560281003
Assessment of Testing Needs:
Oleylamine (9-Octadecenylamine)
Support Document
Proposed Health Effects Test Rule
Toxic Substance Control Act
Section 4
Existing Chemical Assessment Division
Office of Toxic Substances
U.S. Environmental Protection Agency
Office of Pesticides and Toxic Substances
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TABLE OF CONTENTS
Page
I . EXECUTIVE SUMMARY 1
II. GENERAL INFORMATION 8
A. Physical and Chemical Properties 12
B. Natural Occurrence 15
III . PRODUCTION AND CONSUMPTION 16
A. Production 16
1. Production Volumes 16
2. Production Methods 21
B. Imports and Exports 24
C. Consumption 24
1. Products Identified by NIOSH 25
2. Lubricating Oil and Fuel Additives 26
3 . Ore Flotation Agents 27
4. Other Applications 28
D. Distribution 29
IV. ENVIRONMENTAL EXPOSURE 30
A. Environmental Release 30
1. Releases from Manufacturing Sources ,30
2. Releases from Natural Sources and
Miscellaneous Production Sources 31
3. Releases from Processing and Use 31
4. Release from Transport and Disposal 33
B. Environmental Fate 34
1. Partitioning Among Environmental
Compartments 34
2. Aquatic Chemistry 35
3. Atmospheric Chemistry 35
4. Biodegradation 35
5. Bioaccumulation 36
V. HUMAN EXPOSURE 37
A. Occupational Exposure 37
1. Manufacture 39
2. Processing 40
3. Use 40
B. General Population Exposure 46
11
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Page
VI. HEALTH EFFECTS 48
A. Pharmacokinetics 48
B. Acute Toxicity 50
C. Subchronic, Chronic, and Neurotoxic Effects... 53
D. Mutagenicity and Oncogenicity 56
E. Developmental Toxicity and
Reproductive Effects 65
F. Neurotoxicity 75
G. Testing in Progress 75
VII. SECTION 4 (a) FINDINGS 76
REFERENCES 82
ill
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LIST OF FIGURES
Page
II-l Relationships among ODA-containing substances... 9
III-l Reaction steps in the production of primary
amines 23
VI-1 Gene mutation scheme for ODA 57
Vl-2 Chromosomal aberration scheme for ODA 58
IV
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LIST OF TABLES
Page
I-l Testing for ODA , 7
II-l Current Producers of Fatty Amine Mixtures
Containing ODA 10
II-2 Composition of Primary Alkylamine Products 11
II-3 Some Physical and Chemical Properties
of Oleylamine and ODA 13
III-l TSCA Inventory Production Estimates for
Oleylamine in. the United States During 1977 17
III-2 U.S. Production of Primary Amines 18
III-3 Estimation of 9-Octadecenyl Amine Production
from USITC Data for 1982 22
V-l Number of Workers Exposed to Oleylamine,
Listed by Industrial Category 38
V-2 Numbers of Workers Exposed to Oleylamine,
Listed by Occupational Category 38
V-3 Numbers of Employees in Various Job
Categories Where Exposure to Lubricating
Oils Routinely Occurs 42
VI-1 Summary of Toxic Effects of ODA 52
VI-2 Developmental Protocols 68
VI-3 Summary of Data on ODA Hydrofluoride:
Cetylamine Hydrof luoride . 69
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I. EXECUTIVE SUMMARY
In November 1983, the Thirteenth Report of the TSCA
Interagency Testing Committee (ITC) designated oleylamine, or
9-octadecenylamine (ODA, CAS No. 112-90-3), for priority con-
sideration by the Environmental Protection Agency for testing.
The ITC recommended that oleylamine (hereafter abbreviated as ODA
when used to refer to the pure, chemical, 9-octadecenylamine) be
tested for health effects: dermal toxicokinetic studies, to be
followed by genotoxicity (mutagenicity) and teratogenicity
(developmental toxicity) studies if percutaneous absorption is
demonstrated.
The bases of these recommendations were as follows:
production of 4.5 to 5.5 million pounds per year, estimated
occupational exposure of over 3000 workers (National Occupational
Hazard Survey (NOHS) 1972-1974), positive data from dietary and
intraperitoneal teratogenicity (developmental toxicity) studies,
and lack of sufficient data to characterize the effects of
concern for oleylamine.
ODA is a yellow liquid with an ammoniacal odor. It has very
low volatility and water solubility although water is soluble in
it. It is miscible with a variety of organic solvents.
The commercial products that contain ODA are produced from
natural fats such as beef tallow, which consist primarily of
various aliphatic fatty acid esters. When oleic acid is the
major acid constituent, the resulting mixture of fatty amines is
called oleylamine and contains up to 76% ODA. Other commercial
fatty amine products made from beef tallow and ranging from 38 to
45% in ODA content are marketed as "tallowamines." A variety of
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other fatty amine products, containing 2 to 55% ODA, are produced
from other plant and animal fats. The primary amine mixtures are
produced commercially in closed systems. Treating the fats with
ammonia produces ammonium salts, which are converted to amides
and dehydrated to nitriles. In a separate process, the nitriles
are then converted to primary amines by catalytic hydrogenation.
ODA is currently produced by six manufacturers: Akzo Chemie
America (formerly Armak Company); Jetco Chemicals, Inc.; Sherex
Chemical Company; Humko Chemical Corporation, Borg-Warner Corp.
and Tomah Products, Inc. In 1977, the TSCA Public Inventory
listed total yearly production of ODA as 200,000-2 million Ib,
compared to 6.62 million Ib reported by the U.S. International
Trade Commission. (USITC). However, EPA estimates that the total
ODA produced in 1982 as a component of various products.was 18 to
29 million Ib. Actual current production is confidential
business information, but production of oleylamine in 1982 was
estimated to be 4.5-5.5 million Ib by Akzo Chemie America; Akzo
predicts no production change in the forseeable future. No
public information was available on current levels of importation
or exportation of ODA.
The primary amines, which include oleylamine and its
constituent ODA, are cationic, surface-active agents.
Most frequently, they are used as chemical intermediates to make
other cationic surfactants. When used directly they are believed
to be used primarily as additives to lubricants, fuels, and
transmission fluid, in textile finishing, and as ore flotation
agents. In lubricant additive packages, oleylamine may be added
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directly or chemically converted to other derived products prior
to addition. The amounts used in various products are considered
trade secrets. Undisclosed amounts of primary amines containing
ODA are also used in the construction industry as additives in
mold-release coatings for concrete forms. Primary amines
containing ODA have been approved by the Food and Drug
Administration (FDA) for use as indirect food additives and as
such may serve as defoaming agents in paper and paperboard,
glues, and adhesives intended for use in packaging, transporting,
or holding food. They are also reportedly used as vulcanization
activators in rubber compounds that may ultimately contact food
and as anticorrosive agents in steam lines in food-handling
operations.
Because oleylamine is produced and processed in closed
systems and because its vapor pressure is low, little human
exposure is expected during its manufacture and processing. The
National Occupational Hazard Survey (NOHS, 1972 to 1974)
indicated that 3,155 workers in all categories were occupa-
tionally exposed at that time. Exposures during manufacture or
processing would most likely occur via the dermal route during
materials transfer or sampling.
Occupational use of ODA-containing products may result in
substantial human exposure to ODA. The primary occupational
exposure is probably to workers in routine contact with
lubricating oils, gasoline, and diesel fuels in the service,
repair, and overhaul of motor vehicles, farm machinery, and heavy
equipment. In 1983, these categories encompassed roughly 2.8
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million workers who miy^t come in contact with ODA-containing
lubricants. Some construction laborers could also be exposed as
a result of applying concrete mold-release agents containing
ODA. The current number exposed via this use is not available,
but it was reported by the NOHS as approximately 2,400 in the
early 1970's. The primary route of exposure in all occupational
categories would be dermal.
ODA is shipped from nine manufacturing sites as a
constituent of fatty primary amine mixtures. Because production
occurs in closed sytems, environmental releases are expected to
be small. Batch processing also occurs in closed systems and is
expected to result in low environmental releases.
Spills during manufacturing, transport, or processing
present a potential source of accidental release to soil or water
but little potential for release to the atmosphere because of the
low vapor pressure of ODA. Some primary amine may be released to
soil from dispersive sources such as potash fertilizers and
hygroscopic fertilizers, some from use as a release agent for
concrete forms, and some from use as lubricant addditives. No
information was found on environmental release during shipment.
ENPART modeling indicates that most of the ODA released to
the environment will partition into water and soil, with some
collecting at the air-water interface.
Although no supportive data are available for ODA, reports
on analogous compounds indicate that it should degrade fairly
rapidly in the environment by the action of soil and aquatic
microorganisms. Because ODA is the primary amine corresponding
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to the naturally occurring fatty acid, oleic acid, it is not
expected to persist in the environment and should be readily
metabolized in biological systems. Thus bioaccumulation of ODA
is not expected despite its high estimated octanol/water
partition coefficient (log P) value (7.5-8.1).
ODA may be released into the environment owing to improper
disposal of used lubricants and greases. Dispersive release
would in this way lead to low concentrations, however, and be-
cause of the expected rapid biodegradation, human and animal
exposure from environmental sources should be minimal.
Health effects data on ODA are limited. No information
is available on the pharmacokinetics of ODA in any species. The
compound is absorbed through the oral route, as demonstrated by
data on toxicity in experimental animals. Although the dermal
route is the expected primary exposure route, no information was
found on dermal absorption .of ODA. Data on related compounds,
however, indicate that some dermal absorption should occur.
Studies of ODA administered to mice orally or by the
intraperitoneal route (oral LDLo, 3,200 mg/kg; i.p. LD50,
889 mg/kg) indicate a low order of acute toxicity. No informa-
tion was available on subchronic or chronic toxicity of ODA in
any species. At high dose levels, oleylamine was teratogenic and
embryotoxic to mice: It was embryotoxic at 800 and 3,200 mg/kg
orally and 400 and 800 mg/kg intraperitoneally, but teratogenic
only when administered intraperitoneally at 400 or 800 mg/kg. No
information was found on the testing of ODA for mutagenic, car-
cinogenic, or neurotoxic effects.
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The Agency is proposing testing of ODA under section
4(a)(l)(B) of TSCA because it is produced in substantial
quantities, there may be substantial human exposure, and there
are insufficient data to reasonably determine health effects.
Testing for teratogenicity is being proposed under both sections
4(a)(l)(A) and 4(a)(l)(B). Proposed testing is as follows:
oral teratogenicity test
tiered genotoxicity with a trigger to oncogenicity test
90-day dermal subchronic test which includes:
neurobehavioral observations
reproductive parameters
dermal absorption determination
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The ITC recommendations and EPA proposed testing
requirements are summarized in Table 1-1.
Table 1-1. Testing for ODA
ITC
Test Recommendation Proposed Testing
Toxicokinetics yes yes
Genotoxicity yesa yes
Teratogenicity° yesa yes
Oncogenicity no • yesa
90-day dermal subchronic
toxicity no yes
Meurobehavioral
observations no yes
Reproductive parameters no yes
a-conditional
b-referred to in this document as "developmental toxicity*
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II. GENERAL INFORMATION
ODA (CAS No. 112-90-3) belongs to the general group of long-
chain aliphatic amines (hereafter "ODA" will refer to the pure
chemical, 9-octadecenylamine; the term "oleylamine," to fatty
amine mixtures containing 65-76% ODA). These amines correspond
to ammonia with one or more hydrogen atoms replaced by long-chain
aliphatic hydrocarbon moieties. They are classified as primary,
secondary, or tertiary amines, depending on the number of sub-
stitutions on the nitrogen atom. ODA is a primary amine in which
the aliphatic substituent is an 18-carbon chain containing one
double bond. Commercial substances are mainly the cis-isomer but
may also contain undetermined amounts of the trans-isomer.
Of the synonyms for ODA (NIOSH 1983c) listed below, the
last four are sometimes used to refer to the pure chemical and
sometimes mixed products which are predominantly ODA:
o 9-Octadecenylamine
o cis-970ctadecenylamine
o Oleinamine
o Oleamine
o Oleylamine
o Oleylamin (German)
The commercial product described as oleylamine is produced
from beef tallow and contains a number of long-chain, primary
amines in proportions dependent on the relative amounts of the
corresponding fatty acid progenitors present in the original beef
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tallow. The .ODA content of these products ranges between 65 and
76%.
A number of other products contain ODA, notably tallowamine
(38-45% ODA). A variety of primary fatty amine mixtures are
derived from other plant and animal sources and, in this report,
are referred to generically as primary amines.
The six manufacturers of the fatty amine mixtures (first
four are major producers and last two are minor producers)/ which
include ODA, and their locations are listed in Table II-l. The
carbon chain length distribution of amines in the commercial
amine products of the four major manufacturers is presented in
Table II-2. Figure II-l shows the relationships among various
ODA products.
Figure II-l: Relationships among
ODA-containing substances
Animal fats
(e.g. beef tallow)
chemical
transformation
oleylamine.
~70% ODA
•^tallowamine
-40% ODA
other amines
Plant fats
(e.g. coconut oil)
chemical
transformation
primary
amines
I.
cocoamine
~5% ODA
+
other amines
chemical
transformation
chemical
transformation
secondary and tertiary amines and other products
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Table II-l. Current Producers of Fatty Amines
Mixtures Containing ODA
Company '. Location
Major Producers
Akzo Chemie America McCook, IL
Armak Chemical Division Morris, IL
Humko Chemical Memphis, TN
Jetco Chemical, Inc. Corsicana, TX
Sherex Chemical Co., Inc. Mapleton, IL
Oakland, CA
Minor Producers
Borg-Warner Corp.
Spar-mar Dispersants Div. Spartanburg, SC
Tomah Products, Inc. Milton, WI
Pedricktown, NJ
Because available information on ODA is limited, this docu-
ment includes relevant data on structural analogs. The struc-
turally related compounds listed below are expected to behave
similarly in some respects to ODA in biological systems and in
the environment.- Information on them may contribute additional
insight into the environmental fate and biological effects of
ODA. These structural analogs include
o Stearylamine (octadecylamine)
o Palmitoleylamine (9-hexadecene-l-amine)
o Palmitylamine (hexadecylamine or cetylamine)
o Linoleylamine (9,12-octadecadiene—1-amine)
10
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Table II-2. Composition of Primary Alkylamine Products
Product
description
Tallowamine
Oleylaraine
Soyamine
Technical
vegetable amine
Tall oil amine
Cocoamine
Octadecyl amine"
Stearylamine"
Tradenamesa
Armeen* T, TM-97, TD
Adogen* 170, 170-D, 170-D (EO)
Kemamine* P-974D
Jet Araine* PT, PTD
Arraeen* o, OD
Armeen* OL
Adogen* 172, 172-D, 172-D ( EO)
Kemamine* P-989-D
Jet Amine* PO, POD
Armeen* SD
Adogen* 115, 115-D, 115-D ( EO)
Jet Amine* PS, PSD
Kemamlne* P-999
Adogen* 151
Armeen* C, CD
Adogen* 160, 160-D, 160-D ( EO)
Jet Amine* PC, PCD
Armeen* 18, 18D
Adogen* 142, 142-D
Kemamine* P-990D
C8-Cl7
33.5
35 •
33
33
9.5
9.5
5
18
18
17
16
15
92.5
90
90
11
5
10
Saturated
CIB
20.5
20
25
25
14
5
20
10
10
5
14
6
3
2
6
5
87
93
90
Typical carbon chain
C20 C14~16' C18'
2
45
38
38
6.5 67
6.5 76
75
65
65
21
25
55
49
5
composition
Unsaturated
!-• i i piii r* '
*-18 18 20
44C
4
4
3
3
7
7
49 7 1
45
15 5 4
43 5
5.5C
4C
2C
2
aArmeens are produced by Akzo Ctiemie America (Armak 1978), Adogens by Sherex Chemical Co. (n.d.a), Kemamines by
Witco Chemical (1983); Jet Amines by Jetco (n.d.b).
''Each apostrophe signifies one double bond. C\s' *3 9-octadecenylamine.
-Mixture of Cia« and C18''
Synonymous.
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A. Physical and Chemical Properties
ODA is a yellow liquid with an ammoniacal odor
(Armak n.d.). The physical and chemical properties of oleylamine
and ODA are summarized in Table II-3.
Oleylamine is soluble in organic solvents including
methanol, ethanol, acetone, isopropanol, chloroform, toluene,
carbon tetrachloride, kerosene, and white mineral oil (Armak
1978). Oleylamine behaves as a base in solution (Patty's
1981). Although oleylamine has low solubility in water at
neutral pH, water is appreciably soluble in oleylamine. Reported
as percent of solution weight, the solubility of water in oleyl-
amine is 9.59 at 50°C and 4.08 at 80°C (Armak 1978).
The octanol/water partition coefficient (log P) for
ODA, as estimated using the method'of Leo et al. (1971), was
reported by the ITC as 7.5. The Office of Toxic Substances (OTS)
estimated log P for ODA, using the method of Lyman et al. (1982),
to be 8.1 (USEPA 1983a). The water solubility of ODA was listed
by the ITC as "low" and was calculated by OTS as being either
0.5 x 10"3 mg'/l or 0.7 x 10"5 mg/1 (USEPA, 1983a) from respective
log P values of 7.5 and 8.1 (see above).
The freezing point of various commercial oleylamine
products varies as a function of their mixed fatty amine content.
Armak (n.d.) reports a freezing point of 21°C, for Armeen® and
Armine OD*. Jetco (n.d.b) reports that Jet Amine PO® and Jet
Amine POD® are liquids at 25°C. Sherex (n.d.a) reports that
Adogen 172® and Adogen 172-D® are liquids at 15°C.
12
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Table II-3. Some Physical and Chemical Properties
of Oleylamine and ODA
roperty
Characteristic
or value
Reference
olecular formula
olecular structure
cis isomer)
olecular weight
reezing point
oiling point
'lash point
'ire point
Specific gravity
fapor pressure
Tlscosity
/oLatiles
H ' H
267.5a
21°Ca
275-344°C @ 760 ram Hga
154°-160°Ca
177°-182°Ca
0.819 @ 38°Ca
0.5 x 10~4 mm Hg @b
< 1 mm Hg 8 20°C3
56.6-57.0 SSU (25°C)a
1% by volume3
Dctanol water parti- log P = 7.5
tion coefficient
log P = 3.11
Solubility
In water (25°C)
In organic
solvents (25°C)
0.5 x 1Q~1 mg/LJJ
0.7 x 10~5 mg/Lb
Soluble
Methanola
Ethanol3
Acetone3
Isopropanola
Chloroform3
Toluene2
Carbontetrachloride5
Kerosene3
Partly soluble
White mineral oil3
Armak (n.d.)
Armak (n.d.)
Armak (1978)
Armak (1978)
Armak (n.d.)
USEPA (1983a)
Armak (n.d.)
Armak (1978)
Armak (n.d.)
Method of Leo et al.
(1971)
Method of Lyraan et al.
(1982)
Armak (1978)
USEPA (1983a)
USEPA (1983a)
Armak (1978)
"As determined for Armeen 0* and Armeen OD® containing 67% ODA (Armak 1978)
"Estimated for ODA»
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Long-chain primary aliphatic amines, including ODA, are
cationic surfactants. Cationic surface-active agents are
attracted to materials whose surfaces are negatively charged.
The surface-active amines orient themselves with the charge-
carrying nitrogen at the adsorbing surface and the hydrocarbon
"tails" extending outward, presenting a lipophilic or hydrophobic
surface toward the aqueous carrier medium (Armak 1978). This
property makes the primary aliphatic amines suitable for several
industrial applications including ore flotation, corrosion
inhibition, pigment dispersion, fabric finishing and anticaking
(Jetco n.d.a.).. Sherex notes that the primary amines are most
often used as intermediates to make other cationic surfactants;
derivatives generally have wider end use applications than the
primary amines themselves (Sherex n.d.a).
The primary aliphatic amines generally undergo a
variety of reactions used commercially to manufacture a number of
useful products (Armak 1978, Kirk-Othmer 1978). The following
are typical reactions of the primary amines:
(1) reactions with mineral acids and organic acids to form
salts;
(2) reactions with alkyl and aryl halides to form
quaternary ammonium salts;
(3) reactions with ethylene oxide to form ethoxylates;
(4) reaction with chloroacetic acid to form betaines;
(5) reaction with phosgene to form substituted ureas; and
(6) other reactions such as alkylation, acylation, and
condensation with carboxyl compounds and lactones.
14
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B. Natural Occurrence
Although ODA is manufactured from naturally occurring
fatty acid mixtures, no reports on its natural occurrence were
found in the available literature.
15
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III. PRODUCTION AND CONSUMPTION
A, Production
1. Production Volumes
The volumes of "oleylamine produced by the
manufacturers listed in the public portion of the TSCA Inventory
are summarized in Table III-1. Total annual production in 1977
reported by three manufacturers was 200,000 to 2 million Ib (90-
900 kkg). Two other manufacturers chose not to disclose
production volumes publicly but reported volume on a confidential
basis, and one manufacturer reported no production or importation
of oleylamine during 1977 (USEPA 1983b). Table III-2 lists the
production volumes of a number of amine products believed to con-
tain ODA for the period 1977-82 as reported by the U.S. Inter-
national Trade Commission (USITC). The production volume
reported for ODA by the USITC for 1977 (6.62 million Ib) was much
higher than that listed for ODA in the TSCA Inventory for the
same period (USITC 1978; USEPA 1983b). A number of factors may
have contributed to the discrepancy between production volumes
reported by the USITC and the TSCA Inventory. For example, Akzo
Chemie America, formerly Armak, the current leading manufacturer
of fatty acid amines, did not report its 1977 production volume
to the public portion of the TSCA Inventory, but did to the
USITC, which would lead to a large apparent discrepancy between
the two figures.
Furthermore, some manufacturers may have
inadvertently double-counted by reporting both the technical
grade fatty amines and the distilled grades prepared from the
16
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Table III-1. TSCA Inventory Production Estimates for
Oleylamine in the United States During I977a
Volume
Manufacturer
Enenco, Inc.
Ashland Chemical Company
Armak Industrial Chemicals®
Piedmont Chemical Industries
General Mills Chera., Inc.
Manufacturer not specified
TOTALd
Location
Memphis, TN
Mapleton, IL
McCook, IL
High Point, NC
Kankakee, IL
Not specified
Ib (x 1000)
100-1,000
100-1,000
c
b
1- 10
200-2,000
kkg
45 -450
45 -4gO
c
b
0.45- 4.5
90 -900
fuSEPA (1983b).
"Production volume-reported as confidential business information for
1977.
^No manufacture or importation during 1977.
Total volume in rounded numbers.
eNow Akzo Chemie America (Chem Mark Rep 1983).
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Table III-2. U.S. Production of Primary Amines
Primary amine mixture 1977
(Coconut oil alkyDamine
(Hydrogenated tallow alkyD-
amine 3.416
9-Octadecenylamine 6.619
Octadecyl amine
(Soybean oil alkyDamine
(Tallow alkyDamine 9.786
All other 30.332
TOTAL 50.153
Product ion
1978
3.695
3.626
9.168
33.495
49.984
volume
1979
4.182
4.937
-
15.000
7.236
31.355
(in millions
1980
3.670
5.458
8.086
7.386
24.600
of pounds
1981
5.488
0.728
8.505
9.484
24.205
,
1982
1.116
2.312
4.952
0.312
1.275 (sales)
11.520
1.976
23.437
Refers here to the oleylamine mixture containing ODA
Source: USITC (1978; 1979; 1980; 1981; 1982; 1983).
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technical grades. In some instances the production volume of the
oleylamine mixture may have been reported: in other instances,
the ODA itself. Because the term "production" is so ambiguous,
some manufacturers may have reported only net production, that
is, the primary amine which left the plant site as primary amine;
others may have included primary amine which they produced but
used on site to produce other chemicals, such as secondary and
tertiary amines. Additionally, production volumes are not
published by the USITC if publication would directly or
indirectly reveal confidential information about manufacturers.
That there is a problem in accepting production
volumes at face value is evident not only from the discrepancy
between the values reported in the TSCA Inventory and those by
the USITC, but also from the discrepancy between reported
production of primary amines and their derivatives; not nearly
enough primary amine is "produced" in order to sustain reported
production levels of derivatives. It seems most likely that the
reported production levels most closely approximate the amount of
primary amine which leaves the plants as primary amine, rather
than the total amount of primary amine produced by the
manufacturers.
EPA has estimated that the total ODA production
for 1982 (including use as an intermediate in manufacturing other
products) was 18 to 29 million pounds. This estimate varies from
the 1982 production of 4.95 million pounds reported by the USITC
(see Table III-2) for the following reasons:
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1. The USITC data are for the product mixture designated
as oleylamine, not the chemical designated ODA. The
actual chemical (ODA) constitutes about two-thirds of
the oleylamine mixture. Moreover, oleylamine is not
the only commercial material containing ODA. The
several oleylamine products of each producer also have
a wide variety of ODA content. Thus, the overall ODA
chemical content of those oleylamine products and the
total amount of ODA produced can only be estimated.
2. Captive consumption of ODA-containing products (e.g.,
tallowamine or oleylamine) typically is not reported.
Thus, reliance on reported production figures alone is
likely to lead to an underestimation of actual ODA
production levels. For example, over the years from
1972 to 1983, the figures reported for oleylamine sales
and oleylamine production differ by an annual average
of 1'4 percent. However, the difference between
reported production and reported sales accounts for
only a small percentage of the reported production
levels of the many captive derivatives produced.
Similar discrepancies arise in the production and sales
data for other ODA-containing products.
The detailed procedure and assumptions used to
derive EPA's estimated production range of 18 to 29 million
pounds per year are explained in Mathtech (1984).
20
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Oleylamine and other fatty amines are produced by
six manufacturers: Akzo Chemie America (formerly Armak Company,
Chem Mark Rep 1983); Jetco Chemicals, Inc.; Sherex Chemical
Company, Inc.; Witco Chemical Corporation (SRI 1983a); and Toman
Products, Inc. (tallowamine only) and Borg-Warner Corp. (cocoa
amine only). (USITC, 1983). Current production volume and
market share of oleylamine for each of the manufacturers 'were not
available; however, Akzo, which produces more than 50% of the
current total oleylamine volume (Dynamac 1983a), expects total
U.S. production of oleylamine to remain at 4.5-5.5 million Ib
(2,000-2,500 kkg) in the near future (Armak 1982).
2. Production Methods
Primary amines are produced "by Akzo (Armak 1982)
in a closed system, according to the reaction sequence in Figure
III-l. Oleic acid, a fatty acid constituent of plant and animal fat,
is treated with ammonia in process step 1 and the resultant
ammonium salt 'converted to the amide in step 2. Step 3 is the
dehydration of the amide product to form the nitrile. Steps 1
through 3 take place in the same reactor. The fourth step,
catalytic hydrogenation of the nitrile to the amine, is a
separate process. Since the naturally occurring fats contain
various mixtures of fatty acids, the products contain correspond-
ing mixtures of long-chain aliphatic amines (Armak 1978).
Tallowamine and oleylamine mixtures account for more than 90% of
the ODA produced (Table III-3).
21
-------
Table III-3. Estimation of 9-Octadecenylamine
Production from USITC Data for 1982
Product
(Coconut oil alkyl)-
amine
( Hydrogenated tallow
alkyl )amine
9-Octadecenylamined
Octadecylamine
(Soybean oil alkyl)-
amine
(Tallow alkyljamine
All other
TOTAL
Estimated 1982
production
(million Ib)
1.116
2.312
4.952
0.312
1.275b
11.520
1.97
23.463
Typical
ODA content3
(wt %)
4
1
70
1
23
41
10C
ODA
produced
(million Ib)
0.045
0.023
3.466
0.003
0.293
4.723
0.198
8.751
Percent
of
total
0.5
0.3
39.6
0.03
• 3.3
54
2.3
100
aSimple average of products listed in Table III-2; not weighted for relative production
of different products.
"Sales.
cEstimated.
"Refers to the oleylamine mixture containing ODA.
-------
w
0
II
R— C— OH
fitly Kid
NH3
0
-> R—C—O—NH4
ammonium soap
0
II
(23 R—C—O—NH4
ammonium soap
0
II
R—C—NH3
amid*
(3)
0
11
•nid*
he
-------
B. Imports and Exports
No publicly available information was found on the
importation or exportation of ODA or oleylamine.
C. Consumption
The primary amines become protonated at acid pH and
function as cationic, surface-active agents, that is, surfactants
in which the polar component is a positive ion. They can
function as detergents, wetting agents, or emulsifiers.
Specific applications for the primary amines (and their
salts) suggested in the manufacturers' literature include: ore
flotation agents, additives for fuel oils, gasoline, lubricating
compounds, and metal working oils, dispersants and grinding aids
for paint and ink manufacture; mold-release agents for rubber,
plastics, and concrete; corrosion inhibitors; anticaking agents
for fertilizers and other hygroscopic materials; antifoaming
agents for use in manufacturing laundry detergents, biocides,
and paint strippers (Armak 1980, Humko 1978, Jetco n.d.b).
Despite the abundance of potential uses for the primary
amines themselves, they are most often used as intermediates to
make other cationic surfactants (Sherex n.d.a). The major fatty
amine producers (Akzo, Sherex, Witco, Jetco) are also the major
suppliers of secondary and tertiary amines, diamines, quarternary
ammonium salts, and ethoxylated amines (not all of which,
incidentally, are necessarily derived from primary amines;
secondary amines, for example, can be produced directly from the
fatty acids). It appears, therefore, that much, or most, of the
primary amine produced in the United States, therefore, is con-
sumed on the plant site at which it was produced.
-------
Because of the proprietary nature of the products which
could contain primary amines, it is difficult to establish which
products actually do contain primary amines, much less at what
levels. A concomitant difficulty in determining exactly where
ODA itself might be found is the variation in ODA content of the
primary amines produced. In this section, therefore, the most
probable and significant uses for the primary amines, especially
tallowamine and oleylamine, are discussed.
1. Products Identified by NIOSH
The National Occupational Hazard Survey (NOHS)
conducted in 1972-74 (NIOSH 1983b) lists only two tradename prod-
ucts containing oleylamine: White Double Pigment Barethane,
manufactured by Brulin & Company, Inc., Richmond, CA; and Symons
Form Oil, sold under the name of Magic Kote by Symons
Corporation, King of Prussia, PA. According to a representative
of Brulin (Schmidt 1983), White Double Pigment Barethane is not
listed as a current Brulin product. Symons Form Oil or Magic
Kote is actually manufactured by Zea Chemicals, Kansas City, MO
(Grissinger 1983) and is a relatively common brand of mold-
release agent (Johnson 1983). It is applied to forms in which
concrete is poured and prevents the forms from adhering to the
concrete. According to the NOHS (NIOSH 1983b), it contains 5%
oleylamine. According to Zea Chemicals, the 5% oleylamine
25
-------
concentration reported by the NOHS is too high by several orders
of magnitude (Grissinger 1983).
2. Lubricating Oil and Fuel Additives
It appears that various segments of the
lubricating oil industry are the primary consumers of the product
described as oleylamine. According to Akzo, the largest producer
of oleylamine, the substance frequently is chemically reacted
with other materials to form high-molecular-weight, more
thermally stable derivatives. These derivatives are then used in
additive packages that are added to lubricating oils (Armak
1983a). Oleylamine is also incorporated, to a lesser extent, in
additives for gasoline (Armak 1982) and diesel fuel (Torey
1983). Akzo does not process oleylamine further in its plant but
sells it to other firms for processing into various products
(Armak 1983a). One such company is Lubrizol. A spokesman for
Lubrizol indicated that industry uses oleylamine in lubricant
additive packages both "as is" and as an intermediate in the
production of other compounds that are incorporated into
lubricant additive packages (Hoke 1984). The resulting maximum
ODA concentration in petroleum lubricants in less than 1 percent
(USEPA 1984f).
Other sources (SRI 1982, Sherex n.d.a) indicate
that primary amines are used in industrial gear boxes, although
the actual amines used were not specified.
26
-------
3. Ore Flotation Agents
Valuable minerals such as copper, lead,
molybdenum, zinc, phosphate, and potash ores can be separated
from the worthless rock and clay in which they occur by means of
a process called "froth flotation." The crude ore is finely
ground and subjected to a "bubble bath"; those particles with a
hydrophobic surface tend to adhere to the water-air interface of
the bubbles and hence concentrate in the foam phase, and the
hydrophilic particles remain in the water phase. Primary amines
and more typically their acetate and hydrochloride salts, as well
as other fatty amine derivatives, are used to impart the
hydrophobic surface to the minerals recovered from the foam
phase: the cationic amine "heads" stick to the mineral surface
and the long carbon chains radiate outward. Only 50-350 g of
amine is required per ton of ore (Kirk-Othmer 1982, 1980; Hurako
1978). The amine remains,.clinging to some of the minerals in
their end use. For example, in the case of potassium chloride
(80 percent of.U.S. production involves froth flotation
separation from sylvinite) used for fertilizers, primary amine
presence is considered desirable as it keeps the hygroscopic
particles from caking (Kirk-Othmer 1982). On other ores, the
amine is burned off during smelting operations.
The primary amines and their salts are apparently
used mostly in the flotation of potash (Kirk-Othmer 1982),
silica, and mica (Sherex n.d.b, Humko 1978). According to Humko,
technical coconut and tallow primary amines are the most commonly
used collectors, and they are often converted to acetates on site
27
-------
(Humko 1978). Cocoamines, as noted previously, typically contain
little ODA (approximately 5%) and tallowamines, approximately
40%. According to Sherex, their cocoamine flotation reagents are
especially suitable for potash, silica, and mica flotation, and
their tallow and oleylamine reagents are suitable for mica and
feldspar flotation and potash anticaking; their tallowamine can
also be used for silica flotation (Sherex n.d.b). Akzo sells the
acetate salts of cocoamine, octadecylamine, hydrogenated
tallowamine, and tallowamine (Armak 1980), and Jetco will provide
its customers with the amine salt upon request (Jetco n.d.a).
4. Other Applications
Another possible use of oleylamine is as a
defoaming agent in the manufacture of paper and paperboard,
glues, and adhesives. These products could be used in packaging,
transporting, or holding food since oleylamine has been approved
as an indirect food additive in accordance with FDA regulations
(Armak 1983b).. Actual usage in these applications was not
reported in the available literature.
Oleylamine is reportedly used as a vulcanization
material/activator in rubber products, which may contain up to 5%
of the compound by weight. Such rubber products could be used in
food handling (Armak 1983b), but actual use was not documented.
Oleylamine has also received FDA approval for use
as an anticorrosive agent in steam lines (Dynamac 1983a) , where
it forms a nonwetting film on metal surfaces, thereby reducing
oxygen and carbon dioxide attack (Perry and Chilton 1973).
28
-------
A number of other potential uses for oleylamine
have been identified from the patent literature. Patents have
been issued for its use in an anticorrosive organic pigment at
levels of 0.5-5% w/w (Horiguchi et al. 1978), in a toilet bowl
cleaner at levels of 0.1-10% w/w (Raynor 1981), and as an
intermediate in the production of N-substituted glyconitriles
(Distler et al. 1978, Horodysky and Kaminski 1981, Horodysky and
Kaminski 1983, Horodysky 1983). It has been tested for its
ability to impart corrosion resistance to steel (Salensky 1981).
D. Distribution
Akzo ships primary-amine products in 55-gal, non-
• returnable, unlined steel drums, tank cars, or tank trucks. To
.facilitate transfer, the temperature- of oleylamine storage tanks
is maintained at approximately 27°C, i.e., 6°C above its freezing
point. Akzo suggests blanketing the tanks with an inert gas such
as nitrogen in order to prevent oxidative attack (Armak 1976).
29
-------
IV. ENVIRONMENTAL EXPOSURE
This chapter presents information related to the potential
for human exposure to ODA via the environment. Conclusions about
human exposure based on this information are located in
Chapter V, Human Exposure.
A. Environmental Release
The primary amines (including oleylamine and
tallowamine) are currently produced in the United States by six
manufacturers. Most of the primary amines manufactured are
believed to be captively consumed in the production of other
fatty amine derivatives. Environmental releases of primary
amines may occur during production and processing, from the use
of the processed products, and from the disposal of production
and processing wastes and used products.
1. Releases from Manufacturing Sources
Primary amines are produced by Akzo (Armak 1982)
using a four-step process described in chapter III. The entire
production sequence is performed in a closed system, thereby
minimizing emissions to air. The other major manufacturers also
use the closed batch method, resulting in minimal release of
primary amines to the atmosphere.
Spills of primary amine at the manufacturing plant
present a potential source of environmental exposure. It is
assumed that at least a small portion of any spilled material
would reach a wastewater treatment plant. Virtually no vapor
30
-------
release of ODA would result from a spill as the estimated vapor
pressure is very low (0.5 x 10~4 mm Hg at 20°C; USEPA 1983a).
In case of accidental spills, Armak (1976)
recommends cleaning by spreading floor-cleaning compound over
small spills and sweeping up the residue. Larger spills should
be flushed to a collection basin for approved disposal. The
company states that the area should then be cleaned with
detergent and water, and, because oleylamine is a skin and eye
irritant, protective gloves, goggles, and boots should be worn
when treating spills.
2. Releases from Natural Sources and Miscellaneous
Production Sources
No information was available to indicate
environmental releases of primary amines or ODA from natural
sources or miscellaneous production sources.
3. Releases from Processing and Use
Release of primary amines during processing is
likely to be minimal, according to representatives of the
following two confirmed processors of primary amines. A
spokesman for Zea Chemicals, manufacturer of Symons Magic Kote
concrete form oil (which contains ODA), stated that the product
is mixed only once or twice annually and that there are no
environmental releases (Grissinger 1983). Lubri-zol Corporation
produces lubricating oil additive packages in a closed system and
does not release oleylamine to the environment; waste gases are
incinerated (Hoke 1984).
31
-------
Environmental release of ODA is most likely to
occur during the use of products which contain primary amines.
Because of its use as a flotation agent in the separation of some
unsmelted ores, some ODA is likely to enter the environment,
clinging onto potash particles used in fertilizers. The
concentration would be quite low, however, as a quantity of only
50-350 g of mixed primary amine is used per metric ton (i.e., 50-
350 ppm) of ore products (Kirk-Othmer 1982, Humko 1978).
Environmental release from use of ODA-containing
products could occur at gasoline service stations and automotive
repair shops, where spills and leaks of lubricating oils and
gasoline are likely to be common. Similarly, leaks and drips of
lubricating oils and grease from motor vehicles represent a
possible source of ODA release. Although cars do not routinely
drip transmission fluid, a severe leak could lead to the
discharge of 4-6 qt of transmission fluid to the environment.
Also, waste disposal from transmission repair shops is a
potential source of release to the environment. Again, the ex-
tent of environmental exposure would depend on the extent to
which ODA occurs in these products. Owing to the proprietary
nature of transmission fluid and lubicating oil formulations,
information was lacking as to which products actually contain ODA
and, if so, how much. Therefore, levels of possible exposure
from these sources are poorly defined. However, the Agency has
some confidential business information that is consistent with
the position that environmental releases of this type are likely
to be low.
32
-------
Concrete form release agents, such as Symons Magic
Kote, are usually applied at the construction site using a hand
sprayer similar to a garden hose (Johnson 1983). EPA does not
expect this practice to release respirable droplets to the atmos-
phere in significant quantities; intermittent releases to soil
and to storm sewers could result.
4. Releases from Transport and Disposal
Accidental leaks or spills during shipping are a
potential source of release of primary amines to the
environment. According to Akzo (Armak 1976), these products are
normally shipped in 55-gal, nonreturnable, unlined steel drums or
in tank cars or tank trucks. No information was available on the
4
occurrence of spills and leaks during transport of primary amines
or primary amine-containing products.
Small amounts of primary amines may be released to
the environment through disposal of the wastes produced during
the manufacturing process. Akzo (Armak 1982) states that waste
material from venting and distillation equipment is
incinerated. Witco (Dynamac 1983b) flares all release gases but
discharges aqueous wastes into a publicly owned treatment
works. Jetco (Dynamac 1983b) reports that aqueous wastes are
settled and then filtered, resulting in a waste containing
oleylamine at "ppm levels"; this material is placed in
an injection well covered by a Texas Water Quality Board
permit. Sherex (USEPA)
Emptied containers of primary amine at Akzo's
plant (Armak 1978) are returned to drum reconditioners with all
33
-------
precautionary labels intact, or they are perforated or crushed
and buried "in a safe place away from water supplies." These
practices constitute a small potential for environmental
exposure.
B. Environmental Fate
1. Partitioning Among Environmental Compartments
ODA (Table II-3) has a low estimated vapor
pressure (0.5 x 10~4 mm Hg at 20°C), a high boiling point (275-
344°C), very low estimated water solubility (0.5 x 10~3 to 0.7 x
10"^ mg/L), and is estimated to have a very high octanol/water
partition coefficient (log P = 8.1; USEPA 1983a). It also has
properties of a cationic surfactant (Armak 1978) and is therefore
expected to sorb onto soil or sediment particles and collect at
the interfaces between the hydrosphere and the sediment and be-
tween the hydrosphere and the atmosphere. ODA is not expected to
partition appreciably into the atmosphere.
Relative mass distributions for ODA partitioning
into water, soil, and air on a global basis have been calculated
using the equilibrium model ENPART. Assumptions were an
atmospheric mixing depth of 1,500 m; a water column depth of 7 m;
a soil depth of 0.009 m; a half-life of 2 h in the atmosphere, 3
wk in water, and 4-8 wk in soil; and an initial dispersion of ODA
to the environment of 65% into soil, 30% into water, and 5% into
air. Under dynamic equilibrium conditions, most of the un-
degraded ODA (53-93%) would be expected to partition into the
water column, an appreciable fraction (6-46%) into soil, and a
very small amount (1%) into air (USEPA 1984a) . It should be
34
-------
noted that the partitioning of ODA is particularly sensitive to
its estimated water solubility. Most of the spread in estimated
mass distributions results from using two different estimates,
0.5 x 10~3 mg/L or 0.7 x 10~5 mg/L, for the solubility of ODA in
water (USEPA 1983a).
2. Aquatic Chemistry
ODA is expected to dissolve in water at levels
less than 1 ppb (USEPA 1983a), and therefore its aquatic
chemistry is primarily limited to phenomena which occur at the
sediment/wateT, suspended particulate/water, or air/water
interface. It 'is expected to be chemically stable in solution
and only very slowly degraded by reaction with dissolved oxidants
such as the peroxide free radical (RO2; Mill et al. 1980) and
atomic oxygen (0[3P]r Zepp et al. 1977).
3. Atmospheric' Chemistry
Because of the low volatility of ODA, atmospheric
degradation is" not expected to play a major role in its environ-
mental fate. However, if ODA enters the atmosphere it is ex-
pected to be rapidly degraded (half-life <0.24 h) by hydroxyl
radicals ( OH; Darnall et al. 1976).
4. Biodegradation
Biodegradation of ODA is expected to be the major en-
*
vironmental degradative pathway for ODA. ODA is derived from a
naturally occurring fatty acid (oleic acid), and the analogous
saturated amine (stearylamine) is known to biodegrade in acti-
35
-------
vated sewage sludge with a half-life of approximately 7 days
(Yoshimura et al. 1980).
5. Bioaccumulation
ODA has a high octanol/water partition coefficient
and would have a tendency to bioaccumulate. The bioconcentration
factor (3CF) can be estimated from the estimated octanol-water
•
partition coefficient for ODA using the following equation
developed by Veith et al. (1980):
Log BCF - 0.76 log P - 0.23
Substitution of 7.5 for log P (USEPA 1983a) leads to an estimated
BCF of 295,000. A value of this magnitude would indicate that
ODA has a strong tendency to bioconcentrate. However, because
the primary amines would enter the environment at disperse points
and at low concentrations, and because ODA is expected to
biodegrade fairly rapidly, it is not expected to bioaccumulate
significantly in the environment.
36
-------
V. HUMAN EXPOSURE
Human exposure to a chemical can occur during manufacture,
packaging or transport, through its use as an intermediate in
another manufacturing process, from use of a product which con-
tains the chemical, or through the presence of the chemical as a
contaminant in the atmosphere, in water, or in food. Some of the
potential exposures will affect only workers in relevant occupa-
tions while others may affect the general public or some subsets
of it. The primary route of general exposure to ODA and the pri-
mary amines is expected to be dermal.
A. Occupational Exposure
Occupational exposure to ODA can occur at the place of
production, at any plant in which primary amines are used in the
manufacture of another product, or during occupational use of a
product containing primary, amines. All three categories of occu-
pational exposure are reflected in the National Occupational
Hazard Survey (NOHS) conducted in 1972-74 (NIOSH 1983a). These
were the only data available to the ITC on possible occupational
exposure to ODA, but they appear incomplete. According to this
survey (Table V-l), an estimated 3,155 workers, most of whom
(75%) were in the general building contractor industry, were
potentially exposed to ODA in the workplace. Accordingly,
construction workers were reported as receiving the greatest
number of total exposures (75%), as listed in Table V-2. Other
37
-------
Table V-l. Numbers of Workers Exposed to Oleylamine
Listed by Industrial Category3
Industry
General building contractors
Paper and allied products
Chemicals and allied products
Petroleum and coal products
Leather and leather products
Miscellaneous manufacturing
industries
TOTAL
Estimated
plants
317
31
41
16
41
66
512
Estimated
people
2,376
225
207
93
122
132
3,155
Estimated
exposures
2,376
225
207
93
122
132
3,155
aNational Occupational Hazard Survey 1972-74 (NIOSH 1983a)
Table V-2. Number of Workers Exposed to Oleylamine
- Listed by Occupational Category3
Estimated
Occupation plants
Chemical engineers
Chemists
Chemical technicians
Pattern and model makers,
excluding paper
Mixing operatives
Machine operatives, miscel-
laneous specified
Construction laborers,
excluding carpenters'
helpers
Vehicle washers and
equipment cleaners
TOTAL
21
21
41
66
19
53
445
16
— b
Estimated
people
62
41
104
132
189
158
2,376
93
3,155
Estimated
exposures
62
41
104
132
189
158
2,376
93
3,155
^National Occupational Hazard Survey 1972-74 (NIOSH 1983a).
"Estimated plants not additive by occupation.
38
-------
industries within which exposure to ODA could occur were paper
and allied products (7%), chemicals and allied products (7%),
petroleum and coal products (3%), leather and leather products
(4%), and miscellaneous manufacturing industries (4%).
The NOHS survey did not include mechanic or other
machine-related occupations involving potential exposure to ODA-
containing lubricants. The U.S. Department of Labor estimates
the possibility of almost three million workers (see Table V-3)
exposed to ODA-containing lubricants. (Becker 1984).
Neither the American Conference of Governmental
Industrial Hygienists (ACGIH 1982).nor the Occupational Safety
and Health Administration (OSHA 1981) has set threshold limit
values, short-term exposure limits, or standards for oleylamine.
1. Manufacture
Manufacturers of primary amine and primary amine-
containing products and industrial users of primary amine-
containing products were contacted in an attempt to obtain more
detailed information on occupational exposure to ODA. Akzo was
the only manufacturer reporting nonconfidentially on occupational
exposure during manufacture of the chemicals. According to Akzo
(Armak 1982), primary amines are produced in a closed system,
thereby minimizing exposure during production. Because of ODA's
low vapor pressure «1 nun Hg at 70°C; see Chapter II, Table II-3)
inhalation of vapors is not expected to be an important route of
occupational exposure in the manufacturing facilities.
Employee exposure, according to Akzo (Armak 1982),
would be expected to occur only during material transfer and
39
-------
Table V-l. Numbers of Workers Exposed to Oleylamine
Listed by Industrial Category3
Industry
General building contractors
Paper and allied products
Chemicals and allied products
Petroleum and coal products
Leather and leather products
Miscellaneous manufacturing
industries
TOTAL
Estimated
plants
317
31
41
16
41
66
512
Estimated
people
2,376
225
207
93
122
132
3,155
Estimated
exposures
2,376
225
207
93
122
132
3,155
National Occupational Hazard Survey 1972-74 (NIOSH 1983a)
Table V-2. Number of Workers Exposed to Oleylamine
Listed by Occupational Category3
Occupation
Estimated
.plants
Estimated
people
Estimated
exposures
Chemical engineers 21
Chemists , . 21
Chemical technicians 41
Pattern and model makers,
excluding paper 66
Mixing operatives 19
Machine operatives, miscel-
laneous specified 53
Construction laborers,
excluding carpenters'
helpers 445
Vehicle washers and
equipment cleaners 16
TOTAL —b
62
41
104
132
189
158
2,376
93_
3,155
62
41
104
132
189
158
2,376
93_
3,155
^National Occupational Hazard Survey 1972-74 (NIOSH 1983a)
"Estimated plants not additive by occupation.
38
-------
industries within which exposure to ODA could occur were paper
and allied products (7%), chemicals and allied products (7%),
petroleum and coal products (3%), leather and leather products
(4%), and miscellaneous manufacturing industries (4%).
The NOHS survey did not include mechanic or other
machine-related occupations involving potential exposure to ODA-
containing lubricants. The U.S. Department of Labor estimates
the possibility of almost three million workers (see Table V-3)
exposed to ODA-containing lubricants. (Becker 1984).
Neither the American Conference of Governmental
Industrial Hygienists (ACGIH 1982) nor the Occupational Safety
and Health Administration (OSHA 1981) has set threshold limit
values, short-term exposure limits, or standards for oleylamine.
1. Manufacture
Manufacturers of primary amine and primary amine-
containing products and industrial users of primary amine-
containing products were contacted in an attempt to obtain more
detailed information on occupational exposure to ODA. Akzo was
the only manufacturer reporting nonconfidentially on occupational
exposure during manufacture of the chemicals. According to Akzo
(Armak 1982), primary amines are produced in a closed system,
thereby minimizing exposure during production. Because of ODA's
low vapor pressure «1 mm Hg at 70°C; see Chapter II, Table II-3)
inhalation of vapors is not expected to be an important route of
occupational exposure in the manufacturing facilities.
Employee exposure, according to Akzo (Armak 1982),
would be expected to occur only during material transfer and
39
-------
drumming, at which time a maximum of 20 persons would be
exposed. Workers are supplied with protective clothing, gloves,
and goggles. Because primary amines are skin irritants, such
exposure would be noticed quickly and the chemical would be
promptly removed. Some exposure could also occur La the event of
an accidental spill at the plant.
2. Processing
Occupational exposure to ODA may occur during the
production of primary amine-containing products. Lubrizol
Corporation, a major manufacturer of additives for lubricating
oils, stated that the additives are produced in a closed
system. Workers are provided with protective clothing and
Lubrizol maintains that occupational exposure is thereby
minimized (Hoke 1984). Zea Chemicals, manufacturer of Symons
Magic Kote concrete form oil, which contains oleylamine, stated
that there is little potential ?.oc worker exposure. The form oil
is mixed only once or twice annually, and workers are provided
with protective clothing (Grissinger 1983). Exposure is most
likely to occur in handling incoming shipments of primary amine
and in preparing outgoing shipments of the products.
3. Use
The occupational use of lubricating oils,
gasoline, and diesel fuels that contain primary amines as addi-
tives (see Chapter III) is potentially the source of the most
widespread exposure to ODA not mentioned in the NOSH survey;
Table V-3 (Becker 1984) shows the number of: workers who may
40
-------
routinely use such products. The number of workers exposed will
be related to the number and volumes of products containing
ODA. Relevant data here are limited. Generally, the lubricating
oil manufacturers purchase additive packages from the additive
manufacturers and are unaware of the contents. The additives
manufacturers consider the compositions of their products to be
proprietary. The Lubrizol Corporation has confirmed that
oleylamine is used in one or more of their products but declined
to publicly disclose in which products it is used or at what
concentrations (Hoke 1984). Maximum ODA concentration is thought
to be less than 1 percent, however (USEPA 1984f) . The assessment
/
of occupational exposure to lubricating oils is further
complicated by the fact that the ODA-containing primary amine
mixtures and other primary amine mixtures are frequently reacted
with other materials to form more thermally stable compounds
prior to or during incorporation into the additive package (Hoke
1984, Armak 1983a). For these reasons, accurate estimates of
worker exposure during the use of lubricating oils, gasoline, and
diesel fuel ca-nnot be made from information available to the
Agency. However, there is a potential for exposure of large
numbers of people via these products.
41
-------
Table V-3. Numbers of Employees in Various Job Categories
Where Exposure to Lubricating Oils Routinely Occurs*
Job category
Auto services except repairs
Auto mechanics
Bus, truck, and stationary
engine repairs
Aircraft engine mechanics
Small engine repairs
Heavy equipment mechanics
Farro equipment
Auto repair shops
TOTAL
Employed
. during 1983
( thousands)
238
800
299
95
63
162
49
835
2,541
Unemployed
during 1983
( thousands)
29
77
29
7
7
28
5
84
266
*Source: Becker (1984).
According to Akzo, free primary amine is not
stable when heated in air over extended periods of time, as would
be the case with transmission and crankcase oil applications.
There is no report of ODA use in crankcase oil and the level of
ODA in other used lubricating oils and greases should be low.
Worker exposure to ODA in used oils should be correspondingly low
(Armak 1983a) .
Auto mechanics routinely involved in engine
overhaul could be routinely exposed to ODA in various
lubricants. Exposure would be primarily dermal. Detailed
information on concentrations of ODA in lubricants is not
available. However, information submitted by industry, details
of which are claimed confidential, indicates that the maximum
level of ODA in petroleum lubricants is one percent or 10,000 ppm
(USEPA 1984f) , although in many cases only ODA derivatives are
42
-------
added rather than ODA itself. Using this 10,000 ppm value as an
example, dermal exposure of mechanics to ODA may be estimated as
follows using the equation for uptake of lipophilic compounds
through the skin (Higuchi 1960, Scheuplein and Blank 1971):
An'= KpCAt
where
An is the amount penetrating the skin (mg)
Kp is the permeability coefficient (cm/h)
C is the concentration of the compound (mg/cm4)
A is the area of application (cm^)
t is the time of application (h)
Scheuplein and Blank (1971) give a value for Kp of 0.052 cm/h
for n-octanol (in aqueous vehicle) through human epidermis.
The Kp for ODA should be somewhat lower than that for n-oc-
tanol. For a conservative calculation of skin absorption of ODA,
the Kp value for n-octanol was used.
Considering an area of application of 200 cm*
(approximately the area of the palms of the hands) and a time of
exposure of 4 h, the dermal uptake is calculated to be
An = 0.05 cm/h x 10 mg/cm3 x 200 cm2 x 4 h
9
An = 400 mg (for 4 h exposure of the palms of the hands)
43
-------
On the basis of this calculation, mechanics could
be exposed to daily dosages on the order of 400 mg of ODA if they
are exposed for 4 h per day or 6 mg/kg if average human weight is
assumed to be 70 kg. Conceivably, oral exposure could also occur
in those mechanics who failed to wash their hands before placing
food, cigarettes, or other items in the mouth.
Occupational exposure to ODA can occur during
occupational use of other ODA-containing products. However, the
maximum concentration of ODA in products in current use
reportedly is less than 1 percent and generally appears to be
considerably below this level (Chapter III). Form release
agents, for example, are applied at the construction site,
usually with a hand sprayer similar to a garden hose. Less
•frequently, the oil is applied with a paint brush, mop, or rag
(Johnson 1983). Respiratory exposure to ODA is not likely to
occur; dermal exposure could result from handling of sprayed
forms without adequate hand protection. Reliable estimates of
the concentration of primary amines in form oils could not be
obtained, although Zea Chemicals (Grissinger 1983) stated that
the 5% figure appearing in the NOHS survey for Symons Magic Kote
is too high by several orders of magnitude.
The mining industry uses primary amines as
collecting agents in the froth flotation process for separating
desired minerals from the gangue (Chapter III). Typically, only
small amounts of amines (50-350 g/ton; Humko 1978) are required,
and they are frequently converted to the more dispersable acetate
or hydrochloride salt prior to use (Sherex n.d.b). According to
an unpublished NIOSH study (NIOSH 1982)
44
-------
In the mill, the greatest potential for worker
exposure to flotation reagents exists during
their storage and handling. Exposure may also
occur during reagent tank and flotation cell
repair and maintenance. The principal routes of
worker exposure to these reagents are inhalation
of vapors and absorption by skin and eye contact.
Since the long chain primary amines have very low vapor pressure,
there is little possiblity of vapor inhalation. There is a
possibility that workers could inhale the mist above the
flotation chamber; however, virtually all of the amines would be
stuck to the mineral particles which would not remain airborne
for long. The number of workers required in and about the flota-
tion rooms varies from plant to plant; typically, the larger
plants are more automated than the smaller ones and hence require
less human involvement. Although amines constitute only 6
percent of the "collector agents" used in the ore flotation
process, this is the largest use of ODA (in the form of
tallowamine) (SRI 1983b, Mathtech 1984).
EPA believes the potential exposure to ODA of
approximately 2.8 million employees in various job categories
(Table V-3) supports a finding, of substantial human exposure
under section 4(a)(l)(B) of TSCA.
45
-------
3. General Population Exposure
The general population could be exposed to ODA through
use of products containing primary amines or through the presence
of the chemical as a contaminant in the atmosphere, in water/ or
in food.
Of the products that may cont.ain primary amines,
consumers are most likely to come into contact with lubricating
oils, gasoline, and diesel fuel. It is unclear in which types of
automotive fluids primary amines are used.
The dosage of ODA to which a person could be exposed if
lubricants or fuels were to come into contact with the palms of
both hands for 1 h could be approximately 1.5 mg/kg, using the
assumptions and calculations presented in the previous section. •
Consumers may be more or less frequently exposed to gasoline and .
diesel fuel, but only to small amounts for short periods of
time. Again, it is not clear if ODA is used in these fuels, and
if so in which products and at what levels.
ODA.is an FDA-approved indirect food additive if
used in the following ways: as a defoaming agent in the manufac-
ture of paper and paperboard (FDA 1982b);.in glues and adhesives
used in packaging, transporting, or holding food (FDA 1982a,d);
and as a vulcanization material/activator (FDA 1982c) for rubber
products used in food handling. Such uses are covered under the
Federal Food, Drug and Cosmetic Act and are not included in this
evaluation.
Although ODA could be released into the environment
from various dispersive sources, it would be highly dilute and
46
-------
its physical and chemical properties are such that it would be
readily biodegraded (see Chapter IV). Exposure of the general
public from environmental sources is therefore expected to be
insignificant. No information was found in the literature on the
presence of ODA as a contaminant in water, air, or food.
47
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v-- HEALTH EFFECTS
A. Pharmacok i ne t i cs
The ITC recommended initial dermal absorption and
toxicokinetic testing of ODA because of its potential skin
absorption by industrial workers, its high log P, and its
relatively low molecular weight.
There was little information in the available
literature on the absorption, tissue distribution, metabolism, or
excretion of ODA in any species. Data obtained from the
available toxicity studies indicated that ODA is absorbed by the
oral route (Eifinger and Koehler 1977). Although the dermal
route is expected to be the primary route of human exposure, no
information was available on dermal or percutaneous absorption of
ODA. The only data available on analogs are for dodecyldimethyl-
amine oxide (DDAO). Although it is not a close analog of ODA,
DDAO is similar enough for qualitative estimation of the lower
limit of skin penetration potential. Radiolabeled doses of DDAO
applied to the skin of humans, rats, mice, and rabbits (Rice
1977) penetrated at respective rates of <0.2, 6.0, 1.7, and
6.7 nmolh""-'-cm~2. The penetration rate for humans was lower than
for the other mammalian species by at least an order of
magnitude; however, the exposure period was also less (8 h for
human compared to 72 h for other species). The study indicates
that DDAO penetrates human skin, although poorly. ODA, being
less polar, would be more likely than DDAO to penetrate skin
(Scheuplein and Blank 1971).
48
-------
The Agency has no other information on the pharma-
cokinetics of ODA or its analogs.
EPA is proposing dermal absorption testing in
conjunction with the proposed 90-day, subchronic test (see Ch.
VI. D) because data are insufficient to reasonably predict or
determine absorption of ODA and testing is necessary to develop
such data. EPA is not proposing an initial toxicokinetic study
because some dermal absorption is expected to occur, and other
testing would still be required to determine the significance of
whatever absorption did take place.
49
-------
B. Acute Toxicity
The ITC did not recommend testing of ODA for acute
effects. The only acute oral and intraperitoneal toxicity data
available for ODA were obtained from teratogenicity studies using
pregnant female mice (Table VI-1). The compound has low acute
toxicity in the pregnant mouse: the oral TDLo and LDLo were 300
and 3,200 mg/kg, respectively, and the intraperitoneal TDLo and
LDLo were 4°0 and 800 mg/kg, respectively (Eifinger and Koehler
1977). The approximate intraperitoneal LDjQ was 888.6 mg/kg
(Stratmann and Eifinger 1980).
The acute dermal corrosion potential of tallowamine,
halogenated tallowamine, and cocoamine (3-44% ODA content) were
evaluated in New Zealand albino rabbits (Central Instituut voor
Voedingsonderzoek 1979). The intact and abraded skin of six
healthy adult animals was exposed to 500 mg of test compound for
4 h. After exposure, both intact and abraded skin sites showed
distinct ischemia (decreased blood flow) and moderate edema
(swelling). Observations 48 h later showed that severe necrosis
(tissue destruction) and incrustation had developed at the
exposed skin sites. All three primary amine mixtures were
considered to be corrosive to skin.
EPA is not proposing the testing of ODA for acute
toxicity. The great preponderance of potential human exposure to
ODA is to low concentrations that would minimize acute effects.
Industrial precautions consist of the wearing Neoprene gloves and
face shields or splash goggles (Armak n.d.), and worker contact
with the undiluted material results in immediate attention.
50
-------
Finally, some information on acute oral and intraperitoneal acute
toxicity is available, and more information is likely to be
generated by preliminary studies for the proposed 90-day
subchronic (dermal) and the developmental toxicity (oral) studies
(see Chapter VI.C and E).
51
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Table VI-1. Summary of Acute Toxic Effects of Oleyiamine
Species
Route of
adminis-
tration
Dose
Response
Reference
Mouse
(9 days pregnant) Oral
Mouse Oral
(9 days pregnant)
Mouse
(9 days pregnant) i.p.
Mouse
(9 days pregnant) i.p,
Mouse i.p,
(9 days pregnant)
800 mg/kg TDLo
3,200 mg/kg LDLo (1/4
died)
400 mg/kg TD
Lo
888.6 mg/kg LD,
50
800 mg/kg LDLo
died)
Eifinger and Koehler
(1977)
Eifinger and Koehler
(1977)
Eifinger and Koehler
(1977)
Stratmann and Eifinger
(1980)
Eifinger and Koehler
(1977)
-------
C. Subchronic, Chronic, and Neurotoxic Effects
The ITC did not recommend subchronic, chronic or
neurotoxicity testing. There-is very limited information
available on the subchronic, chronic, or neurotoxic effects of
ODA.
A two-year study (Bio/dynamics Inc., 1975a) was done
with dogs in which a 1:1 mixture of ODA hydrofluoride and
cetylamine hydrofluoride was administered orally. Dosages were
1.2, 6.0, and 12.0 mg/kg/day. A similar two-year oral study with
the same chemical mixture (Bio/dynamics Inc., 1975b) was done
with rats. Dosages were 1.2, 6.0 and 30.0 mg/kg/day.
In rats, data obtained after dosing for 6 months of the
2-year study indicated no alterations in appearance, mortality,
hematology, chemistry and ratios of organ to body weight. In the
high-dose group, some animals showed reduction of body weight
gains, but the mid- and low-dose groups exhibited weight gains
above control values. However, "a remarkable enlargement of
mesenteric lymph nodes" was observed in high dose (30 mg/kg day)
animals, the only group other than controls whose lymph nodes
were examined histopathologically. In addition, though no data
are presented, the authors of the rat study note that "there was
evidence of node enlargement also in the lower dose groups."
Thus, Agency scientists conclude that a NOEL cannot be determined
for this study because pertinent data are presented only for high
dose and control groups.
In dogs, the highest dose at the start of the study (30
mg/kg/day) was reduced to 10-12 mg/kg/day after 12 weeks because
53
-------
of excessive salivation, emesis and diarrhea. Thereafter, no
toxicological signs were observed up to 1 year of dosing.
Clinical laboratory values remained within normal limits.
However, the mesenteric lymph nodes were stained a yellow brown
at all dosage levels (12.0, 6.0 and 1.2 mg/kg). In addition, the
lymph nodes were enlarged in many cases. A NOEL cannot be
determined for the dog study. Also, it cannot be determined to
what extent the adverse effects observed may have been influenced
by the presence of the hydrofluoride or the cetylaraine. Thus,
Agency scientists conclude that both studies are insufficient to
characterize adequately the chronic effects of ODA.
Data on the subchronic and chronic effects of a closely
related compound, stearylamine (a commercial mixture consisting
of 80% octadecylamine [stearylamine] and 20% hexadecylamine),
were submitted by Akzo. Deichmann et al. (1958) conducted a 2-yr
feeding study during which the mixture was fed to rats. The
Agency has determined that these stearylamine studies are
inadequate for providing any basis for evaluating subchronic or
chronic effects of ODA. Although the results provide a rough
idea of the type of toxicity associated with a saturated fatty
amine, they do not allow one to determine the added effect of a
double bond, potentially a metabolically reactive site, as occurs
in ODA.
54
-------
In view of EPA1s findings under TSCA section 4(a)(l)(B)
of substantial occupational exposure to ODA-containing substances
and the insufficiency of data, the chronic and neurotoxic effects
of ODA can not be reasonably determined or predicted. The Agency
believes that testing is necessary to develop such data. EPA
proposes a 90-day dermal subchronic test that will also include
neurobehavioral observations (see Ch. VI. G), reproductive system
histopathology (see Ch. VI. F), and a dermal absorption
determination (see Ch. VI. A).
55
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D. Mutagenicity and Oncogenicity
The ITC recommended mutagenicity testing for ODA if
dermal absorption were demonstrated. This recommendation was
based on production in 1983 of 4.5-5.5 million pounds of
oleylamine and the possibility, of substantial occupational
exposure (over 3000 workers, NOHS 1972-1974).
There is no information available in the published
literature on the mutagenic or oncogenic effects of ODA. Akzo
pointed out the results of Ames tests by the National Toxicology
Program on hexadecylamine and octadecylamine, saturated analogs
of ODA. Because of the previously noted differences from ODA in
molecular structure (Chapter VI.C) , test results on these
saturated amines are not adequate to predict the mutagenicity of
ODA.
In view of EPA's findings under TSCA section 4(a)(l)(B)
of substantial occupational exposure to ODA-containing substances
and the insufficiency of data that would reasonably determine or
predict the mutagenic or oncogenic effects .of ODA, EPA proposes
tiered mutagenicity testing with triggers to oncogenicity
testing. Mutagenicity testing will be conducted for gene
mutation (Figure Vl-1) and chromosomal aberration (Figure VI-
2) . A positive or negative test result in any of the tests
listed in these schemes will be defined as specified in the Mew
and Revised Health Effects Test Guidelines published by the
National Technical Information Service (NTIS) under publication
number PB 83-257691. Additional guidance may be obtained from
the Organization for Economic Cooperation and
56
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Figure VI-1. Gene mutation scheme for ODA
Gene
mutation
in
Salmonella
• Negative
Specific
locus
mutation
in cells
in culture
Negative-
No
•further
testing
V
Positive
v
Positive
.rther<
.•sting
•Negative
Sex-linked
recessive
-lethal
assay in
Drospphila
Sex-linked
recessive-
lethal
assay in
Drosophila
•^Negative
V
Positive
V
Positive
Mouse
specific
locus assay
Mouse
specific
locus assay
-------
Figure VI-2. Chromosomal aberration scheme for ODA
In vitro
cyto
genetics
•Negative
In vivo
. cyto
genetics
-> Negative-
v
Positive
No
^further
testing
Positive
Me
further
testing
•Negative-
Dominant
lethal
.assay
Dominant
lethal—
assay
Negative
Positive
Positive
Heritable
translocation
assay
Heritable
translocation
assay
-------
Development (OECD) Test Guidelines for Health Effects as adopted
by the OECD Council on May 12, 1981, and the Pesticide Assessment
Guidelines, published by NTIS-(PB 83-153916). The Agency
t
believes that the proposed testing schemes will elucidate the
mutagenic potential of ODA.
Testing begins with the Salmonella typhimurium
mammalian microsomal reverse mutation assay (Ames assay) (Figure
VI-1.) A positive result in Salmonella leads to a Drosophila
melanogaster sex-linked recessive lethal test. A negative result
in the Ames assay will necessitate a gene mutation test in
mammalian cells. A positive result in this study will require a
Drosophila sex-linked recessive lethal test. A negative result
in the gene mutation test in mammalian cells will terminate gene
mutation testing. A positive result in the Drosophila sex-linked
recessive lethal test will require the mouse specific locus
test. A negative result in the Drosophila sex-linked recessive
lethal test cells will terminate gene mutation testing.
Figure VI-2 shows the proposed chromosomal aberrations
testing scheme starting with in vitro cytogenetics. Negative
results will necessitate an in vivo cytogenetics test. If this
test is negative no more chromosomal aberration testing will be
required. A positive result in the in vitro study or in the in
vivo study will necessitate a dominant lethal study. A positive
result in this study will necessitate a heritable translocation
test. A negative result in the dominant lethal study will
terminate chromosomal aberration testing.
ODA shall be tested in a chronic dermal oncogenicity
bioassay if it yields positive results in any of the following:
-------
1) the gene mutation assay in mammalian cells, 2) the sex-linked
recessive lethal gene mutation assay in Drosophila melanogaster,
3) the in vitro cytogenetics assay, or 4) the in vivo
cytogenetics assay.
The scheme for triggering to higher-tier mutagenicity
and oncogenicity testing is similar to that proposed for the
cresols (48 FR 31812) and the C9 aromatic hydrocarbons (48 FR
23088). The Agency has received and evaluated comments on these
notices and is reviewing its policy on the use of triggers
between mutagenicity tests and from mutagenicity tests to
oncogenicity testing. EPA will publish the results of this
review in the near future.
•
Prior to the late 1960s and early 1970s, it was
generally believed that there was little or no correlation
between mutagenicity and carcinogenicity. Few mutagens had been
shown to be potent carcinogens, and carcinogens which had been
tested for mutagenicity, primarily in microbial assays which
lacked the capacity for metabolic activation, had been designated
"nonmutagenic." As basic understanding of the metabolism of
carcinogenic chemicals increased, it was discovered that many
carcinogens undergo metabolic activation to an ultimate
carcinogenic moiety by mammalian enzyme systems. This discovery
was followed by the development of an in vivo system, the host-
mediated assay, to test for potential mutagenicity (Gabridge and
Legator 1969): and in vitro testing of reactive forms of
carcinogenic chemicals (Ames et al. 1972a, 1972b: Huberman et al.
1971, 1972) which resulted in a demonstration of the mutagenicity
of many known carcinogens.
-------
With the development of exogenous mammalian metabolic
activation systems for use with microbial test systems (Mailing
1971, Ames 1973), correlation between mutagenicity and
carcinogenicity increased still further. In 1975, McCann et al.,
using a preselected list of carcinogens and noncarcinogens, most
of which were tested by the authors, reported a 90 percent
correlation with carcinogenicity and mutagenicity in
Salmonella. Since that time, considerable effort has been
directed toward the development of other short-term assays for
detecting mutagens and other endpoints of genetic toxicity.
Several mechanistic hypotheses have been put forward to
explain the correlation between mutagenicity and carcinogenicity.
Simplistically, an electrophilic moiety, either the chemical
itself or a reactive intermediate, is presumed to enter the cell
and react with cellular macromolecules, primarily DNA but RNA and
protein also, to produce a'change which results in an altered
cell state. This altered cell state may or may not become an
initiated cell' which, under the proper set of circumstances, will
progress to an overt tumor. Assays for mutation or for
premutational events, such as increased DNA repair, are designed
to detect agents which are capable of macromolecular interaction
and, hence, are considered potential carcinogens. Nongenotoxic
carcinogens such as hormones, metals, etc. are believed to act by
mechanisms other than interaction with DNA or other cellular
macromolecules. These mechanisms may include suppression of the
immune system, or other host-defense mechanism, or local
irritation. Nongenotoxic carcinogens may also act as tumor
61
-------
promoters. Some investigators believe that such agents act "after
tumor initiation has taken place.
Whatever the mechanistic basis for the correlation
between mutagenicity and carcinogenicity, there does appear to be
an empirical correlation worth exploiting in the identification
of potential carcinogens. To that end, several short-term in
vitro and in vivo assays have been developed for the detection of
genotoxic agents. These assays measure different genetic end-
points and employ prokaryotes, lower eukaryotes, insects, cells
in culture and whole animal systems. Several of these assays
have been chosen by EPA as "triggers" for oncogenicity testing of
ODA in the belief that positive results in these assays will
suggest carcinogenic potential. These assays include specific
locus gene mutation in cells in culture, in vitro and in vivo
cytogenetics, and the Drosophila sex-linked recessive lethal
assay.
The correlation with carcinogenicity cited for these
assays is based upon a list of carcinogens compiled for use by
Phase I of the U.S. EPA's Gene-Tox Program and may be subject to
some limitations. The list is limited in scope to those
chemicals tested in the National Cancer Institute/National
Toxicology Program bioassay system or reviewed by the
International Agency for Research on Cancer up to 1979.
Therefore, some well-known carcinogens that have been widely
tested in short-term assays are not on the list and were not
considered in making correlations. This may result in
artifically low figures for some assays. The list is biased in
62
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favor of positive results. Of the 393 chemicals on the list,
fewer than 50 are classified as noncarcinogens. A large
proportion of the chemicals on the list (167) have no attendant
mutagenicity/genotoxicity test results. Accuracy of test
systems, therefore, is often judged on the basis of small numbers
of tested carcinogens and may be misleading. Nevertheless, EPA
I
believes that trends indicated by these data are sufficiently
sound that correlations with carcinogenicity may be reasonably
predicted.
Mutation in mammalian cells in culture is widely used
as an indicator of potential mutagenicity/carcinogenicity. The
most commonly used systems include mutation at the thymidine
k.inase (TK) locus of L5178Y mouse lymphoma cells, at the
hypoxanthineguaninephosphoribosyl transferase (HGPRT) locus of
Chinese hamster ovary (CHO) and lung (V-79) cells and at the
Na^/K"1" ATPase (measured by resistance to ouabain) locus in V-79
cells. The TK and HGPRT mutational systems detect base-pair
mutations and' small deletions; the Na'V'K"1" ATPase system detects
base-pair mutations only. The Phase I Gene-Tox reports list 18
chemicals as having been tested in CHO cells (Hsie et al. 1980);
191 chemicals as having been tested in V-79 cells (Bradley et al.
1981); and 48 chemicals as having been tested n L5178Y cells
(Clive et al. 1980). Only 4 chemicals were tested in all
systems; all were uniformly positive. Using the carcinogen list
referred to above, these same authors reported that 16/16
carcinogens and 2/2 noncarcinogens (100 percent) were correctly
identified in CHO cells; 19/23 carcinogens (83 percent) were
63
-------
correctly identified in V-79 cells and 39/44 carcinogens (89
percent) were correctly identified in L5178Y cells. Any of these
assays, therefore, may be used in testing ODA. Other cell
systems with a demonstrated sensitivity to mutagenesis and a
known correlation with chemical carcinogenesis may also be
appropriate.
A total of 62 carcinogens and noncarcinogens were
tested in the Drosophila melanogaster sex-linked recessive lethal
assay. Fifty-six of 62(90 percent) were correctly identified.
Of these 50/55 (91 percent) were carcinogens and 6/7 (86 percent)
were noncarcinogens.
The most widely used assays for detecting chromosomal
damage are in vitro assays for chromosomal aberrations in
mammalian cells and in vivo assays for chromosomal aberrations in
bone marrow cells. In vitro cytogenetics assays may be performed
in continuous cell lines or strains or in primary cultures of
human or rodent peripheral lymphocytes. In vitro cytogenetics
assays suffer from limitations in their ability to metabolize
promutagens/procarcinogens to an active form. Although metabolic
activation systems have been developed for use with these assays,
problems of toxicity, especially with S-9 systems and in vitro
human lymphocyte cultures, often limit their effectiveness
(Preston et al. 1981). For this reason any chemical tested and'
found negative in an in vitro cytogenetics assay should be tested
in an in vivo cytogenetics assay.
64
-------
Preston et al. (1981) reported that 17/18 (94 percent)
of carcinogens tested in one or more cytogenetics assays were
correctly identified.
Therefore, the Agency has determined that the proposed
testing scheme outlined in this document can reasonably serve to
investigate the mutagenic and carcinogenic potentials of ODA.
E. Developmental Toxicity and Reproductive Effects
The ITC recommended teratogenicity (developmental
toxicity) testing of ODA. This recommendation was based on data
showing it to cause developmental effects in studies not designed
to characterize adequately such effects.
A series of five related studies with ODA mixtures was
conducted by Bio/dynamics, Inc. (Bio/dynamics Inc.
1973 a,b,c,d,e). For each study the test agent was a 1:1 mixture
of oleylamine hydrofluoride:cetylamine hydrofluoride administered
orally via intubation at dose levels of 0, 1.2, 6.0 or 30.0
mg/kg/day in 0,.25% methylcellulose. Two factors that differed
among the studies were the period and duration of exposure to the
test substance and the time of sacrifice. Details, including
citations, are presented in Table VI-2. It should be noted that
the Segment II Teratology Study in the rat was repeated and,
therefore, two sets of data (referred to as A and B) were
available for review.
A summary of the results from all five studies is
presented in Table VI-3. Because of the large volume of data
from these studies it is not feasible to discuss the results from
each study in detail. Instead, the data will be presented on the
65
-------
two species separately and the results on vai'ous developmental
parameters will be highlighted with emphasis on identifying
trends and inconsistencies among the results of the various
studies.
Rabbit
0 Maternal toxicity, as evidenced by a marked reduction
in weight gain at all levels of exposure, and mortality at both
the middle and high dose levels was elicited. The developmental
toxicity observed (increased in utero death, litters with
malformed fetuses, and fetuses with ossification variations), may
have been a result of the severe maternal toxicity. Although an
increase in percent of litters that had malformed fetuses was
observed it represented an incidence of 1/10 or 1/11 as compared
to 0/12 for the control group. For the rabbit a no-observed
effect level was not established.
Rat
0 Maternal toxicity - None of the dose levels produced
statistically-significant adverse maternal effects in the Segment
IIA, the Segment I nor the Segment III studies. Statistically-
significant adverse effects were observed only at the high dose
level in the Segment IIB study and for the male rats in the
Segment I study.
0 In utero deaths - An increase in in utero deaths
following exposure to the mixture appeared to be a somewhat
consistent observation among most of the studies. While the mean
number of resorptions was comparable among the treated and
control groups of the two Segment II studies, for the Segment IIB
66
-------
study there was an increase in the percent of dams with
resorptions at all levels and an increase in the percent of
resorptions at the high dose. Results of the Segment I study
revealed that for those dams sacrificed on day 13 of gestation,
there was a slight decrease in percent of resorptions, especially
at the low dose level: however, for those dams that were
sacrificed at weaning a statistically significant increase in the
percent of in utero deaths was observed at the low dose level.
In the Segment III study a dose-related increase in the percent
of in utero deaths was observed; this was of statistical
significance at the high dose.
0 Malformations - While the incidence of malformations
was not of statistical significance, several interesting trends
were observed. An increase in the percent of litters with
malformed fetuses was observed at the high dose in the Segment
IIA study and the middle and high dose levels for the Segment IIB
study. An increased incidence of dilated renal pelvis was
observed among control as well as treated fetuses. When this
malformation was eliminated from the calculations there was still
an increase in the percent of litters with malformations for the
high dose of the Segment IIA study and the middle dose of the
second Segment IIB study. Dilated renal pelvis was not observed
as frequently in the neonates as in the fetuses. This obser-
vation among the fetuses, therefore, may actually represent a
transient delay in renal maturation which has "caught up" to
normal maturation postnatally. This may account for its much
less frequent occurrence in the neonates. Among other
67
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Table VI-2. Developmental Protocols
Species and
Study
Segment II
Rat (A 5, B)
(Bio/dynaraics Inc.
1973a., b.)
Rabbit
Bio/dynamics Inc.
1973c.)
Segment I
Rat
(Bio/dynamics Inc
1973d.)
Males
Females
No. of
Animals
per dose level
Segment III
Rat
(Bio/dynamics Inc
1973e.)
20
14-19
12
22
20
Period and
Duration of Dosing
days 6-15 of gestation
days 7-19 of gestation
at least 60 days prior
to mating until sacrifice
at least 15 days prior
to mating until sacrifice
day 15 gestation
Time of
Sacrifice
day 21 of gestation
day 30 of gestation
Type of
Study
Teratology
Fertility or
one-generation
Reproduction
when pregnancy
assured for 2/3 dams
1/2 dams: day 13 of
gestation
1/2 dams : day 21
postnatally
Perinatal and
Postnatal
day 21 postnatally
-------
Table VI-3. Summary of Data on C > Hydrofluoride: Cetylamine Hydrofluoride
Dose
pecies &
tudy
abbit
egment II
Level
(mg/kg/day
0
1.2
6.0
Maternal
Toxicity
marked deer
marked deer
weight
we.ight
gain*
gain ;
Ln utero
Death
incr
incr
Malformations
incr
incr
% litters
% litters
malf
malf
Ossification I
Variations \
incr
'OStl
/iab
NA
NA
NA
30.0
at
egment II A 0
1.2
6.0
30.0
egment II B 0
1.2
6.0
30.0
3 deaths
marked deer
3 deaths
weight gain; incr
deer weight gain*
incr %
dams with
resorptions
incr %
dams with
resorptions
incr %
dams with
resorptions
incr % litters malf
incr % litters malf
incr % litters malf
incr % litters malf
incr*
NA
—
incr*
incr*
incr*
_
-
NA
NA
NA
NA
NA
NA
NA
NA
-------
malformations, the occurrence of. hydrocephalus and microorchidia
was observed in treated groups in more than one study.
Hydrocephalus was observed in two fetuses from the same litter in
the high dose group of the Segment IIA study, one neonate from
the low dose group of the Segment I study and one neonate from
the middle dose level of the Segment II study. Microorchidia was
observed in one neonate from each high dose group from Segment I
(unilateral) and Segment III (bilateral) studies.
0 Ossification variations - Both Segment II studies
included this category of observations; however, the
investigators failed to identify what they considered an
"ossification variation." Since the actual raw data on the
fetuses and litters were unavailable, it was not possible to
"pool" the data from this category and that of "malformations";
therefore, it is discussed separately here. An increased
incidence of ossification variations was observed at all dose
levels in the Segment IIA study and was of statistical
significance a-t the middle and high dose levels. This increased
X
incidence was observed in the absence of maternal toxicity. In
the second Segment II study, the only increase (statistically
significant) was observed at the high dose level which was also a
maternally toxic level in this one study.
In the Segment IIB study the incidence of ossification
variations for control fetuses (i.e. the concurrent background
rate) was over 20% higher than for control fetuses in the Segment
IIA study (94.2% vs 72.8%). The incidence was also higher for
all the treated groups as well (91.6, 94.6, 100% vs 77.8, 88.9,
71
-------
87.5% for low, middle and high groups, respectively). The
significance in the difference among background rates and their
effect on the results front the treated animals cannot be
determined. The Segment IIA study states that there is no
biological significance to the increased incidence of
ossification variations since there was no effect on postnatal
growth and survival in the Segment I study: it fails to mention,
however, that in the Segment III study there were significant
effects on neonatal viability at all dose levels.
0 Postnatal viability - In the Segment I study a
statistically significant decrease in pup survival was observed
only in the low dose group for the period day 0-day 4. In the
Segment III study, however, postnatal viability was decreased
significantly at all dose levels. For the low and high dose
groups the decrease was observed from day 0 to day 4 and for the
middle dose group from day 4 to 21. It is not possible to
determine why postnatal viability was so markedly affected in the
Segment III study (as compared to the Segment I study) when dams
were treated for a shorter period (day 15 of gestation through
weaning vs. 15 days prior to mating, throughout entire length of
gestation and through weaning). It may be that the dams in
Segment I developed a "tolerance" to the mixture by the time
exposure occurred during their gestation and lactation periods.
0 Although the same dose levels were used in all four rat
studies, maternal toxicity was elicited only once (high dose
group of Segment IIB study). Since this effect was not
reproducible, its biological significance is questionable. Even
72
-------
in the absence of maternal toxicity, adverse effects on
development were produced. However, it is difficult to interpret
the significance of the effects for two reasons: First, these
effects were not always observed at levels of statistical
significance, although it was evident that from study to study
certain similar trends were produced (i.e. observations of
increased in utero death, identical types of malformations).
Second, there was also evidence of inconsistent observations from
study to study (i.e. increased ossification variations at all
dose levels in one Segment II study but not the other and
decreased viability in pups at all dose levels of the Segment III
study but not of the Segment I study). Also, results of the
studies were difficult to interpret regarding the developmental
toxicity of this mixture alone, and it cannot be determined to
what extent the adverse effects observed may have been influenced
by the presence of the hydrofluoride moieties or by cetylamine.
These tests are not adequate to characterize the
potential developmental toxicity of ODA.
In a study by Eifinger and Koehler (1977), pregnant
mice (4-5 per dose group) were exposed to ODA either
intraperitoneally (i.p.) (0, 200, 400, 800, or 1600 mg/kg) or
orally (p.o..) (6.0) (Or 200, 800, or 3200 mg/kg) only on day 9 of
gestation. Maternal lethality was produced in 1/4 dams exposed
to 800 mg/kg i.p., 4/4 exposed to 1600 mg/kg i.p. and 1/4 exposed
to 3200 mg/kg p.o. No other signs of maternal toxicity were
reported. A dose related increase in the percentage of
resorptions was observed following exposure via i.p. (5.7, 6.5,
73
-------
20.6, 25.7%) and p.o. (6.1, 2.9, 24.6, 22.5%) administration.
Skeletal malformations (the only malformations reported) were
observed only following i.p. exposure. The incidence was dose-
related (0, 0, 5.2, 26.9%). A dose-related decrease in the fetal
body weights was also indicated following i.p. exposure (1.38,
1.35, 1.27, 1.19 g). The study failed to report the results of
the statistical analysis and therefore the significance of the
results, although probably limited owing to the small number of
animals, cannot be ascertained.
Some of the inadequacies of this study include: (1)
use of a single mammalian species, the mouse, (2) use of only 4-5
animals per dose group, (3) exposure to oleylamine on only a
single day of gestation (day 9), (4) failure to report any
maternal data (i.e., body weight, food consumption, clinical
signs of toxicity) other than death, (5) limitation of the
analysis of structural malformations to only those skeletal
malformations that can be induced in a mouse on day 9 by known
teratogens and '.consequent failure to evaluate other skeletal
abnormalities and external and soft tissue malformations. The
data from this study are thus not adequate to reasonably
determine or predict the potential developmental toxicity of ODA.
In view of EPA's findings under TSCA section 4(a)(l)(8)
of substantial occupational exposure to ODA-containing substances
and the insufficiency of data, the toxic effects of ODA can not
be reasonably determined or predicted. The Agency believes that
testing is necessary to develop such data. Therefore, EPA is
proposing that such testing be conducted in two mammalian
species.
74
-------
Because there are no adequate reproductive effects studies
on ODA, EPA is proposing that the 90-day subchronic study being
proposed (Ch. VI. C)• include special attention to reproductive
system histopathology.
F. Neurotoxicity
The ITC did not recommend neurotoxicity testing of
ODA. No information was found on the testing of ODA for
neurotoxic effects. In view of EPA's findings under TSCA section
4(a){l)(B) of substantial occupational exposure to ODA-containing
substances and the insufficiency of data, the toxic effects of
ODA can not be reasonably determined or predicted. The Agency
believes that testing is necessary to develop such data.
Therefore, EPA proposes that neurobehavioral observations be
included in the proposed 90-day subchronic testing (Ch. VI. C).
G. Testing in Progress
There are no chronic animal carcinogenicity bioassays
or other testing for ODA either ongoing or planned under the
auspices of the National Toxicology Program (NTP 1983). No
ongoing studies were reported by manufacturers or processors of
ODA under the TSCA section 8(d) Health and Safety Data Reporting
Rule (USEPA 1984b). However, ODA producers, through the Chemical
Manufacturers Association Oleylamine Panel are actively
considering ODA testing (USEPA 1984c,d,e).
-------
VII. SECTION 4(a) BINDINGS
EPA has concluded that, of the numerous ODA-containing
products, the petroleum-based lubricants are the ones with which
consumers and workers (primarily professional auto mechanics) are
likely to come in contact in the greatest numbers. Dermal
absorption through the hands is considered the most likely route
of entry.
1. The section 4(a)(l)(A) findings for developmental
toxicity are as follows:
a. EPA finds that the manufacture, processing, and use of
ODA may present an unreasonable risk of injury to human health
due to developmental toxicity because (i) available animal
studies suggest that ODA may cause developmental toxicity and
postnatal development effects and (ii) in excess of 2.8 million
individuals are potentially exposed to ODA as a result of its
manufacture, processing, and use (Becker, 1984). Although a
relatively small fraction of these 2.8 million individuals are
likely to be women of childbearing potential, the number
comprising the latter group may still be substantial.
b. EPA also finds that there are insufficient animal and
human data to reasonably determine or predict the developmental
toxicity of ODA. The finding of "may present an unreasonable
risk" of developmental toxicity is based in part on a study
(Eifinger and Koehler, 1977) in which pregnant mice (4-5) per
dose group) were exposed to single doses of ODA by either
intraperitoneal injection (i.p.; 200, 400, 800, or 1,600 mg/kg or
orally (200, 800, or 3,200 mg/kg). Maternal lethality was
76
-------
produced in the two highest i.p. groups and the highest oral
group. Dose-related increases occurred in percentages of fetal
resorption (all groups) and skeletal malformations (400 and 800
mg/kg i.p. groups). Dose-related decreases occurred in fetal
body weights in all i.p. groups.
These data are not adequate to characterize the potential
developmental toxicity of ODA. The study was too limited in
design, and analysis and reporting of results failed to provide
enough information to adequately assess ODA's potential as a
developmental hazard.
- Rabbit and rat studies (Bio/dynamics, 1973 a,b,c,d,e),
similarly conducted, also support a finding of a potential
unreasonable risk of adverse developmental effects. Pregnant
rabbits and mice (14-22 per dose group) were exposed orally to a
1:1 mixture of ODA hydrofluoride and cetylamine hydrofluoride
(1.2, 6.0, and 30.0 mg/kg/day) during all or part of the
gestation period until sacrifice or day 21 postnatally.
Developmental toxicity, fertility, reproductive, and perinatal
and postnatal observations were conducted. Compared to controls,
there were increased intrauterine deaths at all dose levels in
the majority of groups and ossification variations and
malformations at the three dose levels in approximately one half
of the test groups.
These data are not adequate to characterize the potential
adverse developmental effects of ODA. The effects were not
always observed at levels of statistical significance; there was
evidence of inconsistent observations from study to study, and it
77
-------
cannot be determined to what extent the adverse effects observed
may have been influenced by the presence of th,e hydrofluoride or
cetylamine constituents.
c. EPA finds that additional developmental toxicity testing
of ODA is necessary to develop additional data to evaluate
reasonably the developmental risks posed by exposure to ODA.
2. The section 4(a)(l)B findings are as follows:
a. EPA finds that ODA is produced in substantial
quantities. Production of oleylamine was reported by the USITC
to be 4.952 million pounds in 1982 (Table III-2). Production
estimates for ODA, however, range to 29 million pounds for 1982
when the ODA portion of captive production as well as production
of all ODA-containing mixtures is taken into account.
b. EPA also finds that there may be substantial human
exposure to ODA. On the basis of the National Occupational
Hazard Survey (NIOSH 1983a') conducted in 1972-1974, eight
occupations in six industries involving 3,155 workers were found
to be subject to exposure to ODA-containing products of various
kinds (Table V-2). The Bureau of Labor Statistics figures of
1984 indicate a potential exposure of approximately 2.8 million
workers to ODA-containing products (Becker, 1984).
c. EPA finds that there are insufficient data available to
reasonably determine or predict the effects of this exposure in
the areas of developmental toxicity, mutagenicity, oncogenicity,
chronic toxicity, neurobehavioral effects, reproductive effects,
and dermal absorption.
78
-------
On the basis of these findings, the Agency is proposing the
testing on ODA outlined below.
In cases of section 4(a)(l)(S) findings for chemicals with
widespread exposure at moderate to high concentration levels such
as 1,1,1-trichloroethane, EPA has generally followed a policy of
requiring a broad range of tests. Such tests include
mutagenicity, acute toxicity, acute dermal irritation/corrosion,
acute eye irritation/corrosion, skin sensitization, oncogenicity,
chronic effects, reproductive effects, developmental toxicity,
and neurotoxicity (Federal Register, June 5, 1981, 46 FR 30302,
33303). This wide range of testing is desirable if adequate data
or ongoing testing are not available for each of these effects.
However, in cases where EPA finds that there is substantial
production and that a substantial number of persons are exposed
but that such exposure is typically to rather low levels of a
chemical, EPA makes a case-by-case judgment as to what testing
should be required. The use of a screening approach seems
appropriate for low-level exposure chemicals for which little or
no toxicity data exist. Adverse effects would only be expected
at these exposure levels for highly toxic chemicals. Screening
tests will enable EPA to judge the toxicity of the chemical and
determine if further testing is necessary.
The low-level exposure situation appears to apply to ODA.
Specifically the Agency notes that use of ODA is not expected to
expand to types of products other than the current use in
lubricants and related products, and that product concentrations
are limited to 1% or less of oleylamine. Thus, in conjunction
with existing data on acute effects and the.developmental
79
-------
toxicity testing proposed above under TSCA section 4(a)(l)(A),
EPA believes that for ODA a screening approach consisting of
mutagenicity tests and a 90 day subchronic test with reproductive
system histopathology and a neurotoxicity satellite is
appropriate. The added reproductive system histopathology in the
subchronic test will screen for reproductive toxicity.
Similarly, a functional observation battery will screen for
neurotoxic effects, and mutagenicity testing will screen for
oncogenic potential.. In all cases, positive results could lead
to a determination that more testing should be done; negative
results would provide reasonable assurance of little or no
potential risk.
Specific tests proposed for ODA are:
1. Oral developmental toxicity. Inadequately designed
studies showed some effects; a properly designed study
is needed for adequate characterization. The oral
route is preferred to the dermal in this case because
of the very limited database for dermal developmental
toxicity studies.
2. Tiered mutagenicity testing with oncogenicity
triggers. This is recommended on the basis of lack of
data for these effects.
3. 90-day dermal subchronic study, including neuro-
behavioral observations, attention to reproductive
system histopathology and a determination of dermal
absorption. This is recommended because of lack of
80
-------
data, to define the approximate degree of dermal
absorption and to obtain data on neurotoxic and
reproductive effects potential without requiring full
studies in these areas.
The scheme for triggering to higher-tier mutagenicity and
oncogenicity testing is similar to that proposed for the cresols
(USEPA 1983d) and the C9 aromatic hydrocarbons (USEPA 1983c).
The Agency has received and evaluated comments on these notices
and is reviewing its policy on the use of triggers between
mutagenicity tests and from mutagenicity tests to oncogenicity
testing. EPA will publish the results of this review in the near
future.
EPA is proposing that the test substance be the purest
commercial form of ODA. The purest ODA generally used in
commerce consists of fatty amine mixtures containing 65 to 76%
ODA. A laboratory grade is also available which is 97% ODA. In
the past the Agency has preferred that the purest form of a
chemical be used for testing, in order that interpretation of
test data will not be complicated by the presence of substantial
quantities of other substances. For many substances, a large
fraction of the expected exposures is to a high purity
material. In the case of ODA, however, only a very small number
of laboratory workers may be exposed to 97% ODA. The Agency is
requesting comment in the Notice of Proposed Rule Making as to
which of these two ODA products would be the most appropriate
test substance. The vehicle should be one such as mineral oil
for which there are historical toxicological data.and which has
innocuous qualities.
81
-------
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ANNUAL AVERAGE INDUSTRY AND OCCUPATION TABLES FOR YEAR ENDING DEC65
MATRIX:00103
DATE 122385
PAGE 729
TABLE 30. EMPLOYED AND EXPERIENCED UNEMPLOYED PERSONS BY DETAILED OCCUPATION, SEX, RACE, AND HISPANIC ORIGIN
IA1 RACE AND SEX » IB1 DETAILED OCCUPATIONS : CCI
IC1 i ANNUAL AVERAGES
; EMPLOYED
TOTAL MHITE BLACK HISPANIC
TOTAL MALE FEMALE TOTAL HALE FEMALE TOTAL MALE FEMALE TOTAL MALE FEMALE
PRECISION PRODUCTION, CRAFT. A REPAIR . . . . 13340 12213 1127 12107 11166 942 945 611 135 992 686 1*4
MECHANICS * REPAIRERS 4475 4322
SUPERVISORS. MECHANICS * REPAIRERS 266 244
MECHANICS • REPAIRERS, EXCEPT SUPERVISORS 4209 4078
VEHICLE t MOBILE EQUIPMENT MECHANICS i REPAIRERS. 1850 1835
• AUTOMOBILE MECHANICS 906 - 900
- BUS, TRUCK, t STATIONARY ENGINE MECHANICS . . . ^347 - 346
AIRCRAFT ENGINE MECHANICS 90 96
SMALL ENGINE REPAIRERS ^ 75 " 75
AUTOMOBILE BODY * RELATED REPAIRERS 212 210
AIRCRAFT MECHANICS, EXCEPT ENGINE 15 14
" HEAVY EQUIPMENT MECHANICS ^162 162
' FARM EQUIPMENT MECHANICS. 43 43
1 INDUSTRIAL MACHINERY REPAIRERS 531 518
-MACHINERY MAINTENANCE OCCUPATIONS 35 34
ELECTRICAL t ELECTRONIC EQUIPMENT REPAIRERS ... 701 644
ELECT REPAIRERS,COMMUNICATIONS,INDUSTRIAL EQUIP 159 150
DATA PROCESSING EQUIPMENT REPAIRERS 119 107
HOUSEHOLD APPLIANCE i POWER TOOL REPAIRERS. . . 50 49
TELEPHONE LINE INSTALLERS * REPAIRERS 68 67
TELEPHONE INSTALLERS I REPAIRERS 229 200
MISC ELECTRICAL t ELECTRONIC EQUIP REPAIRERS. . 75 71
HEATING,AIR CONDITIONING,REFRIGERATION MECHANICS. 251 249
MISCELLANEOUS MECHANICS « REPAIRERS 841 799
CAMERA. HATCH, t MUSICAL INSTRUMENT REPAIRERS . 35 33
LOCKSMITHS t SAFE REPAIRERS 25 24
OFFICE MACHINE REPAIRERS 63 60
MECHANICAL CONTROLS t VALVE REPAIRERS 26 25
ELEVATOR INSTALLERS * REPAIRERS 22 22
MILLWRIGHTS 87 65
SPECIFIED MECHANICS A REPAIRERS, N.E.C 420 394
NOT SPECIFIED MECHANICS * REPAIRERS 162 155
153
22
131
16
6
2
4
0
3
1
0
0
13
2
57
9
12
1
2
29
3
1
42
2
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26
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4073
247
3626
1697
817
320
84
73
197
13
152
42
487
26
626
140
109
45
63
203
67
235
753
32
22
53
22
21
79
376
145
3946
229
3719
1664
812
319
81
72
195
12
152
41
475
26
580
134
99
44
61
179
64
234
720
31
22
51
21
20
77
357
140
125
16
107
13
5
1
3
0
2
1
0
0
12
2
46
6
10
1
2
24
3
1
33
2
1
3
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0
2
21
5
308
17
291
115
68
23
S
2
9
1
6
1
35
7
56
14
6
5
4
21
7
10
65
1
1
6
3
1
6
33
12
285
13
272
113
67
23
4
2
9
1
6
1
33
7
50
11
6
S
4
17
6
10
59
1
1
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19
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0
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0
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0
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1
0
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0
4
1
295
8
286
145
75
20
9
3
22
1
10
5
31
2
45
11
5
2
7
15
5
15
48
2
0
3
3
0
3
25
11
285
7
276
143
74
20
9
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22
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31
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