United States
Environmental Protection
Agency
Industrial Environmental Research EPA 600 2-79 210e
Laboratory December 1979
Cincinnati OH 45268
Research and Development
Status
Assessment of
Toxic Chemicals
Benzidine
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RESEARCH REPORTING SERIES
Research reports of the Office of Research and Development, U.S. Environmental
Protection Agency, have been grouped into nine series. These nine broad cate-
gories were established to facilitate further development and application of en-
vironmental technology. Elimination of traditional grouping was consciously
planned to foster technology transfer and a maximum interface in related fields.
The nine series are:
1. Environmental Health Effects Research
2. Environmental Protection Technology
3. Ecological Research
4. Environmental Monitoring
5. Socioeconomic Environmental Studies
6. Scientific and Technical Assessment Reports (STAR)
7. Interagency Energy-Environment Research and Development
8. "Special" Reports
9. Miscellaneous Reports
This report has been assigned to the ENVIRONMENTAL PROTECTION TECH-
NOLOGY series. This series describes research performed to develop and dem-
onstrate instrumentation, equipment, and methodology to repair or prevent en-
vironmental degradation from point and non-point sources of pollution. This work
provides the hew or improved technology required for the control and treatment
of pollution-sources to meet environmental quality standards.
This document is available to the public through the National Technical Informa-
tion Service, Springfield, Virginia 22161.
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EPA-600/2-79-210e
December 1979
STATUS ASSESSMENT OF TOXIC CHEMICALS:
BENZIDINE
by
S. R. Archer
T. R. Blackwood
Monsanto Research Corporation
Dayton, Ohio 45407
and
N. P. Meserole
Radian Corporation
Austin, Texas 78766
Contract No. 68-03-2550
Project Officer
David L. Becker
Industrial Pollution Control Division
Industrial Environmental Research Laboratory
Cincinnati, Ohio 45268
INDUSTRIAL ENVIRONMENTAL RESEARCH LABORATORY
OFFICE OF RESEARCH AND DEVELOPMENT
U.S. ENVIRONMENTAL PROTECTION AGENCY
CINCINNATI, OHIO 45268
-------
DISCLAIMER
This report has been reviewed by the Industrial Environmental
Research Laboratory - Cincinnati, U.S. Environmental Protection
Agency, and approved for publication. Approval does not signify
that the contents necessarily reflect the views and policies of
the U.S. Environmental Protection Agency, nor does mention of
trade names or commercial products constitute endorsement or
recommendation for use.
IX
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FOREWORD
When energy and material resources are extracted, processed,
converted, and used, the related pollutional"impacts on our
environment and even on our health often require that new and
increasingly more efficient pollution control methods be used.
The Industrial Environmental Research Laboratory - Cincinnati
(IERL-Ci) assists in developing and demonstrating new and im-
proved methodologies that will meet these needs both efficiently
and economically.
This report contains a status assessment of the air emis-
sions, water pollution, health effects, and environmental signi-
ficance of polynuclear aromatic hydrocarbons. This study was
conducted to provide a better understanding of the distribution
and characteristics of this pollutant. Further information on
this subject may be obtained from the Organic Chemicals and
Products Branch, Industrial Pollution Control Division.
Status assessment, reports are used by IERL-Ci to communicate
the readily available information on selected substances to
government, industry, and persons having specific needs and
interests. These reports are based primarily on data from open
literature sources, including government reports. They are indi-
cative rather than exhaustive.
David G. Stephan
Director
Industrial Environmental Research Laboratory
Cincinnati
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ABSTRACT
Epidemiological investigations have clearly demonstrated that
benzidine is carcinogenic in humans. Higher than average inci-
dences of bladder cancer among workers in benzidine production
facilities and processing facilities have been demonstrated,
resulting in increased concern over liquid discharges containing
benzidine.
In 1972, 4.72 x 103 metric tons of benzidine were produced in the
United States by at least three manufacturers (Allied, GAP, and
Fabricolor). Previously the largest producer, Allied phased out
production in 1976. The primary method of manufacture of
benzidine is reduction of nitrobenzene with zinc and sodium
hydroxide; however, a variety of reducing agents are applicable.
Benzidine may enter the environment from benzidine production
facilities, from downstream chemical processing, and from use of
products containing benzidine or benzidine derivatives. Nitrous
acid oxidation is the only wastewater treatment method that has
been implemented at the plant scale and shown to be effective
for the concentrated benzidine manufacturing wastes.
Data from industry indicate that average benzidine discharges
from each of 300 user facilities amount to only 0.68 kg/year.
If this can be confirmed, the environmental significance is
minimal. In the work place, stringent standards already are
in effect under OSHA.
Several areas of information need to be clarified such as the
quantity of benzidine produced and consumed, locations of pro-
duction facilities and consumption sites, and environmental
discharge rates and behavior. This information should be ob-
tained in order to devise a management plan for defining
regulatory action.
This report was submitted in partial fulfillment of Contract
68-03-2550 by Monsanto Research Corporation under the sponsorship
of the U.S. Environmental Protection Agency. This report covers
the period November 1, 1977 to December 31, 1977. The work was
completed as of January 20, 1978.
IV
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CONTENTS
Foreword iii
Abstract iv
Tables v
Conversion Factors and Metric Prefixes vi
Acknowledgement vii
1. Introduction 1
2. Summary 2
3. Source Description 5
Physical and chemical properties 5
Production 6
Process description 7
Uses 8
4. Environmental Significance and Health Effects .... 10
Environmental significance 10
Health effects 11
Population at risk 12
5. Control Technology 14
6. Regulatory Action 17
References 18
TABLES
Number Page
1 Benzidine 2
2 Chemical Properties of Benzidine and Its
Formulations 6
3 Commercial Dyes Derived from Benzidine 9
4 Companies and Locations of Potential Benzidine
. Risk Areas 13
5 Comparison of Potential Treatment Methods 15
v
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CONVERSION FACTORS AND METRIC PREFIXES3
CONVERSION FACTORS
To convert from
Degree Celsius (°C)
Kilogram (kg)
Kilometer2 (km2)
Meter3 (m3)
Meter3 (m3)
Metric ton
Pascal (Pa)
to
Degree Fahrenheit
Pound-mass (pound-mass
avoirdupois)
Mile2
Foot3
Gallon (U.S. liquid)
Pound-mass
Torr (mm hg, 0°C)
Multiply by
t° = 1.8 t° + 32
2.204
3.860 x 10-1
3.531 x 101
2.642 x 102
2.205 x 103
7.501 x 10~3
METRI'C PREFIXES
Prefix Symbol Multiplication factor
Kilo
Mi Hi
k
m
103
io-3
1 kg
1 mm
Example
1 x 103 grams
1 x 10~3 meter
Standard for Metric Practice.
E 380-76£, IEEE Std 268-1976, American Society for Testing and
ANSI/ASTM Designation:
American Society for Te
Materials, Philadelphia, Pennsylvania, February 1976.
37 pp.
VI
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ACKNOWLEDGEMENT
This report was assembled for EPA by Radian Corporation, Austin,
TX, and Monsanto Research Corporation, Dayton, OH. Mr. D. L.
Becker served as EPA Project Officer, and Dr. C. E. Frank, EPA
Consultant, was principal advisor and reviewer.
VII
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SECTION 1
INTRODUCTION
Epidemiological investigations have clearly demonstrated that
benzidine is carcinogenic in humans. Higher than average inci-
dences of bladder cancer among workers in benzidine production
and processing facilities have been demonstrated. Recent
research results suggest that some benzidine-derived azo dyes
may be converted to benzidine in man or in certain environments,
As a result, there is concern over liquid effluent discharges
containing benzidine.
This report was prepared from available literature and includes
information regarding benzidine chemical properties, producers,
uses, and production process. Also included in this report is
information concerning the environmental and health effects of
benzidine, available pollution control technology, and current
regulatory action.
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SECTION 2
SUMMARY
Benzidine (p,p'-diaminobiphenyl), with the empirical formula
C12H12N2, is used in the manufacture of a wide variety of organic
chemicals, as an intermediate for azo dyes, and as a rubber com-
pounding agent. In 1972, 4.72 x 103 metric tons3 of benzidine
were produced in the United States by at least three manufac-
turers (Allied, GAF, and Fabricolor). Previously the largest
producer, Allied phased out benzidine production in 1976.
Table 1 highlights available information regarding benzidine.
TABLE 1. BENZIDINE
Extent of problem
Emission County
quantity, population, Control Current studies and
Emission source kg/day persons/km2 technology regulatory action
Production facilities: 0.454 -3 -3 • OSHA work place standards
GAF Corporation -" 89 Nitrous acid • EPA proposed toxic efflu-
u oxidation ent standard
Fabricolor - 913 -" • Toxicological research by
National Center for
Benzidine-based dye Toxicological Research
manufacturers, • EPA drinking water survey
^300 sites: ®'ff ~ Biodegradation • Possible inclusion under
E. I. Dupont -P 345 (bench-scale, hazardous spill provi-
Fabricolor -u 913 secondary sions of the Federal
J. S. Young - 987 treatment Water Pollution Control
only) Act
• Mining Enforcement and
Safety Administration
proposed standard
• Designated a priority
pollutant under Fed-
eral water Pollution
Control Act
a ~ ' ~~ •—~—-—•
Not applicable.
b
Not available.
Total for all sites.
1 metric ton = 106 grams; conversion factors and metric system
prefixes are presented in the prefatory pages of this report.
2
-------
Benzidine production depends on nitrobenzene, a relatively inex-
pensive raw material. The primary method of manufacture for this
chemical is reduction of nitrobenzene with zinc and sodium
hydroxide; however, a variety of reducing agents are applicable.
The stepwise reduction may be carried through as a continuous
operation, or it may be stopped at any stage for a change in
reducing agent, depending upon process economics, equipment
availability, quantity produced, plant location, and potential
hazards inherent in the reaction.
Benzidine may enter the environment from benzidine production
facilities, from downstream chemical processing, and from use of
products containing benzidine or benzidine derivatives. Industry
reports indicate that benzidine discharges at any production
facility do not usually exceed 0.454 kg/day. Free benzidine is
present in benzidine-derived azo dyes. According to industry,
quality control specifications require that the level not exceed
20 ppm (parts per million), but the discharged benzidine concen-
tration in practice is generally below 10 ppm. Assuming all
free benzidine is discharged in the liquid effluent, an estimated
total of 204.3 kg/yr is discharged from 300 user facility sites,
corresponding to approximately 0.68 kg/yr-facility. If this can
be confirmed, the environmental significance is minimal.
Benzidine and its salts are carcinogenic to humans, with the
bladder being the site of tumor induction. Carcinogenic hazards
to man may result from various types of exposure, including the
presence of benzidine carcinogens in drinking water, recreational
bodies of water, food processing waters, or fisheries.
Various potential wastewater treatment methods are available to
benzidine and benzidine-based dye manufacturers. These include
1) oxidation with nitrous acid (for pretreatment only); 2) oxi-
dation with ozone; 3) adsorption onto activated carbon;
4) adsorption onto polymeric adsorbent; 5) evaporation pond (no
discharge); and 6) biodegradation (for secondary treatment only).
Only the nitrous acid oxidation method has been implemented at
the plant scale and shown to be effective for the concentrated
benzidine manufacturing wastes.
As a result of observed inadequate housekeeping procedures at
benzidine manufacturing sites, the Occupational Safety and
Health Administration (OSHA) has required stringent workplace
standards to reduce environmental discharges. Additional
studies and regulatory actions are indicated in Table 1.
Based upon information presented in this report, the following
items need to be considered in future studies:
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data should be obtained to determine the quantity of
benzidine currently produced and consumed including dye
manufacture.
producers should be identified and locations of use
determined.
emission and effluent rates should be determined for
production facilities and benzidine-based dye manufac-
ture and other users.
environmental behavior as well as environmental levels
should be defined.
information should be obtained to describe current
industrial practice, commercial significance, and
environmental significance.
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SECTION 3
SOURCE DESCRIPTION
PHYSICAL AND CHEMICAL PROPERTIES
Benzidine (4,4'-diaminobiphenyl or p,p'-diaminobiphenyl)
C12H12N2, is used in the manufacture of a wide variety of or-
ganic chemicals, as an intermediate for azo dyes, and as a rubber
compounding agent (1, 2). Benzidine is reported to be a mixture
of three isotropic forms coexisting indefinitely at room temper-
ature (1). Table 2 (3-7) summarizes data regarding the chemical
properties of benzidine and its two standard formulations, sul-
fate and hydrochloride.
Benzidine emits highly toxic fumes when heated to its decomposi-
tion point. -It has been classified as "dangerous" in the latest
edition of Dangerous Properties of Industrial Materials (3).
Benzidine is combustible and darkens upon exposure to air and
(1) Kirk-Othmer Encyclopedia of Chemical Technology, Second Edi-
tion, Vol. 3. John Wiley & Sons, Inc., New York, New York,
1967. pp. 408-414.
(2) Chemical Origins and Markets, Fifth Edition. G. M. Lawler,
ed. Stanford Research Institute, Menlo Park, California,
1977. 118 pp.
(3) Sax, N. I. Dangerous Properties of Industrial Materials,
Fourth Edition. Van Nostrand Reinhold Company, New York,
New York, 1975. 1258 pp.
(4) Registry of Toxic Effects of Chemical Substances.
H. E. Christensen, ed. U.S. Department of Health, Education,
and Welfare, Rockville, Maryland, June 1976. 1245 pp.
(5) Condensed Chemical Dictionary, Eighth Edition. Van Nostrand
Reinhold Company, New York, New York, 1971.
(6) Merck Index, Ninth Edition. M. Winholz, ed. Merck & Co.,
Inc., Rahway, New Jersey, 1976.
(7) Criteria Document: Benzidine. EPA-440/9-76-017 (PB 254
,023), U.S. Environmental Protection Agency, Washington, D.C.,
June 1976. 65 pp.
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TABLE 2. CHEMICAL PROPERTIES OF BENZIDINE
AND ITS FORMULATIONS (3-7)
Property
Benzidine
dihydro-
Benzidine chloride
Benzidine
sulfate
Structure
Crystalline form
Melting point
Boiling point
Density
Solubility
Grayish-yellow, white, or
reddish-gray crystalline
powder
127.5°C to 128.7°C (98.6 kPa)
401.7°C
1.250 at 20°/4°C
1 g in 2,447 g water (12°C)
1 g in 107 g water (100°C)
1 g in 45 g ethyl ether
1 g in 13 g ethanol (28°C)
Crystalline
powder
Soluble in
water and
alcohol
Very slightly
soluble in
water, dilute
acids and
• alcohol
light; thus, storage in dark, sealed containers is recommended
(6). Chemical reactions of benzidine and its derivatives are
well documented in the literature (1).
PRODUCTION
Benzidine, also known as benzidine base or p,p'-diaminobiphenyl,
is produced as a technical grade paste. It is also available in
the hydrochloride form. The 1972 production of benzidine in the
United States was 4.72 x 103 metric tons (8).
Eight possible manufacturers were identified, two of which now
manufacture benzidine (GAF and Fabricolor). Benzidine manufac-
turers produce 2.04 x 10"* metric tons/yr of azo dyes from
benzidine (9). Allied, previously the largest producer, phased
(8) Scoring of Organic Air Pollutants. Chemistry, Production,
and Toxicity of Selected Organic Chemicals. Mitre Corpora-
tion, McLean, Virginia, 1976.
(9) Keinath, T. M. Benzidine: Wastewater Treatment Technology,
EPA-440/9-76-018 (PB 254 024). U.S. Environmental Pro-
tection Agency, Washington, D.C., June 1976. 132 pp.
6
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out benzidine production in 1976. Benzidine base is available
from Orlex Chemical Corporation; the hydrochloride form is
available from Orlex and Conray Chemicals, Inc.; and the dihydro-
chloride form is supplied by American Drug and Chemical Company
(10). City Chemical Corporation is a supplier of the sulfate
form of benzidine (11).
PROCESS DESCRIPTION
Benzidine production depends on nitrobenzene, a relatively inex-
pensive raw material. The primary manufacturing method for this
chemical is reduction of nitrobenzene with zinc and sodium
hydroxide, as shown in Reaction 1 (1).
2C6H5N02 + 5Zn + lONaOH —> C6H5NHNHC6H5 + 5Na2ZnO2 + 4H20 (1)
Nitrobenzene Hydrazobenzene
The resulting hydrazobenzene is then heated with mineral acid in
a distillation step. The second step, shown in Reaction 2,
results in a double semidine rearrangement (better known as the
benzidine rearrangement) with the formation of benzidine and
o,p'-diaminobipheny1.
Mineral acid
C6H5NHNHC6H5 » NH2C6Htt-C6HitNH2 + NH2C6Hit-C6HltNH2 (2)
Hydrazobenzene Benzidine o,p'-diaminobipheny1
(3-15%)
The precipitated dihydrochloride and/or sulfate (depending on
which mineral acid is used) is recovered by filtration. The
benzidine salt may be used directly in the manufacture of azo
dyes. Alternatively, it is converted to the free base by reacL
tion with a weak base and purified by vacuum distillation.
Reaction 1 is allowed to proceed slowly at approximately 100°C.
Control of the reaction, accomplished by the gradual addition of
reactants, is necessary to avoid side reactions such as complete
reduction to aniline. Diluents, such as naphtha, dichloro-
benzene, and alcohol, are also used to minimize the chance of
such side reactions (1).
(10) Chemical Marketing Reporter, 1976-77 OPD Chemical Buyers
Guide, Sixty-fourth Annual Index. Schnell Publishing
Company, Inc., 1976.
(11) 1977 Directory of Chemical Producers. Stanford Research
Institute, Menlo Park, California, 1977.
-------
The stepwise reduction may be carried through as a continuous
operation using the same reducing agent, or it may be stopped at
any stage for a change in reducing agent. Reducing agents, in
addition to zinc, include zinc amalgam, iron, electrolytic
reduction and others such as noble metal or nickel catalysts in
the presence of aqueous alkali. These modifications depend upon
process economics, equipment availability, quantity produced,
plant location, and potential hazards inherent in the reaction
(1).
One modification of this production method is based on electrol-
ysis of nitrobenzene, followed by distillation. A 90% yield of
hydrazobenzene can be obtained by electrolysis of an alkaline
emulsion of nitrobenzene using an iron cathode. This distilla-
tion step is performed in the presence of mineral acid to cause
the benzidine rearrangement (1, 5).
Another production sequence involves nitration of diphenyl, fol-
lowed by reduction of the product with zinc dust in alkaline
solution and subsequent distillation (5).
USES
Benzidine is used considerably in analytical chemistry. It is
employed in the detection and determination of a large number of
inorganic ions and compounds such as cadmium, copper, manganese,
chlorine, fluoride, cyanide, ferrocyanide, ferricyanide,
phosphate, silica, sulfate, tungsten, hypohalites, permanganate,
nitrate, nitrite, and phosphomolybdate. Benzidine has also been
used in the determination of naphthalenesulfonic acids and deter-
gents by the formation of an insoluble precipitate (1).
The"major use of benzidine is as a starting material in the pro-
duction of azo dyes and sulfur dyes. Over 250 dyes based on
benzidine have been reported, and the more prominent ones manu-
factured in the United States in 1962 are those presented in
Table 3 (1). More recent information indicates that benzidine is
no longer used to such a great extent in the production of dyes
(12); thus, further investigation is warranted in this area in
order to determine the quantity of benzidine used in the pro-
duction of dyes.
At least two manufacturers of benzidine, GAF and Fabricolor, pro-
duce 2.04 x lQk metric tons/yr of azo dyes from this intermedi-
ate. The dyes are used by approximately 300 major manufacturers
(12) Riegel's Handbook of Industrial Chemistry, 7th Edition.
J. A. Kent, ed. Van Nostrand Reinhold Company, New York,
New York, 1974.
8
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TABLE 3. COMMERCIAL DYES DERIVED FROM BENZIDINE (1)
Colour Index name
Mordant Yellow 36
Pigment Red 39
Direct Red 28
Direct Orange
Direct Red 10
Direct Red 13
Direct Red 37
Direct Red 1
Direct Brown 2
Direct Orange 1
Direct Violet 1
Direct Blue 2
Colour
Index No.
14135
21080
22120
22130
22145
22155
22240
22310
22311
22370, 22375
22430
22570
22590
Colour
Direct
Direct
Direct
Direct
Direct
Direct
Direct
Direct
Direct
Direct
Direct
Direct
Direct
Index
Blue
Brown
Brown
Brown
Brown
Brown
Black
Black
Green
Green
Green
Brown
Brown
name
6
1
1A
154
6
85
38
4
1
6
8
31
74
Colour
Index No .
22610
30045
30110
30120
30140
30145
30235
30245
30280
30295
30315
35660
36300
of textiles, papers, and leather (13); however, no recent pro-
duction figures are available to indicate the extent of benzidine
usage in the various dye products.
Azo dyes are typically manufactured in small batches with the
amine (benzidine) initially in acid in a well-stirred tub. The
solution is cooled to 0°C to 5°C, and sodium nitrite is added
until the diazotization is complete. The diazonium compound is
added at a slow rate to a second tub containing a coupling com-
pound (phenol, naphthol ether, or a compound with an active
methylene group). As the coupling reaction proceeds, the dye
precipitates. Upon completion of the coupling reaction, the tub
is warmed with steam. The finished dye is recovered in filter
presses and dried in tray dryers (12, 14).
(13) Summary Characterizations of Selected Chemicals of Near-Term
Interest. EPA-560/4-76-004 (PB 255 817), U.S. Environmental
Protection Agency, Washington, D.C., April 1976. 50 pp.
(14) Steadman, T. R., et al. Industrial Process Profiles for
Environmental Use, Chapter 7, Organic Dyes and Pigments
Industry. EPA-600/2-77-023g, U.S. Environmental Protection
Agency, 1977.
9
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SECTION 4
ENVIRONMENTAL SIGNIFICANCE AND HEALTH EFFECTS
ENVIRONMENTAL SIGNIFICANCE
Benzidine may enter the environment from benzidine production
facilities, from downstream chemical processing (most notably dye
manufacture and application), and from use of products containing
benzidine or benzidine derivatives.
The principal environmental concern at benzidine production
facilities has been the quantity of benzidine discharged to
municipal wastewater treatment plants. Discharge measurements to
date, however, have only been made by the industry, and reported
benzidine discharges at any facility usually do not exceed
0.454 kg/day. Benzidine is believed to be present in the sludge
removed from industrial waste pretreatment plants, and the envi-
ronmental adequacy of land disposal of these sludges is unknown -
Industry data indicate that discharges from municipal wastewater
treatment plants contain benzidine at a level lower than its
limit of detection. Levels of benzidine exceeding 5 g/m3 can
inhibit anaerobic digestion wastewater treatment processes; con-
centrations above this level thus present a problem to treatment
plants using this process plus a possible hazard to the receiving
waters (13).
Free benzidine is present in the benzidine-derived azo dyes.
Industry quality control specifications require that the dis-
charged benzidine level not exceed 20 ppm, and in practice this
level is usually below 10 ppm. Assuming all free benzidine is
discharged in the liquid effluent, an estimated total of
204.3 kg/yr is discharged from 300 dye user facility sites,
corresponding to approximately 0.68 kg/yr-facility (13).
In 1951, concentrations of benzidine in a chemical plant workroom
atmosphere averaged 0.024 mg/m3; however, no measurements for
benzidine in ambient air have been reported (15).
The following programs are in progress to develop and evaluate
analytical techniques for environmental monitoring of benzidine:
(15) Documentation of the Threshold Limit Values, Third Edition.
American Conference of Governmental Industrial Hygienists,
Cincinnati, Ohio, 1971.
10
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Monitoring Method Development - Appropriate analytical
methods for benzidine were to be selected by August 1976.
Three EPA laboratories investigated reliability, detection
limits, and feasibility of analytical methods. Initial
evaluations were completed in June 1976, and the recom-
mendations were to follow (personal communication with
John Moran, Office of Research and Development,
Washington, D.C.).
Field Monitoring - Monitoring activities will be con-
sidered when an appropriate method is available (personal
communication with Vincent DeCarlo, Office of Toxic
Substances, Washington, D-C.).
HEALTH EFFECTS
Although many chemicals have been shown to induce cancer in labo-
ratory animals, only a few have been positively identified as
human carcinogens. Benzidine and its salts, without question,
are carcinogenic to humans (9), with the site of tumor induction
being the bladder (7).
Carcinogenic hazards to man may result from various types of ex-
posure, including the presence of carcinogens in drinking water,
recreational water bodies, food processing waters, or fisheries.
It is believed reasonable that the presence of benzidine in the
aquatic environment poses a threat to man and the environment (9).
A high occurrence of bladder tumors in the dye industry has been
established. In a 1949 study, 186 workmen were examined to
follow the evolution of bladder lesions. The study indicated
that benzidine and B-naphthylamine have the highest carcinogenic
potential among the aromatic amines studied. A 1952 study inves-
tigated the incidence of bladder tumors in an English dyestuffs
factory. Sixty-six cases of bladder tumor were reported. Of the
66 cases there were 30 (23 in the manufacturing section and 7 in
the handling section) who were exposed to benzidine and who had
never been exposed to B-naphthylamine (7).
A 1954 study involved workmen engaged in the manufacture and use
of aniline, benzidine, and a- and B-naphthylamines in the British
chemical industry. The data indicated that the incidence of
bladder cancer among persons exposed to benzidine greatly ex-
ceeded that among the general population. The study also showed
bladder cancer to be a fatal disease, only 20% of all cases
having survived more than 10 years from the first detection of
the disease (7).
In 1962, the incidence of urinary bladder tumors in workers ex-
posed to a-naphthylamine, B-naphthylamine, and benzidine was
studied to determine the average incubation period, the average
survival time, and the incidence of malignant tumors other than
11
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those of the bladder. The population studied consisted of 366
male workers in a coal tar dye factory employed between 1912-1962.
Of the 366 workers studied, 76 were exposed to benzidine alone.
Bladder cancer developed in 17, or 21.3%, of these 76 workers.
The induction of bladder cancer from benzidine had an average
incubation period of 18.7 years, calculated from the first expo-
sure to diagnosis of malignancy (7).
Following diagnosis of bladder malignancy in workers exposed to
benzidine, the longest period of survival was 10 years, the
shortest was less than a year. The mean survival time between
diagnosis of cancer and death was approximately three years (7).
There was no evidence of any unusual incidence of malignancies
other than those of the urinary bladder. Among the 366 men
studied, there were 11 recorded malignant tumors other than
cancer of the bladder (7).
Previous cases of bladder cancer have occurred among Allied
Chemical Buffalo Dye Plant workers. In all cases these workers
were exposed to early processes and operations. New manufac-
turing facilities, a catalytic reduction process, elimination of
all base operations, and institution of a variety of process and
administrative controls have drastically reduced exposure levels.
No new cases have occurred among those workers whose only expo-
sure has been to the latest process and equipment commissioned
in 1955. The nature of the risk is such, however, that exposure
must be maintained at the lowest practicable limit through the
promulgation and enforcement of administrative, engineering, and
processing controls, and industrial hygiene practices (7).
POPULATION AT RISK
Industries handling benzidine are 1) the manufacturers of benz-
idine, 2) the dye manufacturers who use benzidine as a starting
material or intermediate, and 3) users of benzidine-based dyes
(e.g., textile industry). Workers in these industries risk expo-
sure. Because benzidine is widely used in clinical and forensic
laboratories as a detection reagent, an additional segment of
the population is potentially exposed through this end use.
Also, benzidine is a contaminant in many disperse dyes. A large
population may risk exposure to benzidine from use of products
dyed in this manner (e.g. benzidine may enter the environment
through wash water from cleaning these materials or through skin
absorption). Table 4 lists some companies identified as possi-
ble producers and users of benzidine and benzidine-derived
chemicals. It was not possible to list all users of benzidine-
based dyes, and industry contact may be necessary to obtain a
more precise list of producers. Since Congo Red reportedly
constitutes a major use of benzidine, manufacturers of this
product are listed as a category of possible benzidine exposure.
12
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TABLE 4. COMPANIES AND LOCATIONS OF POTENTIAL BENZIDINE RISK AREAS
Location/population
Company
City
Population density,
people/km
County
Population
Benzidine producers:
GAF Corporation
Chemical Products
Rensselaer, NY
Fabricolor Chemical Corp. Paterson, NJ
Manufacturers of Direct Red 28
(Congo Red, CI 22120):
E. I. duPont de Nemours
and Co., Inc.
Wilmington, DE
Fabricolor Chemical Corp.
J. S. Young Co.,
Young Aniline Works, Inc.,
Subsidiary
Paterson, NJ
Baltimore, MD
89
913
345
(see above)
987
Rensselaer
Albany
Schenectady
Saratoga
Total
Passiac
Bergen
Total
New Castle
Salem Co., NJ
Cecil Co., MD
Total
5 county total
153,800
288,700
159,900
140,700
743,100
456,200
874,600
1,331,000
395,000
61,700
56,300
513,000
2,140,400
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SECTION 5
CONTROL TECHNOLOGY
Various potential wastewater treatment methods are available to
benzidine manufacturers and benzidine-based dye manufacturers
including: 1) oxidation with nitrous acid (for pretreatment
only); 2) oxidation with ozone; 3) adsorption onto activated
carbon; 4) adsorption onto polymeric adsorbent; 5) no discharge
(evaporation pond); and 6) biodegradation (for secondary treat-
ment only). A comparison of these potential treatment methods
is presented in Table 5 (9).
Of the potential treatment technologies that are available for
the removal of benzidine from process wastewaters, only the
nitrous acid oxidation method has been implemented at the plant
scale (GAP,Corporation) and shown to be effective for the concen-
trated benzidine manufacturing wastes. It is to be noted that
this process was employed only for the treatment of benzidine
manufacturing wastewaters. Residual levels of benzidine in the
nitrous acid treated effluent usually were found to be less than
10 ppb (parts per billion) (9).
Benzidine-based dye manufacturing wastewaters can be treated rel-
atively inexpensively by the patented biodegradation process
(see Table 5). Due to biological toxicity, however, this process
probably cannot be employed for the direct treatment of benzidine
manufacture wastewaters prior to a pretreatment step such as the
nitrous acid oxidation process (9).
Fabricolor, Inc. and GAF Corporation discharge their wastewaters
to municipal biological wastewater treatment systems. The final
product wastewaters, after biological treatment, should show no
detectable benzidine.
No other benzidine treatment technologies have been implemented
at the plant scale; in fact, none have been evaluated beyond the
bench scale. Consequently, plant-scale process efficiencies and
costs have not been established for any of the processes con-
sidered other than the nitrous acid oxidation process (9).
The ranges for actual or projected process costs given in Table 5
are broad because benzidine production methods vary considerably
with respect to the quantity of process wastewaters generated.
14
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TABLE 5. COMPARISON OF POTENTIAL TREATMENT METHODS (9)
Type of treatment
Level of development
and/or application
Effectiveness
Waste treatment cost,
£/kg benzidine produced
Benzidine manufacturing
wastewaters:
Oxidation with
nitrous acid
(pretreatment only)
Oxidation with ozone
Adsorption onto
activated carbon
Adsorption onto
polymeric adsorbent
No discharge/evapo-
ration
Benzidine-based dye
manufacturing wastewaters:
Biodegradation
(secondary treatment
only)
Full scale
Bench scale
(preliminary only)
Bench scale
(preliminary only)
None
None
10 ppb
1-10 ppb (projected)
1-10 ppb (projected)
1-10 ppb (projected)
4.4 - 26.4 (actual)
220 - 1100 (projected)
2.2 - 22 (projected)
Unknown
55 (projected)
Bench scale
Unknown
0.04 (projected)
Includes pretreated benzidine manufacturing wastes.
For treatment of dye mother liquors (basis 0.05 kg/m3).
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If the wastewater volumes produced are high, then the associated
costs are also respectively higher (9).
Substitution of less toxic compounds is another possible control
method; however, it is estimated that substitute compounds are
three to five times as expensive as benzidine, and substitutes
for some derivatives (especially halogenated benzidine compounds)
may not be available.
16
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SECTION 6
REGULATORY ACTION
As a result of inadequate housekeeping procedures at benzidine
manufacturing sites, the Occupational Safety and Health Adminis-
tration (OSHA) has required stringent workplace standards.
In December 1973, the U.S. Environmental Protection Agency (EPA)
proposed a toxic pollutant effluent standard, and the agency is
planning to resubmit a similar standard and a pretreatment re-
quirement. The results of the current animal experiments at the
National Center for Toxicological Research, including chronic
toxicity, carcinogenicity, and metabolic behavior, should be
available in the near future. Benzidine is being examined in
the expanded EPA drinking water survey and is being studied for
possible inclusion under the hazardous spill provisions of the
Federal Water Pollution Control Act (14). The Mining Enforcement
and Safety Administration has proposed a mandatory standard that
would require storage and use of 16 toxic chemicals (including
benzidine) only under strict laboratory conditions approved by a
nationally recognized agency (16). Benzidine is also designated
a priority pollutant under the Federal Water Pollution Control
Act.
(16) Toxic Material News, 4(26):163, 1977.
17
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REFERENCES
1. Kirk-Othmer Encyclopedia of Chemical Technology, Second
Edition, Vol. 3. John Wiley & Sons, Inc., New York,
New York, 1967. pp. 408-414.
2. Chemical Origins and Markets, Fifth Edition. G. M. Lawler,
ed. Stanford Research Institute, Menlo Park, California,
1977. 118 pp.
3. Sax, N. I. Dangerous Properties of Industrial Materials,
Fourth Edition. Van Nostrand Reinhold Company, New York,
New York, 1975. 1258 pp.
4. Registry of Toxic Effects of Chemical Substances.
H. E. Christensen, ed. U.S. Department of Health, Educa-
tion, and Welfare, Rockville, Maryland, June 1976. 1245 pp.
5. Condensed Chemical Dictionary, Eighth Edition. Van Nostrand
Reinhold Company, New York, New York, 1971.
6. Merck Index, Ninth Edition. M. Winholz, ed. Merck & Co.,
Inc., Rahway, New Jersey, 1976.
7. Criteria Document: Benzidine. EPA-440/9-76-017 (PB 254
023), U.S. Environmental Protection Agency, Washington,
D.C., June 1976. 65 pp.
8. Scoring of Organic Air Pollutants. Chemistry, Production,
and Toxicity of Selected Organic Chemicals. Mitre Corpor-
ation, McLean, Virginia, 1976.
9. Keinath, T. M. Benzidine: Wastewater Treatment Technology.
EPA-440/9-76-018 (PB 254 024). U.S. Environmental Pro-
tection Agency, Washington, D.C., June 1976. 132 pp.
10. Chemical Marketing Reporter, 1976-77 OPD Chemical Buyers
Guide, Sixty-fourth Annual Index. Schnell Publishing
Company, Inc., 1976.
11. 1977 Directory of Chemical Producers. Stanford Research
Institute, Menlo Park, California, 1977.
18
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12. Riegel's Handbook of Industrial Chemistry, 7th Edition.
J. A. Kent, ed. Van Nostrand Reinhold Company, New York,
New York, 1974.
13. Summary Characterizations of Selected Chemicals of Near-Term
Interest. EPA-560/4-76-004 (PB 255 817), U.S. Environmental
Protection Agency, Washington, D.C., April 1976. 50 pp.
14. Steadman, T. R., et al. Industrial Process Profiles for
Environmental Use, Chapter 7, Organic Dyes and Pigments
Industry. EPA-600/2-77-023g, U.S. Environmental Protection
Agency, 1977.
15. Documentation of the Threshold Limit Values, Third Edition.
American Conference of Governmental Industrial Hygienists,
Cincinnati, Ohio, 1971.
16. Toxic Material News, 4(26):163, 1977.
19
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TECHNICAL REPORT DATA
(Please read Instructions on the reverse before completing)
1. REPORT NO.
EPA-600/2-79-210e
3. RECIPIENT'S ACCESSION NO.
4. TITLE AND SUBTITLE
Status Assessment of Toxic Chemicals: Benzidine
5. REPORT DATE
December 1979
issuing date
6. PERFORMING ORGANIZATION CODE
7. AUTHOR(S)
T.R. Black-wood, S.R. Archer
N.P. Meserole
8. PERFORMING ORGANIZATION REPORT NO.
9. PERFORMING ORGANIZATION NAME AND ADDRESS
Monsanto Research Corp. Radian Corp
1515 Nichols Road 8500 Shoal Creek Blvd
Dayton, Ohio 1+5^07 P.O. Box 99^8
Austin, Texas 78766
10. PROGRAM ELEMENT NO.
1AB601;
11. CONTRACT/GRANT NO.
68-03-2550
12VSPONSORI.NG AGENQY NAME AND ADDRESS
Industrial Environmental Research Lab
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, Ohio ^5268
- Cinn, OH
13. TYPE OF REPORT AND PERIOD COVERED
Task Final 11/77 - 12/77
14. SPONSORING AGENCY CODE
EPA/600/12
15. SUPPLEMENTARY NOTES
IERL-Ci project leader for this report is Dr. Charles Frank,
16. ABSTRACT
The properties, sources, production processes, and uses of
benzidine are reviewed in the report. Benzidine is a proven
human carcinogen, and its widespread use as a dye intermediate
has led to the high recurrence of bladder cancer in that industry.
OSHA has imposed stringent workplace standards. Further information
is needed on benzidine production and use to better define necessary
regulatory action.
17.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.lDENTIFIERS/OPEN ENDED TERMS
COS AT I Field/Group
Biphenyl, Diphenyl, Aromatic hydrocarbons,
Aromatic polycyclic Hydrocarbons, Hydro-
carbons, polyphenyl compounds, Polyphenyl
hydrocarbons, unsaturated hydrocarbons
Benzidine, Dyes, Rubbei
68A
68D
68G
8. DISTRIBUTION STATEMENT
Release to Public
19. SECURITY CLASS (ThisReport)
Unclassified
21. NO. OF PAGES
28
20. SECURITY CLASS (Thispage)
Unclassified
22. PRICE
EPA Form 2220-1 (Rev. 4-77) PREVIOUS EDITION is OBSOLETE
20
>v U.S. GOVERNMENT PRINTING OFFICE: 1980 -657-146/5517
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