
tics of interest are those readily available parameters
that can signal the presence of potential for economic
impact as a result of regulatory action.
EPA's approa,ch to screening chemicals for economic effects
due to testing requirements is conservative in nature.
That
is, EPA has decided that for this purpose, it is more desir-
able to err on the side of signalling potentially significant
impact when there is none, than it is to conclude that fur-
ther economic analysis of the impact on a chemical is unneces-
sary, when in fact there may be economic effects.
The market characteristics selected for Level I
consideration are also those important for Level II analysis
and fall, generally, into four major categories: demand
sensitivity, market expectations, cost characteristics, and
A-2
-------
industry stucture.
Level II analysis treats these categories
in a more rigorous and quantitative manner.
A.2.1
Demand Sensitivity
The imposition of testing rules under the Toxic Sub-
stances Control Act manifests itself, in an economic sense,
principally through the price mechanism.
This is the basic
premise upon which both Level I and Level II analyses are
based.
The cost of testing chemical substances can be considered
an additional fixed cost; the total cost of testing does not
vary with the total level of production of the chemical.
(However, depending on the reinbursement scheme decided upon,
the cost to an individual firm may be affected by that firm's
level of production, processing or sales.)
As such, the cost
of testing raises the firm's total costs and average cost
(average cost is the total cost divided by the quantity
produced) .
For those firms where the average cost exceeds
the price received, the rational decision is to allocate
resources to other more productive uses rather than to con-
tinue producing the chemical in question.
Thus, the industry
becomes willing to supply less and the price of the product
rises.
Adverse economic impacts generally arise through reduc-
tions in the quantity demanded of the regulated chemical
due to the higher price.
The magnitude of this demand
A-3
-------
reduction (and thus, of impact) is critically dependent
upon the sensitivity of demand to price: that is, how much
demand declines when the price rises.
Level I methodology requires a detailed description of
the uses for the subject chemical substance.
Each use is
examined to determine principal and potential substitute
substances and their prices.
Gi ven this information, "it
is possible to judge the probable sensitivities of the
various markets for the chemical, i.e., many good substitutes
lead to an initial presumption of sensitivity to impact, and
conversely, lack of good substitutes leads to a presumption
of insensitivity.
This is true even for "captive" markets
where vertically integrated firms produce chemicals for their
own use alone.
In the long run, no firm can be expected to
continue consuming its own products if it can buy comparable
~aterials externally at a lower overall cost.
While sensitivity information is assigned consider-
able importance in deciding whether or not to subject a
substance to Level II analysis, demand cannot often be un-
ambiguously labeled either "sensitive" or "insensitive."
Thus, information en substitutability must be integrated
with information from other categories in order for an
informed judgement to be made.
A.2.2
Market Expectations
Level I analysis requires an investigation of chemical
end-use markets to determine their broad, long term outlook.
A-4
-------
In the absence of specific information, current and recent
historical trends are assessed on the presumption that
expectations a~e conditioned, in large part, by near term
performance.
High market expectations, of course, will
tend to lessen the potential for economic impact from
testing regulations, while low expectations will increase it.
Firms will treat the costs of EPA's testing rules in
a manner analogous to conventional capital investment.
This
means that firms will consider not only current profitability
but also future expectations for the chemical to be
regulated.
Obviously, many factors enter into a firm's
assessment of the future, and many exist on a totally ad hoc
basis with .~ittle applicability in a categorical sense among
different firms and products.
Others are capable of at
least limited assessment.
For instance, regulatory requir~-
ments addressing air and water pollution problems may have
powerful market effects quite unrelated to TSCA.
A.2.3.
Cost Characterist~cs
The behavior of production costs at the level of the
firm and of the plant is an important indicator of the
probability of impact.
Generally speaking, if a plant is
operating at a point where product price just covers
average cost, imposition of testing costs will force it to
abandon the market (assuming other factors do not change).
On the other hand, if the industry as a whole is operating
at a point where price exceeds average cost, there is a
A-5
-------
good probability that testing costs can be absorbed (i.e.,
in the form of decreased profit) with no effect on price or
production at all.
There are two particularly important points to be
examined in this area at Level I.
The first is the existence
of" unique production factors.
These could take the form of
a proprietary, low cost production process, a unique source
of raw material, or a particularly advantageous geographical
location (when transportation costs are a factor).
The pre-
sence of any of these factors ~ignals that firms are in a
position to at least partially absorb testing costs.
Another major factor is the presence of complementarity
in production.
Often several chemicals are produced jointly
within the same process.
While the proportions of each
might be subject to variation within physical limits, it is
impossible to produce one without producing significant
quantities of the others.
Thus, an investment decision
involving one of such a group of chemicals must be examined
in light of the entire group.
In such cases, the presence of
a commercially valuable by-product can mitigate the effects
of testing costs, since the incremental average cost would be
distributed over a larger quantity of outputs.
This situa-
tion will tend to insulate the target chemical from the
imposition of testing costs.
On the other hand, if testing
costs make the entire group unattractive economically, the
resulting economic impact can have multiple effects.
A-6
-------
A.2.4
Industry Structure
Industry structure refers in an economic sense to the
number and size distribution of producers.
It is usually
cited as an indicator of the presence of competitive or
noncompetitive forces in a particular market.
The existence
of a single producer, for instance, is usually a strong
indication of monopolistic market behavior, while many small
producers probably indicate competition.
Markets that to one extent or another are noncompetitive
are much more likely to be able to absorb the cost of testing
rules without adverse impact, than are competitive markets.
Again this result follows from the fact that noncompetitive
behavior results in price being set in excess of average cost.
It should be noted that examination of industry structure
does not encompass the overall size of firms.
This is because
testing costs represent an investment in the continuation
of activity in certain markets and, as such, will be evaluated
in the same manner as any other investment opportunity faced
by a firm (i.e., will the return in the particular invest-
ment exceed the firm's cost of capital?).
Each investment
in testing costs will have to stand on its
of the size or structure of the firm.
own,
regardless
A.2.5. Summary
Level I analysis is a means of selecting for further
economic analysis those chemicals or groups of chemicals
~7
-------
which are mos~ likely to be adversely impacted by EPA test-
ing rules.
In general, those selected for in-depth (Level
II) analysis will possess some combination of the following
market characteristics:
o
A number of good technical and economic substi-
tutes in its most important end uses;
o
An "impact prone" industry structure, characterized
by intense price competition;
o
Regional markets uninsulated by transportation
costs;
o
Absence of special production situations that
would allow cost absorption;
o
Nonoptimistic expectations for future market
performance.
The process for ultimately weighing and balancing
these factors at Level I is by necessity somewhat judgemental
and qualitative; however, a key objective is to not
mistakenly reject a substance for Level II consideration.
Therefore, errors will be on the side of additional Level II
analysis (i.e., for chemicals not impacted).
A. 3.
Level II Economic Impact Analysis
For each chemical substance for which it is determined
through Level I analysis that a potential for adverse economic
effect exists, an intensive economic impact analysis is conducted.
Economic impact is considered within the conventional economic
concept of opportunity cost, which is the value of foregone
opportunities.
The following section outlines the general
approach followed in such an analysis and discusses the
A-8
-------
important factors in estimating the economic impacts.
The
steps involved in conducting Level II analysis build upon
the foundation formed by the Level I analysis.
Whereas,
the Level I objective is to identify cases where a potential
for economic impact exists, the Level II analysis attempts
to quantify the factors considered to be of greatest impor-
tance.
In order to estimate the economic impact of testing
requirements, five areas of investigation are involved:
o
Direct cost of the tests;
o
Demand characteristics and substitution
possibilities;
o
Production cost behavior;
o
Industry structure and competition; and
o
Future market expectations.
Each of these will be discussed in turn.
A.3.1.
Direct Costs
The initial step in determining the economic effects
of test requirements is to determine the costs of the tests
that may be required.
The direct costs of testing are the
costs of all tests required in the test rule.
Direct costs
are principally those associated with the testing laboratory.
However, compliance with the test rules will also involve
costs of an administrative nature.
Since costs may vary
substantially depending on the laboratory doing the testing
and the specified parameters (level and number of doses,
A~
-------
duration, labor productivity, and wage rates) a range of
costs will generally be calculated.
This range of costs
is expected to encompass the minimum and maximum.
For economic impact evaluation, the total direct
testing costs are computed on an annualized basis.
Annual-
ized costs depend on expectations about the future markets
for the chemical.
Therefore, the proper procedure is to
discount the costs of testing over the expected life of
the product.
In most cases, a capitalization period of 20
years, and a pre-tax cost of capital of 20 percent, will be
used.
The capitalization period will be revised as necessary
in light of the expectations concerning future markets.
A.3.2.
Demand and Substitution
After the direct costs of the testing program have
been determined, it is necessary to investigate the manner
in which these costs interact with demand and other market
factors to determine changes in price and output.
The
impact on price is of predominate importance, since price
changes are the driving variables behind almost all
subsequent impacts.
The effect of testing costs on the price of the sub-
stance is the result of the interaction of cost and demand
factors.
On the supply side, the total cost of a test rule
can be considered an increase in the fixed cost of producing
the chemical.
That is, the cost depends on the number of
tests required, not on the quantity of the chemical produced.
A-IO
-------
Thus, the marginal cost of producing the chemical is unaf-
fected (marginal cost is additional cost of producing an
additional unit of output) and the supply curve shifts
principally in response to the decisions of individual
firms to dispense with unprofitable facilities or to shift
resources to more productive activities.
The degree to which the price of the chemical product
will increase depends also on the demand for the product.
The price elasticity of demand is used to measure this
sensitivity.
It is defined as the proportionate change
in quantity demanded as a result of a small proportionate
change in price (E:D = % t::. Q/% t::. P) .
The elasticity of demand
reflects such factors as the end-uses for the substance (and
the demand for the final products), the substitutes for it
(and their supply costs), and any complementary goods
associated with it.
Generally, through the use of econo-
metric methods, the relevant variables (e.g., "own" price
elasticity, cross-price elasticities, etc.) are estimated
in order to determine the impact of the testing program on
the production of the chemical substance and the effect on
products which are substitutes for it.
Estimates of demand elasticity, when combined with
information on direct testing costs, provide the essential
basis for impact estimation.
To fully understand the process,
however, supply side variables must also be estimated.
A-II
-------
A.3.3.
Production Costs and Industry Structure
This component of the analysis links the outputs of the
previous section to subsequent impacts on production, employ-
ment, and profitability, etc.
It focuses primarily on the
capital and operating costs associated with the chemical
production process.
Behavior of such costs is of interest
initially in order to assess the ability of producers to
absorb testing costs, and thus, on their ability to
\
continue production.
In this respect, production costs are investigated
from several standpoints.
First of all, the peculiarities
of the production processes involved are of central interest.
The presence of joint products and co~plementarities may
have considerable bearing on the economics of production
for the substance being regulated.
For joint
products
the costs of production must be considered together, in
comparison to the revenues from all of the products.
Thus,
if testing costs are imposed on one product, the impact on
total costs may be minor.
On the other hand, if testing costs
are imposed on several, or all, products, the cumulative
impact on costs may be significant.
In addition, fixed
factors of production, such as patents and inputs from
existing, upstream processes, can greatly affect cost functions.
Such factors are extremely important in determining the ability
of firms to absorb testing costs without adjusting price or
quantity.
They are evaluated through detailed engineering
analysis.
A-12
-------
Also important are questions of industry structure.
These also reflect on the relationship between price and
average cost, and help specify
firm and industry behavior.
The number of firms in the national market, as well as
their plant size and size distribution, are examined.
Transportation costs and market regionalization are investi-
gated in order to determine if geographical location is a
factor insulating firms from the effect of testing costs.
A.3.4.
Expectations
Expectations playa very significant role in the firms'
investment decision concerning testing costs.
The costs of
testing are a form of investment which may provide no
increase in revenue and, thus, may decrease the overall rate
of return on the company's investments.
In estimating the
effect of the testing costs on the investment decision,
expectations about the demand for the product, future costs
of capital, and the future costs of production inputs are
crucial.
If for example, deman& is expected to increase
significantly for a product due to the introduction of a
new end use, the firm may be willing to "invest" in the
testing rather than shut down the operation, which may have
been the decision in the absence of the new market.
Unfortunately, expectations are a most difficult factor
to quantify.
Expectations formation models have been derived
for various uses and these can be applied whenever feasible.
A-13
-------
However, direct expectational information from the industry
sources is perhaps more relevant.
This is collected on an
ad hoc basis and integrated to provide a picture of future
--
trends.
A.3.5.
Impact Assessment
The final step in the economic impact analysis brings
togethe~ the results of each step of the investigation.
At
this point, the econometric estimates of demand elasticities
are combined with the estimates of direct costs in order to
determine price adjustments.
These results are integrated
with the results of the investment and industry analyses in
order to predict the effects on production and emploYment,
profitibility changes, and effects on other markets, etc.
For purposes of this analysis, it is assumed that each pro-
ducing firm pays a share of the test costs for those chemicals
it produces, based on its proportion of production (processing
firms are not considered at this point, since a definition of
such will be clarified through comment on the proposed test rule):
(1)
c.. = Q... T.
J.) J.) J.
where
C.. = Test cost for the ith chemical
J.) paid by the jth firm
P. . IT ( , th
Q.. = J.] P. 1 Firm's share of total production)
J.] J.
T. = Total cost for testing the ith
J. chemical
P.. = producti~B of the ith chemical
J.] by the j firm
TP. = Total'production of the ith
J.
chemical
A-14
-------
The total cost imposed by testing a chemical substance is
the sum of the costs to those. firms pr.oducing it:
(2)
T.
~
= r c. .
J ~J
It follows that the total costs of testing a group of chem-
icals (such as the chlorobenzenes) is the sum of the indi-
vidual costs:
( 3)
Tc = L: T.
i ~
where
TC = Total direct costs of testing
a chemical group.
It should be noted further that this analysis treats
testing costs as though they are all incurred in a single
year.
In reality, they will probably be incurred over a
two-to-three-year period.
To the ex~ent that costs fall
in other years, rather than immediately, the impact will
be less, thus the "single year" assumption reflects the
philosophy of conservatism (i.e., the "worst case" approach).
In addition to the direct effects, the impact on the
users of the product (i.e., its consumers) due to the increase
in price can be estimated.
This utilizes the price elasticity
of demand and the predicted price change to estimate the
effects on consumers of the product.
The measure of this
effect is the change in consumers' surplus, which is the
A-IS
-------
amount consumers would be willing to pay, to purchase given
amounts, in excess of the amount actually paid.
This can
be considered the change in the net benefits consumers
derive from the product.
Of course, the consumers of the
product will in most cases be producers themselves, and the
change in consumers' surplus measures the impact on these
subsequent producers.
In this manner, the results of all parts of the investi-
gation are integrated and summarized.
Thus, the quantified
impacts are combined with the qualitative factors to produce
a unified estimate of the probable economic impact of
testing requirements.
A.3.6.
Additional Considerations
Analysis such as described above, no matter how well
executed, is invariably an uncertain instrument.
Such uncer-
tainty necessitates the use of the most conservative data
and procedures in order that each estimate account for the
"worst case."
This is an overall policy applying to all
components of the analysis at all times.
~he objective is
never to overlook a situation where substantial adverse
economic impact arises from regulatory actions.
The overall approach used here to analyze economic
effects is that of partial equilibrium analysis.
The approach
considers all factors not directly considered in the analy-
sis to be held constant.
In most cases, this assumption is
A-16
-------
valid; the incremental costs of testing are small relative
to total costs and no impacts outside the directly affected
industry are expected.
Thus, for example, the direct costs
of testing are calculated by summing the costs of individual
tests.
However, depending on the tests required and their
temporal sequence, a demand may be placed on testing
laboratories and other specialized resources which, when
combined with the supply or availability of factors may
significantly affect the costs of testing.
The result of
this is that the cumulative .impact of testing requirements
may, in fact, be greater than the sum of the individual
economic impact analyses.
It should also be noted that EPA's policy on testing
cost reimbursement is a major uncertainty and is not thus
far incorporated into the methodology in any rigorous way.
The manner, distribution, and timing of reimbursement cash
flows could conceivably affect the estimation of economic
impact very broadly.
A.3.7.
Summary
In summary, an economic impact analysis of EPA's
test rules involves in-depth investigation of several
factors related to the chemical production process.
These
factors are, for the most part, identified in the Level I
analysis.
The Level II analysis investigates these factors
in more detail and attempts, where possible, to quantify
the important variables.
A-17
-------
After the direct costs of the test rules are ascer-
tained, econometric and investment analyses are required
to determine the impact of these costs on prices and
quantities, which in turn, determine the impacts on pro-
duction and employment.
The result is consciously biased
to present the "worst case" arising from the imposition
of testing regulations.
A-18
-------
APPENDIX B
TEST COST ESTIMATES
Prepared by:
Borriston Laboratories, Inc.
EnviroControl, Inc.
11300 Rockville Pike
Rockville, Maryland 20852
-------
Introduction
The following methodology for estimating the cost of testing protocols
has been designed to provide, as completely as possible, a representative
estimate of testing costs in the United States. The methodology has been
developed from contractor experience, review of previously published cost-
ing methods, and both formal and informal surveys of other testing labor-
atories, chemical and pharmaceutical companies, and prime contractors for
Federal testing programs. The cost estimates are based on the proposed
test standards where available (Federal Register of July 26, 1979; 44FR 44054).
In all other cases the cost estimates are based on the test standards pu~lished
in the Proposed Test Rule.
The component costs considered include task times, salaries, over-
head rates, supply costs, inflation factors and profit margins. The
estimates were made on a per chemical tested basis. The accuracy and
degree of breakdown presented is directly proportional to the detail specified
in each protocol.
The factors to be considered in providing these estimates allow for
many sources of cost variance. An understanding of the nature of the
chemical to be tested may have a large effect on the time and cost estimated
to conduct the study. Compound preparation and dosing times are both
dependent upon the nature of the test article. Solid materials may be
difficult to maintain in sunspension, requiring a more detailed mixing regimen.
Chemical characteristics may dictate especially frequent sampling of dietary
admixtures to assay for purity, stability, and concentration. Inhalation
studies are particularly dependent on the physical state of the test article:
solid, particulate substances require closer, more frequent monitoring of
exposure chamber concentrations than do gaseous substances.
Overhead rates may be significantly different among testing labora-
tories due to numerous interacting factors. The number of years that a
laboratory has been in operation, for instance, may influence the overhead
rate. Relatively new laboratories have a smaller work force (very few of
which are supported on overhead), larger capital expenditure for new equip-
ment, and more sizeable expenditures for marketing to generate new business.
Well established laboratories usually support many more employees on over-
head and spend less on marketing and new equipment, but spend considerably
B-1
-------
more on such items as the archive maintenance of slides, tissues, and
records generated from manY complete studies.
The range and variety of experimental capabilities offered by a
laboratory may also affect the overhead percentage. If the testing
laboratory is one of many operational units, such as a testing laboratory
associated with a large chemical manufacturing company. the overhead rate
may be inordinately burdened by cost factors from other operational units,
and is thus difficult to compute accurately. The more varied the labor-
atory capabilities are, the more equipment and personnel are required for
operation. The more limited the experimental capabilities, the more the
laboratory must rely on expensive consultants and subcontractors to perform
specialized technical tasks.
The efficiency of the work force is also a variable factor. Higher
salary rates for productive, well-qualified personnel may balance against
lower salaries paid to less efficient personnel requiring more training
and exhibiting greater turnover. A high degree of automation may boost
worker speed and efficiency. yet the cost of automation significantly
increases the overhead rate: automatic watering systems reduce animal
care time, but cause an increased capital expenditure. A similar situ-
ation occurs when computerized systems are introduced to collect, pro-
cess and store data, which reduces technician and report writer times.
All expendable supplies required to conduct a study (e.g., animals,
rations, bedding, chemical reagents, etc.) are subject to many factors
which cause variations in acquisition costs. For example, market fluc-
tuations and the availability and choice of supplier directly affect the
price of test animals. The proximity of the testing laboratory to the
animal supplier will affect shipping costs. Laboratories conducting a
high volume of studies are more likely to take advantage of volume dis-
counts.
Marketing strategies employed by various laboratories may also sig-
nificantly affect the costs of conducting different protocols. As in most
businesses, the overall profit realized by a testing laboratory is pro-
portional to the volume of tests performed. In order to encourage volume
B-2
-------
testingt some laboratories will offer discounted prices for multiple
testing packages which are significantly lower than the sum of the costs
of the individual components tests. Low estimates may also be given to
solicit new business when testing volume is lowt or when a laboratory
wishes to expand its testing capabilities into new areas. Acute protocols
are quite often bid at cost or below cost in order to encourage future
business involving high volume and more expensive and profitable studies.
The accuracy and experience of cost estimating personnel can also
significantly affect estimated costs of specific protocols. Personnel
with little experience may completely overlook certain cost components or
under- or over-estimate other components. Some laboratories routinely
conduct certain types of studies, while seldom or never conducting others,
even though they have the necessary equipment and expertise. Cost esti-
mates obtained for the routinely conducted tests will most likely be
accurate, while estimates for other protocols may show marked variation
from average or actual costs.
Whenever possible, laboratory surveys were performed to obtain price
bids for specific studies. These sur~eys have $ubstantiated the variation
present in test costs. Final estimates generated are considered to be
representative within a range of ! 50% of the prices that might actually
be charged for conducting studies.
The following is a summary of the basic cost estimating method
utilized:
B-3
-------
BASIC COST ESTIMATING PROCEDURES
Cost estimates are calculated by separating each protocol
into components and estimating the cost of each component.
The cost of the following components are estimated for each
protocol:
. Direct Labor Cost
- task identification
- personnel requirements
- task time requirements
- personnel salary rates
- inflation and salary adjustment
I Overhead Cost
. Other Direct Costs
- overtime
- expendable supplies
- consultants
- data processing
- inflation adjustment
. General and Administrative Costs
.
Profit or Fee
These components are combined in the following formula -to
calculate the Estimated Final Cost:
DL + OH + ODC + G&A + F = Estimated Final Cost
-
where:
DL = Direct Labor Cost
OH = Overhead. as a % of Direct Labor Cost
ODC = Other Direct Costs
G&A = General and Administrative Cost. as a % of (DL+OH+ODC)
F = Fee. as a % of (DH+OH+ODC+G&A)
An Estimated Cost Range is then calculated as ~50% of the
Estimated Final Cost. In addition, the results of price surveys
are presented whenever possible. Possible explanations for major
differences between price survey ranges and Estimated Cost
Ranges are also described.
B-4
-------
PROTOCOL ESTIMATE: TERATOGENIC HEALTH EFFECTS (772.116-1)
(PHASE 1. RAT)
DIRECT LABOR:
No. of Hourly Total
Personnel Hours Waqe Dollars
Study Di rector 24 $17.80 $ 427.20
Compound Prep. Technician 12 6.00 72.00
Senior Inhalation Technician 387 12.50 4837.50
Study Set Up (8.0)
Randomi za ti on (8.0)
Teratology (293.0)
Dosing (Inhalation) (63)
Record Keepi ng (15.0)
Inhalation Technician 367 8.25 3027.75
Observations (45.0)
Body Wei ghts (4.0)
Dosing (Inhalation) (63)
Breeding (28.0)
Teratology Preparations (227.0)
Animal Caretaker 75 4.00 300.00
Watering (39.5)
Beddi ng Changes (6.5)
Feeding (13.0)
Cage Cl eani ng (13.0)
Room Cleaning (3.0)
Necropsy Supervisor 30 10.00 300.00
Necropsy Technician 90 5.00 450.00
Analytical Chemist 112 7.70 862.40
Analyst 56 4.00 224.00
Board-certified Pathologist 30 24.00 720.00
Report Writing Supervisor 10 10.00 100.00
Report Wri ter 100 6.00 600.00
Computer Programmer 24 8.50 204.00
Computer Coder 24 5.00 120.00
Report Typi s t 50 5.00 250.00
General Secretary 12 6.00 72.00
Quality Assurance Inspector 48 10.00 480.00
TOTAL DIRECT LABOR: $13,046.85
B-5
-------
PROTOCOL ESTIMATE: T~RATOGENIC HEALTH EFFECTS (772.116-1)
(PHASE I. RAT)
TOTAL DIRECT LABOR:
OVERHEAD (115% of Total Direct Labor):
OTHER DIRECT COSTS:
Overtime (6 Technician hours @ $4.50):
(6 Caretaker hours @ $2.00):
Animal Procurement (144 rats @ $3.50):
Bedding (300 sheets @ 15i):
Animal Rations (20 gm/da/rat x 10.25/501b):
Teratology Reagents:
Data Processing (4 weeks @ $50.00):
Laboratory Supplies (10% of Total Labor):
TOTAL OTHER DIRECT COSTS:
--
TOTAL COST BEFORE G & A:
--
G & A (10% of Total):
TOTAL COST BEFORE FEE:
--
FEE (20% of Total):
ESTIMATED FINAL COST
ESTIMATED COST RANGE:
B-6
$13,046.85
$15,003.88
$
27.00
12.00
504.00
45.00
51.25
500.00
200.00
$ 1 304. 69
$ 2,643.94
$30,694.67
$ 3,069.47
$33,764.14
$6,752.83
$40,516.97
$20,258.49 to $60,775.46
-------
PROTOCOL ESTIMATE: TERATOGENIC HEALTH EFFECTS (772.116-1)
(PHASE I I. MI CE)
DIRECT LABOR:
No. of Hourly Total
Personnel Hours Wage Doll ars
Study Di rector 24 $17.80 $ 427.20
Compound Prep. Technician 16 6.00 96.00
Senior Inhalation Technician 345 12.50 4,312.50
Study Set Up (17.0)
Randomization (6.0)
Dosing (54)
Teratology (256.0)
Record Keepi ng (12.0)
Inhalation Technician 324 8.25 2,673.00
Observations (48.0)
Body Wei ghts (2.0)
Dos i ng (54)
Breeding (12.0)
Teratology Preparation (208.0)
Animal Caretaker 70.5 4.00 282.00
Watering (20.5)
Bedding Changes (15.0)
Feeding (10.0)
Cage Cleaning (22.5)
Room Cleaning (2.5)
Necropsy Supervisor 27 10.00 270.00
Necropsy Technician 81 5.00 405.00
Analytical Chemist 96 7.70 739.20
Ana lys t 48 4.00 192.00
Board-certified Pathologist 27 24.00 648.00
Report Writing Supervisor 10 10.00 100.00
Report Wri ter 80 6.00 480.00
Computer Programmer 24 8.50 204.00
Computer Coder 24 5.00 1 20.00
Report Typi s t 30 5.00 150.00
General Secretary 12 6.00 72.00
Quality Assurance Inspector 48 10.00 480.00
TOTAL DIRECT LABOR: $ 11 ,650.90
B-7
-------
PROTOCOL ESTIMATE: TERATOLOGY HEALTH EFFECTS (772.116-1)
(PHASE II. MICE)
TOTAL DIRECT LABOR:
OVERHEAD (115% of Total Direct Labor):
OTHER DIRECT COSTS:
Overtime 16 Technician hours J $4.50):
(6 Caretaker hours @ $2.00)
Animal Procurement (144 mice @ $2.65):
Bedding (300 sheets @ 15~1:
Animal Rations (15 Ida/mouse x 10.25/bag}:
Teratology Reagents:
Data Processing (4 weeks @ $50.00}:
Laboratory Supplies (10% of Total Labor):
TOTAL OTHER DIRECT COSTS:
--
-
TOTAL COST BEFORE G & A:
--
~ (10% of Total):
TOTAL COST BEFORE FEE:
--
FEE (20% of Total):
ESTIMATED FINAL COST:
ESTIMATED COST RANGE:
B-8
$
27.00
1 2 . 00
381.60
45.00
41.00
500.00
200.00
$ 1,165.09
$27.421.13
$30,163.24
$ 11 ,650.90
$ 13,398.54
$ 2,371. 69
$ 2,742.11
$ 6,032.65
36,195.89
$18,097.95 to $54,293.84
-------
PROTOCOL:
TERATOGENIC HEATH :EFFECTS (i72.116-1)
1 T72..116-2 Teratogenic effects leat
8blndan:lL
(a) Sludy design. (1) Species and
.train. Testins mUlt be performed In .t
le..t two maDUDalilID species. The rat.
mouse. hamlter. or rabbit are -
Icceptable. Other Ipecies may be used
Iladequala Justification ia lupplied. One
apecies must be the aa~ as the lpeciea
used In the reproductive ltudy. Slraina
with low Ce\.'UDmty must pot be used:
Historical teratogenic data Cor the
.peciSc atraiDlelled must be submJtted.
(2) Se;c and age. AlllI:st and control
animals must be young. mature.
pregnant females of willorm age. sire.
aDd parity. Prima gravida Cemales are
prc!c;:-;:ci
. (3) Contral groups. Concurrent control
group(s) are required as Collowa:
(I) A positive control group"is
required. unJess historical data Crom the
laboratory performing the lest are
.ubmitted which demoDSt:rate that the
alnllru oC animals being used are
aensitive to known teratogenic agents.
(ii) A vehicle control group is required
'II a vehicle il use~ in administering the
test .ubstance.1n addition. il there are
Insufficient data on toxic properties of
the vehicle used in administering the
lest .ubstance. an untreated (negative)
control group receiving a aham
tre8Unent (e.g.."phY8iologicallallne) Is
also required.
(ill) U no vehicle u used in
Idministering the telt lubstance. a
aeperate control group receiving a sbam
trea~ent (e.g.. physiological la1ine) la
reqwred. .
(4) Number of animals. Each test and
control group must include 20 or-more
pregnant females for rat. mouse. and
hamater. and .t lealt 12 pregnant
(emales Cor rabbit.
(5) DUlTJtlon 01 lest and lilli" 01
delivery. (I) The leat .ubtance mUlt be
.dm1nI.tered doOy beginning at. or
before. the Ome of ImplantaUon and
conlinuInr througb the period of major
organogenelil. Expolure oC each Ipecie.
must encompa.. the geJtation period up
10 the day beCore lerm.
(ii) Fetuses must be delivered by
celarean lection approximately 1 day
prior to term.
" (ill) Females (parents) mtlst ordinarily
be ..ai1iced at time of cesarean sectioo
un1ess conditions indicate earlier
saai.5ce as required by paragraph (ii) of
this lection.
(6) Dosage. (i) At least three dosage
levels must be lested in addition to the
cootrol(a).
(ii) The highest dosage level must
ioduce some fetal or maternal toxicity.
al demonstrated by body wei8ht "
reductioo or other toxic signs. but not
cause more than 10 percent maternal
fata}jties.This.level must be higher than
that expected Cor human exposure.
(Iii) The iotermedJate dose(s) mu.t be
lpeced logarithmically (or al IOme
approximate comparable point) between
the high and low dosage level and must
induce lome observable fetal effecu
attributable to the test substance. when
~D~ .
(iv) The low dosage levelmbst induce
DO ob.ervable adverse effects
attributable to the test lubstance.
(v) The dOle a.dministered \0 each
ao.imal must be based on the Individual
animal'a body wei8ht on the first day of
test aubstance administration..
(vi) Dosing must be scheduled at
approximately the same time during the
day-
8-9
(7) Route 01 adminisllTJtion. To the
exteol possible. route(s) of
administration should be comparable I.l
the expected or known routes of humu
expo.ure. The lest rules In Part 771 wiD
speciCy the route(l) 10 be employed for
particular chemical
(b) Study conducL (1) Animal core.
Food and water must be provided ad
libitum. Pregnant Cemales must be
provided nesting materials or
Justification Cor not providing such
material must be submitted. Animal.
may be I.s1dividually caged or group
caged.
(Z) Observati&n. (I) The requlremen~
Cor observation of anima!! as specified
In Subpart A. ~ 77Z.100-Z(b)(6) apply to
Subpart F. Each 8uch observation must
be made by an appropriately-trained
ob.erver. wiVJ must oote aod record
behavioral abnormalities. and aU
c:linjca.l ligru oC toxicity. l.s1c1uding
morislity.
(ii) Any Cemale .howing ligru of
abortion or prema~ delivery Inust be
lacrifia!d 00 the day 8uch evidence b
observed.. These animals must be
8nalp:ed. and all observations reported
separately.
(iii) Females must be weighed at the
..rst day of test s:Jbstan~
adminiatration aod 8t sacrifice.
(3) Necropsy. (i) Immediately after the
female il .acrificed. the uterus mUlt be
excised and weighed. theo examined fer
fetal resorption. number of live fetuses
and number of dead or resorbed fetuseL.
The litter weight of live fetule. mu.t be
determined.
(ii) One-half of each litter must be
examiDed Cor skeletal anomalies. and
the remaining one-bail oC each liller"
must be examined for IOn tissue
aoomaLies.
-------
(111) External and .011 tiaaue
examination of the fetuse. mu.l be
perlonned by or under the .upervlalon
of an individual experienced and
.ullably tra'ined Interalollenlc .tudle..
The .ex of each fetu. must be
detennlned. if poulble. Gron
observations of the skeleton and
external and Inlernal organa must be
made with the aid of a dissecting
microscope (or other Instrument
providing similar magnification). The
internal gross morphology must be
examined by sectioning througb soft
tissues (using razor blsde sectioning or
comparable techruques),
(iv) The necropsy data must be
recorded and reported in accordance
with paragraph (3) of this section.
(v) Entire fetuses must be preserved
and held in a=rdance with ~ 772.110-
1UJ. Subpart B.
(c) Dala reporong and evaJuotJon. In
addition to the basic information
required by ~ 772.100-2fb)(8). Subpart A.
the final test report mnst include the
following information. presenled in the
format specified:
(1) Test protocol. Rstionale for
seleelion of the specie, and strain used.
(i) Dose levels (expressed as mg/kg of
body weight per day) sdministered. and
the rationale for their seJection: and the
number of days of tesls subsl4nce
a dminiB Ira ti on.
. (ii) Rou4! and method of
administration utilized and the rationale
for selection if other than oral
in tuba lion.
(ill) Positive control data or historical
data ~m the laboratory performing the
test wh"ch, demonstrate the sensitivity of
the s tTa lD.3 being used.
(iv) ]ustification statement for not
providing nestingmaterials for
pregnanat females.. if such materials
were not provided. '
(2) Maternal data. (i) The following
information. arranged by test groups.
muat be supplied in tabular form:
(A) Dala showing. for each animal:
(1) Its identification number:
(2) Its sge (or approximate age) at the
start of the test
(3) Dala.of caesarian section and
sacrifice;
(/), Body weigbt on flJ"!t day of dosing:
(5) Its body weight atlacriIice (actual.
and corrected (by subtracting gravid
uterus)};
(6) Thl: body weIght change based on
the foregoing weight meuuremenla: and
(1) Any Ilgn. of abortion or premature
delivcJ1'.
(H) Data .howing. for each dose level:
(1) The number of animala initially on
.tudy;'
(2) The number and perccnt that died:
(3) The number and percent that were
pregnant: and
(4) The average maternal body weigbt
change.
(ii) The following test Infonnalion
must be supplied in any appropriate
form: A description of all observed signs
of toxicity accompanied by the animal's
identification number. tesl group. and
daters) of observation.
(3) Fe/oj data. When an anomaly is
difficult to describe. a photograph ,oC it
may be submitted. All means must be
accompanied by standard 'devia tion.
The' following infonna tion arranged by
test group must1;>e supplied in tabular
form:
(i) Numerical data showing, for each
li tter.
(A) Identification numbers;
(B) Number and percent of live
fetuses;
(C) Average live fetal weight;
(D) Number of each sex. if
determined;
(E) Number and percent of dead and
resorbed Ietuses;
[Fj Number of implantations: and
(G) Number and percent oC Ietuses
with any soft tissue of skeletBl
abnormality.
(ii) Anomaly data, sbowing, for each
li u er.
(A) Identification number(s);
[B) Number of Ietw;es examined by
'necropsy;
(CJ Number and percent of fetuses
having soft tissue anomalies;
(D) Number oI fetuses examined for
skeletal anomalies;
(E) Number and per;ent of fetuses
having skeletal anomalieS: 'and
[F) Incidence and a full descripUcn of
each type DC anomaly.
,(iii) CwnuJative data ahowiag. for
each dose level;
(A) Identification of the dose level
group:
(B) Number of litters examined;
(CJ Number of implantations per litter.
(D) Average number of live fetuses
per Ii II er:
(E) Average of live fetal weights.
(FJ Percent of dead and resorbed
fetuses per litter.
B-IO
(G) Number and percent of felule.
bcaring anomallea of each kind
observed:
(H) Number and percent of fetusel
bearing any anomaly;
(I) Number and percent of abnorm&1
fetuscs per IIlIer. and
UJ Number and percent of litter.
baving anomaloua Ielusci.
(4) Evaluation. The \iller or dam Is an
accepted unH for evaluation. Dala on
individual fetuses with anomalies
should also be considered.
, (I) Evaluation of the resulls with
respect to observed effects, must
indude:
(A) An evaluation of the relationship,
if any. betweeI) exposure to the lest
substance and the anomalies and aU
other toxic signs observed; and
(B) An indication of the dosage level
at which no toxic efTects attributable to
the test substance would appear.
(ii) Statistical analyses must be
perlormed to assist in the reporting and
evaluation of data. AU slatistical
methods used should be identified by
reference snd/or fully deso-:bed,
-------
PROTOCOL ESTIMATE: REPRODUCTIVE EFFECTS TEST STANDARD (772.116-3)
DIRECT LABOR:
No. of Hourly To ta 1
Personnel Ho urs Wage Doll ars
Study Director 62 $17.80 $ 1,103.60
Compound Prep. Technician 60 6.00 360.00
Senior Inhalation Technician 1716 12.50 21 ,450.00
Study Set Up (50.0)
Randomization (34.0)
Observations (264.0)
Dosing (1 ,100)
Record Keepi ng (248.0)
Audit Preparation (20.0)
Inhalation Technician 1770 8.25 14,602.50
Observations (200.0)
Body Wei ghts (430.0)
Dosing (1 , 1 00)
Sacrifice, interim (12.0)
Breeding (20.0)
Spermatogenesis (8.0)
Animal Caretaker 817.5 4.00 3,270.00
Watering (436.0)
Bedding Changes (70.0)
Feeding (140.0)
Cage Cleaning ( 1 40 . 0)
Room Cleaning (31 .5)
Necropsy Supervisor 33 10.00 330.00
Necropsy Technician 99 5.00 495.00
Histology Supervisor 76.74 10.00 767.40
Histology Technician 306.94 6.00 1,841.64
Analytical Chemist 1973 7.70 15,192.10
Analyst 987 4.00 3,948.00
Board-certified Pathologist 109.74 24.00 2,633.76
Report Writing Supervisor 50 10.00 500.00
Report Wri ter 400 6.00 2,400.00
Computer Programmer 120 8.50 1,020.00
Computer Coder 120 5.00 600.00
Report Typist 150 5.00 750.00
General Secretary 31 6.00 186.00
Quality Assurance Inspector 80 10.00 800.00
SUBTOTAL DIRECT LABOR: $72,250.00
Salary Adjustment (20%) 14,450.00
TOTAL DIRECT LABOR: $86,700.00
B -11
-------
PROTOCOL ESTIMATE: REPRODUCTIVE EFFECTS TEST STANDARD {772.116-3)
TOTAL DIRECT LABOR:
OVERHEAD (115% of Total Direct Labor):
OTHER DIRECT COSTS:
Overtime (60 Technician hours @ $4.50):
(60 Caretaker hours @ $2.00):
Animal Procurement (168 rats @ $3.50):
Bedding (2232 Sheets @ 15~):
Animal Rations (30 gm/da/rat x 10.25/50 1b):
Histology Supplies (7040 samples @ $.33):
Data Processing (60 weeks @ $50.00):
Laboratory Supplies (10% of Total Labor):
SUBTOTAL OTHER DIRECT COSTS:
-
INFLATION ADJUSTMENT (12% of Other Di rect Cos ts) :
TOTAL OTHER DIRECT COSTS:
TOTAL COST BEFORE G & A:
--.--
G & A (10% of Total):
TOTAL COST BEFORE FEE:
FEE (20% of Total):
ESTIMATED FINAL COST:
ESTIMATED COST RANGE:
B-12
$
270.00
1 20 . 00
588.00
335.00
1 , 183. 26
2,323.20
3,000.00
8,670.00
$ 16,489.46
1,978.74
$204,873.20
$225,360.52
$ 86,700.00
$ 99,705.00
$ 18,468.20
$ 20,48732
$ 45,072.10
$270,432.62
$135,216.13 to $405,648.93
-------
PROTOCOL:
REPRODUCTIVE EFFECTS TEST STANDARD (772.116-3)
~ 772.116-3 Reproductive effects tesl
slandsrt!s.
(a) Study design. (1) Species. Testing
must be performed in at least one
mammalian spedes which may be the
same as one of the two species used in
the teratogenic effeds study pursuant to
~ 772.11B-2 of this-subparL The rat is
preferred.
(2) Number and sex of animals. In
testing with rodents. each dose and
control group must contain enough
females to produce approximately 20
litters (20 sampling units) at -each
breeding. assuming typical mating and
fertilitv for the strain. At least 10 fertile
males 'per dose in the first mating of the
F generation must be used.
Subsequently at least 10 males per dose
level are reqWred.
(3) Number of doses and dose
selection. (i) At least three dose level
groups. in addition to the control group.
must be tested.
(ii) The highest do!:e level must
produ.£!:.....an observable toxicological or
pharmacological ~ff~ in the t'est
nnimals.1rnt not cause more then 10
percent fatalffies. Tbislevi! must be
higher "than that expected far Dnman
expormre. -
tiii) Tbe lowest dose 1eve1 must
produC!: no ubaen-aole IIdveI"lle ~ffeds.
(4) Cantrol grrmp. Concurrent control
groups are reqaired as IonowS':
{i) A vehicle c:cutrol group U Tequired
if II ..erode is used in administering the
test substance. if 1lrere lIlT!! instdIicient
data on the 1ox:ic properties cl the
vehicle1JSed in administering the test
substance. a sepaI1lte~ntrol group
receiving no.1:hemkal treatment is also
required.
fnl H no vehicle b U3'ed in
administering the 1ffi s'abstance. a
separate control group receiving a lIham
lreabnent1e.g.. physiological saline) m
required.
{5) ROtlte of administralion. To the
extent possible. TOute{s) of
administration should be comparable to
the expected or hcrwn routes of humHI1
eXposure. The -test roles in Part 771 will
spe~ fite TUute{s)10 be-employed far a
Darhcular chemiCilL
(6) Duration of testing. Ii) The tes1
substHI1ce must be administered to two
generations-1Jf animals. F. and F.. A
third gCTJeration of animals. F.. will 'be
exposed to the test substance in utero
and thrcugn nursing.
(ii) Dosing of B'Dimals in the F.
generation mu6t begin 1IS soan as
p05sib1e after weaning and
acclimatization. and in any case before
the animals .are 6 weeks old. The tes1
substance must be administered daily 10
the F. generation. Dosing must continue
lUIlil all F. generation animals have
been weaned. '
(iii) Dosing of the animals selected
from -the F. generation far breeding must
begin as soon as the' animals are
weaned {approximately 30 days after
birth). The test substance mus1 be
administered daily 10 these animals.
dosing -must continue until 30 days after
all F. animals -have been weaned.
(Dosing of animals from F. generation is
not required if they have not been
selected for breeding).
(b) Study conducL (1) Breeding. After
the F. generation animals sucn as
rodenta and lagomorphs have received
the lest rubstance far at least 100 dayB.
they must be bred to produce the F.
generation. Apprapriate numbers of
males and females must be selected a1
random from different Jitters of the F.
generation for breeding. After the tes1
substance has been adnrinis1ered to
these animals Ior at least 120 days. they
must be bred to produce the F.
generation. FIgure 1 of the Appendix
inlficates an acceptable b~ and
dosing ~chedule.
~!)linjmal-care.1Tegnant females
must "be caged separately and furnished
witn 1!esting materials.
(3) O~ervaticms..The requirements
for observation of animals 811 specified
In Subpart A. 1 77%.1DO-Z(b)(6) apply 10
Subpart F.
fi)Frequency. Eaci1 animal must be
observed Tor eII~ls aa long 1IS it is "being
exposed to (he te!t sQ"bstan~. Anima1.
must be ub8~d as frequently as
necessary io o01ain the data required by
paragraph {c) of this section mrd
_Subpart A. Sec60n 772;1~('bH6).
B-13
(ii) Crowth and delivery data. The
weight of ~ch Wt!snling must be
recorded weeUy to weight maturity and
month1y lherealter. 1ne dates of
delivery must be recorded.
(Hi) Maternal data. Qb5ervatian must
be made uf 1he general condi(jon and
behavior of mothers. including nesting
and_nun;ing. Any-abnormalitie..s must be
recorded.
(ivj Palf!mal duta. Measurments must
be made of spermatDgenesis -of all males
in the F.. F.. -amI F. genera tions used 10
produce the subsequent generations..
Such me.asmemeIIls aboold be
Lmdertaken within CIIJ£ week after
breeding. In addilioD. ar as an
a1ternative. histopathDlogy
examinations of the teJ>.U. 8JI indicated
in pan.graph (c)(l1) of th.i3 section. .must
be underlRkeD. AdditionalllSeful
information maybe obtained by
histopathology e:xIUDin.atiOrul of the tests
of males in the F. and F2 generations.
particularly those males u6ed for
producing the subsequent generations. U
spermatogenesis or histopathology of
tests i:l evaluated inmales in the F. and
F. generations. such males should be of
the same approximal1! age and should
nave oeen dosed lor the same
appraximal1! length of time as males
used in the F. generation (at the -time the
F. genera lion males were examined).
Tv) Liller data. Allliuers must be
examined B.-' sgon .88 possible alter
deHvery. Where possible. effort should
be made to prevent cannibalism of
young. The foIlowing must be recorded:
Utter size: number of stillborn; and
number ofilve births. V.Lability counts
and pup weigbt must be J'ecarded at
birth. Iour days altar birth. and wean~.
Additional viability counts betwun the
fourth day and weaning are required Ior
non-rodents. Any physical or behavioral
abnonnalitics must be recorded.
(4) Cross necropsy and
histopathology:. (i) F. generation. Ten
males and Z5 females from each dole
level and the control group must be
subjected to a complete gross necropsy
-------
and histopathology examination. The
animal. mu.t be cho.en from the F.
lIeneration anlmail u.ed to produce the
F. generation. The animal. mu.t be
.acriCiced at the end of the required
period of do.lng. The necropsy and
hl.topathology examination mu.t
Include examination oC the reproductive
organa.
(Ii) F. and F. generation. A complete
groSi necropsy and histopathology
examination musl be conducled on five
randomly selecled weanlings of each
sex from each lesl group [doae level and
sex) In eac.'1 generation (F. and F.).
(iii) Conduct of eJCominaiions. All
examinations must be conducted by or
under the supervision of a qualified
pathologist. The standards set forth in
~ 77Z.100-2(b)(1) and (7), Subpart A
Apply.
(c) Data reporting and evaluation. The
tester must submilto £FA the following
reports:
;Study Plan" as required In ~ 772.100-
2(b)(Z), Subpart A;
"Interim Quarterly Summary Reports"
outlining the current status of the study
including any significant findings; and a
"Final Test Report".
In addition to the basic information
required by ~ 772.100-Z(bJ(8J. Subpart A.
the "Final Test Report" must include the
following information. presented in the
format specified:
(1) Test protocol. (i) The rationale for
species and strain selection: and
(ii) The rationale for selection for the
dosage levels; dosage levels must be
reported as mg/ks/day as well as ppm.
(2) Animal dolo. For all means in the
data required in this subparagraph. such
means must be accompanied by the
standard deviation.
(i) Female data. The following
information relating to the reproduction
of each female must be supplied In
tables. with foolTlotes and description
where appropriate:
(A) For each animal: Date of delivery;
and unusual or abnonnal behavior
during estrous, gestation. or delivery;
and fertility.
(8) Cumulative data showing means
for controls and each dose level group in
the F. and F. generation: the gestation
index: approximate duration of
gestation: and number and percent of
animals showing behavioral
abnormalities in connection with
reproductive activity.
(C) For each mother: Its identification
num~er, any abnonnalilies in neslin8 or
nursing: total number of offspring per
liller, number and percenl of live and
dead ofTspring: and general condition of
offspring and mother through weaning.
(D) For each dose level and control
IlrouP In the F. and F. generation: The
fertility Index: sverage size of Jitter;
nerage number of dead and live
offspring per litter; and number and
percent of mothen showing behavioral
abnormalities In nesting and nursing.
(iI) Male dolo. For each male
evaluated for spermatogenesis In
sccordance with paragraph (b)(3)(lv) of
this section: Identification number and
the results of the evaluation.
(iii) Litter data on pre weanling
animals. The following liller data on
preweanling animals must be supplied
in tables. with footnotes and
descriplions where appropriate:
(A) For each litter arranged by dose
level and generation: Totalliller size:
number and percent of slillborn; number
and percent of live births; viability
index: lactation index: weekly viabilily
counts and weekly weight of each p-up
from day 4' of life 10 weaning: and
number and nature of physical
abnormalities observed.
(8) For each dose level and
generation: Mean weekly weight of al1
pups from day 4 of life to weaning;
number and percent of pups with
physical or behavioral abnormalities:
number and percent of pups surviving at
birth. 1 week. and 3 weeks; and mean
viability and lactation indices.
(iv) Liller. data on paslweanling and
mature animals. the following
inIormaiton. arranged by test group
(dose level and sex). must be supplied in
tabular form (WIless adequate
justification is supplied to present these
data in another form):
(A) Fo( each animal: Its identificalion
number, its age al the beginning of the
study; its age at death and manner of
death; and its weight. as measured
weekly througb 1 month of age and
monthly thereafter.
(8) Cumulative data showing means
for ear.h control a!\d test group: The
weekly or mo~thJy weights: and the
number and percent. of animals with
behavioral abnormalities.
(3) Gross necropsy data. The
following test information. arranged by
test groups (dose level and sex) must be
reported:
(i) Data showing the identification of
any animal for which any gross
abnormality or lesion was obserVed.
and containing for each such animal a
de~cription of each abnormality or
lesIon. Gross abnormalities or lesions
observed repeatedly in gross necropsies
need be described only once and
thereafter may be described by
reference.
(iliData showing the number of
animals afTeced by each type 'of
B-14
abnormRlity or lc~iun: and the number
of animal~ in which any IIbnormalily or
leiion was ob~rrvcd.
(4) Evaluation. (i) Evaluation of Ihe
rC8ult. with respecl 10 al1 toxic or
pharmllcolo!1ical effecls, Including:
(A) An evaluation of the relationships,
If any, between exposures 10 Ihe lesl
substance and the incidence and
severity of effects ;including effecls on
reproduction. behavior, tumors and
lesions. and mortality).
(8) An Indication of the dosage level
al which no loxic e(fects attribulable 10
the tesllubstance would appear.
(ii) Slatistical analyses musl be
performed to assisl in the reporting and
evaluation of dala. All statistical
methods nscd musl be identified by
reference and/or fully described.
-------
PROTOCOL ESTIMATE: SUBCHRONIC INHALATION TOXICITY (772.112-33)
DIRECT LABOR:
Personne 1 No. of Hourly Total
Hours Wage Dollars
Study Di rector 52 $17 . 80 $ 925.60
Veterinarian 8 14.00 11 2 . 00
Compound Prep. Technician 52 6.00
Senior Inhalation Technician 523.5 12.50 6,543.75
Study Set Up (32.0)
RanQomization (16.0)
Observations (55.5)
Dosing (195)
Blood Collection (27.0)
Urine Collection (4.0)
Pulmonary Testing ( 1 20)
Record Keepi ng (65.0)
Audit Preparation (9.0)
Inhalation Technician 522.5 8.25 4,310.63
Observations (72.5)
Body Wei ghts (35.0)
Food Consumption (69.0)
Dos i ng (195)
Blood Collection (27.0)
Urine Collection (4.0)
Pulmonary Testing ( 1 20)
Animal Caretaker 227 4.00 908.00
Watering (141.0)
Bedding Changes (24.0)
Feeding (8.0)
Cage Cleaning (47.0)
Room Cleaning (7.0)
Clinical Lab Supervisor 66 10.00 660.00
Clinical Lab Technician 202 6.00 1,212.00
Analytical Chemist 347 7.70 2,671.90
Analyst 173 4.00 692.00
Necropsy Supervisor 34 10.00 340.00
Necropsy Technician 102 5.00 510.00
Histology Supervisor 32.26 10.00 322.60
Histology Technician 111 .62 6.00 669.72
Board-certified Pathologist 114 24.00 2,736.00
Report Writing Supervisor 24 10.00 240.00
Report Writer 320 6.00 1,920.00
Computer Programmer 26 8.50 221.00
Computer Coder 26 5.00 130.00
Report Typi st 300 5.00 1 ,500.00
General Secretary 26 6.00 1 56.00
Quality Assurance Inspector 52 10.00 520.00
SUBTOTAL DIRECT LABOR: $27,613.20
B-15
-------
PROTOCOL ESTIMATE: SUBCHRONIC INHALATION TOXICITY (772.112-33)
Salary Adjustment (8%):
TOTAL DIRECT LABOR:
$ 2.209.06
$ 29,822.26
$ 34.925.60
OVERHEAD (115% of Total Direct Labor):
OTHER DIRECT COSTS:
Overtime (15 Technician hours @ $4.50):
(15 Caretaker hours @$2.00):
Animal Procurement rats @$3.50):
Bedding (1600 sheets @ 15~):
Animal Rations (20 gm/da/rat x 10.25/501b):
Clinical Lab Supplies (240 samples @$9.09):
Histology Supplies (2560 samples @ $ .33):
Data Processing (13 weeks @ $50.00)
Laboratory Supplies (10% of Total Labor):
SUBTOTAL OTHER DIRECT COSTS:
$
67.50
30.00
240.00
276.75
2 , 1 81. 50
844.80
650.00
2,982.22
-
-
$ 7,282.87
I NFLATION ADJUSTMENT (5% of Other Di rect Cas 15):
364. 14
TOTAL OTHER DIRECT COSTS: $ 7,647.01
TOTAL COST BEFORE G & A $72,394.81
G & A (10% of Total): $ 7,239.48
TOTAL COST BEFORE FEE: $79,634.35
--
FEE (20% of Total): $ 15,926.87
ESTIMATED FINAL COST: $ 95,561.22
--
ESTIMATED COST RANGE: $47,780.61 to $143,341.83
--
B-16
-------
~ 772.112-33 Subchronlc Inhalallon
tDJ iclty l1ucty.
(o) Study dt'$I.~n. (1) SP"C/l'.< and AJ!~.
Tcsltn~ must be rerlarn.ed on youn~ ..dull
laboralon'1815.
P) NII1~"cr nnd Sc. of 7('$/ ."'nimok A
mimmum 01 10 nnimRls rcr ~e>. rer exposure
Ipvel must be u~l'd. nllS numher must he
incrca~l'd by the number. if Rny'. sch,.dulrd to
ue ~ar.rifjc~d before complet.on of the stud\'.
such 8S. far e>'Rmple. rRls an which'
hematnlogy Rnd blaod chcmistry
d"lerminal.ans ..re made [,dOle Rnd durin~
the 5Iud)'.
(3) J\'umber and seluction of e.\pOSlJre
wncenlration ICI els. (i) AI If'ast three
e,xposllre concentration le\'('ls. in
addilion to the control(s). musl be u~ed.
(ii) The lowest 8tmu~phenc
concentralion must not show toxic
eff ects,
(iii) The highesl ntmospheric
concentralion must demonstrate some
toxicological eITects. but nol cause more
than 10 percent fatalities. This level
should be higher than that e'\pected for
hl'man exposure.
(iv) All exposure le\'els and control I 5)
must be perfonned concurrently.
(4) Duro/ion or tt'slmp. Animuls must
be exposed 10 the lest f;ubstilnce 8t JeAst
6 hours per da~' for al It,!!!t 5 duys per
week over a 90-day period. Longer or
more continuous exposures mny be
selected. dependinEi on the test
substance and the expecled use pAttern
of the test subs\ance. If shorler or.le~s
continuous exposures s('cm at'propriHte,
the tester must cO!'1sult wilh the Agency
concerning thl' exposu.e times.
[5) Use of I'ehide. A vehicle may be
added to the lesl substance. if
necessary, to help genera te an exposure
almosphere. If the product's labding
instructions specify the use of 8 vehicle.
that \'ehicle is preferred. If no vehicle is
specified in the product's labeling
instruclions. the vehicle. if on\'. Iha t has
been used to formulate the pr~duct
should be used. if possible.
(6) Canlrols. (i) Vehicle canlroJ. If liny
vehicle other than water is used in
generatin~ the exposure atmosphere. a
concurrenl solvent control group is
required.
(ii) Negatil'e control. A concurrent
negative cpnlrol group is required. These
control animals must be treated in the
same manner as all other test animals
[including placement in exposure
chambers). except that this control
group must not be exposed to ar.
atmosphere containing the test
substance or any solvent.
(lI) Stud.\' conduct (1) £.\I'n~urr
chu;;rbcr dt:s/~l.!n and 0l'/'ro/loll
InhOllatlon expusure IcdI014Ut.~
dt~~cribed in tl1ls M,cllun IHe based on
th~ use of whule-bodv inhaliJllOn
chambers. In such ch'ambers. the
cxperimental ...nimals receive ",holt'.
body dermal exposure and possibl~'
large oral cxpo~ure. as well as e"posure
by inhalation. In some cases. the Ic'Sler
may wanl 10 u~r other inhalation
exposure techniqllcs invol\'ln!: f.lce
mds\..s. head.onJy exposures,
intratracheal instillation. find other
simi1ar techniqlles which reouce or
Pleclude dermnl and oral expos II res.
Some allerniitl\'e IcchniquC's are
oescribed b~' PhaJen, 19i6. When
...lipmiitl\'e techniqucs arc usC'd, the
prucC'dures and results must be reported
in a manner similar to ,hat required \\'llh
the use of whole-body inhal~!ion
chambers.
(2) Operational measurements, The
follo\\'ing measurements mu~t be ta\..en.
with care to avoid major nucluations in
the air concentrnlions or major
discrepancies in the operation of the
c0a~ 1.;ers:
[i) Air fJow. The rates of air now
throut:h the chamber must be melOsurec
contmuously.
(ii) Chamber concentrations. [A)
Nom;...al concentrations must be
cHlcu!ated for each test exposure b\'
dlvid:ng the amount of the a~ent u~-pd
for the generatmg system by the air flo\\'
throu.::-h the chamber during the
exposure.
IB) Actual concentrations must be
delermined by samples of chamber air
laken near the breathmg zone of the
animals as frequently as necessary 10
obtain an averaged integrat['d external
exposure which is representative of the
enlire exposure period. The svstem used
10 generate the vapor, gas. ae~sol musl
be such thaI the chamber concentrations
are controlled under atable conditions.
reflecting the current state-of-the-art.
and must not vary in a range (Zrealer
than 30 percent of the average (range/
mean equal to or less than 30 percent).
(iii) Temperature and Humiditv. The
temperature must be maintained' at
24 ::t2. C and the humidity within the
chamber at 40-00 percenL Both must be
monitored continuously.
liv) Oxygen. The rate of air flow
through the chamber must be adjusted
to insure that the oxygen content of the
exposure atmosphere is at least 19
percent.
B-1?
(\'J "orlicle size nwusuTCI1I('/Ils.
IA) Gencral. In the case of ~lIses and
\'1II'0r8. fJiJrticle size mea~urcments must
I... carried out al mtervals 10 insure the
I1nimals are not being expusl'd 10
un\..nown Hnd unexpected JnRleriHls.
Aerosol particle size measuremcnts
must be made on samples ("len at the
breathing level of tloe animels. 'D,cse
IInill\'scs must be carried oul using
t,'ch~iqlles and equipment rc.nective of
Ihl' stille'of-the-art. All of the suspcnol'd
IInps(,J Ion a gravimetric bilsis) musl be
nr.collnl,.d for. even when most of Ihe
heruso! is not rcspirable.
(0) Sizing llnalysis. The sizing
an...l\'sis must be in terms of I'lJui\'illcnt
aerod\'nnmic diamelers and Hlllst be
rl'prp;enled as geomet/lc mCKn (median)
diameters and their geomC'lric ~t"nddrd
d('\'iation [see NIOSH syIJabus for
reference) as calculated from log-
probability graphs or compuler
pro~rams. The size analy~es musl be
cilrriC'd out frequent]y during the
dc\'eJopment of the generating s~'slem 10
insure proper stability of aerosol
pnrticles and only as often thereafter
during Ihe exposure as is necessary to
de1ermine adequately the consistency of
particle distributions to which the
Hnimals are exposed. At a minimum.
these analyses must be carried out a
daily basis.
(3) Obsen'otion of animals. All
toxIcological and pharmacological siFn5
mLlS: be recorded daily. includml' their
11mI' of coset. intensity, Hnd duration.
Ob~er\'ations must be made at leasl1:
hours throughout the test period and. in
particular. al the times the animals Are
exposed to the test substance. (Also I'ee
Subpart A. ~ 772.100-2(b)[6).) Such siFns
incillde, but are not limited to: Mortality,;
and cardIovascular. respIratory.
excretory. behavioral. and centra]
ner.'ous system (paralysis. ataxia. and
pupillary reaction) effects. Observations
must be made by an appropriately
trained observer. Food consumption
must be measured weekly durin(Z the
lest. and the animals must be weit!hed 8t
least weekly. Surveillance of animals
must be made according to the
requirements stated in Subpart A.
~ 772.100-2(b)[6).
-------
wl.;):hl'd HI 8uon lis POR'lule olter
dJ"'l'ctlOn 10 8vold drYIl1J;:
(V) 1/11' !!rUR8 nl'crul's~' Ilndln~s must
ue rccordl'd and reported In u[;cord"n[;c
wilh pura!lroph [c)l4) of thIS Sc[;llOn.
(vi) T..sue 8Amples musl ue pre~cr\'ed
Hnd held in IIcr.ordlince with ~ 7n.110-
1(j )
(7) Il1stapat},o/uJ.:I' eJ.ammatian. (I) To
the exlent md,cated helow in
puragruphs (A) and (D). the following
\iMBUCS must be e,-umined
microscopically:
[A) In the contr01 and highest dose-
Icvel Hnimals: Drllin (AI leaf;1 3 levels
from the foreurllin. midbrain. ilnd
hindbruin). eye. piluitary. f,alivilry ~lilnd.
thy. nus, heart. esuphilt:\1s. lungs (with
m.llnslem bronchi). tr.1chl'a. nasal
piJSsHges ilnd par.lIl.ls.11 sinust.s, li\ er.
stom;,ch. smalJ ano In,~e inlcslmes,
spleen. kidneys. thyroid [\';il},
parathyroid), /iou'nills, P;;i1CI cas.
unnar)' b!adJer. aorta, tesles. 0\ arics.
corpus and ceT\'i\ uleri. bune (wilh
marrow). sf-rJt.!ill muscle. skir" and illI
other :issues in ,,,hich If'sions were
ouserved at '1l'crojJsy~ Bnd
(E) In all olher aniinills. the }un~s,
trachea. nasal passages ilnd parLlnilSal
sinuses, liver. kidneys. and ar! A. must
apply.
(IV) The histo[1l1lholog}' findtnFS must
be recordE'd and N')"orll'd ?os required by
paragraph [1')[5) of this scctlon.
(c) Doto rep0;'/In,f! and PI.aluo/ion. In
addition to information mC'cting the
peneral reportmF rC'quln~menls of
9 772.100-2(b)(8). Subpart A. the test
report must contain the following
information. presented in the format
specified;
(1) Test conditions. (i) Chamber and
generaLing system. Description of the
chamber design and operation including
type of chamber, its dlmensians. the
sonTce of make-up air and its
conditioning (heating or cooling) for use
in the chamber. the lrcalrnenl of
exbausted air. the housing and
maintenance of the animals in the
chambers. and similar related
infurmallOn. Equlpml'nl for "H'u~urln~ of
lemperlliurt: und humidity. tl1('
!lenerlll1~ system. und the mclbodB of
u"ulyz.l~ ltirlJUrne cunccntrutlOn8 IInd
purlicle .LZm~ must be dcscrihl'd.
Iii) EXf'UJ;ure data. Tbe followlnR
chumuer opcrutionul dulll must ue
tllbulRled individuully IInd in sllmmur)'
form usins meilns Hnd stnndllrd
deviations (with or without rllnges) in
tubullir formal. The data summarics
must he groupcd IIccordJn~ to
experimenlill groups. nnd the non-
expected diffcrcnces (slich as
temperature or lIirnow) tested for
stulislicalsit:nifl[;lIncc.
(A) Airfiow ra les through Ihe
ch ,un ber:
(13) Chamber lemper
-------
hf'ffialolo"ic; blood cht.mlcal.
chohn!'~lrn\8C InhlUllion. and other
clinicRllitbofillOry lest performed.
(3) Cross N('crol'sy do/no For all
A\'er/l!lr~ in Ihe cia tll required In Ihis
~ubpArllgrllph. Ihe stAndurd deviAtIOn
must be stilted. The following lest
Inform'llion. arranged by lesl groups
(dose If'vcl nnd 5ex). musl be supplied in
t.."ulnr form:
Ii) 0..111 showing lhe idenlificnllon
number of An~'Bnimal in which nny
gross IIbnormulity WHS noled. nnd
contninin!:, fur ('ach such onimal. a
description of ('ach !lross (Junormillity
(includln~ mf'aSUlements), und the date
(if known) "hrn it wos first ousrrved.
Cross nhnormaillit's ohsrrved
repralpdl\' ncrd be described only once
and ma\' therrilfter be dcscrihed b\'
refer('n~e. with any variations nol~d. as
necessaT\'.
(ii) Daia showing the number of
animals in which any type of gross
abnormality was observed.
(iii) Da ta showing, for each animal: Its
rdenlificalion number, weights of ils
organs listed under paragraph (b)(6)(ii)
oCthis section and correspondIng organ-
lo-body weighl ralios.
(iv) Dala showing the mean weights of
each type of organ listed under
paragraph (b)[6)(ii) of Ihis section. and
mea'n o,.~an-to-body weight ratios.
(4) His:opalhoJogy do/a. The following
jnformation must be arranged by lest
group (dose level and sex). AU means
must be accompanied b~' standard
de\"iation. The numuer of data unils on
which ~ calcu!alion is baspd must be
reDorled for a11 percentages and means.
'(i) Description of Lesions. for each
Animal. Data must be submitted in an
aptJl opna Ie form showin!:'
(A) For each animal. its identification
nllfT'ber, Rnd a complete description and
dia~nosi~ of pvcry Irsion In the animal.
Non-neorlRstic lesions which are
observpd frequcntly or "hich are
common in bolh Ireatpd and control
animals musl be graded. (Descriptions
of neoplasms may also include grading.)
A commonlv-used scale such as :t:l. Z. 3.
and 4 for d~~rees ranging from vel')'
sli!lht 10 extreme can be used. but other
scales are also acceptable. If known. the
description and diagnosis must identify
-anv lesion which caused the animal 10
be'moribund or 10 die. The descriplion
a'nd diagnosis musl include the tim~ of
appearance (if known) ior each lesIon..
Abnormalities observed repealedly need
be described only once. and may
subsequenlly be supplied by reference.
with any individual variations noted as
necessary.
(B) For each animal. a paragraph
listins the tissues examined and
deslflnRtion by ched, mar\.. of thun
Ii~sue. found 10 be normal.
(C) If II !lracilng sysl('m Is used. u
dc~cription of the 'ySI('m
(ii) Counts and Incidence of LesIOns.
by Tesl Groups. Dala must be submitted
In tobular from showing, for eoch test
group;
(A) The number of snimBls allhe slart
of the test. the number of animals
survivln!l to the termination of the tcSt.
and the number of animllls in which any
le~iun WIiS found:
(B) The number of animals affected by
each diffrrent type of lesiN\. the average
grude of each Iype of ksinn. the
numbers e:\aminrd for ('orh type of
lesion. Find Ihe 1"'rcenIFip.' of those
animFils e:-.amined which 'Hre affeLted
by each type of lesion: and
(C) The number of each different type
of lesion.
(iii) Incidence of Tur-lOrs. If a tumor is
observed in am' animal. the reporl must
include a compiete descriplion Rnd
diagnosis of each tumor as required in
Section 77Z.113-1(k)(2).
(5) Evaluation of Dolo. An evaluation
of the test results (including their
statistical analysis). based on clinical
findings. gross necropsy findinp. Find
histopathology results. must be made
and supplied. This subr.:ission must
i'lclude an evaluation of the
rela tionship. if any. bet" een the
animals' exposure to the lest substance
and the incidence and severity of a11
abl,onnalities, includ.in~ behavioral and
clinical abnormal!!!es. ,,055 and
hislopa tholo~ic lesions: 0:t:an \\ eight
changes. effects on mor~a!ily. and any
other toxic effecls. The e,~!uation must
8150 include do~e-res?onse cun es for
any toxic or pharm-acoiogical efi ect
which apppar to be cowpound-related
for the various ~roups and a descnptJon
of statisllcal methods.
Appcnwx
fee ti1e Appenni, 10 ~ 77:'112-::3 lor
suitable sources of informal1on on inhalation
toxicology. exposure systems. ~enerall~
"'stems, samplins methods. pulmonaC)'
function leslins, and data inlerpretalion.
B-19
-------
PROTOCOL ESTIMATE: SUBCHRONIC CARDIOVASCULAR TOXICITY
DIRECT LABOR:
No. of Hourly Total
Personne 1 Hours Wage Do 11 ars
Study Di rector 104 $17.80 $ 1,851.20
Veteri nari an ---r2 14.00 168.00
Compound Prep. Technician 52 6.00 312.00
Senior Inhalation Technician 692 12.50 8,650.00
Study Set Up ( 12)
Observations ( 48)
Exposure Challenge (64)
Implant transducers (64)
Dosing (256)
Record Keepi ng ( 1 28)
Analytical Monitoring (1 20)
Animal Technician 678 8.25 $ 5,593.50
Study Set Up (12) -
Ra ndomi za ti on (10)
Observations ( 1 04)
Body Wei ghts ( 48)
Implant transducers (64)
Exposure Challenge (64)
Dosing (256)
Analytical Monitoring ( 1 20)
Audit Preparation (=)
Animal Caretaker 198 4.00 $ 792.00
Watering (60) -
Bedding Changes (30)
Feeding ( 30)
Cage Cleaning (70)
Room Cleaning ( 8)
Analytical Chemist 120 7.70 $ 924.00
Ana lys t 120 4.00 480 . ~O.
Clinical Lab Supervisor 32 10.00 320.00
Clinical Lab Technician 64 6.00 384.00
Necropsy Supervisor 12 10.00 1 20.00
Necropsy Technician 36 5.00 180.00
Histology Supervisor 8 10.00 80.00
Histology Technician 24 6.00 144 . 00
Board-certified Pathologist 28 24.00 672.00
Report Writing Supervisor 35 10.00 350.00
Report Writer 350 6.00 2,100.00
Computer Programmer 38 8.50 323.00
Computer Coder 90 5.00 450.00
Report Typi s t 300 5.00 1 ,500.00
General Secretary 13 6.00 78.00
Quality Assurance Inspector 64 10.00 640.00
B-20
-------
PROTOCOL ESTIMATE: SUBCHRONIC CARDIOVASCULAR TOXICITY
SUBTOTAL DIRECT LABOR
$26,111.70
2,088.94
Salary Adjustment (8 %):
. TOTAL DIRECT LABOR:
$(>8.?00.64
$3?430.74
. OVERHEAD (115% of Total Direct Labor):
Overtime (~ Technician hours @ $4.50):
(~ Caretaker hours @ $2.00):
Animal Procurement (16 Doqs @ $200.00):
Bedding (1092 sheets @ 15~):
Animal Rations (71b/dog/da @10.25/50 lb):
Histology Supplies (360 samples @ ~):
Data Processing (13 weeks @ $50.00):
Laboratory Supplies (10% of Total Labor):
SUBTOTAL OTHER DIRECT COSTS:
INFLATION ADJUSTMENT (~of other Direct Costs):
. TOTAL OTHER DIRECT COSTS:
TOTAL COST BEFORE G & A:
67.50
30.00
3,200.00
163.80
1 ,640.00
11 8 . 80
650.00
2,820.06
8,690.16
434.51
$ 9.1?4.67
$69,756.05
$- 6.975.61
. ~ (10% of Total):
TOTAL COST BEFORE FEE:
. FEE (20% of Total):
$76,731.66
$15.346.33
$92,077 . 99
. ESTIMATED FINAL COST:
$46,039.00 to $138,116.99
. ESTIMATED COST RANGE:
B-21
-------
PROTOCOL:
SUBCHRONIC CARDIOVASCULAR TOXICITY
NOTE:
The assumption was made that four (4) groups of three (3) dogs
(A total of 12) would be utilized for the conduct of this test.
(4 )
Subchronic cardiovascular toxicity
( i)
Required testing
(A) Subchronic cardiovascular testing for dichloromethane
is required to determine the effects of multiple exposures to the
chemical on designated hemodynamic parameters. The diagnostic
technique to be employed for the measurement of intracardiac
pressures, pressure pul se tracings, blood gas sa-_turations, and
the calculation of cardiac output and vascular resistance is
cardiac catheterization in the dog.
Number and Sex of Animals:
Testing must be performed on young adult dogs of either
sex. A minimum of three dogs in the group is required for final
statistical analysis of the data.
Exposure:
The dogs will be exposed to dichloromethane in an inhalation
chamber at least 7 hours per day, 5 days per week for 90 calendar
days: Guidance for the performance of a subchronic inhalation
study can be obtained by reference to 44 FR 44054.
8-22
-------
Study Design
1) The procedure to be used for the cardiotoxicity testing
of dichloromethane is right and left heart catheterization in the
unanesthetized dog. Guidance for the methodology can be obtained
by reference to the procedure of Will and Bisgard (1972).
However, the Agency finds acceptable any established technique
using the unanesthetized dog with the proviso that such a
technique allows for the measurement of the designated
hemodynamic parameters. Several techniques are documented in the
literature which utilize indwelling monitoring devices
(catheters, pressure transducers, etc.); this may lead to
difficulty in maintaining animal survival for the specified
treatment period. However, in the event that such procedures are
adopted, a non-halogenated anesthetic which has no cardiac
activity should be used to carry out the surgical implantation of
such devices. In addition, an adequate postoperative period must
be allowed for recovery from the anesthesia since all hemodynamic
measurements must be determined on the unanesthetized animal.
2)
Each dog will serve as its own control.
3) A control cardiac catheterization must be performed on
each animal following a 1 week exposure to circulating air in an
inhalation chamber for 7 hours per day, 5 days per week.
Following the control period, each dog will be exposed in an
inhalation chamber to an atmospheric concent~ation of 250 ppm
dichloromethane.
This dose has been chosen for subchronic
B-23
-------
testing since Adams (1975) has demonstrated that acute exposure
of dogs to 500 ppm dichloromethane significantly stressed the
heart and the cardiovascular system. Exposure will be for 7
hours per day, 5 days per week over a period of 90 calendar
days. At the end of each 30 day interval, a left and a right
heart catheterization will be performed on each animal. If the
technique of Will and Bisgard (1972) is adopted which
necessitates a catheterization prior to each data collection, a
minimum of a one hour equilibration period is required between
the completion of catheterization and the initiation of data
collection. In the event that indwelling devices are used in the
study a minimum of one hour equilibration period is also required
for each dog after it has been secured to the monitoring
instrument(s).
4) Each dog must be challenged with epinephrine
hydrochloride prior to the exposure to dichloromethane and once a
month thereafter during the 90 day test period. This experiment
should be carried out at times other than those chosen for the
cardiac catheterization (or equivalent technique for hemodynamic
measurements) since it is important that stress to the animal be
minimized during this procedure. The epinephrine should be
admininstered intravenously and only electrocardiographic (EKG)
monitoring is required. Prior to dichloromethane exposure, each
dpg should be challenged with the minimum dose of epinephrine
found to produce low grade arrhythmias in that particular animal,
one-half this dose and one-fifth this dose. EKG changes must be
recorded during each drug challenge. This procedure must then be
repeated at 1,2 and 3 month intervals during exposure to
dichloromethane, again with EKG monitoring. This will determine
whether subchronic exposure to dichloromethane sensitizes the
heart to catecholamines. Any alternative testing procedure which
demonstrates an alteration in the fibrillation threshold in the
heart will also be acceptable.
B-24
-------
5) Animals must be under surveillance for any overt
physiological and behavioral changes during inhalation
exposure. Animals mus.t be weighed at least weekly.
6) All moribund animals should be sacrificed and undergo
gross necropsy: the designated tissues must be taken for
histopathology. Those animals found dead during the course of
the study must undergo gross necropsy and the tissues designated
for histopathology must be salvaged if death occurred within 16
hours of necropsy.
7) At the end of the 90 day experimental period, the dogs
will be sacrificed and undergo gross necropsy. and histology
shall be performed on the tissues specified (see Study Conduct).
Study Conduct:
The parameters which are to be measured in each animal
during the control catheterization and the catheterization
performed at 30 day intervals during exposure are as follows:
a. Atrial and pulmonary capillary wedge pressures
b. Ventricular pressures
c. Aortic and pulmonary artery pressures
d. Blood 02 saturations
e. The calculation of cardiac output (e.g., using the Fick
Principle or the Indicator Dilution Method) and vascular
resistance.
f. LV dP/dt, the rate of rise of left ventricular pressure
with time (a measure of myocardial contractility)
g. Electrocardiogram - Standard lead II
h. Heart rate
i. Carboxyhemoglobin analysis - a control carboxyhemoglobin
measurement must be made followed by a measurement at 2 and 4
weeks after the start of exposure to dichloromethane.
If the 2
and 4 week measurements do not differ statistically from the
control measurement of each dog, carboxyhemoglobin measurements
may be performed at 1 month intervals, thereafter. However, if
B-25
-------
the carboxyhemoglobin levels recorded at the 2nd and 4th weeks
are statistically different from the control measurement,
carboxyhemoglobin analysis should then be performed at 2 week
intervals until the termination of exposure.
j .
Determination of dichloromethane content in the blood.
k. Statistical analysis on all measured hemodynamic
parameters should be carried out using an analysis appropriate to
the repeated measures design of the study- Examples of such
analysis include two-way analysis of variance and profile
analysis; however, the paired t-test or pairwise Hotelling's T2'
on all parameters simultaneously will be considered acceptable.
If, during the 90 day experimental period, exposure to 250 ppm
dichloromethane does not result in statistically significant
alterations from control in the hemodynamic paramenters measured
in (g) and either (b), (e) or (f), then no additional testing
need be done. On the other hand, if exposure to dichloromethane
does cause statistically significant alterations from control in
the hemodynamic parameters measured in (g) and either (b), (e) or
(f), then the 90 day subchronic study must be repeated as many
times as is necessary, each time using one-half the previous
exposure concen~ration, until a no-effect level for
cardiotoxicity is achieved.
k) Histopathology - histology must be performed on the
coronary arteries, the aorta, the renal arteries, five sections
of the ventricular myocardium between the apex and the base of
the heart, three sections of the kidney (cortex, medulla ar.d
cross secti~n of the whole kidney), the lungs and the liver.
Guidance for the pathology procedures can be obtained by
reference to 44 FR 44054.
(ii)
Reporting requirements
(A) A study plan shall be submitted at least 90 days before
the initiation date of this test.
(B) Interim summary reports are required at the conclusion
of each testing sequence.
(C) The final test report is due no later than 36 months
after the effective date of the final test rule.
8-26
-------
PKUIULUL tSilMATE: DERMAL SENSITIZATION STUDY (772.112-26)
DIRECT LABOR:
Personne 1 No. of Hourly To ta 1
Hours Waae Dollars
Study Di rector 2 $17.80 $ 35.60
Compound Prep. Technician 11 6.00 66.00
Senior Technician 41.5 7.70 319.55
Study Set Up (2.0)
Randomi za ti on (2.0)
Observations (23.5)
Record Keeping (14.0)
Animal Technician 41.5 6.00 249.00
Observa t ions (30.5~
Dosing (5.5
Sacrifice (0.5)
Shaving (5.0)
Animal Caretaker 30.6 4.00 122.40
Wa teri ng (10.5)
Bedding Changes (1.1)
Feeding (10.5)
Cage Cl eani ng (5.0)
Room Cleaning (3.5)
Report Writer 32 6.00 192.00
Report Typi s t 16 5.00 80.00
General Secretary 1 6.00 6.00
Quality Assurance I nspec tor 8 10.00 80.00
TOTAL DIRECT LABOR: $1150.55
OVERHEAD (115% of Total Direct Labor): $1323.13
OTHER DIRECT COSTS:
Overtime (7 Technician hours @ $3.00):
(3.5 Caretaker hours @ $2.00):
Animal Procurement (24 Guinea Pigs @ $11.69):
Bedding (60 sheets @ 15~): ,
Anima 1 Ra ti ons (32 gml dalpi 9 x 10.25/50 1 b) :
Laboratory Supplies (10% of Total Labor):
TOTAL OTHER DIRECT COSTS:
21.00
7.00
280.56
9.00
20.50
115.05
$ 453.11
TOTAL COST BEFORE G & A:
G & A (10% of Total):
$2926.76
$ 292.68
TOTAL COST BEFORE FEE:
FEE (20% of Tota 1) :
$3219.44
ESTIMATED FINAL COST:
ESTIMATED COST RANGE:
$ 643.89
$3863.33
$1931.67 to $5795.00
8-27
-------
COST SURVEY:
DERMAL SENSITIZATION STUDY (772.112-36)
Protocol Estimate:
12 Laboratory Survey:
Price Range
$1,950 - 5,800
$ 400 - 10,000
Best Estimate
$3,900
$2,500
Based on the wide range of survey estimates, the
protocol was not clearly understood by all laboratories
surveyed. Thus, survey estimates may be inaccurate.
Also, dermal sensitization studies are often dis-
counted to encourage future business. Thus, market
estimates are often lower than actual cost.
Discrepancy:
PROTOCOL:
DERMAL SENSITIZATION STUDY (772.112-36)
~ 772.112-26 Dermal sensitization study.
(a) Study Design. (1) Condition of test
substance. The test substance must be
applied undiluted. If the test substance
causes marked irritation, it must be
diluled with physiological saline until a
concentration is found which produces
only slight irritation. If the test
substance is a solid to be injected
intradermalJy, it should be dissolved in
a minimum amount of physiological
saline.
(2) Species. The test must be
performed in at leasl one mammalian
species. The albino guinea pig is the
preferred species.
(3) Age and sex. Young adult males
should be used when albino guinea pigs
are lested. Young adults of either sex-
may be used when albino rabbils are
tested.
(4) Number of animals. At least 10
animals must be used.
(5) Number and selection of dose
levels. (i) An initial dose of 0.05 ml must
be injected intradermalJy. This-dose
must be folJowed by injection of 0.1 ml
three times weekly on alternate days for
3 weeks. so that a tolal of 10 treatments
is administered. FolJowing the 10th
sensitizing treatment. the animals
should be set aside for 2 weeks after
which they should be challenged by a
final injection (Landsteiner and Jacobs.
1935).
(ii) U the intradermal injection is
impractical because the substance is
highly irritating or cannot be dissolved
or suspended in a form allowing
injection. topical patch application can
be substituted using the same schedule
but 0.5 ml per application. For patch
apphcations. other materials such as
water or alcohol can be used to moisten
the test subslance (see Buehler. E. V..
19(35). .
(6) Controls. (i) A positive conlroL
using a known sensitizing agenl is
recommended.
(ii) A concurrent vehicle conlrol gTOUp
is not required.
(b) Study conduct. (i) Preparation of
test animal$. Hair must be removed first
by clipping and then by shaving £rom a
strip running from Dank to trunk along
each side of each animal This
procedure must be repea led as
necessary.
Iii) Intradermal injection. After
preparation of the tesl animal the tesl
substance must be injected
intradermally. The fIrst sensitizing
injection must be made by starting at
one em! of one strip. Tbe succeeding
injections must be made by moving
along the shaved strip cboosing a new
location for each treatment.
(c) Observation ond scoring.
Erythema. edema. and other lesions
must be scored at 24 hours and 48 hours
after each application. according to the
standard method (Draize. 1959).
(d) Data reporting and el'aluatian. in
addition to the basic iDiormation
required by ~ 772.1DO-Z(b)(8). Subpart A.
the following information must be
reported:
(1) Tabular data for each animal on
scores for erythema and edema at 24
and 48 hours postapplication or
injection.
(2) Tabular data for the average score
from all sensitizing treatments and the
score of the challenge treatmenl
B-28
-------
PROTOCOL ESTIMATE: ACUTE TOXICITY IN FISH (FLOW-THROUGH)
Rainbow Trout
DIRECT LABOR:
Per
-------
PRICE SURVEY: ACUTE TOXICITY IN FISH (FLOW-THROUGH)
Rainbow Trout
PRICE SUMMARY
PROTOCOL ESTIMATE:
5 LABORATORY SURVEY:
PRICE RANGE
$372 - 1115
$400 - 1250
BEST ESTIMATE
$743
$754
INDIVIDUAL LABORATORY SURVEY RESULTS:
1. $550
2. $625
3. $400-700
4. $1000
5. $1250
PROTOCOL USED IN THIS COST ANALYSIS:
Fish Acute Toxicity Test Standard
(Toxic Substances Control Act, Section 4)
Draft dated June 5, 1980.
8-30
-------
PROTOCOL ESTIMATE: ACUTE TOXICITY IN FISH (STATIC)
Rainbow Trout
DIRECT LABOR:
Personne 1
Study Di rector
Compound Purity Assay
Water Quality Assay
Chemical Analysis and
Calibration
Calculations and Report
Technician
Fi s h Cultu re
Fish Removal
Reagent Preparation
Water Quality Assay
Chemical Analysis and
Calibration
Report Typi s t
. TOTAL DIRECT LABOR:
No. of
Hours
7.5
(1.0)
(1.0)
(2.5)
(3.0)
(3.0)
(4.0)
( 1.0)
(2.0)
(3.0)
. OVERHEAD (115% of Total Direct Labor):
OTHER DIRECT COSTS:
Water Quality Analysis Supplies:
Chemical Reagents:
Fish, Fish Culture:
. TOTAL OTHER DI RECT COSTS:
TOTAL COST BEFORE G & A:
. u.A (10% of Tota 1) :
TOTAL COST BEFORE FEE:
. FEE (20% of Total):
. ESTIMATED FINAL COST:
. ESTIMATED ~ RANGE:
13.0
2.0
B-31
Hourly
Waqe
$12.00
7.70
5.00
Total
Do 11 a rs
$ 90.00
100. 10
10.00
$ 10.00
20.00
10.00
$ 470.22
$ 517.24
Component
Cost
$ 200.10
$ 230.12
$
40.00
$
47.02
$ 103.45
$ 620.69
$310.35 to $931.04
-------
PRICE SURVEY: ACUTE TOXICITY IN FISH (STATIC)
Rai nbow Trout
PRICE SUMMARY
PROTOCOL ESTIMATE:
6 LABORATORY SURVEY:
PRICE RANGE
$310 - $931
$200 - $625.
BEST ESTIMATE
$621
$446
INDIVIDUAL LABORATORY SURVEY RESULTS:
1. $450
2. $400
3. $625
4. $200-400
5 . $500
6. $550
PROTOCOL USED IN THIS COST ANALYSIS:
- Fish Acute Toxicity Test Standard
(Toxic Substances Control Act, Section 4)
Draft Dated June 5, 1980.
B-32
-------
PROTOCOL ESTIMATE: EARLY LIFE STAGE TOXICITY TEST
USING THE FATHEAD OR SHEEPSHEAD
MINNOW
DIRECT LABOR:
No. of Hourly Total Component
Personnel Hours Wage Dollars Cost
Quality Assurance 6 $10.00 $ 60.00
Computer Coder 4 5.50 22.00
Computer Programmer 17 8.50 144.50
Study Di rector 73 12.00 876.00
Observation of embryo and
fry ( 8.0)
Photography of deformed
fish ( 5.0)
Measurement of survivors (10.0)
Report Preparation (50.0)
Technician (Aquatic Biologist) 286 6.70 1916.20
Acclimation, randomization,
and distribution of em-
bryos (20.0)
Monitoring of Stabiliza-
tion period ( 8.0)
Observation of embryo and
fry (34.0)
Daily monitoring of system
conditions (42.0)
Transfer of fry from em-
bryo cups ( 8.0)
Fry, fish culture (72.0)
Photography of deformed
fish (10.0)
Measurement of survivors (20.0)
Analytical Chemist 91 7.70 700.70
Measurement of test sub-
stance concentration
for duration, delivery
concentration and ini-
tial precision analysis- (91.0)
approximately 98 samples
Report Typi st 14 5.00 70.00
. TOTAL DIRECT LABOR:
B-33
$ 3,789.40
-------
PROTOCOL ESTIMATE:
EARLY LIFE STAGE TOXICITY TEST (Continued)
Tota 1
Dollars
. TOTAL DIRECT LABOR:
-
. OVERHEAD (115% of Total Direct Labor):
OTHER DIRECT COSTS:
Reagents for determination of D.O., pH, COD,
Chloride, etc.; Photography supplies
Water and reagents for assessment of flow-
through system
$
300.00
150.00
. TOTAL OTHER DIRECT COSTS:
TOTAL COST BEFORE G & A:
$ 8,597.21
. G & A (10% of Total):
TOTAL COST BEFORE FEE:
$ 9,456.93
. FEE (20% of Total):
. ESTIMATED FINAL COST:
--
. ESTIMATED COST RANGE:
Component
Cost
$ 3,789.40
$ 4,357.81
$
450.00
$
859.72
$ 1,891.39
$11 ,348.32
$5674.16 to $17,022.48
B-34
-------
PROTOCOL ESTIMATE:
EARLY LIFE STAGE TOXICITY TEST
USING THE BROOK OR RAINBOW TROUT
DIRECT LABOR:
No. of Hourly To ta 1 Component
Personnel Hours Wage Do 11 ars Cost
Quality Assurance 8 $10.00 $ 80.00
Computer Coder 4 5.50 22.00
Computer Programmer 17 8.50 144.50
Study Director 103 12.00 1236.00
Observation of embryo and
fry ( 18.0)
Photography of deformed
fish ( 5.0)
Measurement of survivors (20.0)
Report Preparation ( 60 . 0)
Technician (Aquatic Biologist) 338 6.70 2264.60
Acclimation, randomization,
and distribution of em-
bryos (20.0)
Monitori ng of s tab;.l i za-
tion period ( 8.0)
Observation of embryo and
fry (72.0)
Daily monitoring of system (90.0)
conditions
Transfer of fry from em- (8.0)
bryo cups
Fry, fish culture (120.0)
Photography of deformed
fish (10.0)
Measurement of survivors (10.0)
Analytical Chemist 121 7.70 931.70
Measurement of test sub-
stance concentration
for duration, delivery
concentration and ini-
tial precision analysis-
approximately 130 samples(121.0) 20 5.00 100.00
Report Typist
. TOTAL DIRECT LABOR:
8-35
$ 4,778.80
-------
PROTOCOL ESTIMATE:
EARLY LIFE STAGE TOXICITY TEST (Continued)
Tota 1
Dollars
. TOTAL DIRECT LABOR:
-
. OVERHEAD (115% of Total Direct Labor):
OTHER DIRECT COSTS:
Reagents for determination of D.O., pH, COD,
Chloride. etc.; Photography supplies
Water and reagents for assessment of flow-
through system
$
$
400.00
200.00
. TOTAL OTHER DIRECT COSTS:
--
TOTAL COST BEFORE G & A:
$10,874.42
. ~ (10% of Total):
TOTAL COST BEFORE FEE:
$11 ,961. 86
. FEE (20% of Total):
. ESTIMATED FINAL COST:
--
. ESTIMATED COST RANGE:
Component
Cost
$ 4,778.80
$ 5,495.62
$
600.00
$ 1,087.44
$ 2,392.37
$14,354.23
$7177.12 to $21,531.35
B-36
-------
PRICE SURVEY:
EARLY LIFE STAGE TOXICITY TEST
PRICE SUMMARY
PRICE RANGE
BEST E3TIMATE
PROTOCOL ESTIMATE:
(Minnows)
( Trout)
x
$ 5,674-17,022
$ 7,177-21,531
$ 6,426-19,277
$ 9,000-40,000
$11 ,348
$14,354
$12,851
$15,608
5 LABORATORY SURVEY:
INDIVIDUAL
l.
2.
3.
4.
5.
LABORATORY SURVEY RESULTS:
$9,000-40,000
$11,500
$9,295-in minnows
$11,900-in minnows
$11,950-in minnows
NOTES:
1. The test standards described for minnows and trout have basic differ-
ences which will result in differences in cost estimates. The test
in minnows requires a total exposure time of 28 days while the test
in trout requires a total of 90 days. This difference in exposure
time results in a higher cost in the trout test based on increases
in animal care and observation intervals and analytical monitoring
intervals.
The contractor's estimate assumes low mortality of original embryos,
minimal manipulation of compound for analytical assays, and minimal
manifestation of symptoms. If a majority of specimens were to ex-
hibit manifestation of symptoms, more photography and more detailed
description of observations would be required. Specialized physio-
logical description, biochemistry assays or histology could be re-
quired, also, but are not included in the contractor's estimate.
The contractor's estimate includes computer time estimates for
a) randomization of fish placed on study, and b) ANOVA and t-test
statistical analysis of data.
Analytical assay techniques may cause variance in the cost of this
test. The nature of the compound to be tested will dictate the
method of assay. If analysis is performed using Gas Chromatography
using the test in trout as an example (130 samples), 2-4 samples
may be processed per hour. The cost for analysis by Gas Chromato-
graphy would be $990-$1980, depending on the compound. If analysis
is performed using Gas Chromatography-Mass Spectrometer, 1-3 samples
may be processed per hour. The cost for analysis would be $2150-
6500. If analysis is performed using high pressure liquid chromato-
graphy, 2-6 samples may be processed per hour. The cost for analysis
would be $650-1980. The contractor assumed analytical analysis for
the trout test would cost $2000 as an average, $1500 for the test in
minnows.
2.
3.
4.
B-37
-------
PRICE SURVEY:
EARLY LIFE STAGE TOXICITY TEST
(Continued)
PROTOCOL USED IN THIS ANALYSIS:
Test Standard for Conducting an Early Life Stage Toxicity Test Using the
Fathead Minnow (Pimepha~es promeZas), Sheepshead Minnow (Cyprinodon vari.
egatus), Brook Trout (SaZveZinus fontinaZis), or Rainbow Trout (SaZmo
gairdneri) and associated Technical Support Document.
Draft dated August 8, 1980.
B-38
-------
PROTOCOL ESTIMATE: CHRONIC TOXICITY USING DAPHNIDS
IN RENWAL AND FLOW-THROUGH
SYSTEMS
DIRECT LABOR:
No. of Hourly Total Component
Personnel Hours Wage Do 11 a rs Cost
Quality Assurance 3 $10.00 $ 30.00
Computer Coder 1 5.50 5.50
Computer Programmer 2 8.50 17.00
Study Director 49 12.00 588.00
Compound Purity Check ( 2.0)
Toxicant Delivery Check (10.0)
Observations ( 7.0)
Calculations and Report (30.0)
Aquatic Biologist 6.70 64.00 428.80
Acclimation of Daphnia ( 4.0)
Randomization and
Distribution ( 2.0)
-Observati ons (21.0)
Feeding and Husbandry (32.0)
Water Quality Check ( 5.0)
Analytical Chemist 7.70 17.00 130.90
Compound Analysis by
Gas Chromatography (17.0)
Report Typi st 3 5.00 15.00
I TOTAL DIRECT LABOR: $1215.20
I OVERHEAD (115% of Total Di rect Labor): $1397.48
OTHER DIRECT COSTS:
Laboratory Supplies, Reagents, Animal
Care Supplies 100.00
Compound Analysis Supplies, i.e.
Column Packing, Solvents, etc. Using 350.00
Gas Chromatography
I TOTAL OTHER DIRECT COSTS: $ 450.00
TOTAL COST BEFORE G & A: $3062.68
I ~ (10% of Total): $ 306.27
B-39
-------
PROTOCOL ESTIMATE: cHRornc TOXICITY USING DAPHUIDS
IN RENEWAL AND FLOW-THROUGH
SYSTEMS
Total
Dollars
. G & A (10% of Total):
TOTAL COST BEFORE FEE:
$3368.95
. FEE (20% of Total):
. ESTIMATED FINAL COST:
Component
Cost
$ 306.27
$ 673.79
$4042.74
$2021.37 to $6064.11
. ESTIMATED COST RANGE:
B-40
-------
PRICE SURVEY: CHRONIC TOXICITY USING DAPHNIDS
IN RENEWAL AND FLOW-THORUGH
SYSTEMS
PRICE SUMMARY
PRICE RANGE
PROTOCOL ESTIMATE: $2,021- 6,064
5 LABORATORY SURVEY: $ 750-10,000
BEST ESTIMATE
4043
417B
INDIVIDUAL LABORATORY SURVEY:
1. $10,000
2. $ 6,500 (flow-through)
3. $ 3,000-5,000
4. $ 750-2,000
5. $ 2,000
Note:
(1) Prices for tests in renewal systems will be toward
the low end of the range, while prices for test
in Flow-Through Systems will be toward the high end
of the ranges presented above.
(2) Analytical assay techniques may cause variance in
the cost of this test. The nature of the compound
to be tested will dictate the method of analysis.
The assumption that 51 samples for the test substance
would be required (4 replicates x 6 concentrations
x 2 time periods + 3 additional samples) during the
course of the test was made for the purpose of cost
analysis. The preceeding protocol estimate was pre-
pared using the assumption that Gas Chromatography
would be the method of analysis and 17 hours would
be required to analyze the 51 samples. If other
methods of analysis were utilized, which is again
entirely dictated by the nature of the compound. the
price of the study would vary as in Table A.
8-41
-------
PROTOCOL ESTIMATE: LIFE CYCLE TOXICITY USING MYSID SHRIMP
DIRECT LABOR:
No. of Hourly Tota 1 Component
Personnel Hou rs Wage Do 11 ars Cost
Quality Assurance 3 $10.00 $ 30.00
Computer Coder 2 5.50 11.00
Study Director 23 12.00 276.00
Compound Purity Check ( 2.0)
Observations ( 6.0)
Toxicant Delivery Check (10.0)
Calculations and Report (5.0)
Aquatic Biologist 79 6.70 529.30
Acclimation of Mysids ( 4.0)
Water Quality Check
and Monitori ng ( 5.0)
Randomization and
Distribution ( 2.0)
Observations (54.0)
Feeding (14.0)
Analytical Chemist 15 7.70 115.50
Compound Analysis by
Gas Chromatography (15.0)
Report Typi st 2 5.00 10.00
. TOTAL DIRECT LABOR: $ 971. 80
. OVERHEAD (115% of Total Direct Labor): $1117.57
OTHER DIRECT COSTS:
Animal Care Supplies, Feed, etc. 30.00
Reagents and Laboratory Supplies 50.00
Compound Analysis Supplies, i.e.
Column Packing, Solvents, Cooling
Water, etc. Using Gas Chromatography 335.00
. TOTAL OTHER DIRECT COSTS: $ 415.00
TOTAL COST BEFORE G & A: $2504.37
. G & A (10% of Total): $ 250.44
B-42
-------
PROTOCOL ESTIMATE: LIFE CYCLE TOXICITY USING MYSID SHRIt1P
Tota 1
Dollars
. ~ (10% of Total)
TOTAL COST BEFORE FEE:
$2754.81
. FEE (20% of Tota 1) :
. ESTIMATED FINAL COST:
. ESTIMATED COST RANGE:
Component
Cost
$ 250.44
$ 550.96
$3305.77
$1652.89 to $4958.66
B-43
-------
PRICE SURVEY: LIFE CYCLE TOXICITY USING MYSID SHRIMP
PRICE SUMMARY
PROTOCOL ESTIMATE:
LABORATORY SURVEY:
PRICE RANGE
$1653-4959
BEST ESTIMATE
$3306
$3000
INDIVIDUAL LABORATORY SURVEY RESULTS
1. $3000
2.
Note:
Analytical assay techniques may cause variance in
the cost of this test. The nature of the compound
to be tested will dictate the method of analyses.
The assumption that 60 samples for the test sub-
stance would be required (2 replicates x 5 concen-
trations x 6 time points) during the course of the
test was made for the purpose of cost analysis. The
preceeding protocol estimate was prepared using the
assumption ~that Gas Chromatography would be the
method of analysis and that 15 hours would be re-
quired for analysis of the 60 samples. If other
methods of anaiysis were utilized, which is again
entirely dictated by the nature of the compound,
the price of the study would vary as in Table B.
TABLE B
VARIANCES IN PROTOCOL ESTIMATES BASED ON METHOD OF ANALYSIS
Method of
Analysis
Cost/
Hour
No. Hours
Required
For 60 Samples
Cost
($)
Best
Estimate
Thin Layer Chromatography
Gas Chromatography
Gas Chromatography - Mass
Spectrometry
$20
$30
5-30
10-15
100- 600
300- 450
2725-3678
3048-3304
$50
15-30
750-1500
3700-4866
ESTIMATED COST RANGE:
1362-7299
B-44
-------
PRICE SURVEY: LIFE CYCLE TOXICITY USING MYSID SHRIMP (Continued)
PROTOCOL USED IN THIS COST ANALYSIS:
- Life Cycle Toxicity Test Standard
Using Mysid Shrimp
Draft Dated September 19. 1980
B-45
-------
PROTOCOL ESTIHATE: FIVE DAY DIETARY TOXICITY IN 1-1ALLARDS
DIRECT LABOR:
Personnel
Study Di rector
Quality Assurance
Biologist
Set-Up
Record Keepi ng
Observations
Animal Technician
Randomi za ti on
Body Wei ghts
Food Consumption
Compound Preparation
Sacrifice
Observations
Animal Caretaker
Animal Care (bedding,
feeding, watering)
Room Cleaning
Report Writer
Repo rt Typi s t
. TOTAL DIRECT LABOR:
No. of
Hours
( 8..0)
( 7.0)
( 5.0)
( 10.0)
( 4.0)
( 3.0)
( 6.0)
( 6.0)
(11.0)
(10.0)
(10.0)
. OVERHEAD (115% of Total Direct Labor):
OTHER DIRECT COSTS:
1
4
20
40
20
24
8
Animal Procurement (84 Mallards @ $6.10):
Animal Rations (3 bags @ $15.00):
Laboratory Supplies (10% of Total Labor):
. TOTAL OTHER DIRECT COSTS:
TOTAL COST BEFORE G & A:
. G & A (10% of Total):
TOTAL COST BEFORE FEE:
. FEE (20% of Tota 1) :
. ESTIMATED FINAL COST:
. ESTIMATED QQiL ~:
B - 4.6
Hourly To ta 1 Component
Waae Do 11 a rs Cost
$12.00 $ 12.00
10.00 40.00
6.70 134.00
6.00
240.00
4.00
80.00
6.00
5.00
144.00
40.00
$ 512.40
45.00
69.00
$2109.90
$2320.89
$ 690.00
$ 793.50
$ 626.40
$ 210.99
$ 464.18
$2785.07
$1392.54 to $4177.61
-------
PRICE SURVEY:
FIVE DAY DIETARY TOXICITY
1 N ~IALLARDS
PRICE SUMMARY
PROTOCOL ESTIMATE:
3 LABORATORY SURVEY:
PRI CE RANGE
$ 1393-4178
BEST ESTIMATE
$2785
$ 1000-2600
$1640
INDIVIDUAL LABORATORY SURVEY RESULTS:
1.
2.
$1900 - 2600
$1000 - 1200
3. $1500
PROTOCOL USED IN THIS COST ANALYSIS:
- Five Day Dietary Toxicity Test Standard
using Bobwhite (Colinus virginianus) or
Mallard (Anas platyrhynchos).
Draft of May 16, 1980.
B-47
-------
PRDTDCDL ESTIMATE:
DIRECT LABDR:
Personne 1
Study Director
Quality Assurance
Biologist
Set- Up
Record Keeping
Animal Technician
Randomization
Body Weights
Food Consumption
Compound Preparation
Sacrifice
Dbservations
Animal Caretaker
Animal Care (bedding,
feeding, and watering)
Room Cleaning
Report Writer
Report Typist
. TDTAL DIRECT LABOR:
FIVE DAY DIETARY TDXICITY (IN BDBWHITE)
No. of
Hours
1
4
14
(10..0.)
(4.0.)
28
(6.0.)
(3.0.)
(2.0.)
(6.0.)
(6.0.)
(5.0.)
14
(8.0.)
(6.0.)
24
8
. OVERHEAD (115% of Total Direct Labor):
DTHER DIRECT CDSTS:
Animal Procurement (84 Bobwhite @ $2.60.)
Animal Rations (2 Bags @ $15.0.0. ea.):
Laboratory Supplies (10.% of Total Labor):
. TOTAL OTHER DI RECT COSTS:
TOTAL CDST BEFDRE G & A
. G & A (10.% of Total):
TOTAL CDST BEFDRE FEE:
. FEE (20.% of Total):
. ESTIMATED FINAL CDST:
. ESTH~ATED.rosI RANGE:
B-48
Hourly Total Component
Waqe Do 11 ars Cost
$12.0.0. $ 12.0.0.
10.0.0. 40..0.0.
6.70. 93.80.
6.0.0. 168.0.0.
4.0.0.
56.0.0.
6.0.0.
5.0.0.
144.0.0.
40..0.0.
$ 553.80.
$ 636.87
$ 218.40.
30..0.0.
55.38
$ 30.3.78
$1494.45
$ 149.45
$1643.90.
$ 328.78
$1972.68
$986.34 to $2959.0.2
-------
PRI CE SURVEY:
FIVE DAY DIETARY TOXICITY WITH BOBWHITE
PRICE SUNMARY
PROTOCOL ESTIMATE:
PRICE RANGE
$986-2959
BEST ESTIMATE
3 LABORATORY SURVEY: $850-2350
$1973
$1510
INDIVIDUAL LABORATORY SURVEY RESULTS:
1. $1850 - 2350
2. $ 850 - 1000
3. $1500
PROTOCOL USED IN THIS COST ANALYSIS:
- Five Day Dietary Toxicity Test Standard
using Bobwhite (Colinus vir~inianus) or
Mallard (Anas platyrhynchos).
Draft of May 16. 1980.
B-49
-------
PROTOCOL ESTIMATE:
REPRODUCTION IN THE MALLARD (Anav platyrhynchosJ
DIRECT LABOR:
No. of Hourly Total Component
Personne 1 Hours Waqe Do 11 a rs Cost
Study Director 44 $12.00 $ 528.00
Quality Assurance 24 10.00 240.00
Secretary 22 6.00 132.00
Biologist 186 6.70 1246.20
Observations ( 76.0)
Egg Shell Thickness,
Measure ( 80.0)
Record Keeping ( 30.0)
Animal Technician 372 6.00 2232.00
Set-Up and Randomization ( 8.0)
Observations ( 90.0)
Egg Collection (140.0)
Body Weights ( 20.0)
Food Consumption ( 20.0)
Candli ng Eggs ( 48.0)
Egg Shell Thickness,
Measure ( 20.0)
Sacrifice ( 4.0)
Compound Preparation ( 22.0)
Anima 1 Caretaker 186 4.00 744.00
Set-Up ( 8.0)
Animal Care (bedding,
feeding, and watering) (88.0)
Cage and Room Cleaning (90.0)
Report Writing Supervisor 8 10.00 80.00
Report Wri ter 100 6.00 600.00
Computer Coder 22 5.00 110.00
Computer Programmer 22 8.50 187.00
Report Typist 50 5.00 250.00
SUBTOTAL DIRECT LABOR: $6349.20
Salary Adjustment (8%): 507.94
. TOTAL DIRECT LABOR: $ 6857.14
B-50
-------
PROTOCOL ESTIMATE:
REPRODUCTION IN THE MALLARD (Continued)
. TOTAL DIRECT LABOR:
. OVERHEAD (115% of Total Direct Labor):
OTHER DIRECT COSTS:
Overtime (46 Technician hours @ $3.00):
(44 Caretaker hours @ $2.00):
Animal Procurement (115 Mallards @ $6.10):
Bedding (Straw)
Animal Rations (42 bags @ $15.00 each):
Data Processing (22 weeks @ $50.00):
Laboratory Supplies (10% of Total Labor):
SUBTOTAL OTHER DIRECT COSTS:
INFLATION ADJUSTMENT (5% of Other Direct Costs):
. TOTAL OTHER DIRECT COSTS:
--
TOTAL COST BEFORE G & A:
. ~ (10% of Total):
TOTAL COST BEFORE FEE:
. FEE (20% of Tota 1) :
. ESTIMATED FINAL COST:
--
. ESTIMATED COST RANGE:
B-51
Tota 1
Dollars
$
138.00
88.00
701. 50
25.00
630.00
1100.00
685.71
$ 3368.21
168.41
$18,279.47
$20,107.42
Component
Cost
$ 6,857.14
$ 7,885.71
$ 3,536.62
$ 1,827.95
$ 4,021.48
$24.128.90
$12,064.45 to $36,193.35
-------
PRICE SURVEY: REPRODUCTION IN THE MALLARD
(Anas p'LatyrhynahoB)
PRICE SUMMARY
PROTOCOL ESTIMATE:
PRICE RANGE
$12,064-36,193
BEST ESTIMATE
$24,129
3 LABORATORY SURVEY: $12,650-40,000
$24,883
INDIVIDUAL LABORATORY SURVEY RESULTS:
1. $22,000
2. $12,650
3. $40,000
PROTOCOL USED IN THIS COST ANALYSIS:
- A Reproduction Test Standard for
Mallard (Anas pZatyrhynahos)
Draft Dated May 16, 1980.
8-52
-------
PROTOCOL ESTIMATE:
REPRODUCTION IN BOBWHITE (CoLinus virginianuD)
DIRECT LABOR:
No. of Hourly To ta 1 Component
Personne 1 Hours Waqe Do 11 a rs Cost
Study Di rector 44 $12.00 $ 528.00
Quality Assurance 24 10.00 240.00
S,ecretary 22 6.00 132.00
Biologist 147 6.70 984.90
Randomization ( 4.0)
Observations, Record
Keeping (58.0)
Egg Shell Thickness,
~leas ure (50.0)
Record Keeping (35.0)
Animal Technician 295 6.00 1770.00
Observations (105.0)
Body Wei ghts (20.0)
Food Consumption (20.0)
Egg Collection (30.0)
Candling Eggs (48.0)
Egg Snell Thickness,
I~easure (50.0)
Compound Preparation ( 22 . 0)
Animal Care Assistant 147 4.00 588.00
Room Set-Up & Sanitization ( 5.0)
Cage Cleaning ( 6.0)
Animal Care (bedding, (22.0)
feeding, and watering)
Sacrifice ( 4.0)
Egg Co 11 ecti on ( 110.0)
Report Writing Supervisor 8 10.00 80.00
Report Wri ter 100 6.00 600.00
Computer Coder 22 5.00 110.00
Computer Programmer 22 8.50 187.00
Report Typist 50 5.00 250.00
SUBTOTAL DIRECT LABOR: $5469.90
Salary Adjustment (8%): 437.59
. TOTAL DI RECT LABOR: $ 5907.49
B-53
-------
PROTOCOL ESTIMATE: REPRODUCTION IN BOBWHITE (Continued)
To ta 1
Doll ars
. TOTAL DIRECT ~:
. OVERHEAD (115% of Total Direct Labor):
OTHER DIRECT COSTS:
Overtime (44 Technician hours @ $3.00):
(46 Caretaker hours @ $2.00):
Animal Procurement (173 Bobwhites @ $2.60):
Animal Rations (25 bags @ $15.00 each):
Data Processing (22 weeks @ $50.00):
Laboratory Supplies (10% of Total Labor):
SUBTOTAL OTHER DIRECT COSTS:
$ 132.00
92.00
449.80
375.00
1100.00
590.75
$2739.55
INFLATION ADJUSTMENT (5% of Other Dire,t Costs):
136.98
. TOTAL OTHER DIRECT COSTS:
TOTAL COST BEFORE G & A:
$15,577 .63
. G & A (10% of Total):
TOTAL COST BEFORE FEE:
$17 , 135 . 39
. FEE (20% of Tota 1) :
. ESTIMATED FINAL COST:
. ESTIfv1ATED COST RANGE:
Component
Cost
$ 5,907.49
$ 6,793.61
$ 2,876.53
$ 1,557.76
$ 3,427.08
$20.562.47
$10,281.24 to $30,843.71
B-54
-------
PRICE SURVEY:
REPRODUCTION IN BOBWHITE
{Colinus virginianus}
PRICE SUMMARY
PRICE RANGE
BEST ESTIMATE
$20,562
PROTOCOL ESTIMATE:
3 LABORATORY SURVEY:
$10,281-30,844
$10,780-38,000
$21,927
INDIVIDUAL LABORATORY SURVEY RESULTS:
1. $17,000
2 . $10 , 780
3. $38,000
PROTOCOL USED IN THIS COST ANALYSIS:
- A Reproduction Test Standard for
Bobwhite {Colinus virginianus}
Draft Dated May 16, 1980.
B-55
-------
PROTOCOL ESTIMATE: SEED GERMINATION AND ROOT ELONGATION
Test Cost Range:
$ 700 - 1,200
Detailed protocol estimate for
this test is not available at
this time. A revised estimate
will be supplied for the final
draft.
B-56
-------
PROTOCOL ESTIMATE:
PLANT UPTAKE AND TRANSLOCATION
Test Cost Range:
$ 1,000 - 25,000
Detailed protocol estimate for this
test is not available at this time.
A revised estimate will be supplied
for the final draft.
8-57
-------
PROTOCOL ESTIt~ATE: EARLY SEEDLING GROWTH
Test Cost Range:
$ 1,200 - 16,000
Detailed protocol estimate for this
test is not available at this time.
A revised estimate will be supplied
for the final draft.
B-58
-------
PROTOCOL ESTIMATE: BIOCONCENTRATION TEST USING THE FATHEAD MINNOW
DIRECT LABOR:
No. of Hourly Total Component
Personne 1 Hours Wage Do 11 ars Cost
Quality Assurance 16 $10.00 $ 160.00
Report Typist 16 5.00 80.00
Study Director 160 12.00 1920.00
Compound Purity Assay ( 1.0)
Toxicant Delivery Check (14.0)
Chemical Analysis (72.0)
Tissue Analysis (41.0)
Calculations And Report (32.0)
Technician 80 7.70 616.00
Reagent Preparation ( 5.0)
Study Set Up ( 8.0)
Fi sh Culture (21.0)
Observations And
Monitoring (21.0)
Chemical Analysis (25.0)
. TOTAL DIRECT LABOR: $2776.00
. OVERHEAD (115% of Total Di rect Labor): $3192.40
OTHER DIRECT COSTS:
Laboratory Supplies $ 300.00
. TOTAL OTHER DIRECT COSTS: $ 300.00
TOTAL COST BEFORE G & A: $6268.40
. G & A (10% of Total): $ 626.84
TOTAL COST BEFORE FEE: $6895.24
. FEE (20% of Total): $1379.05
B-59
-------
PROTOCOL ESTIMATE: BIOCONCENTRATION TEST USING THE FATHEAD MINNOW
Total
Dollars
Component
Cost
. FEE (20% of Total)
$1379.05
. ESTIMATED FINAL COST:
$8274.29
. ESTIMATED COST RANGE:
$4,137.00 to $12,411.00
B-60-
-------
PRICE SURVEY:
BIOCONCENTRATION TEST USING THE FAFiEAD MINNOW
PRICE SUMMARY
PROTOCOL ESTIMATE:
PRI CE RANGE
$4,137-12,411
BEST ESTIMATE
3 LABORATROY SURVEY: $6,000-16,500
$ 8,274
$12,025
INDIVIDUAL LABORATORY SURVEY RESULTS:
1. 15,000-16,500
2. 12,000-13,300
3. 9,350
4. 6,000
Note:
Bioconcentration studies are currently conducted in
several species of fish, including Fathead Minnows,
Rainbow Trout (Salmo gairdneri), Bluegill (Lepomis
macrochirus), and catfish. The prices above reflect
bioconcentration studies conducted in any of these
species, since the species of fish does not influ-
ence the test procedure, or its cost.
PROTOCOL USED IN THIS ANALYSIS:
- Test Standard for Conducting A
Bioconcentration Test Using
Fathead Minnows (PimephaZes
prome las)
Draft Dated August 26, 1980
B- 61
-------
PROTOCOL ESTIMATE: BIOCONCENTRATION TEST USING EASTERN OYSTER
IN A FLOW-THROUGH SYSTEM
DIRECT LABOR:
No. of Hourly Total Component
Personnel Hours Wage Dollars Cost
Report Typi st 10 $ 5.00 $ 50.00
Quality Assurance 4 10.00 40.00
Study Director 96 12.00 1152.00
Compound Purity Assay ( 3.0)
Water Quality Assay ( 8.0)
Chemical Analysis
Calibration (40.0)
Toxicant Delivery Check
And Pretest System Check (25.0)
Calculations And Report (20.0)
Technician 175 7.70 1347.50
Test Set Up ( 3.0)
Oyster Collections And
Culture (52.0)
Water Quality Testing (25.0)
Daily Observations (45.0)
Removal And Tissue
Analysis (50.0)
. TOTAL DIRECT LABOR: $2589.50
. OVERHEAD (115% of Total Direct Labor): $2977 . 93
OTHER DIRECT COSTS:
Laboratory Supplies and Reagents $ 250.00
. TOTAL OTHER DIRECT COSTS: $ 250.00
TOTAL COST BEFORE G & A: $5817.43
. G & A (10% of Total): $ 581.74
TOTAL COST BEFORE FEE: $6399.17
B-62
-------
PROTOCOL ESTIMATE: BIOCONCENTRATION TEST USING EASTERN OYSTER
IN A FLOW-THROUGH SYSTEM (Continued)
Total
Do 11 a rs
TOTAL COST BEFORE FEE:
$6399.17
. FEE (20% of Total):
. ESTIMATED FINAL COST:
. ESTIMATED COST RANGE:
Component
Cost
$1279.83
$7679.00
$3t839.50 to $11,518.50
B- 63
-------
PRICE SURVEY: BIOCONCENTRATION TEST USING EASTERN OYSTER
IN A FLOW-THROUGH SYSTEM
PRICE SUMMARY
PROTOCOL ESTIMATE
4 LABORATORY SURVEY:
PRICE RANGE
$3,840-11 ,520
BEST ESTIMATE
$7,680
$4,000-10,000
$8,092
INDIVIDUAL LABORATORY SURVEY RESULTS
1. 7,200- 9,000
2. 9,000-10,000
3. 4,000
4. 9,350
PROTOCOL USED IN THIS ANALYSIS:
- B;oconcentrat;on Test Standard
Using The Eastern Oyster In A
Flow-Through System
Draft Dated August 26, 1980.
8-64
-------
PROTOCOL ESTIMATE:
SOIL THIN LAYER CH~G~ATOGRAPHY
(DRAFT OF 12-5-79)
DIRECT LABOR:
No. 0 f
Hours
Study D i rec tor
Report Prepa ra t; on
Soil Scientist
5011 T rea trnen t
P1 ate Prcpara t ion
Solvent Migration
AutorJdiography
Report Typ i s t
2
11
Ho u r 1 y To ta 1 Component
Waqe Do 11 a rs _Cos~
$12 . 00 S 24.00
7.70 84.70
Personnel
(2.0)
( 1.0)
(5.0)
( 1.0)
(4.0)
1
5.00
5.00
. IOr~,=- P!Rf,C_L ~A_B98.:
$113 . 70
. Q..\H;R!~FAD (115% of Total Direct lJbor):
$130.76
OTHER DIRECT COSTS:
Solvents:
X-ray fi 1m:
Liquid scintillation vials:
Developer, fixer, diagram of plate:
TLC plates, soil slurry:
$ 5.00
3.00
5.00
2.00
1.00
. J9IAl OJHU~. DIRECI cosr~:
$ 16. 00
TOTAL COST BEFORE G & A:
$260.46
. LLA (lO~ of Tota 1):
$ 26.04
TOTAL COST BEFORE FEE:
$286.50
. FEE (20% of Total):
$ 57. 30
. ESTIMATED FINAL COST:
$343.80
. ESTIMATED COST RANGE:
$171.90 to $515.70
B-65
-------
PRICE SURVEY:
SOIL THIN LAYER CHRO~ATO~RAPHY
(ORAFT OF 12-5-79)
PRICE SUt111ARY:
PRICE RANGE
BE S T EST !11M E
------
PROTOCOL ESTIMATE:
2 LABORATORY SURVEY:
$172 - 516
390 - 850
$3'14
620
INDIVIDUAL LABORAfORY
1. $850
2. 350
SURVEY RESULTS:
DISCREPANCY BErWEEN PRICE ESTIMArE AND SURVEY:
The rnrthod of analysis, after '.olv(:nt rniC)ration,
is not spt"'cifif'd in the tpst 5tandud. Oifferr~nt
rnl:thons of ,1n.1ly')is will f'I",tJlt in diffr.rr>ot t:o<,ts
for this ,",'),1Y. r10st 1,lIJor.1toril's contacted in-
dicated thrlt aHenltlte mpthods, i.~., column 50il
Inigrdtion dnalysis, w(~re most often IJscn, (1nd
could offer no cost or tt!chnical infollll,1tion on
this test.
The pri ce cs t i Ina te docs not i nc 1 ude cas ts for any
analytical work which may be necessary before the
test can be perfor"med. In practice, te<,ting lab-
oratories receive chemicals in a pure for"m, i1nd
most identification and analytical methodology has
already been developed. [xlr"ction, GS, 11'), pct.
methodology may be rll'cC'<;<;ary, howevl~r, c1nd it is
e<,tilllatcd that this \'lou1d cost less t.hdn )1,000
for 90~ of ch,'mica1 tc:"tl.d.
PRorOCOL U~ED IN [HIS cosr ANALYSIS:
Physical clnd Chemical P,-opertics TC'st
Standard, dated 12-5-79, and Technical
Support Document for Soil Thin Layer
Chromatography.
B-66
-------
I ~EC~N1CAI. R EPQRT OA i A
1 ~1:~OP6 '/. . f,(!:1st! !'taa //T.SlI'UC!JOJlS Qn :h~ f,!Ver!f! '~/ort :. O,""'(fln'!/
EPA 5 0 4.81 004 12. .J ~eCj~~Eo\j-'S .JtC:~$~"~I~ '.C
i I
~. 1'1'':"1..: "'NO SUiilTI 1':";
Economic Impact Analysis of ,3 "~P1' O~T"=
Proposed Test Rule :. y, 1
for Dichloromethane, l,l,l-Trichloroethane 03. :I~;U:O~MI,"~ C~GANIZ~7"~N ::::E
N' z<=>n<=> ' !
7 ...U1''''OPISI
Rao Tadavarthy, Joarme Collins i8. .:I~..:tj:O~MI"'C ~F\~":",\4I;:...7'I:JN :I:'E.:tO~i '~o,
Dave Mavo, Barrv Riordan I 2152-585
9. ~~"'FOPMING OFlC..NIZ...710N "''''MI: ...NO ..00"'1:5S 10. ~I:;!OG~_,\A ;'_=',11;.'1'" '.jC
MATHTEGI, Inc. : B2CL2S -
1611 North Kent Street 1 t. ':=~ ("=t...c ~~~NT '-Ie
Ar lington, Virginia 22209 68-01-5864
12. 5PON50"";1'0 "'C~"'CY ""'MI: "'.'110 "'001'11:55 '1J. -'(8$ ~F ~E?OFl~ Jr..\lO :t~~JC~ '::J\I:~C:C
EPA
401 M Street, S.W. ! 1" S?ONSO""NC "'CI:NCV COOE
,
Washington, D.C. 20460 lA2C69TOOO
IS. Su,.",-:MEN1'''''''Y NOTES
Project Officers: Sarrmy K. Ng, Peter Kimn
16. ...aST~"'C7
This report presents the Level I economic impact analyses
for the proposed test rule (HE-l) on dichloromethane, 1,1,1-
trichloroethane, and nitrobenzene. Each Level I analysis
consists of evaluating four principal market characteristics:
demand sensitivity, costs, industry structure, and market
expectations. Using these factors as the basis for analysis
(along with the costs of the proposed tests), the Level I
analysis is used to determine if the potential for significant
economic impacts exists. The methodology of the analysis is
presented in Appendix A.
For all three chemicals, the Level I analyses conclude that
the proposed test rule will not impose any significant economic
impacts on manufacturers. Appandix B presents cost estimates for
various tests recommended in the proposed test rule.
7.
-------
United States
Environmental Protection
Agency
Washington DC 20460
Postage and Fees Paid
Environmental Pr"tection Agency
~PA-335
Official Business
Penalty for Private Use $300
-::t
o
o
I
,......j
co
I
N
.......
o
~
L/'")
<1j
p..,
~
------- |