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

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                           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

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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.

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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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