United States
Environmental Protection
Agency
Office of Toxic Substances
Washington, DC 20460
fcPA 560/13-79-008
July, 1979
Toxic Substances
Methodology for
Estimating Direct
Exposure to New
Chemical Substances
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EPA-560/13-79-008
July, 1979
METHODOLOGY FOR ESTIMATING DIRECT EXPOSURE
TO NEW CHEMICAL SUBSTANCES
David Becker
Edward Fochtman
Allan Gray
Thomas Jacobius
IIT Research Institute
Chicago, Illinois 60616
Contract No. 68-02-2617
Task No. 8
Project Officer
Daphne Kamely
Pre-Manufacturing Review Division
Office of Toxic Substances
Washington, DC 20460
Program Manager
Joseph McSorley
Operations Program Office
Industrial Environmental Research Laboratory
Research Triangle Park, NC 27711
OFFICE OF TOXIC SUBSTANCES
WASHINGTON, DC 20460
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DISCLAIMER
This report has been reviewed by Office of Toxic Substances, Washington,
DC and approved for publication. Approval does not signify that the contents
necessarily reflect the views and policies of the U.S. Environmental Protec-
tion Agency, nor does mention of trade names or commercial products consti- "
tute endorsement or recommendation for use.
n
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FOREWORD
This study was conducted for the Pre-manufacturing Review Division,
Office of Toxic Substances, Environmental Protection Agency, (EPA), to collect
data and develop procedures for the assessment of direct exposure as an inte-
gral part of the risk assessment scheme for new chemical substances. It
focused primarily upon the initial screening of new chemical substances. How-
ever, this study is not limited to new chemical substances; the methodology
and procedures described are sufficiently broad to be useful to other EPA
programs.
This document was published with the expert advice of Dr. James Falco,
Office of Research and Development, and Dr. Peter Voytek and Mr. Stuart
Cohen, Office of Toxic Substances. Further information can be obtained from
the Pre-manufacturing Review Division; telephone: 202-426-2601; address:
Office of Toxic Substances (TS-794), U.S. Environmental Protection Agency,
401 M Street, SW, Washington, DC 20460.
Daphne Kamely, Ph.D.
Premanufacturing Review Division
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CONTENTS
Disclaimer ii
Foreword iii
Figures vi
Tables . . . vii
1. Introduction 1
General Approach 1
Restrictions and Limitations. 2
Purpose and Scope of this Effort 2
2. Summary 4
Estimation of Physical and Chemical Properties
Important to Direct Exposure 4
Analysis of Projected Uses and Prediction of
Production Growth Rates . 4
Calculations of Exposure of Manufacturing Personnel and
Populations in Near Proximity to these Plants 4
Predictions of Active and Passive Exposure
During Consumer Use 5
Exposure Assessment Procedure 5
3. Prediction of Exposure During Manufacture and Processing. . . 6
Production Rate 6
Process Labor Requirements 7
Manufacturing Source Strength 9
Ventilation Rates 12
Building Size in the Chemical Process Industries 13
Assessment of Exposure Due to Processing 13
4. Prediction of Exposure During Consumer Use 28
Computer Methods 42
Limitations 42
5. Methods of Predicting Production Volume 43
Objective and Scope 45
Procedure 46
Assumptions and Qualifications 51
6. The Correlations of Chemical Structure with Physical, Chemical
and Biological Properties: Applications in Exposure
Assessment. 57
Potential Uses 57
Potential For Direct Systemic Uptake 62
IV
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Potential for By-Product Formation 66
Susceptibility to Environmental Degradation 67
Potential for Bioaccumulation 70
7. Application of Procedure 76
Appendix A-l
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FIGURES
Number
1
2
3
4
5
6
7
8
9
10
11
12
Labor requirements as a function of plant capacity
Building size versus production volume
Ambient air concentration as a function of distance from
the source
Manufacturing exposure worksheet
Plant vicinity population exposure worksheet
Processing exposure worksheet
Manufacturing Exposure, TRIS
Plant vicinity population exposure, TRIS manufacture
Processing exposure, carpet manufacture, TRIS
Idealized new product market growth for five year and ten year
product growth cycles
Effect of chemical properties on systemic uptake
Potential for bioaccumulation
Page
8
14
18
20
21
22
23
24
25
50
65
72
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TABLES
Number
1 Estimated Design for Three Chemical Categories ......... 10
2 Vinyl Chloride Emissions .................... 10
3 Relationship of Emission Routes ................. H
4 Loading and Transportation Emission Factors ........... 15
5 Consumer Use Categories ..................... 30
6 Variables Used to Estimate Consumer Exposure .......... 31
7 Total Number of Firms Competing Vs. Estimated Base
Value Market Share ....................... 48
8 Percent 'Retention of Inhaled Aerosol Particles ......... 64
9 Market Share for Sample "New" Chemicals ............. 78
10 Manufacturing Exposure for Sample "New" Chemicals ........ 79
11 Consumer DOse for Sample "New" Chemicals ............ 80
vn
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SECTION 1
INTRODUCTION
PREMANUFACTURING NOTIFICATION REQUIREMENTS
Section 5 of the Toxic Substances Control Act (TSCA) requires each per-
son who intends to manufacture a new chemical substance for commercial pur-
poses to sumbit a notice to EPA at least 90 days before manufacture commences.
At the end of the notification period the person may manufacture the substance
unless EPA has taken regulatory action under section 5(e) to request addition-
al data or under section 5(f) to ban or otherwise regulate the substance.
Section 5(d)(l) of TSCA requires the manufacturer to report chemical
identity, uses, and exposure data. In addition, the submitter must provide
all test data related to the effects on health and the environment of the
manufacturing, processing, distribution in commerce, use, and disposal of the
new chemical substance to the extent they are known to or reasonably ascer-
tainable by the1 submitter.
On January 10, 1979, the EPA published proposed rules and notice forms
in the Federal Register, and subsequently held a series of public meetings
throughout the country to obtain written and oral comments on the proposed
rule making. On May 15, 1979, EPA published its Interim Policy for the pre-
manufacture program applicable until the Agency promugates its final rules
and forms. Also, in September, EPA reproposed the notice forms for further
public review and comment.
EPA also published three documents with this proposal:
Support Document, Premanufacturing Notification Requirements
and Review Procedures, Office of Toxic Substances Washington,
DC, January, 1979.
Explanatory Appendix, Premanufacturing Notice Forms, Office
of Toxic Substances, Washington, DC, January, 1979.
Impact of TSCA Premanufacturing Notification Requirements,
Office of Toxic Substances, Washington, DC, 1979.
GENERAL APPROACH
EPA's implementation of Section 5 of TSCA will focus upon the assessment
of risks associated with the manufacture, processing, distribution in
1
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commerce, use, disposal of new substances. This risk assessment will involve
developing estimates of both the potential extent of human exposure and
potential toxicological effects on human health and the environment for
each new chemical. Possible risks then can be balanced against economic
and other non-risk factors in order to evaluate the reasonableness of the
risks.
RESTRICTIONS AND LIMITATIONS
The number of new chemicals which will have to be evaluated each year
has not been determined as of this time. Estimates have ranged from as low
as 150 to as many as 1,000. Since one major company states it will attempt
to commercialize 100 new polymers and oligomers per year, it would seem that
the higher estimate will be more realistic.*
The submissions must be acted upon within 90 days and preferably within
a shorter period.
The manufacturer must supply the information which is know to him or is
reasonably ascertainable. It is expected that many manufacturers will be able
to supply only limited information in their notices and that EPA make deci-
sions that are be as definitive as possible based upon this limited informa-
tion.
PURPOSE AND SCOPE OF THIS EFFORT
The purpose of this study was primarily to elaborate procedures for
making direct exposure assessment and was particularly directed toward the
initial screening operation. This involved identifying relevant parameters
of exposure, determining the priority for consideration of these parameters,
developing specific quantitative data and test results for direct exposure
based on the literature, and developing a background for the use of structure-
property relationships.
EPA's Office of Toxic Substances has limited resources for the formula-
tion of decisions on new chemicals. The purpose of this program was to
develop procedures and data which could permit rapid assessment of direct
exposure and which could become an integral part of the unreasonable risk
assessment scheme for new chemicals.
It was fully recongnized that the exposure assessment procedures would
be qualitative in nature and, at the optimum, would result in general cate-
gories or ranges describing the degree of the exposure. Nevertheless numeri-
cal methods were used throughout.
*Wismer, M., Let's Reason Together and Simplify PMN, Chemical Week, May 16,
1979, p. 5.
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To accomplish these objectives the effort was divided into the following
tasks:
• Development of a procedure for prdicting exposure during
manufacture and processing;
• Development of a procedure for predicting exposure during
consumer use;
• Development of a procedure for predicting production volume
for the third and fifth years;
• Study of the relationships of chemical and structure to
physical, chemical and biological properties, and
• Application of these procedures to candidate compounds.
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SECTION 2
SUMMARY
Assessment of unreasonable risks during the production and use of new
chemicals requires consideration of toxicity, exposure, and economic factors.
This effort involved the development of concepts and procedures to predict
the direct exposure during manufacture, processing and use of a new chemical.
The effort was based upon the premise that there would be very little infor-
mation as to the physical or chemical properties of the new chemical, and
only limited information concerning processing steps, production volume,
anticipated growth in production, and potential uses. In spite of these
limitations it is necessary to rapidly screen perhaps as many as 1,000 chem-
icals per year and to separate those chemicals which represent very little
exposure from those that have the potential for high exposure.
The approach developed utilizes the following steps:
ESTIMATION OF PHYSICAL AND CHEMICAL PROPERTIES IMPORTANT TO DIRECT EXPOSURE
Limited physical and chemical data will be available for some candidates
and it will be necessary to estimate properties such as vapor pressure,
octanol-water partition coefficient, chemical stability and possible uses
based upon the chemical structure of the compound. The techniques for pre-
paring such estimates are discussed.
ANALYSIS OF PROJECTED USES AND PREDICTION OF PRODUCTION GROWTH RATES
Evaluation of exposure assessment due to manufacturing and consumer use
requires estimation of production volume for the first, third and fifth
years of production. EPA proposed to request this information on the PMN
forms. However the confidential nature of this information and the possibility
that the form would be modified to delete these estimates made it advisable
to independently predict the production volume and the use categories. A
method of production estimation based upon use categories and data concerning
the applicant company has been developed.
CALCULATION OF EXPOSURE OF MANUFACTURING PERSONNEL AND POPULATIONS IN NEAR
PROXIMITY TO THESE PLANTS
Exposure of production workers can be estimated based upon fugitive
losses, plant size, ventilation rates, and production volume. The number of
workers exposed and the concentration of the chemical in the air can be pre-
dicted for normal chemical plant operations.
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Fugitive losses have been used as source strength to calculate exposure
of populations in the vicinity of the plant.
PREDICTION OF ACTIVE AND PASSIVE EXPOSURE DURING CONSUMER USE
A procedure for estimation of the dose of the chemical recieved by a
consumer whether by inhalation, ingestion or skin adsorption in either the
active or passive phase of the use has been developed along with guidelines
for estimating the total fraction of the population involved.
The approach developed was used to calculate exposure from 30 chemicals
which differ with respect to production volume, physical and chemical proper-
ties, and uses.
The procedure appears to be satisfactory, however, it does require the
use of technical judgement during each phase of the analysis.
It is recommended that the procedure be adopted on an interim basis and
that efforts to refine the data bases and .procedure be continued.
EXPOSURE ASSESSMENT PROCEDURE
The procedure developed during this effort can be used to estimate ex-
posure during manufacture, processing and use. The procedure is general in
the sense that it does not require site-specific information, details on the
processing steps, details as to equipment to be used and only limited data
as to physical or chemical properties. If this information is available, it
will increase the accuracy of the prediction; however, even without these
data a first level estimate of exposure can be made. The procedure is dir-
ected toward conditions of normal chemical production and normal usage, it
does not address the case of poor equipment or plant design, accidental spills
or misuse of the consumer product.
This report presents the procedures for prediction of exposure during
the manufacture, processing and consumer use of a new chemical. Since the
information for these predictions may or may not be available from the Pre-
manufacturing Notice (PMN) forms it was believed necessary to provide proce-
dures for the estimation of critical data such a possible growth in production
volume and those physical, chemical and biological properties which may
affect exposure.
5
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SECTION 3
PREDICTION OF EXPOSURE DURING MANUFACTURE AND PROCESSING
Plant operating personnel will probably be exposed to the highest con-
centration of any new chemical. Regulation of this exposure is a joint EPA/
OSHA responsibility, however, the OTS could make a preliminary assessment of
exposure and then alert OSHA to any potential problem.
In order to accomplish this mission, the OTS will conduct a preliminary
assessment of exposure based upon information supplied in the PMN and upon
accepted industrial practices. A conservative approach must be taken to in-
sure adequate regulation of new chemicals. Thus in the evaluation a "normal"
and "worst case" should be evaluated.
While data specific to the particular production facility may be avail-
able, the evaluation should not be specific to a particular site or set of
conditions.
In the following sections the rationale for the numbers used in calcula-
ting exposure is presented. Literature references are cited where available
and where project personnel exercised engineering judgement, it is so in-
dicated. Periodicals and books devoted to chemical production were searched
up to date; however, many of the most useful articles were published several
years ago. These references were used if, in the judgement of the project
engineers, they were representative of current conditions.
The method used to estimate exposure during manufacture or processing
utilized the following parameters:
Source Strength: as a fraction of production
Building Size: as a function of production
Ventilation Rate: as 10 changes per hour
Workers Exposed: as a function of production volume and number
of processing steps
The exposure of people in the vicinity of the plant was estimated using
a fraction (0.001) of production as the source strength and a diffusion model
PRODUCTION RATE
The annual production rate is requested in the PMN forms and will be
provided by the applicant. A simple annual production figure could be mis-
leading and further details may be necessary. Many specialty chemicals are
6
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produced in existing facilities rather than in facilities designed specifically
for the chemical. This results in mis-match of production rates and equipment
capacities such that some unit processes may be utilized only a small fraction
of the time while others are used continuously. In other cases the total
annual volume could be produced in a 30 or 60 day period. This would result
in exposure of plant operators to a much higher concentration than would be
calculated based upon annual production and 250 days of operation.
Since we are concerned with the introduction of a new chemical there are
some economic constraints imposed upon the production volume. It is expected
that the volume produced would be sufficient to provide test marketing infor-
mation. For some chemicals only a few hundred pounds are required for a test
market whereas with others several thousand pounds are required. For example,
a chemical used to produce urathane foam, might require as much as 6,000 Ibs
for production tests and product evaluation. Another chemical used in an in-
secticide formulation may require less than 200 Ibs. Generally a few thousand
pounds are required for test and evaluation. It is expected that the annual
production listed in the PMN forms will vary from 1,000 to 100,000 Ibs/yr.
PROCESS LABOR REQUIREMENTS
The chemical process industries typically have had a low labor/unit pro-
duction requirement. This results from automated and large scale operations.
The relationship of the labor requirements to the production volume has been
described by the "2 tenths factor rule."1 An example of this rule is given
below.
A chemical plant is operating with 600 man-hours per week and a produc-
tion volume of 100,000 Ib/day. If the production is increased to 500,000 lb/
day, how many man-hours would be required?
man-hours = 600 " = 828 man-hours
Thus an increase of only 38% in labor is required for a 500% increase in
production.
C. H. Chi 1 ton2 gave some typical process labor requirements. These show
a range of from 0.2 to 80 man-hours/ton of product. Included in his article
are high and low volume chemicals and chemicals that require little to exten-
sive processing. The majority of operations fall in the 1-10 man-hours/ton
of product range. While these figures are informative they are not well
suited for use in a model to be used for prediction of labor requirements.
A more useful model is described by Wessel.2 The plant capacity is used
to estimate the labor requirements per ton of product per process step. This
is shown graphically in his article and in Figure 1. This method is the most
general and is incorporated into the exposure model.
In general process labor increases as the production increases and as
the number of steps increases. As the production volume increases beyond
some point it becomes more economical to use a continuous rather than a batch
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10.
O.
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4->
in
s-
QJ
Q.
1.0
S-
0)
Q.
s-
o
•" 0.1
tO
0)
a.
O
0.01
1.0
100
00
Plant capacity, tons/day
Figure 1. Labor requirements as a function of pi ant, capacity (frojn Wessel2).
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process. The decision of batch versus continuous processing is dependent upon
factors such as availability or cost of equipment, production rate, number of pro-
cess steps, number and size of recycle streams and labor requirements. It is
expected that the majority of new chemicals will be initially manufactured by
batch processes.
MANUFACTURING SOURCE STRENGTH
The procedure proposed to evaluate exposure of manufacturing plant per-
sonnel requires an estimate of the amount of product lost during manufacture
or processing. These losses occur due to leaks in pipe joints, gaskets in
piping or reactors, pump seals, vent streams, wash-down during maintenance,
minor spills, etc. These losses may range as high as 3% of the total produc-
ti on.
An attempt was made to categorize the allowable concentrations in the air
at the work place and to relate these concentrations to the physical proper-
ties (i.e. vapor pressure) of the chemical. This effort did not result in
any useful relationships. It appears that the level of contamination in a
plant is more related to worker discomfort or toxicity constraints than to the
physical or chemical properties of the chemical. In other words, the concen-
tration of chemical in the plant depends upon good design, good maintenance
and good housekeeping and not upon the properties of the chemical.
An example of this hypothesis is the manufacture of vinyl chloride poly-
mers. When the.re were no restrictions upon the operations the plant person-
nel (and the surrounding neighborhoods) were subjected to high concentrations.
With current restrictions the concentrations in the plant are below the OSHA
limit of 1 ppm (8 hr TWA). This change has been the result of new designs
and new operating procedures.
An attempt was made to accumulate sufficient information to predict
emissions to air, land, and water from chemical production facilities based
upon the process unit operations involved in the manufacturing process. As
a result of a literature review and several telephone conversations with EPA
staff, it was discovered that there is very little published data in this
area. The U.S. EPA, Chemical Manufacturing Section: Chemical and Petroleum
Branch; Emission Standards and Engineering Division; Office of Air Quality
Planning and Standards; U.S. EPA: Research Triangle Park, is currently in-
volved in a program to generate this data, however, it will not be available
until mid 1980. The work is concerned with air emissions. No water and/or
land emissions data or research efforts were found.
EPA Report No. 560/1-77-0023 lists the three-levels of emission cate-
gories shown in Table 1. These values were apparently estimates based upon
the authors' knowledge of the industry and are not supported with any measure-
ments. These categories incorporate dispersion emissions from product in-
termediate and end use as well as emissions from manufacturing operations.
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TABLE 1. ESTIMATED EMISSION FOR THREE CHEMICAL CATEGORIES
Low Emissions 0-3$ - Chemicals manufactured
for in-plant use.
Medium Emissions 3-50% Chemicals which are not
destructively consumed at
manufacturing site.
High Emissions 100% Chemicals which are dispersed
to the environment (i.e.
aerosols).
The data in EPA Report 450/3-77-008at contains emission factors as a
percent of total production. These are assumed to be 1.5% when no data were
available. The range of emissions reported in this reference varied from
0.7% for hexanol to 3% for several compounds. There is no apparent correla-
tion between the emission values and the physical properties of the substance.
The EPA has studied the manufacture of several individual chemicals for
purposes of exposure assessment. Reports on ethylene dichloride, ethylene
dibromide, benzene, and vinyl chloride contained emission figures for the
manufacture of these chemicals.5'6'7'8
Ethylene cTichloride and ethylene dibromide were assumed to be emitted
at 1.5% of production, benzene emissions were estimated at 0.5% of production.
Vinyl chloride emissions are shown in Table 2.
TABLE 2. VINYL CHLORIDE EMISSIONS
(FOR ETHYLENE DICHLORIDE-VINYL CHLORIDE PROCESS)
: VCM Emissions kg/100 kg
Source (Ib VCM/100 Ib) VCM
Fugitive 0.1215
EDC Finishing Column 0.05
VCM Finishing Column 0.24
Oxychlorination Process 0.0364
Process Water 0.007
TOTAL 0.4479
This shows a total emission of 0.4479% or approximately J$ of vinyl
chloride monomer produced.
The U.S. EPA compiled a list of Air Pollution Emission Factors in Re-
port AP-42.9 This report has a discussion of the emissions from a number of
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chemical manfuacturing operations. As was noted in the report, these figures
were often estimated from yields or material balances since little emission
data were available. The emissions are categorized into raw material, inter-
mediate, by-product, and product emissions thus making these data the most
specific of the information available at this time. Emission factors for
total emissions in controlled situations varied from 0.01% to 8% of the pro-
duction volume. The major factor influencing emissions was the emission con-
trol devices applied. This report is the most useful of the available published
government documents on emission factors.
Emissions from the top 139 organic chemical manufacturing operations were
obtained from Emission Standards and Engineering Division. They list as the
source of their data as State EIQ's, Monsanto Research Corporation, Radian,
Houndry, site visits and product reports. Emissions ranged from 0.0007 Ib/lb
product for linear alky! sulfonate to 0.1098 Ib/lb product for acrylonitrile
and hydrogen cyanide. The majority of emissions are less than 1% with a con-
siderable number of emissions in the 0.1-0.5% range. This report shows sever-
al other interesting items as well, including the various processes used to
manufacture the chemical, gross emission, predicted growth rate, and toxicity
rank.10
Another EPA program characterized production emissions into four categor-
ies:11
Process Vents
Fugitive
Storage and Transportation
Solid and Liquid Waste Emissions
Values for the percent of total emissions in each category is given in
Table 3. Process vents and fugitive emissions account for the majority of
the total emissions.
TABLE 3. RELATIONSHIP OF EMISSION ROUTES
Emission Route % of Total Emissions to Air
1.
2.
3.
4.
Process Vents
Fugitive Emissions
Storage and
Transportation
Solid & Liquid Waste
Stream Emissions
66-70%
15-20%
8-10%
2-5%
An excellent discussion on the problems associated with characterizing
and controlling the emissions from chemical manufacturing facilities is pre-
sented by David Patrick in "The 2nd Year End Report: Synthetic Organic
Chemical Manufacturing Industry Standards Development Program."12 This report
is not released for public distribution but was obtained upon request.
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Emissions generated by new chemicals are not expected to exceed the high-
est reported values in the above mentioned literature. With the use of
appropriate controls, fugitive emissions should range from 0.1 to 0.6% of pro-
duction. The fact that many chemical substances are produced with less than
0.5% emissions indicates that this emission range is reasonable and could be
attained in a properly designed manufacturing facility.
The fugitive emission rate for a reasonably volatile new chemical manu-
factured using conventional design and precautions has been assigned a value
of 0.1% of production rate. A high value of six times this or 0.6% has been
assigned to represent the case where few precautions are taken to protect the
worker.
The above data apply to the case where the emission is volatilized into
the air at or shortly after the leakage point; a somewhat different situation
applies when the emission is a non-volatile material.
If the fugitive emission is in the form of particulate matter, it should
be treated somewhat differently than a vapor or gas. The vapor or gas would
be expected to leave the work place with the ventilating air whereas the par-
ticulate matter may accumulate on such places as equipment, floors, building
surfaces, and operator clothing. The degree of accumulation is again depend-
ent upon plant design, operating procedures and housekeeping practices.
Particles below 5 ym would be expected to remain airborne and to be re-
moved with the .ventilation air. Larger particles may well settle on surfaces
within the plant. Personnel would be exposed to some higher, but unknown,
level than is indicated by the fugitive emission losses. This level would be
dependent upon housekeeping, perhaps water solubility, color, degree of irri-
tation and upon the types of processes such as ball milling, conveying, blend-
ing, packaging, etc.
Many plants operate with a weekly wash-down schedule and such a schedule
is assumed here. Based upon these considerations, the source of non-volatile
fugitive emissions is taken as 3x the amount given as a percentage of pro-
duction or 0.3% of the production rate for the normal case and 1.8% of the
production rate for the case were minimum precautions to protect the worker
are taken.
VENTILATION RATES
Ventilation of process buildings is used to remove odors, toxic chemi-
cals, and excess heat. Ventilation design depends upon the specific process
and quite often local ventilation will be used rather than total building
ventilation to accomplish these purposes. However, for the purposes of the
exposure model a different approach was required in that the number of air
changes per hour for the total plant are needed.
The American Iron and Steel Industries report a general ventilation
rate in steel plants of about 2 ftVnrin ft?.13 Using a ceiling height of 14
ft this gives a ventilation rate of 8.6 air changes per hour. This is a
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reasonable figure and close to the expected range based upon the experience of
the IITRI staff.
The Code of Federal Regulations (1978)1" requires a ventialation rate of
1 cfm per square feet of floor area for processing buildings using Class I
liquids. This includes flammable or combustible liquids and operations such
as mixing, drying, evaporating, filtering, distillation or similar operations
"for example in compounding of cosmetics, Pharmaceuticals, solvents, cleaning
fluids or insecticides."
A ventilation rate of 10 air changes per hour was selected for use in the
exposure model based upon the above and other publications.15'16
BUILDING SIZE IN THE CHEMICAL PROCESS INDUSTRIES (ENCLOSED PLANTS)
The size of enclosed chemical process plant buildings in one of the fac-
tors entering the worker exposure model. It was assumed that any new chemical
would be produced in an enclosed facility. This is a worst case situation
since many chemical plants, especially large ones are constructed outdoors
with only portions of the equipment and the controls indoors.
A model predicting building size based upon production capacity would be
ideal, however, no such data were found in the literature. A search of the
literature did reveal an estimated building size for typical enclosed produc-
tion facilities. The author quotes a typical building size a "65-95 ft in
width and 150-250 ft in length with few exceptions."17 Allowing a ceiling
height of 13 ft and 2-3 floors gives a range in building size of 250,000-
925,000 ft3.
Since the production volume is expected to relate to the plant size, the
following model is proposed.
The range of sizes, 250-925 thousand ft3 (7 to 26 thousand m3) is assumed
to be linearly proportional to the production volume in the range 1,000 to
10,000 Ib/day (450 to 4500 kg/day). A graph of this relationship is given in
Figure 2. Sizes outside this range can be determined by extrapolation.
ASSESSMENT OF EXPOSURE DUE TO PROCESSING
Exposure during the processing of the chemical can be estimated in a
manner very similar to the procedure used for the estimation of exposure
during manufacture.
In many instances the new chemical is chemically or physically combined
with other materials to produce a product. For instance, pigments are
physically combined with solvent and binder to make paint, and dichloroethylene
is chemically modified to make a new product, vinyl chloride.
The source strength is considered to be the fraction of the new chemical
in the processed product times the amount of the new product and the estima-
tion of exposure proceeds in the same manner as was used for the manufacture
of the chemi cal.
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900
800
"S 700
o
.s
u
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TRANSPORTATION EMISSIONS
Emissions originating from the transportation of chemicals depends on
the equipment and emissions controls used, the physical state of the chemical,
and the vapor pressure of the chemical. The predicted emissions from the
transport of volatile organic liquids were prepared and will soon be reported
by the U.S. EPA. A preliminary copy of the final report on this subject was
obtained from the Emission Standards and Engineering Division, Office of Air
Quality Planning and Standards. An emission factor for new chemicals can be
derived from this information based upon the vapor pressure of the chemical
of interest. These factors are given below in Table 4.
model.
To date, transportation losses have not been considered in the exposure
TABLE 4. LOADING AND TRANSPORTATION EMISSION FACTORS
Vapor Pressure,
KPa*
Loading Loss
Kg Lost/Kg Produced
Transportation Loss Total kg Loss
Kg Lost/Kg Produced Kg Produced
0.001- 6.9
1.4 - 3.5
3.5 - 6.9
6.9 - 10.3
10.3 - 20.7
20.7 - 34.5
34.5 - 51.7
51.7 - 69.0
69.0 -103.4
Above 103.4
0.0000199
0.00006999
0.000124
0.000187
0.000299
0.000399
0.000622
0.000872
0.000995
Negligible
(Closed System)
0.00000354
0.0000125
0.0000271
0.0000453
0.0000814
0.000144
0.000226
0.000317
0.000361
Negligible
(Closed System)
0.0000234
0.0000825
0.000151
0.000232
0.000380
0.000543
0.000849
0.00119
0.00136
Negligible
*ki1opascals (mm Hg)
ASSESSMENT OF EXPOSURE IN THE PLANT VICINITY
Turner's Gaussian plume model was used to estimate, within an order of
magnitude, average concentration in an area around a point source of effec-
tive height H, emitting at a steady rate of Q gms/sec.le
The following assumptions were made:
Basis:
• All calculations were based on uniform atmospheric stability,
class D.
• Average wind speed, U, equals-5.5 m/sec.
15
-------
• There are no "prevailing wind" directions, the wind blows at the
average speed for equal interval of time from each of the 16
compass directions.
• The point source emits at a steady, uniform rate of Q gm/sec.
Then Turner's equation for average concentration 1( becomes:
- 0.5 l^b
where Q = source strength gm/sec
U = wind speed, m/sec
X = distance, m
H = effective plume height, m
crz = standard deviation of plume concentration distribution
in vortical direction, m
Consideration has been given to the exposure of the general population
in the vicinity of manufacturing or processing plants. Atmospheric diffusion
models can be applied to gases or the very small particles which remain air-
borne. The simple models do not account for deposition of particles or re-
action of the gases or vapors. The simple model was considered to be suffi-
ciently accurate for the predictions required for preliminary evaluation.
Plots of this equation for two values of H are illustrated in the Figure
3. This figure may be used to estimate the radius of a circle in which the
average pollutant concentration is X, released from a point source at effec-
tive height H, emitting at a steady rate Q.
Generally, for short sampling time (^2 hrs), Turner's model is expected
to be within a factor of 2 to 3. However, in attempting to estimate long
term, yearly averages the accuracy would rapidly decrease and would probably
be within 2 to 3 orders of magnitude.
Effective Stack Height H
Effective stack height H is the sum of stack height (HH) and plume rise
(AH). Plume rise is defined as the distance between the top of the stack and
the axis of centroid of the pollutant distribution. It has been found to be
dependent upon exit velocity of stack, diameter of stack, mean wind (hori-
zontal) speed, atmospheric stability class, lapse rate and the temperature
difference between the stack gases and ambient air.
16
-------
There are numerous plume rise formulae. Most of these are semi -empirical
For a review of these see Moses, Strom, and Carson.19
An empirical equation was presented by Holland which may be used to esti-
mate AH. This equation frequently underestimates the effective height of
emission, therefore, it often provides a slight "safety" factor.
Hollands equation is:
"3 Ts Ts
AH = (1.5 + 2.68 x 10"3p Ts Ta d)
where AH = rise of the plume above the stack
Vs = stack gas exit velocity, m/sec
d = inside stack diameter, m
U = wind speed, m/sec
p = atmospheric pressure, mb
Ts = stack gas temperature °K
Ta = air temperature °K
and 2.68 x 10~3'is a dimensional constant having units of (mb)"1m~1. From
Figures it is apparent that the more conservative estimate would utilize
H = 0. For the purposes of estimation of population exposure it is suggested
that the stack height plus plume rise be considered as equal to zero. The
worksheets for exposure in the vicinity of the plant are based upon
H + AH = 0.
Population Density
The number of people exposed to chemical emissions is a function of the
population density near the emission source. Source-specific information
can be derived from Census Bureau Information.
A more general model was sought since information as to the specific
manufacturing location may not be available or may change after the chemical
goes into production. Three sources of population density statistics were
selected and used to derive a best estimate average population density for
typical manufacturing sites.
The first source of population density was obtained from EPA CRESS Re-
port No. 39 (July, 1978). °'21 The range of population densities for cities
with plants manufacturing ethylene dibromide was from 552-1604 people/km2.
The second source of population density data was obtained from U.S. EPA
450/2-75-009, a report on exposure to vinyl chloride.22 Data presented in
17
-------
Distance, Km
with Distance for Two Heights of Emission (H in Meters), Class D Stability
Figure 3. Ambient .air concentration as a function of distance from the source.
-------
this report indicate an average population density of 388 people/km2 within a
radius of 5 miles of vinyl chloride and polyvinyl chloride production facili-
ti es.
The third and most detailed general population density data were obtained
from U.S. EPA CRESS Report No. 27 on coke oven emissions.23 Average popula-
tion densities at several distances from 65 coke plants were calculated and
are given below.
Distance From Coke Plant (Km) Population Density (People/km2)
0.0 - 0.5 641
0.5 - 1.0 757
1.0 - 3.0 1006
3.0 - 7.0 885
7.0 -15.0 618
Selecting the population density to be used in the exposure model was
basically a matter of engineering judgement. Note, however, that the range
of population densities noted above is from 388-1604. The maximum density
is thus only a factor of 4 larger than the smallest. A population density
of 3 times the minimum or 1164 people/km2 was chosen. It is believed that
this figure represents the high side of the expected population densities.
However, this figure was chosen so that the model will tend to slightly over-
estimate and not underestimate the number of people likely to be exposed to
emissions from .production and processing facilities.
Routine Estimations
The estimation of exposure due to manufacturing and processing can
be simplified and requires only a very short time for any one particular
compound and site. Forms for such calculations and an example are shown on
the following pages.
19
-------
MANUFACTURING EXPOSURE
CHEMICAL: NO.
Annual Production, P, kg/yr
Number of Plants, N,
Number of Days in Production, D,
Number of Process Steps, S,
Persistence, R, Gas = 1.0 Nonvolatile = 3.0
Maximum Daily Production Pmd kg/day
In-Plant Concentration, normal operations, Cn =
(4.167)(R)(Pmd)
Cn = ~(4.67)(Pmd)+5660 "
Number of workers exposed, W,
u - (2.3 x 10"3)(N)(Pmd)(S) _
W = — 1>?8
U09--,
EXPOSURE:
Normal: mg/m3
Worst Case: mg/m3 (6 times normal case)
No. of Workers:
Figure 4. Manufacturing exposure worksheet.
20
-------
PLANT VICINITY POPULATION EXPOSURE
CHEMICAL;
Maximum Daily Production, Pmd,
Xi = chemical concentration, mg/ra3
X = distance from source, km
Pmd= maximum production, kg/day
Xi = (1.04 x 10"5)(Pmd) for 1 km
X
km Factor
1 1.04 x 10~5
2 3.11 * 10~6
3 , 1.53 x 10"6
5 6.32 x 10"7
10 1.89 x 10"7
20 5.66 x 10"8
Cone.
mg/m3
NO.
kg/day
Number of Plants
, .. Population
Exposed per Plant
3,660
14,600
32,900
91,400
365,700
1,462,700
TOTAL
Figure 5. Plant vicinity population exposure worksheet.
21
-------
PROCESSING EXPOSURE
CHEMICAL:
Use:
NO.
Annual Production, P,
Number of Plants, N,
kg/yr
Number of Days in Production
Number of Process Steps __^_____
Persistence, R, Gas =1.0
Fraction of Chemical in Product, P,
Maximum Daily Production, Pmd
Maximum Daily Use, (FX) (Pmd) = A ._
Nonvolatile = 3.0
kg/day/plant
kg/day
In-Plant Concentration, normal operations, Cn =
Cn -
(4.67KAJ+566
mg/m-
Number of Workers Exposed, W
u _ (2.3 x 10"3)(N)(R)(Pmd)
fPrnd-]0-78
1.909. 1J
Exposure:
Normal:
Worst Case:
mg/m3
mg/m3 (6X normal)
No. of Workers:
Figure 6. Processing exposure worksheet.
22
-------
MANUFACTURING, EXPOSURE
CHEMICAL: TRIS (2,3 dtbromo.propyl- phosphate) NQ.
Annual Production, P, 4.07 x 10 kg/yr
Number of Plants, N, 1 '
Number of Days in Production, D, 360
Number of Process Steps, S, 3
Persistence, R, Gas = 1.0 Nonvolatile =3.0
Maximum Daily Production Pmd n Tspp kg/day
In-Plant Concentration, normal operations, Cn =
(4.167)(R)(Pmd) = (4.167)(1)(11,300) Q Q „, 3
Cn = l4.67)(Pmd)+5660 " (4.67)(11,3.00)+ 2830 = b'8 mg/m
Number of. workers exposed, W,
u = (2.3 x 10"3)(N)(Pmd)(S) = (2.3 x 10"3)(l)(n ,300)(3) _ ,,
909.1
909.1
EXPOSURE:
Normal; p.g mg/m3
Worst Case: 4.8 mg/m3 (6x)
No. of Workers: ^
Figure 7. Manufacturing exposure, TRIS.
23
-------
PLANT VICINITY POPULATION EXPOSURE
CHEMICAL: TRIS (2,3 dibromopropyl phosphate) N0. 1
Maximum Daily Production, Pmd, 11,300 kg/day
Xi = chemical concentration, mg/m3
X = distance from source, km
Pmd= maximum production, kg/day
Xi = (1.04 x 10~5)(Pmd) for 1 km
X
km
1
2
3
5
10
20
Factor
1.04 x 10~5
3.11 x 10~6
1.53 x 10~6
6.32 x 10"7
1.89 x 10"7
5.66 x 10"8
Cone.
mg/m
0.117
0.035
0.017
0.0071
0.00213
0.00064
Population
Exposed
3,660
14,600
32,900
91 ,400
365,700
1,462,700
Figure 8. Plant vicinity population exposure, TRIS manufacture.
24
-------
PROCESSING EXPOSURE
CHEMICAL: TRIS (2.3 dibromopropyl phosphate) NO.
Use: Carpet Manufacture '•.-- -";": -' ••
Annual Production, P, 2.95 x 107 kg/yr
Number of Plants, N, 10 ___
Number of Days in Production 360 • ^ -> '
• • • *•' 1 "^ * •
Number of Process Steps 5
Persistence, R, , Gas = 1.0' Nonvolatile = 3.0 _
Fraction of Chemical in Product, F, Q.IQ _
Maximum Daily Production, Pmd _ 8,000 _ kg/day/plant
Maximum Daily Use, F* Pmd = A _ 800 _ kg/day
In-Plant Concentration, normal operations, Cn =
Cn • (n • (4-156) '3' '800' _ • 1M
(4.67) (800) + 5660
Number of Workers Exposed, W
L909.ll 8000 .78
909.1
Exposure;
Normal: t!..0
Worst Case: 6.0
mg/m3
mg/m3
No. of Workers: 169
Figure 9. Processing exposure, carpet manufacture, TRIS.
25
-------
REFERENCES
1. Chilton, C.H., Process Labor Requirements, Chem Eng, McGraw-Hill, New
York, Febuary 1951.
2. Wessel, Henry E., New Graph Correlates Operating Labor Data for Chemical
Processes, Chem Eng, McGraw-Hill, New York, July 1952.
3. Venezian, Emilio C., Pre-Screening for Environmental Hazards, EPA Report
No. EPA-56011-77-002; A.D. Little; April, 1977. U.S. EPA, OTS, Washing-
ton, DC.
4. Fuller, B., et.al., Preliminary Scoring of Organic Pollutants, EPA Report
No. EPA-450/3-77-008a; The Mitre Corp., October 1976. U.S. EPA Research
Triangle Park.
5. Johns, R., Air Pollution Assessment of Ethylene Dibromide, Mitre Techni-
cal Report No. 7222, U.S. EPA Contract No. 68-02-1495, The Mitre Corp.,
May 1976. ,
6. Patterson, R.M. et. al., Assessment of Benzene as a Potential Air Pollu-
tion Prolbem, GCA-TR-75-32-G(4) U.S. EPA Contract No. 68-02-1337, Task
Order No. 8, GCA/Technology Division, January 1976.
7. No Author Cited, Standard Support and Environmental Impact Statement:
Emission Standard for Vinyl Chloride, EPA Report No. EPA-450/2-75-009,
OAQPS Research Triangle Park, October 1975.
8. Johns, R., Air Pollution Assessment of Ethylene Dichloride, Mitre Techni-
cal Report No. MTR-7164, U.S. EPA Contract No. 68-02-1495, The Mitre
Corp., May 1976.
9. No Author Cited, Compulation of Air Pollutant Emission Factors, Second
Edition, EPA Report No. Ap-42, OAQPS Research Triangle Park, Febuary 1976.
10. Erickson, D.G., Emission Control Options for the Synthetic Organic Chemi-
cals Manufacturing Industry, EPA Contract No. 68-02-2577, Storage and
Handling Report, Hydroscience, October 1978 (not in print), U.S. EPA
Research Tri angle Park.
11. Erickson, D.G., and Kalcevic, V., Emissions Control Options for the Syn-
thetic Organic Chemicals Manufacturing Industry, EPA Contract No. 68-02-
2577, Fugitive Emissions Report, Hydroscience, March 1979 (not in print),
U.S. EPA Research Triangle Park.
26
-------
12. Patrick, David, 2nd Year End Report: Synthetic Organic Chemical Manufac-
turing Industry Standards Development Program, March 1979 (not in print),
U.S. EPA Research Triangle Park.
13. Steel Mill Ventilation, American Iron and Steel Institute, New York, 1965.
14. Code of Federal Regulations, V29, 1910.106, p. 228, 1978.
15. McDermott, H.J., Handbook of Ventilation, Ann Arbor Science, Ann Arbor,
Michigan 1976.
16. Industrial Ventilation, 15th ed., American Conference of Industrial
Hygienists, Edwards Brothers, Ann Arbor, Michigan.
17. Kern, Robert, Arranging the Housed Chemical Plant, Chem Eng, Mc-Graw-
Hill, New York, July 17, 1978.
18. Turner, D.B., Handbook of Atmospheric Dispersion Estimates, U.S. Depart-
ment of Health, Education and Welfare, No. 999-AP-26.
19. Moses, H., Strom, G.H., and Carson, J.E., Effects of Meteorological and
Engineering Factors on Stack Plume Rise. Nuclear Safety, 6,1, 1964.
20. Mara, Susan J., Assessment of Human Exposures to Atmospheric Benzene, U.S.
EPA-450/3-78-031, U.S. EPA Office of Air and Waste Management, June 1978.
21. Mara, Susan J.9 Atmospheric Ethylene Dibromide: A Source Specific Assess-
ment, EPA CRESS Report No. 39; SRI International, July 1978.
22. U.S. EPA, Standard Support and Environmental Impact Statement for Vinyl
Chloride, U.S. EPA-450/2-75-009, U.S. EPA-Office of Air and Waste Manage-
ment, October 1975.
23.' Suta, Benjamin E., Human Population Exposures to Coke-Ovens Atmospheric
Emissions, EPA CRESS Report No. 27, SRI International, November 1977.
27
-------
SECTION 4
PREDICTION OF EXPOSURE DURING CONSUMER USE
While some new chemicals will lose their identity during processing,
others will be used by the general public, either as produced or as an essen-
tial component of a formulation. Thus it was necessary to specify and docu-
ment procedures for rapid estimation of the chemical dose (mg/person) and the
population receiving that dose (person) due to the use of consumer products.
Dose is defined to be the amount of a chemical that enters the human body.
Exposure is the amount of chemical in proximity to the human body in a form
such that it has substantial probability of becoming dose.
People receive chemical dose from consumer products via oral, inhalation
and skin contact routes. Though in a given case, any one of these routes may
be dominant, generally speaking, the oral route is most significant, then
inhalation, then skin contact. Statistics compiled by the National Center
for Health Statistics (NCHS) suggest that at least 1,200 people yearly receive
oral doses of between 5 and 30 grams of single chemicals in paints, cleaning
agents, disinfectants and petroleum products, based on the number of fatali-
ties and the corresponding toxicities (Gleason 1969). Inhalation doses can
also be in the range of grams per year. Since a person breathes about one
cubic meter of air per hour when active (Handy 1974), a chemical with a
molecular weight of about 100, present at one part per thousand, would result
in an inhalation of about 5 grams per hour, not all of which would become
dose. For carbon monoxide, the LCLo dose (lowest published lethal concentra-
tion) is 4000 ppm for 30 minutes (Fairchild 1977), which is about 2.6 g of
breathed CO. Based on NCHS statistics, at least 1,100 people per year are
exposed to CO at these levels, including exposure resulting from motor vehicle
exhaust. Consideration of odor thresholds (Dravniaks 1976) also suggests
that inhalation dose from volatile chemicals often reaches levels of grams
per person. Skin contact dose is generally smaller, usually milligrams per
person or less. Even though carbon tetrachloride has a mean oral lethal dose
of 5 to 10 g, it is not associated with acute contact lethality. However,
for aniline (mean lethal oral dose 15 to 30 g (Gleason 1969)) there have been
many deaths due to skin contact: canvas shoes (Miner 1919), laundry markers
and oral dose (Greenberg 1964). Iodine has caused contact poisoning death
when more than one third of a person's body was painted with it (Gleason 1969).
Method and Rationale
Clearly one should be able to estimate the amount chemical dose result-
ing from exposure to consumer products by considering the form of the products,
the characteristics of the chemicals they contain and the way they are used.
28
-------
Products like polishes, waxes and paints, which involve skin contact with
liquids, obviously represent a greater potential for dose than do chemicals
immobilized in, say, appliance coatings or building materials. Similarly,
volatile materials used indoors constitute a greater potential for inhalation
dose than they would if they were used outside. Products may also involve
oral contact (silverware, utensil finishes, pottery finishes, etc.).
Because of the variety of routes and exposure patterns that are involved
in the use of consumer products—any one of which may be dominant in a given
case—many variables would be required to characterize consumer dose at an
engineering level of description. Some exposure evaluation schemes (TSCA
1978, Stalder 1979) have sidestepped the details of an engineering evaluation
by scoring various component variables (duration of contact, degree of con-
tact, volatility of component, etc.) and computing an overall score roughly
representative of dose. These measures reflected only a "low resolution"
estimate of dose, and are difficult to factor into a quantitative risk assess-
ment. A recent exposure evaluation equation (Becker 1978, 1979) had more of
an engineering orientation, but it did not contain sufficient variables (some
were scored) and it could not be used to compute disposal masses or material
balance. In an effort to address these needs (more accurate dose levels,
disposal mass estimate and material balance) an engineering approach using
some 34 variables, was chosen to predict consumer exposure. Of the 34 var-
iables, about 20 characterize products and the ways they are used. Estimated
values of these variables are cataloged on Table 5 for major classes of
products. Twelve of the other 14 variables are obtained from the results of
estimation of Physical-Chemical Parameters and Use Classes and 2 are obtained
from estimation of production.
Parameters
All of the variables used to estimate consumer exposure are listed in
Table 6. Of those variables, the ones relating to chemical-physical-use in-
clude: C, D, Dens, F, FNC, MW, Pi, Pv, Sol, Tres, U and Use. Of these, C,
Dens, FNC, MW, Pi, Pv, U and Use are discussed in depth in Sections 5 and 6 of
this report. D, the diffusivity, expresses the ability of the chemical, C,
to escape from the product, as compared to its escape from the pure chemical.
For example, a volatile pigment would volatilize in a given amount of time,
as a pure substance. However, when combined with a textile, it may volatil-
ize more slowly—or not at all—depending on the strength of its bond to the
textile. D equal zero corresponds to no release, and D equal 1 corresponds
to volatilization equal to that of the pure chemical.
The parameter F represents the fraction of products in a use class that
contain a given chemical function category, FNC, e.g. what fraction of
clothing contains flame retardant? The parameter Tres represents the time
for which C would be stable in the air following volatilization. Values of
Tres less than 1 hour are significant. If Tres is greater than 1 hour, the
effective residence time is limited by ventilation rates. The marketing
parameters used include f and Ship.
29
-------
TABLE 5. CONSUMER USE CATEGORIES
110 •Structural Components
113 'Caulk « Speckle
115 Brick
116 Hood
117 Concrete
120 *Pa1nt - All
121 *Pa1nt Exterior and Materials
122 «Pa1nt Interior;
Kail pa per and Materials
124 Floor; Furniture and
Shoe Hax
130 Furniture
140 Plumbing * Suppl les
141 "Hater Softening and
Other Treatment
144 *San1t1zer - Cleaner
46 "Corrosion Treatment
150 Heating; Cooling
151 Oven Cleaners
160 Eating
172 •Metal Polish
173 •Deodorizer
175 Fire Extinguishers
200 Clothing (additives)
210 Fabric
220 Jewelry
233 •Cleaners; Detergents
Soaps; etc.
236 •Bleach
305 Dust Control Agents
311 'Fuel
312 Tires
313 *011 and Grease (car)
114 •Batteries
315 •Antifreeze
410 Hair Spray
420 «Soap
130 Body Powder - Cosmetics
440 Antlpersptrants
450 Cologne
160 Suntan Lotions
170 Beplllattrlei
MO •Agriculture and
Gardening Chemicals
630 «Bath and Swlmetng Chemicals
MO •Books and Printed Materials
570 Fireworks * Explosives
680 *Crafts
691 •Correction Fluid
100 «P*ckag1ng Ron-Food. Food
720 «Adhes1ves
WO -Propellents
900 •Consumer Plastic
901 •Consumer Rubber
110 'An1m al * Insect Repellents
Pa
0.15
0.15
0.02
O.OS
0.1
0.15
0.15
0.15
0.60
0.0.
0.1
0.4
0.50
0.15
0.05
0.1
1.0
0.15
0.30
0.1
0.0
0.0
0.0
1.0
0.5
0.05
1.0
0.0
0.0
1 0
0.20
0.3
1.0
1.0
1.0
0.3
0.2
0.2
0.03
0.001
0.0
0.05
0.1
0.1
0.0
1.0
1.0
0.0
0.0
0.1
pp
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
o.s
1.0
o.s
1.0
0.5
0.1
1.0
1.0
0.1
1.0
1.0
1.0
1.0
1.0
0.3
1.0
1.0
1.0
In
.u
0.20
1.0
0.0
1.0
1.0
1.0
0.0
0.0
0.20
0.5
1.0
0.1
1.0
0.1
1.0
1.0
1.0
1.0
1.0
0.0
Ta
(hr)
6.0
4.0
S.O
5.0
10.0
24.0
24.0
24.0
24.0
0.0
24.0
12
25
0.2
0.5
10
10'
12
20
2
0
0
0
100
0.1
so
0.0
10'
0.0
01
*i
0.1
10
so
8
S
10'
100
10
1
1
100
2
ICO
10
0
10
1
0
0
1
Tp
(hr)
10'
10'
10'
10'
10'
10*
10'
10'
10'
-
2
10'
10'
100
1
J.Sxld
10*
10'
-
10'
10'
Wt
10"
10"
10"
10"
10"
0
0
100
10'
2
0
10*
.
1
10"
10"
1
Vola
(=')
400
400
400
400
400
100
400
40
40
0
40
40
40
40
40
40
40
40
40
40
40
0
0
40
40
40
400
400
400
400
40
40
40
40
40
400
400
400
400
40
400
40
40
40
40
40
0
0
400
Volp
On')
400
400
400
400
400
100
400
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
400
400
400
400
40
40
40
40
40
0
0
400
400
40
400
40
40
40
40
40
40
40
400
Sa
O.OS
0.05
0.03
O.OS
0.05
0.05
0.02
0.02
0.05
0.0
0.03
0.01
0.02
O.OS
0.001
0.03
0.01
0.02
1.0
0.95
0
0
0
0.05
0.02
0.03
0.02
0.0
0.0
Oni
.ui
O.OI
0.3
0.30
0.31
0.2
0.2
0.2
0.2
0.2
0.02
0.001
0.3
0.15
0.10
0.0
O.OS
0.95
0.01
0.01
0.98
Sp
0.10
0.15
0.03
0.03
0.03
0.30
0.50
0.05
1.0
0.01
0.01
0.01
0.01
0.01
0.001
0.03
0.01
0.005
0.0
0.0
0.05
O.OS
0.01
1.0
0.0
1.0
0.98
0.5
0.05
0.05
0.05
0.05
0.02
0.02
0.2
0.2
0.0
0.0
0.7
0.90
0.001
0.3
0.05
0.0
0.1
0.0
0.0
0.05
0.3
0.0
Sbp
C.O
0.0
0.0
0.0
0.0
0.0
0.0
0.0
O.OS
0.0
0.0
0.0
0.95
0*0
0.0
0.98
0.0
0.99
0.0
0.05
O.OS
0.05
0.0
0.98
0.99
0.96
0.0
0.0
0.0
0.94
0.94
0.3
0.95
0.90
0.6
0.6
1.0
1.0
0.0
o.oa
1.0
0.0
0.80
0.90
0.0
0.95
O.OS
0.0
0.0
0.02
Da
(•rtn)
20
20
10
10
20
10'
10'
10'
7SO
0
10'
10'
100
in
1U
i
so
500
10
S
0
0
0
3 x 10'
1
100
0
0
0
1
3
10'
' 3000
[ 500
10'
10'
taio'
300
20
60
6x10'
1 5
6x10'
60
0
10
0.95
0.0
0.0
1.0
Op
5
5
5
S
10
10
10
10
100
10'
10'
10'
200
0
0
50
500
0
0
10'
10'
10'
10'
10'
2
10
60
100
0
0
0
1 0
. 0
10r
i 0
0
0
, 0
6x10*
0
0
0
0
10'
20
t
i 0
100
! 100
10
Ha
1
1
1
1
1
1
1
1
1
0
1
1
0
0
0
1
1
1
0
0
0
^05
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.2
l.w
0.1
1.0
1 1.0
1.0
0.0
1.0
0.2
: o.o
i 0.0
1.0
H.P
0.01
0.01
0.01
0.01
0.01
0.03
0.01
0.05
0.05
0.1
0.01
0.01
0.01
0.01
0.03
0.2
0.05
0.0
0.3
0.3
0.3
0.1
0.02
0.01
0.2
0.2
0.1
0.1
0.01
0.2
0.0
1 0.2
1.0
1.0
0.0
0.0
0.05
0.01
0.01
i
0.3
0.1
0.05
0.1
O.OS
0.2
1.0
1.0
0.0
Ymln
(mln)
10.0
S.O
10.0
S.O
10.0
1.0
1.0
1.0
0.2
S.O
2.0
2.0
0.1
0.0
1.0
2.0
0.05
3.0
O.OS
1.0
1.0
1.0
0.1
1.0
«.o
s.o
s.o
O.OS
0.02
0.01
0.01
O.OS
0.05
0.05
.
0.05
3.0
1.0
0.05
1.0
1.0
S.O
5.0
-
Ma
0.2
1.0
0.03
0.03
0.3
1.0
1.0
1.0
1.0
0.0
2.0
2.0
1.0
1.0
1.0
0.01
1.0
1.0
1.0
0.0
0.0
0.0
1.0
1.0
1.0
1.0
0.0
0.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.3
1.0
0.1
0.1
1.0
1.0
0.0
o.s
1.0
0.0
0.0
1.0
»
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.02
0.01
0.01
1.0
1.0
1.0
0.01
1.0
1.0
1.0
0.05
O.OS
0.01
1.0
1.0
1.0
1.0
0.5
1.0
1.0
1.0
0.0
1.0
1.0
1.0
0.0
0.0
0.1
1.0
0.1
1.0
1.0
0.0
0.1
0.1
1.0
0.01
0.3
0.0
Aa
{If}
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.2
0.2
0.0
0.2
0.1
0.02
0.02
0.01
O.I
0.1
0.1
0.2
1.0
0.0
0.0
0.1
0.0
0.1
0.0
0.0
0.0
0.1
0.1
2.0
0.1
0.2
0.3
0.6
0.3
0.1
0.1
0.0
0.1
0.1
O.I
0.0
0.1
0.2
0.1
0.1
0.2
Ap
{"')
0.1
0.1
0.1
0.1
0.1
0.1
0.01
0.1
0.1
0.2
0.1
0.2
1.0
0.0
0.0
0.1
0.1
0.1
0.2
1.0
1.0
0.05
2.0
0.0
0.1
O.I
0.1
0.1
0.0
0.0
2.0
0.0
0.0
0.0
0.0
0.0
0.1
2.0
0.1
I
0.0
0.1
0.1
0.1
0.1
0.2
0.1
0.1
0.2
30
-------
TABLES. VARIABLES USED TO ESTIMATE CONSUMER EXPOSURE
Symbol
Aa
Ap
C
Ca
Cp
D
Da
Dens
Dose a
Dose p
Dp
f
F
FNC
Fva
Fvp
La
Lp
Ma
Mp
W
Meaning
Body area in contact with
product during active phase
Body area in contact with
product during passive phase
Name of chemical
Effectiveness of skin contact with
chemical -active phase
Effectiveness of skin contact with
chemical -passive phase
Chemical Diffusivity
Contact duration with product per
year per person active phase
Chemical Density
Active phase chemical dose per ex-
posed person per year
Passive phase chemical dose per
exposed person per year
Contact duration with product per
year per person passive phase
Predicted market penetration by C
Fraction of product in a USE class
containing specific FNC
EPA chemical Function Category
Fraction of chemical in product
volatilized during active phase
Fraction of chemical remaining in pro-
duct volatilized during passive phase
Population loading active phase
Population loading passive phase
Fraction of remaining mass of C avail-
able to become dose - active phase
Fraction of remaining mass of C avail-
able to become dose - passive phase
Molecular weight of C
Units
M2
M2
--
-(0-1)
-(0-1)
-(0-1)
minutes
g/cc
mg/(person-yr)
mg/(person-yr)
minutes
-(0-1)
-(0-1)
—
-(0-1)
-(0-1)
-(0-1)
-(0-1)
-(0-1)
-(0-1)
AMU
Source of
Evaluation
Table 5
Table 5
PMN
Page 34
Page 34
Section 6
Table 5
Section 6
Page 35
Page 35
Table 5
Section b
Section 6
Section 6
Page 36
Page 36
Table 5
Table 5
Table 5
Table 5
Section 6
31
-------
TABLES, (cont.)
Symbol
Pa
Pi
Pop(a)
Pop(p)
Pp
Pv
Sa
Sbp
Ship
Sol
Sp
Ta
Tp
Trel
Tres
U
Use
Vola
Volp
Y
Meaning .
Fraction of total population using pro-
ducts in a use class - active phase
Partition coefficient of C
Population exposed to C, active phase,
due to a specific use
Population exposed to C, passive phase,
due to a specific use
Fraction of total population using pro-
ducts in a use class - passive phase
Vapor pressure
Fraction of C in product undergoing
non-volatile release - active phase
Fraction of C in product undergoing non-
volatile release - passive bypass phase
Total Shipments in one FNC category
Solubility of C in water
Fraction of C remaining in product non-
volatile release - passive phase
Average lifetime of pro-
duct - active phase
Average lifetime of pro-
duct - passive phase
Time for 50% of C to be volatilized from
product
Residence time for C in respirable air
Fraction of C used in a specific USE
class
Use category
Dilution volume - active phase
Dilution volume - passive phase
Thickness of the chemical layer in the
product
Units
-(0-1)
--
people
people
-(0-1)
mm of Hg
-(0-1)
-(0-1)
kg
mass fraction
-(o-i)
-(0-1)
sec
sec
sec
sec
-(0-1)
--
m3
m3
mm
Source of
Evaluation
Table 5
Section 6
Page 35
Page 35
Page 35
Section 6
Table 5
Table 5
Table A-3
Section 6
Table 5
Table 5
Table 5
Page 33
Section 6
Section 6
Section 6
Table 5
Table 5
Table 5
32
-------
The market penetration parameter, f, is generated as discussed in Sec-
tion 5 and equals the fraction of a given FNC market that C would be expected
to capture. Ship equals the total shipments in an FNC market, so that f ship
equals the projected shipments for a new chemical due to use in one FNC
market.
;; ' 1 '
The parameters of product use listed on Table 6 include Aa, Ap, Ca, Cp,
Da, Dp, La, Lp, Ma, Mp, Pa, Pp, Sa, Sp, Sbp, Ta, Tp, Vola, Volp, and Y.
The "population active" parameter, Pa, has a range of from 0 to 1 and
equals the fraction of the total population that is involved with the "active
phase" use of a product. The "active phase" term is used to distinguish the
different ways in which the chemicals in a product may be encountered. For
example, a house paint gives dose to the painter (active phase) and to the
people who later live with the painted materials (passive). Similarly, floor
polishes, furniture polishes, paint strippers, detergents, soaps, bleaches,
and many other classes of consumer products result in "active phase" and
"passive phase" exposure, each involving separate parameters. The population
active refers to those persons exposed during the active phase. The passive
population (0-1) refers to the population exposed during the passive phase.
The "population loading factors" (0-1) refer to the probability that a
person is present during the relevant phase of exposure. So, for painting,
the loading factor for the active phase is 1, since someone must be present
to do the painting. However, the loading factor for the passive phase is
estimated to be only about 0.05, indicating that, taking into account all the
different kinds of painting that are done; a person is in the presence of a
specific painted surface only about 5% of the time. The population loading
factor is significant in that it should be roughly proportional to population
dose—i.e. the population gets more dose if it has greater exposure.
The "material thickness" parameter, Y, equals the thickness (mm) of the
material in which the chemical is embedded. In the case of a paint, the
thickness is about 1 mm. Some fabric finishes have thickness of only 0.1 mm.
Structural materials (housebrick, tile, etc.) have larger characteristic dim-
ensions. The thickness parameter contributes to the estimate of how long it
takes for volatiles to escape from the material.
*:&
The "contact" parameter characterizes the degree of contact between the
product and the skin. This parameter is assigned in accord with the follow-
ing examples:
-------
Contact Description
1 pure substance (liquid):
ammonia, alcohol
% comp substance in a matrix that
does not inhibit escape:
swimming pool chemicals,
paint, polish and soap
% comp D substances in a retentive
matrix: clothing, handles,
books, appliances, decora-
tions
The "duration" parameters (min), Da and Dp are a measure of the amount
of time that contact is maintained between the amount of the product that a
person would buy in one year (active and passive phases) and the skin, during
the lifetime of the product. Note that the lifetime of the product may be
longer than 1 year.
Duration (min) Product Classes
3 x 10s Clothing
1 x 10" Soap
3600 Magazine Covers
300 Furniture Wax
100 Propel 1 ants
1 Fuels, Heating
System Chemicals
The "area" parameters (Aa and Ap) equal the skin area of a person that
is generally involved with exposure to the chemical. For a swimming pool
chemical, or for a chemical used in clothing, all of the person's area would
be in contact with the product. Items like paints, polishes and books involve
only smaller values. The total skin area is assumed to be 2.0 m3.
The "material" parameters (0-1) (Ma and Mp) equal that fraction of the
chemical available to become contact dose at some time during the product
lifetime. For example, in painting, virtually all of the paint is available
for dose during active painting, whereas, in plastic, some of the material
is never available for dose. In general, liquids and gases have high "mater-
ial" availability values, and solids have lower values.
The "mass lost" parameters (0-1) are used to account for the fraction
of bulk mass of the material of a product that is present at the beginning
of each phase (active-Sa, passive-Sp, passive-bypass-Sbp) but lost by the
end of that phase due to non-volatile processes (spilling, abrasion, etc.).
The passive bypass phase involves a disposal of material following active
use - such as the disposal of polishing agents, laundering agents and clean-
ing agents. The idea is that during each activity, such as painting, some
of the mass of the material is lost, and that by keeping track of where it
is lost, one can also keep track of where the chemicals it contains are
34
-------
lost—a materials balance approach to consumer exposure. For painting, the
mass lost parameter for the active phase is estimated to equal 0.05, meaning
that about 5% of paint is released"during the active phase. Similarly, the
mass lost parameter for the passive bypass phase for furniture polish is
estimated to be about 0.95. The non-volatile dose in the active phase is in-
cluded in Sa. The volatile dose is separate.
The residence time parameter Tres, (seconds) equals the time that 50% of
the volatilized chemical would survive in the air and be available for in-
halation dose. Direct consumer inhalation dose is most significant for ex-
posure within houses and enclosures where the concentration of the chemical
is confined. Under those circumstances, the concentration is limited by
several processes: ventilation, surface adsorption and chemical reaction.
The work of Young et al 1978 suggests that the ventilation limited value for
residence time is about 1 hour. In the absence of additional data, this
value will be assumed to apply.
The "exposure time" parameters (Ta, Tp) (hours) characterize the amount
of time that the product obtained in one year lasts to give inhalation dose in
the active and passive phases. So, for example, if the active phase of
painting lasts for about 8 hours (active phase exposure time), but if some
volatile components are not completely volatilized for 100 hours, (Trel = 100
hours) the dose during the 8 hour period is characterized by the released
material (about 8/100 of the total volatilized). Alternatively, if all the
material is volatilized during the active period, then none remains to lead
to dose during, the passive period.
The "dilution volume" parameters (Vola and Volp) equal the average volume
into which the volatile material may be expected to diffuse. For uses typi-
cally indoors,' the dilution volume was chosen to be 40 cubic meters. For
outdoor exposure the volume is essentially unlimited by barriers, and the de-
gree of chemical concentration in the air is heavily dependent on the wind
conditions. To simulate the diffusion limitations under still air conditions,
the value of the dilution volume for outdoor exposure was chosen equal to 400
cubic meters.
The variables calculated from these parameters include: Dose (a), Dose
(p), Fva, Fvp, Pop (a), Pop (p) and Trel.
As indicated earlier, Trel is the amount of time it takes for C to vola-
tilize from a product. (If C is non-volatile, Trel is infinite.) Fva is the
fraction of C that volatilizes in the active phase. In a simple case, if the
active phase lasts 8 hours, and Trel is 200^hours, then Fva would be at most
0.04 (subject to competition from other routes). Fvp is defined similarly,
as the fraction of C volatilizing during the passive phase.
Pop (a) and Pop (p) are the populations (persons) expected to receive a
dose of C during the active and passive phases respectively. So, for example,
if a new flame retardant were to come on the market an I be expt.cted to cap-
ture 10% of it, the exposed passive population would be about 6 x 106 people,
i.e. (3 x 108 people using clothes) (20% of clothes contain flame retardant)
(0.1 market fraction).
35
-------
Dose (a) and Dose (p) are the average dose for C received by the active
and passive populations, respectively. So, if 1 million people are exposed
to some C and collectively internalize 100 kg of it, the average dose is 100
mg.
Calculation of Dose Per Person, Exposed Population, Release and Disposal Mass
The equations for dose per person are:
Dose
(a)
_ (Fva +
Max (1,
Min ..
0.01
Fva' +
0.99
Sa)
Sa)
106
S,
Tres *
3600 Vola
i La Ship
La
Pa-
Ship
3xl02
Max (1, Fva + Sa)
Aa Da Ca/boic MW •
(Fvp + 0.01 Sp)
" Max (1, Fvp + Sp)
Tres
(1)
3600 Volp/
0.99 Sp 106 Lp Ship Max (0,l-(Fva + Sa)(l-Sbp)
Max (1, Fvp + Sp) Pp-3xl08
. 1()(4-0.6|log (Pi) |)1
Lp Ship Max [0,l-(Fva + Sa)1 (1-Sbp)
+ Min
Ap Dp Cp/Solc MVI • io^-u-Dl'°9 iri;m (2)
J
There are two equations for dose because, for many products, dose may
result from different kinds of use. For example, a housepainter receives dose
while painting a wall, Dose (a), while the people who live there will receive
dose for many years thereafter, Dose (p), by virtue of chemicals that slowly
escape from the surface.
The equations for the size of the exposed populations are:
Pop (a) = Pa • f • F • 3 x 108 (3)
Pop (p) = Pp • f • F • 3 x 108
Again, there are two exposed populations— as above, the number of people
who paint, and the number of people who live near painted surfaces.
The equations for the disposal mass and the volatile and non-volatile
release are:
Rv - ShiD-f-F [ .FVa * Fvp (1-Sbp) Max [0,l-(Fva+Sa)]1 (5)
Rv - bmp T h|Max (i, Fva+Sa) Max (1, Fvp + Spj J
cu- * r- F Sa ^ Sp (1-Sbp) Max (0,l-(Fva+Sa)) 1
Rnv = Ship-f-F i Max (1> Fva+Sa) + Max^fl, Fvp + Sp) J
Disp = Ship'f-F [Sbp + (1-Sbp) (Max (0,1-Fvp + Sp)}
- Max (0,l-[Fva + Sa])] (7)
36
-------
where Fva = Win (Ta, Tre1)/Trel
FVp = Min (Tp, Trel)/Trel
Trel -
D Pv (jijnHg) m (AMU)
As an example of the use of these equations, consider the TRIS used in
rugs.
From Section 6 we obtain:
D = (0.0 to 0.025), Dens = 2.24, F = 0.8, FNC = Flame Retardant,
MW = 297, log Pi = 7.5, pv = 10~5 mm,
Sol = 10"3 Tres _< 1, U = 0.9, use = Rugs
From Section 5 we obtain:
f = 0.03, Ship = 1.6 x 108
Since the use category, "rugs" is not explicitly present on Table 6
(which will often be the case) the following values were obtained by rule of
thumb extrapolation from the table (X means not needed).
Aa = x; Ap = 0.1, Ca = X, Cp = 0.1, Da = X,
Dp = 5000, La = X, Lp = 0.1, Ma = X, Mp=10"3,
Pa = X, Pp = 0.9, Sa = X, Sbp = 0.05, Sp = 0.05,
Ta = X, Tp=3.6xl08, Vola = X, Volp = 40
This set of assumptions leads to the following results:
Trel = 8.8 x 106 Y/(D Pv MW) >'
Fva - Min (Ta, Trel) _ x
hva ' Trel " *
c.,« Min (Tp, Trel) . 3.6 x 1Q8 _ n «
FVP = - - L< ar * 9-
5>8x 10a
Pop (a) = Pa-f-F-3 x 108 = X
Pop (p) = Pp-f-F.3 x 108 = (0.9)(0.03)(0.8)(3 x 108) = 6.4 x 106
Dose (a) = X
37
-------
Dose M -106C(0.06)-+ (0.01)(0.05) 3600 (O.l) ' (1.6 x 108)
VM; Max (1, 0.06 + 0.05) 360Q 40 (0.9) (3 x 10s)
Max (0,1-[0.06 + 0.05])(1-0.05) +
M. r (Q.99) 106 (0.05)(0.2)(1 6 x 1Q8) Max (O.WO 06 + O.O
Max (1, 0.06 + 0.05)(0.9)(3 x lOe)
1
(0.1)(5 x 103)(0.1)V10-3«297~. i0(4-°-6l7-5l)
Dose fp) = 7.5 + 8.0 * 16 jng
Rv = (1.6 x 108)(0.03)(0.9)[0 + ^Pl (1 - 0.05)(1)J* 2.2 x 10s kg
Rnv = (1.6xl08)(0.03)(0.9)[0 + Max (0'1)] ~ 2'° x IQ* kg
Disposal = (1.6 x 108)(0.03)(0.9)[(0.05) + (0.95)(Max 0, 0.89)]Max (0,1)
= 3.8 x 106 kg
Discussion of Example—
Although the vapor pressure of TRIS is very low, rugs have such a long
lifetime in the home that it is conceivable that some appreciable fraction of
it could vaporize. Because it takes about 40 machine launderings to remove
most TRIS from pajamas, the bond between TRIS and fiber must be fairly strong
—leading to the estimate that the diffusivity lies in the range between 0
and 0.025. If the diffusivity were as high as 1, the expected Trel would have
been 2.9 x 108, so that most of it would have been volatilized during its
lifetime in spite of the low vapor pressure. However, using the upper bound
value for D of 0.025 leads to a prediction that only 6% is volatilized. The
prediction that market penetration would be 3% and that 90% of that would be
used on rugs leads to the estimate that 4.3 x 106 kg would be used on rugs each year
and that 6-4 million people would be exposed to it. Since the TRIS would be
professionally applied to the carpet, there would be no active phase consumer
dose. The dose equation predicts a per person dose of about 0.16 mg. The
volatile release is about 2.2 x 10s kg, non- volatile release is 2.0 x 10s kg
and the amount of Tris destined for disposal is 3.8 x 106 kg. The 16 mg would
be taken up over a period of perhaps 20 years, for a rate of about 0.8 mg per
year. Because of the uncertainties involved, this estimate may be in error
by several orders of magnitude. However, it does focus attention on the
critical parameters and indicates the problable dose range.
Engineering Details
Conceptually, analysis begins with the active phase dose. During the
active phase, a volatile chemical may become dose (or release) by either a
volatile or a non-volatile route (contact). The procedure used to account
for this competition of routes is to calculate "rates" for each one separately,
as if each route had sole access to all of the chemical, and then to appor-
tion chemical to each route based on the calculated rates. The first step
is to calculate the release volatile time. This is done by using the equa-
ti on : .
38
-------
(sec ) = 4-4 x 1Q6. Y D
lsec'; Pv MW (10)
where D = diffusivity (0-1)
Y = thickness of the material layer (mm)
Pv = the vapor pressure of the chemical (mm Hg)
MW = the molecular weight of the chemical (AMU)
The derivation for this equation is given in the Appendix, and is based on the
following argument. In a static system, the vapor released by the volatili-
zing material is in equilibrium with the material condensing out of the air.
In that circumstance, the rate of re-entry of material (which equals the out-
flow) can be calculated in terms of the vapor pressure. Then, under non-
equilibrium conditions, the rate of volatilization can be calculated by using
this rate in a solution of the one-dimensional diffusion equation.
After the release volatilization time has been calculated, the initial
estimate for the fraction of the chemical that undergoes volatile release in
the active phase can be calculated via the equation:
Fva = (Min [Ta, Trel]/Trel)
This estimate will be good unless competition with non-volatile release
is severe. The corresponding estimate for the fraction of non-volatile chem-
ical release during the active phase is Sa, a scored parameter. So, taking
the competition into account, the revised estimates are:
Sa)
Sa
Max (1, Fva + Sa)
The volatilized material that results in direct inhalation dose during
the active phase is then given (rag) by:
Inhalation Dose Active Direct = 106 Fva' Tres La Ship (13)
3600 Vola Pa. 3x10°
The basis for this equation is the following. Suppose that a vapor is
released into a closed room. Suppose that the vapor will remain in the room
for only one hour, and that after that it will either be swept out, be ven-
tilated or it will chemically decompose. Suppose that a person is in that
room and that during the one hour that the chemical is there, he will breathe
1 cubic meter of air (Handy 1974). Then, the amount of vapor that he will
breathe during the 1 hour ts: - ' •' •
Vapor breathed = (Vapor present) (1 cubic meter/ room volume)
39
-------
The loading factor should also be present in equation because the vola-
tile material leads to dose only when a person is present. Actually, for
total dose, it makes no difference over what time schedule the volatile is
released. No matter what rate it is released at, on the average, any concen-
tration will persist for 1 hour and will be subject to the same probability
of being inhaled. If, however, the release time is longer than the product
lifetime, then the volatile will exit via the disposal stream. This will
occur for some highly volatile materials with short use times (cleaning
fluids) and for many low volatility materials present in products of inter-
mediate use times (flame retardants in clothes). Note that all inhaled ma-
terial is treated as dose. A less conservative model would also account for
material exhaled.
Similarly, using Sa1 the amount of non-volatile chemical released in the
active phase may be calculated as:
Non-Volatile Active Phase = Sa1 La Ship f F
availability of C
Some of this material results in contact dose, some in aerosol inhalation
and the rest in release. The aerosol inhalation dose could, in principle, be
calculated by the methods presented above. However, the results would depend
strongly on the particle size distribution and morphology. In special cases
(e.g. asbestos) this data may be available to allow the effective residence
time to be calculated. In the absence of additional data, 1% of the avail-
able non-volatiles are added to the volatilized fraction of chemical leading
to inhalation dose, to account for the aerosols. The 1% figure is intended
to account for the settling time of heavier particles. With this addition,
the active inhalation dose per exposed person becomes:
106 (Fva1 + 0.01 Sa1) La Ship Tres/ (3600 Vola Pa 3xl08(14)
Then, the contact dose is given by:
Contact-Dose-Active-Direct = Aa Da Ca 10(4'°'6lL°s(Pl)' VsolcMWc (15)
for Dose « Ma
The derivation for the contact dose active direct equation is given in
the Appendix, and it is based on the following arguments. The standard equa-
tion for diffusion from a region of high concentration, through a membrane,
to a region of negligible concentration is:
Permeability = mass/(area time concentration)
when the flow is controlled by Pick's law. More detailed discussion of pore
size phenomena and other mechanisms are discussed in Section 6. Under these
conditions, the permeability is a constant for a given, membrane and a given
chemical. That is, the ratio of the amount of mass diffusing through the
40
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membrane in a given period of time to the product of the area of the membrane
with the time period and the external concentration of the chemical is a con-
stant. Treherne (1956) (among others) determined permeability constants for various
chemicals and related them to the corresponding partition coefficients. Other
workers have related them to molecular weight and water solubility as well.
Using these relations, one can estimate the permeability of skin for a given
chemical. Then, one must express the chemical concentration in terms of
product parameters. For products of high diffusivity, estimation is more
difficult. If the surface material is removed as dose, additional material
may not diffuse out from the interior. In that case, the surface concentra-
tion falls to a low value and dose delivery stops. To account for that case,
the restriction is imposed that:
Dose Mass < Ma Mass
in other words, that the dose is less than the mass available to become dose
(the dose may approach Ma Mass as an upper limit).
Next, subtract the amount of material lost during the active phase and
calculate the material lost during passive-bypass by using the equation:
Passive-Bypass Material * Sbp (Mass Remaining) (16)
Then subtract the material lost due to passive-bypass; the calculations
are essentially repeated for the passive phase. Using equation (11) the
volatiles released during the passive phase are calculated via:
Release Vol Passive = (Mass Remaining) M1n ^^Tre1^ (17)
and the associated doses are:
Inhalation Dose Passive Direct = 106 (Fvp1 + 0.01 Sp1) La 3500^01 p
Ship Max (0.1-[Fva + Sa])(l-Sbp) (18)
Pp .3x10°
Contact Dose M,n 0.99 10s Sp' Ma Lp Ship (Max [0.1-(Fva + Sa)])(l-Sbp)
Passive Direct " mn Pp .3xlOd
,(4-0.6|log(P1)|)
Ap Dp Cp /Sole MWC 10
Then, the mass remaining is added to the total for disposal.
Finally, the dose distribution is calculated for cases where several
overlapping populations are exposed to the same chemical by the use of several
different products. To do this, it is assumed that the use of each product
type is independent (i.e. that use of one product type does not affect the
probability of also using another product type—for example, using housepaint
does not affect the probability of also using dog repellent). Other assump-
tions could be used where warranted. The calculation proceeds by identifying
the various distinct subpopulations (i.e. how may people use Jl and J2). Each
such population is estimated via:
41
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Population fraction (Jl and J2) = (Pjl)(Pj2) (20)
That is, the probability of using Jl and J2 equals the product of the frac-
tion of the people using each one alone. The dose that this population gets
equals the sum of the doses from Jl and J2. This procedure must be repeated
for each of the possible subpopulations, which increase in number as 2 to the
Nth power, where N is the number of separate contributing product classes.
COMPUTER METHODS
The procedures for exposure calculation defined in this report can be
efficiently implemented as an interactive computer program. Some of the data
would be entered at an interactive terminal while the rest of it would be
read from data files. Because much of the data is merely to be copied from
tables, use of a program would greatly speed up the data transfer process, and
reduce the possibility of errors. Naturally, once the steps have been com-
pleted, the computation steps could also be done by the computer program.
Because the final task of this project was to evaluate a significant
number of commercial chemicals for exposure "as if they were new chemicals,"
a computer program having many of the characteristics listed above was
written to facilitate the process. This program, called "EXPOSE," is a pro-
totype program, in that it lacks the efficiency and convenience a polished
program; nevertheless, it does query the user for the data that
it requires and it does do all of the calculations required. The program,
which is in the computer language BASIC, was run on a POP 11/34 computer
running under the operating system RSX11M.
LIMITATIONS
The consumer exposure model was designed to serve as a rough screen pre-
dictor of probable consumer chemical dose obtained from the use of products
containing new chemicals. Via a combination of estimation and computation
procedures, it yields predictions of the desired parameters in a uniform and
documentable manner for all chemicals. However, additional development work
would be desirable to refine a number of features in the model to reduce
uncertainty in the predictions. The highest priority features for refinement
are: chemical diffusivity within a product, size and mass distributions of
typical aerosols, rules for prediction of capture efficiency by the lungs,
direct dose that results from unusual circumstances (fire, accidental inges-
tion, etc.) and estimated values of product use parameters. If these limita-
tions are overcome, the model may contribute to dose evaluation analysis at a
very refined level.
42
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REFERENCES
*'* •
1. Astrand, I., Gamberale, F., Effects on Humans of Solvents in the Inspir-
atory Air: A Method for Estimation of Uptake. Env. Research 15:1-4,
April 1978.
2. Becker, D.S., Design of a Chemical Hazard Ranking System, Final Report,
Consumer Product Safety Commission Contract No. CPSC-C-77-0068, December
27, 1978, also: IITRI Report Project C6408.
3. Becker, D.S., Algorithmic Ranking of Consumer Chemicals by Potential
Health Hazard. 1979 Conference on Disposal and Risk Assessment, Florida,
1979.
4. Breuer, M.M., The Interaction Between Surfactants and Keratinous Tissues.
J. Soc Cosmet Chem, 30:41-64, January 1979.
5. Dravniaks, A., Correlation of Odor Intensities and Vapor Pressure with
Structural Properties of Odorants, IIT Research Institute Report 1976.
6. Fairchild, E.J., Lewis, R.J.,. Tatken, R..L., Registry of Toxic Effects of
Chemical Substances, DHEW No. 78-1Q.4-B, September 1977.
7. Faucher, J.A., Goddard, k.D., Interaction of Keratinous Substrates with
Sodium Laurel Sulfate: 1. Sorption, 2. Permeation, J Soc Cosmet Chem,
29:323-352, May 1978.
8. Gleason, M.N., Gosselin, R.E., Hodge, H.C., Smith, R.P., Clinical Toxi-
cology of Commercial Products, The Williams and Wilkins Company 1969.
9. Greenberg, H.B., Syncope and Shock Due to Methemoglobinemia, Arch Envirn
Health, 9:762-764, 1964.
10. Handy, R., Schindler, A., Estimation of Permissable Concentrations of
Pollutants for Continuous Exposure EPA-600/2-76-155, June 1976.
11. Idson, B., Biophysical Factors in Skin Penetration, J Soc Cosmet Chem,
22:615-634, 1971. . .,,•
12. Interagency TSCA Committee, Initial Report of the TSCA Interagency Test-
ing Committee to the Administrator, Environmental Protection Agnecy, EPA
560-10-78/001, January 1978.
43
-------
13. Jellinek, S.D., Chemical Use List, Federal Register 43(143):3222-32251,
Tuesday July 25, 1978.
14. Jellinek, S.D., Toxic Substances Control - Premanufacture Notification
Requirements and Review Procedures, Federal Register 44(7):2242-2348
Wednesday January 10, 1979.
15. Leidel, N.A., Busch, K.A., Lynch, J.R., Occupational Exposure Sampling
Strategy Manual, U.S. HEW, NIOSH DHEW No. 77-173, January 1977.
16. Miner, C.S., Methemoglobinemia Due to Poisoning by Shoe Dyes, J. Amer
Med Assn, 72:593 1919.
17. Noble, P., Kline Guide to the Chemical Industry, Charles H. Kline and
Company, Inc. 1974.
18. Oettingen, W.F. von, The Aromatic Amino and Nitro Compounds, Their Tox-
icity and Potential Dangers, U.S. Public Health Service Bulletin No. 271
1941.
19. Patty, F.A., Industrial Hygiene and Toxicology, Interscience Publishing
Company, Inc., New York, 1973.
20. Peterson, R., Carcinogens in the Environment - Reprinted from the 6th
Annual Report of the Council on Environmental Quality. U.S. Super Doc
041-011-0030-1, 1975.
21. Ramachandra, G. et. al., The Green Hair Problem: A Preliminary Investi-
gation, J Soc Cosmet Chem, 30:1-8 January 1979.
22. Reiss, F., Percutaneous Absorption, a Critical and Historical Review,
Amer J Med Sci, 252:588, 1966.
23. Shippee, F., Personal Communication, April 1979.
24. Stalder, E., Chemical Use Scoring Data, Personal Communication, March 1979.
25. Suzuki, M., Asaba, K., Komatsu, H., Mochizuka, M.; Autoradiographic
Study on Percutaneous Absorption of Several Oils Useful for Cosmetics,
J Soc Cosmet Chem, 29:2.65^282, May 1978.
, v-
26. Suzuki, F. et. al., Application of Lower Titanium Oxides in Cosmetics,
J Soc Cosmet Chem, 29:59-64, 1978.
27. Treherne, J.E., The Permeability of Skin to Some Non-Electrolytes, J^
Physio!, 133:171-180, 1956.
28. Young, R., Rinsky, R.A., Infante, P.F., Benzene in Consumer Products,
Science, 199:248, 1978.
44
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SECTION 5
METHODS OF PREDICTING PRODUCTION VOLUME
The Premanufacture Notice (PMN) forms as proposed in the Federal Register
January 10, 1979 required the applicant to state the anticipated production
volume for the first year and the predicted volume of the third and fifth
year. Modifications and simplification of these forms may result from the
hearings and it would be desirable for the OTS to have a technique to inde-
pendly predict the production growth rate of the new chemical.
Estimation of the exposure during manufacturing and during consumer use
is based upon production volume and this becomes an important basic parameter
for exposure assessment.
A system to predict production yolume has been developed. The system
utilizes the function and use categories for consumer products along with data
as to the total production and number of competitors.
OBJECTIVE AND SCOPE
The objective of this task was to develop a procedure and a supporting
data base to estimate the, market share which a new chemical has the potential
of capturing. The production volume is thus estimated for the first, third,
and fifth years following market introduction. This can then be applied to
estimated values of production volume as listed in Table A-l, to obtain mar-
ket share by volume for first, third, and fifth year penetration. (A list of
references used for many of the production volume estimates is presented at
the end of Table A-l.) The chemical industry, according to U.S. Industrial
Outlook and other sources, appears to experience annual volume growth ranging
from 3-10%, depending on the particular chemical function category. In sum-
mary, the market share estimates which will result from the procedure are
multiplied by the appropriate annual production volume figures and by an over-
all growth estimate of 3-10% (based on the judgement of the evaluator) to
obtain one, three, and five year estimates of production volume for a new
chemi cal.
It must be recognized at the outset that this procedure is intended as a
preliminary, gross screening mechanism, and is in no way intended to repre-
sent a definitive or highly precise means of modeling the chemical market-
place or in predicting market share. The limits of this procedure are
characterized in a later section in order for the user or other interested
parties to understand the degree to which it represents a tentative means of
45
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estimating potential market share and production volume for new chemical pro-
ducts. Determination of market share for industrial market research purposes
is a difficult task and typically requires a considerable level of effort in
time and dollars to confidently and reliably analyze a market.
The procedure presented here identifies many of the key determining fac-
tors for a new product's market share estimation, and represents a means for
estimating within an order of magnitude the likely market share, hence the
production demand, for the new 'chemical. The procedure for estimating market
share of a new chemical in specific chemical categories (i.e., markets) and
the base of data needed to apply this procedure are discussed below.
PROCEDURE
The procedure for estimation of production volume is dependent upon the
identification of appropriate chemical function categories as predicted on the
basis of structure and/or information in the PMN forms. The procedure is
applied to each identified function category in order to develop a list of
the appropriate categories and corresponding market share estimates for each,
for the first, third, and fifth years following introduction. Market share
estimates are based on factors specific to each chemical category and on fac-
tors specific to each firm planning to introduce a new chemical. As a result
market share estimates, and hence production demand estimates, cannot be
stated explicitly for each category without some information about the firm
itself in relation to the expected competition. These issues are discussed
in the paragraphs which follow.
Five Year Market Share Estimation
The procedure .begins with an estimate of the market share for the fifth
year following introduction, rather than the first or. third years. This is
done since the fifth year value more nearly represents the total potential
of a product in relation to its applications under "equilibrium" competitive
market conditions. Following estimation of the fifth year potential share^
the first and.third year shares can be estimated based on reasonable assump-
tions about the market share growth for a new product.
We have developed a parametric approach for estimating new chemical mar-
ket share (five years) which is based on a minimum of key variables which are
(1) characteristic of the chemical category or (2) characteristic of the firm.
The general relation and a description of the variables in provided below:
16 5nc ' abc "Sbv
where MSg = fifth year market share estimate for a new chemical
MSbv = "base value" estimate of market share for a new chemical
46
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• The base value essentially represents a nominal, imaginary estimate
which is an inverse function of the number of.competitors in a given
chemical cateogry identified for a new chemical. For ex-
ample, if there are 25 firms competing in a category, then a start-
ing point (i.e. base value) for estimating market share for the new
chemical would be 100% i 25 = 4% (0.04) market share for each firm.
This represents an initial inference of no concentration of business,
which is adjusted by assignment of a value to factor 'a' defined
below.
• Data concerning the total number of competitors, needed for defining
MSbv, is described in the following section.
'a1 = Factor applied to MS. which takes into account whether the firm
proposing the new chemical is a large or small in relation to the
chemical industry as a whole.
*.
• This is determined by the evaluation based on a list of chemical
companies with sales of over 5 million dollars, available from
the Kline Guide to the Chemical Industry, 1977.
• If a firm is large it is expected to have the potential to compete
with the larger market share firms in the chemical category and
thus for the 80% of the business which 20% of the firms represent
in most industries (set a = 5).
• If a firm is small it is expected to have the potential to compete
at a level comparable to the smaller market share firms in the
chemical category and thus for 20% of the business which 80% of
the firms represent (set a = 1.25).
'b' = Factor applied to MSb which takes into account whether the firm
is currently competing in the chemical category or not, and thus
whether it has progressed along the learning curve, established
distribution channels, established reputation, etc. This factor
accounts for whether a new chemical would be able to capture its
full potential market in about five years, based on the "current
involvement (or not) of the firm in the chemical category. (Set
b = 1 if the firm is currently competing in the category, set b =
0.5 if it is not.) It is expected that this information would be
determined based on knowledge of the firm and its premanufacture
notice submittal. The values of 'b1 are intended to provide a
relative indication of the impact of the firm in penetrating the
market with a new chemical. It is understood that study of his-
torical data is needed to refine these estimates in order to de-
fine their absolute value.
'c' = Factor applied to MS. which takes into account whether the chem-
ical category is dynamic and rapidly changing (i.e., short product
life cycle) or not, in terms of new product acceptance and pro-
pensity for change. This factor also determines whether a new
47
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chemical could achieve its full market potential in five years).
Set c = 1 if the chemical category is "dynamic," set c = 0.5 if it
is not. This information has been estimated by IITRI for each
function category. (See Table A-2 column labeled "Function Type
'c1".) The values of 'c1 are intended to provide a relative in-
dication of the impact of the industry structure in penetrating! the
market with a new chemical. It is understood'that study of
historical data is needed to refine these estimates in order to
define their absolute value.
Determination of Number of Competitors in a Chemical Category In Order to
Identify for MSbv
Once a chemical category is identified Table A-2 is used to
determine the estimated number of competitors, NT, is the category. The base
value market share can then be selected from the table below. For example,
if it is determined that a new chemical is represented by category number
015, Algicides, then the range for NT is between 26 and 50. the value of MSh
is then selected from the table below as 0.030. Dv
TABLE 7. TOTAL NUMBER OF FIRMS COMPETING
VS ESTIMATED BASE VALUE MARKET SHARE
Total Number of Firms
Competing, NT, in a
Chemical Category
NT <.25
25 < NT < 50
50 < NT < 100
100 < N
Base Value
Market Share, MSbv
0.065
0.030
.0.0125
0'.005
*Percent values of market share are obtained by
multiplying the fractional values^ indicated by
100.
The table was developed based on the recognition, through experience
in market research, that there is a greater propensity for a higher
market share per firm if there are fewer firms competing. (This is
then refined based on whether the firm is large or small, etc.)
The base value market shares are segmented in the table in terms
of ranges of Ny in order to not propose a continuous, deceptively
accurate equation. This is done due to a relatively low confidence
in identifying the actual specific number of firms in a category
without conducting a research study. (The number is also subject
to fluctuation over time.) We therefore choose not be make the
relationship seem more accurate than the raw data permits.
48
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These estimates are intended to be on the conservative side, though
with a relatively broad range of fluctuation possible. That is,
if the table were plotted with NT on the horizontal axis and MS.
on the the vertical axis, the curve which results would be shifted
to the right of what we would expect in reality. Our use of the
ranges is based on mid- range values to calculate MS. , with the
extreme limits representing the level of fluctuation: The second
range value was developed as follows:
• The mid- range of 25 < NT <_ 50 is about 38. This would re-
present a nominal 0.026 market share per firm (1 * 38). We
selected 0.030 in order to err on the conservative side.
• The resulting fluctuation limits are calculated at each
extreme. For NT - 26, MS. , could be 1 * 26 = 0.038. For
NT = 50, MSby could be 1 ?V50 = 0.020.
• In summary, MS. = 0.030 n'nin- Since tne confidence is
low in predicting the exact* Mi; we rely on the mid- range
value.
In summary, to estimate the fifth year market share potential, the fac-
tors 'a1, 'b1, and 'c' are applied to MS based on Tables 6 and A-2. This
then permits a determination of the one and three year estimates as described
below.
One and Three Year Market Share Estimation
The one and three year estimates of market share are derived following
the five year estimate. Most product growth histories follow the pattern
illustrated in Figure 10 on the following page, assumed to be applicable for
chemical function categories as well.1"1*
One represents the case of potential market share attained within 5 years
(i.e., a relatively short life cycle, dynamic product category). A second
curve represents the case of potential market share attained within about 10
years (i.e., a relatively long life cycle, stable purchase patterns, mature
product category).
The procedure for estimating one and three year market share is based on
applying the following relationships:
and
Mslnc = d
MS3nc = e MS5nc
where: MS, = first year market share estimate for a new chemical
MS- = third year market share estimate for a new chemical
49
-------
100
90
t
IB
•r"
S 80
o
a.
(U
01
o
CO
•»->
(U
^
•o
0)
-P
to
LU
(0
4->
O
70
60
50
40
30
20
10
0
3 4 "5 6 7
Years Following Product Introduction
8
10
Figure 10. Idealized new product market growth
for five year and ten year product growth cycles.
-------
MS5nc = f1fth year market share estimate for a new chemical
d E factor which indicates the proportion of market share
attainable after one year. (Set d = 0.2 for a chemical
category which is identified as c = 1. Set d = 0.05 for
for a chemical category which is identified as c = 0.5.)
e = factor which indicates the proportion of market share
attainable after three years. (Set e =0.8 for a chem-
ical category which is identified as c = 1. Set e =
0.25 for a chemical category which is identified as c =
0.5.)
Applying the variables to the two equations will yield estimates of the
magnitude of the market share which could be attained after one and three years
respectively, given the estimate of market share for the fifth year. (Refer
to the example at the end of this section.)
ASSUMPTIONS AND QUALIFICATIONS < "'
The following list of assumptions and qualifications is provided to
assure a clear understanding of the limits of this market share estimation
procedure, and the basis for its representation as a preliminary gross screen-
ing mechanism.
a) Firm may have an extensive product line, all in the same markets,
and therefore the new chemical will only represent a fraction
of its total business in those markets. Thus the market share
estimate may be higher than would in reality exist, by assuming
that a firm only offers one product in a given category. (This
can be clarified in some cases by reviewing chemical catalogs,
discussion with the firm, or referring to U.S. ITC reports,
Thomas Register, etc.)
b) Different products of the same function may be specially tailored
to distinct applications and/or user markets. Thus the market
share estimate may be higher than would in reality exist, by
assuming that a firm offers its product across all applications
and market segments.
c) The new chemical may only represent a one-time batch quantity
in which case no planned, massive investment is specifically
anticipated and therefore no rational market share projections
are meaningful. A cursory review of the chemical advertising
literature can provide an indication, of the extent to which
batch quantities are represented in the market place.
d) It is likely that most of the commercialized innovations, hence,
the new chemicals will corae from the major chemical firms (e.g.
annual sales greater than 5 million dollars.) in a chemical
category. This is based on research of trends in innovation
i
51
Materials Er-lo'-r To:
OPPT Library
401 M Stree.. 3W (T.3-703)
Washington, £ J 20480
-------
by leading universities, and the indication that costs of regu-
latory compliance will impact on the ability of smal.l business
to commercialize innovations.
e) Most new chemicals are extensions, modifications of a firm's
existing product line.
f) It is less likely that a new commodity-type chemical will be
introduced than a specialty chemical, due to the greater
commitment required for large volume production capabilities
and lesser degree of innvoation in commodity chemicals than
specialty chemicals.
g) It is assumed that about 20% of the firms competing in any
category will represent 80% of the business in that category.
This is based on historical market indications to this effect
gained in numerous market research projects over many years.
Refer also to the 1972 U.S. Census of Manufactures, Concentra-
tion Ratios in Manufacturing.
h) A primary determinant in estimating market share potential is
the number of firms competing in the chemical category. In
fact it is estimated that long term penetration varies inversely
to the number of firms competing for a product having similar
cost, performance and service attributes, (i.e., a breakthrough
which Will capture all of the market is the exception rather
than the rule.)
i) Concomitant with the previous point is the importance of the
size of the firm (offering the new chemical) on its potential
impact (i.e., market share or penetration) within a chemical
category. A large firm is likely to beget a larger market
share than a small firm due to 1) resources for regulatory
compliance and R&D, and 2) innovation capacity, and 3) resources
for production, promotion, distribution, etc.
Thus a firm which is large has a greater potential, hence
likelihood, for being one of the 20% of the firms with 80%
of the business rather than one of the 80% of the firms with
20% of the business.
j) Commodity-type is defined as a fairly standardized, high-volume
chemical, whereas a specialty is a high performance, market-
volatile, relatively Tow volume chemical. (Commodity is repre-
sented by most basics and intermediates.) The commodity-type
typically has a longer product life cycle than the specialty-
type chemi cal.
k) The new chemical can be targeted cost-effectively to the entire
U.S. market (vs. only regional, where plant is located.) (i.e.,
this analysis ignores the transportation cost effect when esti-
mating market share, in order to assume the highest market share
potential possible.)
52
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1) Cost of selling varies from one category to the next, (packaging,
distribution, form of product, variance in specifications, etc.)
but is not considered as part of this procedure.
•,' ' *'/ •' -s.
m) Concentration of users/purchasers/customers has an effect on
market share potential. (If only.one or two firms purchase the
product vs. 100 or 200 it may be more difficult to penetrate
the market. Some estimate of potential use will be provided
in the PMN, however the reviewer must exercise judgement.)
n) Some firms identified as competitors may in fact have the
capability to manufacture the chemical but may not currently
be doing so. This can only be accurately determined by sur-
veying the firms who are identified as competitors in the trade
literature. Implicit in the fact as to whether a firm is large
or small is whether the sales force is adequate, the production
capacity is adequate, etc. with respect to the competition.
o) The firm planning to manufacture the new chemical is assumed
to have a patent position at least for the first five years,
thus implying that there are no others who could offer the
identical product for several years. The actual length of time
protecting a patent position in the market is based on the time
used to obtain regulatory approval.
p) In general, factors which should be taken into consideration
in any detailed analysis of a new product market potential can
be represented by the following summary:
Initial Considerations—
• New Markets versus Existing Market
• Standarized versus Non-Standarized (i.e. Commodities vs. Specialties)
• Industrial versus Consumer (i.e. Basic, Intermediate, End)
Production-
Raw Material Available/Cost
Process Technology
Experi ence
Production Costs
Scale of Production
Forward/Backward Integration
Capacity Utilization
Product—
• Quality and Specifications
• Pricing Policy (i.e. profit margins, competitive philosophy, etc.)
• Service
53
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Market--
• Market Segment Sizes (Volumes) by Function
• Market Segment Sizes (Volumes) by Applications
• Market Segment Maturity (i.e. Stage in the Life Cycle)
• Market Segment Historical Growth
• Market Segment Competition
• Opportunity to Substitute for Non-Chemical-Derived Products (i.e.
New Market or Existing Market Expansion)
• Price Elasticity of Demand (i.e. Commodity vs. Specialty)
• Rate of Product Acceptance within a Function/Application
External Variables-
Impact of Imports/Exports
The Economy
Government Regulations
Materials Availability
Energy
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EXAMPLE MARKET SHARE ESTIMATION
Chemical: Tris (2,3-dibromopropyl) phosphate
Function: Flame Retardant (Function Code No. 220)
Market Share Estimation:
. Fifth Year Market Share Estimate
Using MS5nc = abc MSbVj
where MSby = .030 (25
MS5nc = .15,
d = .2 (From 5 year new product growth cycle)
MSlnc = .2X.15
MSlnc = .03 (3%)
Similarly, ,MS3nc = e MS5nc
where e = .8 (From 5 year new product growth cycle)
then
MS
3nc = .8x.l5
MS
'3nc = .12 (12%)
55
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REFERENCES
1. Cox, William E. Jr., Industrial Marketing Research, John Wiley and Sons,
New York, 1979.
2. Kotler, Philip, Marketing Management: Analysis, Planning and Control,
Prentiss Hall, Englewood Cliffs, New Jersey, 1972.
3. Sullivan, W.G. and Claycombe, W.W., Fundamentals of Forecasting, Prentiss-
Hall, Res ton, Virginia, 1977.
4. Giragosian, N.H., Chemical Market Research, Reinhold Publishing Company,
New York, 1967.
56
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SECTION 6
THE CORRELATION OF CHEMICAL STRUCTURE WITH PHYSICAL, CHEMICAL AND
BIOLOGICAL PROPERTIES: APPLICATIONS IN EXPOSURE ASSESSMENT
Where there are gaps in the informational data base predictions based on
judicious application of available correlations of chemical structure with
physical, chemical and biological properties can contribute to the develop-
ment of reasonable estimates of exposure levels. Such correlations can be
helpful in developing predictions in the following areas relevant to exposure
assessment:
a) Potential uses of a new chemical;
b) Potential for direct transport through the environment;
c) Potential for direct systemic uptake of the chemical by exposed
humans;
d) Potential for formation of by-products, co-products and
degradation products during manufacture and processing of the
chemical and identification of such products;
e) Susceptibility to chemical and biological degradation in the
environment and identification of degradation products; and
f) Potential for bioaccumulation.
The operative modifier, "judicious application," needs to be emphasized.
In general, to derive meaningful predictions from structure-property corre-
lation, the advice of consultants expert in the particular field should be
sought.
POTENTIAL USES
The techniques of pattern recognition appear particularly well suited
to the purpose of anticipating potential uses of a new substance.1'2'3
Supplementary insight can be gained by a consideration of available infor-
mation on physical and chemical properties. For computer operation, pattern
recognition methods would require quite sophisticated hardware and software.
At this time, the NIH-EPA Structure and Nomenclature Search System, which
contains over 100,000 different compounds, might serve the purpose10. To
57
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fulfill the objective of defining potential uses, however, computer operation
may not be necessary. Since an experienced chemist should be able to do the job
and do it more quickly and economically.
The procedure would be essentially as follows:
a) Inspection of the molecular structure and the properties
of the chemical;
b) Selection of information for similar structural patterns;
c) Identification of existing uses of compounds of like
structure and properties; •
d) Estimation of the probable cost Of manufacture of the
new chemical and matching of manufacturing cost against
the list of possible uses to assess market potential, and
e) Listing of potential uses of the new compound.
The Chemical Use List elaborated by the EPA21 forms an excellent basis
for the purpose of classifying potential uses of a new compound. In general,
pattern recognition techniques would be better used in predicting "function"
than "application" as defined in the EPA list.
It should be noted that estimation of the probable cost of manufacture
can again be most conveniently done by an experienced chemist. Computer
techniques, essentially based on pattern recognition but far more sophisti-
cated still,*-7 could conceivably be used for the mapping and costing of
synthetic processes but at this time would certainly be unwidely, impractical
and unnecessary.
The concept of pattern recognition is based on the observed relatively
high probability that compounds with like structural patterns will have like
properties. Chemists seeking to design new compounds having certain proper-
ties tend to use as a model an existing compound already known to have those
properties. For example, with respect to identification of possible uses,
if one discerns a substituted phenoxyacetic acid moiety in the molecular
structure and there are few extraneous polar, functional or bulky groups
present, one could conclude that the compound might find use as a herbicide.
0-CHCOOH (possible herbicide)
R
(D
The conclusion would be reinforced if R = Cl. Depending on the nature of
substituents, the compound might also have anti-inflammatory properties, use
as an anti-inflammatory agent would, however, be unlikely unless the company
proposing to introduce the compound was in fact an ethical pharmaceutical
house.
58
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If a compound contained a long aliphatic hydrocarbon chain terminating
in a highly polar group, either antonic, cationic or nonionic, depending on
its lipophilic-hydrophtlic balance, there would be a high probability the
compound could find use as a detergent, surfactant, foam stabilizer, wetting
agent, emulsifier, etc.
R - (CH2)2 - X (possible surfactants, etc.) (2)
X = -OCO - Na+ (anionic) (2a)
X = -N(CH2CHzOH)2 (cationic) (2b)
X = -C(=0) - N(CH2CH20H)2 (nonionic) (2c)
An aralkyl quaternary ammonium salt3 could be a bactericide, algicide,
disinfectant, emulsion stabilizer, etc.
CH3
- CH2 - N* - RX" (possible bactericide, etc.) (3)
.CH3
A relatively low molecular weight compound with an activated, terminal double
bond4 could serve as a polymerization intermediate.
CH2 = C - X (possible polymerization intermediate) (4)
, R t;;'«.
A multitude of other examples could be cited but these should serve to illus-
trate the principle. It should be noted that pattern recognition can also be
used to identify known analogs for which regulatory actions have already
been taken.
ii,
Potential for Direct Transport
The extent to which a compound could be transported through the environ-
ment, and its distribution in the environment will depend on environmental
conditions as Well as upon on the following properties of the compound8:
a) Physical state (liquid, sol id-(particle size), gas;
b) Volatility;
c) Density;
d) Lipophilic-hydrophilic balance;
e) Solubility in water;
f) Chemical stability.
59
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Certain of these terms describe overlapping, but not precisely coinci-
dental , features of a compound. For example, with respect to a), b), and c),
a solid can have higher volatility and lower density than a liquid. With re-
spect to d) and e), solubility of a solid in water will depend not only on
lipophilic-hydrophilic balance but also on crystal lattice energy.
It is possible to make reasonable predictions of transport through the
environment by means of mathematical-computer techniques. The limited amount
of data on the properties of a new compound requires careful development of
estimates.8
First, in order to be transported any distance from the source, the
chemical must have sufficient chemical stability to survive the time it takes
to migrate that distance. For purposes of this program, it was assumed that
the compound would be sufficiently stable to be transported. A compound with
a half-life of less than 12 hours might be considered to undergo breakdown
sufficient to render stability a significant influence on direct transport.
Transport can occur through water and/or air; the material will be dis-
tributed in the air, water, and in and on solid surfaces (land). In addition
to the physical and chemical nature of the compound, major determinants of
the rate of transport and concentration at a given distance are factors ex-
ternal to the inherent properties of the substance, viz., rates of flow of
air and water, volume of water, and ambient temperature. The properties of
the molecule have the major influence on steady state concentrations of the
substance in air, water and land therefore this discussion has been confined
to consideration of steady state concentrations.
The steady state concentration in air of a solid at a distance from the
source will be a direct function of its volatility, and inverse functions of
its density, particle size and water solubility. The steady state concentra-
tion of a solid in water will be inverse functions of its volatility and its
lipophilic-hydrophilic balance—which may be expressed in terms of partition
coefficient between octanol and water9—and a direct function of its water
solutibility. Concentration on land will be inverse functions of its vola-
tility and water solubility and direct functions of its density and partition
coefficient, Corresponding relationships can be formulated for liquids and
gases.
Information as to the physical state of the materials, although possibly
not the particle size of the solid, will certainly be available from the man-
ufacturer. Data relating to volatility, density and water solubility may al-
so be available, but, information with respect to lipophilic-hydrophilic
balance may not be available.
Volatility is a property determined not only by the vapor pressure of
the compound but also by its latent heat of vaporization and its partition
coefficients between air and water and between air and soil. That is, the
degree to which the compound is held, or possibly even complexed, in water
or by soil will be important influences on the proportion of the substance
released to air from the latter geospheres. Although information on vapor
60
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pressure may be available, data on the heaFt'of vaporization and on air-water
and air-soil partition coefficients will almost certainly not be available.
Estimates can be made based on molecular weight, which will have an inverse
relationship with volatility, presence of polar, hydrogen bonding and/or ion-
izable groups, which can have a profound effect in decreasing volatility.
Density of a gas can be simply estimated because gas density will vary
directly with molecular weight. If we assume that there is no intermodular
association, (which is a reasonable approximation for a gas at low concentra-
tion), and that the substance obeys the ideal gas law, we can actually cal-
culate the density based on the fact that 1 mole of a perfect gas occupies a
volume of 22.4 liters at 0°C and 1 atmosphere pressure. Thus the density in
grams/liter at standard temperature and pressure can.be calculated:
H - . Wt.
"
22.414
Density of a liquid may be estimated based on the fact that density will
vary directly with degree of intermolecular association. Compounds without
polar, hydrogen bonding, ionizable groups or available bonding electrons and
bonding orbitals (e.g., saturated hydrocarbons) will have a low density (<1).
Density will increase with the introduction of groups capable of entering in-
to progressively stronger intermolecular bonding interactions. Fluorocarbons,
presumably because the fluorine atom holds its electrons very tightly and is
unwilling to share them, are nearly equivalent to hydrocarbons in their low
density and high volatility. Other halocarbons, chloro, bromo and iodo de-
rivatives, do enter into intermolecular associations and have very high den-
sities and low volatility. As a general rule, the heavier elements, elements
of the second row of the periodic table and beyond, with unsatisfied outer
shells, are more capable of entering into intermolecular bonding associations
than are the lighter elements.
Density of a solid is much more difficult to predict because it depends
so much on the crystal structure—the distance between molecules in the crys-
tal lattice. Moreover, a solid can have more than one crystal structure.
The morphology of its crystals, and therefore their density, can vary depend-
ing on the conditions Of formation. Estimates can best be made on the den-
sities of the most closely analogous compounds.
There is considerable information concerning the lipophilic-hydrophilic
balance of organic molecules which is expressed in terms of the partition
coefficient (P) between 1-octaonol and water. The partition coefficients of
a large number of compounds have been determined and tabulated.9'11-1** Also
tabulated are a large number of substituent constants (n) which indicate the
effect of a particular substituent on the partition coefficient of a parent
molecule.9'15'13'15-17'32 To calculate an approximate partition coefficient
for a new compound, the value(s) of the relevant, subs tituent(s) are added to
the log P of the most closely related parent compound for which data are
available, and the antilog of the sum is determined:
Px = Antilog (II. + II. + IT + log Po)
3— i a— 2 * "
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Px is the partition coefficient of the new compound, Po is the coefficient of
the closest known parent compound and It is the substituent constant of the
nth substituent. The more closely relatea the substituent(s) and the parent
compound are to the;new compound the more confidence one can have in the valid-
ity of the calculated partition coefficient. The larger the partition co-
efficient, the more lipophilic the substance and the less its compatibility
with aqueous systems. Polar, hydrogen bonding and ionizable groups will lower
partition coefficients.
The partition coefficient may be used to estimate the water solubility of
a liquid or a gas. The smaller the partition coefficient, the greater the
water solubility. The solubility of compounds with acidic or basic groups
will be markedly affected by the pH of the aqueous medium. That is, a sub-
stance with a low pKa (acid) will be solubilized in water at a high pH
(alkaline) whereas the converse will be true of a substance with a high pKa
(base). The solubility of gases and liquids with a high vapor pressure at
ambient temperature decreases with increasing temperature whereas the solu-
bility of liquids with low vapor pressure (and solids) usually, but not
always, increases.
The water solubility of a solid also depends on its partition coefficient
and on the presence or absence of acidic or basic functions. In addition the
water solubility of a solid can be markedly influenced by its crystal lattice
energy. For example, the stronger the forces stabilizing the crystalline
form, the more the thermodynamic equilibrium between the crystalline solid
and dissolved solid will be shifted toward the crystal. Dipolar ionic sub-
stances, for example amino acids, have much lower solubilities in water than
would be expected on the basis of their polarity, presumably because of elec-
trostatic stabilization of the crystal lattice. Solubility can be markedly
increased in a medium that is sufficiently acid or alkaline to convert the
charge-neutralized molecule to a salt form.
Chemical stability in the context of environmental degradation will be
discussed in a later section.
To estimate the effect of the chemical properties on the direct trans-
port and distribution of a substance, one should collect available data on
the physical state, volatility, density, lipophilic-hydrophilic balance,
water solubility and, if the compound is likely to be very unstable, its
chemical stability. Estimates of direct transport can then be made based on
data available for known compounds.
POTENTIAL FOR DIRECT SYSTEMIC UPTAKE
Exposed humans may take in a chemical by absorption through the skin or
other membranes, by inhalation and/or by ingestion through the gastrointes-
tinal tract. The proportionate amount of a dose of a chemical an exposed
human recieves will depend on the route(s) of uptake and on the properties
of the substance.
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The skin and other external membranes are basically composed of layers of
lipids with thin water-soluble polar groups facing outward and their non-polar
carbon chains held together on the inside.18"20 The lipid layers are stabil-
ized by layers of protein molecules. It is believed that large numbers of
tiny water-filled chemicals or pores are distributed throughout these mem-
branes. The presence of pores is inferred from the behavior of the membranes;
the effective pore size appears to be about 4A. The main difference between
the skin and other outer membranes (of the mouth, nasal cavities, etc.) is
that the skin has an additional outer, horny layer densely packed with keratin
(a protein). Rates of absorption through the skin are slower than through
other external memberanes and varies qualitatively with variations in proper-
ties of the substances being absorbed.
Most foreign substances are absorbed through these membranes by passive
diffusion processes.18"20 The ability of substances to diffuse through the
skin is directly proportional to their lipophilic-hydrophilic balance, i.e.,
their octanol-water partition coefficient. The more lipophilic the substance,
the better it will be absorbed. It should be noted that extremely lipid-
soluble materials will rapidly diffuse into the membrane but then be held in
the lipid layer and diffuse into the systemic circulation only slowly. Highly
polar, lipid-insoluble substances cannot be absorbed through the skin unless
their molecular size is small enough, no more than the equivalent of about a
3-carbon atom chain (or 4A), to pass through the presumed water-filled chan-
nels.
Particle s.ize will markedly influences absorption through the skin. In
order to be absorbed by passive diffusion, a substance must not only be lipid-
soluble but must be in a form available for dissolution in the lipid layer.
Thus the rate of absorption will vary inversely with particle size.
A substance will usually enter the gastrointestinal tract via the oral
route. From the mouth, where the pH TS approximately neutral, a substance
will pass into the acid milieu (pH 1-4) of the stomach, thence to the small
intestine, where the pH again approaches neutrality, and finally to the large
intestine. Systemic absorption can take place in any of these regions but
the major fraction of the absorption generally takes place in the small
intestine.
The principles governing absorption of foreign substances from the gast-
rointestinal, tract are the same as for absorption through the skin and other
membranes.18~20 Absorption is generally by pasive diffusion and absorbabil-
ity varies directly with octanol-water partition coefficient. Acids and
bases will more readily pass through the wall of the gastrointestinal lumen
in their unionized form. Therefore, bases, which will normally exist in the
protonated ionic form in the acid environment of the stomach, will be largely
absorbed from the intestines whereas lipid-soluble acids and neutral mole-
cules can be abosrbed from the stomach. Highly polar substances will not be
absorbed unless they are small enough to pass through the water-filled chan-
nels or, in exceptional cases, are carried across by active transport. Active
transport processes will be available only to substances closely resembling
normal substrates (e.g., glucose, L-amino acids, uracil).
63
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Degree of absorption of a solid win vary inversely with particle size.
In order to be absorbed, a lipid-soluble substance must be in a form avail-
able for dissolution in the lipid layer of the intestinal wall.
Since the stomach provides a strong acid environment and the entire gas-
trointestinal tract provides a variety of digestive enzymes capable of break-
ing down proteins, carbohydrates and, neutral fats and the colon contains
colonies of bacteria capable of effecting a range of chemical transformations,
one must consider the possbility that an ingested substance, itself unable to
be absorbed, might be susceptible to degradation to absorbable breakdown
products. Acid-labile substances, protein-Tike or carbohydrate-like materials,
and high molecular weight esters should be evaluated in this context.
It should be noted that a substance absorbed from the gastrointestinal
tract will normally immediately enter the portal circulation and be channeled
directly to the liver where it could undergo degradation by microsomal
enzymes.
Substances present in the air, i.e., gases, volatile compounds and
aerosols can be inhaled into the lungs. Ability of aerosols to reach the
lungs depends on particle size (Table 8).20 Large particles (>10 microns)
are almost completely retained in the nasal passages. As the particles be-
come smaller, increasing proportions will reach the alveoli. Insoluble
particles retained in the upper respiratory tract are rapidly cleared by a
mucous blanket which covers the tract down to the terminal bronchioles and
which is propelled upward by ciliary movements.
TABLE 8. PERCENT RETENTION OF INHALED AEROSOL PARTICLES
Particle Size, ym Percent Retention in Nasal Passages
>10 VLOO
5 50
2 20
<1 0
Absorption of materials reaching the lower respiratory tract and the
alveoli can be extremely rapid. Ttye rate of absorption into the systemic
circulation through the alveolar eridothelium is influenced by. the properties
of the sbustance being absorbed in th>e same manner as through other biologi-
cal membranes. Absorption rate increases with increasing bctanol-water
partition coefficient and with decreasing particle size.
The process for estimating the effect of chemical properties on systemic
uptake of a new substance by exposed humans may be generically illustrated as
in Figure 11.
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PROPERTIES VARYING DIR
ICILY WITH ABSORPT
Partition Coefficient
Partition Coefficient
Active Transport Routes
Partition Coefficient
Volatility
PROPERTIES VARYING IN
Particle size, Molecular
size of Polar Compounds
lonizability
(acids, bases)
ERSELY WITH ABSORPTION
Particle size, Molecular
size of Polar Compounds
lonizability
(acids, bases) <
Chemical Lability
Particle Size, Molecular
size of Polar Compounds
lonizability
(acids, bases)
Estimated Systemic Uptake
Figurell. Effect of chemical properties on systemic uptake.
65
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POTENTIAL FOR BY-PRODUCT FORMATION
Estimation of the potential for formation of by-products and degradation
products during manufacture and processing, and prediction of the identity of
such products will be required for adequate premanufacture review.
With respect to manufacture, one must first define the synthesis route being
used, starting materials, reagents, conditions, and purification procedures.
Some information as to the method of synthesis may be supplied by the chemi-
cal manufacturer but surely not precise details-of conditions used and in-
plant operational procedures. Information not supplied will have to be
estimated. Since there is generally more than one potentially useful route
to a compound and since other manufacturers might choose to go into produc-
tion, one will have to identify and evaluate alternative syntheses. Thus,
before beginning to estimate possibilities for by-products formation, one
must:
a) review supplied information on the existing, syntheses route;
b) estimate or obtain operational details that are not supplied;
c) identify and evaluate alternative syntheses.
Given the syntheses route, it will be possible to make reasonable
estimates of the conditions used and of operational procedures. Potential
alternative syntheses may be identified by pattern recognition techniques as
discussed earlier. In its simplest form, this would entail reviewing a suit-
able data base such as the NIH-E.PA Structure and Nomenclature Search System
for compounds with a similar molecular structure. Sophisticated computer
techniques have been developed for the purpose of syntheses analysis but
do not appear to have evolved to the point where they would be useful for the
present purpose.
This information can be used to predict the principal kinds of by-
products, co-products and degradation products that could form during manu-
facture and be present in process streams and/or the final product.
Predicting of the by-products which may be formed in trace amounts will be
difficult if not impossible at this point.
With respect to processing, one must consider:
•,
a) the chemical properties, especially the stability of the
compound;
!
b) the conditions of processing for the existing use; and
c) potential additional processes in which the compound
might be used.
By inspection of the structure of the compound, consideration of the
functional groups and the existence of labile features, it is possible to
predict the stability and the conditions under which it might degrade as
66
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well as the products that might be formed* Although there is always the pos-
sibility that unanticipated trace and/or unobvious degradation products can be
formed, reasonably accurate predictions are possible. For example, if the com-
pound has an unhindered ester function with some water solubility and is to be
heated in water during processing, the possiblity of hydrolysis of the ester
group is obvious. If the compound has an allylic alcohol grouping and is
treated with acid during processing, there are the possibilities for dehydration
and/or rearrangement depending on the molecular structure. There is also the
possibility of air oxidation. If the compound is a silver salt, there are
possibilities for deposition of silver oxide, or, in the presence of a reducing
substance, free silver.
Some information regarding processing for proposed uses, e.g., as a
pigment in the formulation of paints, as a foam stabilizer for foamed rubber,
as a gelling agent for adhesives, etc., may be supplied but details of pro-
cessing conditions probably will not be supplied. General knowledge of the
type of processing and discussion with users can be used to make reasonable
estimates for processing conditions.
For the purpose of predicting additional processes in which the compound
might be used, it will be necessary to:
a) predict other applications where the compound may be used and
b) judge if the compound might have other potential functions and
consequent applications.
The physical and chemical properties of the compound can be used to pre-
dict applications where the compound might have-utility. With the aid of
pattern recognition techniques, and suitable data base such as that already
referenced, one can identify known compounds having analogous molecular
arrangements and similar properties. Based on the functions and applications
of these known materials and with the aid of the Chemical Use List published
by the EPA, one can project potential additional uses of the new compound.
Processing conditions can then be estimated for these additional application
areas. With these estimates in hand, projections can be made of degradation
products that might form during processing.
SUSCEPTIBILITY TO ENVIRONMENTAL DEGRADATION
In evaluating the susceptibility of a compound to chemico- and bio-
degradation in the environment, it is necessary to consider its structure,
physical and chemical properties, and the physical, chemical and biological
stresses to which it will be exposed. Physical and chemical forces in the
environment that might cause degradation include: heat, ultraviolet radia-
tion, oxygen, water, acid, alkali, oxidizing systems, and reducing systems.
Biodegradation could result from uptake by microorganisms, insects, fish,
birds, mammals, and could involve successive ingestion through the biological
chain.8 :
From inspection of the molecular structure of a new compound, it is
possible to predict the physical and chemical forces in the environment which
may affect it and to predict probable products. From the physical
67
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characteristics, water solubility, partition coefficient, and volatility, a
prediction of the distribution of the compound in the environment is possible.
This effort can be supplemented by a computerized pattern recognition search
of a data base in order to identify compounds possessing analogous structural
features and functional groups for which environmental fate has been studied.
Frequently sufficient literature data are available to enable the develop-
ment of reasonably quantitative estimates of rates of degradation.
For example, considerable information is available on the effects of
substitution on the susceptibility of benzene and its derivatives to physical
and chemical actions in the environment.22"25 Benzene itself is not suscep-
tible to degradation by water, acid, alkali or reducing systems under environ-
mental conditions and is substantially more stable than other hydrocarbons to
oxidative and photochemical degradation. The effects of substitution on oxida-
tive degradation are consistent with electrophilic attack on the^beneze ring.
Thus, introduction of electron-donating substituents—alkyl, hydroxy, amino--
markedly enhances substituents such as chloro or bromo.and further stabilize the
ring to oxidative attack. .Of course, the substituent itself can be sensitive
or engender lability to other agents, e.g., the sensitivity of nitrotoluenes
and of phenols to alkali. Chlorinated aromatics are subject to photochemical
dechlorination; for example, the polychlorodibenzodioxins are dechlorinated
by sunlight when present in very thin films or dilute solutions but are other-
wise extremely resistant to attack.2lf~25
Estimates of possible biodegradation can be made by experts in the areas
of microbiology-and biochemistry. Knowledge of the molecular structure of
the new compound, its physical and chemical properties, coupled with know-
ledge of the possibilities for uptake by micro- and macro-organisms and of the
metabolic pathways available to these organisms26, will permit estimation of
susceptibility to metabolic degradation and the probable products of such
degradation. A pattern recognition search to identify compounds with similar
structural features and for which information on biodegradation is available
can be used to assist in development of predictions. The rate of biodegrada-
tion can be expected to be much more sensitive to subtle changes in structure,
steric factors, and lipophilic hydrophilic balance than would the rate chemical
degradation.
In order to be metabolized a compound must first be taken up by the
organism. This uptake requires penetration, of biomembranes and follows the
same general rules discussed for human uptake. In addition, microorganisms
can take in foreign bodies by engulfing them (pinocytosis). A high octanol-
water partition coefficient will generally favor uptake. ' Microorganisms can
take up substances by means other thari absorption through a biomembrane, and
have great versatility in their ability to metabolize foreign compounds.
The metabolized products may then be tn a form more readily absorbed by higher
organisms (for example, the conversion by some bacteria of mercury to the
readily absorbable methylmercury and dimethylmercury). Thus it is not pos-
sible to rule out absorption of a compound simply because in its unmetabolized
form it would be incapable of absorption through membranes.
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Once absorbed, the metabolic processes to which a compound would be
subjected will depend on its distribution in the organism and its ability to
reach the appropriate enzyme systems. While distribution will not be a factor
with microorganisms, it can have major significance with higher organisms.
A compound with .a lipophilic-hydrophilic balance in an intermediate range can
concentrate in the liver, gain ready access to the microsomal enzymes con-
tained therein, and then be a candidate for metabolic degradation. A highly
polar substance may be rapidly excreted unchanged through the kidneys whereas
an extremely lipophilic compound may be stored in the fat and released slowly,
if at all, into the circulatory system where it can be brought into contact
with metabolic enzyme systems.
In general, metabolic processes convert lipophilic substances into less
lipophlic, more polar products.26 These metabolic products are usually, but
not always, less toxic than their parents.
Microorganisms are extremely versatile in their metabolic abilities:
they have a broad array of metabolic enzyme processes at their disposal and
frequently can develop enzyme systems to metabolize compounds that they were
originally unable to handle.28 Nevertheless, microorganisms have their
limitations. For example, bacteria that produced adaptive enzymes to degrade
a specific phenolic compound were readily able to metabolize a variety of
phenols, benzoic acids and benzaldehydes but had little or no ability to
metabolize benzene, toluene, nitrobenzene or halogenated aromatic compounds.28
Metabolic processes that can be effected by mammalian systems include:26'29
1) Oxidation by microsomal enzymes
a) epoxidation and hydroxylation of aromatic compounds
b) hydroxylation of alkyl chains
c) deami nation
d) N-dealkylation
e) 0-dealkylation
f) N-oxidation
g) S-oxidation
2) Reduction by microsomal enzymes
a) reduction of azo and hydrazo groups
b) reduction of nitro groups
3) Other oxi dative systems
a) aroma tizati on
b) oxidation of alcohols and reduction of aldehydes and ketones
c) oxidation of aldehydes
4) Hydrolysis of esters and amides
5) Conjugation
a) formation of glucuronides
b) formation of sulfate esters
69
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c) mercapturic acid conjugation
d) methylation :
e) acylation
6) Covalent binding to tissue proteins and/or nucleic acids
Clearly, an absorbed compound will be subjected to a broad range of
metabolic processes. Most of these will produce more polar substances which
can be excreted. Obvious exceptions are processes resulting in covalent bond
formation with proteins and nucleic acids. Such bond formation can occur if
the compound has an electrophi1ic center, or has an electrophilic center met-
abolically generated, which is sterically accessible for binding to a nucleo-
philic site on biopolymers. Chloromethyl methyl ether is an example of a
direct alkylating agent. Di methyl riitros ami ne and benzo(a)pyrene are examples
of compounds which are first oxidized by microsomal enzymes to generate spe-
cies capable of covalent binding to nucleophilic sites. 7s28
Compounds with an appropriate Tipophilic^hydrophilic balance, having the
kinds of structural features or functions which would be susceptible to attack
in any of the listed enzymatic processes and which are not sterically in-
accessible, can be expected to be metabolized after absorption. To be sus-
ceptible to attack by an oxidative enzyme, the compound whould be readily
capable of donating electrons to the enzymatic acceptor. Thus aromatic com-
pounds with electron-donating substituents (e.g., acetanilide) are readily
enzymatically oxidized whereas those with electron-with drawing groups (e.g.,
halogenated aromatics) are resistant to metabolic oxidation. For enzymatic
reduction on the other hand, the compound must have groups able to accept
electrons (e.g., the nitro group of nitrobenzene). For conjugation, a com-
pound must have a group capable of being conjugated (e.g., hydroxyl, amino,
sulfhydryl). A compound can undergo sequential attack by a series of enzyme
systems, for example: hydrolysis of an ester followed by oxidation of the
resultant aniline; hydroxylation of an alkyl group followed by conjugation of
the alcohol.
POTENTIAL FOR BIOACCUMULATION
In order for a compound to have a potential for bioaccumulation, be
resistant to chemico- and bio-degradat'ion and thus be persistent in both geo-
and bio-spheres; it must be capable of undergoing uptake by living organisms,
and must be resistant to excretion.8
Compounds resistant to chemico- and bio-degradation in the environment
will be those having attributes to discussed previously such as resistance
to the physical, chemical and biochemical processes with which it may come in
contact. Thus stable compounds that do not have structural features subject
to ready breakdown are candidates for bioaccumulation.
To be capable of undergoing uptake by living organisms, compounds must
either: a) have some degree of lipid solubility; b) if highly polar, be ex-
tremely small in molecular size; or c) be subject to active transport.
Highly polar compounds will be excreted, unchanged and/or metabolized, about
70
-------
as rapidly as they are taken in and thus generally will not be subject to
bioaccumulation. A compound taken in by an active transport process, since it
will resemble a normal substrate, would be expected to follow the metabolic
and excretary pathways of the prototype and thus not, itself, be accumulated
although a metabolite could emulate the normal, metabolite and be incorporated
into biopolymers. •;*
Resistance to excretion normally requires an extremely lipophlic molecule
which will be distributed to, and stored in, fatty tissues where it will not
suffer enzymatic breakdown and from which it will be released only slowly.
In general, compounds that will be subject to bioaccumulation are chem-
ically and biochemically stable, highly lipophilic substances. Typical of
such compounds are certain halogenated aromatic hydrocarbons, well-known
illustrations of which are DDT and PCB's.30 The potential, for the bioaccumu-
lation of halogenated aromatic hydrocarbon depends on their degree of lipoph-
ilicity, which determines their relative distribution between the fat and the
liver, and the number and exact positions of their halogen substituents, which
largely determines their chemical stability and lack of susceptibility to
microsomal enzymes. Birds and fish appear to be particularly subject to bio-
accumulation of stable, lipophilic compounds like the halogenated aromatic
hydrocarbons.
In addition to stable, lipophilic molecules which may be distributed to
adipose tissue and there accumulate without undergoing chemical transforma-
tion, certain compounds may, in the course of undergoing transformation, be-
come covalently bound to biopolymers, and thus not the compounds themselves
but their metabolic products may be bioaccumulated. As mentioned earlier,
compounds closely resembling normal substrates may suffer such a fate by
being incorporated into biopolymers in place of the normal substrate. A more
common possibility, is that of a compound, such as any carcinogen whose
mechanism of action has been elucidated, being itself capable of forming cov-
alent bonds with nucleophilic sites on biopolymers or of being converted into
a metabolite capable of such action. It should be noted that this route of
accumulation, through covalent bonding to a biopolymer, would only be accumu-
lation in the individual organism and would not result in bioaccumulation
through the food chain. This is so because the trigher organism ingesting the
substituted biopolymer would have to break it down before absorbing it and the
resulting fragments would no longer be likely covalent bond-forming agents.
Thus one may distinguish between individual bioaccumtrtation and bioaccumula-
tion in the food chain.
A procedure for conducting the bioaccumulation prediction is represented
schematically in Figure 12.
71
-------
New Compound
i
Octanol-Water Partition Coefficient
i
Examination of; Chemical Structure
I
Pattern Recognition. Search
Possible Uptake in the Bio-
sphere
Possible Distribution in
Living Organisms
Chemical and Biochemical Stability
Potential for Covalent Bonding to
Biopolymers
I
Potential for Individual Bio-
accumulation
Potential for Bioaccumulation in the
Food Chain
Figure 12. Potential for bioaccumulation.
72
-------
REFERENCES
1. B.R. Kowalski and C.F. Bender, J Am Cnem Soc, 94:5632, 1972.
2. B.R. Kowalski and C.F. Bender, J Am Chem Soc, 95:686, 1973.
3. A. Cammarata and Q.K. Menon, J Med Chem, 19, 739, 1976 and References
sited therein.
4. E.J. Corey, Pure and Appl Chem, 14, 19, 1967.
,5. W.T. Wipke, Computer Representation and Manipulation of Chemical Infor-
mation, W.T. Wipke, S.R. Heller, R.J'. Feldman and E. Hyde, ED., John
Wiley and Sons, New York, 1974, p. 147.
f
• r.
6. P. Gund, Ann Repts Med Chem, 12, 288, 1977.
7. H.6. Gelernter, et.al., Science, 197, 1041, 1977.
• • <$.
8. Principles for Evaluating Chemicals in the Environment, National Academy
of Sciences, Washington, DC 1975, pp 45-81.
9. C. Hansch, Accts Chem Res, 2, 232, 1969.
10. Q.W.A. Milne, S.R. Heller et. al., J. Chem Inform Comput Sci, 18, 181
1978.
11. C. Hansch, Drug Design, Vol. 1, E.J. Ariens, Ed., Academic Press, New
York, 1971.
12. R.D. Cramer III, Ann Repts Med-Chem, 11, 301, 1976.
13. W.P. Purcell, Q.E. Bass, and J.M. Clayton, Strategy of Drug Design,
Wiley-Interscience, New York, 1973.
14. R.N. Smith, C. Hansch and M.M. Ames, J Pharm Sci, 64, 599, 1975.
15. C. Hansch, A. Leo, et. al., J Med Chem, 16, 1207, 1973.
16. C. Hansch et al., IBID, 20, 304, 1977.
17. F.E. Norrington et al., IBID, 17, 604, 1975.
73
-------
18. D.R.H. Gourley, Medicinal Chemistry, 3rd Ed. A. Burger, Ed. John Wiley
and Sons, New YorK, 1970, pp 32-35.
19. A. Albert, Selective Toxicity, 5th Ed., Chapman and Hall, London, 1973,
pp 29-40.
20. A. Goldstein, L. Aronow and S.M. Kalman,- Principles of Drug Action, Har-
per and Row, New York, 1969, pp 108-160.
9°
21. Federal Register, 43, No. 143, 32222, 1978,
22. J.A. Manning and R. Johnson, Atmospheric Benzene Emissions, EPA Report
450/3-77-029, Prepared by PEDCO Environmental, Inc., 1977.
23. W.A. Glasson and C.S. Tuesday, Envir $ci Tech, 4, 916, 1970.
24. D.G. Crosby, A.S. Wong, J.R. Plimeer and E.A. Woolson, Science, 173,
748, 1971.
25. D.G. Crosby, A.S. Wong, Science, 195, 1337, 1977.
26. J.R. Gillette, Progr. Drug Research, 6, 13, 1963.
27. J.A. Miller, Cancer Research, 30, 559, 1970.
28. C.W. Chambers and P.W. Kabler, Developments in Industrial Microbiology,
5, 85, 1964.
29. P.N. Magee, Essays in Biochemistry, 10, 105, 1974.
30. H.W. Matthews and S. Kato, International Conference on Health Effects of
Halogenated Aromatic Hydrocarbons, New York Academy of Sciences, June
1978.
31. M.L. Spann, K.C. Chu, W.T. Wipke and G. Ouchi, J Envirn Pathol Toxicol,
2, 123, 1978.
32. K.M. Kim, C. Hansch, P.N. Craig, et a!., J Med Chem, 22, 366, 1979.
74
-------
INFORMATION SOURCES
The most generally useful sources of information on the chemical proper-
ties of compounds were:
1. The Merck Index.
2. Handbook of Chemistry and Physics (particularly for data on vapor
pressure at different temperatures).
3. A. Lev, C. Hansch, and D. Elkins, Chem. Reviews, 71, 525 (1971);
and C. Hansch et £]_., J. Med. Chem., 16, 1207 C1973) (for data
permitting estimation of octanpl-water partition coefficients).
4. Chemical Use List, EPA, Federal Register, 44, 16240 (1979) (for
information on use classification^
5. Manufacturers' technical bulletins.
>
6. Personal knowledge.
75
-------
SECTION 7
APPLICATION OF PROCEDURE
The procedures discussed in the previous sections were applied to 30
chemicals selected by the EPA. This list included some well established
chemicals in addition to chemicals produced in the small volumes expected for
the pre-manufacturing notice chemicals. Since the procedures were developed
for small volume chemicals there was some difficulty when they were applied
to large volume chemicals that have many different uses; in these cases (benzene,
acetone, etc.) the results are illustrative only, and not definitive. In all
cases expert judgement was required. ";
The estimated physical and chemical properties of the chemicals were ob-
tained and are given for each chemical in the appendix.
These data, along with potential use data and market data were used to
estimate production volumes, number of plants arid number of processing steps.
The estimated market share for each of the 30 chemicals for the 1st, 3rd, and
5th year are given in Table 9.
Table 10 lists the predicted number of manufacturing personnel and the
predicted concentration of the chemical in the work space. This table also
lists the number of people and the concentration of the chemical in the vicin-
ity of the plant.
Table 11 lists the consumer dose for the 30 chemicals. Of these chemi-
cals, 8 were predicted to lead to no direct consumer exposure because they
would be completely reacted during industrial processing (chemical intermedi-
ates) or because they would be contained within closed industrial cycles
(catalysts).
For inhalation, most of the remaining chemicals were predicted to lead
to dose by volatilization (about 8 have negligible diffusivity) and virtually
all to dose via aerosols. Naturally, the inhalation route is very signifi-
cant in direct exposure for high vapor pressure solvents that are rapidly
volatilized, but it can be equally significant for low vapor pressure chemi-
cals that are kept in the home a long time. The significant parameter is the
ratio between the time over which the chemical takes to volatilize (Trel) and
the product lifetime in the home (Ta + Tp). The yearly inhalation doses are
conservative by a factor of about 10 because no allowance has been made for
inhaled chemical that is later exhaled. Some evidence shows that the capture
or retention efficiency of the lungs commonly ranges between 10 and 100 per-
cent (Astrand 1978). Thus, for example, though the model predicts a probable
76
-------
average inhalation dose of 865 g of acetone to home house painters, the actual
average might be aslow as 86 g due,.to this factor. Also, the inhalation dose
is uncertain by virtue of the chemical diffusivity, and separate calculations
have been done for minimum and maximum estimated values.
*.
For contact, about 7 chemicals lead to no dose because one or more of the
following parameters are effectively zero: water solubility, diffusivity,
duration of skin contact and liquid-water penetration (a function of partition
coefficient). Contact dose is usually most significant for chemicals with
only low inhalation exposure, as otherwise the inhalation route would deliver
a larger dose. Wherever data were not available, worst case assumptions are
made (i.e. partition coefficient, solubility, etc.).
77
-------
TABLE 9. MMXET SHARE FOR SWHE 'NEW CHEMICALS
Sample
Chemical Function
No. NMC Code
1
2
3
»
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
23
29
Tris (2.3 dlbromopropyl Phosphate)
Carpet Manufacture
Benzene
Asbestos
Cement Pipe Manufacture
Ethylene dlchloride
Acrylon1tr1le
Benzidine Yellow
Uni-Rez 2642
011 of Cedar leaf
Flavor Uses
2-benzothlazole-sulfon-
amlde, N-(l,l-d1 methyl ethyl)
3-n1tro Isatolc anhydride
Olmercaptothl ad1 azol e
Fomulated to Cutting 011s
Adi pic acid -1.4-butanedoil -
4,4'-diphenyl methane dllsocyanate
Benzyl trimethyl ammonium methoxlde
Vitride DHTD
Strontium titan«e
Acetone
ityrene Polysulfide
Hydrogenated Tallow Adds, ethanol
wine condensate. ethoxylated
Sjrfynol 104(2, 4,7.9- tetramethyl)-
4,7 dihydroxy-deca-5-yne)
Allyl alcohol-Styrene Copolymer
Benzenedlazonium. 2,5-dibutoxy-4-
(4 norpholinyD-sulfate
n-butyl ethyl -magnesium
Arcberlyst Resin Catalyst
Ranev Nickel
?no$phorodithioic acid.
S,S1-(thiodi-4.1,phenylene)
Hexachlorobenzene
Trichloroethylene
Sulfuric acid
Iron (II) Sul'ide
220
1211
318
352
2602
1211
352
1211
1212
299
1330
009
1211
1211
1211
1212
381
009
132
211
304
112
319
1211
318
352
3581
-
150
3620
3621
3627
128
132
213
304
1330
112
112
112
299
1211
236
1211
153
318
352
302
318
1331
195
272
3!8
No. of
Coopetltors:
Range
25 - 50
51 - 100
2S - 50
• 100*
1 - 25 "
51 - 100
100*
51 - 100
26 - 50
1 - 25
26 - 50
100*
100*
51 - 100
51 - 100
51 - 100
26 - 50
1 - 25
100+
100*
1 - 25
26 - 50
50 - 100
1 - 25
51 - 100
26 - 50
100*
25 - 50
-
50 - 100
50 - 100
50 - 100
50 - 100
26 - 50
100*
50 - 100
26 - 50
26 - 50
SO - 100
50 - 100
50 - 100
1 - 25
51 - 100
26 - 50
51 - 100
1 - 25
26 - 50,
100*
1 - 25
26 - 50
50 - 100
1 - 25
100*
26 - 50
«bv
0.030
0.0125
0.030 .
0.005
0.065
"0.0125
0,005
0.0125
0.030
0.065
0.030
0.005
0.005
0.0125
0.0125
0.0125
0.030
0.065
0.005
0.005
0.065
0.030
0.0125
0.065
0.0125
0.030
0.005
0.030
0.0125
0.0125
0.0125
0.0125
0.030
0.005
0.0125
0.030
0.030
0.0125
0.0125
0.0125
0.065
0.0125
0.030
0.0125
0.065
0.030
0.005
0.06S
0.030
0.0125
0.065
0.005
O.Oin
a
5
'5
5
5
5-
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
C
5
5
5
5
5
5
b
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
-
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
i
c
1
0.5
0.5-
0.5
0.5
0.5
. °-.5
0.5
0.5
0.5
0.5
0.5
1
0.5
0.5
0.5
0.5
1
0.5
0.5
1
1
0.5
0.5
0.5
0.5
0.5
0.5
1
0.5
0.5
1
0.5
0.5
1
1
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
.1 S
K>rc
0.15
0.03
0.08
0.01
0.16
0'.03
0.01
0.03
0.08
0.16
0.08
0.01
0.03
0.03
0.03
0.03
0.08
0.16
0.01
0.01
0.33
0.15
0.03
0.16
0.03
0.08
0.01
0.08
0.06
0.03
0.03
0.06
0.08
0.01
0.06
0.15
0.08
0.03
0.03
0.03
0.16
0.03
0.08
0.03
0.16
0.08
0.01
0.16
0.08
0.03
0.16
0.01
n f>
d
O.Z
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
O.Z
0.05
0.05
0.05
0.05
O.Z
0.05
0.05
O.Z
O.Z
0.05
0.05
0.05
0.05
0.05
0.05
.
O.Z
0.05
0.05
O.Z
0.05
0.05
0.2
O.Z
0.05
0.05
0.06
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
O.OS
0.05
n.-";
"'re
0.03
2 x 10-'
4 x 10-'
5 x 10-»
0.01
Z x 10-'
5 x 10-»
2 x 10-'
4 x 10-'
0.01
4 x 10-'
5 x 10-*
0.01
2 x 10-'
Z x 10-'
2 x 10-'
4 x 10-'
0.03
5 x 10-*
5 x 10-"
0.07
0.03
2 x 10-'
0.01
2 x 10-'
4 x 10-'
5 x 10-*
4 x 10-'
0.01
2 x 10-'
2 x 10-'
0.01
4 x ID"'
5 x 10-*
0.01
0.03
4 x 10-'
2 x 10-'
Z x 10-'
2 x 10-'
0.01
2 x 10"'
4 x 10-'
2 x 10-'
0.01
4 x 10-'
5 x 10—
0.01
4 x 10"'
2 x 10-'
0.01
5 x 10—
t y 1-1-1
e
0.8
0.25
0.25
0.25
O.Z5
0.25
0.25
0.25
0.25
O.Z5
O.Z5
0.25
0.8
0.25
0.25
0.25
0.25
0.8
0.25
0.25
0.8
0.8
0.25
0.25
0.25
0.25
O.Z5
0.25
0.8
0.25
0.25
0.8
0.25
0.25
0.8
0.8
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
n ?s
*'rc
0.12
0.01
0.02
3 x 10-'
0.04
0.01
3 x 10"
0.01
0.02
0.04
0.02
3 x 10-'
0.02
0.01
0.01
0.01
0.02
0.14
3 x 10-'
3 x 10-'
0.26
0.12
0.01
0.04
0.01
0.02
3 x 10-'
0.02
0.05
0.01
0.01
0.05
0.02
3 x 10-1
0.05
0.12
0.02
0.01
0.01
0.01
0.04
0.01
0.02
0.01
0.04
0.02
3 x 10-'
o.ot
0.02
0.01
0.04
3 x 10-'
o."'>
78
-------
TABLE 10. MANUFACTURING EXPOSURE FOR SAMPLE "NEW" CHEMICALS
•vl
UD
No.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
Name
Tris (2,3 dlhromopropyl Phosphate)
Carpet Manufacture
Benzene
Benzene to Styrene
Asbestos >
Cement Pipe Manufacture
Ethyl ene d1 chloride
Et. Dlchloro to Vinyl chloride
Acrylonltrlle
Benzidine Yellow
Unl-Rez 2642 .
011 of Cedar leaf
Flavor Uses
2-benzothlazole-sulfon-
amlde, N-(l,l-d1methyl ethyl)
3-nitro Isatolc anhydride
Dlmercaptothl adlazol e
Formulated to Cutting Oils
Ad1p1c acid -1,4-butanedoil -
4,4'-dipheny1 methane dllsocyanate
Benzyl trlmethyl aiunonlum metnoxide
VttHdeDMTD
Vltride - Cutting Oil Manufacture
Strontium titanate
Acetone
Styrene Pol ysul fide
Hydrogenated Tallow Acids, ethanol
amlne condensate, ethoxylated
Surfynol 104(2, 4,7, 9-tetramethyl-
4,7 dlhydroxy-deca-5-yne)
Ally] alcohol -Styrene Co polymer
Benzenedlazonlum, 2,5-dibutoxy-4-
(4 morphol1nyl)-sulfate
n- butyl ethyl -magnesi urn
Amberlyst Resin Catalyst
Raney Nickel
Phosphorodithioic acid,
S,S'-(thiod1-4)l,phenylene)
0,0,0',0' tetramethyl ester
Hexachlorobenzene
Trichloroethylene
Sulfurlc acid
Iron (II) sulfide
poly (oxy-l,2-ethane-diyl),
a-phenyl-u-hydroxy-, phosphate
Production
kg/yr
4.07 x 106
2.95 x 107
4.67 x 109
2.10 x 10"
8.76 x 107
2.10 x 10"
3.90 x 109
7.70 x W7
6.90 x 10"
6.80 x 10s
1.00 x 10*
4.50 x 109
9.00 x 10s
1.00 x 10s
1.00 x 106
3.75 x 10s
1.00 x 10s
1.04 x 10"
2.00 x 10s
4.00 x 109
1.30 x 10"
1.00 x 10s
2.00 x 109
5.00 x 10"
5.00 x 10*
5.00 x 10s
5.00 x 10s
5.00 x 10s
5.00 x 105
5.00 x 105
1.00 x 10s
5.00 x 10s
1.60 x 106
2.70 x 10"
3.00 x 10"
5.00 x 10s
5.00 x 10s
No. of
plants
1
10
34
15
7
14
18
48
6
4
1
2
100
1
1
1
5
7
1
1
1
1
22
1
1
1
1
1
1
1
1
1
10
5
160
2
7
Max dally
prod, kg
(plant)
11,300
8,000
380,000
38,900
49,700
60,000
600,000
214,000
320,000
640
100
75
360
400
4,000
1,500
2,600
61,000
800
60
430
40
115,000
2,000
2,000
200
2,000
2,000
2,000
1,000
2,800
1,390
4,500
150,000
520,000
700
250
Persist- Operator Exposure
ence - Number mg/ma
1
3
1
1
3
3
1
1
1
3
3
1
1
3
1
3
3
2
3
2
2
3
1
2
2
2
1
2
3
3
3
3
3
1
2
1
3
11
169
1350
574 .
176
371
314
1335
274
31
5
10
172
9
3
12
13
185
10
6
4
4
533
13
13
17
13
13
8
7
11
12
149
64
6760
16
8
0.8
1.0
0.89
0.86
2.6
2.23
0.87
0.89
0.89
0.92
0,20
0.05
0.001
0.66
0.68
2.70
2.60
1.75
l.W
0.08
0.019
0.086
0.88
1.11
1.11
0.25
1.11
1.11
1.67
1.21
1.87
1.43
2.11
0.89
1.78
0.33
0.54
Plant
1.0 km Radius
Number
3,660
124,000
51,000
66,000
22,000
14,600
3,660
7,300
_
3,660
3,660
3,660
-
26,000
3,600
3,600
.
3,600
81,000
3,600
3,600
3,600
3,600
3,600
3,600
3,600
3,600
3,600
36,000
18,000
586,000
7,300
3,600
mg/m*
0.117
3.9
0.6
6.2
3.33
0.07
0.001
0.0008
0.004
0.041
0.0156
0.624
0.083
0.0006
0.0004
1.196
0.021
0.021
0.0021
0.021
0.021
0.021
0.020
0.029
0.014
0.047
1'.56
5.41 2
0.007
0.0026
Vicinity Exposure
2.0 km Radius
Number
14,600
496,000
204,000
263,000
88,000
58,400
14,600
29,200
14,600
14,600
14,600
102,000
14,600
14,600
14,600
321,000
14,600
14,600
14,600
14,600
14,600
14,600
14,600
14,600
14,600
146,000
73,000
,336,000
29,200
14,600
5.0 km Radius
mg/m3 Number
0.035
1.2 3
0.18
1.9 1
0.99
0.02
0.0003
0.0002
0.0010
0.0124
0.005
0.187 :
O.Q25
0.0002
0.0001
0.358 2
0.006
0.006
0.0006
0.006
0.006
0.006
0.003
0.009
0.004
0.014
0.466
1.62 14
0.002
0.0008
91 ,400
,108,000
461,000
,645,000
548,000
366,000
..
_
91,400
91,400
640,000
91,400
_
M
,011,000
91,400
91 ,400
91,400
91,400
91 ,400
91,400
91,400
91,400
91,400
914,000
457,000
,624,000
182,800
91,400
mg/ms
0.007
0.20
0.088
0.4
0.20
0.004
_
_
0.002
0.0009
0.038
0.005
'-
.
0.073.
0.001
0.001
0.0001
0.001
0.001
0.001
0.0006
0.002
0.0008
0.003
0.094
0.328
0.0004
0.0002
-------
TABLE 11. CONSUMER DOSE FOR SAMPLE "NEW" CHEMICALS
No.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
Chemical
TRIS
Benzene
Asbestos
Ethyl ene
bichloride
Acrylonltrile
Benzidine
yellow
Unl Rez
011 of Cedarleaf
2-Benzoth1azole-
sulf on amide
3-nltro Isatoic
Acid
Vanchem DMTD
Adi pic Acid
BenzyltH-
nethyianflon-
lum methoxide
VltHde
Strontium
Tltanate
Acetone
Use
Flame
Retardant
Clothes
Flame
Retardant
Rugs
Paint
Adheslves
Heat
Insulation
Auto Brakes
Appliances
Paint
Polish
Pesticide
Paint
Ink
Clothes
Adhesive
Binder
Cosmetic
Chem. Int.
Vulcanlzer
Dye Paint
Dye Clothing
Catalyst
Reducer
Seal-
Conductor
Paint
Active
Active Inhal .
Popln. Dose (g)
0
0
1.8x10" 865
1.2x10' 31
1.9x10* 0.005
2.5x10' 0.0006
5.0x10' 0.0002
1.9x10" 216
7.5x10" 31-216
1.7x10' 2.3
1.5x10' 0.14
1.0x10* 0.06
1000 6
1.3x10' 0.75
2.5x10* 9
No Consumer Dose
No Consumer Dose
7.6x10' 5.0x10"*
1.8x10* 0.006
1.2x10' 0.4
No Consumer Dose
No Consumer Dose
No Consumer Dose
1.5x10' 665
Active
Contact
Dose (g)
„
48
0.17
0
0
0 .
81
12
4.0x10"'
3.2 (5.0)
0.38
0.95 (1.6)
0.27
0
0
8.7
0.07
K4
Active
Release (g)
6.7x10*
1.6x10*
9.0x10'
7.2x10'
1.7x10*
1.6x10*
1-6x10'
1.6x10'
1.5x10'
4.3x10*
4.3x10'
7.0x10'
9.2x10*
3.0x10'
5.4x10'
2.1x10'
5.2x10"
Passive
Popln.
2.2x10'
6.0x10'
1.3x10*
1.3x10*
1.3x10'
2.5x10'
5.0x10*
1.3x10*
1.3x10'
2.5x10*
1.0x10'
1.0x10'
1.0X10'
1.3x10'
2.5x10'
1.5x10'
1.3x10'
1.3x10'
1.0x1(1*
Passive Passive
Inhal . Contact
Dose (g) Dose (g)
0.071 2.7x10""
0.55 1.6xlO"s
0 0
0 0
O.OC04 0
0.025 0
2.3x10'' 0
0 0
0-0.14 0.08
1.8x10"' 0
6.0x10"' 0.16
5.0x10"' 0.47
4:5x10'' 3.6
0.003 0.02
0 0
0.007 0
0.002 0.014
0.0003 14
0 0
Passive
Release
(g)
2.9x10'
2.1x10'
0
0
9.8x10'
3.2x10*
1.9x10*
0
3-5x10'
1.4x10'
1.3x10'
4.7x10'
3.6x10'
3.5x10'
0
4.5x10'
3.4x10'
1 .BxlO'
2.3x10"
Disposal
(9)
2.9x10*
4.1x10'
0
0
9.3x10"
4.5x10'
1.8x10'
0
0-5.3x10"
0
2.2x10*
4.7x10'
8.7x10'
6.4x10"
0
1.0x10"
7.9x10'
4.3x10'
0
Styrene Polysulflde
Hydrogenated Tallow Acid
Surfynol
AlTyl Alcohol
Copolymer
Benzenediazonlum
2,5-D1butoxy-4
(4-morpholynl)-
Sulphate
n- butyl ethylmag-
meslum
Amberlyst
Raney Nickel
Phosphorodlthlolc
Add
Hexachloro-
Benzene *
Trichloro ethyl ene
Sulfuric Acid
Iron Sulfide
Poly (oxy-1,2-
ethane-diyl, a-
phenyl-w-hydroxy- ,
phosphate
Cl eaner
Cleaner
Dye Paint
Dye Cloth
Catalyst
Catalyst
Catalyst
Pesticide
Pesticide
Paint
Adhesive
Cleaner
Eletrolyte
Paint
Electrolyte
5.0x10' 0.04
1.0x10' 0.003
1.5x10' 0.006
10* 0.4
No Consumer Dose
No Consumer Dose
No Consumer Dose
1.8x10' 0.035
7.0x10' 0.71
1.9x10* 108
1.3x10' 28
6.3x10" 19C
2.5x10' 1.0x10"'
7.5x10* 0.027
2.5x10' 1.0x10'
8.6
14
6.5x10"*
7.8x10"'
0
4.8x10"'
4.4
0.004
0.45
1.1
2.8x10"*
1.0xlO'«
9.5x10'
1.4x10'
4.3x10'
1.7x10'
2.8x10*
1.1x10*
8.4x10'.
1.5x10'
5.9x10*
3.6x10'
9.5x10*
3.6x10*
5.0x10*
1.0x10'
1.0x10'
1.0x10'
2.5xlOs
1.0x10'
1.3x10'
1.3x10*
1.3x10*
2.5x10'
5.0x10'
2.5x10'
O.OCC3 3.8
0.00024 1.6
0.001 6.5x10"°
0.002 0.23
0 0
1.8xlO"'-2.5xlO"' 0
0 0
0-0.005 0-0.001
0 0
8.0x10"' 0
5.5x10"' 5.5x10''
0 0
3.9xlOT
4.2x10'
7.1X10'
1.4x10'
0
1.0x10'
0
7.6x10'
0
1.8x10'
5.7x10'
4.'.xlO'
1.9x10'
7.5x10"
6.4x10'
3.5x10'
0
7.3x10'
0
1.5x10"
0
1.6x10'
1.3x10*
1.6x10*
-------
APPENDIX
Table A-l. Production Volume for Various Use Functions A-l
Sources of Market Data A-3
Table A-2. Market/Product!on Competitive Data by Auerbach Code . . . A-4
Table A-3. Production Volume for Chemical Function Categories. . . . A-ll
B. Physical and Chemical Properties of "New" Chemicals ....... A-15
C. Development of Diffusion Parameter A-45
D. Chemical Permeability Parameter A-48
E. Sample Calculation for Tris - Consumer Dose A-49
A-l
-------
TABLE A-l. PRODUCTION VOLUME FOR VARIOUS I USE FUNCTIONS.
Function
Code
0032
004, 007
331
308
009
014
049
056
087
102
102
293
296
354
112
114
123
1330
1331
1331
137
141
163
173
180
136
200
206
211
212
217
220
224
236
271
272
2722
305
331
3390
341
341
370
349
3542
362
365
372
382
Descriptor
Ultraviolet Absorbers
Accelerators, Activators,
Vulcanizing Agents
Polymerization Regulators
Aerosol Propel 1 ants
Antifreezes
Anti-Knock Agents
Antistatic Agents
Blowing Agents
Blowing Agents ^^*^
Oxidation Inhibitors /
Ozonation Inhibitors ?"
Stablizers )
Catalysts
Caulking Compounds
Cleaners
Dyes
Pigments (Organic)
Pigments (Inorganic)
Corrosion Inhibitors
Crossl inking Atents
Deemulsifiers
Detergent Builders
Antiseptics
Dryers
Enzymes
Explosives
Fertilizers
Feber Forming Compounds
Fire Extinguishing Agents
Flame Retardants
Flocculating Agents
Fungicides
Lubricant Additives
Lubricants
Internal Lubricants
Plasticizers
Rust Inhibitors
Chelaflng Agents
Sizes (Textile)
Sizes "2
Thickeners _^
Soil Conditioners
Heat Stabilizers
Surfactants
Tanning Agents
Toners
Mater Repellents
Production
Year Ib
/ V
1977V" 152x10'
r
1977(") 1.35x10*
1977*') 198x10'
1977ll) 264x10'
197?(') 69x10'
197?(') 28x10'
1977(>) 15.4x10'
1977(l) 6x10'
1977(l) 143x10'
1977^ '' 1.5x10'
/ \
1977"' 1.8x10'
1977(l) 168x1 0°
1977(l) <236xlO'
1977(l) 4.7x10'
1977^ 62x10'
1977^ ') 67x10'
Year
1973la)
/ ^
197711'
1977(:)
1977(1=)
1975(lo)
1980(")
1977(2)
1977(2>
1977ll)
1978(u)
1977(l)
1976^'
1977
1977
1976l:)
1977(2)
1977(2)
1978(io)
1977(.o)
1977
1977
1977(l)
1976(2)
1976(2)
1977
1978(io)
1977(n)
1977
1977
1977
1978(li)
1977<2)
1977
1977do)
1977
1977(2)
197?(2)
1977
1977(l)
1977
1977
1977
1977U)
Sales
' Ib •-.
9.9x10*
83.2x10*
4.1x10*
375x10'
218*xlO'
320x10
4.4x10'
355x10'
117x10'
1.0x10'
1.8x10'
254x10'
57x10'
2.8x10'
29.5x10
75x10*
9.8x10'
11.1x10'
10.9x10'
3.3x10'
97x10*
355x10'
15*xlO'
360x10'
60x10'
133x10'
1.3x10'
450x10'
66x10'
1.7xi09
20x10'
140x10'
40x10'
< 219x10'
94x10'
-, 2.5x10'
56x10'
56x10'
Dollars
35x10'
95.7x10*
1.4x10*
90x10'
435x10'
5x10'
167x10'
143x10'
670x10'
325x10'
1.5x10'
690x10'
268x10'
1.3x10'
1.4x10'
45x10'
42.2x10'
10.6x10'
52x10'
450x10'
6.8x10'
171x10'
8x10''
190x10'
5.9x10'
189x10'
492x10'
45x10"
'632xl06'
70x10'
360x10'
• <416xlO'
80x10'-
875x10'
25x10'
237x10'
60x10'
Annual
Growth
Rate %
6-10
5
6
1.5-3
3
9
5
12
4
3
6
9
4
7
10
3
1
4.5(2)
6
4
8
4
0
10
15
3
6
15
0
4
6
2
0
—
6
24
Selling
Price
Range, $/lb
2.80- 10.50
0.64-3.37
0.17
0.12-0.60
2.19*
0.47
1.22
0.67
0.18
2.70
4.66-25
0.40
1.53
20
1.39-6.40
0.65-155
0.14
0.33-0.64
0.53*
0.53
0.79-1.10
0.38-7.70
0.26-0.73
0.68
0. 28-71
0.43-0.93
0.50-3.11
0.85
0.16-1.39
0.43-0.49
4.71
Number
of
Competitors
11
15
750
7
11
13
30
41
35
10
7
8
50
12
20
9
33
11
2
40
31
29
20
54
8
164
7
35
•Gallons
A-2
-------
SOURCES OF MARKET DATA
1. Synthetic Organic Chemicals, U.S. Production and Sales, 1977, U.S.
Government Printing Office, Washington, D.C., 1978.
2. Kline Guide to the Chemical Industry, Third Edition, Charles H. Kline
and Company, Inc., Fairfield, New Jersey, 1977.
3. U.S. Industrial Outlook, 1978, U.S. Government Printing Office, Wash-
ington, D.C., 1978.
4. Faith. Keyes & darks' Industrial Chemicals, Fourth Edition, John Wiley
and Sons, New York, New York, 1975.
5. Chemical Week Buyer's Guide, 1979, McGraw-Hill Publishing Co,, New York,
New York, 1979.
6. Modern Plastics Encyclopedia, 1976, McGraw-Hill Publishing Co., New
York, New York, 1976.
7. 1978-79 OOP Chemical Buyers' Directory, Schnell Publishing Company, New
York, New York, 1978.
8. Textile Chemist and Colorist Buyer's Guide, 1978, American Association
of Textile Chemists and Colorists, Research Triangle Park, North Caro-
lina, 1978.
9- 1977 Rubber Red Book, Bill Communications, Inc., Akron, Ohio, 1977.
10- Pulp and Paper Buyer's Guide, 1979, Miller Freeman Publications, San
Fransisco, California, 1979.
11- 1975 Directory of Chemical Producers, SRI International, Chemical
Information Services, Stanford, Research Institute, 1975.
A-3
-------
TABLE A-2. MARKET/PRODUCTION COMPETITIVE DATA BY AUERBACH CODE
Function
Code
001
002
003
0030
0031
0032
004
007
008
009
012
013
014
015
021
029
030
034
035
036
041
045
046
047
048
049
056
069
070
071
0710
075
076
077
079
081
082
083
084
086
087
088
096
Function
Description
Ablatives 7°
Abrasives
Absorbents
Gas
Liquid
Ultraviolet
Accel erators
Activators
Adhesion Promoters
Adhesives
Adsorbents .
Aerating Agents
Aerosol Propellents
Algicides
Animal Repellents
Antiblocking Agents
Anti caking Agents
An ti cracking Agents
Anticratering Agents
Anti crock Agents
Antifelting Agents
Anti flooding Agents
Antiflame Agents
Anti fogging Agents
Antifouling Agents
Antifreezes
Antiknock Agents
Anti pi 11 ing Agents
Antiplasticizers
Anti protozoa! Agents
Amebicides
Antisagging Agents
Antlscaling Agents
Antiscorching Agents
Antiseptics
Antisettling Agents
Antiskid Agents
Antiskinning Agents
Anti slip Finishing Agents
Anti staining Agents
Anitstatic Agents
Antitack Agents
Bactericides
Function
Type*
-------
TABLE Ar2. (CONT.)
Function
Code
.097
098
099
100
101
102
1020
103
104
105
106
108
110
1100
112
114
118
119
120
121
1210
1211
1212
127
128
129
130
131
132
133
133
133
136
137
138
139
140
141
142
143
144
145
146
Function
Description
Bacteriostats
Binders
Bleaches
Bleaching Assistants
Bloom Inhibitors
Blowing Agents
Air Entraining Agents
Bluing Agents
Boil off Assistants
Bright Dips
Bright en ers
Carbonizing Agents
Carriers
Dye Carriers
Catalysts
Caulking Compounds
Chain Extenders
Chain Stoppers
Chain Transfer Agents
Chemical Intermediates
Inorganic
Organic
Polymerization
Clarifiers
Cleaners
Cloud Point Depressants
Coagulants
Coalescents
Coatings
Coloring Agents
Coloring Agents, Clothes
Coloring Agents, Paint
Correction Fluids
Corrosion Inhibitors
Coupling Agents
Crabbing Assistants
Greaseproof ing Agents
Crossl inking Agents
Curing Agents
Currying Agents
De- inkers
Deaerating Agents
Deasphalting Agents
Function
Type*
'c1
1
1 :
0.5
1
1
1
1
1
1
1
1
1
1
1
0.5
0.5
1
1
1
0.5
0.5
0.5
0.5
1
0.5
1
1
1
0.5
0.5
•0.5
0.5
1
1
1
1
1
1
1
1
1
1
1
Total No.
Competitors
Within Range
1-25
51-100
1-25
1-25
1-25
1-25
1-25
1-25
1-25
1-25
1-25
1-25
1-25
1-25
5 -100
25-50
1-25
1-25
1-25
100+
51-100
'51-100
26-50
1-25
26-50
1-25
1-25
1-25
100+
100+
26^50
51-100
1-25
51-100
1-25
1-25
26-50
"' 1-25
26-50
1-25
1-25
1-25
1-25
A-5
-------
TABLE A*2, (CONT.)
Function
Code
147
1470
149
1490
1491
1492
150
151
153
154
155
156
157
158
159
160
161
162
163
164
166
1660
167
169
170
171
172
173
174
1740
175
179
180
185
186
187
188
189
190
191
192
193
194
195
1950
Function
Description
Dechlorinating Agents
Antichlors
Decontamlnants
Mercury
Poison Gas
Radioactivity
Def earners
Defoliants
Degreasers
Degummers
Dehalring Agents
Dehumidifiers
Deydrating Agents
De-icers
De-ionizers
Del 1gn1fi cation Agents
Delustrants
Demineralizers
Demulsiflers
'Denaturants
Deodorants
Masking Agents
Dep1tch1ng Agents
Descaling Agents
Desiccants
Desizing Agents
Detackifiers
Detergent Builders
Developers
Dye Developers
Devulcanlzing Agents
Discharge Printing Agents
Disinfectants
Drawing Compounds
Dri ers
Drilling Mud Conditioners
Drilling Muds
Dry Strength Agents
Dust Control Agents
Dusting Atents
Dye Reserving Agents
Dye Retardants
Dye Retention Aids
Electrolytes
Peptlzing Agents
Function
Type*
,c,
1
1
1
1
1
1
1
1
0.5
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1 :
1
0.5
0.5
Total No.
Competitors
Within Range
1-25
1-25
1-25
1-25
1-25
1-25
50-100
1-25
1-25
1-25
1-25
1-25
1-25
1-25
1-25
1-25
1-25
1-25
1-25
1-25
26-50
1-25
26-50
1-25
1-25
1-25
1-25
1-25
1-25
1-25
1 25
1-50
26-50
1-25
1-25
26-50
1-25
1-25
1-25
26-50
1-25
1-25
-,;, 1-25
1-25
1-25
A-6
-------
TABLE A-2. (CONT.)
Function
Code
196
199
200
205
206
2060
2061
207
208
210
211
212
213
214
215
217
219
220
221
224
227
2270
2271
2272
2273
2274
228
230
232
233
234
236
237
2370
2371
239
241
243
244
2440
2441
2442
248
250
251
Function
Description
Eluting Agents
Entraining Agents
Enzymes
Explosion Inhibitors
Explosives
Blasting
Propel 1 ant
Extenders
Feed Chemicals
Ferti 1 izer Condi 1 1 on ers
Fertilizers
Fiber Forming Compounds
Fillers (Augmentation)
Fillers (Patching)
Filtration Aids
. Fire Extinguishing Agents
Fixatives (Dye)
Flame Retardants
Flatting Agents
flocculating Agents
Fluxes
Brazing
Galvanizing
Soldering
Tinning
Welding
Foam Inhibitors
Formation Aids
Frothing Agents
Fuels
Fulling Agents
Fungicides
Fung is tats
Mildew Preventives
Mold Inhibitors
Gelling Agents
Greaseproof ing Agents
Heat Sealing Agents
Heat Transfer Agents,. ,._ ...
Calefactants
Coolants
Refrigerants
Herbicides
Hunectants
Humidity Indicators
Function
Type*
'c'
1
1
1
1
0.5
0.5 ,
0.5
1
0.5
1
0.5
1
1
1
1
1
1
1
1
1
0.5
0.5
0.5
0.5
0.5
0.5
1
1
1
0.5
1
0.5
I
1
1
1
1.
1
1
1
1
1
0.5
i
1
Total No.
Competitors
Within Range
1-25
1-25
26-50
1-25
1-25
1-25
1-25
26-50
1-25
1-25
26-50
1-25
51-100
1-25
26-50
1-25
1-25
26-50
1-25
26-50
1-25
1-25
1-25
1-25
1-25
In25
51-100
1-25
1-25
26-50
1-25
26-50
1^5
1-25
1-25
1-25
1-25
1-25
,. 1^5
1-25
1-25
1-25
26-50
1-25
1,25
A-7 '
-------
TABLEAU. (CONT.)
Function
Code
252
2520
256
257
259
2590
260
2600
2601
2602
261
2610
262
2623
263
264
265
266
269
2690
2691
271
272
273
275
276
277
278
282
283
2830
284
285
286
287
288
290
293
294
295
296
298
299
2991
300
Function
Function Type*
Description 'c1
Hydraulic Fluids
Automatic Transmission
Incendiaries
Inflating Agents
Insect Repel 1 ants
Mothproofing Agents
Insulating Compounds
Acoustical
Electrical
Heat
Intensifiers
Dye Intensifiers
Ion Exchange Compounds
Flotation Agents
Kier Assistants
Lachrymators
Laminating Agents
Laundry Soaps
Leveling Agents
, Dye Leveling
Vulcanization Leveling
Lubricant Additives
Lubricants
Markers (Textile)
Mercerizing Agents
Metal Conditioners
Microbiological Culture Media
Mordants
Nucleating Agents
Nutrients
Bacteriological
Obscuring Agents
Odorants
Oil Repellents
Oiliness Agents
Opacifiers
Optical Brighteners
Oxidation Inhibitors
Oxi dati on-Reducti on indicators
Oxidizers
Ozonation Inhibitors
Pearl i zing Agents
Pesticides (Fumlgants)
Insecticides
pH Control Agents
0.5
0.5
1
1
0.5
0.5
0.5
0.5
0.5
0.5
1
1
1
1
1
1
1
1
1
1
1
1
0.5
1
1
1
1
1
1
1
I
I
1
I
1
1
1
1
1
1
1
1
0.5
0.5
1
Total No.
Competitors
Within Range
1-2S
1-25
1-25
1-25
1-25
1-25
51-100
1-25
26-50
1-25
1-25
1-25
1-25
1-25
1-25
1-25
1-25
1-25
1-25
26-50
1-25
26-50
100+
1-25
1-25
1-25
1-25
1-25
1-25
1-25
1-25
1-25
1-25
1-25
1-25
1-25
1-25
26-50
1-25
1-25
1-25
1-25
26-50
AI—
1-25
1^5
A-8
-------
TABLE A«?*-.(CONT.)
__. ... . _. .
Function
Code
301
302
304
305
308
309
310
311
312
315
316
318
319
320
322
323
325
327
328
329
331
332
333
335
336
337
338
339
3390
3391
340
341
342
344
345
346
347
348
349
350
351
352
353
Function
Description
pH Indicators
Pickling. Agents
Plastic-forming Compounds
Plastldzers
Polymerization Inhibitors
Pres potting Agents
Preservatives
Prevulcanization Inhibitors
Protective Agents
Pulping Retention Aids
Radiation Protective Agents
Reaction Media
Reducers
Refining Agents
Repulping Aids
Resists
Rotproofing Agents
Rubber-forming
Rubber Reclaiming Agents
.Rubbing Fastness Agents
Rust Inhibitors
Rust Removers
Scavengers
Scouring Agents
Scrooping Agents
Sealants
Semiconductors
Sequestrants
Chelating Agents
Complex! ng Agents
Shrinkage Controllers
Sizes
SUme Preventives
Soaking Agents
Soap Builders
Soaping Agents
Soaping-off Assistants
Softeners
Soil Conditioners
Soil Release Agents
Soil Retardants
Solvents
Spreading Agents
Function
Type*
'c'
1
0.5
1
1
1
1
1
1
1
1
1
0.5
0.5
1
1
0.5
1
1
1
1
1
1
1
1
1
0.5
0.5
1
1
1
1
1
1
1
1
1
., 1
0.5
0.5
1
1
0.5
1
Total No.
Competitors
Within Range
1-25
1-25
26-50
51 -100
1-25
1-25
51-100
1-25
1-25
1-25
1-25
26-50
1-25
1-25
1-25
1-25
1-25
26-50
1-25
1-25
51-100
26-50
1-25
26-50
26-50
51-100
1-25
26-50
26-50
1-25
1-25
26-50
1-25
1-25
1-25
1-25
1-25
51-100
1-25
26-50
1-25
100+
1-25
A-9
-------
TABLE A-2. (CONT.)
Function Function
Code
354
3540
3541
3542
355
356
357
358
3580
3581
3582
359
360
362
3620
3621
3622
3623
3624
3625
3626
3627
363
364
365
3650
366
367
368
369
370
372
379
380
3800
3801
3802
381
382
383
384
385
Description
Stabilizers
Emulsion
Foam
Heat
Stains
Starch Improvers
Stiffening Agents
Stri ppers
Dye
Paint
Wax
Structural Binders
Structural Components
Surfactants
Detergents
Dispersants
Emulsifiers
Floatation Agents
Penetrants
- Rinse Aids
Soil Suspending Agents
Wetting Agents
Swelling Agents
Tackifiers
Tanning Agents
Bates
Tar Removers
Tarnish Removers
Textile Conditioners
Texturizers
Thickeners
Toners
Vat Printing Assistants
Viscosity Adjusters
Thixotropic Agents
Viscosity Depressants
Viscosity Improvers
Vulcanizing Agents
Water Repellents
Water Proofing Agents
Weighting Agents
Wet Strength Agents
Function
Type*
•c.1
1
1
1
1
1
1
1
0.5
1
0.5
0.5
1
1
0.5
0.5
0.5
0.5
0.5
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
Total No.
Competitors
Within Range
26-50
1-25
1-25
1-25
1-25
1-25
1-25
26-50
1-50
26-50
1-25
1-25
1-25
100+
51-100
51-100
51-100
51-100
51-100
26-50
26-50
51-100
26-50
26-50
1-25
1-25
1-25
1-25
1-25
1-25
26-50
1-25
1-25
1-25
1-25
1-25
26-50
1-25
26-.50
26-50
1-25
1-25
*0.5 =
1 =
Slow-to-Penetrate Current Market
Quick- to-Penetrate Current Market
A-10
-------
TABLE A-3. PRODUCTION VOLUME FOR CHEMICAL FUNCTION CATEGORIES
2
2
3
3
8
9
9
14
15
21
30
34
35
36
41
45
46
47
48
49
56
69
70
75
77
79
81
82
84
86
87
88
96
97
99
102
103
106
114
127
130
132
132
133
133
133
Function
Abrasives
Abrasives
Absorbents
Absorbents
Adhesion Promoters
Adhesives
Adhesives
Aerosol Propel 1 ants
Algicides
Animal Repellents
Anti caking Agents
Anticraking Agents
Anti crater ing Agents
Anti crock Agents
Anti felt ing Agents
Anti flooding Agents
Anti fume Agents
Antifogging Agents
Anti foul ing "Agents
Antifreezes
Antiknock Agents
Art ti pi 11 ing Agents
Antiplasticizers
Antisagging Agents
Antiscorching Agents
Antiseptics
Anti sett! ing Agents
Antiskid Agents
Antislip Finishing Agents
Anti staining Agents
Antistatic Agents
Anti tack Agents
Bactericides
Bacteriostats
Bl eaches
Blowing Agents
Bluing Agents
Brighteners
Caulking Compounds
Clarifiers
Coagulants
Coatings
Coatings
Coloring Agents
Coloring Agents
Coloring Agents
Annual Production, kg
4.2xl07 KG
4.2xl07 KG
l.SxlO7 KG
l.SxlO10 KG
8.3xl08 KG
l.lxlO8 KG
5.5xl07
5.5xl07
2.6xl06
2.6xl06
2.6xl08
2.6xl06
l.OxlO8
l.SxlO10
3.7xl09
6.6xl08
2.6xl06
2.1xl09
2.9xl08
8.8xl09
2.4xl07
5.5xl07
l.lxlO9
5.5xl08
2.2xl06
9.7xl06
5.3xl07
14 *i /\Q
.IxlO9
5.5xl07
7.9xl08
2.2xl08
S.lxlO8
2.0xl06
1.2xl09
6.6xl07 (ink)
l.lxlO9 (clothes)
4.4xl08 (paint)
A-ll
-------
TABLE A-3. (cont.)
136
137
140
141
142
143
150
151
153
158
161
162
166
170
171
173
174
180
186
189
190
193
195
200
206
207
210
211
212
213
214
217
220
221
227
228
230
233
236
237
239
241
243
244
259
260
261
262
Function '•
Correction Fluid
Corrosion Inhibitor
Creaseproofing Agents
Cross! inking Agents
Curing Agents
Currying Agents
Defoamers
Defoliants
Degreasers
Deicers
Delustrants
Demi n era lizers
Deodorants
Dessi cants
Desizing Agents
Detergent Builders
Developers
Disinfectants
Dri ers
Dry Strength Agents
Dust Control Agents
Dye Retardents
Electrolytes
Enzymes
Explosives
Extenders
Fertilizer Conditioners
Fertilizers
Fiber Forming Compounds
Fillers
Fillers (Patching)
Fire Extinguishing Agents
Flame Retardents
Flatting Agents
Fluxes
Foam Inhibitors
Formation Aids
Fuels
Fungicides
Fungi stats
Gelling Agents
Greaseproof ing Agents
Heatsealing Agents
Heat Transfer Agents
Insect Repel! eents
Insulating Compounds
. Intensifiers
Ion Exchange Compounds
Annual Production, kg
1.2xl07
S.OxlO8
6.6xl07
6.6xl07
2.6xl09
1.2xl07
6.6xl06
6.2xl08
1.3xl07
6.6xl07
2.2xl08
S.lxlO8
6.6xl07
2.0xl09
5.5xl07
2,4xl07
2.4xl07
1.2xl09
6.6xl07
8.8xl08
2.2xl07
7.2xl09
4.3xl08
2.2xl08
l.lxlO10
7.9xl08
4.2xl08
4.4xl07
2.6xl08
7.9xl08
2. 2x10 8
>2.2xl06
9.9xl07
9.9xl07
l.OxlO12
2 8xl08
t. • W/\ J, w
1.2xl09
2.2xl07
2.2xl07
2, 2x10 7
8.8xl08
2.2xl07
5.0xl07
A-12
-------
TABLE A-3. (cont.)
.
269
271
272
273
276
283
285
286
287
290
293
294
295
296
298
300
301
304
305
310
312
321
325
327
329
331
332
335
339
340
341
342
345
346
348
350
351
352
352
352
354
356
357
358
359
360
Function .*: •
Leveling Agents
Lubricant Additives
Lubricants
Markers (Textile)
Metal Conditioners
Nutrient
Odorants
Oil Repellents
Dili ness Agents
Optical Brighten ers
Oxidation Inhibitors
Oxidation Reduction Indicators
Oxidizers
Ozonation Inhibitors
Pearl izing Agents
pH Control Agents
pH Indicators
Plastic Forming Compounds
Plasticizers
Preservatives
Protective Agetns
Reinforcing Agents
Rotproofing Agents
Rubber Forming Compounds
Rubber Fastness Agents
Rust Inhibitors
Rust Removers
Scouring Agents
Sequest rants
Shrinkage Controllers
Sizes
Slime Preventers
Soap Builders
Soaping Agents
Softeners
Soil Release Agents
Soil Retardents
Solvents
Solvents
Solvents
Stabilizers
Starch Improvers
Stiffening Agents
Strippers
Structural Binders
Structural Components
Annual Production, kg
7.0xl06
4..0xl06
9.9xl08
*
4.4xl07
>2.2xl06
>2.2xl06
1.2xl08
3. 2x10 6
4.2xl07
2.6xl08
2.2xl06
4.2xl08
2.0xl06
>2.2xl06
>2.2xl06
4.4xl09
4.0xl09
2.6xl07
8.8xl07
2.6xl09
2.2xl07
8.8xl07
2.6xl08
4.4xl07
1.2xl07
1.2xl08
8.8xl07
1.7xl08
l.SxlO7
4.0xl06
4.0xl06
4.4xl09 (paint)
2.2xl08 (adhesive)
2.2xl09 (cleaners)
2.9xl08
4.4xl08
2.6xl08
1.2xl08
A-13
-------
TABLE A-3. Ccont.)
Function Annual\ Production, kg
362
362
364
366
367
370
372
380
382
383
384
385
Surfactants
Surfactants
Tackifiers
Tar Removers
Tarnish Removers
Thickeners
Toners
Viscosity Adjusters
Water Repellents
Waterproofing Agents
Weighing Agents
Wet Strength Agents
Waxes
6nvi n9
. UXJ.U
1.2xl07
4. 4x10 6
1.2xl07
9.0xl08
8.8xl07
1.4xl08
6.6xl07
4.4xl08
1.2xl09
8. 8x10 6
A-14
-------
NO.
CHEMICAL' Tris (2,3-dibromopropyl) phosphate
STRUCTURE: (BrCH2BrCHCH20)3P = 0
INFORMATION SOURCES;
1. Computer search of Chemical Abstracts
2. Personal knowledge
3. Handbook of Chemistry and Physics, 58th ed.
4. A. Leo, C. Hansch and D.E. Chin, Chem. Rev. , 71, 525 (1971)
5. C. Hansch et al., J. Med. Chem.. j£, 1207 (1973)
6. Chemical Use List, EPA, Federal Register, 43, 32222 (1978)
7. Aldrich Catalog, 1979
PROPERTIES: Oil, very low volatility, moderate chemical stability
Log p**>5 (est.) =2.53 (tripropylphosphate) + 5 (6 Br) = 7.5
m.p. °C: _ Water Sol. extremely low
b.p. °C: (est'). >40° _ Vapor Pressure > 20°C 112°c d7 2.24
USES: Flame retardant for plastic, textiles, rubber, other materials
DIRECT TRANSPORT; Low potential for wide distribution. Steady state concentration
should be: Air: extremely low
Land: high
Water: extremely low-would sink to bottom
DIRECT SYSTEMIC UPTAKE: Capable of rapid absorption through skin and other membranes,
through lungs and through walls of G.I. tract.
BY-PRODUCT FORMATION: a) Manufacture; May be produced by reaction of 2,3-dibromopropanol
with phosphorous oxychloride or phosphorous pentachloride or by bromination of triallyl
phosphate. Possible by-products: bis-and mono-dibromopropyl phosphate esters, bromopro-
penyl phosphate esters, bromopropenol, dibromopropene, allyl alcohol, hydrochloric acid,
hydrobromic acid, phosphoric acid and salts, b) Processing: Possible by-products:
bis-and mono-dibromopropyl phosphate esters, dibromopropanol tris-(bromopronenyl)
phosphate esters, bromopropenol, dibromopropene, hydrobromic acid, phosphoric acid,
tribromopropane, bromopropene.
DEGRADATION IN THE ENVIRONMENT: Subject to partial and complete hydrolysis of the
phosphate ester functions,- dehydrohalogenation, oxidation, and biodegradation. Also
alkylating agent, capable of alkylating biomaterials (alkyl halide function).
BIO-ACCUMULATION: Not subject to bioaccumulation in the food chain. Could accumulate
in the individual animal by alkylation of biopplymers.
A-15
-------
NO.
CHEMICAL: Benzene ., .,.'... ? :-,... .-..
STRUCTURE:
>
INFORMATION SOURCES:
i'1"
1. Merck Index, 9th ed., 1976
2. C. Hansch et al, J. Med. Chem., 16, 1207 (1973)
3. Personal knowledge
4. Chemical Use List, EPA, Fed. Register, 43, 32222 (1978)
5. Handbook of Chemistry and Physics .
6.
7.
PROPERTIES: Liquid, volatile, chemically stable
Log P2 = 2.13
m.p. °C: Water Sol. Q.07%1
b.p. °C: 80 Vapor Pressure @ 20°C 75mm He
Flash Pt I0-l2°c1 d1* 0.88
USES: Chemical intermediate-organic compounds. Solvent for waxes, oils, resins, etc.
Reaction medium, manufacture of organic compounds, drugs, dyes, artificial leather,
linoleum, airplane dopes, varnishes, lacquers. Veterinary medicine.
DIRECT TRANSPORT; Potential for wide distribution in the environment. Steady state
concentrations should be Air: high
Land: intermediate
Water: low-capable of spreading on surface of water
DIRECT SYSTEMIC UPTAKE: Capable of rapid absorption through skin and other membranes,
through lungs, and through walls of gastrointestinal tract.
BY-PRODUCT FORMATION: /
11 •• • — ' ' ---- -4 '-..
a ) Manufacture: Produced from coal during coking and cracking processes .
By-Products include a variety of coal ta.r chemicals .
b) Processing: Relatively stable compound. Unlikely to be significant amounts
of by-products formed during processing except when used as chemical inter-
mediates.
DEGRADATION IN THE ENVIRONMENT: Subject to photOQhemical, oxidative and bio-
degradation. Initially, hydroxylated products would be formed .(phenolic compounds) .
BIO-ACCUMULATION: Not subject to bioaccumulation.
A-i
-------
NO.
CHEMICAL: Asbestos Calcium-Magnesium Silicates (Native)
STRUCTURE:
INFORMATION SOURCES;
lm Merck Index, 9th Ed.
2. IITRI Information
3. Chemical Use List, EPA
4.
5.
6.
7.
PROPERTIES: Fine fibers,.. stable, nonr-volatile. Tnsnlnhlp in
organic solvents i , •• ' •
m.p. °C: Water Sol. insoluble
b.p. °C: r__ Vapor Pressure @ 20°C
•
Flash Pt d 2-5~3
Heat insulating compound for building construction, cements, furnace
and hot pipe coverings, inert filler medium, fireproof gloves, clothing, brake
linings.
DIRECT TRANSPORT; LOW potential for distribution. Steady state concentrations
should be: Air: Low but fine dust can be suspended in air and carried by air
currents, Land: High, Water: Low; again fine particles can remain suspended
and carried by water currents.
DIRECT SYSTEMIC UPTAKE; Cannot be systemically absorbed through skin, lungs or
intestinal walls. Can be retained embedded in lung tissue.
BY-PRODUCT FORMATION:
«0 Manufacture; Obtained in mining operations. Only by-products would be
associated minerals present in the mine.
b) Processing; By-products formation: negligible
DEGRADATION IN .THE ENVIRONMENT: Stable (based on extensive experience, use).
BIO-ACCUMULATION; Not subject to bioac.qumula.tion in the food chain. Could
accumulate in the lungs of an individual.
A-17
-------
NO.
CHEMICAL: Ethylene Dirhlnr-Mp _ - - •' • • _
STRUCTURE: C1CH2CH2C1
INFORMATION SOURCES:
1- Merck Index, 9th Ed.
2. Personal knowledge
3- A. Leo, C. Hansch and D. Elkins, Chem. Rev. , 71, 525 (1971)
4. C. Hansch et al, J. Med. Chem., JU5, 1207 (1973)
5. Chemical Use List, EPA
6. Handbook of Chemistry and Physics, 45th Ed.
7-
PROPERTIES: Liquid, volatile, moderate chemical stability
Log P3'* (estimated) =1.54 (C2H5C1) +0.71 (Cl) =2.25
m.p. °C: _ Water So1.o._82 _
b.p. °C: 83-84 _ Vapor Pressure @ 20° C (approximated 65mm Hg
Flash Pt I5°c ~ d2° 1.26 _ : _
USES: Solvent for fuels, oils, waxes, gums, resins, rubber; solvent used in
manufacture of acetyl cellulose and in tobacco extraction. Chemical inter-
mediate.
DIRECT TRANSPORT; Potential for wide distribution in environment. Steady state
concentrations should be: Air: high
Land : intermediate
Water: moderate-would tend to sink to bottom
DIRECT SYSTEMIC UPTAKE: Capable of rapid absorption through skin and other
membranes, through lungs and through walls of G.I. tract.
BY-PRODUCT FORMATION:
a) Manufacture; Produced by chlorination of ethylene a"nd by addition of hydrogen
chloride to acetylene. Possible by-products; vinyl chloride, polyvinyl chloride,
starting materials.
b) Processing; Possible by-products: vinyl chloride, poiyvinyl chloride, hydrogen
chloride, alkylated materials.
DEGRADATION IN THE ENVIRONMENT: Subject to dehydrohalogenation, oxidation, and bio-
degradation. Also alkylating agent of relatively low reactivity. Capable of
alkylating biomaterials (alkyl balide function) .
BIO- ACCUMULATION : Not subject to bioadcumulation in the food chain. Could accumulate
in the individual animal by alkylation of biofpo'lymersv
• A- 18
-------
NO.
CHEMICAL: Asbestos CalciunHMagnesium Silicates (Native)
STRUCTURE:
INFORMATION SOURCES:
lm Merck Index, 9th Ed.
2. IITRI Information
3. Chemical Use List, EPA
4.
5.
6.
7.
PROPERTIES: Fine fibers, stable, non-r-volatile. Inanliihlp. in vr?
organic solvents '
m.p. °C: " Water Sol. insoluble
b.p. °C: . Vapor Pressure @ 20°C
Flash Pt d 2-5~3 :,
OSES: Heat insulating compound for building.construction, cements, furnace
and hot pipe coverings, inert filler medium, fireproof gloves, clothing, brake
linings.
DIRECT TRANSPORT: LOW potential for distribution., Steady state concentrations
should be: Air: Low but fine dust can be suspended in air and carried by air
currents, Land: High, Water: Low; again fine particles can remain suspended
and carried by water currents. . , •
DIRECT SYSTEMIC UPTAKE: Cannot be systemically, absorbed through skin, lungs or
intestinal walls. Can be retained embedded in lung tissue.
_BY-PRODUCT FORMATION;
a) Manufacture: Obtained in mining operations., Only by-products would be
associated minerals .present in the mine,
b) Processing; By-products formation: negligible
DEGRADATION IN THE ENVIRONMENT: Stable (based on extensive experience, use).
BIQ-ACCUMULATION: Not subject to hiqaccumulation in-the food chain. Could
accumulate in the lungs of an individual. »
A-17
-------
NO. ____
CHEMICAL: Ethylene TVtphtoride
STRUCTURE: C1CH2CH2C1 C2H^C12
INFORMATION SOURCES:
-------
NO.
CHEMICAL: Acrvlonitrile ^^TT^^P_
STRUCTURE; CH2 - CH - CN C3H3N
INFORMATION SOURCES:
1. Merck Index, 9th Ed.
2. Personal knowledge
3- Handbook of Chemistry and Physics, 45th Ed.
4. Chem. Reviews. 71, 525 (1971)
5. Chemical Use List, EPA
6.
7.
PROPERTIES: liquid, volatile, unstable
Log P - 0.92
m.p. °C: Water Sol. 7% @ 20°c
b.p. °C: 77.5 Vapor Pressure @ 20°C 87mm He
t
Flash Pt o°ccP§ 0.8
USES: Chemical intermediate. Polymerization intermediate for manufacture of acrylic
fibers, plastics, coatings and adhesives; modifier for natural polymers. Organic
intermediate for synthesic of antioxidants, Pharmaceuticals, dyes. Pesticide fumigant
DIRECT TRANSPORT; . , for %Tain-
Potential for wide distribution in the environment. Steady state concentrations
should be: Air: high Land: low Wafer: high
DIRECT SYSTEMIC UPTAKE: Capable of rapid absorption through skin and other membrances,
through lungs, and through walls of G.I. tract.
BY-PRODUCT FORMATION:
a) Manufacture; Produced by dehydration pf acrylamide with phosphorouspentoxide, by
addition of hydrogen cyanide to acetylene and by a special catalytic oxidation of
propene. Possible by-products: starting materials, acrylic acid, acrylonitrile
. \ polymers, succinonitrile.
' Processing; Possible by-products: hydrogen cyanide, acetylene, acrylamide, acrylic
acid, polymeric matetials, ammonia.
DEGRADATION IN THE ENVIRONMENT; Unstable compound. Subject to air oxidation, photo-
chemical degradation, polymerization, loss of hydrogen.cyanide, hydrolysis; sensitive
to acid, alkali, readily biodegraded. Capable of alkylating biomaterials (a-B-
unsaturated carbonyl compound).
_BIQ-ACCUMULATION: Not subject to bioaccumulafion in the food chain. Could accumulate
in the individual animal by alkylation of biopolymers.
A-19
-------
NO.
CHEMICAL: Benzidine dye Benzidine yellow
STRUCTURE: fC6H5NHC = C - -N = N - /~"\_A_
C = 0
INFORMATION SOURCES:
CH3 C1
l^ E.A. Apps, "Printing Ink Technology," Chemical Publishing Co., NY, 1959
2. Personal knowledge
3 Chemical Use List, EPA
4.
5.
6.
7.
PROPERTIES: Solid, non-volatile, moderate chemical stability r insoluble in
water
m. p.
°C: Water Sol. ^soluble
b.p. °C: Vapor Pressure @ 20°C
Flash Pt d 1.7 ,
USES: Pigment for use in printing inks, plastics, rubber, paint, papers, pottery,
glassware, fabrics, - •' ''••
DIRECT TRANSPORT: LOW potential for distribution in environment. Steady state
concentrations should be: Air: low;fine;dust could disperse in air
Land: high -;
Water: low; fine powder could be transported -in suspension
DIRECT SYSTEMIC UPTAKE: LOW potential for direct systemic absorption.
BY-PRODUCT FORMATION: j
\ Manufacture: Produced by tetrazotizing 0,Q-djLchiorobenzidine with sodium nitrite
and hydrochloric acid and reacting the .tetrazpnium.salt-with acetoacetanilide.
Possible by-products: starting,materia^s,_ 2J2'-dichloro^4,4'-biphenol,3,3l-dichloro-
biphenyl, aniline, phenol, acetoacetic acid, nitrogen oxides.
b) Processing: Low potential for by-productrf9rmatipn, during.processing. Possible by-
products: hydrolysis and cleavage products (aniline, acetic acid).
DEGRADATION IN THE ENVIRONMENT: Resistant to water, acid, alkali, resistant to heat
but sensitive to photochemical degradation. j>ubject to oxidative and biodegradation
(based on literature information and properties'-of fuiietions present).
BIO-ACCUMULATION: Not subject to bioaceumulatiori.
,' •"
A-20
-------
NO.
CHEMICAL; Uni-Rez 2642
STRUCTURE:
INFORMATION SOURCES:
1. Chemical Week, March 28, 1979, p.7
2. Union Camp Literature
3. Personal Knowledge
4. Chemical Use List, EPA
5.
6.
7.
PROPERTIES: Solid resin, non-volatile, chemically stable
m.p. °C: 164 Water Sol.
b.p. °C: Vapor Pressure @ 20°C
Flash Pt d n Q«
Adhesive, binder, heat sealing agent for plastics and metals
DIRECT TRANSPORT:
Extremely little potential for distribution in environment. Steady
state concentration should be: Air: essentially none
Land: high
Water: essentially none
DIRECT SYSTEMIC UPTAKE: No potential for direct systemic absorption.
BY-PRODUCT FORMATION;
aJ Manufacture: No information on chemical process or composition. Presumabley,
monomer starting materials (dibasic acids, alkylenediamines and/or w-amino acids
could be present).
"/ Processing; No information on chemical composition other than that it is a
polyamide. Dibasic acids, alkylenediamines and/or w-amino acids could be by-
products.
DEGRADATION IN THE ENVIRONMENT: A polyamide. material would be expected to be subject
to very slow hydrolytic and oxidative degradation in the environment and to slow
biodegradation by microorganisms.
BIO-ACCUMULATION: Not subject to bloaceumalation.
-------
NO. 8
CHEMICAL; Oil of Cedar Leaf _ ,
STRUCTURE: TSCA Candidate
- CAS# 61789-90-2
INFORMATION SOURCES:
1- Merck Index, 9th Ed.
2- Chem. Reviews, 71. 525 (1971)
3- Personal knowledge
4. Chemical Use List, EPA
5. Computer Search, Chem. Abstracts
6.
7-
PROPERTIES : Oil. volatile, moderate chemical stability. • Mixture of terpenes :
a-pinene, d-thujone and a-fenchone. Estimated log P = 3.5
m.p. °C: _ _ Water Sol. Practically insoluble in water
b.p. °C: 150-200 _ Vapor Pressure @ 20°C (approx.^ 0.3-3 mm Hg
Flash Pt ______ _ d _ 0.91-0.92 _
USES: perfume, flavor
DIRECT TRANSPORT: Potential for moderate distribution in environment. " Steady
state concentrations should be: Air: moderate Land: moderate
Water: low; capable of spreading on surface of water
DIRECT SYSTEMIC UPTAKE: Potential for moderately rapid 'absorption through skin
and other membranes, through lungs and G.I. tract.
BY-PRODUCT FORMATION:
a) Manufacture ; Produced by steam distillation from 'fresh leaves of Thuja
occidentalis L. , Pinaceae, a 'coniferous' tree. Possible by-products include:
other terpenes, rearrangement and oxidation products. '
b) Processing; Possible by-products : rearrangement *"and~oxidation products.
'
DEGRADATION IN THE ENVIRONMENT: : Sensitive to light, air- -oxidation, subject to
acid-catalyzed rearrangement, biodegradable
-------
NO.
CHEMICAL: 2-Benzothiazolesulfonamide, N-(1,1-dimethyl ethyl)
STRUCTURE:
SO* NH - C - CH3
INFORMATION SOURCES:
lf Computer search of Chem. Abstracts
2. Personal knowledge
3. Chem. Reviews. 71, 525 (1971)
4. J. Med. Chem.. 16_t 1207 (1973)
5^ Handbook of Chemistry and Physics
6.
7.
PROPERTIES:
Solid, P.vf.1*<»mp1y 1 OtJ W^la-H 1-t f-yj mp^g-raf-p r-Viom-ir-al c-t-gK-i 1-i f
Log P (estimated) = 2.01 (benzothiazole) + (-1.82)(S02NH2) + 1.98 (C(CH3)3) = 2.2
m.p. °C: Water Sol. yery slight-
b.p. °C: Vapor Pressure @ 20°C
Flash Pt ct >]
USES: Possible chemical intermediate. Possible pharmaceutical, human or
veterinary use.
DIRECT TRANSPORT; LOW potential for wide distribution in the environment. Steady
state concentrations should be: Air: low Land: high Water: low
DIRECT SYSTEMIC UPTAKE: Capable of moderately rapid absorption by every route.
BY-PRODUCT FORMATION:
a) Manufacture; Can be prepared by oxidative chlorination of benzothiazole-2-thiol
followed by treatment of the resultant benzothiazole-2-sulfonyl chloride with
t-butylamine. Possible by-products include: starting materials, chlorine, acetic
acid, hydrochloric acid, benzothiagole-2-sulfonyl chloride and 2-sulfonic acid.
DJ Processing; Benzothiazole-2-sulfpnic acid, t-butylamine
DEGRADATION IN THE ENVIRONMENT: Subject to hydrolytic, oxidative, photochemical,
and biodegradation (based on presence of hydrplygable sulfonamide function and
thiazole nucleus).
BIO-ACCUMULATION: Not subject to bioaccumulation.
• •/•-'"
A-23
-------
NO. 10
CHEMICAL: 5-Nitroisatoic Anhydride ; .- ..
STRUCTURE: 02N ^^^^^ -jl C8H,N205
INFORMATION SOURCES:
1- Sherwin-William Company Technical Bulletins
2- Personal knowledge
3. Chemical Use List, EPA
4. Chem. Reviews, ^n, 525 (1971)
5. J. Med. Chem., J.6, 1207 (1973)
6.
7.
PROPERTIES: Solid, non—volatile. moderate chemical stability
Log P (est.) = 1.15 (phthalimide) + (-0.28)(nitro) + (-0.02)(OMe) - 0.56 (Me) = 0.3
m.p. °C: 259-263 (dec.) Water Sol. some solubility in water
b.p. °C: Vapor Pressure @ 20°C -
Flash Pt d
USES: Chemical intermediate, organic for dyes, Pharmaceuticals, etc.
DIRECT TRANSPORT; Potential for wide distribution in the environment. Steady state
concentrations should be: Air: low Land: high Water: high
DIRECT SYSTEMIC UPTAKE; Potential for rapid systemic absorption by all routes.
BY-PRODUCT FORMATION: \
a) Manufacture: Produced by nitration of isatoic anhydride. .By-products include
starting material, nitric acid, sulfuric acid, anthranilic acid, carbon dioxide,
5-nitroanthranilic acid.
b) Processing: 5-nitroanthranilic acid, carbon dioxide
DEGRADATION IN THE ENVIRONMENT: Subject to photochemical, oxidative, hydrolytic and
biodegradation. (based on presence of hydrolyzable, cyclic anhydride structure and
nitrobenzene ring).
BIO-ACCUMULATION; Not subject fco bio-acc^ulatlon.
A-24
-------
NO. ^
CHEMICAL: Vanchem DMTD „____
STRUCTURE: o_^x>S\ . C2H2N2S3.
HS HT^ ^^ OTT
\ /Dimercaptothiadiazole
N /
INFORMATION SOURCES;
\f Vanderbilt Company Literature
2. Personal knowledge
3. Chem. Rev., 7JU 525, (1971)
4. J. Med. Chem., 16, 1207 (1973)
5. Chemical Use List, EPA
6.
7.
PROPERTIES: Solid, powder, very low volatility, moderate stability
Log P (est.) = 0.44 (thiazole) + (-0.40)(pyrimidine) - 0.64 (pyridine) + 0.78 (2 SH)
, :
m.p. °C: 155-161 Water Sol. 3%
b.p. °C: Vapor Pressure @ 20°C
t
Flash Pt d 1.79
USES; Chemical intermediate, organic, for preparation of corrosion inhibitors,
industrial organic chemicals; polymerization intermediate. Vulcanizing agent.
DIRECT TRANSPORT: Potential for moderate distribution in the environment. Steady
state concentrations should be: Air: low (fine powder could form aerosols)
Land: high Water: high
DIRECT SYSTEMIC UPTAKE: Potential for moderately rapid absorption through skin,
walls of G.I. tract and through lungs (dust).
BY-PRODUCT FORMATION:
a\ Manufacture; No information on process from company but may be produced by reaction
of hydrazine with carbon disulfide or of hydrazine with phosgene and hydrogen sulfide.
Possible by-products include: starting materials, nitrogen, 2,5-dihydroxy-l,3,4,-
thiadiazole,2,5-dichloro-l,3,4,-thiadiazole, uncyclized adducts of hydrazine and
carbon disulfide or phosgene.
b) Processing: Possible by-products include: nitrogen, hydrogen sulfide, DMTD-disulfides,
hydroxythiadiazoles, carbon disulfides
DEGRADATION IN THE ENVIRONMENT: Subject to hydrolytic, oxidative and biodegradation
in the environment (based on presence of sulfhydryi functions).
-*ACCUMULATION; Not subject to bioaccumulation.
AT25
-------
NO.
CHEMICAL: Adipir Acid, 1 jd-hntanedinl-A^'-^tHpli^nyTTn^t-Hanp. rHisoryanate
STRUCTURE: CA526375-23-5
r •
INFORMATION SOURCES:
1. Computer Search Chem. Abstracts
2- Personal knowledge
3. Chemical Use List, EPA
4.
5.
6.
7.
rRUPERTIES: Resin polymer, non-volatile
Moderate chemical stability
m.p. °C: Water Sol. insoluble in water
b.p. °C: Vapor Pressure @ 20°C
i
Flash Pt d
USES: Coating for leather, fabrics, textiles, adhesive for leather, textiles,
fiber forming compound, noncellulosic organic. Plastic forming compound, leather
substitute, permeable thermoplastic elastomer, films, foils
DIRECT TRANSPORT: Low potential for wide distribution in the environment. Steady
state concentrations should be: Air: essentially zero Land: high
Water: essentially zero
DIRECT SYSTEMIC UPTAKE: Not subject to direct systemic uptake
BY-PRODUCT FORMATION:
a) Manufacture: Produced by heating a mixture of poly-Cl^-butanediol adipate),
diphenylmethane 4,4'-diisocyanate and 1,4-butanediol. Possible by-products
include: starting materials, adipic acid, 4,4t-diaminodiphenylmethane, oligomers,
b) Processing: Oligomers, adipic acid, 1,4-hutanedibi, 4,4'diaminodiphenylmethane
DEGRADATION IN THE ENVIRONMENT: Subject to photochemical,hydrolytic, oxidative
and biodegradation (based on presence of ester fraction and aromatic rings with
electron-donating substituents).
BIO-ACCUMULATION: Not subject to bioaccumulation
A-26
-------
NO. 13
CHEMICAL: Benzyltrimethylammonium Methoxide
STRUCTURE: +
CSH5-CH N (CH3)3 OCRs' CioHi6N-CH30
Supplied as 40% solution in Methanol
INFORMATION SOURCES:
Hexcel Specialty Chemicals Literature: Technical Data sheet, Material Safety
!• Data Sheet, Toxicity Infprmation
2- Personal knowledge
3- Chemical Use List, EPA
4- Chem. Reviews, 71, 525 (1971)
5- J. Med. Chem.. 16, 1207 (1973)
6.
7.
PROPERTIES:
as liqniH spliif-inn . f^mmpniir^ if-aol-p TjniiTH Ko a
relatively unstable, strong base, non-volatile.
m.p. °C:
b.p. °C: fMethanol") 65
Water Sol. WT^
Vappr -Pressure C
r QnlllK1
» 20°C f]
•in wfli-er
^h-n«1^ .«n.^.
Flash Pt (Methaol l°r. _ d SolnMnn -QT
Estimated Log P (CeHgCHaN (CH3)3) = 2.13 (benezene)
USES; + (-4.15)((CH2)3 N*(CH3)3) - 1.02 (C2H5) = -3.0
Catalyst, basic, for polymerization, industrial organic chemicals.
DIRECT TRANSPORT: Strong base, would be rapidly neutralized on exposure to moist, acidic
environment, carbon dioxide. Therefore, limited potential for direct transport of
benzyltrimethylammonium methoxide itself. Relative steady state concentrations of the
quaternary ammonium compound would be: Air: essential zero Land: moderate Water: high
DIRECT SYSTEMIC UPTAKE; Methanol would be subject to rapid absorption but the quaternary
ammonium compound would undergo essentially no direct systemic absorption.
BY-PRODUCT FORMATION; a) Manufacture; Probably produced by reaction of benzyl chloride
with trimethylamine followed by treatment of the product with sodium methoxide in meth-
anol. Can also be prepared by reaction of benzylamine with excess methyl halide or
dimethyl sulfate, again followed by sodium- methoxide treatment. By-products indicated
on the data sheet are: chloride ion, trimethylamine. Other possible .by-products include:
starting materials used, benzyl alcohol, benzyldimethylamine, sodium salts, benzylmethyl
ether. b)Processing; Benzyl alcohol, trimethylamine, methanol, benzyldimethylamine,
benzyl methyl ether.
DEGRADATION IN THE ENVIRONMENT:
Methanol subject to oxidative and biodegradation.
Quaternary ammonium compound thermally unstable, subject to degradation by heat,
neutralization by acids, carbon dioxide, biodegradation.
BIO-iACCUMULATION; Not subject to bioaqcumulation.
A-27
-------
NO. _L4
CHEMICAL; Vitride . . !'•''":'. ':
STRUCTURE: NaAlH2(OCH2CH2OCH3)2.
70% solution in toluene
INFORMATION SOURCES:
Hexcel Specialty Chemicals Literature: Detailed Technical Bulletin; Technical
1. Data Sheet; Material Safety and Handling Data Sheets; Toxicity Statement
2. Personal knowledge
3. Handbook of Chemistry and Physics
4. Chem. Reviews, _71, 525 (1971)
5. Chemical Use List, EPA
6.
7.
PROPERTIES: Compound itself is highly reactive, non-volatile solid.
Properties of 70% solution in toluene: Strongly alkaline, non-pyrophoric.
Reacts rapidly with water. Log P (toluene") = 2.69 ;
m.p. °C: Water Sol. 'j
b.p. °C: 140 Vapor Pressure @ 20°C (est^> 8mm Hg
Flash Pt -io°c d20 1.04^
USES: Reducer (chemical technology)
DIRECT TRANSPORT: Agent itself would react rapidly with moisture and therefore would
not be subject to direct transport. Toluene would be subject to wide distribution in
the environment. Steady state concentrations of the toluene would be: Air: moderately
high Land: high Water: low
DIRECT SYSTEMIC UPTAKE: Agent again would Decompose on contact with moisture in body
tissues and therefore not be subject to direct systemic uptake. Toluene would be capable
of rapid absorption by all routes.
BY-PRODUCT FORMATION:
a) Manufacture: Produced by reaction -of sodium aluminum hydride with methoxyethanol.
Possible by-products include: starting materials, sodium carbonate, sodium hydroxide,
alumina. ' '
. - • ; Vi'' ? ****• •
b) Processing: Methoxyethanol, sodium carbonate, aluminum hydroxide, sodium hydroxide.
DEGRADATION IN THE ENVIRONMENT: Agent itself would be rapidly degraded on contact
with moisture in environment. Toluene slibjesct to oxidation and biodegradation.
BIO-ACCUMULATION: Not gubject fco bioaccumulat:Lon;
A-28
-------
NO. __
CHEMICAL:
STRUCTURE;
Strontium Tjtanate
SrTio3
INFORMATION SOURCES:
1. Hackh's Chemical Dictionary (1969)
2. Chemical Abstracts search
3_ Personal knowledge
4. Chemical Use List, EPA
5.
6.
7.
PROPERTIES: Snl-M
m n °T-
ui,\i. i> . Very p^gn TP° 't* "*nj
b.p. °C:
Flash Pt
Water Sol. *„«„!
Vapor Pressure @
d
iif>1«> in wal-^r
20° C
USES: Electrical insulating compounds: ceramic insulators, capacitators, resistors
isulating films. Semiconductors, photoelectrpdes, thermoelectric, photoelectric,
optical materials, lenses, artificial gemstones, imitation diamonds
DIRECT TRANSPORT:
Very low potential for wide distribution in the environment.
Steady state concentrations should be: Air: essentially zero Land: high
Water: essentially zero
DIRECT SYSTEMIC UPTAKE: Not subjected to significant systemic absorption.
BY-PRODUCT FORMATION:
a) Manufacture ; Produced by reaction of a strontium salt, (e.g., SrClz) or alkoxide
with a titanium salt, titanium dioxi.de ' or titanium alkoxide. Possible by-products
include: starting materials, salt metathesis products, acids, alcohols, radioactive
h) strontium isotopes (9.°Sr)
Processing: Radioactive strontium isotopes.
DEGRADATION IN THE ENVIRONMENT: Resistant to chemical and biodegradation (based
reported uses and literature information).
on
jl (H- ACCUMULATION:
*
Not subject to bipaccumuiation.
A-29
-------
NO. 16
CHEMICAL: Acetone _^_
STRUCTURE: ' \
INFORMATION SOURCES: f
1- Merck Index
2- Personal knowledge
3. Handbook of Chemistry and Physics
4- Chem. Reviews. 71., 525 (1971)
5. Chemical Use List, EPA
6.
7.
PROPERTIES: Volatile liquid, moderate rhemjpal stability
Log P* = -0.24
m.p. °C: Water Sol. completely mlsrible with water
b.p. °C: 56.5 Vapor Pressure @ 20°C (MM 1ftn n™ wg
Flash Pt -2n°r. d25 n.7««
USES;Solvent for fats, oils, waxes, resins, rubber, plastics, lacquers, varnishes,
cement. Chemical intermediate, organic, industrial chemicals. Reaction medium
used in manufacture of airplane dopes, rayon, photographic films, isoprene, in extrac-
tion of plant and animal substances. Stripper paint and varnish.
DIRECT TRANSPORT;
Potential for wide distribution in the environment. Steady state concentrations
would be: Air: high Land: low Water: high
DIRECT SYSTEMIC UPTAKE: Capable of rapid absorption by every route.
BY-PRODUCT FORMATION:
a) Manufacture; Can be produced by: A) fermentation B) oxidation of isopropyl alcohol
C) oxidative cleavage of cumene D) oxidative cracking of petroleum fraction. Pos-
sible by-products include: starting materials, butanol, peroxides, phenol, propane
u\ and other hydrocarbons, acetic acid, methanol, formaldehyde.
Processing: Condensation products, isopropyl alcohol, acetic acid.
DEGRADATION IN THE ENVIRONMENT; Subject to oxidative and biodegradation
BIO-ACCUMULATION: Not subject to bioaccumulation
A-30
-------
NO.
17
CHEMICAL: Styrene polysulfide
STRUCTURE:
unknown or variable composition; inadequate information
for prediction of properties.
INFORMATION SOURCES;
1.
2.
3.
4.
5.
6.
7.
PROPERTIES:
m.p. °C:
b.p. °C:
Flash Pt7
USES:
Water Sol.
Vapor Pressure @ 20°C
d7
DIRECT TRANSPORT:
DIRECT SYSTEMIC UPTAKE:
BY-PRODUCT FORMATION:
a)
b)
DEGRADATION IN THE ENVIRONMENT:
BIO-ACCUMULATION:
\
A-31
-------
NO. 18
CHEMICAL: Hydrogenated tallow acids; condensate, ethoxylated
STRUCTURE:
unknown or variable composition; inadequate information
for prediction of properties.
INFORMATION SOURCES:
1.
2.
3.
4.
5.
6.
7.
PROPERTIES:
m.p. °C:
b.p. °C:
Flash Pt7
USES:
Water Sol.
Vapor Pressure @ 20°C
d7
DIRECT TRANSPORT:
DIRECT SYSTEMIC UPTAKE:
BY-PRODUCT FORMATION:
a)
b)
DEGRADATION IN THE ENVIRONMENT:
BIO-ACCUMULATION:
A-32
-------
NO. 19
CHEMICAL: Surfynol 104'
STRUCTURE: 2,4,7,9-tetramethyl-4,4-dihydroxydeca-5-yne
OH l/\/
- c—f Y CllfH2602
OH I
INFORMATION SOURCES:
1. Air Products and Chemicals Technical Bulletin
2. Personal knowledge
3. Chem. Reviews, 7^, 525 (1971)
4. J. Med. Chem., JJ6, 1207 (1973)
5. Chemical Use List, EPA
6.
7.
PROPERTIES: Waxy solid, moderate chemical stability, non-volatile
Log P (est.) =1.27 (decamethyleneglycol) + 0.4 (C = CH) -1.02 (C2H5) +2.24 (4CH3) = 2.9
m.p. °C: 37 Water Sol. 0.1%
b.p. °C: ._ Vapor Pressure @ 20°C
t
Flash Pt d 0.89
USES: Surfactant, defearning, nonionic, defoamer, detergent, cleaning metal surfaces.
Dispersant, wetting agent for water-based coatings, inks, pigments, and paints.
DIRECT TRANSPORT; Intermediate potential for wide distribution in the environment.
Steady state concentrations should be: Air: low Water: moderate Land: high
DIRECT SYSTEMIC UPTAKE: Capable of rapid systemic absorption by all routes.
BY-PRODUCT FORMATION:
a) Manufacture; Produced by reaction of sodium acetylide with methyl isobutyl ketone.
Possible by-products include: starting materials, sodium hydroxide, ethynyliso-
butylmethylcarbinol, acetylene.
"' Processing; By-products not likely to form during processing but possible ones
include: tetramethyl-5-oxodecanediol, ethynylisobutylmethylcarbinol, methylisobutyl
ketone.
DEGRADATION IN THE ENVIRONMENT: Subject to oxidative, alkaline and biodegradation
In the environment.(Based on presence of acetylenic function and adjacent hydroxyl
substituents.)
BIQ-ACCUMULATION: Not subject to bioaccumulation.
A-33
-------
NO. 20
CHEMICAL: Allyl Alcohol Styrene Copolymer CAS 25119-6Z-4
STRUCTURE: (CeHe«C3H66)x- •-
INFORMATION SOURCES:
1. Computer search Chem. Abstracts
2. Personal knowledge
3. Chemical Use List, EPA
4. "
5.
6.
7.
PROPERTIES: Hgg-in nimPT- non-volatile , moderate chemical stability
m. p. °C: _ Water Sol. insoluble
b.p. °C: Vapor Pressure @ 20°C
Flash Pt d
USES: Coating component, lithographic offset printing plates, electrodeposition, etc.
Plastic forming compound. Filler (augmentation) for printing inks. Cleaning composi-
tions, dental plates.
DIRECT TRANSPORT: Low potential for wide distribution in the environment. Steady
state concentrations sould be: Air: essentiall zero Land: high
Water: essentially zero
DIRECT SYSTEMIC UPTAKE: Not subject to direct systemic-uptake.
BY-PRODUCT FORMATION:
a) Manufacture; Produced by radical copolymer'ization of styrene and allyl alcohol.
Possible by-products include monomers, oligomers, traces of radical initiator
and its reduction product(s) (e.g., t-tutyl hydroperoxide, t-butyl alcohol,
propanethiol, dipropyl disulfide.
") Processing: Oligomeric breakdown products.
DEGRADATION IN THE ENVIRONMENT: Subject to photochemical, oxidative, thermal and
biodegradation. (Based on presence of aliphatic alcohol groups, alkyl-
substituted benzene rings.)
BIO-ACCUMULATION; NOC subject to bioaccumulation.
A-34
-------
NO.
CHEMICAL: Benzenediazonium, 2,5-dibutoxy-4-(4-morpholinyl)-sulfate (1:1)
STRUCTURE:
HSO"
INFORMATION SOURCES:
!• Computer search of Chem. Abstracts
2- Personal knowledge
3.
4.
5.
6.
7.
PROPERTIES: Thermally unstable aoHfl, nnn-vnlat-il P., phot-neon0"1' .
m.p. °C: Water Sol.
b.p. °C: Vapor Pressure @ 20°C
Flash Pt d
; Dyes, nonsilver halide photo films, diazo process masters
DIRECT TRANSPORT: Sensitive to light and heat. Little or no chance for wide
distribution by direct transport.
DIRECT SYSTEMIC UPTAKE: Highly polar. Little or no potential for direct systemic
absorption.
BY-PRODUCT FORMATION:
aj Manufacture; Produced by treatment of 2,5-Tdibutoxy-4'-(4-^morpholinyl)-aniline
with sodium nitrite and sulfuric acid. ;. Possible by-products include: starting
materials, nitrogen, nitrogen oxides, dibutoxymorpholinylphenol, dibutoxymor-
pholinylbenzene, sodium hydrogen sulfate, N-nitrosomorpholine..
b) Processing: Corresponding azo dye, substituted phenol, benzene.
DEGRADATION IN THE ENVIRONMENT: Will be rapidly degraded by light and heat.
Brp-flCCUMULATION: No potential for bioaccumulation.
A-35
-------
NO. 22
CHEMICAL: n-Butylethylmagnesium (BEM) -'
Supplied as 10-15% solution in heptane.
i> I KULI UKhI
INFORMATION SOURCES: T
1- Stauffer Chemicals Technical Bulletin
2- Personal knowledge
3- Handbook of Chemistry and Physics
4. Chem. Reviews. 7J,, 525 (1971)
5. J. Med. Chem.. _1£, 1207 (1973)
6. Chemical Use List, EPA
7.
PROPERTIES: Reagent unstable, waxy solid-, reacts explosively with waterr
pyrophoric. Solution in heptane, non-pyrophoric liquid but reacts vigorously
with water and air.
m.p. °C: _ Water Sol. Heptane insoluble in water
b.p. °C: (n-heptane") 98.4 Vapor Pressure @ 20°C (heptane*) IQmm Hg
Flash Pt (hetane** -1 °n d (solution 1 0.7 0
_
Solution contains small amounts of Al and Cl. Log P (heptane, est.): 2.41 (heptanol)
USES: + °-56 (methyl) - (-1 . 03) (CH2OH) =4
"Catalyst for formation of plastics and rubber materials, olefin polymerization,
synthetics. Industrial organic chemicals.
DIRECT TRANSPORT: BEM would be rapidly decomposed and would not be subject to direct
transport in the environment. Heptane solvent would be subject to wide distribution.
Steady state concentrations should be: Air: high Land: moderately high Water: low.
DIRECT SYSTEMIC UPTAKE: BEM would react vigorously with biological tissue, be decom-
posed, and would not be subject to direct absorption. Heptane solvent would be rapidly
absorbed by all routes.
BY-PRODUCT FORMATION:
_\ Manufacture: May be produced by reaction of butyl and ethyl chlorides with magnesium
or of the corresponding alkyl lithium reagents with magnesium chloride. By-products
may include starting materials, lithium chloride, butane, ethane, butene, ethylene,
butanol, ethanol. ' «
b) Processing ; Butane, ^ethane, magnesium 'oxide, butene, ethylene, butanol, ethanol,
magnesium alkoxides.
DEGRADATION IN THE ENVIRONMENT: BEM subject to rapid decomposition by air and moisture.
Heptane subject to oxidative and biodegradation.
BIO- ACCUMULATION: Not subject to bioaccumulation.
A-36
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NO. 23
CHEMICAL; Amberlvst 15 .
STRUCTURE: Synthetic resin catalyst
INFORMATION SOURCES:
1. Rohm and Haas Technical Bulletin
2. Personal knowledge
3. U.S. Pharamacopeia (1970)
4.
5.
6.
7.
PROPERTIES: Sulfonic acid resin. Solid, bead form, strongly acidic resin,
non-volatile, stable. Particle size approximately 95% in the range 0.3-0.8 mm diam.
m.p. °C: ^___ Water Sol. insoluble
b.p. °C: Vapor Pressure @ 20°C
Flash Pt d 0.6
USES: Catalyst, industrial organic chemicals:i polymerization of olefins to
form rubbers.
DIRECT TRANSPORT: Little potential for direct- transport. Steady state concen-
trations should be: Air: essentially zero Land: high Water: essentially zero.
DIRECT SYSTEMIC UPTAKE: No potential for direct systemic absorption.
BY-PRODUCT FORMATION:
» Manufacture: No information as to chemical composition other than that material
' is a sulfonic acid polymeric resin. Therefore, can say little about manufacturing
process or possible by-products. May be prepared by sulfonation of a polymer or
by polymerization of an unsaturates sul,fbnic acid derivative. Possible by-products
would be monomers, ollgomers, sulfuric acid.
b) Processing; Possible formation of sulfur trioxide, sulfuric acid.
DEGRADATION IN THE ENVIRONMENT; Resistant to environmental degradation. May be
somewhat susceptible to oxidative and thermal degradation. (Based on information
from manufacture.)
BIQ-ACCUMULATION: No potential for bioaccumulation.
\ A-37
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NO. 24.
CHEMICAL: Raney Nickel .... , •.. .
STRUCTURE:
INFORMATION SOURCES:
!• Merck Index
2 L.F. Feiser and M. Feiser, "Reagents for Organic Synthesis," John Wiley & Sons,
NY, 1967.
3- Personal knowldege
4- Chemical Use List, EPA
5« Handbook of Chemistry and Physics
6.
7.
PROPERTIES: Pyrophoric; supplied as 50:50 alloy with aluminum or covered
with solvent, generally water or ethanol. Solid, non-volatile powder.
Dissolves in acid with release of hydrogen.
m.p. °C: Water Sol. insoluble
b.p. °C: 2.730 Vapor Pressure @ 20°C
Flash Pt d >i
USES: Catalyst, hydrogenation of organic chemicals.
DIRECT TRANSPORT; Catalyst, when released from alloy with aluminum and not covered
with solvent, ignites spontaneously in air and is converted to nickel oxides.
Therefore, essentially no potential for direct transport.
DIRECT SYSTEMIC UPTAKE: Essentially no potential for direct systemic uptake.
BY-PRODUCT FORMATION:
a) Manufacture: Produced by fusing 50 parts nickel with 50 parts aluminum,
pulverizing the alloy and dissolving out most of the aluminum with aqueous
sodium hydroxide. By-products include aluminum, sodium hydroxide aluminum
u\ hydroxide, nickel oxides.
Processing; Aluminum, aluminum hydroxide,; nickel oxides, nickel salts.
DEGRADATION IN THE ENVIRONMENT: Rapidly converted to nickel oxides, nickel salts
in the reactions with air, acids. ' -•
BIO-ACCUMULATION: Not subject to direct accumulation-. Nickel-'salts, oxides,
could conceivably be accumulated.
A-38
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NO. 25
CHEMICAL: Phosphorodithioic acid, S,S'-(thiodi-4,l-phenylene)
tetrametnyi ester :. .-.~ . ' "" '
STRUCTURE: s S
Ci6H2oOi»S5
II /— \ /^V II
MeO-P — S \)- S -\_y~S-P-OMe
OMe DMe
INFORMATION SOURCES: No ?pec±f±c information on compound available
lt Personal knowledge
2.
3.
4.
5.
6.
7.
PROPERTIES: Solid, non-volatile
m.p. °C: Water Sol. insoluble
b.p. °C: Vapor Pressure @ 20°C
Flash Pt d
USES: Insecticide, pesticide
DIRECT TRANSPORT; LOW potential for wide distribution in the environment.
Steady state concentration should be: Air: very low Land: high Water: very low
DIRECT SYSTEMIC UPTAKE; Capable of slow absorption by all routes.
BY-PRODUCT FORMATION:
a) Manufacture; May be produced by reaction of dimethyl chlorothiophosphate with
bis (4-mercaptophenyiy-sulf tide in the presence of alkali. Possible by-products
include: starting materials, disulfides, methyl thiophosphoric acid, sodium
u\ chloride.
Processing: Phosphoric acid derivatives, his-(4-mercaptophenyl) sulfide and
disulfides.
DEGRADATION IN THE ENVIRONMENT: Subject: to photochemical thermal, hydrolytic and
biodegradation. (Based on presence of phosphatiester functions and sulfur-
containing groups.)
BIO1-ACCUMULATION: Not subject to bioacci|mu||afion .in.the food-chain.
A-39
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NO. 26
CHEMICAL: Hexachlorobenzene
STRUCTURE:
INFORMATION SOURCES:
j_ Merck Index
2. Personal knowledge
3^ Handbook of Chemistry and Physics
4. Chem. Review, T±t 525 (1971)
5> J. Med. Chem. _1£, 1207 (1973)
g_ Chemical Use List, EPA
7.
PROPERTIES: Solid, low volatility, very stable -
Log P (estimated) = 2.13 (benzene) + 4.26 (6CD = 6.4
m.p. °C: 231 Water Sol. extremely low
b.p. °C: 323-326 Vapor Pressure @ 20°C rest.) io~3mm Hg
Flash Pt d 2.04-
USES; Chemical intermediate, organic, fungicide
DIRECT TRANSPORT: LOW potential for wide distribution in environment. Steady state
concentrations could be: Air: low Land: high Water: low
DIRECT SYSTEMIC UPTAKE;- Capable of slow absorption through skin and dther membrane
lungs and walls of 6.1. tract.
f
BY-PRODUCT FORMATION: '/
a) Manufacture; May -be produced by perchlorination of benzene in the presence of
iron catalyst. By-products may include: iron salts, benzene, chlorine, lower
chldrobenzene homo logs,''hydrogen chloride, benzene -hexachloride.
b) Processing: By-products may include lower chlorb'enzenes hdmologs.
DEGRADATION IN THE ENVIRONMENT: Resistant to chemical and .biodegradation.
Subject to photochemical degradation and degradation by alkali. (Perhalogenated
aromatic.)
BIO-ACCUMULATION: 'High potential for bioaccumulation.
A-40
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NO. 27
CHEMICAL:
STRUCTURE: C1,C = CHC1
INFORMATION SOURCES;
j Merck Index
2m Personal knowledge
3> Chem. Review. 7±t 525 (1971)
4e J. Med. Chem., _!£., 1207 (1973)
5^ Chemical Use List, EPA
6.
7.
PROPERTIES: Liquidr nonf|La,inmabler t^oderate stability.
Log P (estimated) =1.54 (ethyl chloride) +1.42 (2 Cl) +0.17 (allyl alcohol)
- (+0.34) (propvl alcohol^ = 2.8
m.p. °C: _^ Water Sol. practically insoluble in water
b.p. °C: 86.7 _^_ Vapor Pressure @ 20°C eo mm Hg
t
Flash Pt d20 1.46
USES: Solvent for fats, oils, waxes, resins, rubber, paints, varnishes, cellulose
esters and ethers. Solvent for dry cleaning, solvent for extraction, industrial
chemical intermediate, organic, reaction medium, stripper, degreasing.
DIRECT TRANSPORT; Potential for wide distribution in the environment. Steady state
concentrations should be: Air: high Land: intermediate Water: low '
DIRECT SYSTEMIC UPTAKE: Capable of rapid absorption by every route.
BY-PRODUCT FORMATION;
a) Manufacture: Produced by dehydrohalogenation of tetrachloroethane. Possible
by-products include: starting material, calcium carbonate, calcium chloride,
hydrochloric acid, dichloroacetylene, glyoxal, oxalic acid, chloroacetic acid.
b) Processing: Hydrochloric acid, dichlor.pacetylene, oxalic acid, chloracetic acid,
glyoxal.
DEGRADATION IN THE ENVIRONMENT; Slowly decomppsed by light in the presence of
moisture. Also subject .to degradation by heat; alkali, air oxidation. Relatively
resistant to biodegradation. (Qlefinic function stabilized by polychloro
nibrtitution.)
BIO-ACCUMULATION: Significant potential ,for bioacpumulation. •
A-41
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NO. 28_
CHEMICAL: Sulfuric Acid .- ...•;-.• - '• '.
STRUCTURE:
INFORMATION SOURCES:'
1. Merck Index
2. Personal knowledge
3. Handbook of Chemistry and Physics
4. Chemical Use List, EPA
5.
6.
7.
PROPERTIES: Corrosive, oily liqujd,- hygrospjapii-, mndp-rai-g stability
m.p. °C: - -• Water Sol. Miscible with water
b.p. °C: 330 (approx.) Vapor Pressure @ 20°C (est.) 2 x IQ-^mm Hg
Flash Pt ,^..... d •:• 1.84'
USES: Reaction medium, inorganic reagent chemical used in manufacture of fertilizers
explosives, dystuffs, other acids, parchment-* paper, glue, purification of petroluem,
etc., pickling agent • ' ' -" - ,
DIRECT TRANSPORT: Highly reactive compound; undiluted acid will dehydrate and/or
oxidize the majority of materials with which it comes in contact. Potential for
relatively wide distribution of unreacted acid. Steady state concentrations should
be: Air: low (can form aerosols) Land: low Water: high
DIRECT SYSTEMIC UPTAKE: Undiluted acid'will.char tissues with which it comes in
contact. Diluted acid can be absorbed by all routes.
BY-PRODUCT FORMATION:
\ Manufacture; Produced by the oxidation, qf sulfur dioxide (e.g., with oxygen and
' nitric oxide) followed by hydration of the resultant sulfur trioxide. Possible
by-products include: starting matlrlslls. sulfuEous acid, nitrogen dioxide, sulfur
trioxide, water.
b) Processing: Sulfur tridxidej sulfur"dioxide, sulfurouSI acid, water. "
DEGRADATION IN THE ENVIRONMENT; Will be diluted by absorption of water from its
surroundings and reduced on contact with materials that can be oxidized; neutralized
by basic substances, can enter into metabolic processes.
BIO-ACCUMULATION: Not subject to bioaccumulation. "C^'
A-42
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NO. 29
CHEMICAL: Iron (II) Sulfide FeS
STRUCTURE:
INFORMATION SOURCES;
2.
3.
4.
5.
6.
7.
Merck Index
Personal knowledge
Handbook of Chemistry and Physics
Chemical Use List, EPA
PROPERTIES : Sn"Hr nrm— im" al-i' 1 P nmrloT-af-o
a ah-i 1 i"
y .
m.p. °C:
b.p. °C:
Flash Pt
Water Sol.
Vapor Pressure @ 20°C
d A RA
USES: Inorganic chemical reagent used in the laboratory. Stain for ceramics,
pigment for paints, lubricant coating, electrode material.
DIRECT TRANSPORT: LOW potential for direct transport. Steady state concentrations
should be: Air: essentially ze.ro (except when aerosolized); Land: high
Water: extremely low
DIRECT SYSTEMIC UPTAKE: Essentially no potential for direct systemic uptake
BY-PRODUCT FORMATION:
a/ Manufacture; Produced by reaction of iron with sulfur. Also available as the
natural mineral. Possible by-products include: starting materials, hydrogen
sulfide, iron oxides.
b) Processing: Sulfur, iron oxides, hydrogen sulfide.
DEGRADATION IN THE ENVIRONMENT; Subject to oxidative degradation by moist air,
decomposition by acids; biodegradation by microorganisms. (Based on literature
information.)
BIO- ACCUMULATION: Not subject to bioaccumulation.
A-43
-------
poly (oxy-l,2-ethane-diyl) a-phenyl-w-hydroxy-, NO.
CHEMICAL; phosphate ... .,
STRUCTURE:
INFORMATION SOURCES:
1.
2.
3.
4.
5.
6.
7.
PROPERTIES:
Unknown or variable composition, inadequate information
for prediction of properties.
m.p. °C:
b.p. °C:
Flash Pt
USES:
Water Sol.
Vapor Pressure @ 20°C
d
DIRECT TRANSPORT:
DIRECT SYSTEMIC UPTAKE:
BY-PRODUCT FORMATION:
a)
b)
DEGRADATION IN THE ENVIRONMENT:
BIO-ACCUMULATION:
A-44
-------
C. DEVELOPMENT OF DIFFUSION PARAMETER
The release:
n = parts/cm3
D = cm^/sec
"At equilibrium,
dn
For 1-dimensional problem, z
n = AZ + B
(D
Suppose that n ^ 0 (i.e. removed by convective processes) at a distance (Z1)
of about 10 1 from the surface (1 = mean free path, 3 x 10 5 cm in air).
Then
0 <\,AZ' + B or A = -B/Z1
'
Fluid
Surface aP
ap1
boundry zone
0
->Jz free air
10 1
The rate at which molecules escape from the fluid surface due to a
finite vapor pressure is
I-
/2HmkT
= cxP,
A-45
-------
where P = the vapor pressure (dyne/ cm2)
m = the particle mass (g)
kT = the thermal energy per particle (ergs)
T~ = the flux outward (particles/cm2 sec)
However, the effective rate at which evaporation occurs is usually smaller
than this number because of back diffusion. For a closed system, at equili-
brium, the backward flow equals the outward flow (e.g. j). For an open system,
some material would carry away sufficient heat as to cause the liquid to
freeze (i.e. like blowing very hard on hot soup). The condition at the boun-
dary zone is:
ctP = aP1 -
where P1 is the partial pressure of the vapor phase in the boundary zone
and is equal to
i _ nRT
"
where N = Avogadro's number - 6.023 x 1023 particles/mole
pi _
"
23
N = the particle density (number/ cm3)
R = the gas constant 8.64 x id6 ergs/°K mole
f = the absolute temperature (°K)
This constraint is thus:
Using (1) - evaluated at Z = 0
Using (2)
aP = B - DA
o
« _ aRT „ , DB _ B aRT D
aP - -B + - - + T
R - aP A - •• aP
B ~ :TDTn > " ~
D ' " aRTZ'
But J,1 - -D|y = -JTT — - is the rate at which material leaves the surface
z az oiaz_ + D (part1cle/cm2 sec)
A-46
-------
So
,_ DaP p"xMw C
uz " aRTZ1 + NQD
is the rate of boil off in the units (cm/sec) from a mixture containing
percent of the chemical of density p, (g/cc) and molecular weight Mw.
Thus, the time required for 50% the material in a film to be released
(assuming no surface retardation) is:
tj, release ~ y/(2Jz)
where y = the thickness of the film (cm)
t, release ~ . Nn p)
\ release ~ p a p Mw c°
Note that t^ approaches zero as D and P become larger. For room temper-
ature substances?
a ^ 6 x 1016 (Mw)"2
D e
A-47
-------
0. CHEMICAL PERMEABILITY PARAMETER
'
The defining equation for the chemical permeability (P) of a membrane
with respect to a given chemical at concentration C on one side of it and Ci
on the other side of it is:
where V = the volume containing Ci
A = membrane area
t = time
P is constant for times t long enough to go beyond transient conditions
For human skin and various chemicals, this time appears to be about 30
minutes.
If Ci« CQ, then
P = TTF - In (1 - £*• ^ J p1 = molar dose
"
o o Ate
or
mass dose = AtCQP MW
Now, the value of P can be estimated from the data of Treherne, and
others, in terms of the partition coefficient (Pi) of the chemical, its mole
cular weight and solubility. The relationship is:
-»- Pi I
where Beta ^ 10" 3
Discussion of relations of this type is in Idson. Using this value,
mass dose = AtCft /Sol W lo'' P1D, for A (m2), t (min), C
(moles/liter, Sol flnass fraction) and MW (AMU). °
A-48
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E. Sample Calculation for Tris - Consumer Dose
RUN EXPOSE
STANDARD SETUP (0) OR SPECIAL (i)
? 0
INPUT THE NAME OF THE CHEMICAL TO BE EVALUATED
? TRIS
INPUT THE VAPOR PRESSURE (MM HG) FOR TRIS.
? 1E-5
INPUT THE MOLECULAR WEIGHT OF.TRIS.
.? 297
INPUT THE DENSITY (G/CC) OF TRIS
? 2.24
INPUT WATER SOLUBILITY <0 - 1)
? 1E-4
INPUT PARTITION COEFFICIENT - IF UNKNOWNr ENTER 1
? 7.5\5.7\4E7
INPUT THE NAME OF THE EPA FUNCTION CATEGORY
? FLAMERETARDENT
INPUT MARKET SHARE ESTIMATE (0-1) FOR TRIS IN EPA
FUNCTION CATEGORY FLAMERETARDENT.
? .03
INPUT TOTAL SHIPMENTS
-------
(cont.)
INPUT THE MINIMUM AND MAXIMUM VALUES FOR THE
EFFECTIVE DIFFUSIVITY AND/OR ABSORPTIVITY
WITHIN THE MATERIAL (0 TO 1).
(NOTE - 1 MEANS MAXIMUM VOLATILE'RELEASE AND'0 MEANS NO RELEASE
? . 2 f , 2
INPUT CONTACT FACTORS FOR THE ACTIVE AND PASSIVE "
STAGES - (0 TO 1> WHERE 1 IS MAXIMUM CONTACT.
? Ifl
INPUT CONTACT DURATION FACTORS FOR THE ACTIVE AND PASSIVE
? If60000
INPUT SKIN AREA IN CONTACT WITH THE CHEMICAL DURING
THE ACTIVE AND PASSIVE EXPOSURE PERIODS - (0 TO 1)
WHERE 1 REFLECTS WHOLE BODY EXPOSURE.
? . 1 y . 8 -
INPUT THE FRACTION OF THE MATERIAL ACTUALLY IN CONTACT
IN CONTACT WITH THE'SKIN AT ANY GIVEN TIME FOR THE
ACTIVE AND PASSIVE STAGES (0 TO 1).
? .If .5 :
INPUT THE FRACTIONS OF SOLID LOST DURING THE ACTIVE*
PASSIVE AND PASSIVE-BYPASS STAGES OF ACTIVITY (0.0 TO 1.0)
? .02f.5j.48
INPUT THE CHARACTERISTIC EXPOSURE TIMES FOR THE
ACTIVE AND PASSIVE STAGES OF PRODUCT USE (HRS).
? Of 800
INPUT TH.E EFFECTIVE DILUTION-"VOLUME'S FOR THE ACTIVE
AND PASSIVE STAGES OF PRODUCT USE (M CUBED).
7 40f40
POPULATION DOSE(KG) --TREL(SEC) T-ACT(SEC) T-P.ASS(SEC)
0 0 2.45587E+08 0' 2.B8000E+06
100
2 .0191235 2.86852E+06
3 0 9.60000E+06
A .383542 1.20870E+08
5 0 3.46662E+08
INPUT THE FRACTION (0.0 - 1.0) OF TRIS ESTIMATED
TO BE PRODUCED THAT WOULD BE USED IN PRODUCTS IN THE
EPA USE CATEGORY - RUGS.
? .9
INPUT 7. COMPOSITION OF PRODUCT THAT TRIS MAKES UP.
? .3
INPUT ACTIVE POPULATION (0 TO 1) FOR RUGS
? 0
INPUT PASSIVE POPULATION (0 TO 1) FUR RUGS
? 1
INPUT THE POPULATION LOADING FACTORS FOR THE
ACTIVE AND PASSIVE STAGES .
? if.4 ' r '
IMPUT TWG FKACT\ON Co TO-D OF PRODUCTS IN THE
CATEGORY RUGS THAT CONTAIN FLAMERET.ARDEN.T
? 1
A-50
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TECHNICAL REPORT DATA
(Please read Instructions on the reverse before completing)
TREPORT NO. 2.
EPA- 568/13-79-008
4. TITLE ANDSUBTITLE
METHODOLOGY FOR ESTIMATING DIRECT EXPOSURE TO NEW
CHEMICAL SUBSTANCES
• AUTHOR(S)
David Becker, Edward Fochtman, Allan Gray,
Thomas .Jacobius
i PERFORMING ORGANIZATION NAME AND ADDRESS
IIT Research Institute
10 West 35th Street
Chicago, Illinois 60616
12. SPONSORING AGENCY NAME AND ADDRESS
Office of Toxic Substances
1 Washington, DC
3. RECIPIENT'S ACCESSION NO.
5. REPORT DATE
July 1979
6. PERFORMING ORGANIZATION CODE
8. PERFORMING ORGANIZATION REPORT NO.
C6390C08
10. PROGRAM ELEMENT NO.
11. CONTRACT/GRANT NO.
68-02-2617
Task 08
13. TYPE OF REPORT AND PERIOD COVERED
Final, Feb. 19/^9- June 1979
14. SPONSORING AGENCY CODE
EPA-560/13
•5. SUPPLEMENTARY NOTES
.u. ABSTRACT
The Toxic Substances Control Act (TSCA) requires each person who intends to
manufacture a new chemical to submit a Premanufacturing Notice to the EPA at least
90 days before manufacture commences. The work reported here was directed toward the
development of a procedure for the orderly and rapid prediction of direct human
exposure which might result from such manufacture, the procedure developed involves
the following stepts: (1) prediction of unavailable physical and chemical properties
from analogs and general chemical knowledge, (2) prediction of production volume
based upon company size, current markets and total market volume, (3) prediction of
chemical operator exposure and exposures in the vicinity of the plant based upon
fugitive emissions and (4) prediction of consumer exposure based upon active use
and passive use of the chemical.
The procedure will permit rapid screening however further refinements will
enhance the usefulness.
' KEY WORDS AND DOCUMEN^ ANALYSIS
DESCRIPTORS
Exposure Assessment
Consumer Exposure
Toxic Substances
Premanufacturing Notice
Manufacturing Exposure
Prediction of Chemical & Physical
Properties
a. DISTRIBUTION STATEMENT •
Release to public
b.lDENTrplERS/OPEN ENDED TERMS
19. SECURITY CLASS (This Report)
Unclassified
20. SECURITY CLASS (This page >
Unclassified
c. COSATI l-icld/Group
21. NO. OF PAGES
22. PRICE
"A Form 2220-1 (Rev. 4-77) PREVIOUS EDITION is OBSOLE'
A-51
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