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 ------- 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. ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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. ------- 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: ------- 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. ------- 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. ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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). ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- |