Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 198
Chapter 8
2,4-DIAMINOTOLUENE
NH2
\
H3C of/ \ - NH2
~ .
2,4-Diaminotoluene (toluene-2,4-diamine; 2,4-DT) is a colorless
crystal that melts at 99°C. It is soluble in hot water.
2,4-DT synthesis takes place in three steps, beginning with the
nitration of toluene in a mixture of nitric and sulfuric acids at 30°C
to 70°C. The resultant mononitrotoluene mixture is then nitrated again
in a somewhat stronger acid medium to a mixture of dinitrotoluene
isomers, of which the largest fraction is 2,4-dinitrotoluene {75.89~.
A number of processes can then be used to produce 2, 4-DT from
2,4-dinitrotoluene. All of these methods involve catalytic
hydrogenation, followed by pur if ication, to remove unwanted isomers and
byproducts,
PRODUCTION
Table 8-1 lists the current producers of 2,4-DT, their locations,
and (where available) their estimated annual capacities (Chemical
Economics Handbook, 1977-1978; Stanford Research Institute
International 1979; United States International Trade Commission, 1979~.
198
OCR for page 199
TABLE 8-1
Producers of 2,4-DT
Company and Plant location
Air Products and Chemicals, Inc.
Industr ial Gases Div.
Middlesex, N . J.
Pasadena, Tex.
A1 1 fed Chemica 1 Corpora tion
Specialty Chemicals Division
Moundsville, W. Va.
Amer lean Cyanamid Co.
Organic Chemicals Division
Bound Brook, N. J.
BASE Wyandotte Corporation
Polymers Group
Urethane Division
Geismar, La.
E. I . du Pont de Nemours & Company, Inc.
Elastomer Chemicals Department
Deepwater, N. J.
Hobay Chemical Corporation
Estimated Annual
Capacity as of
January 1, 1979a
mousends of metric tons
(owned by Bayer AG, Federal Rep. of Germany}
Polyurethane Division
Cedar Bayou, Tex.
New Martinsville, W. Va.
Olin Corporation
O1 ins Chemicals Group
Ast~tabula, Ohio
Brandenburg, Ky.
Lake Charles, La.
Rochester, N. Y.
Rubicon Chemicals Inc.
(jointly owned by Uniroyal, Tnc., and Imperial
Chemical Industr ies Limited, United Kingdom)
Geismar, La.
NIP
57a
30
Not
36
25
47
36
11
NOR
36
NIP
15
Estimates of production capacities are based on an assumed 2,4-
diaminotoluene capacity of O .8 mete ic tons for each aetr ic ton of
eoluene diisocyanate capacity, except for Air Products and Cbemicals,
Inc., which does not produce toluene diisocyanate.
b Not repor ted .
199
OCR for page 200
Total U.S. production of 2,4-DT has declined in recent years
(U. S. International Trade Cc~mmisaion, 1976-1978) as shown in Table
8-2 .
USES
2,4-DT is used almost exclusively for the production of toluene
d i isocyanate . Other V. S. . consumption is estimated to amount to less
than 230 metr ic tons annually (Chemical Economics Mandbook,
197 7-197 8 ) .
Mixtures of isomers of 2, 4-DT are normally used to produce
toluene diisocyanate. The most important mixture contains 80% of
the 2 ,4-isomer and 209 of the 2,6-isomer. Eight U.S. companies
produced 284, 072 . 4 metr ic tons of the 80/20 toluene di isocyanate
mixture in 1978 (International Trade Commission, 1978~. A mixture
containing 65% 2 ,4-isomer and 351 2,6-isomer is also used in
significant quantities. Only a small quantity of 2,4-DT is isolated
for oonver s ion to pure 2, 4 -toluene di i~ocyanate .
The Chemical Economics Handbook (1977-1978 ~ estimated the U. S .
consumption pattern for toluene diisocyanate in 1978 as Down in
Table 8-3.
2, 4-DT can be used to produce (approximately} 60 dyes, which are
used to color silk, wool, paper, boat f ibers, cellulosic f ibers, and
cotton. The following nine dyes are believed to have been produced
from 2,4-DT in the United States during 1978: Basic Brown 4, Basic
200
OCR for page 201
Table 8-2
Annual Production of 2, 4-DTa
. .
Year
1976
1977
1978
Thousands of metr ic tons
105 e 9
lOle 1
63 e3
a Data from U. S. International Trade Commission, 1976-1978.
201
OCR for page 202
Table 8-3
U.S. Consumption of Toluene Di-isocyanate in 1978a
Use
~ _
Flexible polyurethane foams
Polyurethane surface coatings
Polyurethane elastomers
Other (including rigid polyurethane foam)
Total
Percent of Total
83%
6
3
8
100%
a Data from Chemical Economics Handbook, 1977-1978.
202
OCR for page 203
Orange 1, Direct Brown 2, Direct Brown 154, Direct Black 4, Leuco
Sulphur Orange 1, Leuco Sulphur Brown 10, Solvent Brown 12, and
Sulphur Black (Colour Index, 1975; U.S. International Trade
Commission, 1978) . They are used in spirit varnishes and wood
stains as indicators, in the manufacture of pigments, and as
biolog to s ta ins .
2,4-DT is used as a developer for direct dyes, particularly to
obtain black, dark blue, and brown shades, and to obtain navy blue
and black colors on leather. It is also used to dye furs and was an
ingredient in hair dye formulations until banned in 1971
(International Agency for Research on Cancer, 19781.
EXPOSURE
More than 99% of the 2,4-DT produced in the United States is
used to produce toluene di isocyanate, generally at the site of
production. The s ingle exception is the Air Products and Chemicals
Plant at Pasadena, Tex., which produces no toluene diisocyanate and
conversely, a 45,000 metric ton/year capacity toluene diisocyanate
plant at Freeport, Tex. operated by Dow Chemical, which does not
produce its own 2,4-DT. Therefore, the main sources from which
humans are exposed will be the plants listed in Table 8-1. However
there is no information on which to base an analysis of either
occupational or general exposures from plant emissions.
Because the substance is solid at ambient temperatures, air
emissions from 2,4-DT production do not appear to be significant.
203
OCR for page 204
However, contamination of wastewater discharges from the plants is a
likely route of exposure. The hydrogenation of dinitrotoluene
yields 4 mol of water for every mat of 2 ,4-DT produced (600 1 of
water per metric ton of 2,4-DT) . This water is separated in a
dehydration column at 100°C-150°C at atmospheric pressure (Milligan
and Gilbert, 1978~. Because the vapor pressure of 2,4-DT is 11 mm
Hg at 150°C and it is soluble in hot water, the separated water is
undoubtedly highly contaminated. This wastewater is probably
treated before it is discharged.
Some 2 ,4-DT could find its way into consumer products as an
impurity in dyes. However, such exposure is nearly impossible to
quantify.
Under the U. S . Food and Drug Administration (FDA) regulation
concerning 2,4-DT, (21 CFR 177) is listed under the category of
ant ioxidants and ant iozonants . The total of these components is not
to exceed S ~ by we ight of rubber product.
The U.S. Occupational Safety and Health Administration does not
have an occupational standard covering the exposure of workers to
2,4-Dr.
2()4
OCR for page 205
ANALYTIC METHODS
Jones et al. (1978) reported separations of nondye components in
the commercial food color preparation Brown FK. The dye, which is
manufactured by the reaction of diazotized sulfanilic acid with a
mixture of m-phenylenediamine and 2,4-diaminotoluene, has been shown
to consist of six major colored components. High-pressure liquid
chromatography (HPLC) and thin-layer chromatography (TLC) procedures
were evaluated for their ability to separate a mixture of the six
dye components as well as the starting compounds (e.g., 2,4-DT) used
in the synthesis. Two different columns and solvent systems were
used in the HPLC investigations with a W absorption detector set at
254 nm. One of the systems, which consisted of a column of Partisil
5 loaded with 7% aminopropyl phase, was subjected to a 30-minute
linear gradient from acetonitrile-water (2:3) to acetonitrile-water
(2:3 containing sodium biphosphate (2 g/1~. Only partial resolution
of the components was obtained. The other HPLC system, which
consisted of a column of Chromosorb Si 100 loaded with a 21%
octadecyl phase subjected to a 17-minute linear gradient from 5% to
40% acetonitrile in water (containing 1.2 and 2.4 g/1 of sodium
biphosphate and sodium hypophosphate, respectively} was more
successful: all nine components of the mixture were separated with
essentially baseline resolution.
Unger and Friedman (1979) developed an HPLC procedure to assay
2,6- and 2,4-DT. Their technique was adaptable to biomonitoring and
metabolic studies with samples of urine and plasma from rats. A
normal-phase silica column was used with a mobile phase consisting
205
OCR for page 206
of acetonitrile-water saturated chloroform (8:2) and a 250 nm W
absorption detector. The two compounds were resolved as 'sharp peaks
in 3 minutes, and from 1 ng to 2 ng of each substance was
quantitatede Dichloromethane extraction of urine and plasma "piked
with 2,4-DT (10 to 200 ppm), yielded recoveries of about 90% or more.
TEC tests were performed by using Inactivated silica gel G
plates (layer thickness 0.25 mm) with a solvent system of
phenol~ater (4 :1) . The starting materials of the manufacturing
process {e . g ., 2 , 4-DT) were detected by spraying with 19 Ehrlich 's
reagent in 50% acetic acid. Although the TLC system resolved for
the six dye components, it was not suitable for the other compounds
since sulfanilic acid was not resolved from one of the dye
components. The two aromatic amines (2,6- and 2,4-DT) were not well
resolved and ran close to the solvent front.
Spectrophotofluor imetry {SPF} was the basis for a method
described by Guthrie and Mckinney (1977) to analyze 2,4- and 2,6-DT
in flexible polyurethane foams at levels as low as 1 ppm. me
amines were extracted wi th methanol, separated by TLC, and assayed
by SPF after reaction with Fluram reagent. The SPF assay was
accomplished by uniformly spraying the developed and dried TLC plate
with an 0.015% solution of Fluram in acetone and measuring the
fluorescent spots (NEX = 390, XEm = 500 nm) with a "bin-film
chromatographic scanner. The instability of the Fluram derivative
required that quantitative measurements be completed within 1 hour.
The nonuniform cbaracteristic of foams was determined by assaying
sample extracts in duplicate at the 10 to 15 ppm level. Precision,
206
OCR for page 207
usually within +10% for a given extract, was +30% for six different
samples of tbe same foam.
Lepri et al. (1976} investigated the behavior of several
coloring agents (including 2,4-DT} used in oxidation-type hair dyes
on thin layers of various ion exchangers. Some of the systems
provided un ique separations. Examples of such systems are AG 1-X4
(CH3co2-) developed with 0.1 mol acetate buffer in a 4:1
water-methanol mixture; BD-cellulose developed with 0.5 mol acetate
buffer solution; Dowex 50-X4 (H+) with O .1 mo1 acetate buffer in a
1:1 mixture of water-methanol; Rexyn 102 (H+) developed with
various mixtures of dimethy~formamide-water; and AG 3-X4A developed
with 95% ethyl alcohol. Rf values were tabulated for some IS
compounds .
Two direct gas chromatography {GC) procedures for separation and
analysis of isomeric diaminotoluenes were reported in 1968.
Willeboordse _ al. (1968} separated mixtures of 2,3-, 3,4-, 2,4-,
2,5-, and 2,6-DT using a mixed partitioning agent of Carbowax 20M
and Saponate DS-10 on base-loaded Chromosorb G. followed by Saponate
DS-10 on the same solid support. Boufford (1968) separated a
mixture of 3,4-, 2,3-, 2,4-, 2,5-, and 2,6-DT on a column of 5%
Bentone 34 plus 155 Hyprose SP-80 [octakis(2-hydroxypropyl)-sucrose]
on potassium-hydroxide-treated Chromosorb W at 170°C. Helium
carrier gas and a hydrogen flame ionization detector (FID) were used.
The analysis of 2,4-DT was specifically mentioned in several of
the procedures described for primary aromatic amines. Additional
207
OCR for page 208
discussions in the literature (details unavailable) involve in situ
TLC determinations of toluenediamine and methylenedianiline isomers
in the products of hydrolytic degradation of polyurethanes (Lesiak
and Orl ikowska, 1978 ~ and an ultrasonic method to assay amine
!
solutions, including toluenediamine (Bogdanova et al., 1976)
4
208
.
OCR for page 217
significantly different for the control and 2, 4--treated groups.
Similar results were obtained for the other compounds.
Chromosomal Damage in Humans . No data are available on the
possible genotoxic effects of 2,4-DT Eer se in humans. However, in
a recent epidemiologic study of the potentially genotoxic effects
of hair dyes (Kirkland et al., 1978), chromosomal damage was
investigated in peripheral-blood lymphocytes of professional hair
colorists. The authors found no significant differences in
chromosomal damage in cultured per ipheral-blood lymphocytes from 60
professional ha ir colorists as compared with those of 36 control
subj ects closely ma tched for age and sex. There was a
statistically signif icant excess of chromosomal damage (mainly
chromatic breaks ~ in women wi th dyed ha ir when age-matched women
were regrouped according to whether their hair was dyed or not.
Men (mean age 22 .9 years) with dyed hair had signif icantly less
cheomosomal damage than did men (mean age 31.5 years) whose hair
was not dyed.
Possible confounding factors in these findings are that most
tinters wear gloves when applying hair dyes and, even without
gloves, percutaneous absorption of ha ir dye constituents may be
effectively impeded by the horny surface of the bands and by the
lack of sebaceous glands in the palms ; ha ir dye constituents are
readily absorbed through the scalp, which contains numerous
sebaceous glands; and the lower frequency of chromosomal
aberrations in young men with dyed hair (compared with the
frequency in slightly older men without dyed hair) is
217
OCR for page 218
probably due to an age effect. This preliminary evidence on
the genotoxic effects of hair dyes in humans warrants further
study in view of the known mutagenicity and carcinogenicity in
animals of several hair dye constituents.
C NCLUSIONS
2,4-DT is carcinogenic in rats and mice after oral
administration; the produces amine produces liver and mammary
gland tumors. There is some evidence that it also induces
sarcomas at the site of subcutaneous injection in rats.
Published data on the carcinogenicity of 2,4-DT after
application to mouse skin are not adequate for evaluation.
2,4-DT is a potent mutagen in microbial test systems and
causes germ cell mutation in D. melanogaster. The substance
may cause chromosome! damage to (chromatic and chromosome gaps
and breaks) in humans. It also induces cell transformation in
an _ vitro mammalian carcinogenesis test system. However,
there are no data, such as case reports or epidemiologic
studies, on the carcinogenicity of 2,4-DT in humans.
RECOMMENDATIONS
There is absolutely no information available on the
218
OCR for page 219
mechanism by which 2,4-DT is activated in susceptible species,
including rats and mice.
However , given the demonstration of
carcinogenicity in two species of animals and the data on the
genotoxic effects in In vitro systems, it is prudent to assume
that humans are under some increased rink from exposure to
2, 4-DT. Recommendations for future research with 2,4-DT
include studies of the mechanism by which the chemical is
activated in rats, mice and humans, testing for carcinogenicity
in additional species to obtain more data on the relationship
between metabolism and carcinogenicity, and examination of the
in vitro metabolism of 2,4-DT in human tissues to supplement
the preliminary observations of Glinsukon et al. {19757. This
kind of additional data would make it easier to estimate the
extent of risk to humans exposed to 2,4-DT
219
.
OCR for page 220
REFERENCES
Production, Uses, Exposure
Chemical Economics Handbook. 1980. Stanford Research Institute
International, Menlo Park, Calif .
Code of Federal Regulations.
food and additives: Polymers.
1980. Title 21, Part 177. Indirect
Office of the Federal Register,
National Archives and Records Service, General Services
Administration, Washington, D.C.
Colour Index. 1971. Third edition, volume 4. m e Society of
Dyers and Colourists, Bradford, Yorkshire.
International Agency for Research on Cancer. 1978.
2,4-Diaminotoluene. Pp. 83-95 in IARC Monographs on the
Evaluation of the Carcinogenic Risk of Chemicals to Man. Volume
16. International Agency for Research on Cancer, Lyon.
Milligan, B., and K.E. Gilbert.
1978. ~nines,
aromatic--Diaminotoluenes. Pp. 321-329 in Kirk-Othmer
Encyclopedia of Chemical Technology, Third edition, volume 2.
John Wiley & Sons, New York .
SRI International. 1979.
1979 Directory of Chemical Producers:
United States of America. Stanford Research Institute
International, Menlo Park, Calif. 1122 p.
220
OCR for page 221
V. S. International Trade Commission.
1977. Synthetic Organic
Chemicals . Un ited States Production and Sales, 1976 . USED
Publication 833. U.S. Government Printing Office, Washington,
D.C. 357 pp.
UPS. International Trade Commission.
1978. Synthetic Organic
Chemicals. United States Production and Sales, 1977. USTTC
Publication 920. U.S. Government Printing Office, Washington,
r).c. 417 pp.
U. S. International Trade Commission .
1979. Synthetic Organic
Chemicals. United States Production and Sales, 1978. USITC
Publication 1001. U.S. Government Printing Office, Washington,
D.C. 369 pp.
221
OCR for page 222
Analytic Methods
Bc~danova, T.M., P.V. Mulyanov, N.M. Monabarzh, and M.L. Piroshkova.
1976. Ultrasonic method for analysis of amine solutions. Zavod.
Lab. 42:1486-1487. [Chem. Abs. 86:199421s, 1977.]
Boufford, C.E. 1968. Determination of isomeric diaminotoluenes by
direct gas-liquid chromatography. J. Gas. Chromatogr. 6:438-440.
Guthrie, J.L., and R.W. McKinney. 1977. Determination of 2,4- and
2, 6-diaminotoluene in flexible urethane foams. Anal. Chem.
49: 1676-1680 .
Jones, A.D., D. Hoar, and S.G. Sellings. 1978. Separation of non-dye
components of Brown FK by high-performance liquid chromatography.
J. Chromatogr. 166:619-622.
Lepri, L., P.G. Desideri, and V. Coas. 1976. Separation and
identification of colouring agents in the oxidation-type hair dyes
by ion exchange thin-layer chromatography. Ann. Chim. (Rome)
66:451-460.
Lesiak, T., and H. Orlikowska. 1978. ~In situ~ determination of
toluenediamine and methylenedianiline isomers in the products of
hydrolyltic degradation of polyurethanes after separation by
thin-layer chromatography. Chem. Anal. (Warsaw) 23:469-475. [Chem.
AbS. 89: 216094u, 1978.]
222
OCR for page 223
Anger, P.D., and M.A. Friedman. 1979. High-performance liquid
chromatography of 2,6- and 2,4-diaminotoluene and its
application to the determination of 2,4-diaminotoluene in
urine and plasma. J. Chromatogr. 174:379-384.
Willeboordse, F., Q. Quick, and E.T. Bishop. 1968.
Direct gas
chromatographic analysis of i~omeric diaminotoluenes. Anal.
Chem. 40:1455-1458.
223
OCR for page 224
Health Effects
Ames, B.N., H.O. Kammen, and E. Yamasaki. 1975. Hair dye. are
mutagenic:
ingredients.
Identification of a variety of mutagenic
Proc. Natl. Acad. Sci. U.S.A. 7~:2423-2427.
Aune, T., S.D. Nelson, and E. Dybing. 1979. Mutagenicity and
irreversible binding of the hepatocarcinogen
2,4-diaminotoluene. Chem. Biol. Interact. 25:23-33.
Blij~even, W.G.H. 1977. Mutagenicity of four hair dyes in
Drosophila melanogaster.
Mutat. Res. 48:181-186.
Burnett, C., B. Lanman, R. Giovacchini, G. Walcott, R. Scala,
and H. Keplinger.
Oxidation of ha ir dyes.
Fahmy, M.J., and O.G. Fahmy.
1975. Long-term toxicity studies on
Food Cosmet. Toxicol. 13: 353-357 .
1977. Mutagenicity of hair dye
components relative to the carcinogen benzidine in Drosophila
melanogaster.
Mutat. Res. 56: 31-38.
Giles, A.L., Jr., C.W. Chung, and C. Kommineni. 1976. Dermal
carcinogenicity study by mouse-skin painting with
2,4-toluenediamine alone or in representative hair dye
formulations. J. Toxicol. Environ. Health 1:433-440.
224
OCR for page 225
Glinsukon, T., T. Benjamin, P. Granthem, E. Weiaburger, and
Poller. 1975. Enzy~na tic N-acetylation of
2,4-toluenediamine by liver cytosole from various species.
Xenobiotica 5 (87: 475-483.
Gosselin, R.E., H.C. Hodge, R.P. Smith, and M.N. Gleason.
1976. Section II, p. 141 in Clinical Toxicology of
Commercial Products: Acute Poisoning. E our th ed. Williams
and Wilkins, Baltimore.
Grantham, P.H., L. Mohan, T. Ben jamin, P.P. Poller, J.R.
Miller, and E.K. Weisburger. 1979. Comparison of the
metabolism of 2,4-toluenediamine in rats and mice. J.
Environ . Pathol. Toxicol. 3 :149-166.
Hossack, D.J.N., and J.C. Richardson. 1977. Examination of
the potential mutagenicity of hair dye constituents using the
micronucleus test. Exper ientia 33:377-378.
International Agency for Research on Cancer. 1978.
2,4-Diaminotoluene. Pp. 83-95 in lARC Monographs on the
Evaluation of the Carcinogenic Risk of Chemicals to Man.
Volume 16. International Agency for Research on Cancer, Lyon.
Ito, N., Y. Hiasa, Y. Konishi, and M. Marugami. 1969. The
development of carcinoma in liver of rats treated with
m-toluylenediamine and the synergistic and antagonistic
effects with other chemicals. Cancer Res. 29 :1137-1145.
225
OCR for page 226
Kirkland, D.J., S.D. Lawler, and S. Venitt. 1978. Chromosomal
damage and hair dyes. Lancet 2:124-128.
National Cancer Institute. 1979. Bioassay of
2,4-Diaminotoluene for Possible Carcinogenicity. CAS No.
95-80-7. ITS Carcinogenesis Technical Report Series No.
162. DHEW Publication No. (NIB) 79-1718. U.S. Dept. of
Health, Education, and Welfare, Public Health Service,
National Institutes of Health, Bethesda, Md. 122 pp.
National Institute for Occupational Safety and Health. 1978.
Pp. 1233 in Registry of Toxic Effects of Chemical
Substances, 1978, Lewis, R.J., Sr., ed. DHEW (NIOSH)
Publication No. 79-100. U.S. Department of Health,
Education, and Welfare, Public Health Service, Center for
Disease Control, National Institute for Occupational Safety
and Health, Cincinnati, Ohio.
Ong, T. 1978. Use of the spot, plate and suspension test
systems for the detection of the mutagenicity of
environmental agents and chemical carcinogens in Neurospora
crassa. Mutat. Res. 53:297-308.
Pienta, R.J., M.J. Shah, W.B. Lebherz III, and A.W. Andrews.
1977. Correlation of bacterial mutagenicity and hamster cell
transformation with tumorigenicity induced by
2,4-toluenediamine. Cancer Lett. 3:45-52.
226
OCR for page 227
thneda, M. 1955. Production of rat sarcoma by injections of
propylene glycol solution of m-toloylenediamine. Gann.
46: 597-604 .
Unger, P.D., A.Je Salerno, W.C. Hess, and M.A. Friedman.
1980 . Tissue distr ibution and excretion of 2, 4- ~ 14C]
Toluenediamine in the mouse. J. Box. Environ. Health.
6: 107-114 .
venitt, S. 1978.
Mutagenicity of hair dyes: Some more
evidence and the problems of its interpretation. Mutat. Res.
53: 278-279 . (Abstract No. 214 ~ .
Waring, R.H., and A.E. Pheasant.
1976. Some phenolic
metabolites of 2, 4-diam~notoluene in the rabbit, rat and
guinea-pig .
Xenobiotica 6: 257-262.
Weisburger , E.K., A.B. Russf ield, F. Hombur'3er , J.H.
Weisburger, E. Boger, C.G. Van Dongen, and K.C. Chu. 1978.
Testing of twenty-one environmental aromatic amines or
der i~ratives for long-term toxicity or carcinogen icity. J.
Environ . Pathol . 0~xicol. 2: 3 25-356 .
227
Representative terms from entire chapter:
international trade
