PREFACE
This collection of 40 Chemical Hazard Information Profile
(CHIP) reports was prepared by the Office of Toxic Substances
(OTS) between August 1, 1976, and August 1, 1978. Each CHIP
report has been reviewed by OTS staff, and a tentative course of
action for further consideration of the subject chemical has been
selected and documented in the form of a cover sheet for the CHIP
report. Although these tentative dispositions indicate the
current plans of OTS concerning further evaluation of the chemi-
cals, these dispositions should not be construed as final Agency
decisions or policy with respect to the subject chemicals. The
CHIP reports and tentative dispositions are being published as an
"External Review Draft" report at this time to elicit a range of
review and comment on the tentative OTS dispositions concerning
these chemicals. Comments on the CHIP reports and their tentative
dispositions are sought and should be directed to:
Frank D. Kover, Chief
Chemical Hazard Identification Branch
Office of Toxic Substances (TS-792)
U.S. Environmental Protection Agency
401 M Street S.W.
Washington, DC 20460
Comments are sought on both the accuracy and completeness of the
information contained in the CHIP reports and on the tentative
dispositions. All comments received will be available for inspec-
tion and copying in the OTS reading room,* unless specifically
claimed as confidential, in accordance with applicable EPA rules
and procedures (see 40 CFR Part 2 [41 F.R. 36902, September 1,
1976]) .
Readers and commenters should be aware of the intentionally
limited depth of CHIP reports and of their role in the process of
chemical risk assessment conducted by OTS. These topics are dis-
cussed in the following paragraphs.
Preparation of CHIP Documents
Chemicals are chosen for CHIP preparation on the basis of
information indicating a potential for adverse health or environ-
mental effects, along with evidence of significant commercial
production or environmental exposure. Such information may come
from a variety of sources, including official submissions to EPA,
scientific articles in the open literature, government reports,
scientific papers presented at meetings, recommendations from the
public, etc.
The CHIP itself is a brief summary of readily available informa-
tion concerning the health and environmental effects and exposure
*Room E447 at EPA Headquarters, 401 M Street SW. , Washington1, DC
20460.
-------
27777
potential of a chemical. Information gathering for a CHIP is
generally limited to a search of secondary literature sources such
as computerized data bases, abstracts, government reports, scientific
review documents, and reference works. The literature search for a
CHIP is not intended to be exhaustive; however, indepth searches on
specific topics may be done on a case-by-case basis. Relevant
literature is usually reported in the form of a narrative summary.
Key experimental conditions and results are briefly described for
relevant studies. The information in a CHIP is reported as it
appears in the published literature; in general, no attempt is made
to evaluate or validate information at this stage of assessment.
Role of CHIP Documents in the OTS Chemical Risk Assessment Process
The OTS risk assessment process is a sequential one in which
chemical problems are evaluated in greater detail at each succeeding
stage of the process. In its early stages, limited amounts of
information are evaluated on a relatively large number of chemicals;
in the later stages, more comprehensive information on a relatively
few chemicals is assessed. At every stage, the decision is made to
further evaluate a chemical or allow it to exit from the process.
The decisions which can be made at any given stage are limited by
the scope and depth of the data gathering and analysis completed at
that stage. Thus, decisions made at the early stages of assessment
tend to be more general and tentative than those made at the later
stages.
Preparation of a CHIP is part of the first stage in this
overall assessment process. The CHIP is OTS's initial attempt to
collect and organize into a report a broad range of information on
a chemical of concern. The purpose of a CHIP is to enable OTS to
tentatively decide on an appropriate course of action for the
subject chemical. Determination of need for specific regulatory
action is not the immediate goal of the CHIP; rather, it is intended
to identify and characterize problems that subsequently may require
more thorough investigation and evaluation.
A broad range of possibilities exists regarding the steps
taken following the CHIP. Some common alternatives for follow-up
action include:
(1) Consideration for more detailed assessment within OTS.
(2) Consideration for a testing rule under Section 4 of the
Toxic Substances Control Act (TSCA).
(3) Acquisition of more information via Section 8 of TSCA.
(4) Referral to other EPA'offices or other government agencies
for further consideration and follow-up, as appropriate.
(5) Assignment of "low priority" for further assessment by
OTS.
ii
-------
CONTENTS
Preface i
Acetonitrile 1
Acrolein 8
Adipate Ester Plasticizers 16
Aluminum and Aluminum Compounds 32
Aniline 49
Benzyl Chloride 55
Bromine and Bromine Compounds 62
Carbon Black 77
Cutting Fluids 98
Cyclohexylamine 108
1,6-Diaminohexane 128
1,2-Dichloroethane 133
N,N-dimethylformamide 152
Dinitrosopentamethylenetetramine 159
2,4-Dinitrotoluene 164
Ethanolamines 170
Ethylamines 176
Ethylenediamine 183
Hexachlorocyclopentadiene 188
Hexamethylphosphoramide 197
n-Hexane \ 205
Isopropyl Alcohol 218
Lithium and Lithium Compounds 225
Maleic Anhydride \ \ 245
Methanol ] 252
Methylamines ! ! ! 269
Morpholine ! ! ! 283
2-Nitropropane | 288
2-Pentanone ] \ 297
Phenylenediamines ] \ 301
Phosgene • ] [ 315
Sodium Azide ! ! ! 325
Styrene Oxide ..!!! 338
Sulfur Hexafluoride ! ! ! 343
Tetrahydrofuran '.'.'. 349
2,4,6-Tribromophenol ] ] 351
Trichlorobutylene Oxide 355
1,1,2-Trichloroethane [ 370
Trimellitic Anhydride [ 377
Vinyl Bromide .- [ 382
Vinyl Fluoride 333
Vinylidene Bromide | 334
Vinylidene Fluoride | 385
iii
-------
CHEMICAL HAZARD INFORMATION PROFILE
Acetonitrile
Date of report: March 9, 1978
This chemical was chosen for study because of its structural
similarity to acrylonitrile, a suspected carcinogen.
The following recommendations are made regarding further OTE
evaluation of the possible health or environmental hazards of
acetonitrile:
(1) Obtain better information on potential for environmental
release and human exposure—Available information indicates
that significant quantities of acetonitrile may be
released to the environment. Use of TSCA Section 8(a)
authorities and EPA monitoring of potential release
sources should be considered to obtain such information.
(2) Require TSCA Section 8(d) submissions—Information on
carcinogenicity and teratogenicity is quite sketchy.
Reported teratogenicity studies indicate equivocal
results.
(3) Refer to EPA-ORD for mutagenicity testing—No mutageni-
city data are currently available.
(4) Update this Chemical Hazard Information Profile based on
the additional data found.*
This report represents a preliminary investigation of the
subject chemical's potential for injury to human health and the
environment. The information contained in the report is drawn
chiefly from secondary sources and available reference documents.
Because of the limitations of such sources, it necessarily follows
that this report may not reflect all available information on the
subject chemical.
Any recommendations based on this report are tentative and
should not be construed as final Agency policy with respect to the
subject chemical.
*Subsequent to the review of this CHIP document and the selection
of the tentative dispositions given above, the TSCA Interagency
Testing Committee recommended acetonitrile for primary consideration
for possible testing under Section 4(a) of TSCA (44 F.R. 31866).
-------
CHEMICAL HAZARD INFORMATION PROFILE
Acetonitrile
Date of report: March 9, 1978
CHEMICAL CHARACTERISTICS
Acetonitrile (CH3-CsN) is a colorless liquid with an aromatic
odor. Its boiling point is 81°C, and its melting point is
-41.9°C. Acetonitrile's density is 0.7868 (at 20°C) , and its
vapor pressure is 100 mm Hg (at 27°C). It has a high polarity,
which may contribute to its strong reactivity. Acetonitrile is
freely miscible with water, alcohol, ethyl acetate, acetone,
ether, chloroform, carbon tetrachloride, and ethylene chloride
(ITU, 1976). It is explosive at concentrations of 4.4 to 16.0%
by volume in air. Acetonitrile is considered a dangerous dis-
aster hazard since it emits toxic cyanide fumes when heated to
decomposition (120°C with alkali). It will react with water,
steam, or acids to produce toxic and flammable vapors and can
react vigorously with oxidizing materials (Sax, 1968). Synonyms
for acetonitrile include methyl cyanide, cyanomethane, and
ethanenitrile.
PRODUCTION AND USE
Acetonitrile can be manufactured by the vapor-phase ammonol-
ysis of glacial acetic acid. The acetonitrile yield is 85-95%
after dehydration of the reaction products (Ingwalson, 1971).
Another source of acetonitrile is as a by-product of the propylene-
ammonia process for the manufacture of acrylonitrile (Hawley,
1977).
There are only two domestic producers of acetonitrile: E. I.
du Pont de Nemours and Co., Inc. (Elastomer Chemicals Department,
-------
Beaumont, Tex.) and Standard Oil Co.'of Ohio (Vistron Corp., a
subsidiary, Chemicals Department, Lima, Ohio) (SRI, 1975).
Annual production has been estimated to be 135 x 10 Ib (Dorigan
et al., 1976).
Acetonitrile is used as a solvent in hydrocarbon extraction
processes (especially for butadiene) and as a specialty solvent.
Acetonitrile is the starting material for acetophenone and
naphthalene-acetic acid, thiamine, and acetamine. It is a chemical
intermediate in the manufacture of vitamin E., substituted pyrimi-
dines, and Pharmaceuticals. Acetonitrile is used as a solvent in
the separation of fatty acids from vegetable oils (Hawley, 1977).
BIOLOGICAL ASPECTS
The TLV for acetonitrile is 40 ppm (ACGIH, 1971). This is
also the time weighted average for worker exposure. Acetonitrile
is easily absorbed through mucous membranes because of its high
solubility in water. The oral LD50 for rats is 3,800 mg/kg.
Four-hour rat inhalation studies give an LC5Q of 8,000 ppm. The
LD5Q for intraperitoneal injections of acetonitrile in mice is
500 mg/kg. LD5Q for standard application of acetonitrile to
rabbit skin is 1,250 mg/kg. The 96-hr aquatic toxicity rating is
1,000 ppm (NIOSH, 1976).
The toxic action of acetonitrile is the same in most animals
as it is in man. The compound is metabolized to hydrocyanic
acid, which can be found in high levels in the brain, heart,
kidney, and spleen (Haguenoer, 1975). Acute symptoms of acetoni-
trile inhalation include headache, dizziness, increased respiration
rate, rapid pulse, vomiting, unconsciousness, and convulsions
Acetonitrile may be used as a speciality solvent to dissolve
cationic textile dyes (Textile World, 1974), to recrystallize
steroids, and to remove tars, phenols, and coloring matters
from petroleum hydrocarbons (Stecher, 1969).
-------
(coma and death). Chronic symptoms of acetonitrile inhalation
include headache, anorexia, dizziness, weakness, and dermatitis
(ITII, 1976). Other chronic effects may include growth retarda-
tion, metabolic disturbances, and liver enlargement (Dorigan et
al., 1976).
Acetonitrile is easily absorbed through mucous membranes
because of its high solubility in water. Human inhalation studies
on acetonitrile have been conducted. Three subjects were exposed
to 40 ppm for 4 hr and two subjects were exposed to 80 and 160
ppm for 4 hr. No adverse reactions were reported at the 40 ppm
and 80 ppm inhalation levels. At 160 ppm, one subject noted a
slight flushing of the face 2 hr after inhalation and a slight
feeling of bronchial tightness 5 hr later. There was no detect-
able blood cyanide at 40 or 80 ppm. At 160 ppm, there were
insignificant changes in blood cyanides. At 40 ppm, one subject
exhibited a slightly elevated urinary thiocyanate level. The
urinary thiocyanate level changes were insignificant at 40 ppm;
they were inconsistent at 80 ppm and not significant at 160 ppm
(Pozzani, 1959).
Inhalation of high concentrations of acetonitrile vapors can
be fatal. Symptoms are usually delayed 4 to 16 hr and begin with
stomach pains and vomiting. Headache, chest pain, asthenia,
hypotension, generalized pain, and weakness may follow. The
victim may then lapse into coma and convulsions. Death is preceded
by a failing of the central nervous system (Desquidt, 1974)'.
The toxic action of acetonitrile is due to the in vivo
metabolism to hydrocyanic acid. Autopsy of one victim revealed
densification of the inferior lobes of the lungs and total diffuse
necrosis of the brain (Desquidt, 1974). Liquid acetronitrile may
also cause skin irritation by direct contact (Stecher, 1969).
-------
No references to the mutagenicity of acetonitrile have been
found. The reported teratogenic effects of acetonitrile are
conflicting. Fetal malformations have been reported in rats
from intraperitoneal doses from 0.2 to 1.0 ml/kg (Dorigan et
al., 1976). However, other investigators have been unable to
produce malformations in fetal pigs (Crowe, 1973). Attempts to
produce teratogenic effects in rodents have produced inconsistent
results.
ENVIRONMENTAL ASPECTS
Based on an estimated annual production of 135 x 10 Ib
of acetonitrile, 69.5 x 10 Ib is released to the environment
annually (Dorigan et al., 1976). It is unclear whether this
release rate accounts for acetonitrile waste from acrylonitrile
production. This process may produce and release over 20 x 10
Ib per year (Gruber, 1976). In the atmosphere acetonitrile is
highly reactive to oxidising materials. It is infinitely
soluble in water (Dorigan et al., 1976) and has been found to
2
be relatively stable in water. The BOD of 1 mg acetonitrile
has been estimated to be 1.4 mg.
2
A concentration of approximately 2.4 mg/1 can be maintained in
reservoir water for 4 days (Rubinskii, 1969).
-------
REFERENCES
American Conference of Governmental Industrial Hygienists (ACGIH).
Documentation of TLV's. Cincinnati, Ohio. 1971.
Crowe, M. W. Teratogenic capability of tobacco (Nicotiana tobacum)
and those chemicals commonly applied to the growing plant.
Tob. Health Workshop Conf. Proc. 42^:98-202, 1973.
Desquidt, J. et al. Poisonings by acetonitrile. A fatal case.
Eur. J. Toxicol. ;K2):91-97, 1974.
Dorigan, J. et al. Scoring of Organic Air Pollutants. MITRE
Corp. (for EPA). 1976.
Gruber, G. I. Assessment of Industrial Hazardous Waste Practices,
Organic Chemicals, Pesticides and Explosives Industries.
Redondo Beach, Calif., TRW (for EPA). 1976.
Haguenoer, J. M. et al. Experimental acetonitrile intoxication:
Acute intoxication by an intraperitoneal route. Eur. J.
Toxicol. 8_(2) :94-101, 1975.
Hawley, G. G. (ed.). Condensed Chemical Dictionary, 9th ed. New
York, Van Nostrand Reinhold Co. 1977.
Ingwalson, R. W. Nitriles. In Kirk-othmer Encyclopedia of Chemical
Technology, Supplement. "T971.
ITII (International Technical Information Institute). Toxic and
Hazardous Industrial Chemicals Safety Manual. Tokyo. 1976.
NIOSH. ' Registry of Toxic Effects of Chemical Substances, 1976 ed.
Pozzani, U. C. et al. An investigation of the mammalian toxicity
of acetonitrile. J. Occup. Med. !L:634, 1959.
Rubinskii, N. D. Effect of acetonitrile and succinonitrile on the
sanitary conditions of reservoirs. Gig. Naselennykj Mest
8_:20-24, 1969. (From Chem. Abstr. 73_:91026j)
Sax, N. I. Dangerous Properties of Industrial Materials, 3rd ed.
New York, Van Nostrand Reinhold Co. 1968.
SRI (Stanford Research Institute). Directory of Chemical Producers.
Menlo Park, Calif. 1975.
Stecher, P. G. (ed..) . The Merck Index. Rahway, N.J., Merck and
Co., Inc. 1969.
*This document was prepared for the U.S. Environmental Protection
agency by the MITRE Corp. It is a secondary source and does not
cite its primary references. Thus, verification of some informa-
tion is not possible. The environmental release data were taken
from the NSF/Rann Research Program on Hazard Priority Ranking of
Manufactured Chemicals.
-------
ADDENDUM
It has been found that a standardized (Crowe, 1976) second
puff of cigarette smoke contains 0.31 mg acetonitrile. A smoker
may absorb between 73 and 82% of this, depending on past smoking
habits.
Reference
Dahlman, T. et al. Mouth absorption of various compounds in
cigarette smoke. Arch. Environ. Health 1£(6) : 831-835,
1968.
-------
CHEMICAL HAZARD INFORMATION PROFILE
Acrolein
Date of report: March 10, 1978
This chemical was chosen for study because of its reported
presence in air and water samples.
Acrolein is not recommended for further priority evaluation
within OTS at this time. Available information indicates that
most human exposure to acrolein is confined to the workplace.
There is an existing OSHA standard for acrolein. Significant
environmental exposure is unlikely because of acrolein's high
reactivity and apparently low release rate.
This report represents a preliminary investigation of the
subject chemical's potential for injury to human health and the
environment. The information contained in the report is drawn
chiefly from secondary sources and available reference documents.
Because of the limitations of such sources, it necessarily follows
that this report may not reflect all available information on the
subject chemical.
Any recommendations based on this report are tentative and
should not be construed as final Agency policy with respect to
the subject chemical.
-------
CHEMICAL HAZARD INFORMATION PROFILE
Acrolein
Date of report: March 10, 1978
Acrolein (2-propenal, acrylaldehyde, or allyl aldehyde) is a
colorless to yellowish liquid. It has a highly disagreeable,
choking odor and is flammable. Acrolein is soluble in water,
alcohol, and ether. It has a boiling point of 52.7°C. Upon
exposure to light and air, acrolein polymerizes to form disacryl,
an inactive, gelatinous substance (Hawley, 1971).
PRODUCTION AND USE
Acrolein is currently produced only by Shell Chemical Co.,
Norco, La., and Union Carbide Corp., Chemicals and Plastics
Division, Taft, La. (SRI, 1977). The only method used to manu-
facture acrolein is the catalytic vapor-phase oxidation of pro-
pylene (School, 1973). U.S. production of isolated acrolein in
1974 is estimated to have been 61 million Ib. An additional 100-
150 million Ib was produced and consumed captively for production
of acrylic acid and esters (U.S. EPA, 1977b).
The U.S. consumption pattern of isolated acrolein in 1974
was estimated as follows: glycerin, 50%; synthetic methionine,
25%; other applications, 25%. "Other applications" include:
manufacture of 1,2,6-hexanetriol, glutaraldehyde, glyceraldehyde,
perfume, colloidal forms of metals, and numerous other organic
compounds; as an aquatic herbicide, molluscicide, slimicide, and
algicide; and in etherification of food starch (U.S. EPA, 1977b).
-------
HEALTH ASPECTS
General Toxicity
Acrolein is a severe irritant to the eyes and respiratory
tract. Yant et al. (1930) reported that 1 ppm caused "practically
intolerable eye irritation with lacrimation" within 5 min of
exposure. The rat inhalational LC5Q is 0.75 mg/1 for 10-min
exposure (Champeix and Catilina, 1975). Rat oral LD is 46
mg/kg, and human LCLQ is 153 ppm/10 min (NIOSH, 1975).
Rats continuously exposed to 0.55 ppm acrolein for 11 to 21
days had significantly lower body weight, liver weight, and serum
acid phosphatase levels than controls. They also showed signs of
upper respiratory tract irritation, significant lowering of
alveolar macrophage number, and high susceptibility to Salmonel-
la enteritidis infection (Bouley et al., 1976).
Continuous 90-day exposure at 0.22 ppm caused inflammation
in liver, lung, kidney, and heart of monkeys, guinea pigs, and
dogs. Exposure to 1.8 ppm caused sguamous cell metaplasia and
basal cell hyperplasia of the trachea in monkeys (Lyon et al.,
1970).
Carcinogenicity
In a study with hamsters, Peron and Kruysse (1971) found "no
tumors attributable to acrolein exposure (4.0 ppm, 7 hr/day, 5
days/week, 52 weeks). Acrolein exposure did not increase the
number of tumors in animals treated with both acrolein and either
benzo(a)pyrene or diethylnitrosamine.
10
-------
Mutagenicity
Acrolein has been found to be mutagenic -in the yeast S_. cere-
visiae (Izard, 1973) , the alga D_. bioculata (Izard, 1967) , and
the fruit fly D. melanogaster (Rapoport, 1948).
Negative results have been found in the.bacteria E. coli
(Ellenberger and Mohn, 1976) and S. typhimurium (Anderson et al.f
1972) and in the mouse dominant lethal test CEpstein et al.,
1972).
Hygienic Standards
U.S. Occupational Health Standard - air: TWA, 0.1 ppm.
American Conference of Government Industrial Hygienists:
TLV, 0.1 ppm.
ENVIRONMENTAL ASPECTS
The total release rate of acrolein into the environment is
not known. Besides fugitive emissions from industrial processes,
acrolein is formed in the environment by burning tobacco and by
heating fats or glycerine (Plotnikova, 1957).
In water, oxidation of acrolein by RO radical may be fairly
rapid (U.S. EPA, 1977a). Biodegradation in water also appears
rapid, as the 10-day BOD is 33% of the theoretical value (Dorigan
et al., 1976). In air, aldehydes are expected to photodissociate
to RCO and H atoms rapidly and competitively with their oxidation
by HO radical, for a half-life of 2 to 3 hr (Caivert and Pitts,
1966; Hendry, 1977).
11
-------
The 24-hr and 48-hr LC5Q values to harlequin fish are,
respectively, 0.14 and 0.06 ppm (Alabaster, 1969). Exposure to
1.0 ppm totally inhibited multiplication of the marine alga
D. bioculata (Champeix and Catalina, 1975). Acrolein has demon-
strated ciliastatic effects in mammals (Guillerm et al., 1961),
molluscs (Wynder et al., 1965), and algae (Izard and Testa,
1968).
12
-------
REFERENCES
Alabaster, J. S. Survival of fish in 164 herbicides, insecticides,
fungicides, wetting agents and miscellaneous substances.
Int. Pest. Contr. 11(2): 29-35, 1969.
Anderson, K. J., E. G. Leighty, and M. T. Takahashi.. Evaluation
of herbicides for possible mutagenic properties. J. Agr.
Food Chem. 2(3) :649-656, 1972.
Bouley, G., A. Dubreuil, J. Godin, M. Boisset, and C. Boudene.
Phenomena of adaptation in rats continuously exposed to low
concentrations of acrolein. Ann. Occup. Hyg. 1£(1) : 27-32,
1976.
Calvert, J. G., and J. N. Pitts. Photochemistry. New York, John
Wiley and Sons. 1966. (As cited by U.S. EPA, 1977a)
Champeix, J., and P. Catilina. Les Intoxications par 1'Acroleine.
Masson, Paris, 1975. (As cited by Izard and Libermann,
Mutat. Res. £7:133, 1978)
*Dorigan, J., B. Fuller, and R. Duffy. Scoring of Organic Air
Pollutants. Chemistry, Production and Toxicity of Selected
Synthetic Organic Chemicals. MITRE Corp. 1976.
Ellenberger, J., and G. R. Mohn. Comparative mutagenicity of
cyclophosphamide and some of its metabolites. Mutat. Res.
38:120-121, 1976. (As cited by Izard and Libermann, Mutat.
Ris. 4_2:125, 1976)
Epstein, S. S., E. Arnold, J. Andrea, W. Bass, and Y. Bishop.
Detection of chemical mutagens by the dominant lethal assay
in the mouse. Toxicol. Appl. Pharmacol. 2^:288-325, 1972.
(As cited by Izard and Libermann, Mutat. Res. 47_:132, 1978)
Guillerm, R. , R. Dadre, and B. Vignon. Effects inhibiteurs de la
fumee de tabac sur 1'activite ciliavie de I1 epithelium
respirative, et natures des composants responsables. C. R.
Acad. Nat. Med. I45_:416-425, 1961. (As cited by Izard and
Libermann, Mutat. Res. £7:123, 1978)
Hawley, G. G. (ed.). The Condensed Chemical Dictionary, 8th ed.
New York, Van Nostrand Reinhold Co. 1971.
Hendry, D. G. Private communication, 1977. (As cited by U.S.
EPA, 1977a)
*This document was prepared for the U.S. Environmental Protection
Agency by the MITRE Corp. It is a secondary source and does not
cite its primary references. Thus, verification of some informa-
tion is not possible. The environmental release data were taken
from the NSF/Rann Research Program on Hazard Priority Ranking of
Manufactured Chemicals.
13
-------
Izard, C. Recherches sur les effects mutagenes de I1 acroleine et
de ses deux epoxydes: le glycidol et le glycidal, sur
Saccharomyces cerevisiae. C. R. Acad. Sci. Ser. D 276 ;3037-
3040, 1973. (As cited by Izard and Libermann, Mutat. Res.
47_:126, 1978)
Izard, C. Sur la multiplication de Dunaliella bioculata en presence
de la phase gayeuse de fumee de cigarette et sur 1'obtention
de mutations en presence d' acroleine. C. R. Acad. Sci. Ser.
D 265^:1799-1802, 1967. (As cited by Izard and Libermann,
Mutat. Res. £7:128, 1978)
Izard, C., and P. Testa. Recherches sur les effects de la fumee
de la cigarette et de certains constituants sur la motilitie '
et la multiplication du Dunaliella bioculata. Ann. Dir.
Equip. Exploit. Ind. Tab. Alumettes, Sec. 1, No. 6, p. 121-
156, 1968. (As cited by Izard and Libermann, Mutat. Res.
£7:124, 1978)
Lyon, J. P., T. J. Jenkins, Jr., R. A. Jones, R. A. Coon, and J.
Siegel. Repeated and continuous exposure of laboratory
animals to acrolein. Toxicol. Appl. Pharmacol. 17(3):726-
732, 1970.
NIOSH. Registry of Toxic Effects of Chemical Substances. 1975.
Peron, V. J., and A. Kruysse. Effects of exposure to acrolein
vapor in hamsters simultaneously treated with benzo(a)pyrene
or diethylnitrosamine. J. Toxicol. Environ. Health 3:379-
394, 1971.
Plotnikova, M. M. Acrolein as an atmospheric air pollutant. Gig.
Sanit. 22^(6) :1015, 1957. From B. S. Levine (ed.), U.S.S.R.
Literature on Air Pollution and Related Occupational Diseases,
vol. 3, 1960, p. 188-194.
Rapoport, I. A. Mutatsii pod vlianiem mepredel1 nyh al1 degidov.
Dokl. Akad. Nauk SSSR 6^:713-715, 1948. (As cited by Izard
and Libermann, Mutat. Res. £7:131, 1978)
SRI (Stanford Research Institute). Directory of Chemical Producers,
Menlo Park, Calif. 1977.
School, G. E. Make acrolein from propylene. Hydrocarbon Process.,
Sept. 1973, p. 218-220.
U.S. EPA. Review of the Environmental Fate of Selected Chemicals
Task 3. EPA 560/5-77-003, PB 267121/AS. 1977a. p. 52.
U.S. EPA. A Study of Industrial Data on Candidate Chemicals for
Testing. EPA 560/5-77-006. 1977b. p. 487, 488.
14
-------
Wynder, E. L., D. A. Goodman, and D. Hoffman. Ciliatoxic components
in cigarette smoke, II. Carboxylic acids and aldehydes.
Cancer 18_: 505-509, 1965. (As cited by Izard and Libermann,
Mutat. Res. £7^:123, 1978)
Yant, W. B., H. Schrenk, P. Patty, and R. Sayers. Acrolein as a
warning agent for detecting leakage of methyl chloride from
refrigerators. U.S. Bureau of Mines Report of Investigation
No. 3027. (As cited by Kane and Alarie, Sensory irritation
to formaldehyde and acrolein during single and repeated
exposures in mice, American Ind. Hyg. Assoc. J., vol. 38,
1971)
15
-------
CHEMICAL HAZARD INFORMATION PROFILE
Adipate Ester Plasticizers
Date of report:January 5, 1978
This category of chemicals was chosen for study after inci-
dents of respiratory ailments ("meat-wrappers syndrome") were
reported in workers exposed to food wraps which contain adipate
ester plasticizers. Although no information supporting these
claims was found in the course of preparing this document, infor-
mation was found which indicates a potential for mutagenic and
teratogenic effects.
Phase I assessment is recommended for the adipates. Rela-
tively little information was found concerning either the amount
of adipate esters released into the environment or the environmental
fate of these chemicals. This lack of information, coupled with
the fact that adipate esters are produced in fairly high volume,
suggests that environmental monitoring may be needed to allow
better estimation of the extent of nonoccupational exposure to
adipate esters. Monitoring data obtained by SAD will be forwarded
to CREB for use in the Phase I assessment.
It is also recommended that CHIB perform a chemical technology
review of diacid plasticizers.
This report represents a preliminary investigation of the
subject chemical's potential for injury to human health and the
environment. The information contained in the report is drawn
chiefly from secondary sources and available reference documents.
Because of the limitations of such sources, it necessarily
follows that this report may not reflect all available information
on the subject chemical.
Any recommendations based on this report are tentative and
should not be construed as final Agency policy with respect to the
subject chemical.
16
-------
CHEMICAL HAZARD INFORMATION PROFILE
Adipate Ester Plasticizers
Date of report: January 5, '1978
0 = C - CH2 - CH2 - CH2 - CH2 - C = 0
OR OR
General formula for adipic acid esters
A plasticizer is an organic compound added to a high-molecular-
weight polymer both to facilitate processing and to increase the
flexibility and toughness of the final product by internal modifi-
cations (solvation) of the polymer molecule. The polymeric
structure is initially held together by secondary valence bonds;
the plasticizer replaces some of these with plasticizer-to-
polymer bonds, thus aiding movement of the polymer chain sections.
Plasticizers are classified as primary (high compatibility) and
secondary (limited compatibility).
* •
Adipate ester plasticizers are nonvolatile oily liquids or
low-melting solids. They are generally used to improve the low-
temperature flexibility of polyvinyl chloride (PVC) compounds
(CCD, 1977).
The most widely used adipate ester plasticizer is di(2-
ethylhexyl) adipate, which accounts for about two-thirds of the
adipate ester plasticizer market. The other large-volume com-
ponent of this market is n-octyl n-decyl adipate, representing
approximately 13% of the total. The balance is divided among a
number of adipic acid esters including diisodecyl adipate, diisooctyl
adipate, n-hexyl n-decyl adipate, di(2-butoxyethoxy)ethyl adi-
pate, and others (CEH, 1976).
17
-------
PRODUCTION AND USE
Most plasticizers are products of simple esterification
reactions, which can be readily carried out in heated kettles
with agitation and provisions for water take-off. Nevertheless,
while some plants produce plasticizers by such batch methods,
other, newer plants operate continuously and in a highly auto-
mated fashion. Esterification catalysts such as sulfuric acid or
p-toluenesulfonic acid speed the reaction and are later removed
in a washing step. The purity requirements for commercial
plasticizers are very high; adipate esters are usually almost
colorless and have little odor (CEH, 1976).
Adipic acid esters are prepared via the reaction of adipic
anhydride with an aliphatic alcohol to yield the desired product
(CEH, 1976).
The production of adipate esters has increased appreciably
in recent years. The major producers of adipate plasticizers are
Hatco, Monsanto, Rohm and Haas, Tennessee Eastman, and U.S.S.
Chemicals. Only Monsanto is a major producer of adipic acid and
is also believed to be the largest producer of the most popular
adipate plasticizer, di(2-ethylhexyl) adipate. Refer to Table 1
for annual domestic production figures. Table 2 presents the
1971 production figures for the major adipate plasticizers.
Along with the major adipate plasticizers are a number of apparently
small-volume adipate plasticizers used in specialty applications.
Table 3 lists all the adipate plasticizers identified in the
Modern Plastics Encyclopedia (1975). Despite the significant
production volume of the adipate plasticizers, as a class they
represent only a small fraction of the total plasticizer market.
As can be seen in Table 4, adipates represent less than 5% of a
market dominated by phthalate esters.
18
-------
Table 1. ANNUAL DOMESTIC PRODUCTION
OF ADIPATE PLASTICIZERS
(millions of pounds)
Di(2-ethylhexyl)
Year adipate Others Total
1955
1960
1965
1970
1974
2.7
3.0
14.7
35,0
40.6
7.9
14.3
33.1
19.0
23.5
10.6
17.3
47.8
54.0
64.1
alncludes primarily n-octyl n-decyl adipate and the
following: diisodecyl adipate; diisooctyl adipate;
n-hexyl n-decyl adipate; and di(2-butoxyethoxy)ethyl
adipate.
Source: CEH, 1976.
Table 2. ADIPATE ESTER PRODUCTION - 1971
Type Percentage
Di(2-ethylhexyl) adipate (DOA) 55
Dioctyl adipate 14
n-Octyl n-decyl adipate 13
Diisodecyl adipate 6
n-Hexyl n-decyl adipate 5
Di(2-butoxyethoxy)ethyl
adipate 3
Source: CEH, 1976.
19
-------
Table 3. COMMERCIAL ADIPATE ESTER PLASTICIZERS
Name No. of producers and suppliers
Benzyloctyl adipate 2
Butyl carbitol adipate 1
Dimethyl adipate 2
Dibutyl adipate 7
Diisobutyl adipate 7
Di(2-ethylhexyl) adipate (DOA) 30
Dinonyl adipate 2
07-09 linear adipate 1
Dicapryl adipate 2
n-Octyl n-decyl adipate 9
Straight-chain alcohol adipate 3
Diisodecyl adipate 17
Dimethoxyethyl adipate 1
Diethoxyethyl adipate 1
Dibutoxyethyl adipate 3
Dibutoxyethoxyethyl adipate 2
High-molecular-weight adipate (P) 3
Polypropylene adipate (P) 4
Dilinear alkyl adipate 1
a(P) - polymeric.
Source: Modern Plastics Encyclopedia, 1975.
Table 4. U.S. PRODUCTION OF PLASTICIZERS
BY MAJOR TYPE - 1974
Type Percentage
Phthalate esters 71.8
Epoxy esters 8.8
Phosphate esters 7.3
Adipate esters 3.8
Polymeric plasticizers 3.0
Other aliphatic esters 1.1
Other plasticizers 4.2
Source: CEH, 1976.
20
-------
Over 85% of all aliphatic adipate ester plasticizers are used
to impart low-temperature flexibility to polyvinyl chloride (PVC)
formulations (see Table 5). Adipates represent the predominant
category of aliphatic plasticizers; azelates and sebacates are
small-volume speciality aliphatic plasticizers. In recent years,
with the increased availability of cheaper linear phthalates, the
total consumption of aliphatic plasticizers has remained virtually
static. Non-PVC applications of aliphatic plasticizers include
use as functional fluids and, to a small extent, as plastification
agents in some synthetic elastomers (CEH, 1976).
Table 5. DOMESTIC ALIPHATIC PLASTICIZERa
CONSUMPTION - 1974
(percentage)
Application Consumption
Use with polymers
PVC resins 76
Other vinyl resins
Cellulose ester plastics 3
Synthetic elastomers
Other polymers
Other uses 21
Total 100
Includes adipates (predominantly), sebacates, and
azelates.
Source: CEH, 1976.
In addition to PVC applications, adipate plasticizers are
used to a much lesser extent with natural and synthetic rubbers,
polystyrene, and cellulose derivatives (e.g., nitrocellulose
lacquers). These plasticizers are characterized by low initial
21
-------
viscosity and good viscosity stability for plastisol formula-
tions, excellent clarity for sheeting and film, good electrical
resistivity, and low volatility for high-temperature applications
such as wire covering and insulation.
In PVC plasticizers, adipate diesters [chiefly di(2-ethyl-
hexyl) adipate] are used to impart low-temperature flexibility
and resilience when, and to the extent, needed. Examples of PVC
plastics containing discrete amounts of adipate plasticizers
include coated fabrics for automobile seating, film for produce
and meat packaging, insulation of certain types of electrical and
communication wires, and others. Adipate plasticizers were among
the first plasticizers approved by FDA for use in food storage
and preparation areas, where they have found increasing popular-
ity (e.g., coating for refrigerator shelves and kitchen appli-
ances) . The major application of adipate plasticizers in this
field is in food wraps and packaging, and this market is expand-
ing rapidly (CEH/ 1976).
One of the chief concerns involved in the selection of the
correct adipate plasticizer is the compatibility each has for the
particular resin. Adipic acid esters of linear alcohols, chiefly
in the n-octyl to n-decyl range, for example, have found increas-
ing use because their effectiveness in imparting low-temperature
flexibility is somewhat greater than that of esters of branched
alcohols; in addition, they are also much less volatile. On the
other hand, their compatibility and fusion characteristics are
inferior to those of di(2-ethylhexyl) adipate (CEH, 1976). Refer
to Table 6 for a summary of compatibility qualities of several
adipate plasticizers.
22
-------
Table 6. ADIFATE PLASTICIZER COMPATIBILITY
WITH VARIOUS PLASTICS3
Plasticizer
Diisobutyl adipate
DOA
Diisodecyl adipate
Di (2-butoxyethyl)
adipate
CA
U
P
F
P
CAB
C
c
C
c
CN
C
C
c
c
EC
U
C
c
c
PM
U
P
P
c
PS
U
c
P
c
VA
C
F
P
P
VB
U
P
P
C
FVC
C
C
C
C
aResins used: CA, cellulose acetate; C7aB, cellulose acetate-
butyrate; CN, cellulose nitrate; EC, ethylcellulose; PM,
polymethyl methacrylate; PS, polystyrene; VA, polyvinyl
acetate; VB, polyvinyl butyryl; PVC, polyvinyl chloride.
Code for compatibility: C, compatible; P, partially com-
patible; U, unknown.
Source: Darby and Sears, 1968.
HEALTH EFFECTS
Dominant Lethal Mutations and Antifertility Effects
«
Male mice of demonstrated fertility were injected IP with a
single dose of 0.5, 1.0, 5.0, or 10.0 ml/kg of di (2-ethylhexyl)
adipate (DOA) or a single injection of 0.44, 0.72, 1.10, or 1.46
ml/kg of diethyl adipate (DEA). Ten males were injected at each
dose level and allowed to mate with two virgin females per week
for 8 weeks. Both DOA and DEA produced dose-related antifer-
tility and mutagenic effects, as indicated by a reduced percent-
age of pregnancies and an increased number of early fetal deaths.
The highest dose of DCA and the tv/o largest doses of DFA yielded
a distinct reduction in the incidence of pregnancies, especially
during the first 3- to 4-week period postinjection. This antifer-
tility effect was less evident with the lower dose levels. There
also occurred a reduction in the number of implantations and live
fetuses per pregnancy for one or more of the higher dose levels
of both DOA and DEA. Mutagenic effects, as expressed by an
increase in the number of early fetal deaths, displayed a significant
23
-------
degree of dose dependence, with the higher doses yielding more
early fetal deaths than the lower doses. These dominant lethal
mutations were observed for both adipates during the 3-week
period immediately following injection. However, DOA also
induced dominant lethal effects during the period 4-8 weeks
postinjaction. This indicates that DOA produced dominant lethal
mutations in both the postmeiotic and premeiotic stages of
spermatogenesis in mice (Singh et al., 1975).
Embryotoxic and Teratogenic Effects
Seven adipates were evaluated for their embryonic-fetal
toxicity and teratogenic effects in rats. The tested adipates
included dimethyl, diethyl (DBA), dipropyl, diisobutyl, di-n-
butyl, di(2-ethylhexyl) (DOA), and dicyclohexyl adipate. The
adipates were tested in female rats by the IP injection of vary-
ing doses on the 5th, 10th, and 12th days of gestation (see Table
7). The administered doses were based on the acute toxicity of
each compound as follows: 1/30, 1/10, 1/5, and 1/3 of the acute
LD5Q for each substance (except DOA, which had little apparent
acute toxicity). The rats were sacrificed on the 20th day of
gestation- (1 day before expected parturition) and examined for
gross, skeletal, and visceral abnormalities.
7vll of the adipates were found to exert some degree of
damage upon the developing embryo and fetus:
(a) Dicyclohexyl adipate caused a significant increase in
resorptions at all four dose levels, indicating an
early embryotoxic effect. In addition, dead fetuses
were found at all dose levels, indicative of a later
toxic action as well. A number of gross abnormalities
were noted at the three higher doses; most abnormalities
took the form of hemangiomas of various parts of the
body, although twisted hindlegs were often also observed,
24
-------
Table 7. EMBRYONIC-FETAL TOXICITY OF ADIPATE
ESTERS ON RAT FETUSES
Abnormalities
Injection vol
Adipate ester
Dimethyl
Diethyl
(DEA)
Dipropyl
Diisobutyl
Di-n-butyl
Di(2-ethylhexyl)
(DOA)
Dicyclohexyl
(ml/kg)
0.0603
0.1809
0.3617
0.6028
0.0837
0.2512
0.5024
0.8373
0.1262
0.3786
0.7572
1.2619
0.1983
0.5950
1.1900
1.9833
0.1748
0.5244
1.0488
1.7480
1.00
5.00
10.00
0.1700
0.5100
1.0201
1.7002
Resorptions (%)
6.8
14.1
1.8
5.7
1.9
7.0
9.3
10.7
3.2
10.9
9.8
20.0
3.6
1.6
4.8
3.2
3.8
4.9
2.9
9.4
5.3
3.1
7.0
14.5
19.6
19.4
20.0
Gross
0
1.8
3.6
8.0
0
1.9
2.0
4.2
0
2.0
3.6
5.6
0
3.2
1.7
8.3
0
1.7
3.0
5.4
0
1.6
3.8
0
10.0
6.3
8.5
Skeletal
0
7.4
13.8
19.2
0
0
4.0
8.0
0
0
0
5.3
0
6.3
10.0
9.7
0
0
0
6.7
3.6
3.4
7.1
0
0
3.8
4.0
Visceral
0
0
0
0
8.3
0
4.0
0
0
0
0
0
0
0
0
3.4
0
3.7
0
3.8
0
3.2
4.0
0
0
0
0
Source: Singh et al., 1973.
25
-------
Skeletal abnormalities were seen in a few mice at the
two highest dose levels, while no visceral changes were
seen in any of the groups.
(b) Dimethyl adipate also displayed a considerable degree
of embryotoxicity and teratogenicity. In the highest
dose group, several fetuses had hemangiomas, 5 of 26
examined fetuses had skeletal abnormalities, 1 fetus
lacked a left kidney, and 1 had an angulated anal
opening. In the second highest dose group, 1 fetus did
not have a tail and 4 of 29 examined had skeletal
abnormalities. The next lower dose level produced
several abnormal fetuses, albeit at a lower frequency,
with changes similar to those seen at the two higher
levels. The lowest dosage did not produce any noted
abnormalities.
(c) Diisobutyl adipate produced a number of abnormal changes
in the offspring of treated rats. At the highest
level, hemangiomas were noted in several fetuses, as
were twisted hindlegs and other skeletal malformations.
The next lower dose groups yielded fetuses with hemangi-
omas and skeletal malformations but no examples of
twisted hindlegs. No abnormalities were seen in the
lowest group.
(d) Diethyl, dipropyl, di-n-butyl, and di (2-ethylhexyl)
adipate produced few gross, skeletal, or visceral
abnormalities; these occurred predominantly at the
higher dose levels.
The study concluded that, while all of the tested adipates
exerted some deleterious effects on the developing embryo and
fetus, the degree of injury was significantly less than that seen
with similar doses of phthalate ester analogs (Singh et al.,
1973) .
26
-------
Acute Toxicity
The adipate esters are characterized by a low to moderate
degree of acute toxicity. Table 8 presents a summary of the
results from several acute toxicity studies.
Table 8. SUMMARY OF ADIPATE ESTER
ACUTE TOXICITY STUDIES
Adipate ester
Dimethyl
Diethyl
Dipropyl
Di-n-butyl
Diisobutyl
Dicyclohexyl
Di(2-ethylbutyl)
Di(2-ethylhexyl)
(DOA)
Di ( 2-hexyloxyethyl )
Di [ 2- ( 2-ethylbutoxy ) ] ethyl
Didecyl
fjsingh et al. , 1973.
°Fassett, 1963.
^Singh et al. , 1975.
Smyth et al. , 1951.
Oral LD50
(g/kg)
v,
1.613
12.9rt
5-6d
Q 1 U
h
20-50D
4.3e
3'3b
25.0°
12.8-25.8
IP LD50
(ml /kg)
1.8a
2.5a
2.2C
•5 Q^
5 . 2
6.0a
5.1a
a
50. Oa
100. 0C
h
u
Species
Rat
Rat
Mouse
Rat
Rat
Rat
Rat
Rat
Rat
Rat
Mouse
Rat
Rat
Rat
Mouse
'Smyth et al., 1954.
Gaunt et al. (1969) tested the acute toxicity of dialkyl 79
adipate (ester of adipic acid and a mixture of alcohols with 7-9
carbon atoms) in rats and mice. The oral LD in mice was betwe
8 and 12 g/kg; 20 g/kg administered orally to rats produced
diarrhea as the only symptom. (Dialkyl 79 adipate is used as a
plasticizer for PVC.)
27
-------
Subacute Toxicity
The subacute toxicity of di(2-ethylhexyl) adipate has been
tested by several investigators. Fassett (1963) reported a study
in which rats were fed diets containing 0.5, 2.0, or 5.0% DOA
(approximately 250, 1,000, or 2,500 mg/kg/day for about a month)
and were without effect except for growth retardation at the 5%
level. The same study found only a transient loss of appetite in
dogs fed 2 g/kg/day of DOA for 2 months.
Smyth et al. (1951) fed DOA to rats at doses ranging from
0.16-4.74 g/kg/day for 30 days. The investigators found altered
organ weights and a reduction in appetite and growth in rats
receiving 2.92 g/kg daily. Doses of 4.74 g/kg were subacutely
lethal, while 9.11 g/kg was acutely fatal. The no-effect dose
was 0.6 g/kg.
Dialkyl 79 adipate was fed to rats at 0.0, 0.125, 0.25r 0.5,
or 1.0% of the diet (approximately 0, 63, 125, 250, or 500 mg/kg/day)
for 98 days. No effects were seen at or below 0.25% of the diet.
At the 1.0% level, weight gain was lower in females, the relative
kidney weight increased in both sexes, and the hemoglobin concentra-
tion was reduced, also in both sexes. In the 0.5% group, females
displayed an increase in relative kidney weight (Gaunt et al.,
1969) .
ENVIRONMENTAL EFFECTS
MITRE Corp. (1976) estimates that 39.4 million Ib of di(2-
ethylhexyl) adipate was released to the environment in 1972.
Di(2-ethylhexyl) adipate has been identified at a concentra-
tion of 30 ppb in the Monatiquot River in Massachusetts. This is
apparently the first time that an adipate plasticizer has been
28
-------
identified in water and indicates that plasticizers in addition
to phthalates (which are recognized widespread environmental
contaminants) are entering the aqueous environment' (Kites,
1973).
The biodegradability of three adipate esters was determined
in acclimated, activated sludge systems. Rapid primary degradation
(67-99+%) was observed at 3 and 13 mg/1 feed levels for di(2-
ethylhexyl) adipate, di-n-hexyl adipate, and hexyl nonyl adipate
over a 24-hr period (Saeger et al., 1976).
The phytotoxic effects of gases emitted by PVC plastic
covering materials were tested on various vegetable crops. Among
25 plasticizers tested, diisobutyl phthalate and di(2-ethylhexyl)
adipate were the most injurious to vegetable plants. These
plasticizers were apparently volatilized to a phytotoxic degree
from the plastic sheets under "normal" conditions (Inden and
Tachibana, 1975).
0
Several studies (Rubin, 1973; Easterling et al., 1974) have
demonstrated the migration of di(2-ethylhexyl) adipate from
plastic biomedical devices into blood. Up to 4 mg of DOA was
extracted from "medical grade" PVC tubing by human plasma circulated
for 6 hr at 37°C. DOA was also found in blood stored in plastic
packs.
29
-------
REFERENCES
Chemical Economics Handbook (CEH). Menlo Park, Calif., Stanford
Research Institute. 1976.
Condensed Chemical Dictionary CCCD), 9th ed. New York, Van Nostrand
Reinhold Co. 1977.
Darby, J. R., and J. K. Sears. Plasticizers. In Kirk-Othmer
Encyclopedia of Chemical Technology, vol. IT. New York,
Interscience Publishers. 1968. p. 720.
Easterling, Ronald E. et al. Plasma extraction of plasticizers
from "medical grade" polyvinylchloride tubing (38389). Proc.
Soc. Exp. Biol. Med. 147_:572, 1974.
Fassett, David W. Esters. In, Frank A. Patty (ed.), Industrial
Hygiene and Toxicology, vol. II. New York, Interscience
Publishers. 1963. p. 1890.
Gaunt, I. F. et al. Acute (rat and mouse) and short-term (rat)
toxicity studies on dialkyl 79 adipate. Food Cosmet. Toxicol.
7:35, 1969.
Kites, R. A. Analysis of trace organic compounds in New England
rivers. J. Chroraatogr. Sci. IjL(ll) :570, 1973.
Inden, T., and S. Tachibana. Damage on crops by gases emitted
from the plastic materials for covering. Mie Daigaku Mogakuba
Gakujutsu Hokoku. 5_0:1, 1975. (Summary)
MITRE Corp. - Scoring of Organic Air Pollutants: Chemistry, Production,
and Toxicity of Selected Synthetic Organic Chemicals. September
1976.
Modern Plastics Encyclopedia, 52(10A). New York, McGraw-Hill.
1975.
Rubin, R. J. Biomedical implications of the migration of phthalate
ester plasticizers from PVC plastic. Tech. Pap., Reg. Tech.
Conf. Soc. Plast., March 20-22, 1973, 81. (Abstract)
Saeger, V. W. et al. Activated sludge degradation of adipic acid
esters. Appl. Environ. Microbiol. 3_1(5):746, 1976.
Singh, A. R. et al. Embryonic-fetal toxicity and teratogenic
effects of adipic acid esters in rats. J. Pharm. Sci.
62_(10):1596, 1973.
*This document was prepared for the U.S. Environmental Protection
Agency by the MITRE Corp. It is a secondary source and does not
cite its primary references. Thus, verification of some informa-
tion is not possible. The environmental release data were taken
from the NSF/Rann Research Program on Hazard Priority Ranking of
Manufactured Chemicals.
30
-------
Singh, A. R. et al. Dominant lethal mutations and antifertility
effects of di-2-ethylhexyl adipate and diethyl adipate in
male mice. Toxicol. Appl. Pharmacol. 32_:566, 1975.
Smyth, Henry F. et al. Range-finding toxicity data: List IV.
Arch. Ind. Hyg. 4.: 119, 1951.
Smyth, Henry F. et al. Range-finding toxicity data: List V.
Arch. Ind. Hyg. 10:61, 1954.
31
-------
CHEMICAL HAZARD INFORMATION PROFILE
Aluminum and Aluminum Compounds
Date of report: September 1, 1976
This group of compounds was chosen for study because of its
high production volume and high exposure potential.
Aluminum is not recommended for further priority evaluation
within OTS at this time. None of the available information indi-
cates that aluminum may present a hazard to humans or to the envi-
ronment .
This report represents a preliminary investigation of the
subject chemical's potential for injury to human health and the
environment. The information contained in the report is drawn
chiefly from secondary sources and available reference documents.
Because of the limitations of such sources, it necessarily follows
that this report may not reflect all available information on the
subject chemical.
Any recommendations based on this report are tentative and
should not be construed as final Agency policy with respect to the
subject chemical.
32
-------
CHEMICAL HAZARD INFORMATION PROFILE
Aluminum and Aluminum Compounds
Date of report: September 1, 1976
PHYSICAL PROPERTIES
Aluminum is the most abundant metal and third most abundant
element, making up 7.5% of the earth's crust. The atomic number of
aluminum is 13 and the atomic weight is 26.98. The melting point
is 660°C and the boiling point is 2,327°C. Aluminum's density is
2.7 g/ml. Aluminum is an excellent thermal and electrical conductor
and is highly resistant to most corrosive agents, aided by the
formation of a thin protective film of oxide on exposure to the
moisture in air. In its pure form, aluminum is a silvery white
metal with the highest reflectivity of any metal in the visible and
ultraviolet spectra. Pure aluminum is very malleable and ductile,
and many alloys with copper, zinc, silicon, manganese, and magne-
sium are produced for various commercial applications.
Aluminum does not exist naturally in the elemental form, but
is a constituent of many minerals, both rare and abundant. Alumi-
num oxide, A1203, exists naturally in many forms, including the
precious stones sapphire, ruby, and emerald and the minerals baye-
rite, bohemite, diaspore, gibbsite, and corundum. The minerals
differ primarily in their degree of hydration and crystal struc-
ture, and are often grouped under the collective term bauxite.
They are water insoluble and increase in density from 2.4 to 4.0
g/ml as the water content decreases from the trihydrate to the
anhydrous form. Corundum, the natural form of anhydrous aluminum
oxide, has a hardness of 9 on the Mohs scale as compared with 1 for
graphite and 10 for diamond, and finds widespread applications as
an abrasive. Other naturally occurring aluminum minerals include
albite, NaAlSi3og; amonthite, CaAl2Si208; biotite and muscovite,
33
-------
complex micas; cryolite, Na-AlFg? kaolinite, Al^Si.O.. Q (OH) „;
orthoclase, KAlSi30Q; and spinel, MgAl204.
Most inorganic aluminum compounds are white or colorless
crystals that are sparingly soluble in water and insoluble in
ethanol. The organic salts tend to be yellowish solids that are
readily soluble in water and organic solvents. Aluminum halides
and hydrides are violently reactive with water and generally solu-
ble in nonpolar organic solvents. Most aluminum salts possess
astringent and antiseptic properties.
Organoaluminum compounds are highly reactive liquids. Those
in the lower alkyl series are spontaneously flammable in air unless
diluted to 25% or less with organic solvents. All types are highly
pyrophoric and will react with any source of active hydrogen.
A complete list of commercially important aluminum compounds
is given in "Aluminum Compounds and Uses."
PRODUCTION
Bauxite is the starting material for the commercial production
of refined aluminum oxide, known commonly as alumina, and aluminum
metal. Most of the bauxite processed in the United States is
imported, chiefly from Jamaica and Surinam. Virtually all domestic
bauxite is mined in Arkansas. Alumina is prepared by dissolving
the bauxite in aqueous NaOH to form soluble sodium aluminate.
After removing the insoluble impurities, the solution is cooled and
aluminum hydrate is precipitated by seeding. The aluminum hydrate
is collected and calcined at 1,200°C, yielding alumina. This is
known as the Bayer process.
Metallic aluminum is produced commercially by the electrolytic
reduction of pure aluminum oxide in a bath of molten cryolite
34
-------
(3NaF'AlF_). Synthetic cryolite is currently used, due to deple-
tion of the natural supply. It takes 2.26 tons of dry bauxite to
yield 1 ton of pure A1203, and 1.817 tons of pure'Al20- is neces-
sary for the production of 1 ton of the pure metal.
Aluminum is also recovered from old and new scrap aluminum,
aluminum alloys, and aluminum chemicals for secondary production.
Aluminum sulfates and other chemicals are generally produced
directly from bauxite or other aluminum minerals by conversion with
acids. More highly purified chemicals can be produced from alumina.
Aluminum chloride can be produced by mixing alumina and hypochlor-
ous acid, but the chief mode of production is by reacting molten
aluminum metal with chlorine gas.
Alkyl aluminum compounds are prepared by direct synthesis
using the appropriate alkyl compounds and aluminum hydride, A1H3,
prepared by reacting powdered aluminum metal with hydrogen. Due to
the present availability of cheap olefins, this synthesis is econom-
ical on a large scale.
Figure 1 shows the production pathways for aluminum compounds.
Available production and consumption data for aluminum compounds
are given in Tables 1 and 2.
ALUMINUM COMPOUNDS AND USES
Bauxite; Starting material for other aluminum- compounds; can also
be utilized without further chemical conversion in production of
abrasive materials and refractory fire brick.
Aluminum metal; Structural material for diverse applications, food
processing apparatus, reducing agent in thermite process to obtain
other metals from their oxides.
35
-------
Aluminum sulfate
and
Other aluminum compounds
(Synthetic cryolite)
I
Aluminum metal
1
Organo-aluminums
Aluminum chloride
Figure 1. Production pathways for aluminum compounds.
36
-------
Table 1. BAUXITE PRODUCTION AND CONSUMPTION STATISTICS
(millions of tons)
Bauxite production
U.S. production Imports
1960
1961
1962
1963
1964
1965
1966
1967
1968
1969
1970
1971
1972
1973
1,998
1,228
1,369
1,525
1,601
1,654
1,796
1,654
1,665
1,843
2,082
1,988
1,812
1,879
8,739
9,206
10,575
9,212
10,180
11,199
11,529
11,594
10,976
12,160
12,620
12,326
11,428
11,240
For
alumina
8,141
8,034
9,878
10,596
11,769
12,622
13,108
13,570
13,165
14,574
14,653
14,633
14,359
15,509
Bauxite consumption
For
chemicals
directly
from
bauxite Abrasives
304
234
244
249
255
261
294
306
326
318
307
319
284
313
284
188
261
230
240
266
296
246
225
254
280
207
253
259
Refractory
94
112
138
179
219
298
313
315
311
366
370
380
403
496
37
-------
Table 2. PRODUCTION OF ALUMINUM AND ALUMINUM CHEMICALS
(millions of tons)
Primary
aluminum
1960
1961
1962
1963
1964
1965
1966
1967
1968
1969
1970
1971
1972
1973
2,014
1,904
2,118
2,313
2,553
2,755
2,986
3,269
3,255
3,793
3,976
3,925
4,122
4,529
Secondary
aluminum
329
340
462
506
552
641
693
698
817
901
781
816
946
1,038
U.S.
alumina
production
3,896
3,699
4,402
4,817
5,319
5,577
5,884
6,046
5,859
6,672
6,563
6,445
6,204
6,785
Alumina
imports
227
488
952
1,316
1,887
2,555
2,175
2,850
3,375
Aluminum
chloride
31.2
28.8
31.7
32.6
38.0
40.6
42.9
44.0
42.4
46.2
37.8
34.7
Aluminum
sulfate
533
541
563
576
610
642
679
665
716
758
723
722
798
845
38
-------
Alumina (aluminum oxide, AljO..) : Intermediate for aluminum metal
and other aluminum compounds, calcined for abrasive materials,
refractory brick for high- temperature furnaces, ceramics, absorbent,
drying agent, catalyst for organic chemistry, cosmetics, pigments,
paper coatings, electronic equipment, filler in plastics and resins.
Aluminum sulf a te ; Antiperspirant, water purification, mordant in
dyeing, lubricating compositions, tanning, deodorizer and decolor-
izer, ore flotation, cosmetics, Pharmaceuticals, pigments, paper
sizing.
Ammonium, potassium, and sodium aj-yp1 Baking powder, medicine,
mordant in dyeing, dressing of hides, water purification, paper
sizing.
Aluminum hydroxide ; Absorbent, catalyst, ceramics, mordant in
dyeing, paper sizing, water purification, waterproofing, cosmetics,
medicinals.
Aluminum chloride; Catalyst for organic reactions, cosmetics,
antiper spirant, antiseptic, wool carbonizing, photofixing baths,
wood preservative.
Sodium aluminate : Paper sizing, water treatment, cleaning composi-
tions, mordant in dyeing, sewage treatment, clarification of sugar,
welding fluxes, delustering of rayon, enamel slips.
Aluminum phosphate ; Organic catalyst, ceramics, glass manufacture,
dental cements, high- temperature bonding agent for refractories.
Aluminum f luor ide ; Production of aluminum metal, ceramics, repres-
sant of alcoholic side fermentations, organic catalyst.
Trie thy 1 aluminum, triisobutyl aluminum, diisobutyl aluminum
hydride ; Polymerization cocatalysts for production of polyolefins,
reducing agents, initiators for syntheses of linear alpha-olefins
and linear primary alcohols.
39
-------
Aluminum acetate solution; Astringent, antipruritic, antiseptic.
Aluminum bis(acetyIsalicylate); Analgesic, antipyretic.
Aluminum borate; Polymerization catalyst, glass manufacture.
Aluminum borohydride; Reducing agent, preparation of other boro-
hydrides, jet and rocket fuel additive.
Aluminum bromide; Acid catalyst in organic synthesis.
Aluminum calcium hydride; Reducing agent.
Aluminum carbide; Generating methane, reduction of metal oxides,
manufacture of aluminum nitride.
Aluminum chlorate; Antiseptic, astringent.
Aluminum diacetate; Manufacture of color lakes, waterproofing and
fireproofing fabrics, antiperspirant, disinfectant.
Aluminum e thox i de; Reducing agent, polymerization catalyst.
Aluminum hydride; Polymerization catalyst, reducing agent, prepara-
tion of other metal hydrides.
Aluminum hydroxychloride; Astringent, antiperspirant.
Aluminum isopropoxide; Organic syntheses, manufacture of aluminum
soaps, paints, and textile waterproofing.
Aluminum lactate; Foam fire extinguishers, dental impression
materials.
Aluminum lithium hydride; Reducing agent, preparation of other
hydrides.
40
-------
Aluminum nitrate; Leather tanning, antiperspirant, corrosion
inhibitor/ uranium extraction, nitrating agent.
Aluminum JD lea te; Lacquer for metals, sizing agent, waterproofing,
high-temperature grease.
Aluminum p almitate; Thickening agent for lubricants, waterproof-
ing, sizing and glazing paper and leather.
Aluminum s ilicatet Dental cements, glass manufacture, manufacture
of semiprecious stones, enamels, and ceramics.
BIOLOGICAL ASPECTS
Due to the presence of aluminum in plant and animal matter and
the utilization of aluminum in food processing apparatus and con-
tainers, it has been estimated that amounts of up to 200 mg are
ingested daily by humans (Campbell et al., 1957). Aluminum is not
readily absorbed through the intes-tine, and only trace amounts
appear in tissues (Campbell et al., 1957). Ondreicka and his
associates (1966) found that rats fed a diet containing 2,835 ppm
aluminum retained 20 times as much aluminum as those fed a normal
diet. Accumulation was highest in the skeleton, liver, adrenals,
and testes. Chronic dosing of rats and mice at 350 ppm in diet
caused growth stunting in the second and third generations. Addi-
tional effects of chronic and acute aluminum poisoning were inter-
ference with intestinal phosphate absorption and inhibition of
phosphorylation mechanisms for incorporation of phosphorus into
DNA, .RNA, ATP, and phospholipids (Ondreicka et al., 1966). High
levels of dietary aluminum may also cause rickets due to the move-
ment of bone phosphorus to the serum to counteract the decreased
availability of ingested phosphorus (Underwood, 1973). High doses
of aluminum hydroxide, as used for an antacid or in therapy for
renal caliculi, produce no symptoms other than mild gastrointes-
tinal irritation (Campbell et al.r 1957). The disruption of
41
-------
phosphate metabolism is a potential cause for alarm, and extensive
removal of phosphate from bones could seriously weaken susceptible
individuals, but no symptoms of toxicity are produced from normal
dietary intake of aluminum.
Aluminum salts have long been the substances of choice in
antiperspirant solutions. Solutions of 5% A1C1- (Landsdown, 1974)
and 10% A12(N03), (Landsdown, 1973) applied to the skin of mice,
rabbits, and pigs caused dermal irritation due to the affinity of
the Al ion for skin keratin in acid solutions. Compounds showing
no irritancy, except to highly sensitive skin, include 25% solu-
tions of aluminum chlorhydrate (the most extensively used antiper-
spirant) and 10% solutions of aluminum hydroxide, acetate, and
sulfate (Landsdown, 1973). The mechanism of the antiperspirant
activity is not understood.
The effects of inhalation of aluminum dusts and powders are
not completely understood. Goralewski (1947) reported acute pul-
monary degeneration in workers in an aluminum powder stamping mill,
with extensive pulmonary fibrosis in several cases. The powders
were coated with mineral oils to prevent aggregation. Pulmonary
fibrosis has also been reported in England in workers exposed to
stearin-coated powders (McLaughlin et al., 1962; Mitchell et al.,
1961). Fibrosis has been reported in rats injected intratracheally
with fine aluminum dusts, both coated and uncoated, but not with
granular dusts (Corrin, 1963). These observations are countered by
studies by Crombie and associates (1944), who found that workers in
an aluminum stamping mill in Pittsburgh had as good health as any
others in the plant. Crombie et al. also experimented with alumi-
num powder as treatment for silicosis. Of 34 men receiving 200-300
treatments with the powder, 19 showed clinical improvement in
breathing capacity, while the condition of the other 15 stabilized.
Fine metallic aluminum powders inhaled by hamsters, rats, and
guinea pigs caused no fibrosis, but reversible alveolar proteinosis
was present in all species. Intratracheal injection did produce
42
-------
focal pulmonary fibrosis, an effect which was probably due to
physical irritation from this mechanism of exposure (Gross et al.,
1973). Some of the discrepancies in the reported effects could be
due to the different types of powders and different coatings that
have been investigated, but harmful effects seem obvious, even if
only mechanical. Other lung afflictions have been reported from
exposure to various dusts in the aluminum industry, but since most
aluminum minerals contain silicates as well as alumina, the causa-
tive mechanisms are unclear.
The American Conference of Governmental Industrial Hygienists
(1974) rates A12°3 an ^nert particulate, with a TLV of 3 million
particles per cubic foot. No exposure limit for airborne aluminum
metal has been established. In view of the conflicting evidence
and the many unquestionable dangerous effects reported, it cannot
be denied that inhaled aluminum powders are potentially debilitat-
ing and conditions producing them should be strictly monitored.
Metallic aluminum has been tested for carcinogenic activity,
with no tumors resulting (Furst, 1971).
Alkyl aluminum compounds are extremely dangerous. Contact
with skin produces immediate deep painful burns. Inhalation of
vapors is destructive to lung tissue, and the fumes of the combus-
tion products are also toxic. All these materials present a serious
hazard to human health.
Aluminum in water at concentrations of over 1.5 ppm causes
physiological and behavioral aberrations and acute mortality in
rainbow trout (Freeman and Everhart, 1971). A1C13 at 44 ppm in
seawater is harmless to marine organisms, 88 ppm is fatal to most
fish, and 132 ppm is universally lethal to all organisms except
sporulative bacteria (Pulley, 1950).
43
-------
Aluminum chloride hexahydrate has been evaluated for toxicity
to goldfish and the narrowmouth toad. One ppm (expressed as alumi-
num, in water pH 7-8) was the LC5Q concentration for newly hatched
goldfish, while 75 ppm was lethal to all individuals. Four days
after hatching, the LC5Q for goldfish was 0.5 ppm and the LC100
was 5 ppm, with some anomalous effects appearing in the 0.001- to
0.01-ppm range. Tests on newly hatched toads gave an LC50 value of
0.1 ppm and an LC10Q value of 10 ppm. Four days after birth, the
LC5Q was between 0.05 and 0.1 ppm and the LC100 about 0.5 ppm, with
anomalous effects occurring at concentrations between 0.01 and 0.05
ppm. Most of these values are within the natural range for dissolved
aluminum and place the toxicity of aluminum about equivalent to
that of zinc; that is, less toxic than cadmium or mercury, but more
toxic than selenium or arsenic (Black, 1976).
Aluminum is present in all soils from the decomposition of
clays and other aluminum-containing minerals. At low pH it is
present as the free trivalent ion. As the pH rises past 4, it
begins to precipitate out as hydroxide. In the presence of pho-
sphate, solubility is further decreased, with virtually complete
precipitation by pH 4.4. In alkaline conditions (pH > 8), aluminum
reappears in solution, but this does not represent any actual
environmental conditions. Many studies have demonstrated the toxic
effect of aluminum on plants at soil pH values below 5. Potatoes
grown in medium with aluminum concentrations above 5 ppm showed
reduced vegetative growth and lower total tuber production by
weight (Lee, 1971). Dry plant matter production from several
grasses grown at soil concentrations of aluminum higher than 100
kg/hectare decreased significantly in similar studies using soils
of varying acidity (Hutchinson and Hunter, 1970). The toxic
effects are exhibited most markedly in roots as elongation is
sharply curtailed (Rorison, 1958; Clarkson, 1966). Possible
mechanisms for this effect include phosphate starvation due to
44
-------
precipitation of aluminum phosphates in the soil or in cell-free
spaces in the roots (Rorison, 1958), direct inhibition of mitotic
division in the root tip (Clarkson, 1966), or the loss of elasti-
city in the cell walls due to the aluminum-induced precipitation of
pectins (Rorison, 1958). Liming of soil to pH 6 reduces the
aluminum solubility to a point where it no longer affects plant
growth (Hutchinson and Hunter, 1970).
ENVIRONMENTAL ASPECTS
In the Bayer process of purifying alumina, large amounts of
Al-O., dust are released. Because of the economic value of these
particulates, efficient control procedures including multiple
cyclones, electrostatic precipitators, and wet scrubbers are used.
In the electrolytic reduction of alumina to aluminum, various
gaseous and solid fluorides as well as other particulates, depend-
ing on the type of cell used, are produced. The gaseous effluents
are fairly efficiently controlled by such techniques as spray
towers and floating bed scrubbers/ as well as a pathway in which
the alumina feed adsorbs the fluorides, which then reenter the
reduction bath. These techniques, plus cyclones, also remove most
of the particulates. The degree of efficiency of these systems is
largely determined by how well the effluent gases from the cell can
be contained, and cell types best adapting themselves to these
controls are being favored. Most of the emissions are returned to
the production process, although some, especially fluorides, may
appear in wastewater.
Alum and aluminum sulfate have been used as coagulants and
clarifying agents in water treatment facilities, resulting in
precipitation of 80% of the bacteria in organic matter. Dissolved
aluminum concentrations are usually lowered in waters treated by
these methods (Campbell et al., 1957). Other sources of aluminum
45
-------
in wastewater include mining operations, the chemical industries,
the dye and pigment industries, paper mills, textile plants, and
dyeing and tanning factories. Because of the very low solubility
of aluminum hydroxide at normal pH levels, almost all aluminum
ions entering the water systems will promptly precipitate out as
the hydroxide. This situation may lead to increased localized
deposits of aluminum hydroxide, but there are no data which show
that this occurs. Monitoring of various water systems has shown
that the aluminum content of drinking water rarely exceeds 1 ppm
and is more likely to be below 0.5 ppm. Waters from mine drainage
contain no higher levels, but weathering of rocks with acid
waters can give levels of 10-20 ppm. Acid mineral springs may
contain several hundred ppm. These levels would apparently
present potential dangers to sensitive fish such as rainbow
trout, but no incidents of fish kills due to aluminum have been
reported.
Use of recyclable .aluminum beverage cans is a viable alter-.
native to the use of reusable bottles for prevention of solid
waste problems. In 1974, 2.3 billion cans worth about $13 million
were returned for reprocessing. This was estimated at about 35%
of the aluminum cans produced. To be competitive with reusable
bottles, a recycling program would need to return about 90% of
the cans, indicating that more public cooperation in this area
will be necessary since without effective recycling programs,
aluminum cans are a solid waste problem themselves.
Organoaluminum compounds cannot exist in the environment
since their extreme reactivity would result in immediate destruc-
tion upon contact with air or water. The stringent care necessary
for safe handling of these materials in industrial use also
serves to prevent their release.
46
-------
REFERENCES
American Conference of Governmental Industrial Hygienists.
Documentation of the Threshold Limit Values. 1974.
Black, Jeffery. University of Kentucky, personal communication.
1976.
Campbell, I. R., J. S. Cass, J. Cholak, and R. A. Kehoe. Aluminum
in the environment of man. AMA Arch. Ind. Health 15;359-448,
1957.
Clarkson, D. T. Aluminum tolerance within the species Agrostis.
J. Ecol. 5_4:167-178, 1966.
Corrin, B. Aluminum pneumoconiosis. II. Effect on the rat lung
of intratrachear injection of stamped alumina powders contain-
ing different lubricating agents and a granular aluminum
powder. Br. J. Ind. Med., vol. 20, 1973. (As cited by Gross
et al., 1973)
Crombie, D. W., J. L. Blaisdell, and G. MacPherson. The treatment
of silicosis by aluminum powder. Can. Med. Assoc. J. 50:
318-328, 1944.
Freeman, R. A., and W. H. Everhart. Toxicity of aluminum hydr-
oxide complexes in neutral and basic media to rainbow trout.
Trans. Am. Fish Soc. 1£0 (4):644-658, 1971.
Furst, A. Trace elements related to specific chronic diseases:
Cancer, Geol. Soc. Am. Memoir 123:109-130, 1971.
Goralewski, G. Arch. Gewerbepathol. Gewerbe Hyg., vol. 9-11, 17,
1939-41, 1943.
Gross, P., R. Harley, and R. A. deTreville. Pulmonary reaction to
metallic aluminum powders. Arch. Environ. Health 26(5):227-
236, 1973.
Hutchinson, F. E., and A. S. Hunter. Exchangeable aluminum levels
in two soils as related to lime treatment and growth of six
crops species. Agron. J. 6J£(6) :702-704, 1970.
Industrial Hygiene and Toxicology. New York, Interscience Publishers.
1963.
Jones, H. R. Pollution Control in the Nonferrous Metals Industry.
Park Ridge, N.J., Noyes Data Corp. 1972.
Kirk-Othmer Encyclopedia of Chemical Technology. New York, Inter-
science Publishers. 1974.
Landsdown, A. B. G. Aluminum compounds in the cosmetics industry.
Their action as antiperspirants and safety in use. Soap
Perfume Cosmet. £7 (5):209-212, 1974.
47
-------
Lee, C. R. Influence of aluminum on plant growth and tuber yield
of potatoes. Agron. J. 6_3 (3) : 363-364, 1971.
McLaughlin, A. L. G. et al. Pulmonary fibrosis and encephalopathy
associated with the inhalation of aluminum dust. Br. J. Ind.
Med., vol. 19, 1962. (As cited by Gross et al., 1973)
Mitchell, J. Pulmonary fibrosis in workers exposed to finely
powdered aluminum. Br. J. Ind. Med., vol. 18, 1961. (As
cited by Gross et al., 1963)
Ondreicka, R., E. Ginter, and J. Kortus. Chronic toxicity of
aluminum in rats and mice and its effects on phosphorus
metabolism. Br. J. Ind. Med. 23,:305-312, 1966.
Perry, K. M. A. Diseases of the lung resulting from occupational
dusts other than silica. Thorax 2_:91-120, 1947.
Pulley, T. E. The effect of aluminum chloride in small concentra-
tions on various marine organisms. Tex. J. Sci, £(3):405-
411, 1950.
Rorison, I. H. The effect of aluminum on legume nutrition. Proc.
Univ. of Nottingham Easter School of Agr. Sci. 5_: 43-61,
1958.
Underwood, E. J. Trace elements. Toxicants Occurring Naturally
in Food £:43-87, 1973.
Water Quality Criteria Data Book, vol. 2. Inorganic Chemical
Pollution of Freshwater. Cambridge, Mass., Arthur D. Little,
Inc. 1971.
48
-------
CHEMICAL HAZARD INFORMATION PROFILE
Aniline
Date of report: January 20, 1978
This chemical was chosen for study because of its high pro-
duction volume.
It is recommended that OTS wait for completion of the scheduled
NIOSH Criteria Document and the NCI carcinogenicity study before
initiating any further evaluation of aniline. This CHIP should be
updated based on the additional information.
This report represents a preliminary investigation of the
subject chemical's potential for injury to human health and the
environment. The information contained in the report is drawn
chiefly from secondary sources and available reference documents.
Because of the limitations of such sources, it necessarily follows
that this report may not reflect all available information on the
subject chemical.
Any recommendations based on this report are tentative and
should not be construed as final Agency policy with respect to the
subject chemical.
49
-------
CHEMICAL HAZARD INFORMATION PROFILE
Anj. line
Date of report: January 20, 1978
Aniline (phenylamine, aminobenzene) is a colorless, oily liquid
having a boiling point of 184°C. Aniline is miscible with alcohol,
benzene, and chloroform; it is soluble in water (Stecher, 1969;
Weast, 1971).
USES
Aniline is produced commercially by the reduction of nitro-
benzene or the ammonolysis of chlorobenzene (Lowenheim and Moran,
1975). Annual domestic production of aniline is currently around 500
million Ib. The major producers of aniline are American Cyanamide
Co. (two plants; West Virginia and New Jersey), E. I. du Pont de
Nemours (two plants; Texas and New Jersey), First Mississippi Corp.
(one plant; Mississippi), and Rubicon Chemicals, Inc. (one plant;
Louisiana) (SRI, 1977).
Table 1. ANILINE CONSUMPTION PATTERN
Isocyanates 40
Rubber chemicals 35
Dyes and intermediates 6
Hydroquinone 4
Drugs 4
Miscellaneous 9
Source: SRI, 1977.
As can be seen from Table 1, aniline is most commonly used as a
chemical intermediate for the production of other products. Miscel-
laneous uses of aniline include: production of resins (formaldehyde,
50
-------
furfural, epoxy, and others); corrosion inhibitor to protect some
metals from attack by wet carbon tetrachloride; manufacture of
explosives, phenolics, surfactants, herbicides, fungicides, di-
phenylamina, varnishes, and perfumes; in textile, paper, metallurgi-
cal, and petroleum refining industries; catalyst; stabilizer (espe-
cially as polymerization inhibitor); intermediate in dye industry
(Stecher, 1969; CCD, 1977; Kouris and Northcott, 1967).
HEALTH EFFECTS
Methemoglobinemia is the most prominent symptom of aniline
poisoning in man (Hamblin, 1963). The symptoms of the toxic methe-
moglobinemia are those of oxygen lack proportional to the percentage
of hemoglobin that is tied up. Levels of methemoglobin below 20%
generally cause no symptoms; 20-50% methemoglobin can result in
dyspnea, tachycardia, headache, and dizziness; concentrations above
60-70% may produce coma and death (Harrison, 1977).
Inhalation of 7-53 ppm of aniline vapor causes only slight
symptoms of methemoglobinemia, while exposure to concentrations in
excess of 100-160 ppm for over 1 hr can cause serious difficulty
(Henderson and Haggard, 1943).
IARC (1973) reviewed the carcinogenicity data on aniline and
concluded that the presently available information appears to indi-
cate that aniline is not a human or animal carcinogen. McCann et al,
(1975) reported that aniline was negative in the Ames test for
mutagenicity.
ENVIRONMENTAL EFFECTS
MITRE Corp. (1976), in an EPA-sponsored report, estimates that
6.15 million Ib of aniline was released to the environment in 1974.
The U.S. production of aniline for that year totaled 551 million Ib.
Aniline in the atmosphere degrades photochemically to N-methyl-
aniline, N,N-dimethylaniline, acetanilide, isomeric hydroxyanilines,
51
-------
and phenols (MITRE Corp., 1976). (The first four compounds can cause
methemoglobinemia in similar fashion to that seen with aniline [Sax,
.1975].)
In a model ecosystem, aniline (0.01-0.1 ppm) was rapidly and
completely detoxified to polar metabolites by Daphnia and freshwater
snails. Algae and mosquito larvae, however, were found to retain li-
me thy 1- and N,N-dimethylaniline, respectively. Mosquito fish retained
small amounts of unchanged aniline (with ecological magnification)
and other metabolities (Lu and Metcalf, 1975) .
Aniline is fairly toxic to nitrifying bacteria such as Nitrosomas
sp. and Nitrobacter sp. A concentration of 7.7 mg/1 of aniline
inhibits nitrification in activated sludge by approximately 75%
(Tomlinson et al., 1966).
Aniline degrades readily in soil, as it has a half-life of less
than 1 week (Thompson, 1969).
52
-------
REFERENCES
CCD (Condensed Chemical Dictionary), 9th ed. New York, Van Nostrand
Reinhold Co. 1977.
Hamblin, D. 0. Aromatic nitro and amino compounds. In F. A.
Patty (ed.), Industrial Hygiene and Toxicology, 2nd ed. New
York, Interscience Publishers. 1963. p. 2105.
Harrison, M. R. Toxic methemoglobinemia. Anaesthesia 22:270,
1977.
Henderson, Y., and H. W. Haggard. Noxious Gases, 2nd ed. New
York, Reinhold Publishing Co. 1943. As cited in Documentation
Of the TLV, ACGIH, 1971.
IARC (International Agency for Research on Cancer). IARC Monographs
on the Evaluation of the Carcinogenic Risks of Chemicals to
Man, vol. 4. 1973. p. 27.
Kouris, C. S., and J. Northcott. Aniline and its derivatives. Iii
Kirk-Othmer Encyclopedia of Chemical Technology, vol 2.
1967. p. 411.
Lowenheim, Frederick A., and Marguerite K. Moran. Faith, Keyes,
and Clark's Industrial Chemicals. New York, John Wiley and
Sons. 1975.
+
Lu, P. Y., and R. L. Metcalf. Environmental fate and biodegrada-
bility of benzene derivatives as studied in a model ecosystem.
Environ. Health Perspect. 1.0:269, 1975.
McCann, Joyce et al. Detection of carcinogens as mutagens in the
Salmonella/microsome test: Assay of 300 chemicals. Proc.
Natl. Acad. Sci. U.S.A. 7_2_(12) : 5135, 1975.
*MITRE Corp. Scoring of Organic Air Pollutants. Chemistry,
Production, and Toxicity of Selected Synthetic Organic Chemicals,
1976.
Sax, N. Irving. Dangerous Properties of Industrial Materials, 4th
ed. New York, Van Nostrand Reinhold Co. 1975..
SRI (Stanford Research Institute). Chemical Economics Handbook.
Menlo Park, Calif. 1977.
Stecher, P. G. (ed.). The Merck Index, 8th ed. Rahway, N.J.,
Merck and Co. 1969.
*This document was prepared for the U.S. Environmental Protection
Agency by the MITRE Corp. It is a secondary source and does not
cite its primary references. Thus, verification of some information
is not possible. The environmental release data were taken from
the NSF/Rann Research Program on Hazard Priority Ranking of
Manufactured Chemicals. e
-------
Thompson, F. R. Persistence and effects of some chlorinated
anilines on nitrification in soil. Can. J. Microbiol.
lj>(7):791, 1969.
Tomlison, T. G. et al. Inhibition of nitrification in the
activated sludge process of sewage disposal. J. Appl.
Bacteriol. 2_9(2):266, 1966.
Weast, Robert C. (ed.). CRC Handbook of Chemistry and
Physics, 52nd ed. Cleveland, Chemical Rubber Co. 1971,
54
-------
CHEMICAL HAZARD INFORMATION PROFILE
Benzyl Chloride
Date of report: December 9, 1977
This chemical was chosen for study because of its relatively
high production volume.
It is recommended that TSCA Section 8(a) and 8(d) submissions
be required for benzyl chloride. More definitive information on
exposure potential is needed as well as additional information to
supplement the relatively scanty data on health effects. A
contractor literature search on environmental aspects is recom-
mended because very little information was found in the preparation
of this report. This Chemical Hazard Information Profile should
be updated based on the additional data obtained.
This report represents a preliminary investigation of the
subject chemical's potential for injury to human health and the
environment. The information contained in the report is drawn
chiefly from secondary sources and available reference documents.
Because of the limitations of such sources, it necessarily follows
that this report may not reflect all available information on the
subject chemical.
Any recommendations based on this report are tentative and
should not be construed as final Agency policy with respect to
the subject chemical.
55
-------
CHEMICAL HAZARD INFORMATION PROFILE
Benzyl Chloride
Date of report: December 9, 1977
CHEMICAL CHARACTERISTICS
Benzyl chloride (CgH5CH2Cl) is a colorless, highly refractive
liquid with a pungent aromatic odor. It freezes at -39*0 and
boils at 179.4°C. The density of benzyl chloride is 1.1002 at
20°C. The vapor pressure of benzyl chloride is 1.4 mm at 25°C.
It is immiscible in water, but decomposes in hot water to give
benzyl alcohol. At room temperature it is miscible with ethanol,
ether, and chloroform. Its explosive limit in air is lower than
1.1% by volume. It is considered a moderate fire hazard and a
moderate explosion hazard (violent with metals) (Lowenheim and
Moran, 1975, and other sources). Benzyl chloride is a dangerous
disaster hazard since it will react with water or steam to pro-
duce toxic and corrosive fumes; it can react vigorously with
oxidizing materials (Sax, 1968). Synonyms for benzyl chloride
include alpha-chlorotoluene and alpha-tolyl chloride.
PRODUCTION AND USE/CONSUMPTION
The only processes in commercial use in the United States
for the manufacture of benzyl chloride are the direct chlorination
of boiling toluene in the dark and the photochlorination of
toluene. Boiling toluene is chlorinated in the dark until there
is a 37.5% increase in weight. The reaction mixture is then agi-
tated with mild alkali and distilled. Benzal chloride and
benzotrichloride are formed as by-products of benzyl chloride in
a ratio of 1:0.1:10. In the photochlorination process, chlorina-
tion is continued until a 20 to 25% weight increase in the reaction
mixture is achieved. Using this procedure, it is possible to
avoid the formation of benzotrichloride. In this case the ratio
of benzyl chloride to benzal chloride is 10:1 (Lowenheim and
Moran, 1975).
56
-------
The still bottoms of benzyl chloride production are a hazardous
waste discharge to land disposal and contain 0.001 kg of highly
dangerous components (benzyl chloride and benzotrichloride) per kg
of benzyl chloride produced (Gruber, 1976).
The major commercial producers of benzyl chloride and their
capacities (as of December 1975) are:
Producers
Monsanto, Bridgeport,
N.J.
Stauffer, Edison, N.J.
Tenneco, Fords, N.J.
Total
Capacity
(millions of Ib per yr)
75
11
_9
95
Monsanto had plans to bring another benzyl chloride plant on
stream at East St. Louis, Mo. (Sauget, 111., according to CEH,
November 1976) in 1977 to feed a new benzyl butyl phthalate plant,
The plant capacity was expected to be at least 75 million Ib per
year. The annual demand for benzyl chloride was 90 million Ib in
1975 (Chemical Marketing Reporter, December 12, 1975). Benzyl
chloride is available commercially in an anhydrous form or stabi-
lized with aqueous sodium carbonate solution (Hawley, 1977).
Major uses of benzyl chloride are:
Benzyl butyl phthalate
Benzyl alcohol
Quaternary Amines
Other
Total
67%
13
12
_8
100
Source: Chemical Marketing Reporter,
December 12, 1975.
57
-------
Benzyl butyl phthalate is used as a plasticizer in the
manufacture of flexible vinyl, especially floor coverings.
Growth in demand for flexible vinyl, and hence for benzyl butyl
phthalate, is expected to continue. Benzyl alcohol is used as a
dye assist, as a photographic developer, and in making Pharmaceu-
ticals and perfumes. Benzyl chloride serves as a raw material
for disinfectants, bactericides, perfumes, and Pharmaceuticals.
Benzyl chloride may be used in synthetic tannins and synthetic
penicillin, as a gasoline gum inhibitor, and as an intermediate
in other processes. Benzyl chloride is also used as an inter-
mediate in the production of benzyl acetate, benzyl cyanide,
benzyl salicylate, and benzyl cinnamate. Use of benzyl chloride
as an irritant gas has been reported (IARC, 1976).
BIOLOGICAL ASPECTS
The TWA established by OSHA for benzyl chloride in air is 1
ppm. (Soviet standard for- benzyl chloride in the work place is
0.1 ppm [Hoecker et al., 1977].} The 96-hr aquatic toxicity
rating is 10 to 1 ppm. The LDcg f°r °ral administration of
benzyl chloride is 1,231 mg/kg for rats and 1,624 mg/kg for mice.
Inhalation of benzyl chloride vapors by mice and rats gives LC5Q
values of 80 and 150 ppm, respectively, for 2 hr of exposure
(NIOSH, 1976) . Reaction of guinea pigs to dermal application of
benzyl chloride indicates that it is a strong sensitizing agent
(Hoecker et al., 1977). Benzyl chloride has been found to be
weakly mutagenic in Salmonella typhimurium (TA100) after treatment
with 2 mg benzyl chloride per plate in the Salmonella/microsome
test (McCann et al., 1975).
Benzyl chloride is absorbed by the lungs and the digestive
tract. It appears to be metabolized to benzyl mercapturic acid
following injection in rats and rabbits and oral administration
in dogs. Following oral administration in rabbits, it is excreted
in the urine as mercapturic acid and benzoic acid (IARC, 1976).
58
-------
Fourteen week-old rats were given subcutaneous injections of
40 mg/kg benzyl chloride in arachis oil for 51 weeks. Three
animals developed local sarcomas within 50 days. Of eight rats
given 80 mg/kg benzyl chloride for 51 weeks, six developed local
sarcomas in 500 days.
Most animals also developed lung metastases. Injection of
arachis oil did not produce local tumors in control rats. Based
on this information, the IARC considers benzyl chloride to be a
carcinogen in rats.
Mice given intraperitoneal injections of benzyl chloride
three times a week for 2 to 4 weeks (total dose of 600, 1,500, or
2,000 mg/kg) did not show significant changes in tumor incidence
(Hoecker et al., 1977) .
The human TCLo for inhalation of benzyl chloride has been
found to be 16 ppm. This level of exposure was found to be
intolerable within 1 min (ACGIH, 1971).- Benzyl chloride is
highly irritating to eyes, ears, nose, and throat and can cause
lung edema. It may depress the central nervous system (ITII,
1976) .
ENVIRONMENTAL ASPECTS
Benzyl chloride contamination of aquatic environments seems
unlikely since it is insoluble in water. Benzyl chloride reacts
with oxidizing agents (Dorigan et al., 1976). Benzyl halides are
considered very reactive, having a half-life (hydrolysis) of only
a few minutes. Benzyl chloride is lipophilic as indicated by
its log P value of 2.30 (Radding et al., 1977).
59
-------
REFERENCES
American Conference of Governmental Industrial Hygienists (ACGIH).
Documentation of the Threshold Limit Values. 1971.
Chemical Marketing Reporter, December 12, 1975.
*Dorigan, J. et al. Scoring of Organic Air Pollutants: Chemistry,
Production and Toxicity of Selected Organic Chemicals. MITRE
Corp. (for EPA). 1976.
Gruber, E. I. (Project Manager). Assessment of Industrial Hazardous
Waste Practices, Organic Chemicals, Pesticides, and Explosives
Industries. U.S. Environmental Protection Agency. 1976.
Hawley, Gessner G. Condensed Chemical Dictionary, 9th ed. New
York, Van Nostrand Reinhold Co. 1977.
Hoecker, Jane E. et al. Information Profiles on Potential Occupational
Hazards. Center for Chemical Hazard Assessment (for NIOSH).
1977.
International Agency for Research on Cancer (IARC). IARC Monographs
on the Evaluation of Carcinogenic Risk of Chemicals to Man,
vol. II. Lyon, France. 1976. p. 217-221.
International Technical Information Institute (ITII). Toxic and
Hazardous Industrial Chemicals Safety Manual. Tokyo. 1976.
Lowenheim, Frederick, and Marguerite Moran. Faith, Keyes and
Clark's Industrial Chemicals, 4th ed. New York, John Wiley &
Sons, Inc. 1975.
McCann, Joyce et al. Detection of carcinogens as mutagens in the
Salmonella/microsome test: Assay of 300 chemicals. Proc.
Natl. Acad. Sci. U.S.A. 7£(12) :5135-5139, 1975.
NIOSH. Registry of Toxic Effects of Chemical Substances, 1976 ed.
Radding, Shirley B. et al. Review of the Environmental Fate of
Selected Chemicals. Stanford Research Institute (for EPA).
May 1977.
Sax, N. Irving. Dangerous Properties of Industrial Materials, 3rd
ed. New York, Van Nostrand Reinhold Co. 1968.
*This document was prepared for the U.S. Environmental Protection
Agency by the MITRE Corp. It is a secondary source and does not
cite its primary references. Thus, verification of some information
is not possible. The environmental release data were taken from
the NSF/Rann Research Program on Hazard Priority Ranking of Manu-
factured Chemicals.
60
-------
Stanford Research Institute (SRI). Chemical Economics Handbook,
Menlo Park, Calif. 1976.
Stanford Research Institute. Directory of Chemical Producers.
Menlo Park, Calif. 1975.
61
-------
CHEMICAL HAZARD INFORMATION PROFILE
Bromine and Bromine Compounds
Date of report: November 1, 1976
This group of chemicals was chosen for study because of a
report describing damage to vegetation near bromine production
facilities.
It is recommended that this group of chemicals be considered
for further testing needs. The high potential for the development
of new bromine compounds and new uses for old compounds is the
impetus for testing consideration.
This report represents a preliminary investigation of the
subject chemical's potential for injury to human health and the
environment. The information contained in the report is drawn
chiefly from secondary sources and available reference documents.
Because of the limitations of such sources, it necessarily follows
that this report may not reflect all available information on the
subject chemical.
Any recommendations based on this report are tentative and
should not be construed as final Agency policy with respect to the
subject chemical.
62
-------
CHEMICAL HAZARD INFORMATION PROFILE
Bromine and Bromine Compounds
Date of report: November 1, 1976
GENERAL INFORMATION, PRODUCTION, AND CONSUMPTION
Bromine belongs to the group of nonmetallic elements known
as the halogens, which includes fluorine, chlorine, iodine, and
the extremely rare element astatine. Elemental bromine exists in
the diatomic form, Br2» and it is a volatile liquid at ordinary
room temperature (boiling point 58.8°C at atmospheric pressure).
Bromine is a strong oxidizing agent similar to but weaker than
chlorine. The most stable valence states of bromine are -1 and
+5, although valence states of +1 and +3 are also known.
Bromine is widely distributed in nature in both the solid
portion of the earth's crust (1.6 ppm) and in ocean water (65 ppm
by weight). Bromine is also abundant in the waters of salt lakes
found in closed basins and in the brines or saline deposits left
by the evaporation of such salt lakes during earlier geologic
periods. Brines serve as the primary source of bromine in the
United States; seawater is used as a bromine source in other
parts of the world but not, at this time, in the United States.
Eighty percent of the bromine produced in the United States
is extracted from natural brines in the El Dorado-Magnolia area
of southern Arkansas; most of the remainder is produced in Michigan
(see Table 1). Bromine exists as the bromide ion in these brines,
and obtaining elemental bromine from them entails four essential
steps: oxidation of the bromide in the brine to bromine, removal
of bromine vapor from solution, condensation of the vapor, and,
finally, purification of the product. Initially the brines are
heated from the ground recovery temperature of 90°C to just below
the boiling point of 107°C. Chlorine is added to oxidize the
63
-------
Table 1. DOMESTIC BROMINE PRODUCERS, PLANT LOCATIONS,
AND CAPACITIES (1976)
Company
Arkansas Chemical Inc.
Dow Chemical USA
Ethyl Corp.
Great Lakes Chemical Corp.
Kerr-McGee Corp.
Morton-Norwich Products, Inc.
Northwest Industries, Inc.
Locations
El Dorado, Ark.
Luddington, Mich,
Magnolia, Ark.
Midland, Mich.
Magnolia, Ark.
El Dorado/ Ark.
Marysville, Ark.
Trona, Calif.
Manistee, Mich.
El Dorado, Ark.
St. Louis, Mich.
Capacity
(106 Ib)
60
15
85
105
160
95
45
Unknown
25
5
Total
597
Source: CEH, 1976.
64
-------
bromide ions and replace them in the brine. The released bromine
is separated from the brine by "blowing out" with steam and is
then purified by distillation and dried with sulfuric acid. The
chlorine is recycled, and bromine recovery is generally in excess
of 95% (Stenger, 1964; CEH, 1976).
Table 2 shows the annual production and consumption of
bromine for recent years. As can be seen from these data, most
of the elemental bromine is used to manufacture bromine-
containing compounds. The largest end use of bromine, currently
accounting for about 50-60% of bromine consumption, is for the
production of ethylene dibromide (EDB), which is used primarily
as a lead scavenger in gasoline. In past years, EDB has accounted
for well over 90% of bromine consumption. The decline in EDB use
in recent years has been due largely to the lowering of the lead
content of gasoline and the conversion to nonleaded gasoline for
newer model cars. The second largest end use of bromine is for
the production of methyl bromide, which is used as a pesticide,
soil and grain fumigant, and fire-extinguishing fluid.
«
.The elemental bromine consumption data shown in Table 2
refer to that which is sold by primary producers. Some of this
is used directly for such applications as a bleaching and disinfect-
ing agent/ swimming pool sanitation, and water purification; some
is sold to other companies to be used in the production of bromine
compounds.
The "Other" category in Table 2 includes the numerous
organic and inorganic bromine compounds that are produced by too
few companies for production data to be available from the Inter-
national Trade Commission. In addition to elemental bromine
itself, the major inorganic bromine compounds are hydrobromic
acid and the bromide salts (potassium, sodium, and ammonium).
Hydrobromic acid is used as an industrial chemical for the pro-
duction of other bromine compounds; the alkalai bromides are used
65
-------
Table 2. U.S. REPORTED PRODUCTION, IMPORTS, EXPORTS, AND
CONSUMPTION OF BROMINE AND BROMINE COMPOUNDS3
(millions of pounds)
Year
1970
1971
1972
1973
1974
1975
Br0
2
production
350
356
387
418
432
417
Percentage (bromine content)
Imports'
0.14
0.01
0.05
0.06
0.02
0.03
Exports
8
20
30
55
69
70
r> Ethylene
2 dibromide
7 73
9.5 68.5
9.5 70
9.5 69.5
11 59
92
Methyl
bromide Other
-b 20
-b 22
5.5 15
4.5 16.5
4 26
8
Consumption as compounds sold by primary producers of bromine; Br~ consumption
for direct use and intermediate use by secondary users.
blncluded in "Other" for 1970-71.
Source: CEH, 1976.
-------
in the preparation of sedatives, medicines, and photographic
emulsions. The end use of inorganic bromine compounds noted as
having future growth potential is that of water and waste treatment.
Elemental bromine, as noted above, and bromine chloride (BrCl)
are the bromine compounds likely to be important in such applications.
There are many organic bromine compounds, both aliphatic and
aromatic, which are available commercially for a variety of
applications, including uses as intermediates, agricultural
chemicals, photographic chemicals, dyes, inks, medicinals, hydraulic
fluids, coolants, cosmetics, and reagents. The fastest growing
end use for organic bromine compounds, however, is in the area of
fire- and flame-retardant chemicals. Consumption of bromine for
this end use has grown from 10 million Ib in 1964 to 56 million
Ib in 1974, with the largest growth in the most recent years.
Some of these compounds are used as fire-extinguishing agents
(bromotrifluoromethane and bromochlorodifluoromethane), some are
used as monomers for fibers, plastics, and foams (for example,
tetrabromobiphenol A and tetrabromophthalic anhydride), and some
are simple additives to synthetic resins [for example, tris(2,3-
dibromopropyl) phosphate, though this compound is now being
phased out].
The most notable feature of the bromine industry at this
time is its changing character with respect to outlets. The lack
of market diversification in the past, when almost all of the
bromine produced was converted to EDB, is now being overcome as
the number of bromine compounds available and the specific applica-
tions of these are on the increase. The general trend appears to
be toward continued, vigorous growth, particularly in the flame
retardants market, and possibly significant growth in the area of
water and waste treatment.
67
-------
HEALTH AND ENVIRONMENTAL PROBLEMS
The following are brief discussions of the health and environ-
mental problems relating to bromine that appear, from this prelimi-
nary investigation, to be of particular importance.
Bromism
"Bromism" is the clinical term for the condition associated
with excessive tissue levels of bromide ions. The symptoms of
bromism are subtle, though well established: slowing of cerebra-
tion, impaired memory, anorexia, skin rash, headache, slurring of
speech, confusion (Campbell, 1949), weakness, disturbed reflexes
(Neiswander, 1958), drowsiness, and mild conjunctivitis (Woodbury,
1972). The blood bromide concentration needed to evoke the
symptoms of bromism is dependent upon the individual; severe
reactions are known to occur with bromide levels as low as 0.5
rag/ml of blood. Generally/ however, intoxications of 0.5-1.5
mg/ml of blood are deemed moderate, while levels above 1.5 mg/ml
are severe (Campbell, 1949).
The most common cause of bromism is the abuse of bromide-
containing patent medicines, although occupational exposure
(Shapovalov et al., 1974) and ingestion of well water with high
bromide levels (Fried and Malek-Ahmadi, 1975) may also lead to
the onset of the condition. Chronic exposure to a bromide source,
even at low concentrations, may lead to bromism because of the
long plasma half-life of the bromide ion. Woodbury (1972) estimates
that the half-life of the ion in the human is at least 12 days.
Ingested bromide ions are preferentially retained by the kidneys
at the expense of chloride; thus chloride levels in the body are
depressed in direct proportion to the bromide elevation. For
instance, the CNS effects of bromism are traceable to bromide
replacement of chloride ions in the brain. Bromism, however,
does not result in permanent damage to the CNS or other body
68
-------
functions; with removal of the bromide source, recovery is generally
rapid (Woodbury, 1972).
There is one instance reported in the literature of a possible
teratogenic effect associated with bromism. Opitz et al. (1972)
detail a woman who had two normal children prior to a 5-year bout
with bromism. During the period of heaviest bromide intake, she
had two boys who differed from the two siblings born previously.
The two boys were short (second percentile for age) and had small
heads (one was definitely microcephalic), and the microcephalic
child had a congenital heart defect. Following this period, the
woman was taken off bromides and gave birth to a normal boy.
The metabolism of bromides is closely related to the function-
ing of the thyroid gland in man. Bromide blocks the entry of
iodide into the thyroid and, with chronic bromide administration,
can lead to thyroid tissue hyperplasia, better known as goiter.
Several of the effects of bromism are identical to those attributed
to hypothyroidism.
Toxicity of Organic Bromine Compounds
Organobromines tend to exhibit greater toxicity than inorganic
bromine compounds. The effects associated with organobromine
compounds include damage to the CNS, male reproductive system,
kidneys, and liver. In addition, several organic bromide compounds
have been implicated as mutagens and/or carcinogens.
A summary of the toxic effects of some common organic bromides
follows:
(a) Methyl bromide—chronic exposure to low levels can be
fatal due to CNS and kidney damage (Sax, 1968).
69
-------
(b) Bromoform—has a. narcotic effect similar to that of
chloroform, but is more toxic to the liver (Sax/ 1968).
(c) Ethyl bromide—less toxic than methyl bromide, but can
damage the liver and kidneys (Sax, 1968).
(d) Ethylene dibromide (EDB)—affects the liver and kidneys
(Sax, 1968); has been shown to damage the male repro-
ductive system in bulls (Amir, 1973) and rats (Edwards
et al., 1970).
(e) l,2-Dibromo-3-chloropropane (Nemagon, DBCP)—chronic
exposure leads to liver, kidney, and lung damage
(Gleason et al., 1969); has been shown to affect the
male reproductive system in rats (Gleason et al., 1969;
Faidysh and Avkhimenko, 1974).
Nemagon and EDB are also"known mammalian carcinogens (Olson
et al., 1973), while several organobromine compounds have been
found mutagenic:
(a) 1,2-EDB, 1,1-EDB, l-bromo-2-chloroethane, 1,5-dibro-
mopentane, 1,2-dibromo-2-methylpropane, and 1,1,2,2-
tetrabromopentane in E. coli and S. typhimurium (Brem
et al., 1974).
(b) 1,2-EDB and 1,2-dibromopropane in Drosophila melanogaster
(Vogel and Chandler, 1974).
Generally, organobromo compounds have greater mutagenic and
DNA-modifying activity than their chloro analogs (e.g., EDB >
EDC). In addition, the biological activity is enhanced when more
than one bromine is attached to the same carbon atom (1,1-EDB >
1,2-EDB). When the halogens are on different carbons, however,
the distance between the halogens has no appreciable effect on
the activity (Brem et al.f 1974).
70
-------
Bromine Phytotoxicity and Other Problems in Arkansas
As noted previously, most domestically produced bromine Is
extracted from brines in the El Dorado-Magnolia area of Arkansas.
Bromine released as a consequence of these production activities
has had serious effects upon vegetation in the locale. The first
noted manifestation of a problem was damage to coniferous trees
near the bromine plants. Needle tip necrosis after 13- to 14-
month and 1- to 2-month exposure times was very evident within a
3-mile radius of all bromine facilities sampled. At further
distances of 3.5 to 12 miles, tip damage was sporadic, varying
from tree to tree, and not evident on 1- to 2-month-exposure
needles. The foliage burn and death of trees within 0.5 to 1
mile of each plant site was extreme. Conifers were decidedly
more susceptible to the bromine emissions than were broadleaf
trees, shrubs, and grasses. Chlorophyll (a and b) levels were
greatly reduced in the conifer trees surrounding the bromine
plants. This was taken as a strong indicator of extreme air
pollution problems because chlorophyll does' not reflect environ-
mental problems until they become overwhelming (Gordon, 1976).
The evidence of vegetative damage prompted the initiation of
air-monitoring activities in the locality. Preliminary results
have shown the presence of several potentially dangerous organo-
bromine compounds in the air near the bromine production sites.
Bromine and Stratospheric Ozone
In the past few years, there has been increasing concern
over the depletion of the earth's protective stratospheric ozone
layer by various human activities. The reduction of stratospheric
ozone could have severe adverse effects on climate, agriculture,
and skin cancer rates. At the forefront of this area, recently,
has been the theory that certain widely used chlorofluorocarbon
aerosol propellants and refrigerants are transported into the
71
-------
stratosphere by atmospheric motions, where the chlorine atoms in
the molecules are released by photolysis. The chlorine then
acts, through a catalytic cycle, to destroy ozone molecules. It
has also been recognized that, like chlorine, any bromine entering
the stratosphere will also destroy ozone catalytically. Further-
more, the bromine cycle is believed to be more efficient in
destroying ozone than is the chlorine cycle.
Many of the manmade bromine compounds do not appear to be of
significance to stratospheric ozone because of properties or use
patterns which would preclude their reaching the stratosphere.
Others have been identified as potential problems, such as methyl
bromide, for which Wolfsy et al. (1975) have cautioned against
unconstrained growth in use. Still other compounds, now produced
in too small a quantity to be a significant threat (for example,
•the fire-extinguishing agents bromotrifluoromethane and bromo-
chlorodifluoromethane), have properties which clearly indicate
that they could, if produced in larger amounts, be of serious
concern.
Bromine Compounds in Water
r
One of the potential growth areas for bromine is in the
purification of drinking water. The switch from chlorine to a
bromine or bromine chloride water sanitation system is not without
possible health implications. Bunn et al. (1975) found that the
addition of KBr to natural Missouri River water caused a substantial
reduction in the chloroform concentration while increasing the
levels of bromodichloromethane, dibromochloromethane, and bromoform
found in the sample. As noted earlier in this report, brominated
compounds generally display greater biological activity than
their chlorinated analogs. In view of this, any purification
technique which may increase the levels of brominated methanes in
drinking water should be carefully evaluated before being allowed
to come into operation.
72
-------
Another aspect of this problem is the influence of man's
other activities on the bromine levels found in natural surface
waters. Bromine should be a conservative property of water
(Skopintsev [1973] estimates bromine's half-life in the Black Sea
to be 1,800 years) and will not be efficiently removed via biological
or sedimentation processes. Tiffany et al. (1969) report that
the bromine concentration in the Great Lakes has increased
steadily with time as a consequence of both pollution and natural
processes. The major pollution sources are auto emissions and
industrial effluents.
A final problem with bromine concerns the naturally occurring
levels of bromine found in well waters. Fried et al. (1975)
speculate that some instances of bromism in rural areas are
actually due to bromide contamination of drinking water. They
cite the occurrence of 0.08% bromine in a soft-water source in
Kansas as an extreme example of what may be a real, though unrecog-
nized, problem.
SUMMARY AND CONCLUSIONS
Bromine is found naturally in the environment at relatively
low levels. As a consequence of human activities, however, the
concentration of bromine found in the ambient environment has
greatly increased. Most of this rise is due to bromine released
to the atmosphere following the combustion of leaded gasoline,
although other sources (industrial processes, wastes, etc.) have
contributed as well.
The long-term health and environmental implications of
elevated bromine levels, while not known with certainty, are of
some concern. The carcinogenic and mutagenic activity associated
with organobromine compounds represents the most immediately
evident of these concerns. The significance of the other problem
areas outlined in this paper is more difficult to appreciate.
73
-------
Bromism, for instance, may occur as the direct result of increased
exposure to Br~ in air and, particularly, water. Current exposure
data, however, are not available to assist in the delineation of
the problem. This, in combination with the subtle nature of
bromism, keeps the problem vague. The bromine-stratospheric ozone
situation, bromine as a water sanitizer, and the extent of the
Arkansas problem are also poorly defined. The information gaps
preclude any considered assessment of the significance of each at
this time.
Presently, bromine use and consumption patterns are changing
and thereby altering the nature of the anthropogenic source. The
declining demand for EDB is forcing the bromine industry to find
new outlets for the anticipated bromine glut. Fire- and flame-
retardant materials are currently seen as one of the growing
consumptive uses of bromine; however, other product types must be
developed before the bromine market will firm up. The anticipa-
tion is that TSCA will play a large role in decisions as to the
acceptability of these new products and uses.
74
-------
REFERENCES
Amir, D. Sites of spermicidal action of ethylene dibromide in
bulls. J. Reprod. Pert. 3J[(3) :519-525, 1973.
Brem, H., A. B. Stein, and H. S. Rosenkranz. The mutagenicity and
DNA-modifying effect of haloalkanes. Cancer Res. 34:2576-
2579, 1974.
Bunn, William E., Bernard B. Haas, Edward R. Deane, and Robert D.
Kleopfer. Formation of trichloromethanes by chlorination of
surface water. Environ. Lett. 10.(3) :205-213, 1975.
Campbell, J. D. Bromide intoxication. South. Med. J. 42:697-
673, 1949.
Chemical Economics Handbook (CEH). Menlo Park, Calif., Stanford
Research Institute. 1975, 1976.'
Edwards, K. et al. Studies with alkylating agents. II. A chemi-
cal interpretation through metabolic studies of the anti-
fertility effects of ethylene dimethane-sulfonate and ethyl-
ene dibromide. Biochem. Pharmacol. 19^:1783, 1970.
Faidysh, E, V., and M. G. Avkhimenko. Effect of the nematocide
nemagon on the reproductive function of an organism. Tr.-
Uzb. Naucho-Issled. Inst. Sanit., Gig. Profzabol. 8:42-43,
1974. (Abstract) ""
Fried, Frederick E., and Parviz Malek-Ahmadi. Bromism: Recent
perspectives. South. Med. J. 6£(2):220-222, 1975.
Gleason, M. N., R. E. Gosselin, H. C. Hodge, and R. P. Smith.
Clinical Toxicology of Commerical Products, 3rd ed. Balti-
more, The Williams and Wilkins Co. 1969.
Gordon, C. C. Report on coniferous vegetation collected in Union
County and Magnolia area, Arkansas. Unpublished report, July
1976.
Neiswander, A. C. Bromide poisoning. J. Am. Inst. Homeopathy
5_1:104-105, 1958.
Olson, W. A. et al. Induction of stomach cancer in rats and mice
with halogenated aliphatic fumigants. J. Natl. Cancer Inst.
5jL(6) :1993-1995, 1973.
Opitz, J. M., F. R. Grosse, and B. Haneberg. Congenital effect of
bromism. Lancet U7741):91-92, 1972.
Sax, N. Irving. Dangerous Properties of Industrial Materials, 3rd
ed. New York, Van Nostrand Reinhold Co. 1968.
75
-------
Shapovalov, Y. D. Effect of elemental bromine and its compounds
on the organism of workers. Vrach. Pelo 12_: 110-115, 1974.
(Abstract)
Skopintsev, B. A. Average residence times of some elements in
Black Sea water. Okeanologiya 1_3_(6) : 1015-1019, 1973.
(Abstract)
Stenger, V. A. Bromine. In Kirk-Othmer Encyclopedia of Chemical
Technology, 2nd ed., vol. 3. 1964. p. 750-766.
Tiffany, Mary A., John W. Winchester, and Ronald H. Loucks.
Natural and pollution sources of iodine, bromine and chlorine
in the Great Lakes. J. Water Pollut. Control Fed. 41(7):1319-
JL329, 1969.
Vogel, E., and J. L. R. Chandler. Mutagenicity testing of cycla-
mate and some pesticides in Drosophila melanogaster. Experi-
mentia 310:621-623, 1974.
Wolfsy, Steven C., Michael B. McElroy, and Yuk Ling Yung. The
chemistry of atmospheric bromine. Geophys. Res. Lett. 2(6):215-
218, 1975.
Woodbury, D. M. Antiepileptic "drugs: Bromides. In Antiepileptic
Drugs. 1972. p. 519-527.
76
-------
CHEMICAL HAZAED INFORMATION PROFILE
Carbon Black
Date of report: August 1, 1976
This chemical was chosen for study because of its high production volume
and its potential for adsorbing carcinogenic substances.
It is reccmnended that OTS update its literature search on carbon black,
since this report was written sane time ago. Carbon black is reccmnended for
testing consideration because of the potential for widespread exposure to the
PNAs present in carbon black.
This report represents a preliminary investigation of the subject chem-
ical's potential for injury to human health and the environment. The infor-
mation contained in the report is drawn chiefly from secondary sources and
available reference documents. Because of the limitations of such sources,
it necessarily follows that this report may not reflect all available infor-
mation on the subject chemical.
Any reconrnendations based on this report are tentative and should not be
construed as final Agency policy with respect to the subject chemical.
77
-------
CHEMICAL HAZARD INFORMATION PROFILE
Carbon Black
Date of report: August 1, 1976
ABSTRACT
Carbon black, the darkest and most finely divided substance
known to man, is produced in large quantities and is used primarily
as a reinforcing agent in the manufacture of rubber tires. While
there appears to be no significant direct toxic effect of carbon
black itself, there is a question of a hazard due to carcinogenic
polycyclic aromatic hydrocarbons known to be adsorbed en some
types of carbon black. The bioavailability of these adsorbed
carcinogens under conditions of human exposure has not yet been
adequately demonstrated, and therefore the human health hazard of
carbon black is equivocal. Pollution from the production of
carbon black is minimal, but through tire wear and disposal of
old tires, carbon black can reach the general environment.
PHYSICAL AND CHEMICAL PROPERTIES
Carbon black is elemental carbon in particulate form. The
individual carbon atoms are arranged in platelets measuring 12 x
24 angstroms (A), similar to graphite, but with the platelets
stacked only roughly parallel to one another. There are four
basic types of carbon black, generally classified according to
the production processes used for their manufacture. The four
major processes for carbon black production are the furnace
(either oil or gas) process, the thermal process, the channel
process, and the lamp process. Acetylene black is a special type
of thermal black utilizing acetylene as the make gas.
The properties of carbon blacks are a function of the process
used to make the material. Table 1 presents the ranges of properties
78
-------
Table 1. TYPICAL ANALYTICAL PROPERTIES FOR SELECTED CARBON BLACKS
10
Type and process
Channel process gas blacks
High-color channel
Medium-color channel
Regular-color channel
Easy-processing channel
Medium-processing channel
Medium-flow channel
Long- flow channel
Furnace process gas blacks
Fine furnace
High-modulus furnace
Semireinforcing furnace
Furnace process oil blacks
Superabrasion furnace
Intermediate superabrasion
furnace
Intermediate superabrasion
furnace, low structure
Intermediate superabrasion
furnace, high structure
High-abrasion furnace
High-abrasion furnace,
low structure
High-abrasion furnace,
high structure
Fast-extruding furnace
General-purpose furnace
Conductive furnace
Average
particle
diameter
(A)
90-140
150-170
220-290
300-290
250-280
230-250
220-280
400-500
600
600-800
180-220
230-250
200-230
225
260-280
250-265
220-250
400-450
500-550
210-290
Surface
area (N-
adsorption,
m2/q)
1000-400
550-320
140-100
100
110-120
200-210
300-360
40-50
30-40
25-30
90-125
115
110-130
110-130
74-100
85-110
80
40-45
25-30
125-200
Volatile
matter
content (%)
16-5
10-5
5
5
5
7-8
12
1.0
1.0
1.0
1.0
1.0
1.5
1.5
1.5
1.5
1.5
1.0
1.0
1.5-2.0
£H
3-4
4-5
5
5
5
4
3.5
8-S
8-9
8-9
8-9
8-9
8-9
8-9
8-9
8-9
8-9
9
9
8-9
Benzene
extract
(%)
None
None
None
None
None
None
None
0.05
0.10
0.15
0.05
0.05
0.05-0.1
0.05
0.05
0.05
0.05
0.05
Of\ C.
.05
0.06
Oil
adsorption
(cm3/g)
2-4
1.5
IT
. 1
1.0
1.0
1.1
1*^
.2
0.9-1.1
0.85
0.7-0.8
1.5
1.3
0.8-0.9
1.4-1.6
11 C
.15
0.7-0.8
1.4-1.6
In -I M
. 3-1.4
OQ
. y
1-5
. 0
-------
Table 1 (Continued)
Thermal process gas blacks
Fine thermal
Medium thermal
1,800
4,700
Other processes
Lampblack 650-1,000
Acetylene black Shawinigan 420
13
7
20-40
64
0.05
0.05
0.4-9
0.3
9
8
1.75
0.3
3-7 0.01-0.5
5-7 0.1
0.3-0.5
0.3-0.5
1.3-2
3.4
CO
o
-------
for different kinds of carbon blacks. Distinctions between types
of various carbon blacks are based on particle size, surface
area, chemical composition of the surface, and the extent of
particle-to-particle association.
Under an electron microscope, all types of carbon blacks
appear to be spherical particles that are more or less associated
into loose chains. This tendency to form chains is known as
chain structure, or simply structure, and has been correlated to
compressibility and oil absorption. Structure has an important
effect on the properties that carbon blacks give to rubber formu-
lations, affecting ease of extrusion, electrical conductivity,
and elastic modulus. Generally, channel and thermal blacks
are low in structure, lampblacks are high, and furnace blacks
exhibit a wide range, depending on production procedures.
Channel carbon black particles range from 100-400 A, thermal
blacks from 1,400 to over 4,000 A, lampblacks from 600-4,000 A,
and the versatile furnace blacks from 180-800 A. Surface area
values, expressed in m^/g of black, are usually determined in one
of two ways. One method of calculation is by measurement of
average particle diameter; however, errors are introduced into
this method through decreases in surface area in aggregated
particles. A more convenient method is determining N2 adsorption
at -193°C, where the quantity of N2 corresponding to monolayer
coverage can be graphically determined. This method gives external
and internal surface area, and in porous blacks values two or
three times those obtained through calculations from measured
diameters may result. Highly porous blacks are those with a more
irregularly arranged crystalline structure.
When first collected, the bulk density of carbon black is
about 3-10 lb/ft3. Removal of occluded air raises this to 6-15
lb/ft3. When pelletized for shipping, the bulk density of carbon
81
-------
black ranges from 20-30 lb/ft3. More precise values for specific
density, obtained through helium displacement methods, give
values of about 1.86 g/cm3.
The chemical composition of certain carbon blacks is shown
in Table 2. Carbon black is 90-99% pure carbon. Oxygen and
hydrogen are present primarily as complexes with surface carbon
resulting from interactions after the black has been formed.
Some such complexes are hydroxyl, carbonyl, and carbonic acid
groups, some aromatic hydrogen, lactones, and heterocyclic ethers.
Many carbon blacks adsorb polycyclic aromatic hydrocarbons (PAHs)
during production; PAHs that have been identified include benzo-
pyrene, naphthalene, acenaphthylene, phenanthrene, fluoranthrene,
pyrene, cyclopentapyrene, phenalenone, benzperylene, anthanthrene,
and coronene. PAHs comprise what is often referred to as the
benzene extractable content of carbon black. Other contaminants
include 0.01-0.2% sulfur from that present in the raw material
and a few tenths of a percent of ash from the water used to
quench the hot black in manufacture. The volatile content of
carbon black is the percent weight loss after heating to 927°C.
This is mostly carbon monoxide or carbon dioxide, and is generally
between 1 and 2%, though in some channel blacks this may be up to
181. The chemical properties and reactions of carbon black
resemble those of polynuclear aromatic compounds, and most blacks
exhibit a typical -aromatic basicity, with normal pH values ranging
from 8-10. A high proportion of surface oxygen groups tends to
lower the pH, correlating nicely with an increased volatile
content.
PRODUCTION
All types of carbon blacks are produced by thermal decomposi-
tion of hydrocarbons, either through partial burning or by straight
heating. High temperatures that promote uniform conditions for
rapid heat transfer, rapid production of particles, proper dilution
82
-------
Table 2. CHEMICAL COMPOSITION OF CERTAIN CARBON BLACKS
(% by weight)
C_ 0 H Volatile content
High-color channel 88.4 11.2 0.4 18
Long-flow channel 90.0 8.7 0.8 12
Reinforcing channel 95.2 3.6 0.6 5
Semireinforcing channel 99.2 0.4 0.3 1.2
Reinforcing oil furnace 98.0 0.8 0.3 1.4
Thermal acetylene 99.5 — 0.05 0.06
83
-------
of starting material, and protection from oxidation are necessary
for production of small and uniform particle size. Lampblack is
produced by burning petroleum oils and coal tar by-products in
shallow open pans with a restricted air supply. In the channel
process, natural gas is burned in many small fan-shaped flames
just below continuously moving channel irons. Insufficient air
for complete combustion is provided, and carbon black forms in
the flame and is deposited by impingement on the channel.
Stationary scraper blades remove the black from the channels.
About 5% of the carbon in the gas is recovered as black, but new
techniques of enriching the gas with oil are being used because
of the rising price of natural gas.
Thermal blacks are produced by the thermal decomposition of
natural gas in the absence of air. Unlike all the other methods
of carbon black production, the thermal process is cyclic rather
than continuous in operation. The generator, which is a large
furnace filled with a checkerwork of silica brick, is heated to
2,400-2,800°C by complete combustion of natural gas and air.
When the desired temperature is obtained, the air is cut off and
natural gas is admitted for the decomposition stage. The heat
from the brickwork cracks the gas to elemental carbon and hydrogen
gas. When the brick is too cool for further cracking, the gas is
cut off and the. carbon smoke is flushed from the generators. The
cycle then repeats, with reheating of the checkerbrick by com-
bustion of gas and the hydrogen produced in the decomposition
cycle. About 40-50% of the carbon in the fuel is recovered. The
particle size can be controlled somewhat by diluting the natural
gas with recirculated resultant gas, which allows smaller carbon
particles to form in the more dilute atmosphere.
The furnace process, which now dominates the carbon black
industry, is similar to the channel and lamp processes in that it
also involves incomplete combustion of hydrocarbons, but in the
furnace process this takes place in a large furnace with a single
flame utilizing large volumes of hydrocarbons and air. In the
84
-------
gas furnace process, air and natural gas are mixed and ignited in
the ratios required for properly incomplete combustion. Adjust-
ment of air/gas ratio, flow, and turbulence allows the character-
istics and yield of the black to be regulated. For larger size
gas furnace blacks, the yield may be between 25 and 30%, while
the production of small particles recovers only about 10-15% of
the total carbon. In the oil furnace process, air and natural
gas are burned completely in a process separate from the decompo-
sition step. The oil, typically a highly aromatized petroleum
oil, is atomized and injected into the heat of the swirling zone
of complete combustion, where it is decomposed to a fine carbon
smoke and hydrogen gas. Here again, the qualities of the black
can be adjusted, but over a very wide range in this case, by
changing ratios in the oil/air/gas mixture and in furnace and
injector design. Yields in this process are high, typically
around 55%, and will vary between 35 and 65%.
After the thermal decomposition step has taken place, the
black must be collected and packaged for further use. In the
lamp process, most of the black is collected through precipitation
in large settling chambers. Channel black is primarily collected
directly by scraping from the channels themselves. Neither of
these measures is completely efficient, and collecting devices
such as cyclones, precipitators, and filters are employed to
varying degrees. The off-gas from the thermal and furnace processes,
which contains the suspended carbon black particles, must first
be cooled to about 500°C in a spray tower. Following this step,
collection devices such as electrostatic precipitators, wet
scrubbers, cyclones, and bag filters are used to collect the
black. In older plants, electrostatic precipitators and cyclones
were widely utilized, but due to economic and versatility problems
with precipitators as well as greatly improved designs for bag
filters, the presently preferred set-up for collection systems
consists of an agglomerating device or cyclone followed by bag
filters. This sequence of collectors will remove over 99% of the
carbon black from the combustion gases.
85
-------
The recent trends in carbon black production have been to
shift emphasis away from channel black, which historically played
a large role, to furnace black due to advances in furnace tech-
nology which allow a wide range of blacks with properties similar
to channel blacks to be produced. Furnace black now makes up
almost 92% of U.S. production, thermal black about 8%, with
channel and lampblack together comprising less than 0.1% of the
total output.
Production data for carbon blacks are shown in Tables 3 and
4.
USES
Carbon black consumption data are shown in Table 5. About
93% of the carbon black produced in the United States is consumed
by the rubber industry; of this, 90% is used as a reinforcing .
agent in rubber tires. About 6-7 Ib of carbon black goes into
each tire, the primary effect of which is to extend the abrasion
resistance and thus the useful life of the tire. The type of
carbon.black used and the amount added also affect the electrical
conductance, heat buildup, resilience, flex resistance, and
processing characteristics of the rubber. Besides tire treads,
carbon black is also added to rubber belts, hoses, wire insulation,
flooring, motor mounts, and rubber gaskets. All kinds of carbon
black are utilized for these applications, depending on the
specific characteristics required.
The second largest consumer of carbon black is the ink
industry, especially for use in newsprint. Furnace black has
largely replaced channel black for this application. Channel and
furnace blacks are also used in book, letterpress, lithographic,
gravure, carbon paper, and typewriter ribbon inks. Other pigment
applications for various grades of carbon black include uses in
paints, lacquers, enamels, coloring plastics, black paper, nylon
and other fibers, tinting dispersions, and as a toner in electrostatic
copying machines.
86
-------
Table 3. CARBON BLACK PRODUCTION BY
(millions of pounds)
PROCESS
Year
1960
1961
1962
1963
1964
1965
1966
1967
1968
1969
1970
1971
1972
1973
1974
Furnace
1,612
1,572
1,677
1,686
1,821
1,933
2,142
2,028
2,364
2,505
2,506
2,629
2,930
3,170
3,116
Thermal
149
145
172
194
232
272
276
306
305
326
312
342
249
316
274
Channel
292
262
207
179
170
148
153
149
143
132
114
46
22
14
^ ^"
Total
2,054
1,980
2,056
2,059
2,223
2,354
2,572
2,484
2,812
2,963
2,931
3,017
3,201
3,500
3,390
Table 4. CARBON BLACK PRODUCTION BY RAW MATERIALS
(millions of pounds)
Year
1960
1961
1962
1963
1964
1965
1966
1967
1968
1969
1970
1971
1972
1973
1974
From natural gas
638
598
537
543
574
593
524
466
455
456
381
322
271
246
•__
From liquid hydrocarbons
1,415
1,381
1,520
1,516
1,649
1,761
2,048
2,018
2,357
2;507
2,550
2,695
2,930
3,254
3,207
87
-------
Table 5. CARBON BLACK CONSUMPTION BY END USE
(millions of pounds)
Year
1960
1961
1962
1963
1964
1965
1966
1967
1968
1969
1970
1971
1972
1973
1974
Elastomers
1,363
1,383
1,551
1,630
1,789
1,946
2,131
2,072
2,446
2,616
2,486
2,678
2,954
3,115
2,925
Printing inks
48
43
41
46
46
54
64
64
68
73
73
75
82
84
83
Paint
12
15
16
13
18
11
12
13
13
18
15
19
21
22
19
88
-------
Other useful applications of carbon black are as an anti-
static agent in phonograph records, to prevent photo and thermal
oxidation in polyolefins, in black tape for wrapping high-voltage
transmission cables, in dry-cell batteries (acetylene black), for
high-temperature insulation, and in carbon electrodes (lampblack).
The Food and Drug Administration (PDA) has lifted its con-
ditional approval of channel black for use as a food color additive
for licorice and jellybeans. This was done because the industry
could not meet the conditions of approval, which were requirements
for specifications to differentiate channel from other types of
black and for analytical methods to detect PAHs in channel black
at a level of 2 ppb. The only other black approved for food-
associated use by the FDA is furnace black, which may be incor-
porated at less than 10 ppb into rubber articles for repeated use
in food preparation.
BIOLOGICAL ASPECTS
Much of the original toxicity testing of carbon black was
carried out by Carl Nau, Jack Neal, and Vernie Steinbridge in the
late 1950's, and their work is still the most complete body of
information on carbon black available. Their work, like most of
the available literature, concentrates on the carcinogenic poly-
cyclic aromatic hydrocarbons, especially benz(a)pyrene, that are
known to be adsorbed on several types of black. Channel blacks
are low in this benzene extractable content, thermal and lamp-
blacks are high, and furnace blacks fall into an intermediate
category. Blacks with average diameters under 300 A usually
contain no PAHs, while those over 500 A contain a variety (Steiner,
1954).
Male mice fed a diet containing 10% furnace black for 72
weeks showed no gross changes from controls, while alive or when
autopsied, whereas animals given the benzene extract of this
black incorporated into the diet developed a significant number
89
-------
of tumors in the gastrointestinal tract (Nau et al., 1958). In
another study, various air pollutant particulates including
carbon blacks were incorporated into the diet of 83 mice, of
which 8 developed gastric tumors (Neal and Rigdon, 1969).
Nau and his associates (1958) painted the skins of mice,
rabbits, and monkeys with a 20% suspension of carbon black in
water, cottonseed oil, or mineral oil three times per week for a
year and observed no changes from controls, while the benzene
eluted component of the same black induced skin malignancies in
all three species.
In another set of experiments, 300-mg pellets of carbon
black from which benz(a)pyrene could be eluted were injected
subcutaneously into mice and induced two sarcomas in 50 mice. A
black which did not yield any PAHs on benzene elution was able to
induce one sarcoma in 50 mice when similarly injected, although
the same carbon black with 0.09 mg of benz(a)pyrene added failed
to produce any sarcomas. The benz(a)pyrene-containing carbon
black induced 18 tumors in 50 mice when 300 mg was injected
subcutaneously with tricarprylin, an oily solvent (Steiner,
1954).
Pylev (1970).reintroduced benzopyrene into channel and
thermal blacks from which the absorbed compounds had been "burned
out" by heating at 900°C. These carbon blacks, containing 0.01
mg of benzopyrene per 1.0 mg of black, were given in 60-mg doses
to rats by intratracheal intubation. The channel black thus
administered induced tumors in 40.4% of 52 rats in 16 months, and
the thermal black induced lung tumors in 24% of 50 rats in 10
months.
Nau and his associates (1962) carried out a fairly extensive
series of inhalation studies on carbon black. Mice (for their
lifespan), guinea pigs, and monkeys (up to 13,000 total hours)
were exposed to 1.6 mg/m3 of various types of furnace blacks for
*
7 hr per day, 5 days per week. No tumors were induced in any of
90
-------
the animals studied. In histological studies, carbon black was
found scattered through lung tissue both free-lying and inside
macrophages (scavenger cells). In mice, the black was diffuse
and finely distributed, while monkeys progressively developed
diffusely distributed areas of nodularity where the black was
concentrated. The walls of the alveoli tended to be thickened,
and in some animals there was some minimal fibrosis which did not
progress with continued exposure. Carbon black was observed to
infiltrate the pulmonary lymph nodes, and was also present in the
liver/ spleen, and kidneys of exposed animals but with no apparent
effect. Inhalation of furnace black did produce an increase in
the heart weight/body weight and lung weight/body weight ratios
in mice. Monkeys inhaling furnace carbon black showed electro-
cardiographic changes indicative of atrial and right ventricular
strain after 2,500 hr of exposure. Inhalation by monkeys of a
thermal black resulted in right and left ventricular and septal
hypertrophy. Tests of pulmonary function in mice exposed to
thermal blacks and monkeys exposed to furnace blacks indicated no
changes in air flow or gas exchange.
The key question in the problem of carbon black carcino-
genicity appears to be the degree to which the adsorbed carcino-
genic PAHs are able to be removed from the carbon black under
conditions of human exposure. Human blood plasma, artificial
gastric juice, or artificial intestinal juice did not elute any
PAHs from channel or furnace blacks after 120.5 hr at 28°C and 60
hr at 37°C with intermittent shaking. Cottonseed oil, aqueous
citric acid (pH 3.85), 3% aqueous acetic acid, 3% aqueous sodium
bicarbonate, 3% aqueous sodium chloride, and whole milk did not
remove any PAHs from carbon blacks incorporated into a commercial
rubber fabrication after 7 days at 138°F (Neal et al., 1962).
Alveolar and peritoneal macrophages are able in vitro to elute
benzopyrene from carbon blacks to which it has been added (Tomingas
et al., 1971).
One segment of the carbon black'industry has been examined
for overall mortality rate and for specific mortality due to
91
-------
cardiovascular disease and cancer. The overall annual mortality
for carbon black workers was low over the 17.5-year period (1939-
56) examined: 3 deaths per 1,000 among carbon black workers
versus an expected annual mortality of 4,9 per 1,000. Death due
to cardiovascular diseases was less than expectancy, as was death
from cancer, at 1.2 rather than 1.46 deaths per 1,000 (Ingalls
and Risquez-Iribarren, 1961). This last statistic was not broken
down for types of cancers reported and may thus be misleading;
two of the five cancerous lesions reported in carbon black workers
were melanocarcinomas of the skin, of a type conceivably traceable
to carbon black.
Studies have been made of pulmonary function in workers at a
carbon black plant (type unspecified) exposed to concentrations
of carbon dust in the air averaging less than 10 mg/m3. The
parameters of function analyzed were forced vital capacity (FVC)
and forced expiratory volume in 1 sec (FEV^). The average annual
decline in FVC for the carbon black workers was more than four
times that expected for a normal male population, while the
average annual decline in FEVi was almost three times the pre-
dicted va'lue over the 7 years (1964-71) of the survey. Radio--
logical lung changes consisting of discrete reticular and finely
nodular fibrosis were detected in 6 out of the 35 workers (17.1%)
examined. The average exposure of'these 6 was 15.6 years (Valic
et al., 1975).
The results outlined in the above presentation can scarcely
be called conclusive in any direction. It appears that carbon
blacks naturally containing adsorbed PAHs do not product tumors,
while both positive and negative reports on blacks with added
benz(a)pyrene have been presented. It seems possible that under
conditions where a proper lipid solvent is present, such as on
the skin or in certain pathogenic lungs, the carcinogenic PAHs
adsorbed on carbon black may be eluted and thus become available;
however, this question cannot be resolved from the available
scientific literature.
92
-------
ENVIRONMENTAL ASPECTS
The carbon black industry is interesting from the pollution
control aspect in that the objective is to produce large quantities
of dense carbon smoke that would under any other circumstances be
regarded as highly undesirable by-products. But because this
highly divided particulate matter is the product of the carbon
black industry, careful and generally highly efficient methods
have been developed for complete collection for purely economic
reasons. In the thermal and furnace process plants, systems of
electrostatic precipitators, cyclones, and bag filters will
collect over 99% of the black. The general procedure is to burn
the waste gases from the furnace process after the black has been
removed; the major pollutants after this has been completed are
carbon dioxide and, if a sulfur-containing fuel had been used,
sulfur dioxide. The off-gas from the thermal process is contained
and utilized as a fuel due to its caloric value from the high
content of hydrogen gas. In the channel process, the carbon is
collected by impingement on long-channel irons. Much of the
carbon does not impinge in this way, however, and can escape to
the atmosphere.
Channel plants are notorious for the great volumes of black
smoke which they produce and which can be seen over 30 miles
away. Any attempt to regulate the escape of the gases from the
burning houses would require controlling the ventilation to an
extent where the production processes themselves would be irre-
versibly impaired. Only one channel black plant is in operation
in the United States, built near a natural gas field in remote
western Texas. Therefore, complaints of pollution from this
source seldom arise. Since the channel process has been largely
superseded by new furnace technology and no new channel black
plants have been built in the United States since 1950, this
would not seem to present any major problems for the future.
Sources of carbon black to the atmosphere other than from
production processes mainly arise through maintenance procedures,
93
-------
leaks in plant conveying systems, or loading and unloading opera-
tions. A plantwide vacuum system and good housekeeping procedures
where all spillage is picked up and combusted or recycled can
eliminate most problems from this source. Similar controls
should be instituted where carbon black is handled in further
processing (i.e., rubber plants).
The Effluent Guidelines Division of EPA has recommended
criteria of no discharge of carbon black into wastewater from any
type of carbon black plant. The basis for this decision lies in
the fact that the lamp and channel processes are dry, with no use
of water or entry of carbon black into the water. The thermal
and furnace processes are designated as net water consumers,
namely, at the stage where water is used to quench the hot black
immediately after production. Any waters contaminated with black
through cleanup or wet scrubbers later in the separation process
could be recycled to the quenching step, and the black contained
therein could be reintroduced into the separation process. The
criterion of no discharge into wastewater seems to be achievable
with little impact on the production cost of carbon black.
Since the bulk of the carbon black produced is utilized as a
reinforcing agent for rubber tires, the ultimate disposal of
carbon black into the environment comes through tire wear.
Carbon black contaminated with rubber is thus lost in substantial
quantities along the roadways, although it appears that most of
these particles settle out within a few feet of the road, ulti-
mately entering the soil or being washed into the waterways.
There are no data-on the action of carbon black in ecological
media, but it would be expected to be inert under normal con-
ditions, with little washout of any adsorbed chemicals.
Carbon black has some potential for human exposure. Indi-
viduals encountering the highest levels of carbon black will do
so in an industrial environment, such as the carbon black, tire,
94
-------
or printing ink industries. However, a wider population may also
be exposed to low levels of carbon black inhaled in minute quantities
as a component of tire dust.
95
-------
REFERENCES
Allan, D. L. The prevention of atmospheric pollution in
the carbon black industry. Chem. Ind., p. 1320-
1324, 1955.
Drogin, I. Carbon black. Air Pollut. Control Assoc.
18^(4) :216-228, 1968.
Environmental Protection Agency. Carbon black manu-
facturing point source category. Interim final
rule making. Fed. Reg. 41^(97) : 20496-20504, 1976.
Ingalls, T. H., and R. Risguez-Iribarren. Periodic
search for cancer in the carbon black industry.
Arch. Environ. Health 2_: 429-433, 1961.
Kirk-Othmer Encyclopedia of Chemical Technology. New
York, John Wiley and Sons. 1965.
Nau, C. A., J. Neal, and V. Sternbridge. Physiological
effects of carbon black. I. Ingestion. AMA Arch.
Ind. Health r?:21-28, 1958.
Nau, C. A., J. Neal, and V. Sternbridge. Physiological
effects of carbon black. II. Skin contact. AMA
Arch. Ind. Health 18_: 511-520, 1958.
Nau, C. A., J. Neal, V. Sternbridge, and.R. N. Cooley.
Physiological effects of carbon black. IV. Inhala-
tion. Arch. Environ. Health 4_(4) :415-431, 1962.
Neal, J., and R. H. Rigdon. Stomach cancer and air
pollution: An experimental study in a petrochemical
area. Tex. Rep. Biol. Med. 2_7_(3) :787-793, 1969.
Neal, J., M. Thornton, and C. A. Nau. Polycyclic hydro-
carbon elution from carbon black or rubber products.
Arch. Environ. Health 4_:598-606, 1962.
Pylev, L. N. Induction of experimental lung cancer by
chemical substances. Oncology 2_: 441-446, 1970.
Stanford Research Institute. Chemical Economics Handbook.
Menlo Park, Calif. 1976.
Steiner, P. E. The conditional biological activity of
the carcinogens in carbon blacks, and its elimina-
tion. Cancer Res. 14:103-110, 1954.
96
-------
Tomingas, R., H. U. Lange, E. G. Beck, N. Manojlovic/ and
W. Dehnen. The elution of benzo(a)pyrene adsorbed
on particles by macrophages cultured in vitro.
Zentralbl. Bakteriol. Parasitenkd. Infektionskr. Hyg.
Erste. Abt. Orig. Reihe B Hyg. Praev. Med. 155^(2) ;
148-158, 1971.
Valic, F., D. Beritic-Stahuljak, and B. Mark. A follow-up
study of functional and radiological lung changes in
carbon black exposure. Int. Arch. Arbeitsmed.
34:51-63, 1975.
97
-------
CHEMICAL HAZARD INFORMATION PROFILE
Cutting Fluids
Date of report: May 1, 1977
These substances were chosen for study because of the"demon-
strated presence of nitrosodiethanolamine, a carcinogen, in
certain synthetic cutting fluids.
No further work by this Office concerning occupational
hazards appears necessary because a NIOSH Criteria Document on
cutting fluids is in progress. It is recommended that this
report be referred to the Office of Solid Waste for consideration
of disposal problems. It appears that inadequate disposal methods
represent the major source of nonoccupational exposure to cutting
fluids.
This report represents a preliminary investigation of the
subject chemical's potential for injury to human health and the
environment. The information contained in the report is drawn
chiefly from secondary sources and available reference documents.
Because of the limitations of such sources, it necessarily follows
that this report may not reflect all available information on the
subject chemical.
Any recommendations based on this report are tentative and
should not be construed as final Agency policy with respect to
the subject chemical.
98
-------
CHEMICAL HAZARD INFORMATION PROFILE
Cutting Fluids
Date of report: May 1, 1977
Cutting fluids are liquids applied to a metal cutting tool
to assist in the machining operation by washing away metal chips
or serving as a coolant or lubricant. Many materials find common
usage as cutting fluids: water solutions or emulsions of deter-
gents and oils; mineral oils; fatty oils; chlorinated mineral
oils; sulfurized mineral oils; and mixtures of the above (Condensed
Chemical Dictionary, 1971).
The exact composition of commercially used cutting fluids is
difficult to determine because of proprietary considerations and
the common practice of additive incorporation at the place of use
(e.g., the machine shop). Table 1 presents a breakdown of the
most commonly encountered constituents of commercial cutting
fluids.
No information was located on the manufacture of cutting
oils, although Bennett (personal communication, 1976) related
that many producers are small "garage-back yard" operations which
produce only enough to satisfy a machine shop or two.
Bennett (personal communication, 1976) estimated the annual
domestic production of all types of cutting fluids at over 90
million gallons of the virgin product. Finklea (1976) claims
that there are over 1,000 domestic producers and that in excess
of 780,000 people are occupationally exposed to cutting fluids in
the United States.
HEALTH
Documented health problems associated with cutting fluids
are related to occupational exposure. The nature and scope of
99
-------
TABLE 1. COMPOSITION OF COMMERCIAL CUTTING FLUIDS
(A) Synthetic cutting fluid or chemical coolant
50-90% (1) Water
1-10% (2) Rust inhibitors and detergents
(a) sodium nitrite
(b) di- and triethanoleamines
(c) potassium or sodium soaps
25-50% (3) Lubricating agents
(a) polyether glycols
(b) alkyl-phenol-ethylene oxide
condensation products
0-1% (4) Bactericides
(a) chlorophenols
(b) organic mercurials
(c) iodine compounds
(d) formaldehyde releasers
(e) quaternary ammonium compounds
(f) hexachlorophene
Note: Synthetic cutting fluids are diluted
(20-150:1) with water prior to use.
(B) Soluble or semisynthetic cutting fluids
60-90% (1) Mineral oils
1-5% (2) Water
5-30% (3) Emulsifiers
(a) sodium and amine soaps
(b) sodium sulfonates, naphthenates,
rosinates
1-20% (4) Coupling agents
(a) alcohols
(b) glycol ethers
(c) glycols
1-10% (5) Rust inhibitors
(a) amines
(b) sodium nitrite
(c) fatty oils
(d) sulfurized fatty oils
0-10% (6) Bactericides
(as above)
Note: Soluble cutting fluids are diluted with
water prior to use.
(C) Insoluble or straight oils
80-100% (1) Mineral oils (including sulfurized
mineral oils)
1-40% (2) Fatty oils (including sulfurized
fatty oils)
0-10% (3) Sulfur (combined and suspended)
0-10% (4) Chlorine
(a) chlorinated paraffins; rarely
chlorinated aromatics
0-1% (5) Phosphorus
(a) organic phosphates and phosphites
Source: Gleason et al., 1969.
100
-------
the difficulties arising from environmental exposure to cutting
fluid wastes are not well defined. The composition of those
cutting oil effluents reaching a drinking water source is also
obscure. Large users of cutting fluids, however, are more likely
to have pollution restraints on their effluent than the relatively
small-volume users, who may merely pour their spent fluids down a
drain or onto the ground.
Known Occupational Hazards
The problems associated with occupational exposure are many:
eye irritation, pneumonitis, allergic skin sensitization, and
acne and folliculitis which can lead to keratosis and hyperkera-
tosis, ultimately resulting in malignant dyskeratosis and squamous
cell carcinoma if exposure continues (Seba, 1976).
Diethanolnitrosamine
Zingmark and Rappe (1976) first reported the formation of
diethanolnitrosamine in a grinding fluid under simulated gastric
conditions. Development of a chemiluminescent detector sensitive
to the N-nitroso group has greatly increased the capacity for
rapid detection of nitrosamines (although problems with the
method remain). Using this instrument, Fan et al. (1977) reported
concentrations of diethanolnitrosamine in commercial cutting
fluids ranging from 0.02 to 2.99% (eight reported samples).
Concern has arisen that the entry of appreciable quantities of
this nitrosamine into a drinking water source may create a health
problem.
Druckrey et al. (1967) reported that diethanolnitrosamine
was a liver carcinogen in rats. A determination of the acute
toxicity of diethanolnitrosamine showed it to have no lethal
effects despite a large dose (7.5 g/kg). An initial long-term
(feeding?) study established that the compound could induce liver
cancer with an average daily dose of 1 g/kg (total dose, 300
101
-------
g/kg). This study was repeated at a lower average daily dose
level of 0.6 g/kg until one-half of the previous total dose was
administered (total of 150 g/kg over 240 days). Following the
cessation of treatment, all rats from the initial population of
16 died with liver cancer. Four of the 16 also had kidney adenomas.
(No information was reported as to the fate of any controls.)
The authors concluded that diethanolnitrosamine was an active
carcinogen on the basis of the short induction period and the
subsequent rapid development of tumors. They added, however,
that the required active dose is at least 200 times greater than
that with diethylnitrosamine (one of the most potent carcinogenic
nitrosamines). The replacement of the diethylamine group with
the diethanolamine function apparently weakened the carcinogenic
activity but did not alter the organ specificity.
Other Problems
Several additional components of cutting fluid formulations
have potential for causing problems in the health area. These
have been more or less summarized in the next section.
ENVIRONMENTAL EFFECTS
Methods of Disposal
Many synthetic cutting fluids can be successfully biode-
graded prior to disposal. This is based upon the relative ease
with which long-chain fatty acids can be broken down into shorter
chained fatty acids, thus reducing the "oily" character of the
spent cutting fluid. Oil-base cutting fluids present a special
problem because of the low allowable concentration of oil in
wastewater. Biological degradation of hydrocarbons proceeds
slowly, and therefore it is a common practice to subject spent
cutting oils to physicochemical separation procedures. A process
such as this attempts to separate the oil and water phases such
that each can be dealt with individually. The aqueous phase
102
-------
often retains some oil, however, and must undergo additional
treatment prior to disposal. The final disposal method is
incineration of either the separated oil or the untreated cutting
fluid. In the latter case, water is driven off as steam and the
recovered oil is used to fuel the unit. This method solves the
water pollution problem but is somewhat costly and may create an
air problem (Bennett, 1973; Bouveng et al., 1972).
Cutting Oil Components
Mejbals. Spent cutting fluids may contain significant concentra-
tions of metal salts which can adversely affect the efficiency of
sewage disposal plants. Metallic ions may also cause problems if
they accumulate to levels higher than the environment can tolerate
(Bennett, 1973).
Rust inhibitors. Cutting fluids contain significant amounts of
rust inhibitors such as sodium, potassium, or lithium nitrites in
their formulations. At low environmental concentrations, nitrites
can be used as an energy source by microorganisms, while high
levels can reduce the activity of sewage bacteria (Bennett,
1973) . Several European countries have reportedly limited the
use and release of nitrites because of their relatively toxic
character (Fine, personal communication, 1976).
Phosphates. Some metalworking fluids contain high concentrations
of phosphates which are implicated in excessive algal growth and
eutrophication problems (Bennett, 1973).
Others. Both hydraulic fluids and cutting fluids may contain
polychlorinated biphenyls (PCBs), though their use is currently
being phased out. Boron compounds are being included in some
cutting fluid formulations at a time when the boron levels in
rivers are increasing. Boron is difficult to remove by conven-
tional waste treatment methods, and at high concentrations (over
1,000 ppm) it can interfere with the efficiency of disposal
103
-------
plants. Some newly developed, more exotic cutting fluids contain
fluorides, iodides, and cadmium salts. These, however, are
apparently rather low-volume products at this time.
An additional difficulty is the presence of biocides in
cutting oil formulations. While the biocide concentrations are
low (initially and especially after dilution), the tremendous
volume of spent cutting fluids generated domestically can add a
sizable environmental burden, especially in localized heavy-use
areas. Another aspect is the apparently common practice of
adding additional amounts of biocides to cutting fluid products
at user sites to "ensure" effective microbial control (Bennett,
1973; Bennett, personal communication, 1976).
Nitrosamines
Diethanolnitrosamine has been identified as a contaminant of
several commercial cutting fluids. Fan et al. (1977) reported
diethanolnitrosamine concentrations as high as 2.99% in an undiluted,
commercially available virgin cutting fluid. The authors pre-
dicted that most cutting fluids containing di- or triethanolamines
and nitrites as additives would also be contaminated with this
nitrosamine. Health or environmental problems could arise follow-
ing the disposition of nitrosamine-containing cutting fluids in a
drinking water supply. None of the noted disposal methods (with
the possible exception of incineration) are known to remove or
reduce this potential problem with any certainty.
Druckrey et al. (1967) reported that diethanolnitrosamine is
very soluble and quite stable in water under laboratory conditions
(no indication as to the presence or absence of light). In
natural waters, diethanolnitrosamine may undergo photolytic
decomposition; however, there are no studies to indicate the
half-life of diethanolnitrosamine under such conditions. Never-
theless, photolytic decomposition is effective only at the surface
104
-------
of waters, and if the nitrosamine is evenly dispersed throughout
a reservoir, only a fraction would reside at the air/water
interface.
It remains to be demonstrated that nitrosamines are present
in user effluent and that the levels found in water subsequent to
dilution are high enough to present a problem.
105
-------
REFERENCES
Bennett, E. 0. The .disposal of metal cutting fluids.
Lubr. Eng. 2^:300-307, 1973.
Bouveng, H. 0. et al. Handling of spent oil-based
products in the mechanical engineering industry.
Pure Appl. Chem. 2_9(l-3):201-217, 1972.
Condensed Chemical Dictionary, 8th ed. New York,
Van Nostrand Reinhold Co. 1971.
Druckrey, H. et al. Organotrophic carcinogenic effects
of 65 different N-nitroso compounds on BD-rats.
Krebsforsch. 69:103-201, 1967. (Translated by
G. Semeniuk ancT~C. Auer)
Fan, T. Y. et al. N-nitrosodiethanolamine in synthetic
cutting fluids: A part-per-hundred impurity.
Science 196_: 70-71, 1977.
Finklea, John F. Current Intelligence Bulletin:
Nitrosamines in Cutting Fluids. October 6, 1976.
Hart, Andrew W. Alkanolamines. In Kirk-Othmer Encyclo-
pedia of Chemical Technology, 2nd ed., vol. I.
1963. p. 809-824.
Seba, Douglas B. Letter, April 20, 1976.
Zingmark, P. A., and C. Rappe. On the formation of
N-nitrosodiethanolamine from a grinding fluid
under simulated gastric conditions. Ambio
5:80, 1976.
106
-------
ADDENDUM
Chemical Week (1977) reported that diethanolnitrosamine has
been identified by David Fine as a contaminant in several popular
consumer products (shampoos, cosmetics, hand and body lotions).
Lijinsky et al. (1972) demonstrated that triethanolamine is
readily nitrosated when treated with sodium nitrite under acidic
conditions. There is some likelihood that the problem of di-
ethanolnitrosamine contamination may be common to other products.
During the course of this project, several additional, more
wide-ranging questions came into view. Perhaps the most signifi-
cant are the health and environmental consequences of the large-
volume use and release of nitrates and nitrites. There is a mul-
titude of problems associated with these materials aside from the
possible nitrosamine implications.
References
Chemical Week, March 30, 1977, p. 29.
Lijinsky, W. et al. J. Natl. Cancer Inst. 49:1239, 1972.
107
-------
CHEMICAL HAZARD INFORMATION PROFILE
Cy clohexy1amine
Date of report: October 21, 1977
This chemical was chosen for study because of reports of its
toxicity in the scientific literature.
Since many other chemicals, especially other aliphatic amines,
are also used as corrosion inhibitors and would therefore have
similar exposure patterns, it is recommended that a contractor
review the entire class of volatile corrosion inhibitors. This
contractor report would serve as the basis for a Phase I document.
The carcinogenic potential of these chemicals is the major impetus
for further assessment.
This report represents a preliminary investigation of the
subject chemical's potential for injury to human health and the
environment. The information contained in the report is drawn
chiefly from secondary sources and available reference documents.
Because of the limitations of such sources, it necessarily follows
that this report may not reflect all available information on the
subject chemical.
Any recommendations based on this report are tentative and
should not be construed as final Agency policy with respect to the
subject chemical.
108
-------
CHEMICAL HAZARD INFORMATION PROFILE
Cyclohexylamine
Date of report: October 21, 1977
Cyclohexylamine (CHA)
Cyclohexylamine is a colorless liquid at room temperature and
has an unpleasant fishy odor. It has a boiling point of 134.5°C
and is a strong organic base (p^ = 3.3). Cyclohexylamine forms
an azeotrope with water (boiling point, 96.4°C) and is miscible
with most organic solvents (Condensed Chemical Dictionary, 1977).
PRODUCTION AND USE
The three processes used in the manufacture of Cyclohexylamine
(CHA) are the catalytic hydrogenation of aniline, ammonolysis of
cyclohexyl chloride or cyclohexanol, and the reduction of nitro-
cyclohexane (Shreve, 1967). The first reaction is apparently the
most common and involves the hydrogenation of aniline in the
liquid phase at 135-137°C and 50-500 atmospheres of pressure in
the presence of a catalyst. The CHA yield is approximately 80%
(Kouris and Northcott, 1967). The other reaction products are
.unchanged aniline and a high-boiling residue containing cyclohexyl-
aniline and dicyclohexylamine (Merck Index, 1968).
CHA is a reactive primary amine and serves as an intermediate
for a variety of derivatives. These compounds find use in numerous
industries including chemical, paper, rubber, plastic, textile,
pharmaceutical, dye, pesticide, and petroleum. Cyclohexylamine
can be added to boiler water and at concentrations of 5 ppm will
prevent corrosion and scaling by maintaining sufficient alkalinity
109
-------
to protect surfaces against carbonic acid. Because CHA forms an
azeotrope with water, the chemical enters the steam phase (vapor-
phase corrosion inhibitor), thus protecting steam lines and vapor
equipment as well as the boiler. Many derivatives of CHA are also
used as ferrous corrosion inhibitors (see Appendixes A, B, and D).
The rubber industry uses CHA mixed with other chemicals to retard
the degradation and discoloration of certain rubber mixtures.
Various salts of cyclohexylamine have long been used as vulcani-
zation accelerators (Condensed Chemical Dictionary, 1977; CEHf
1975; Holderried, 1967; Shreve, 1967).
Cyclohexylamine formerly found a good market in the produc-
tion of sodium and calcium cyclamates, which were used as artificial
sweeteners. However/ the FDA prohibited the use of cyclamates for
this purpose in 1969 (CEH, 1975; Holderried, 1967).
Annual sales figures, as reported by the U.S. International
Trade Commission, are as follows: 1971, 4.8 million Ib; 1972, 4.2
million Ib; 1975, 4.2 million Ib. Figures are not available for
1973 and 1974. The producers of CHA are listed in Table 1.
Approximately 90% of all CHA produced domestically is used in
boiler water treatment; the remaining 10% is used in the production
of various rubber chemicals (Bill Papogash, Monsanto, personal
communication, 1977).
HEALTH EFFECTS
Human
Cyclohexylamine is caustic to skin and mucous membranes, and
its systemic effects in man include nausea, vomiting, anxiety,
restlessness, and drowsiness (Gleason et al., 1969). Cyclohexyl-
amine may also be a skin sensitizer (Mallette and von Haam,
1952).
110
-------
Table 1. DOMESTIC PRODUCERS AND SUPPLIERS OF CYCLCHEXYIAMIME
Capacity
Producer/location (10° Ib)
Abbott LabS*'3 10
Wichita, Kan.
Monsanto Co.a'b 2
Sauget, 111.
Virginia Chemicals, Inc.a'b 8
Portsmouth, Va.
Suppliers
BASF Wyandotte, Inc. Mot reported
Betz Labs3 Not reported
Pennwalt Corp.*5 Not reported
Total " 20C
?As noted in the Directory of Chemical Producers (1975).
bAs noted in Chemical Wsek 1977 Buyers Guide (1976).
cCyclohexylamina and derivatives.
Ill
-------
In a human volunteer study of CHA, Eichelbaum et al. (1974)
found a significant increase in the urinary excretion of catecholamines
following the oral administration of 10 mg/kg of CHA. These
findings were consistent-with others noting the indirectly acting
sympathomimetic effects of cyclohexylamine.
The Food and Drug Administration banned the use of cyclamates
as artificial sweeteners in 1969 because of their metabolic con-
version to cyclohexylamine, which was found to be carcinogenic in
rats (Price et al., 1970). There is no evidence that CHA is a
human carcinogen.
Laboratory Animal
Mutagenicity. Cyclohexylamine appears to have potential for
chromosome damage. However, the results of studies (both in vitro
and in vivo) conducted over the last several years have been
contradictory. Several of the studies are summarized below.
In vitro studies. Cyclohexylamine caused a significant
increase in chromosome breaks in cultures of human and Chinese
hamster fibroblasts (Bladon and Turner, 1971; Dixon, 1973), in a
rat kangaroo cell line (Green et al., 1970), and in human lymphocyte
cultures (Stolt2 et al., 1970). On the other hand, Brewen et al.
(1971) did not observe a significant increase in chromosome aber-
rations (chromatid breaks) in human lymphocyte cultures, while
Schoeller (1971) , who noted no significant increase in the frequency
of chromosome breaks, observed a considerable increase in chro- .
matid breaks and gaps.using a human lymphocyte culture.
In vivo studies. No mutagenic activity was seen in the host-
mediated assay by Brewen et'al. (1971) or Voogd et al. (1973).
The dominant lethal test indicated no mutagenic activity attrib-
utable to cyclohexylamine in rats or mice (Bailey et al., 1972;
Cattanach and Pollard, 1971; Lorke and Machemer, 1974).
112
-------
CHA failed to induce sex-linked recessive lethals in Dro-
sophila (Knaap et al., 1973).
Other studies failed to demonstrate an increase in the
relative frequency of chromosome aberrations in rat, mouse, or
Chinese hamster spermatogonia (Bailey et al., 1972; Cattanach and
Pollard, 1972; Machemer and Lorke, 1976). In support, Dick et al.
(1974) found no chromosome-damaging effects caused by CHA in rats
or in a group of four human subjects.
Other studies, however, directly contradict these findings
with demonstrations of chromosome damage following in vivo
administration of CHA. Legator et al. (1969) noted a significant
increase in chromosome breaks in the spermatogonia and bone marrow
cells of rats; Petersen et al. (1972) found a significant increase
in dominant lethal effects in mice; Turner and Hutchinson (1974)
indicated an increase in chromosome abnormalities in peripheral
lymphocytes of fetal lambs; van Went-de Vries et al. (1975) found
chromosome-damaging effects in Chinese hamsters following oral
treatment with CHA.
No clear-cut conclusions as to the mutagenic potential of
cyclohexylamine can be reached because of the many conflicting
studies. Nevertheless, the van Went-de Vries et al. (1975) study
appears the strongest because the purity of their CHA samples was
checked by mass spectrometry and the compound, which is easily
oxidized, was handled at a low pH (2.2-2.4) and in a nitrogen
atmosphere. All other studies reporting the pH of the CHA sample
used values between 7.0 and 7.3, which are not optimal conditions.
It appears likely that much of the lack of agreement among the
published results is attributable to the use of impure CHA (van
Went-de Vries et al., 1975).
Carcinogenicity. A 10:1 mixture of sodium cyclamate and sodium
saccharin (C/S) was added to the diet of rats in concentrations
providing a daily intake of 0, 500, 1,120, or 2,500 mg/kg/day.
113
-------
Many of the rats were found to convert cyclamate to cyclohexylamine.
In the 79th week, one-half of the animals in each group were given
supplemental amounts of cyclohexylamine hydrochloride in the diet
at 25, 56, or 125 mg/kg/day. Papillary transitional cell tumors
were found in the urinary bladders of 8 of the initial 80 rats
receiving 2,500 mg/kg/day of the C/S mixture. In all but one
instance, the tumors developed in rats that were found to convert
cyclamate to CHA. There were three bladder tumors in rats that
received the CHA supplements and five in those that did not (Price
et al., 1970) .
Cyclohexylamine sulfate was fed in the diet to groups of 50
rats at daily doses of 0, 0.15, 1.5, and 15.0 mg/kg. At the end
of the 2 years, CHA-related organ changes were noted only in rats
receiving the highest dosage. A single bladder tumor (transitional
cell carcinoma, grade 2) was found in one of the eight male survivors
in the high-dose group. Spontaneous bladder tumors have never
been recorded in control rats at the testing facility (Industrial
Bio-Test Laboratories) and are reported to be rare (Price et al.,
1970).
This finding of carcinogenic activity attributable to cyclo-
hexylamine has not been supported by the results of subsequent
investigators. The results of four studies are summarized in
Table 2. These studies are discussed further under "Chronic.
Toxicity."
Fertility and Teratogenic Effects. Cyclohexylamine has been shown
by several investigators to affect male fertility in rats (Khera
and Stoltz, 1970; Khera et al., 1971; Green et al., 1972; Oser et
al., 1976). These studies demonstrated that males treated with
cyclohexylamine (or its sulfate or hydrochloride salt) produced
smaller litters than untreated males. CHA was not found to affect
the fertility of female rats.
Pregnant female rats were given daily oral doses of CHA (1.8,
3.6, 18.0, or 36.0 mg/kg/day) for a period of 7 days corresponding
•
114
-------
Table 2. RESULTS OF RECENT CARCINOGENESIS STUDIES ON CHA
ui
Animal
Rat
Rat
Rat
Mouse
Duration
2 years
2 years
2 years
80 weeks
Maximal
dose
(mg/kg/day)
150
150
300a
400a
Conclusion
Negative
Negative
Negative
Negative
Author
Bailey et al . ,
1972
Oser et al. ,
1976
Gaunt et al. /
1976
Hardy et al. ,
1976
Approximate.
-------
to the 7th through 13th days of gestation. No significant differ-
ences were seen between the treated and control groups in main-
tenance of pregnancy, fetal development, resorption, or malforma-
tion rates (Tanaka et al., 1973). In a similar experiment, CHA
was orally administered to pregnant mice at 20, 50, or 100 mg/kg/day
for 6 days either from day 0 to day 5 or from day 6 to day 11 of
gestation. Cyclohexylamine once again failed to exhibit any
teratogenic effects in any of the groups. At 100 mg/kg/day,
however, CHA significantly decreased the body weight of living
fetuses and was also embryolethal when administered from day 6 to
day 11 of gestation (the level of embryotoxicity of CHA was about
the same as its subacute toxicity in the adult female) (Takano and
Suzuki, 1971).
Chronic Toxicity. Cyclohexylamine was found relatively nontoxic
to mice (Hardy et al., 1976) and rats (Bailey et al., 1972; Gaunt
et al., 1976; Oser et al., 1976) when administered in the diet
over extended periods of time (see "Carcinogenesis" section for
maximal dosages and duration of studies). Growth retardation at
the higher levels was the only noted effect of Cyclohexylamine on
the test animals.
Multigeneration (F^ through F4) rat studies conducted with
CHA at dosages of 0, 15, 50, 100, or 150 mg/kg/day over a 2-year
period yielded results that were substantially within normal
limits. Nonprogressive growth retardation and a slight reduction
in litter size and weanling weights were the only changes evident
in the highest dosage groups (Bailey et al., 1972; Oser et al.,
1976).
Acute and Subacute Toxicity. Watrous and Schulz (1950) exposed
rabbits, guinea pigs, and rats to CHA vapors for 7 hr/day, 5
days/week, at an average concentration of 150, 800, or 1,200 ppm.
At the highest level, all animals except one rat showed extreme
irritation and died after a single exposure. Fractional mortality
occurred after repeated exposures at 800 ppm. At 150 ppm, four of
116
-------
five rats and two guinea pigs survived 70 hr of exposure; however,
one rabbit died after only 7 hr. The chief effects were irrita-
tion of the respiratory tract and eye irritation with the develop-
ment of corneal opacity. No convulsions were observed.
The IP LD5Q of CHA in mice was 619 mg/kg, and the lethal dose
for rats and dogs was estimated at 350 mg/kg IP and 200 mg/kg IV,
respectively. Smaller IV doses in the mouse caused nervous system
depression and slight paralysis in the hindlegs (also exhibited by
dogs given 5-50 mg/kg of CHA). In all cases, death was attributed
to respiratory arrest. Cyclohexylamine caused liberation of
histamine in all three animal species as evidenced by severe
scratching. In addition, CHA produced a rise in blood pressure
and increased cardiac contractile force through release of endo-
genous catecholamines (Miyata et al., 1969).
A 13-week feeding study with CHA. at approximately 30, 100, or
300 mg/kg/day produced growth retardation and reduced testis
weight in rats receiving the two highest dosages. The reduced
testis weight at the highest level was accompanied by histopatho-
logical evidence of reduced spermatogenesis, amounting to complete
arrest and loss of the germinal epithelium in 40% of the rats
given 300 mg/kg/day. Despite this development, a limited repro-
duction study showed no statistically significant differences
between the offspring of treated and untreated males (Gaunt et
al., 1974).
ENVIRONMENTAL EFFECTS
Little or no information was available on the environmental
impact of cyclohexylaraine. A study by Jungclaus et al. (1976)
identified CHA in the effluent from a tire-manufacturing plant at
an approximate concentration of 0.01 mg/1 (+30%).
117
-------
APPENDIX A. DICYCLOHEXYLAMINE
Dicyclohexylamine
(di-CHA)
Dicyclohexylamine (di-CHA) is a colorless liquid with a faint
amine odor. It has a boiling point of 256 °C and is sparingly
soluble in water. Dicyclohexylamine is strongly basic (pKD =
3.3) (Merck Index/ 1968; Condensed Chemical Dictionary / 1977).
The literature outlines several schemes for the manufacture
of dicyclohexylamine. The first process involves the hydrogena-
tion of equimolar amounts of cyclohexanone and cyclohexylamine
(Merck Index , 1968) . A second process uses the hydrogenation of
aniline in the vapor phase in the presence of a nickel catalyst to
produce up to 95% di-CHA (Kouris and Northcott, 1967) .
Dicyclohexylamine is a strongly basic secondary amine having
a reactive amine group which readily yields N-substituted deriva-
tives. "It is widely used as a chemical intermediate. Dicyclohexyl-
amine salts of fatty acids and sulfuric acid have soap and deter-
gent properties useful to the printing and textile industries.
Metal complexes of di-CHA are used as catalysts in the paint,
varnish, and ink industries. Several vapor-phase corrosion inhibitors
are solid di-CHA derivatives. These compounds are slightly volatile
at normal temperatures and are used to protect packaged or stored
ferrous metals from atmospheric corrosion (Holderried, 1967) .
Dicyclohexylamine is also used for a number of other purposes:
plasticizer; insecticidal formulations; antioxidant in lubricating
oils, fuels, and rubber; and extractant (Condensed Chemical Dictionary,
1977).
No annual production figures are available for dicyclohexyl-
amine. The domestic producers are: Abbott Laboratories, Wichita,
Kans. (Directory of Chemical Producers, 1975; Chemical Week 1977
Buyers Guide, 1976); Virginia Chemicals Inc., Portsmouth, Va.
CDirectory of Chemical Producers, 1975); BASF Wyandotte, Inc.; and
Monsanto Co.
Dicyclohexylamine is somewhat more toxic than cyclohexylamine.
Poisoning symptoms and death appear earlier in rabbits injected
with 0.5 g/kg di-CHA (as opposed to CHA) . Doses of 0.25 g/kg are
just sublethal, causing convulsions and reversible paralysis.
Dicyclohexylamine is a skin irritant (Carswell and Morrill,
1937) .
118
-------
Pliss (1958) conducted a series of animal experiments with
di-CHA. The first involved mice which received daily subcutaneous
injections of 0.05 ml of a 2.6% oily solution of di-CHA. The mice
often showed transient convulsions following the injection. Of
the original 57 mice, 15 were alive after 12 months. At this
time, several of the mice began developing local tumors. Post-
mortem of several of the mice revealed a high incidence of degenera-
tive changes in the liver and kidneys. The results of this study
are summarized below.
Species of
animal (no.)
Mice (57)
Rats (50)
Route of
administration
SC injection
Feeding
Duration of
administration
(months)
11-12.5
12
Total
dosage
(mg)
60.1-79.3
8,875
No. of
tumors
Type of
tumor
Sarcomas
One hepatoma
and one
sarcoma
The second part of Pliss1 experiment involved a rat feeding
study. (For 2 months, administration was actually via subcutaneous
injection of 30 mg. However, local tissue necrosis forced the
change.) The rats were given 0.5 ml of a 5% oily solution of di-
CHA in the food six times a week. Of the 50 original rats, 36
survived for over 12 months, 22 for more than 18 months. Most of
the animals died of pneumonia. Among the remaining rats, one
developed a liver tumor after 21 months and another developed a
sarcoma after 22.5 months. See above for a summary of this aspect
of the experiment.
Pliss concluded that di-CHA was rather weakly carcinogenic,
since relatively few animals developed tumors and the timespan for
tumor development was rather long.
119
-------
APPENDIX B. DICYCLOHEXYLAMINE NITRITE
H
Dicyclohexylamine nitrite
(di-CHAN)
Dicyclohexylamine nitrite is a solid nitrite salt having some
degree of volatility at room temperature and higher. It is used
as a vapor-phase corrosion inhibitor whereby it vaporizes either
from the solid state or from solution and offers protection against
atmospheric rusting. Wrapping paper, plastic wraps, and other
materials may be impregnated with di-CHAN to protect metal parts
during packaging and storage (Nathan, 1967; Archer and Wishnok,
1976).
No production figures are available for di-CHAN; however, the
Directory of Chemical Producers (1975) lists the Olin Corp., East
Alton, 111., as a producer.
Prolonged exposure to dicyclohexylamine nitrite vapor is
reported to lead to changes in the CNS, erythrocytes, and methe-
moglobinemia and to disturb the functional state of the liver and
kidneys of human workers. The_author recommends a maximum allow-
able concentration of 0.2 mg/m in the workshop (Paustovskaya et
al., 1973) .
The LD5Q of di-CHAN by gavage was 80 mg/kg in mice and 325
mg/kg in rats (Paustovskaya, 1974).
Pliss (1958) reported that di-CHAN is a carcinogen in mice
and rats. In the mouse study, each animal received a daily SC
injection of 0.1 ml of a 1% aqueous solution of di-CHAN. Transient
convulsions and excitement sometimes accompanied the injections.
Tumors remote from the site of injection were found in 5 of 54
mice. The first rat study involved once-weekly SC injections of
0.5 ml of a 2% aqueous solution. Remote tumors were found in 7 of
50 rats. In the second rat experiment, di-CHAN was fed daily in
the diet, six times a week, as 1 ml of a 3% aqueous solution. One
rat out of a population of 30 developed a tumor. The results are
summarized below.
120
-------
Species of
animal (no.)
Mice (54)
Rats (56)
Rats (30)
Route of
administration
SC injection
SC injection
Feeding
Duration of
administration
(months)
12-13
11-13
12
Total
dosage
(mg)
51-59
480-1,195
9,180
No. of
tumors
5
7
1
Pliss concluded that di-CHAN was weakly active, although all
tumors developed at different tissue sites remote from the point
of injection.
Marhold et al. (1967) contested Pliss1 (1958) finding of
carcinogenic activity associated with di-CHAN. In a prolonged
feeding experiment, 14.2 mg/kg of di-CHAN was added to the diet of
rats 7 days a week for their lifetimes. No tumors were found in
the population of 20 rats. A second study was conducted using
three dogs which were fed 5-10 mg/kg, 5 days a week for life (dogs
were 14 months old at initiation of the experiment). No tumors
were found in any of the dogs. Despite the small number of animals
studied, and notwithstanding Pliss1 results, the authors concluded
that dicyclohexylamine nitrite was not a carcinogen (or at best a
very weak one, or so the article implies) based on the dose given
and the length of the study.
121
-------
APPENDIX C. N-NITROSODICYCLOHEXYLAMINE
0
N-nitrosodicyclohexylamine
Any situation in which nitrite ions and a secondary amine
(such as dicyclohexylamine) are in contact under acidic aqueous
conditions has the potential for production of nitros amines (Mirvish,
1975) . Nitrosodicyclohexylaraine may be a contaminant of dicyclo-
hexylamine nitrite and also perhaps of dicyclohexylamine. However,
nitrosodicyclohexylamine is not carcinogenic (Norred, 1975; Nishie,
1974) . Its lack of carcinogenicity may be traceable to the presence
of only one hydrogen on each carbon alpha to the nitrogen (Lijinsky,
1977).
122
-------
APPENDIX D. OTHER CYCLOHEXYLAMINE DERIVATIVES
Many other salts of cyclohexylamine are used as vapor-phase
corrosion inhibitors. There is very limited information available
on these compounds in Western literature; however, the Russians
have published a number of studies. Refer to Tables D-l and D-2
for a summary of the acute toxicity associated with several of
these salts.
Table D-l.
LD5Q VALUES FOR CYCLOHEXYLAMINE DERIVATIVES
Substance
CHA-benzoate
CHA-o-nitrobenzoate
CHA-m-nitrobenzoate
CHA-p-nitrobenzoate
CHA-3 , 5-dinitrobenzoate
CHA-carbonate
CHA-chromate
Mouse LD50
Route (mg/kg)
Gavage
Gavage
Gavage
Gavage
Gavage
Gavage
Gavage
1,400
2,075
490
1,590
925
—
224
Rat LDgQ
(mg/kg)
3,300
—
4,800
1,950
1,600
820
228
Source: Paustovskaya, 1974.
Table D-2. LD5Q VALUES FOR DICYCLOHEXYLAMINE DERIVATIVES
Substance
di-CHA-benzoate
di-CHA-o-nitrobenzoate
di-CHA-m-nitrobenzoate
di-CHA-p-nitrobenzoate
di-CHA-carbonate
Route
Gavage
Gavage
Gavage
Gavage
Oral
Mouse LD5Q
(mg/kg)
290
300
364
318
w«
Rat LDqQ
(mg/kg)
700
925
1,060
1,620
1,075
Source: Paustovskaya, 1974; Garshenin et al., 1973.
The chromates, benzoates, and nitrobenzoates were also found
toxic following dermal application. One study indicated that the
daily application of 625 mg/kg of CHA-chromate to the shaved skin
of rabbits and rats caused the death of five of seven animals
within 3-10 days, and the daily application of 1,500 mg/kg CHA-
chromate caused the death of all experimental animals within 4
days. Necropsy revealed an enlarged bladder, blood in the urine,
and dystrophy of nerve cells, liver, and kidneys (Paustovskaya and
Rappoport, 1966).
123
-------
REFERENCES
Archer, M. C., and J. S. Wishnok. The nitrous acid test for
amines—A potentially hazardous reaction. J. Chem. Educ.
£3:559, 1976.
Bailey, D. E. et al. Chronic toxicity, teratology, and mutageni-
city studies with cyclohexylamine in rats. Toxicol. Appl.
Pharmacol. 22^330, 1972.
Bladon, M. T., and J. H. Turner. Independent and joint effects of
caffeine and cyclohexylamine upon (KDCS) WI-38. Mairan. Chrom.
Newsl. 12_:5, 1971.
Brewen, J. G. et al. Cytogenetic effects of cyclohexylamine and
N-hydroxycyclohexylamine on human leukocytes and Chinese
hamster bone marrow. Nature New Biol. 230;15, 1971.
Carswell, T. S., and H. L. Morrill. Cyclohexylamine and dicyclo-
hexylamine. Ind. Eng. Chem. 29_:1247, 1937.
Cattanach, B. M., and C. E. Pollard. Mutagenicity tests with
cyclohexylamine in the mouse. Mutat. Res. 1^:472, 1971.
Chemical Economics Handbook (CEH). Menlo Park, Calif., Stanford
Research Institute. 1975.
Chemical Week 1977 Buyers Guide, Part 2. New York, McGraw-Hill.
1976.
Condensed Chemical Dictionary, 9th ed. New York, Van Nostrand
Reinhold Co. 1977.
Dick, C. E. et al. Cyclamate and cyclohexylamine: Lack of effect
on the chromosomes of man and rats in vivo. Mutat. Res.
2£:199, 1974.
Directory of Chemical Producers. Menlo Park, Calif., Stanford
Research Institute. 1975.
Dixon, C. H. In vitro effects of sodium and calcium cyclamates,
cyclohexylamine and sucrose on growth rate and chromosomes of
Chinese hamster fibroblasts. Diss. Abstr. 59-33 B, 1973.
Eichelbaum, M. et al. Pharmacokinetics, cardiovascular and meta-
bolic actions of cyclohexylamine in man. Arch. Toxikol.
31:243, 1974.
Garshenin, V. F. et al. Sanitary-toxicological characteristics of
inhibitors of atmospheric corrosion. Gig. Sanit. Okhr.
Vodoemov, p. 81, 1973. (Abstract)
124
-------
Gaunt, I. F. et al. Short-term toxicity of cyclohexylamine
hydrochloride in the rat. Food Cosraet. Toxicol. 12(5-
6)1609, 1974.
Gaunt, I. F. et al. Long-term toxicity of cyclohexylamine hydro-
chloride in the rat. Food Cosmet. Toxicol. 14_:255, 1976.
Gleason, M. et al. Clinical Toxicology of Commerical Products,
3rd ed. Baltimore, The Williams and Wilkins Co. 1969.
Green, S. et al. In vitro cytogenetic investigation of calcium
cyclamate, cyclohexylamine and triflupromazine. Food Cosmet.
Toxicol. £:617, 1970.
Green, S. et al. Effects of cyclohexylamine on the fertility of
male rats. Food Cosmet. Toxicol. 1Q_:29, 1972.
Hardy, J. et al. Long-term toxicity of cyclohexylamine hydro-
chloride in mice. Food Cosmet. Toxicol. 14_:269, 1976.
Holderried, J. A. Amines. In Kirk-Othmer Encyclopedia of Chemical
Technology, vol. 2, New York, Interscience Publishers.
1967. p. 116.
Jungclaus, G. A. et al. Identification of trace organic compounds
in the manufacturing of plant waste water. Anal. Chem.
4IM13) :1894, 1976.
Khera, K. S., and D. R. Stoltz. Effects of cyclohexylamine on
rat fertility. Experimentia 2£:761, 1970.
Khera, K. S. et al. Reproduction study in rats orally treated
with cyclohexylamine sulfate. Toxicol. Appl. Pharmacol.
18_:263, 1971.
Knaap, A. G. A. C. et al. Lack of mutagenicity of the cyclamate
metabolites in Drosophila. Mutat. Res. 2_1:341, 1973.
Kouris, C. S., and J. Northcott. Aniline. In Kirk-Othmer Encyclo-
pedia of Chemical Technology, vol. 2. New York, Interscience
Publishers. 1967. p. 411.
Legator, M. S. et al. Cytogenetic studies in rats of cyclohexyl-
amine, a metabolite of cyclamate. Science 165;1139, 1969.
Lijinsky, William. How nitrosamines cause cancer. New Sci.
January 1977, p. 216.
Lorke, D., and L. Machemer. Investigation of cyclohexylamine
sulfate for dominant lethal effects in the mouse. Toxicology
2:231, 1974.
125
-------
Machemer, L. , and D. Lorke. Evaluation of the mutagenic potential
of cyclohexylamine on spennatogonia of the Chinese hamster.
Mutat. Res. 4_0(3):243, 1976.
Mallette, F. S., and E. von Haam. Studies on the toxicity and
skin effects of compounds used in the rubber and plastics
industries. I. Accelerators, activators, and antioxidants.
Arch. Ind. Hyg. Occup. Med. 5_:311, 1952.
Marhold, J. et al. On the carcinogenicity of dicyclohexylamine.
Neoplasma 1£(2) :177, 1967.
Merck Index. Rahway, N.J., Merck and Co. 1968.
Mirvish, S. S. Toxicol. Appl. Pharmacol. 3_1:325, 1975.
Miyata, T. et al. Pharmacological characteristics of cyclohexyl-
amine, one of the metabolites of cyclamate. Life Sci.
£(1):843, 1969.
Nathan, C. C. Corrosion inhibitors. In_ Kirk-Othmer Encyclopedia
of Chemical Technology, vol. 6. New York, Interscience
Publishers. 1967. p. 317.
Nishie, K. et al. Effect of short-term administration of n-nitroso
compounds on liver histology and on pentobarbital-induced sleep-
ing time in mice. Res. Commun. Chem. Pathol. Pharmacol.
8_(2):301, 1974. (Abstract)
Norred, W. P. et al. Effect of short-term administration of nitros-
amines on rat hepatic microsomal enzymes. Biochem. Pharmacol.
24J13-14) :1313, 1975.
Oser, L. et al. Long-term and multigeneration toxicity studies
with cyclohexylamine hydrochloride. Toxicology 6_:47, 1976.
Patty, F. A. (ed.). Industrial Hygiene and Toxicology, vol. 2.
New York, Interscience Publishers. 1963.
Paustovskaya, V. V. The toxicity of inhibitors of atmospheric
corrosion of metals. Prot. Met. KK3) :310, 1974. (English
translation, March 1975)
Paustovskaya, V. V., and M. B. Rappoport. Toxicity of cyclohexyl-
amine chroma te entering through the skin. Vrach. Delo
1966. (Abstract)
Paustovskaya, V. V. et al. Hygienic characteristics of the
working conditions when protecting metalware with rust
inhibitor dicyclohexylamine nitrite. Gig. Tr. Prof. Zabol.
17_(1):35, 1973. (Abstract)
Peter sen, K. W. et al. Dominant- lethal effects of cyclohexylamine
in C57 Bl/Fe mice. Mutat. Res. 1£:126, 1972.
126
-------
Pliss, G. B. The carcinogenic activity of dicyclohexylamine and
its nitrite salt. Probl. Oncol. 4_(6):22, 1950.
Price, J. M. et al. Bladder tumors in rats fed cyclohexylamine
or high doses of a mixture of cyclamate and saccharin.
Science 16^:1131, 1970.
Schoeller, L. Chromosomal effects of cyclohexylamine. Wiss.
Veroeff. Dtsch. Ges. Ernaehr. 2£:125, 1971. (Abstract)
Shreve, R. N. Amination by reduction. In Kirk-Othmer Encyclo-
pedia of Chemical Technology, vol. TT New York, Interscience
Publishers. 1967. p. 76.
Smyth, H. F. et al. Range-finding toxicity data: List VII. Am.
Ind. Hyg. Assoc. J. 3_0_:470, 1969.
Stoltz, D. R. et al. Cytogenetic studies with cyclamate and
related compounds. Science 167;1501, 1970.
Takano, K., and M. Suzuki. Cyclohexylamine, a chromosome-aberration
inducing substance: No teratogenicity in mice. Congenital
Anomalies 11. (2) : 51, 1971.
Tanaka, S. et al. Studies on the teratogenicity of food additives
• (2). J. Food Hyg. Soc. 1£(6):542, 1973.
Turner, J. H., and D. L. Hutchinson. Cyclohexylamine mutagenicity:
An in_ vivo evaluation utilizing fetal lambs. Mutat. Res.
26_:207, 1974.
U.S. International Trade Commission. Synthetic Organic Chemicals.
1971, 1972, 1975.
van Went-de Vries, G. et al. In vivo chromosome-damaging effect
of cyclohexylamine in the Chinese hamster. Food. Cosmet.
Toxicol. 13_:415, 1975.
Voogd, C. E. et al. Investigation of mutagenic activity of
sodium cyclamate, sodium saccharinate and cyclohexylamine.
Natl. Inst. Public Health Rep. 15/73 Chemo.
Watrous, R. M., and H. N. Schulz. Ind. Med. Surg. 19:317, 1950.
(As cited in Patty, 1963}
127
-------
CHEMICAL HAZARD INFORMATION PROFILE
1,6-Diaminohexane
Date of report:June 6, 1978
This chemical was chosen for study because of its possible
presence in consumer products and its potential for nitrosamine
formation.
The following recommendations are made regarding further OTE
evaluation of the possible health or environmental hazards of 1/6-
diaminohexane:
(1) Require TSCA Section 8 (a) submission—Better information
is needed on uses so that EPA can estimate the extent of
nonoccupational exposure to this chemical.
(2) Consider need for testing—Diaminohexane is a high-volume
chemical which has demonstrated toxic effects at low
doses.
(3) Transmit to NIOSH on an FYI basis—NIOSH has scheduled a
criteria document for aliphatic di- and polyamines.
This report represents a preliminary investigation of the
subject chemical's potential for injury to human health and the
environment. The information contained in the report is drawn
chiefly from secondary sources and available reference documents.
Because of the limitations of such sources, it necessarily follows
that this report may not reflect all available information on the
subject chemical.
Any recommendations based on this report are tentative and
should not be construed as final Agency policy with respect to the
subject chemical.
128
-------
CHEMICAL INFORMATION HAZARD PROFILE
1,6-Piaminohexane
Date of report: June 6, 1978
1,6-Diaminohexane (hexamethylenediamine) / cgHigN2' ^s a
colorless, combustible solid which melts at 39-42°C. It is
somewhat soluble in water, ethanol, and ether (Hawley, 1971).
PRODUCTION AND USE
Diaminohexane can be manufactured in two ways (Hawley,
1971):
(1) Reaction of adipic acid and ammonia (catalytic vapor
phase) to yield adiponitrile, followed by liquid-phase
catalytic hydrogenation.
(2) Chlorination of butadiene followed by reaction with
sodium cyanide (cuprous chloride catalyst) to 1,4-
dicyanobutylene, and hydrogenation.
The production volume of diaminohexane was 750 million Ib
in 1975 (U.S. International Trade Commission, 1977). The 1975
Directory of Chemical Producers lists the following manufacturers
of diaminohexane (SRI, 1976): Celanese Corp., Celanese Chemical
Co. Division, Bay City, Tex.; E. I. du Pont de Nemours & Co.,
Inc., Polymer Intermediates Department, Orange, Tex., and Victoria,
Tex.; El Paso Natural Gas Co., El Paso Products Co., subsidiary,
Odessa, Tex.; Monsanto Co., Monsanto Textiles Co., Pensacola,
Fla.; and R.S.A. Corp., Ardsley, N.Y.
Celanese Chemical Co. states that diaminohexane is used as
a raw material for nylon fiber and plastics; in the manufacture
of oil-modified and moisture-area types of urethane coatings; in
the manufacture of polyamides for printing inks, dimer acids,
129
-------
and textiles; and as an oil and lubricant additive (probably as
a corrosion inhibitor) (McCurdy, 1977). Diaminohexane is also
used in paints and as a curing agent for epoxy resins (Tkachenko,
1976) .
HEALTH ASPECTS
Continuous 90-day inhalation of 1 mg/m of diaminohexane by
albino rats caused an increase in the number of reticulocytes
(only at the beginning of the exposure) and an increase in the
Vi antibody concentration. The animals also exhibited a decrease
in the number of eosinophils, suppressed leukocytic activity,
. retarded growth, and a disturbance of the chronaxy correlation
of the muscle antagonists. Diaminohexane at a concentration of
3
0.04 mg/m caused similar but less pronounced changes. Diamino-
hexane at 0.001 mg/m had no effect (Kulakov, 1965).
Exposure of rats to an atmosphere containing 1.25 mg/m
diaminohexane for 4 hr/day for 8 days decreased the threshold of
neuromuscular excitability/ increased blood leucocyte and liver
glycogen levels, caused disorders of renal excretory capacity,
and altered the phagocytic activity of neutrophils (Tkachenko,
1976) .
Diaminohexane inhibited DNA and RNA formation in vitro in
studies using rat embryo and human amnion cell cultures (Trakhtenberg
et al., 1976).
Intraperitoneal injection of diaminohexane into rats
inhibited ovarian ornithine decarboxylase activity which had
been stimulated by human chorionic gonadotropin (Guha and Janne,
1977). Diaminohexane injected into mice bearing ascites-carcinoma
cells powerfully decreased ornithine decarboxylase activity in
the carcinoma cells (Kallio et al., 1977).
130
-------
An in vitro study showed that diaminohexane inhibited
collagen-induced human platelet aggregation (Jobin and Tremblay,
1969).
Occupational exposure to epoxy resins and their hardeners
(including diaminohexane) was studied in 488 workers. Prolonged
contact caused skin damage, allergic rhinitis, bronchial asthma,
impairment of bronchial permeability, toxicoallergic hepatitis,
gastritis, colitis, hypergammaglobulinemia, increased transaminase
activity, and eosinophilia of the peripheral blood (Gul'ko,
1971).
ENVIRONMENTAL ASPECTS
The estimated release rate of diaminohexane to the environment
is 12.8 million Ib/year. Diaminohexane is reactive toward
oxidizing agents (Dorigan et al., 1976).
131
-------
REFERENCES
*Dorigan, J., B. Fuller, and R. Duffy. Scoring of Organic Air
Pollutants. Chemistry, Production, and Toxicity of Selected
Synthetic Organic Chemicals. 1976.
Guha, S. K., and J. Janne. Inhibition of ornithine decarboxylase
in vivo in rat ovary. Biochem. Biophys. Res. Commun. 7_5(1) :
136-142, 1977. (As stated in CBAC abstract)
Gul'ko, S. N. Damage to respiratory organs under the occupational
effects of epoxide resins. Klin. Med. 4_2(12) :107-109, 1971.
(As stated in HEEP abstract)
Hawley, G. G. (ed.). The Condensed Chemical Dictionary, 8th ed.
New York, Van Nostrand Reinhold Co. 1971.
Jobin, F., and F. Tremblay. Platelet reactions and immune processes.
II. Inhibition of platelet aggregation by complement inhibi-
tors. Thromb. Diath. Haemorrh. 2_2(3) :466-481, 1969. (As
stated in CBAC abstract)
Kallio, A., H. Poso, S. K. Guha, and J. Janne. Polyamines and
their biosynthetic enzymes in Ehrlich ascites-carcinoma
cells. Modification of tumour polyamine pattern by diamines.
Biochem. J. 166(1);89-94, 1977. (As stated in author abstract)
Kulakov, A. E. The effect of small concentrations of hexamethyl-
enediamine on experimental animals under conditions of chronic
inhalation poisoning. Gig. Sanit. 30^(5) :15-20, 1965. (English
translation)
McCurdy, P. P. (ed.). Chemical Week 1978 Buyers Guide. New York,
McGraw-Hill, Inc. 1977.
SRI International. Directory of Chemical Producers. Menlo Park,
Calif., Stanford Research Institute. 1976.
Tkachenko, A. E. Experimental data on the nature of the primary
response of an animal under the effect of hexamethylenediamine.
Gig. Tr. Prof. Zabol. 12:51-52, 1976. (As stated in CBAC
abstract)
Trakhtenberg, I. M., I. S. Brit, and Y. I. Morgunova. Use of
spectral microanalysis of cell cultures for evaluating the
comparative toxicity of new chemical substances. Gig. Sanit.
1£:54-56, 1976. (As stated in CBAC abstract)
U.S. International Trade Commission. Synthetic Organic Chemicals.
U.S. Production and Sales, 1975. U.S. ITC Publ. No. 804.
1977.
*This document was prepared for the U.S. Environmental Protection
Agency by the MITRE Corp. It is a secondary source and does not
cite its primary references. Thus, verification of some informa-
tion is not possible. The environmental release data were taken
from the NSF/Rann Research Program on Hazard Priority Ranking of
Manufactured Chemicals.
132
-------
CHEMICAL HAZARD INFORMATION PROFILE
1,2-Dichloroethane
Date of report: September 1, 1977
This chemical was chosen for study because of its high
production volume.
It is recommended that OTS continue its ongoing hazard
assessment of lf2-dichloroethane and then proceed to a Phase I
report. The reasons for concern about 1,2-dichloroethane are its
potential carcinogenicity and its high rate of release into the
environment. A requirement for TSCA Section 8(d) submissions is
also recommended in order to improve the base of information for
Phase I assessment.
This report represents a preliminary investigation of the
subject chemical's potential for injury to human health and the
environment. The information contained in the report is drawn
chiefly from secondary sources and available reference documents.
Because of the limitations of such sources, it necessarily follows
that this report may not reflect all available information on the
subject chemical.
'Any recommendations based on this report are tentative and
should not be construed as final Agency policy with respect to
the subject chemical.
133
-------
CHEMICAL HAZARD INFORMATION PROFILE
1,2-Dichloroethane
Date of report: September 1, 1977
1,2-Dichloroethane (DCE) is a colorless oily liquid with a
chloroform-like odor. It is stable to water, acids, and bases,
and also resists oxidation. Ethylene dichloride is miscible with
most common solvents but is only slightly soluble in water. It
has a boiling point of 83.5°C. In 1975, DCE was the 16th highest
volume chemical produced in the United States (CCD, 1977).
PRODUCTION AND USE
1,2-Dichloroethane is produced by the vapor- or liquid-phase
reaction of chlorine with ethylene in the presence of a catalyst.
When chlorine is combined with ethylene, both substitution and
addition reactions occur; ethylene dichloride is the major product
only under certain-conditions. In a representative industrial
scheme, chlorine (combined with ethylene dibromide and heated to
50°C) reacts with a stream of ethylene gas and is passed to a
condenser. The ethylene dibromide liquefies and is recycled.
DCE is subsequently condensed and purified by fractional distil-
lation. The yield is approximately 96-98%. Metallic chlorides
(e.g., ferric, aluminum, copper, or antimony) are commonly used
as the catalyst. Most commercial producers currently use a
ferric chloride catalyst in a liquid-phase process. When consider-
able excess hydrogen chloride is available, the oxychlorination
of ethylene is the preferred method of DCE synthesis. This
process reacts ethylene, hydrogen chloride, and air in a fluidized
or fixed-bed catalytic process. The catalyst is copper chloride
(SRI, 1975; Hardie, 1967; Lowehheim and Moran, 1975).
Table 1 lists the major producers of 1,2-dichloroethane in
the United States. The available supply of DCE for the merchant
market is less than the production capacities contained in Table
1 because only the 1,2-dichloroethane produced by the direct
134
-------
Table 1. DCE PRODUCERS, PLANT LOCATIONS, AND CAPACITIES
Capacity as of Dec. 1974
Producers and plant locations (10^ lb)
Allied Chemical Corp. 650
Baton Rouge, La.
American Chemical Corp. 300
Long Beach, Calif.
Conoco Chemicals
Lake Charles, La. 1,000
Diamond Shamrock Chem. Co.
Deer Park, Tex. 260
Dow Chemical U.S.A.
Freeport, Tex./Oyster Creek, Tex. 2,400
Plaquemine, La. 1,160
Ethyl Corp.
Houston, Tex. 260
Baton Rouge, La. 550
B.F. Goodrich Chem. Co.
Calvert City, Ky. 1,000
PPG Industries
Lake Charles, La. 1,000
Guayanilla, P.R. 835
Shell Chem. Co.
Deer Park, Tex. 1,200
Norco, La. 1,165
Union Carbide Corp.
Taft, La. 150
Texas City, Tex. 150
Vulcan Materials Co.
Geismar, La. 240
Total • 12,320
Source: SRI, 1975.
135
-------
chlorination of ethylene can be isolated and sold. 1,2-Dichloroethane
manufactured via the oxychlorination of ethylene is used captively
as an intermediate in vinyl chloride production and cannot be
separated from that production (SRI, 1975). Table 2 offers a
compilation of production and sales figures .for DCE over the last
several years.
The great majority of all 1,2-dichloroethane produced in
the United States is used as the starting material in the manu-
facture of vinyl chloride monomer (VCM). Formerly, DCE, either
by itself or in combination with other solvents, was of considerable
importance as a commercial solvent and extractant. At this time,
however, 1,2-dichloroethane has been replaced in these applications
by'methyl chloroform, trichloroethylene, and perchloroethylene,
all of which are made from ethylene dichloride. Other important
commercial products derived from ethylene dichloride include
vinylidene chloride and ethyleneamines. Formulations of tetra-
ethyl lead, the gasoline antiknock additive, incorporate DCE as
a lead scavenger. This application of DCE is expected to continue
to decline because of the phasing out of leaded gasolines.
Miscellaneous uses of 1,2-dichloroethane include solvent applica-
tions (e.g., textile cleaning, metal degreasing, and in some
formulations of acrylic-type adhesives), production intermediate
for polysulfide elastomers, constituent of nitrile and polysulfide
rubber cements, component of upholstery and carpet fumigants, and
in the manufacture of grain fumigants (SRI, 1975; Gleason et al.,
1969). Additional uses reported in the Condensed Chemical
Dictionary (1977) include: paint, varnish, and finish removers;
soaps and scouring compounds; wetting and penetrating agents; and
ore flotation. See Table 3 for a listing of the major uses of
ethylene dichloride; Table 4 presents a breakdown of the consump-
tion patterns for 1974 and 1976.
Domestic consumption of DCE is projected to increase by an
estimated 4% annually through 1979. Currently, over 90% of the
vinyl chloride produced in the United States is based on DCE;
136
-------
Table 2. PRODUCTION3 AND SALES OF DCE
(106 Ib)
Year
1960b
1965b
1970C
1973C
1974C
1975C'd
Production
1,267
2,850
7,460
9,293
9,165
7,977
Sales
438
309
1,314
1,351
1,314
762
Production totals may be understated because
some EDC is produced but not separated or
accurately measured, and therefore not accurately
reported by some producers.
bSRI, 1975
CU.S. International Trade Commission, 1970,
1973, 1974, 1975.
Reasons for the production decline are not
clear; however, the dropoff may only reflect
short-term recessionary influences.
137
-------
Table 3. DCE CONSUMPTION PATTERN
1974 1976
Vinyl chloride
Methyl chloroform
Trichloroethylene
Perchloroethylene
Vinylidene chloride
Ethyleneamines
Lead scavenger
Miscellaneous
Exports
81
3
3
3
2
3
2
neg.
3
100
86
3
2
2
—
3
2
—
-
TZV~-
Source: SRI, 1975; EPA, 1977a.
138
-------
the remainder is manufactured by the addition of hydrogen chloride
to acetylene. The latter process was responsible for 48% of U.S.
vinyl chloride production in 1963 and could be used to replace
the currently favored DCE route (U.S. EPA, 1977a).
HEALTH EFFECTS
Human
The primary effects of DCE exposure are CNS depression and
gastrointestinal upset. These symptoms are characteristic of
acute, subacute, and chronic exposure to 1,2-dichloroethane.
Liver, kidney, and adrenal injuries occur in a dose-related
fashion. The symptom of nausea and vomiting is quite striking
and is similar to that seen from carbon tetrachloride (Irish,
1963).
The NIOSH Criteria Document on 1,2-dichloroethane (1976) is
replete with documented cases of fatal and nonfatal human exposure
to ethylene dichloride. Most of the injurious exposures were
acute episodes and occurred through either accidental or industrial
exposure. Ingestion of 20 to 50 ml (30-70 g) of DCE is often
fatal within a few days at most (Gleason et al., 1969). Blood
disorders appear characteristic of DCE ingestion, with clotting
difficulties being the most common. Death is often attributed to
circulatory and respiratory failure, with varying degrees of
liver and kidney damage (NIOSH, 1976).
The effects of acute exposure to DCE by skin absorption and
inhalation are similar to those seen following ingestion, although
blood disorders are less prominent. Headache, weakness, eye
irritation, cyanosis, nausea, and vomiting appear first, followed
by loss of consciousness and respiratory and circulatory failure.
Postmortem findings often include damage to the liver, kidneys,
and lungs (NIOSH, 1976).
139
-------
Although fatal cases have been reported following chronic
exposure to DCE, fatalities are more commonly associated with
acute episodes. Nonetheless/ progressive chronic effects can
result if DCE exposure is not adequately limited. Rosenbaum
(1947) reported that symptoms of acute exposure can rapidly
develop following several exposures to 75-125 ppm of DCE. A
number of Rosenbaum1s cases resulted in death when the worker
experienced acute poisoning symptoms two or more times over a 2-
to 3-week period. Urosova (1953) reported that 1,2-rdichloroethane
appeared in the milk of nursing mothers who were occupationally
exposed to DCE by inhalation and skin adsorption. In a related
experiment/ the author measured the amount of DCE in breath and
milk samples from a woman exposed to approximately 15.5 ppm of
1,2-dichloroethane for an unspecified length of time. Eighteen
hours following the exposure, 0.20-0.63 mg/100 ml 1,2-dichloroethane
was found in her milk and 0.01-0.02 mg/1 (2-4 ppm) was found in
her breath.
Animal
Animal studies with DCE have demonstrated effects similar to
those reported in humans, including narcosis, pulmonary congestion
and edema, blood clotting disorders, and liver, adrenal, and
kidney damage (NIOSH, 1976; Irish, 1963). Heppel et al. (1944)
demonstrated corneal clouding in dogs following DCE exposure;
however, this has not been observed in humans.
EPA was officially notified by NCI on November 14, 1977, of
the preliminary results of a 90-day rat and mouse feeding study.
The preliminary findings were as follows:-
Rat—Male: Squamous cell cancer of the forestomach;
hemangiosarcomas at all sites, e.g., liver, spleen. Female:
Mammary adenocarcinoma.
140
-------
M&F
M
F
50 mg/kg
100
150
100 mg/kg
200
300
Mouse—Male: Hepatocellular carcinoma? Lung adenoma?
Hepatocellular carcinoma? Lung adenoma? Female: Mammary
adenocarcinoma; lung adenoma? Endometrial polyps?
1,2-Dichloroethane was also studied as part of NCI's biossay
program. DCE was administered by gastric intubation to mice and
rats of both sexes five times per week over a period of 78
weeks. The following dose levels were used:
Species Sex Low dose High dose
Rat
Mouse
The study has not been finalized; however, the preliminary
results described below appear to indicate that DCE is
carcinogenic in both species.
Male rats developed statistically significant numbers
of squamous cell carcinomas of the forestomach (a rare growth in
the rat species tested) as well as statistically significant
numbers of hemangiosarcomas of the circulatory system. Female
mice and rats, on the other hand, developed statistically signifi-
cant numbers of mammary gland adenocarcinomas. The tentative
conclusion of the bioassay report is that DCE is a carcinogen in
male and female rats and female mice (Dr. Sidney Siegel of NCI,
meeting presentation, December 15, 1977).
The tumors observed in the DCE experiment are similar to
those seen by Olson et al. (1973) in their gastric intubation
study of ethylene dibromide (EDB), the brominated analog of DCE.
However, the growths observed .in the DCE study were not as dramatic
as those associated with EDB in terms of both the numbers of
tumors observed and the rapidity of their development (Dr. Ciprieno
Cueto of NCI, personal communication, November 3, 1977;
Dr. Sidney Siegel of NCI, meeting presentation, December 15,
1977).
141
-------
1,2-Dichloroethane has been shown to be weakly mutagenic in
bacteria without metabolic activation (Voogd et al., 1972; Voogd,
1973; Brem et al., 1974; Rosenkranz et al., 1974). Attempts to
increase the bacterial mutagenic activity of DCE using a rat
liver homogenate for activation (Ames test) -were unsuccessful.
The authors ascribed the difficulty to metabolic inefficiencies
in the in vitro system (McCann et al., 1975). The major metabolic
products of DCE in mammalian systems have been tentatively
identified as chloroacetic acid/ chloroethanol, and chloroacetalde-
hyde (Yllner, 1971; Heppel and Porterfield, 1948). In the Ames
test, chloroacetic acid was negative while chloroethanol responded
weakly, in similar fashion to DCE. Chloroacetaldehyde, however,
was hundreds of times more effective than DCE or chloroethanol
•
(on a molar basis) in reversion of Salmonella bacterial strains
(McCann et al., 1975).
Chloroacetaldehyde and chloroethylene oxide have been
implicated as likely in vitro metabolites of vinyl chloride
(Gothe et al., 1974). Chloroethylene oxide is known to rearrange
spontaneously to Chloroacetaldehyde (Zief and Schramm, 1964).
Furthermore, both compounds have been found mutagenic in the Ames
test (McCann et al., 1975; Malaveille et al., 1975), suggesting
that one or both of these metabolites may be the true active
carcinogenic form of vinyl chloride (McCann et al., 1975). If
the preceding is verified and Chloroacetaldehyde is found to be
the active metabolite of both DCE and vinyl chloride, the implica-
tions for DCE would obviously be of great significance. McCann
et al. (1975) reported that Chloroacetaldehyde, on the basis of
its potent mutagenic activity, is likely to be a carcinogen and
should be evaluated for its carcinogenic potential. Lawrence et
al. (1972), in an extensive study of Chloroacetaldehyde, observed
lung changes in exposed rats that are suggestive of a premalig-
nant condition.
In mutagenic studies, 1,2-dichloroethane displays greater
killing and mutagenic effectiveness than monofunctional agents
142
-------
(such as methyl methanesulfonate). This phenomenon (shared by
neutrons and bifunctional alkylating agents, among others) has
been described as "genetic death" and is characterized by the
ability to cause considerable damage to DNA and equal damage to
proteins (as measured by enzyme inactivation). As an example,
consider ethylene oxide and diepoxybutane: while both exhibit
the same approximate immediate toxicity, the bifunctional agent
provokes a delayed killing response that renders diepoxybutane
two orders of magnitude more toxic at the stage of maturity of
barley plants (in this instance). This difference can be explained
in terms of the severe consequences of the cross-linking of DNA,
especially with respect to the inability of exposed cells to
duplicate DNA and perform mitosis. Furthermore, cross-linking
may follow primary alkylation at a site which is not, per se,
considered to be involved in mutagenesis, and thus the effect of
the bifunctional agent is considerably enhanced over that seen
for monofunctional chemicals (Ehrenberg et al., 1974).
ENVIRONMENTAL ASPECTS
The annual release of DCE to the environment has been
estimated in two EPA-sponsored reports. One investigation (U.S.
EPA, 1976a) estimates that 560 million Ib of DCE was released
domestically in 1973. The second report (U.S. EPA, 1975a) claims
that the actual release rate of DCE is somewhat lower, with 163
million Ib released in 1974. This latter figure was generated in
a more careful fashion since losses from several specific categories
were considered, whereas the first report used only percentages
of production and consumption. In the second EPA report, emissions
of DCE during the manufacture of end products, principally vinyl
chloride, were identified as the major source of environmental
losses. Production of DCE was cited as the next largest emissions
category. Of the two processes used to manufacture DCE, the
oxychlorination method was felt to emit five times as much DCE as
the direct chlorination scheme for the same quantity of product.
The third major source of DCE emissions was its use as a solvent
143
-------
(100% losses assumed). Storage and distribution of DCE were
identified as the last major loss category. Refer to Table 4 for
further information.
Figure 1 presents a schematic of the losses and waste
products associated with vinyl chloride production. Waste
streams 4 and 5 in the figure represent the most hazardous
process wastes associated with vinyl chloride production. These
"heavy ends" (often called DCE tars) are most commonly disposed
of via uncontrolled incineration in the United States. This is
not considered an environmentally adequate method, as controlled
incineration practices will reduce air pollution while having no
impact on water and noise pollution (U.S. EPA, 1976b).
In some European countries, DCE tars are dumped in ocean
waters (e.g., the North Sea) where the tars may have adverse
effects on the marine environment (Jensen et al., 1975). This
method of disposal is apparently not used in the United States,
although this could not be confirmed.
1,2-Dichloroethane, being a vicinal or neighboring dihalide, •
is virtually unreactive in water. The half-life of DCE in water
(via chemical degradation only) is estimated to be on the order
of thousands of years (U.S. EPA, 1977b).
DCE has been found in 11 raw water locations at levels from
less than 0.2 to 3.1 ug/1 and in 26 finished water locations
(32.0 of total) at levels ranging from 0.2-6.0 yg/1 (U.S. EPA,
1975b). A more recent EPA-sponsored study (1977c) of ambient
surface waters collected from 204 sites near heavily industrialized
areas across the United States 'identified DCE in 53 of the samples
(26% of total). The reported values ranged from 1 ppb (detection
limit) to 90 ppb (Delaware River site) (U.S. EPA, 1977c).
144
-------
Table 4. 1,2-DICHLOROETHANE EMISSIONS ESTIMATE
(based on 1974 domestic DCE production of 9,300 million Ib)
Source strength DCE emissions
Source (106 Ib) % Loss (10b Ib)..
End product mfg. 8,500 1.0 85.0
DCE production
Oxychlorination 3,906 1.2 48.3
Direct chlorination 5,394 0.2 9.7
Solvent uses 14 100 14
Storage/distribution 9,300 0.06 6
Total 163
Source: EPA, 1975a.
145
-------
HCL SEPARATOR
PYROLYSIS
FURNACE
VINYL
CHLORIDE
SEPARATION
BASIS: 1 KG VINYL CHLORIDE MONOMER
VINYL CHLORIDE 1.0
ETHYLENE 0.50
.u
en
REFLUX
CONDENSOR
VENT
CHLORINE 1.22
CHLORINATION
REACTOR
FEED
NEUTRALIZATION
FILTER
LIGHT ENDS
REMOVAL
HEAVY ENDS
REMOVAL
CAUSTIC WASH AGE (WATER;) (2)
1.2-DICHLOROETHANE 0.00435
SODIUM HYDROXIDE 0.00090
SODIUM CHLORIDE
VINYL CHLORIDE
METHYL CHLORIDE
ETHYL CHLORIDE
0.00033
0.00093
0.00035
0.00085
I
FILTER EFFLUENT (SOLID)
TARS TRACE
SOLIDS (AS CARBON) 0.00008
FILTER EFFLUENT (LIQUID)
1,2-DICHLOROETHANE 0.0005
SODIUM HYDROXIDE TRACE
TO WATER
TO LAND
Figure 1. Vinyl chloride monomer manufacture.
Source: EPA, 1975b.
-------
VENT ON REFLUX CONDENSOR (GAS)
ETHANE 0.0049
1,2-DICHLOROETHANE 0.012
METHANE 0.0049
TO AIR
HEAVY ENDS
1,2-DICHLOROETHANE 0.0024
1,1,2-TRICHLOROETHANE 0.004
TETRACHLOROETHANE 0.004
TARS i TRACE
TO LAND
HEAVY ENDS
HEAVY ENDS
1,2-DICHLOROETHANE
TARS
SO LIDS ASH
TO LAND
0.037
0.0008
0.00005
0.0002
Figure 1. (Continued)
147
-------
Data available in 1975 estimate that the atmospheric half-
life of DCE is 3-4 months (U.S. EPA, 1975c). The stability
estimate is based on the reaction of DCE with free hydroxy radicals,
Subsequent to the formulation of this half-life estimate, the
projected atmospheric concentration of hydroxyl radicals was
revised downward. This would imply a longer atmospheric lifetime
for DCE than formerly estimated. The increased half-life of DCE
may be significant with respect to the ozone depletion controversy
if it can be demonstrated that DCE or its reaction products are
stable enough to enter the stratosphere (Frank Letkiewicz, U.S.
EPA, personal communication, November 8, 1979). The expected
major products of the reaction between DCE and hydroxyl radicals
are monochloroacetvl chloride, hydrogen chloride, and monochloro-
acetic acid (U.S. EPA, 1975c).
1,2-Dichloroethane is slightly lipophilic in biological
systems and thus has a slight tendency to bioaccumulate in the
fat. However, bioaccumulation appears to be minimal (U.S. EPA,
1977b).
148
-------
REFERENCES
Brem, Henry et al. The mutagenicity and DNA-modifying effect
of haloalkanes. Cancer Res. 34_:2576, 1974.
Condensed Chemical Dictionary (CCD), 9th ed. New York, Van
Nostrand Reinhold Co. 1977.
Ehrenberg, L. et al. On the reaction kinetics and mutagenic
activity of methylating and 3-halogenoethylating gasoline
additives. Radiat. Bot. 15^185, 1974.
Gleason, M. N. et al. Clinical Toxicology of Commercial Products.
Baltimore, Williams and Wilkins Co. 1969.
Gothe, R. et al. Trapping with 3,4-dichlorobenzenethiol of
reactive metabolites formed in vitro from the carcinogen
vinyl chloride. Ambio 3^:234, 1974. (As cited in McCann
et al., 1975)
Hardie, D. W. F. Chlorocarbons and chlorohydrocarbons. Iri
Kirk-Othmer Encyclopedia of Chemical Technology, vol~5.
New York, Interscience Publishers. 1967. p. 149.
Heppel, L. A. et al. Toxicology of dichloroethane: I. Effect on
the cornea. AMA Arch. Ophthalmol. 32_:391, 1944. (As
cited in Irish, 1963)
Heppel, L. A., and V. T. Porterfield. Enzymic dehalogenation of
certain brominated and chlorinated compounds. J. Biol. Chem.
17_£:763, 1948. (As cited in McCann et al. , 1975)
Irish, D. D. Halogenated hydrocarbons: I. Aliphatic. In_ F.
A. Patty (ed.), Industrial Hygiene and Toxicology, vol.
II. New York, Interscience Publishers. 1963. p. 1280.
Jensen, S. et al. On the chemistry of EDC-tar and its biological
significance in the sea. Proc. R. Soc. London Ser. B 189;
333, 1975.
Lawrence, W. H. et al. Toxicity profile of chloroacetaldehyde.
J. Pharm. Sci. 61:19, 1972. (As cited in McCann et al.,
1975)
Lowenheim, Frederick A., and Marguerite K. Moran. Faith, Keyes,
and Clark's Industrial Chemicals, 4th ed. New York, John
Wiley and Sons. 1975. p.' 392.
Malaveille, C. et al. Mutagenicity of vinyl chloride, chloro-
ethylene oxide, chloroacetaldehyde, and chloroethanol. Biochem.
Biophys. Res. Commun. 63:363, 1975. (As cited in McCann
et al., 1975)
149
-------
McCann, Joyce et al. Mutagenicity of chloroacetaldehyde, a possible
metabolic product of 1,2-dichloroethane (ethylene dichloride),
chloroethanol (ethylene chlorohydrin), vinyl chloride and
cyclophosphamide. Proc. Natl. Acad. Sci. U.S.A. 72^(8) :3190,
1975.
National Institute of Occupational Safety and Health (NIOSH).
Criteria for a Recommended Standard. Occupational Exposure
to Ethylene Dichloride. 1976.
Olson, W. A. et al. Induction of stomach cancer in rats and mice
with halogenated aliphatic fumigants. J. Natl. Cancer Inst.
51(6):1993, 1973.
Rapoport, I. S. Reaction of gene proteins with ethylene chloride.
Akad. Nauk. SSSR Dokl. Biol. Sci. 134;745, 1960. (As cited
in McCann et al., 1975)
Rosenbaum, N. D. Ethylene dichloride as an industrial poison.
Gig. Sanit. 12(2):17, 1947. (As cited in NIOSH, 1976)
Rosenkranz, S. et al. 2-Haloethanols: Mutagenicity and reactivity
with DNA. Mutat. Res. 26:367, 1974. (As cited in McCann et
al., 1975)
Shakarnis, V. F. Induction of X-chromosome nondisjunction and
recessive sex-linked lethal mutations in females of Drosophila
melanogaster by 1,2-dichloroethane. Genetica 5_:89, 1969.
(As cited in McCann et al., 1975)
Stanford Research Institute (SRI). Chemical Economics Handbook.
Menlo Park, Calif. 1975.
Urosoya, T. P. About a possibility of dichloroethane absorption
into milk of nursing women when contacted under industrial
conditions. Gig. Sanit. 18:36, 1953. (As cited in NIOSH,
1976) —
U.S. Environmental Protection Agency (U.S. EPA). Assessment of
Ethylene Dichloride as a Potential Air Pollution Problem,
vol. III. 1975a.
U.S. Environmental Protection Agency. Draft Report for Congress:
Preliminary Assessment of Suspected Carcinogens in Drinking
Water. 1975b. (As cited in EPA, Potential Industrial
Carcinogens and Mutagens, EPA 560/5-77-005, 1977)
U.S. Environmental Protection Agency. Report on the Problem
of Halogenated Air Pollutants and Stratospheric Ozone.
ESRL-ORD, EPA 600/9-75-008, 1975c.
150
-------
U.S. Environmental Protection Agency. Scoring of Organic Air
Pollutants: Chemistry, Production and Toxicity of Selected
Synthetic Organic Chemicals. 1976a.
U.S. Environmental Protection Agency. Assessment in Industrial
Hazardous Waste Practices, Organic Chemicals, Pesticides
and Explosives. 1976b.
U.S. Environmental Protection Agency. A Study of Industrial
Data on Candidate Chemicals for Testing. EPA 560/5-77-006,
1977a.
U.S. Environmental Protection Agency. Review of the Environmental
Fate of Selected Chemicals. EPA 560/5-77-003, 1977b.
U.S. Environmental Protection Agency. Monitoring to Detect
Previously Unrecognized Pollutants in Surface Waters. EPA
560/6-77-015, 1977c.
U.S. International Trade Commission. Synthetic Organic Chemicals.
1969, 1971, 1973, 1974, 1975.
Voogd, C. E. et al. On the mutagenic action of dichlorovos.
Mutat. Res. 16:413, 1972. (As cited in McCann et al.,
1975)
Voogd, C. E. Mutagenic action of epoxy compounds and several
alcohols. Mutat. Res. 21:52, 1973. (As cited in McCann
et al., 1975)
Yllner, S. Metabolism of 1,2-dichloroethane- C in the mouse.
Acta Pharmacol. Toxicol. 30:257, 1971. (As cited in McCann
et al., 1975)
Zief, M., and C. H. Schramm. Chloroethylene oxide. Chem. Ind.
1£:660, 1964. (As cited in McCann et al., 1975)
*This document was prepared for the U.S. Environmental Protection
Agency by the MITRE Corp. It is a secondary source and does not
cite its primary references. Thus, verification of some informa-
tion is not possible. The environmental release data were taken
from NSF/Rann Research Program on Hazard Priority Ranking of
Manufacturing Chemicals.
151
-------
CHEMICAL HAZARD INFORMATION PROFILE
N,N-dimethyIformamide
Date of report: April 13, 1978
This chemical was chosen for study because of the exposure
potential associated with its use as a solvent and because of an
inquiry regarding its health effects.
The following recommendations are made regarding further OTE
evaluation of the possible health or environmental hazards of N,N-
dimethylformamide (DMF):
(1) Check TSCA inventory for production volume—Good produc-
tion figures are not currently available.
(2) Consider need for testing—The use patterns of DMF along
with its potential for a greatly increased market imply a
potential for widespread exposure. Also, the results of
teratogenicity studies performed to date are somewhat
conflicting.
(3) Require Section 8(a) submission—Determine the extent to
which DMF is used in consumer products.
This report represents a preliminary investigation of the
subject chemical's potential for injury to human health and the
environment. The information contained in the report is drawn
chiefly from secondary sources and available reference documents.
Because of the limitations of such sources, it necessarily follows
that this report may not reflect all available information on the
subject chemical.
Any recommendations based on this report are tentative and
should not be construed as final Agency policy with respect to the
subject chemical.
152
-------
CHEMICAL HAZARD INFORMATION PROFILE
N,N-dimethylformamide
Date of report: April 13, 1978
N,N-dimethylformamide is a liquid which boils at 153°C and
has a vapor pressure of 3.7 iran Hg. It is infinitely soluble in
water, alcohol, and ether (Weast, 1971; MITRE Corp., 1976).
PRODUCTION AND USE
Dimethylformamide (DMF) is produced commercially by reacting
dimethylamine and methyl formate (Louderback, 1965). Production
figures for DMF itself could not be found because there are only
two producers (U.S. ITC, 1975). However, the EPA Organic Chemical
Producer's Data Base does contain data on DMF production. In
1972, SRI estimated that about half the dimethylamine produced
was used for the manufacture of DMF and dimethylacetamide; 96
million Ib of dimethylamine was produced in 1972.
Dimethylformamide is a polar, relatively nonvolatile
solvent used in the manufacture of films, fibers, adhesives, and
coatings. Examples of polymer products made in this solvent are
polyacrylonitrile fibers, polyvinyl chloride, urethane fabric
coatings, and Orion®. DMF is a component in paint strippers and
is a solvent for pigments of low solubility. These pigments
include azo dyes and nitroso compounds and are used in textiles,
paper, and plastics. Antifreeze gasoline additives contain
small quantities of DMF. DMF is used as a selective extractant
in the purification of oils and gases and is also used as catalyst
and intermediate in the production of acetals, aldehydes,
esters, and other compounds (Louderback, 1965).
HEALTH EFFECTS
Single exposures to dimethylformamide are not particularly
hazardous, but irreversible systemic damage can occur when DMF
153
-------
is inhaled or absorbed through the skin over a period of time
(Louderback, 1965).
DMF has low acute oral toxicity; the rat oral LD5Q is 4,200
mg/kg. Central nervous system toxicity was reported in humans
who inhaled concentrations of 20 ppm (NIOSH, 1975). In a case
of acute occupational exposure involving both inhalation and
dermal exposure, DMF caused severe abdominal pain and hepatic
abnormalities. Disturbed porphyrin metabolism was suggested as
a possible mechanism; other symptoms included anorexia, vomiting,
dermal irritation, hypertension, and weakness (Potter, 1973) .
Among workers exposed to DMF, allergic gastritis and
dermatitis have been reported (DiLorenzo and Grazioli, 1972).
DMF enhances skin penetration (Wiles and Narcisse, 1971), so
precautions are normally taken to avoid skin contact. In a
fiber plant where DMF, methyl methacrylate, and acrylonitrile
were present, workers complained of skin and nervous system
disorders (Stamova et al., 1976). Workers have also noted
headaches and a flushed feeling after drinking alcohol; there is
evidence that ethanol alters DMF metabolism in rats (Hanasono et
al., 1977).
Several Russian scientists have done experiments which
attempt to measure chronic health effects of nonoccupational
exposure to DMF. Measurable quantities of DMF were present in
underwear made from polyacrylonitrile fibers. Aqueous extracts
from the cloth produced no changes in blood or liver functions
in 4 months in animals exposed dermally (Rapoport et al., 1974).
Shoes made from unstable polymers allowed both DMF and styrene
to migrate through the skin (Es'Kova Soskovets, 1973),
Carnaghan (1967) reports that no tumors were observed after
32 months in 19 rats. DMF was administered once by gastric
intubation.
154
-------
DMF can cross the placenta and does accumulate in the fetus
of rats (Sheveleva et al., 1977). DMF was applied to the skin of
pregnant rabbits during fetal organogenesis; no teratogenic
effects were seen, but slight embryotoxicity was noted (Stula and
Krauss, 1977). DMF was reported as not teratogenic to chick
embryos (reference unknown). Pregnant rats exposed via inhalation
produced normal fetuses; however, high doses led to a weight loss
in the fetus (Kimmerle and Machemer, 1975). Repeated doses of
DMF were teratogenic for mice; no other details were given (Scheufler,
1976).
Although the mechanism of DMF metabolism is not understood,
it is known that the majority of DMF is eliminated within 24 hr
in humans (Kimmerle and Eben, 1975). To estimate total exposure
to DMF, the concentration of DMF and its metabolites, mono-
methylformamide and formamide, in the urine may be measured
(Barnes and Henry, 1974). Dogs exposed chronically to 10 ppm
did not accumulate DMF (Kimmerle and Eben, 1975). The TLV for
DMF is 10 ppm (ACGIH, 1971).
ENVIRONMENTAL EFFECTS
Dimethylformamide has been found in Polish industrial
wastewater; it is not known to what extent industrial effluents
are a problem domestically (Dojlido, 1977). Due to its infinite
solubility in water, DMF does present a water treatment problem.
Romadina (1975) and Begert (1974) report that DMF can be biodegraded
by bacteria. At high DMF concentrations, though, the bacteria
are poisoned (Begert, 1975).
Dimethylformamide is listed in EPA's Chemical Spills File
and would be considered a hazardous material in the event of an
accidental spill.
155
-------
REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists).
Cincinnati, Ohio. 1971.
Barnes, J. R., and N. W. Henry. The determination of N-methyl
formamide and N-methyl acetamide in urine. Am. Ind. Hyg.
j., p. 84, February 1974.
Begert, A. Biological purification of dimethylformamide-
containing industrial sewage. Von Wasser 4_3:403, 1974.
Begert, A. Purification of chemical textile plant sewage.
Oesterr. Abwasser-Rundsch. 2_0:98, 1975. (Abstract)
Carnaghan, R. B. A. Br. J. Cancer 21.: 811, 1967. (Cited in
PHS 149)
DiLorenzo, F., and C. Grazioli. Hematologic, hematochemical
and gastric function findings in workers exposed to inhalation
of dimethylformamide vapor. Lav. Urn. 24_(4):97, 1972.
(Abstract)
Dojlido, J. Testing of biodegradability and toxicity of organic
compounds in industrial wastewaters. U.S. Environmental
Protection Agency. Polish/U.S. Symp. Wastewater Treat.
Sludge Disposal. 1977. p. 122.
Es'Kova-Soskovets, L. B. Biological effect of chemical substances
migrating from shoes during their wearing. Gig. Sanit. 3_8_:
101, 1973. (Abstract)
Hanasono, G. K., R. W. Fuller, W. D. Broddle, and W. R. Gibson.
Studies on the effects of N,N'-dimethylformamide on ethanol
disposition and monoamine oxidase activity in rats. Toxicol.
Appl. Pharmacol. 39_:461, 1977.
Kimmerle, B., and A. Eben. Metabolism studies of N,N-dimethyl-
formamide: II. Studies in persons. Int. Arch. Arbeitsmed.
34_(2):127, 1975. (Abstract)
Kimmerle, G., and L. Machemer. Studies with N,N-dimethylformamide
for embryotoxic and teratogenic effects on rats after dynamil
inhalation. Int. Arch. Arbeitsmed. 3£(3):167, 1975.
(Abstract)
Llewellyn, G. C., W. S. Hastings, and T. D. Kimbrough. The effects
of dimethylformamide on female mongolian gerbils, Reriones
ungulculatus. Bull. Environ. Contain. Toxicol. 11 (5) ;467,
1974.
Louderback, H. Kirk-Othmer Encyclopedia of Chemical Technology,
2nd ed., vol. 10. New York, John Wiley and Sons, Inc.
1965. p. 109.
156
-------
MITRE Corp. Scoring of Organic Air Pollutants. Chemistry/ Production,
and Toxicity of Selected Synthetic Organic Chemicals. 1976.
NIOSH. Registry of Toxic Effects of Chemicals, 1975 ed.
Potter, H. Phelps. Dimethylformamide-induced abdominal pain and
liver injury. Arch. Environ. Health 2J7-.340, 1973.
Rapoport, K. A., S. F. lonkina, and L. A. Mintseva. Hygienic
evaluation of underwear made of polyacrylonitrile fibers and
their mixtures with natural fiber. Gig. Sanit. 12^:85, 1974.
(Abstract)
Romadina, E. S. Direct action of microorganisms. Biol. Samoochish-
Chemie 2nd, 110, 1975. fAbstract)
Scheufler, H. Experimental testing of chemical agents for
embryotoxicity, teratogenicity, and mutagenicity. Biol.
Rundsch. 1£(14):227, 1976. (Abstract)
Schottek, W. Experimental animal studies on the toxicity of
dimethyl formamide under repeated use. Acta Biol. Med. Ger.
2^(2) :359, 1970. (Abstract)
Sheveleva, G. A., 0. V. Sivochalova, S. A. Osina, and L. S.
Sal'nikova. Permeability of placenta to dimethylformamide.
Akush. Ginekol. 5_:44, 1977. (Abstract)
Stamova, N., N. Ginceva, M. Spasovski et al. Labor hygiene during
the production of Bulana synthetic fibers. Khig. Zdraveopaz.
:134, 1976. ("Abstract)
Stanford Research Institute (SRI) . Chemical Economics Handbook.
Menlo Park, Calif. 1975.
Stula, E. F., and W. C. Krauss. Embryotoxicity in rats and
rabbits from cutaneous application of amide- type solvents
and substituted ureasP. Toxicol. Appl. Pharmacol. 41(1):
35, 1977. (Abstract)
Tanka, K. I. Toxicity of dimethylformamide to the young female
rat. Int. Arch. Arbeitsmed. 7£(2):96, 1971. (Abstract)
Ungar, H., S. F. Sullman, and A. J. Zuckerman. Acute and protracted
changes in the liver of Syrian hamsters induced by a single
dose of aflatoxic PI1. Br. J. Exp. Pathol . 57(2) :157,
1976. (Abstract)
*This document was prepared for the U.S. Environmental Protection
Agency by the MITRE Corp. It is a secondary source and does not
cite its primary references. Thus, verification of some informa-
tion is not possible. The environmental release data were taken
from NSF/Rann Research Program on Hazard Priority Ranking of
Manufacturing Chemicals.
157
-------
U.S. International Trade Commission (U.S. ITC). Synthetic
Organic Chemicals, United States Production and Sales. 1975,
Weast, Robert C. (ed.). CRC Handbook of Chemistry and Physics,
52nd ed. Cleveland, The Chemical Rubber Co. 1971.
Wiles, J. S., and J. K. Narcisse. The acute toxicity of dimethyl-
amides in several animal species. Am. Ind. Hyg. Assoc.
J. 32(8):539, 1971. (Abstract)
158
-------
CHEMICAL HAZARD INFORMATION PROFILE
Dinitrosopentamethylenetetramine
Date of report:June 1,1978
This chemical was chosen for study because of worker complaints
received by OSHA. Workers at a dinitrosopentamethylenetetramine
(DNPT) plant complained of fainting, dizziness, cyanosis, and
convulsions.
It is recommended that judgment on DNPT be deferred until OSHA
completes its report on occupational health problems associated
with the chemical. The OSHA study should provide a much better
characterization of the problem than is currently available.
This CHIP should be updated based on the additional information
obtained.
This report represents a preliminary investigation of the
subject chemical's potential for injury to human health and the
environment. The information contained in the report is drawn
chiefly from secondary sources and available reference documents.
Because of the limitations of such sources, it necessarily follows
that this report may not reflect all available information on the
subject chemical.
Any recommendations based on this report are tentative and
should not be construed as final Agency policy with respect to the
subject chemical.
159
-------
CHEMICAL HAZARD INFORMATION PROFILE
Dinitrosopentamethylenetetramine
Date of report: June 1, 1978
Synonyms: DNPT; 3,7-dinitroso-l,3,5,7-tetraazabicy-
clononane
CAS No.: 101-25-7
CHEMICAL CHARACTERISTICS
A structural diagram of DNPT is shown below:
CH2 N CH2
0-N-N CH, N-N-0
CH2 N CH2
DNPT is a light-yellow solid which decomposes at 207^C.
When used with rubber or plastics, its decomposition temperature
is lowered to 130-190HC. It is slightly soluble in water,
alcohol, and benzene, and dissolves readily in dimethyIformamide
(IARC; 1976; McCaleb, 1978).
PRODUCTION AND USE
IARC reports U.S. consumption of DNPT at 3 million Ib in
1970. SRI estimates annual production at 2-3 million Ib. The
U.S. ITC (1975) reports one producer, Stepan Chemical Co.
DNPT is used as a blowing agent in rubbers and plastics.
Natural and synthetic unicellular rubber, which is made using
DNPT, is used as carpet underlay-, weatherstripping, insulation,
shoe lining, and cushioning. DNPT is also an effective blowing
agent for polyvinyl chloride plastisols and epoxy, polyester,
and silicone resins.
160
-------
DNPT is produced from hexamine (hexamethylenetetramine),
HC1, and sodium nitrite. During its use as a blowing agent,
acidic substances such as phthalic anhydride and ethylene glycol
are often added to accelerate the reaction and to lower the
temperature of the decomposition process. Decomposition products
are not fully elucidated; possible ones are amines, water,
nitrous oxide, nitrogen gas, formaldehyde, and ammonia. A fishy
odor, due to the amines, and the high decomposition temperature
make DNPT an unsuitable blowing agent for many plastics, though
it is the most widely used blowing agent for rubber sponges
(McCaleb, 1978).
HEALTH ASPECTS
The chemical was referred to us by OSHA (Stewart, 1978),
which is investigating complaints of fainting, dizziness, cyanosis,
and convulsions at a DNPT production plant. All ten workers
reported one or more symptoms. An OSHA medical team plans to
carefully inspect the plant during the week of May 30, 1978.
No health effects information was found aside from the IARC
report, which is summarized below.
The rat oral LD was 940 mg/kg. A dose of 80 mg/kg injected
intraperitoneally for 30 days was tolerated. Higher doses
produced toxic effects within the central nervous system, including
depression of conditioned reflexes and tonic and clonic spasms
(Desi et al., 1967).
No tumors were induced in female rats given a single oral
dose of 90 mg DNPT within 6 months (Griswold et al., 1966), nor
were tumors induced after 18 months in 15 male and 15 female
rats given 9 mg DNPT by oral gavage daily for 1 year (Weisburger
et al., 1966). Rats fed 0.03, 1, 3, or 9 mg DNPT 4 days/week for
a year did not have an increased tumor incidence after 18 months
(Hadidian et al., 1968).
161
-------
Boyland et al. (1968) reported that of 24 male rats given
weekly IP injections of 25 mg DNPT for 26 weeks, 13 survived
over 16 months. One developed a hepatoma and another developed
a pituitary tumor. However, one of the controls developed a
hepatoma, and IARC concluded that DNPT is not a rat carcinogen
by oral administration or by intraperitoneal injection.
162
-------
REFERENCES
Boyland, E. et al. Carcinogenic properties of certain rubber
additives. Eur. J. Cancer 4_:233, 1968.
Desi, F. et al. Investigations on the nervous effects of N,N-
dinitrosopentamethylenetetramine (Mikrofor) in rats. Med.
Lav. 58_:22, 1967.
Griswold, P. P. et al. On the carcinogenicity of a single intra-
gastric dose of hydrocarbons, nitrosamines, aromatic amines,
dyes, coumarins, and miscellaneous chemicals in female Sprague-
Dawley rats. Cancer Res. ^£:619, 1966.
Hadidian, Z. et al. Tests for chemical carcinogens. J. Natl.
Cancer Inst. £1:985, 1968.
International Agency for Research on Cancer (IARC). Evaluation of
Carcinogenic Risk of Chemicals to Man, vol. 11, 1976. p.
241.
McCaleb, Kirt, at SRI International, Menlo Park, Calif., personal
communication, May 18, 1978.
Stewart, Trish, OSHA, personal communication, May 18, 1978.
U.S. International Trade Commission (U.S. ITC). 1975.
Weisburger, J. H. et al. New carcinogenic nitrosamines. Natur-
wissenschaften 5_3:508, 1966.
Additional Sources Suggested for Further Study
Encyclopedia of Polymer Science and Technology, vol. 2, Blowing
Agents (Chapter) has a few pages on DNPT.
Reed, R. A. Plastic progress. London, Iliffe and Sons Ltd. 1955.
p. 51-80.
Reed, R. A. Br. Plast. 3_3(10) :469, 1969.
Rubber Age, February 1976, p. 22.
Rubber World Blue Book 1975. Useful for trade names.
163
-------
CHEMICAL HAZARD INFORMATION PROFILE
2,4-Dinitrotoluene
Date of report: March 9, 1978
This chemical was chosen for study because of a deter-
mination of its carcinogenicity in an NCI bioassay.
If the contractor report on nitroaromatics does not provide
adequate use information on 2,4-dinitrotoluene, TSCA Section
8(a) submissions should be required. Use information will be
necessary for exposure estimates. A revised Chemical Hazard
Information Profile should be prepared when satisfactory use
information is obtained.
This report represents a preliminary investigation of the
subject chemical's potential for injury to human health and the
environment. The information contained in the report is drawn
chiefly from secondary sources and available reference documents.
Because of the limitations of such sources, it necessarily
follows that this report may not reflect all available information
on the subject chemical.
Any recommendations based on this report are tentative and
should not be construed as final Agency policy with respect to
the subject chemical. *
164
-------
CHEMICAL HAZARD INFORMATION PROFILE
2,4-Dinitrotoluene
Date of report: March 9, 1978
CHEMICAL CHARACTERISTICS
2,4-Dinitrotoluene (C_HgN 0 ) exists as yellow crystalline
needles at room temperature. Its melting range is from 69.5 to
70.5°C. 2,4-Dinitrotoluene (2,4-DNT) decomposes at 300°C. Its
molecular weight is 182.1, and its density is 1.521 (at 15°C).
2,4-DNT is sparingly soluble in water (0.027 g/100 ml at 22°C)
and is soluble in ether and in alcohol. Synonyms for 2,4-DNT
(CAS No. 121-14-2) include 2,4-dinitrotoluol and l-methyl-2,4-
dinitrobenzene. 2,4-DNT is considered a moderate fire and
explosion risk. It can be detonated only by a strong initiator
but may become an explosion hazard when involved in fire (Sax,
1968).
PRODUCTION AND USE
Dinitrotoluene can be produced by batch or continuous
process. The starting material is usually 2- or 4-nitrotoluene,
although toluene itself is sometimes used. The dinitrotoluene
resulting from use of 2-nitrotoluene will contain both the 2,4-
and 2,6-isomers. The continuous process may consist of several
reactors joined in series. The raw materials (toluene/nitrotoluene
and an acid mixture of H2SO^ and HNO-) are added only to the
first reactor. Successive chambers provided additional reaction
time. This exothermic reaction has an overall yield of roughly
96%. The acid is then removed. The crude dinitrotoluene is
washed and neutralized. Most of the product that is formed goes
directly to a reduction step, forming diaminotoluene; however,
some material may be distilled if high-purity 2,4-dinitrotoluene
is needed (U.S. EPA, 1976).
165
-------
Shipping solids, such as 2,4-DNT, in a molten state in tank
cars is a common practice. The price of 2,4-DNT was 22.SC/lb
(in tanks) in 1975 (U.S. EPA, 1976).
Manufacture of toluene diisocyanate consumes much of the
2,4-DNT produced. In 1976, 560 million Ib of toluene diisocyanate
was produced. This production consumed roughly 389 million Ib
of toluene (SRI, 1976). A total of 389 million Ib of toluene
would produce approximately 740 million Ib of 2,4-DNT, assuming
96% yield (U.S. EPA, 1976). 2,4-DNT is also used as a gelatinizing
and waterproofing agent in explosives and as a dye intermediate
(SRI, 1976).
Year
1971
1972
1973
1974
1975
U.S. DNT production
Substance
2,4- (and 2,6-) DNT
2,4- (and 2,6-) DNT
2,4- (and 2,6-) DNT
2,4- (and 2,6-) DNT
2,4-DNT
2,4- (and 2,6-) DNT
Pounds produced
352,746,000
433,885,000
471,237,000
522,842,000
308,257,000
272,610,000
Source: U.S. ITC, 1973-77.
Based upon the growth projections for the major uses
of DNT, demand should increase by 6.5 to 7.5% per year
(U.S. EPA, October 1977).
2,4-DNT is produced by Air Products & Chemicals, Inc.,
Pensacola, Fla., and by Rubicon Chemicals, Inc., Geismar, La.
2,4- (and 2,6-) DNT is produced by E. I. du Pont, Deepwater,
N.J., and by Mobay Chemicals Corp., Cedar Bayou, Tex., and New
Martinsville, W. Va. (SRI, 1975). Other companies may manu-
facture 2,4-DNT as a chemical intermediate for captive use.
166
-------
BIOLOGICAL ASPECTS
The TLV (and TWA) of 2,4-DNT is 1.5 mg/m3 (air). It may be
absorbed through intact skin. Symptoms of DNT exposure include
headache, vertigo, fatigue, shortness of breath, anorexia,
palpitation, arthralgia, insomnia, tremor, and paralysis (ITU,
1976). Advanced cases show symptoms such as jaundice and secondary
anemia (ACGIH, 1971).
Exposure of rats to 50 mg/kg 2,4-DNT (orally) or to 200 ppm
2,4-DNT (1-hr inhalation) produced no mortality. The oral LD
is 268 mg/kg for rats and 1,625 mg/kg for mice. There is evidence
that a high-fat, low-protein diet renders rats more susceptible
to TNT and DNT poisoning. Application of 200 mg/kg to the skin
of rabbits did not cause mortality, nor was it corrosive to the
skin. The LDLo for oral administration of 2,4-DNT to cats is 27
mg/kg (U.S. EPA, 1976). NCI has conducted a bioassay of 2,4-
DNT. It was fed to rats at 0.02% or 0.008% of their diet. Both
levels increased the incidence of fibroma of the skin and
subcutaneous tissue in male rats. The high dose caused a
statistically significant incidence of fibroadenoma of the
mammary gland in female rats. Mice fed 0.04% or 0.008% 2,4-DNT
did not show tumors which could be attributed to the compound.
NCI considers the results of this bioassay to be positive.
ENVIRONMENTAL ASPECTS
The aquatic toxicity rating of 2,4-DNT is 100 to 10 ppm for
96 hr of exposure (NIOSH, 1976). 2,4-DNT depressed or killed
colonies of Lemna perpusilla (an aquatic flowering plant) at
concentrations of 1 ppm and above.
Nitroaromatics are, generally, very stable in water under
neutral conditions. 2,4-DNT is an o-alkyl nitroaromatic compound,
and therefore is probably susceptible to photochemical alteration
167
-------
since such compounds isomerize to highly colored compounds which
may react further (U.S. EPA, 1976).
EPA has identified 2,6-DNT in drinking water. Kite (1961)
detected 2,4-DNT in the red water wastes from a TNT plant (Picatinny
Arsenal, Dover, N.J.) by using solvent extraction, column chroma-
tography, and infrared spectrometry. Investigators have found
DNT in the wastewater effluents of other TNT plants and in the
plant, the raw wastes, and the pond effluent of an explosives
plant (U.S. EPA, 1976).
Biodegradation experiments conducted using microorganisms
in soil, compost, or moved from a catalytic cracking plant waste
lagoon, adapted to phenol, showed that the ratio of the test
oxygen uptake rate to the endogenous rate was nearly 2.5 for
2,4-DNT. This implies that it is biodegradable to some degree.
In another study, Soviet scientists estimated that 95 to 97% of
2,4-DNT was removed after the second stage of activated sludge
digestion (U.S. EPA, 1976). Enriched pure soil culture will
slowly/partially degrade 2,4-DNT in soil.
Most of the DNT produced is used captively. However, based
on the presence of DNT in sewage wastes from TNT and explosives
manufacturing plants, environmental and water supply contamination
seems to be a distinct possibility.
168
-------
REFERENCES
American Conference of Governmental Industrial Hygienists (ACGIH).
Documentation of the Threshold Limit Values/ 3rd ed. 1971.
International Technical Information Institute (ITII). Toxic and
Hazardous Industrial Chemicals Safety Manual. Tokyo. 1976.
Kite, D., Jr. Air and stream pollution control: Preliminary
survey of thermal methods for trinitrotoluene red water
disposal. 1961. (As cited in U.S. EPA, 1976)
NIOSH. Registry of Toxic Effects of Chemical Substances, 1976
ed.
Sax, N. Irving. Dangerous Properties of Industrial Materials.
New York, Van Nostrand Reinhold Co. 1968.
Stanford Research Institute (SRI). Directory of Chemical Producers
Menlo Park, Calif. 1975.
SRI. Chemical Economics Handbook. Menlo Park, Calif. 1976.
U.S. Environmental Protection Agency (U.S. EPA). Investigation
of Selected Potential Environmental Contaminants: Nitro-
aromatics. June 1976.
U.S. Environmental Protection Agency. Information Profiles on
Potential Occupational Hazards. October 1977.
U.S. International Trade Commission (U.S. ITC). Synthetic
Organic Chemicals, U.S. Production and Sales, 1973-1977.
169
-------
Monoethanolamine 2,100 mg/kg
Diethanolamine 710 mg/kg
Triethanolamine 8,680 mg/kg
However, ethanolamines are irritating, and triethanolamine
may be sensitizing to the skin and mucous membranes (Lopukhova,
1964).
An occupational standard has been set only for monoethanolamine,
The TLV is 3 ppm (ACGIH, 1971).
Ethanolamines are a normal constituent of human urine; they
are metabolized rapidly and are ultimately incorporated into the
phospholipids of the liver and kidney (Taylor and Richardson,
1967). There is one known occupational case of acute poisoning
by monoethanolamine in which toxic liver damage and chronic hepa-
titis occurred (Jindrichova and Urban, 1971). In subacute rodent
feeding studies, all three compounds induced liver and kidney
weight changes, and diethanoiamine caused fatty degeneration of
the liver (Sutton, 1963; Hartung and Cornish, 1970). Other
pathological changes included inhibition of cholinesterase by all
ethanolamines (Hartung and Cornish, 1968).
Bose (1972) showed that triethanolamine induced meiotic
irregularities in onion cells. However, in another study (SRI,
1976) monoethanolamine did not affect meiosis in onions and did
not induce point mutations in a bacterial species. SRI experts
do not believe that either of these systems.has been adequately
characterized as a screen for mammalian gene damage.
An industry study showed that hair dye with a base containing
22% monoethanolamine did not increase the incidence of birth
defects in dogs, rabbits, or rats. The rats and dogs were exposed
orally, and the rabbits by gavage (Wernick et al., 1975).
172
-------
Kostrodymova et al. (1976) reported that a triethanolamine
solution was not carcinogenic to rats exposed via the skin; no
other details were given. Grinding fluid containing triethanol-
amine and sodium nitrite at gastric pH formed N-nitrosodiethanol-
amine (Zingmark and Rappe, 1976). Druckery et al. (1963) fed nitro-
sodiethanolamine intermittently to rats for 41 weeks, and all
developed liver cancer. David Fine (personal communication,
1977) has found concentrations of 0.02 to 3% nitrosodiethanolamine
in synthetic cutting fluids. N-nitrosodiethanolamine has been
found at levels as high as 48 ppm in cosmetics and toiletry
products (C&E News, 1977). Enviro Control Inc. has a contract
with NIOSH to study the carcinogenic effects of hydraulic and
cutting fluids which contain diethanolamine and nitrite (Tox-
tips, November 1977).
ENVIRONMENTAL EFFECTS
The MITRE Corp. (1976) reports an annual environmental
release rate for diethanolamine and triethanolamine as 36 million
Ib for each compound.
The aquatic toxicity ratings indicate that diethanolamine is
an "insignificant hazard" and that monoethanolamine and tri-
ethanolamine are "practically nontoxic" (NIOSH, 1976).
Apostol (1975) reports that he first noted acute effects in
aquatic organisms at 100 mg/1 and chronic effects at 1 mg/1. The
most sensitive organisms were daphnia, ciliated protozoa, and
amoeba.
173
-------
REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists).
Documentation of Threshold Limit Values. Cincinnati, Ohio.
1971.
Apostol, S. Ethanolamine toxicity to aquatic invertebrates.
Stud. Cercet. Biol. 2_7_(4):345, 1975. (Cited in Chem. Abstr.
£5:73051G)
Bose, S. Preliminary studies on triethanolamine induced meiotic
irregularities in onion (Allium cepa L.) Sci. Cult. 38(3):
146, 1972.
C & E News. N-nitrosoamines found in toiletry products. March
28, 1977.
Druckrey, H., R. Preussmann, and D. Schmahl. Carcinogenicity and
chemical structure of nitrosamines. Acta. Un. Int. Cancer
1£(3-4):510, 1963.
Hart, A. W. Alkanolamines. Ill Kirk-Othmer Encyclopedia of
Chemical Technology, vol. 1. 1967. p. 810-824.
Hartung, R., and H. H. Cornish. Cholinesterase inhibition in the
acute toxicity of alkyl-substituted 2-aminoethanols. Toxicol.
Appl. Pharmacol. 128 ;486y 1968.
Jindrichova, J., and R. Urban. Acute monoethanolamine poisoning.
Prac. Lek. 23_(9):314, 1971. (Cited in KEEP 72_:09648)
Kostrodymova, G. M., V. M. Voronin, and N. N. Kostrodymov. Toxicity
from the complex action and the possibility of carcinogenic
and cocarcinogenic properties of triethanolamine. Gig.
Sanit. _3:20, 1976. CCited in Chem. Abstr. 8_4_:174886t)
Lopukhova, K. A. Current problems on the effect of synthetic deter-
gents on the skin. Gig. Tr. Prof. Zabol. £(12):38-42, 1964.
MITRE Corp. Scoring of Organic Air Pollutants. Chemistry, Produc-
tion, and Toxicity of Selected Synthetic Organic Chemicals.
1976.
NIOSH. Registry of Toxic Effects of Chemical Substances. 1976.
SRI (Stanford Research Institute). A Study of Industrial Data on
Candidate Chemicals for Testing. EPA-560/5-77-006, August
1977. p. 3-179.
*This document was prepared for the U.S. Environmental Protection
Agency by the MITRE Corp. It is a secondary source and does not
cite its primary references. Thus, verification of some informa-
tion is not possible. The environmental release data were taken
from NSF/Rann Research Program on Hazard Priority Ranking of
Manufacturing Chemicals.
174
-------
Sutton, W. L. Aliphatic and alicyclic amines. In F. A. Patty
(ed.), Industrial Hygiene and Toxicology, 2nd ed. New York,
Interscience Publishers. 1963.
Taylor, R. J., Jr., and K. E. Richardson. Ethanolamine metabolism
in the rat. Proc. Soc. Exp. Biol. Med. 124(1);247, 1967.
Tox-tips. Notice of Research Project. November 1977.
U.S. ITC (U.S. International Trade Commission). Synthetic Organic
Chemicals, United states Production and Sales, 1975.
Wernick, T., B. M. Lanman, and J. L. Fraux. Chronic toxicity,
teratologic, and reproduction studies with hair dyes.
Toxicol. Appl. Pharmacol. 32_(3) : 450, 1975.
Zingmark, P. A., and C. Rappe. On the formation of N-nitrosodi-
ethanolamine from a grinding fluid under simulated gastric
conditions. Ambio 5(2): 80, 1976.
175
-------
CHEMICAL HAZARD INFORMATION PROFILE
Ethylamines
Date of report: April 1, 1978
These chemicals were chosen for study because of their
potential for being nitrosated and thereby forming nitrosamines.
Certain nitrosamines are known carcinogens.
The following recommendations are made regarding further OTE
evaluation of the possible health or environmental hazards of
ethylamines:
(1) Refer to OSHA—Toxic effects have been seen in both
humans and test animals at ethylamine concentrations
below the current OSHA standard,
(2) Refer to OPP—Diethylamine was found as a degradation
product of a commercial pesticide. This diethylamine
was subsequently nitrosated to form diethylnitrosamine.
(3) Refer to the Office of Air Quality Planning and Standards-
Significant amounts of amines may be released into the
ambient air from manufacturing sites.
(4) Require Section 8(a) submission—Determine the presence
of ethylamines in consumer products and revise this
Chemical Hazard Information Profile accordingly.
This report represents a preliminary investigation of the
subject chemical's potential for injury to human health and the
environment. The information contained in the report is drawn
chiefly from secondary sources and available reference documents.
Because of the limitations of such sources, it necessarily follows
that this report may not reflect all available information on the
subject chemical.
Any recommendations based on this report are tentative and
should not be construed as final Agency policy with respect to
the subject chemical.
176
-------
CHEMICAL HAZARD INFORMATION PROFILE
Ethylamines
Date of report: April 1, 1978
Monoethylamine is a gas which condenses at 16.6°C. Diethyl-
amine is a volatile liquid which boils at 55.5°C; trie thy lamine
is also a liquid and boils at 89.3°C. All three compounds are
soluble in water, have an ammoniacal odor, and are quite basic
(MITRE Corp., 1976) .
Vapo.r pressure
(mm Hg at 200C)
Monoethylamine 3.36 -
Diethylamine 3.39 195
Triethy lamine 3.29 53.5
Source: Sutton, 1963.
PRODUCTION AND USE
In 1975, 12.4 million Ib of diethylamine was produced.
In the preceding year over 46 million Ib of all ethylamines,
excluding diethylamines, was manufactured. This figure may
include some salts but should reflect the combined amount
of monoethylamine and triethylamine manufactured in 1974
(U.S. ITC, 1974, 1975).
The ethylamines are used mostly as chemical intermediates
for the production of pesticides, textile chemicals, medicinals,
and corrosion inhibitors. Detailed breakdowns of use categories
are not available, but some specific uses are listed below.
Monoethylamine (MEA) is used as an intermediate in the
manufacture of the following chemicals: triazine herbicides,
1,3-diethylthiourea (a corrosion inhibitor), ethylaminoethanol,
4-ethylmorpholine (urethane foam catalyst), ethyl isocyanate, and
177
-------
dimethylolethyltriazone (agent used in wash-and-wear fabrics).
The cuprous chloride salts of MEA are used in the refining of
petroleum and vegetable oil.
Diethylamine (DBA) is used in the manufacture of the follow-
ing chemicals: diethyldithiocarbamate and thiourams (rubber
processing accelerators), diethylaminoethanol (medicinal inter-
mediate) diethylaminopropylamine (epoxy curing agent), N,N-diethyl-
m-toluamide (insecticide), and 2-diethylaminoethylmethacrylate.
Triethylamine (TEA) is used as a corrosion inhibitor in
paint removers based on methylene chloride or other chlorinated
solvents. TEA is used to solubilize 2,4,5-T in water and serves
as a selective extractant in the purification of antibiotics.
Octadecyloxymethyltriethylammonium chloride, an agent used in
textile treatment, is manufactured from TEA (SRI, 1975).
HEALTH ASPECTS
Ethylamines produce strong local irritation when inhaled or
on contact with the skin. Inhalation of small quantities of
monoethylamine or triethylamine may cause death or permanent
injury. Human effects are usually local; inhalation may cause
eye irritation, lacrimation, conjunctivitis, nose and throat
irritation, or coughing. Systemic symptoms such as headache,
nausea, faintness, and anxiety may result from inhalation of
ethylamines (Sax, 1975).
Rat oral LD5Q values are as follows (NIOSH, 1975):
Monoethylamine 400 mg/kg
Diethylamine 540 mg/kg
Triethylamine 460 mg/kg
Brieger and Hodes (1951) exposed rabbits to 50 or 100 ppm
ethylamines for 6 weeks. At the higher dose all three compounds
178
-------
produced degenerative changes in the liver, lungs, and kidneys.
Only triethylamine weakened the heart. Eye irritation and slight
liver damage were reported at the lower dose for each compound.
In a 5-year Russian study of children who lived near a
factory which released monoethylamine, increases in acute respira-
tory, ear, and mastoid infections were noted. Additional changes
reported were enhanced blood cholinesterase activity, disturbed
porphyrin metabolism, and an elevated number of eye infections.
The mean diurnal atmospheric concentration of MEA was 0.037 mg/m
(0.02 ppm), with a maximum of 0.293 mg/m (0.16 ppm). In a 3-
month study, rats were exposed to 3.69 mg/m (2.0 ppm). A
decrease in blood cholinesterase activity and changes in porphyrin
metabolism were seen. A no-effect level was seen at 0.01 mg/m
(0.005 ppm) (Tkachev, 1969).
Hussain and Ehrenberg (1974) showed that a combination of
monoethylamine and sodium nitrite is significantly more mutagenic
than either compound alone. In this assay, E. coli mutated to
streptomycin independence. Isakova et al. (1971) exposed rats to
an ambient concentration of 1 mg/m (0.25 ppm) triethylamine for
3 months. The number of rats having cells with an abnormal
number of chromosomes in the bone marrow increased.
The major reason for our concern with ethylamine is that
under conditions found in the digestive tract, diethylnitrosamine,
an animal carcinogen, may be formed. Sodium nitrite and the HC1
salt of diethylamine were incubated in human gastric juice (pH
1.2-1.9), and measurable amounts of diethylnitrosamine (DEN) were
found. DEN was found in the stomachs of rabbits and cats who had
been fed diethylamine and nitrite (Sen et al., 1969). Schweinsberg
and Sander (1972) showed that nitrous acid and tertiary amines
4
react to form nitrosamines, but much less is formed when compared
to the corresponding secondary amine. In a 1-year feeding
study, rats developed no tumors after exposure to both triethylamine
and nitrite. Sander et al. (1968) showed that the amount of
179
-------
nitrosamine formed from a secondary amine depends on the basicity
of that amine. Since the ethylamines are quite basic, one would
expect a small amount of diethylnitrosamine to be formed. In a
long-term feeding study, DEN produced liver tumors in 18 of 20
guinea pigs after 30 months. However, two groups fed combinations
of diethylamine and nitrite suffered no ill effects other than
weight loss (Sen et al., 1975).
The TLV values for occupational exposure are (ACGIH, 1971):
U.S.A. u.s.s.R
Monoethylamine 10 ppm
Diethylamine 25 ppm 10 ppm (1966)
Triethylamine 25 ppm 2.5 ppm (1967)
ENVIRONMENTAL ASPECTS
Monoethylamine is a normal constituent of human urine
(Asatoor, 1969), and both monoethylamine and diethylamine are
present in edible fish (Gruger, 1972). Little additional work
has been done on the metabolism of ethylamines.
Normal commercial amounts of the pesticide diethyldithio-
carbamate were converted to diethylamine in soil; measurable
amounts of diethylnitrosamine were found (Tate and Alexander,
1974). Mosier (1974) showed that in a laboratory setting with
pure water and no other organism, both MEA and DEA inhibit the
growth of fresh-water algae. NIOSH's Aquatic Toxicity Rating
ranks all three compounds as "slightly toxic."
180
-------
REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists).
Documentation of Threshold Limit Values. 1971.
Asatoor, A. M. Tea as a source of urinary ethylamine. Nature
2J.£(5043) :1358, 1969.
Brieger, H., and W. A. Hodes. Toxic effects of exposure to vapors
of aliphatic amines. Arch. Ind. Hyg. Occup. Med. 3:287,
1951. (Cited in Button and PHS 149)
Gruger, E. H. Chromatographic analyses of volatile amines in
marine fish. J. Agr. Food Chem. 2£(4):781, 1972.
Hussain, S., and L. Ehrenberg. Mutagenicity of primary amines
combined with nitrite. Mutat. Res. 2£:419, 1974.
Isakova, G. K., B. Y. Ekshtat, and Y. Y. Kerkis. Mutagenic action
of chemical substances in substantiation of hygienic standards.
Gig. Sanit. 36i(ll):9, 1971.
MITRE Corp. Scoring of Organic Air Pollutants. Chemistry, Produc-
tion, and Toxicity of Selected Organic Chemicals. 1976.
Hosier, A. R. Effect of cattle feedlot volatiles, aliphatic amines,
on Chlorella ellipoidea growth. J. Environ. Qual. 3(1):26,
197T:
NIOSH. Registry of Toxic Effects of Chemical Substances. 1975.
Sander, J., F. Schweinsberg, and H. Menz. Formation of carcinogenic
nitrosamines in the stomach. Hoppe-Seyler's Z. Physiol.
Chem. 3_4£(12) :1691, 1968.
Sax, N. I. Dangerous Properties of Industrial Materials, 4th ed.
New York, Van Nostrand Reinhold. 1975.
Schweinsberg, F., and J. Sander. Carcinogenic nitrosamines from
simple aliphatic tertiary amines and nitrite. Hoppe-Seyler's
Z. Physiol. Chem. 3531(11) : 1671, 1972.
Sen, N. P., D. C. Smith, and L. Schivenghamer. Formation of N-
nitrosamines from secondary amines and nitrite in human and
animal gastric juice. Food Cosmet. Toxicol. 7(4):301, 1969.
*This document was prepared for the U.S. Environmental Protection
Agency by the MITRE Corp. It is a secondary source and does not
cite its primary references. Thus, verification of some informa-
tion is not possible. The environmental release data were taken
from NSF/Rann Research Program on Hazard Priority Ranking of
Manufacturing Chemicals.
181
-------
Sen, N. P. et al. Failure to induce tumors in guinea pigs
after concurrent administration of nitrite and
diethylamine. Food Cosmet. Toxicol. 13_(4):423, 1975.
SRI (Stanford Research Institute). Chemical Economics
Handbook. Menlo Park, Calif. 1975.
Sutton, W. L. Aliphatic and alicyclic amines. In
F. A. Patty (ed.), Industrial Hygiene and Toxicology/
2nd ed. New York, Interscience Publishers. 1963.
Tate, R. L., and M. Alexander. Formation of dimethyl-
amine and diethylamine in soil treated with
pesticides. Soil Sci. 118(5):317, 1974.
Tkachev, P. G. Monoethylamine in the atmosphere: Hygienic
significance and standards. Gig. Sanit. 34 (8);7/
1969.
U.S. ITC (U.S. International Trade Commission). Synthet-
ic Organic Chemicals, U.S. Production and Sales,
1974 and 1975.
182
-------
CHEMICAL HAZARD INFORMATION PROFILE
Ethylenediamine
Date of report: May 9, 1978 •
This chemical was chosen for study because of its presence in
consumer products (pharmaceuticals) and its potential for nitros-
amine formation.
The following recommendations are made regarding further OTE
evaluation of the possible health or environmental hazards of
ethylamines:
(1) Consider need for testing—Ethylenediamine is a rela-
tively high-volume/ high-exposure chemical with very
limited information on toxicity.
(2) Require Section 8(a) submission—More specific informa-
tion on uses is needed for exposure estimates.
(3) Refer to CPSC—Possibly present in products under CPSC's
authority.
(4) Transmit to NIOSH on an FYI basis—NIOSH has scheduled a
criteria document for aliphatic di- and polyamines.
This report represents a preliminary investigation of the
subject chemical's potential for injury to human health and the
environment. The information contained in the report is drawn
chiefly from secondary sources and available reference documents.
Because of the limitations of such sources, it necessarily follows
that this report may not reflect all available information on the
subject chemical.
Any recommendation based on this report are tentative and
should not be construed as final Agency policy with respect to the
subject chemical.
183
-------
CHEMICAL HAZARD INFORMATION PROFILE
Ethylenediamine
Date of report: May 9, 1978
Ethylenediamine (1,2-diaminoethane), C_H N , is a colorless
t, O f,
liquid (boiling point, 116-117°C) with an ammonia-like odor. It
is soluble in water and alcohol, slightly soluble in ether, and
insoluble in benzene (Hawley, 1971).
PRODUCTION AND USE
Ethylenediamine is produced by heating ethylene dichloride
and ammonia (Hawley, 1971). The 1978 Directory of Chemical Pro-
ducers (SRI, 1978) lists the following manufacturers and plant
capacities for ethylenediamine production:
Annual capacity
(millions of Ib)
Dow Chem. U.S.A., Freeport, Tex. 30
Union Carbide Corp., Taft, La. 39
Chems. and Plastics Div., Texas City, Tex. 24^
Total ' 93
Ethylenediamine is used by the synthetic fiber manufacturing
industry as a stabilizer in the production of caprolactam polymers
(Wiithrich, 1972). It is used by the pharmaceutical industry as a
stabilizer in aminophylline, which is used in antiasthmatic drugs,
and in Mycolog®, an antibiotic cream (Provost and Jillson, 1967).
Ethylenediamine is also used as a solvent stabilizer, as a
neutralizer in rubber products, in dyes, waxes, dimethylolethylene-
urea resins, fungicides, insecticides, and asphalt wetting agents,
and in the manufacture of the chelating agent EDTA (Baer and
Ramsey, 1973; Hawley, 1971).
184
-------
HEALTH ASPECTS
Ethylenediamine's action as a contact allergen is well
established. The North American Contact Dermatitis Group (1975)
compiled results of skin patch tests conducted from July 1, 1972,
to June 30, 1974. Six percent of the 3,216 patients tested exhibited
sensitivity to 1% ethylenediamine-HCl solution. Baer and Ramsey
(1973) reported patch tests performed on patients at the New York
University Skin and Cancer Unit. A 1% solution of ethylenediamine
elicited a positive response in 13.2% of the 158 patients tested.
Significant case studies involving ethylenediamine exposure
include:
(1) A patient with a history of allergic reaction to Mycolog®
cream was treated with aminophylline suppositories
following hospitalization for acute dyspnea. He developed
a generalized exfoliative dermatitis. Both drugs con-
tain ethylenediamine-HCl (Petrozzi and Shore, 1976).
(2) A patient who had handled epoxy resins and hardeners in
an electrical appliance factory developed dermatitis
following the use of Mycolog cream. Exposure to the
Mycolog cream occurred 3 years after a 6-month exposure
to the epoxy resins and hardeners. Two other patients
developed dermatitis following repeated use of Mycolog
cream. All three patients showed sensitivity to ethy-
lenediamine in skin patch tests (Van Hecke, 1975).
The OSHA standard for workplace exposure to ethylenediamine
is 10 ppm. This value is also the American Conference of Govern-
mental Industrial Hygienists1 threshold limit value.
185
-------
ENVIRONMENTAL ASPECTS
The estimated release rate of ethylenediamine is 22.5 million
Ib per year. It is reactive toward atmospheric oxidants. The 20-
day BOD is 70% of the theoretical value (Dorigan et al., 1976).
The 96-hr LCc0 for aquatic life (test species unknown) is 10-
100 ppm (NIOSH, 1977) .
Ethylenediamine is a degradation product of the agricultural
fungicide maneb. A field study was conducted to determine levels
of degradation products found on beans and tomatoes sprayed with
maneb. Fourteen days after the final application of maneb, 0.09
ppm of ethylenediamine was found on beans and 0.05 ppm was found
on tomatoes (Newsome et al., 1975).
186
-------
REFERENCES
Baer, R. L., and D. L. Ramsey. The most common contact allergens.
Arch. Dermatol. l£8_:74-78, 1973.
*Dorigan, J., B. Fuller, and R. Duffy. Scoring of Organic Air
Pollutants. Chemistry, Production, and Toxicity of Selected
Synthetic Organic Chemicals. MITRE Corp. 1976.
Hawley, G. G. (ed.). The Condensed Chemical Dictionary, 8th ed.
New York, Van Nostrand Reinhold Co. 1971.
Newsome, W. H., J. B. Shields, and D. C. Villeneuve. Residues of
maneb, ethylenethiuram monosulfide, ethylenethiourea, and
ethylenediamine on beans and tomatoes field treated with
maneb. J. Agr. Food Chem. 23_(4) :756-758, 1975.
NIOSH. Registry of Toxic Effects of Chemical Substances. 1977.
North American Contact Dermatitis Group. The frequency of contact
sensitivity in North America 1972-74. Contact Dermatitis
1^:277-280, 1975.
Petrozzi, J. W., and R. N. Shore. Generalized exfoliative dermati-
tis from ethylenediamine. Arch. Dermatol. 112;525-526, 1976.
Provost, T. T., and 0. P. Jillson. Ethylenediamine contact
dermatitis. Arch. Dermatol. 9j6:231-234, 1967.
SRI (Stanford Research Institute). Directory of Chemical Producers,
Menlo Park, Calif. 1977.
Van Hecke, E. Ethylenediamine sensitivity from exposure to epoxy
resin hardeners and Mycolog cream. Contact Dermatitis 1^344-
348, 1975.
Wiithrich, B. Occupational eczema due to ethylenediamine in the
synthetic fiber manufacturing industry. Berufs-Dermatosen
20(4) :200-203, 1972. (As stated in Biol. Abstr.)
*This document was prepared for the U.S. Environmental Protection
Agency by the MITRE Corp. It is a secondary source and does not
cite its primary references. Thus, verification of some informa-
tion is not possible. The environmental release data were taken
from the NSF/Rann Research Program on Hazard Priority Ranking of
Manufactured Organic Chemicals.
187
-------
CHEMICAL HAZARD INFORMATION PROFILE
Hexachlorocyclopentadiene
Date of report: March 15, 1977
This chemical was chosen for study because of its detection
in air, water, and fish samples.
The following recommendations are made regarding further OTE
evaluation of the possible health or environmental hazards of
hexachlorocyclopentadiene CHCCPD):
(1) Check TSCA inventory for production volume—Reliable
production information is not currently available.
(2) Wait for hazard assessment document from ORNL—Further
OTS assessment at this point would simply be duplicative
of ORNL's effort.
(3) Update this Chemical Hazard Information Profile based
upon the additional information obtained.*
(4) Refer to Office of Solid Waste—HCCPD has been identified
as a waste by-product of pesticide manufacture.
This report represents a preliminary investigation of the
subject chemical's potential for injury to human health and the
environment. The information contained in the report is drawn
chiefly from secondary sources and available reference documents.
Because of the limitations of such sources, it necessarily follows
that this report may not reflect all available information on the
subject chemical.
Any recommendations based on this report are tentative and
should not be construed as final Agency policy with respect to the
subject chemical.
*Subsequent to the review of this CHIP document and the selection
of the tentative dispositions given above, the TSCA Interagency
Testing Committee recommended hexachlorocyclopentadiene for priority
consideration under Section 4(a) of TSCA (44 F.R. 31866).
188
-------
CHEMICAL HAZARD INFORMATION PROFILE
Hexachlorocyclopentadiene
Date of report: March 15, 1977
Hexachlorocyclopentadiene (HCCPD) is a dense, oily, slightly
water-soluble liquid used commercially as an intermediate. Only
two companies produce HCCPD in the United States: Hooker Chemical
Co. at Montague, Mich., and Niagara Falls, N.Y., and Velsicol
Chemical Corp. at Memphis, Tenn. (SRI, 1978). Hooker sells HCCPD
as C-Se®; it is occasionally referred to in the literature as
"hex."
The important products derived from HCCPD (via Diels-Alder
reactions) are the chlorinated cyclodiene insecticides aldrin,
dieldrin, endrin, chlordane, heptachlor, endosulfan, Kepone®, and
mirex; the fire-retardant monomers chlorendic acid (CA) and chlorendic
anhydride (CAN), used primarily in polyester resins for marine,
^
automotive, and construction applications, and to a lesser extent
in alkyd resin coatings; and the fire-retardant plastic additives
known as Dechloranes®. (In the past, Dechlorane® was the trade
name under which mirex was sold for use as a fire-retardant addi-
tive.) The insecticide- dienochlor is also derived from HCCPD, but
via catalytic reduction rather than a Diels-Alder reaction. The
chemical structures of HCCPD and these derivatives are shown in
the appendix.
PRODUCTION AND USE
Because there are but two producers of HCCPD, production
statistics are not public information. Lu et al. (1975) stated
that production of HCCPD could not be less than 50 million Ib per
year, based on production levels of the chlorinated insecticides
for the early 1970's. This estimate, however, preceded EPA actions
taken against most of these insecticides, which have severely
limited their allowable applications. Within the past 2 years
aldrin and dieldrin have had their registrations canceled, chlordane
189
-------
and heptachlor have had their registrations suspended, and endrin
and Kepone® have been presumed against. Limited, specific uses of
aldrin/dieldrin and chlordane/heptachlor are permitted under their
respective cancellation and suspension orders. The current mirex
formulation is to be phased out by 1978 and replaced by a new
formulation. Dienochlor and endosulfan have not had any action
taken against them to date.
The chlorendic acid/chlorendic anhydride outlet for HCCPD is
a significant market. An estimated 10 million Ib of CA/CAN was
produced in 1974, and the expected growth rate is 10%/year through
1980 (SRI, 1976). Production of 10 million Ib of CA/CAN requires
7-7.5 million Ib of HCCPD. These compounds are also produced only
by Hooker and Velsicol.
The production levels of the Dechlorane fire retardants are
unknown. Dechlorane fire retardants are Hooker products.
Based on the above, HCCPD production at this time is at least
7 million Ib per year and is substantially less than 50 million Ib
per year. Using data on current production capacities of dienochlor
and endosulfan, allowing for some small production of the canceled
and suspended insecticides for their few allowable uses, and
assuming that Dechlorane® fire-retardant production is on the
order of 1 million Ib per year, an upper limit on current HCCPD
production of 15 million Ib per year can be assumed.
HEALTH ASPECTS
The toxicological hazards (particularly carcinogenicity),
persistence, and widespread environmental contamination with
certain of the HCCPD-derived insecticides are well known (IARC,
1974), and these features have formed the basis of the restrictive
actions that have been taken against them. Very little is known
about the health and environmental effects of HCCPD, and the
190
-------
available information on CA/CAN and the Dechlorane materials is
practically nonexistent.
HCCPD produces systemic toxicity of unknown mechanism in
mammals via ingestion, inhalation, and dermal exposure. Degenera-
tive changes in the brain, heart, adrenals, liver, kidneys, and
lungs are observed in severely poisoned animals by all routes of
administration. The oral LD,-0 in rats is 500-600 mg/kg. Rats
receiving 30, 100, or 300 ppm HCCPD in their diets did not show
any abnormalities after 90 days. Rats fed 0.002, 0.0002, or
0.00002 mg/kg daily for 6 months showed no abnormalities. The
minimum lethal dose of HCCPD applied to rabbit skin is 430-610
mg/kg. Rats, rabbits, and guinea pigs survived 150 7-hr exposures
to 0.15 ppm HCCPD in.the air over a 216-day period; however, this
exposure level was lethal to four of five mice. All species
showed mild degenerative changes in the liver and kidneys. Most
animals in all four of these species died from a single 7-hr
exposure to 3.2 ppm HCCPD in the air (Ingle, 1953; Treon et al.,
1955; Naishstein and Lisovskaya, 1965).
No data are available on the carcinogenicity, mutagenicity,
or teratogenicity of HCCPD.
For aquatic species, the reported 96-hr TLM's are 25 ppm for
sunfish, 20 ppm for bass, and 0.059 ppm for fathead minnows (Davis
and Hardcastle, 1959; U.S. Department of Health, Education, and
Welfare, 1956).
A model ecosystem study showed that HCCPD has considerable
ecological stability and moderate biomagnification potential in
aquatic organisms (Lu et al., 1975).
HCCPD has been qualitatively identified as a contaminant in
the discharge of a pesticide production plant (probably Velsicol)
in Memphis, Tenn., on seven occasions, most recently in December
1975 (Donaldson, 1977). This past May at the Hooker plant in
Michigan, HCCPD was qualitatively identified in air, in the plant's
191
-------
aqueous discharge (56 ppb; 170 ppb), and in fish tissue in the
receiving stream (4-18 ppb). According to Dennis Swanson of the
Michigan State Department of Natural Resources, Hooker has agreed
to limit the HCCPD in its aqueous discharge to 10 ppt (limit of
detection).
The only effects information available for CA/CAN is an 1^50
value of 0.5 g/kg for CAN given to rats via stomach tube (Kowalski
and Bassendowska, 1965). No reports of environmental contamination
with CA/CAN were found.
No health or environmental data for the Dechlorane products
were found.
192
-------
APPENDIX. CHEMICAL STRUCTURES
Cl Cl
Hexachlorocyclopentadiene
(HCCPD)
COOH
COOH
Chlorendic Acid
(CA)
Cl
Chlorendic Anhydride
(CAN)
R=<
75-90%
H
Cl
5-24%
1-5%
Dechlorane 604
®
1 DO
-------
APPENDIX (Continued)
Dechlorane 25
Cl
Dechlorane 515 (same structure,
different particle size)
Cl
Cl,
Cl
°£:
S Cl
Cl
NCI
Mirex (was formerly
Dechlorane®as well)
Cl
Cl
Cl
194
-------
APPENDIX (Continued)
Cl
Cl
Cl
•Cl
Cl
Kepone®
Cl
Cl Cl Cl Cl
Dienochlor
195
-------
REFERENCES
Davis, J. T., and W. S. Hardcastle. Biological assay of herbicides
for fish toxicity. Weeds 7^:397-404, 1959.
Donaldson, W. Analytical Chemistry Branch, Environmental Research
Laboratory, Athens, Ga., private communication, 1977.
IARC (International Agency for Research on Cancer). IARC Monographs
on the Evaluation of Carcinogenic Risk of Chemicals to Man:
Some Organochlorine Pesticides (vol. 5). 1974.
Ingle, L. Toxicity of chlordane vapors. Science 118; 213-214,
1953.
Kowalski, Z., and E. Bassendowska. Acute toxicity of phthalates
used in the plastic industry. Med. Pr. 16_(2) : 109-112, 1965.
Lu, P., R. L. Metcalf, A. S. Hirive, and J. W. Williams. Evalua-
tion of environmental distribution and fate of hexachloro-
cyclopentadiene, chlordene, heptachlor, and heptachlorepoxide
in a laboratory model ecosystem. J. Agr. Food Chem. ^3_(5) :967-
973, 1975.
Naishstein, S. Ya., and E. V. Lisovskaya. Maximum permissible
concentration of hexachlorocyclopentadiene in water bodies.
Gig. Sanit. 3_0:117-181, 1965.
SRI (Stanford Research Institute). Chemical Economics Handbook
(Unsaturated Polyester Resins; Maleic Anhydride). Menlo
Park, Calif. 1976.
r
SRI. Directory of Chemical Producers, United States of America.
Menlo Park, Calif. 1978.
Treon, C., F. Cleveland, and J. Cappel. The toxicity of hexachloro-
cyclopentadiene. Arch. Ind. Health 11_:459-472, 1955.
U.S. Department of Health, Education, and Welfare. Bio-Assay
Investigations for International Joint Commission. Hooker
Electrochemical Co., Niagara Falls, N.Y. 1956.
196
------- |