EPA-560/2-76-004 BIOLOGICAL EFFECTS AND ENVIRONMENTAL ASPECTS OF 1,3-BUTADIENE (SUMMARY OF THE PUBLISHED LITERATURE) MAY 1976 FINAL REPORT ENVIRONMENTAL PROTECTION AGENCY OFFICE OF TOXIC SUBSTANCES WASHINGTON, D,C, 20460 ------- TECHNICAL REPORT DATA (Please read Instructions on the reverse before completing) CRT NO. I EPA 560/2-76^004 2. 3. RECIPIENT'S ACCESSION-NO. 4. TITLE AND SUBTITLE Biological Effects and Environmental Aspects of 1,3-Butadiene (Summary of the Published Literature) S. REPORT DATE Hay 1976 6. PERFORMING ORGANIZATION CODE 7. AUTMOR(S) T.B. Parsons Glynda E. Mil kins 8. PERFORMING ORGANIZATION REPORT NO. 9. PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT NO. Radian Corporation 8500 Shoal Creek Blvd. Austin, Texas 78766 11. CONTRACT/GRANT NO. 68-01-3249, Task #7 12. SPONSORING AGENCY NAME AND ADDRESS Office of Toxic Substances U.S. Environmental Protection Agency Washington, D.C. 20460 13. TYPE OF REPORT AND PERIOD COVERED Final • • 14. SPONSORING AGENCY CODE 19. SUPPLEMENTARY NOTES This task was initiated because of a reported increased incidence of leukemia among workers in certain styrene-butadiene synthetic rubber manufacturing plants. 16. ABSTRACT This report is a summary of the literature on the biological effects and environmental aspects of 1,3-butadiene and was prepared from articles and abstracts identified through a search of the technical literature. The report contains information on the effects of 11,3-butadiene in environmental samples and on the reactivity of 1,3-butadiene in environmental media. 17. KEY WORDS AND DOCUMENT ANALYSIS DESCRIPTORS b.lDENTIFIERS/OPEN ENDED TERMS COSATl Field/Group 1,3-butadiene 13. DISTRIBUTION STATEMENT Document available to the public through the National Technical Information Service Springfield, Virginia 22151 19. SECURITY CLASS (ThisReport) 21. NO. 20. SECURITY CLASS (Thispage) Unclassified EPA Form 2220-1 (9-73) ------- EPA-560/2-76-004 BIOLOGICAL EFFECTS AND ENVIRONMENTAL ASPECTS OF 1,3-BUTADIENE (Summary of the Published Literature) Final Report Prepared by T.B. Parsons Glynda E. Mil kins Contract No. 68-01-3249, Task 7 Frank Letkiewicz Project Officer Office of Toxic Substances U.S. Environmental Protection Agency Washington, D.C. 20460 May 1976 ------- NOTICE This report has been reviewed by the Office of Toxic Substances, EPA, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Environmental Protection Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. : b ------- • TABLE OF CONTENTS Page 1.0 INTRODUCTION ............... .... 1 2 . 0 BIOLOGICAL EFFECTS ....... ..... .... 2 2.1 Plant Studies ....... ...... ... 2 2.2 Animal Studies ............ ..••'• 3 2.2.1 Organs and Systems .......... 4 2.2.1.1 Reproductive System. .... 4 2.2.1.2 Circulatory System ..... 5 2.2.1.3 Hematopoietic Organs, Formed Elements , and Plasma ......... . . • * 2.2.1.4 Liver ......... ... 9 2.2.1.5 Kidneys. . ...... . . .10 2.2.1.6 Respiratory System . ... . 10 2.2.1.7 Skin ........ .... 11 2.2.1.8 Nervous System ..... ' ... 11 2.2.1.9 Gastrointestinal Tract ... 12 2.2.2 Various Metabolism Disturbances ... 13 2.3 Observed Effects on Humans ......... 14 2.3.1 Circulatory System .......... 14 2.3.2 Hematopoietic Organs, Formed Elements, and Plasma ...... ... .. .16 2.3.3 Liver ................. 18 2.3.4 Kidneys .......... ....... 19 2.3.5 Respiratory System .......... 19 2.3.6 Skin ................... 20 ii ------- TABLE OF CONTENTS (Continued) 2.3.7 Eyes. . , 21 2.3.8 Nervous System 22 2.3.9 Gastrointestinal Tract. ...... 23 2.3.10 Endocrine System. . 24 3.0 ENVIRONMENTAL ASPECTS ..... 25 3.1 Occurrence 25 3.2 Reactivity ........... 28 4.0 BIBLIOGRAPHY 33 5.0 ADDITIONAL REFERENCES 49 111 ------- 1.0 Introduction This literature summary was prepared by Radian Corporation for EPA under task 7 of contract number 68-01-3249, Information Concerning Selected Chemicals. According to the task statement, abstracts concerning biological properties, environmental effects and analytical methods for butadiene were to be collected using several abstracting indices. A narrative summary of literature describing biological and environmental aspects was to be pre- pared. The literature search and summary were to be completed within a two-week time period. Literature describing biological aspects of butadiene is summarized in Section 2.0. Plant, laboratory animal, and human studies are described. The majority of published infor- mation on biological aspects was written in Russian, and many of the references were unavailable in full text English trans- lations. Information from these sources was obtained from the abstracts. If an abstract rather than a full text article was the source of information, the abstract number was given in the literature citation. If the full text was consulted, the liter- ature citation contains the author's name and the year of publication. Information on environmental occurrence and reactivity of butadiene is summarized in Section 3.0. Most of the infor- mation on this subject was available in full text in English. References cited in the text are listed in the Bibli- ography in Section 4.0. Some references were not available in full text in time to be described in the summary. Some abstracts did not contain the information of interest. References in these two categories were not described in the literature summary but are expected to contain useful information. These additional references are listed separately in Section 5.0. -1- ------- 2.0 Biological Effects This section contains a summary of responses of plants, animals, and humans to 1,3-butadiene and to mixtures of ,1,3- butadiene with other substances as reported by various researchers in the technical literature. 2.1 Plant Studies A summary of the available literature concerning effects of 1,3-butadiene and mixtures of 1,3-butadiene with atmospheric components on plant life is included in this section. Only three reports of plant studies of this type were found. The effects of hydrocarbon gases representative .of the Ci- Ci» range on plant growth and development were individually examined by Heck and Pires (1962). Fumigation with 1000 ppm of.1,3-butadiene produced some indication of injury in cotton, cowpeas, and tomatoes, although the symptoms were too slight to be identified. No effect was reported on coleus, sorghum, and soybean. Further fumigation experiments at 10 and 100 ppm (v/v) gas in air for 3-week periods produced no easily recognizable effect from 1,3-butadiene on cotton, cowpeas, and tomatoes. It was therefore eliminated from further studies. (Heck and Pires, 1962). Abeles and Gahagan (1968) examined the role of ethylene and ethylene analogs in bean plant abscission acceleration studies. Of the seven test gases studied, 1,3-butadiene was least active in accelerating abscission and only displayed a 10% stimulation at 10,000 ppm exposure for four hours. -2- ------- Research conducted by Haagen-Smit, et al. (1951) in trying to duplicate symptoms induced by smog on plants in the Los Angeles area indicates both typical and atypical injury to plants from exposure to a mixture of butadiene with ozone for five hours. The typical symptoms used for diagnosis were silvering of leaves on spinach, endive, and beet .along with speckled necrosis on oats and alfalfa. Atypical damage encoun- tered was wilting, the formation of large necrotic areas, tip burning, chlorosis, bleaching, or minute pitting of leaves. Further experimentation with mixtures of N02 and butadiene showed typical smog damage symptoms at 5 ppm butadiene and 7 ppm NO2 in the absence of sunlight or UV irradiation. Lower con- centrations of 0.5 ppm butadiene and 4.5 ppm N02 without sunlight or UV irradiation resulted in no symptomatic response. Results of experiments with butadiene, NOX and UV irradiation or sunlight were not reported. The authors concluded from their work that the plant damaging species were oxidation products of unsaturated hydrocarbons (Haagen-Smit, et al, 1952). The three articles summarized in this section support the hypotheses that 1,3-butadiene itself may have little effect on plants. However, conditions and substances present in the atmosphere may result in the formation of reactive compounds causing plant damage. 2.2 Animal Studies This section describes the effects of 1,3-butadiene on laboratory animals. Reported observations of the effects on several organs and systems and metabolism are included. Exposure to 1-3 butadiene either alone or in combina- tion with a-methylstyrene, toluene, N-phenyl-B-naphthylamine, iso- prene and toluene was accomplished most often by inhalation of -3- ------- vapors, although a few studies utilized oral administration. The laboratory rat was the most often used animal; guinea pigs, rabbits, mice and cats were also utilized. 2.2.1 Organs and Systems In an effort to facilitate reading and utilization of reported data concerning effects of 1,3-butadiene and mixtures of 1,3-butadiene with other substances on animals, the informa- tion was organized by organ or system. The categories included are the reproductive system; the circulatory system; hematopoietic organs, formed elements, and plasma; liver; kidneys; respiratory system; skin; the nervous system; and the gastrointestinal system. 2.2.1.1 Reproductive System Female . . During the first month of exposure by an unspecified method to 1,3-butadiene and a-methylstyrene, a decrease in the number of primordial cells and maturing follicles is noted. Large numbers of corpora lutea are preserved in the active state. If poisoning by 1,3-butadiene and a-methylstyrene continued for 2-3 months, adaptation occurred (CA75:96902t). Another survey (CA72: 30037w) describing effects of administering butadiene and toluene by inhalation reported prolongation of estrous caused by both chronic and acute poisoning. A normal cycle was reestablished in 507» of the rats within five months after cessation of chronic poisoning. Male _ :• • Chronic vapor inhalation of a-methylstyrene and 1,3- butadiene by rats resulted in inhibited spermatogenesis with -4- ------- dysplastic and necrotic changes noted. Signs of adaptation and restoration of spermatogenesis did occur more than 24 days after cessation of the 60 to 90 day course of poisoning (CA75: 96900r). 2.2.1.2 Circulatory System Hemodynamic disturbances with increased permeability of vessel walls were the result of chronic exposure of rats to 1,3-butadiene for 81 days at concentrations of 30 mg/ra3 (CA75: 107774f). Chronic vapor inhalation by rats of a-methylstyrene and 1,3-butadiene resulted in disturbed permea- bility of testicular veins with accumulation of blood proteins in vein walls and testicular stroma (CA75: 96900r). Chronic exposure in another study of the same two substances resulted in vascular dystonia in respiratory structures (CA78: 106680x). During long-term administration of 1,3-butadiene and a-methylstyrene by inhalation, an initial .toxic reaction observed was increased permeability of blood vessels in rat lung. Later, sclerotic processes developed in perivascular and peribronchial zones, and blood vessel permeability decreased (CA75: 107749b). Chromotropic compounds accumulated in blood vessel walls of rats subjected to chronic exposure by inhalation of a-methylstyrene and 1,3-butadiene mixtures. After 90 days of poisoning, chromotropic compounds were found in perivascular connective tissue. Again, signs of sclerosis were observed and outlasted the arrest of poisoning (CA75: 96881k). The chronic exposure of rats to 0.03 mg/i 1,3-butadiene for 81 days caused decreased arterial pressure (CA66: 118540s). Specific histopathology described in one study of rats ingesting 100 mg/kg 1,3-butadiene daily (subacute) for a 2.5 month course were as follows: cytoplasm of the heart showed granular and hydropic dystrophy, cytolysis, neuronophagia, homogenation of vascular walls with permeability disturbance, -5- ------- and lymphohistiocytic infiltration (HEEP/72/03574). Rabbits subjected to chronic exposure to 1,3-butadiene (100 mg/m3) exhibited fragmentation of muscle fibers in the myocardium (Batkina, 1966) . .. 2.2.1.3. Hematopoietic Organs, Formed Elements, and Plasma Hematopoietic Organs and Formed Elements A 120-day test exposing rats to vapors of 5 mg 'a-methyl- styrene/m3 air and 100 mg 1,3-butadiene/m3 produced disturbances in the tissues and cells of the bone marrow, lymph glands, and spleen, which began to normalize at 90-120 days. Protein metab- olism changes were noted in lymphocytes, normoblasts, and unripe granulocytes during the experiment. The results point to the myelotoxic effect of the combination of the two compounds (CA75:116947s). A change in the cell distribution in rabbits was observed with the administration, in an unspecified manner, of 200 mg/i of 1,3-butadiene. The ratio of erythroblasts to granulocytes was , increased (CA74:97300m). A separate study using inhalation of 99.8 mg 1,3- butadiene and 5.2 mg of a-methylstyrene per m3 demonstrated a decreased level of leukocytes in rats (CA78: 106680x). The effect was also reported (CA75: 107786m) with specific reference to decrease in neutrophils. Hypochromic anemia was also observed, indicating inhibited hemopoiesis. Leukopenia was found in mice exposed to fumes from heated butadiene rubber. The fumes con- tained 0.012 mg/& N-phenyl-B-naphthylamine and 0.339 mg/I 1,3-butadiene (CA71: 41988n). Another study (CA66:118541t) performed on rats exposed by inhalation of butadiene for 81 days also resulted in erythrocytosis and leukocytosis with a neutrophilic shift to the left. -6- ------- A study of both acute and chronic poisoning of experimental animals was reported by Batkina, 1966. Acute poisoning of rats and rabbits caused leukocytes is with neutropenia and relative lymphocytes is along with changes in protein distri- bution in the serum. Chronic poisoning of rats with concentra- tions of 2200 mg/m3 caused a tendency toward leukopenia along with an increase in the number of pseudoeosinophils and in lymphopenia. In rats and rabbits an inhibition of phagocytic activity of neutrophils developed earlier in the animals subjected to chronic dosages of 2200 mg/m3 than in those subjected to dosages of 100 mg/m3. Rabbits subjected to chronic exposure exhibited an increase in erythrocyte sedimentation rate and a decrease in blood hemoglobin content as well as hyperplasia of the spleen pulp (Batkina, 1966). Chronic exposure of rats to butadiene and a-methylstyrene supressed phagocytic activity of leukocytes (CA78: 106680x), but this activity was increased in macrophages of rats exposed to butadiene (CA75: 107773e). Additionally, chronic exposure of rats to concentrations of 1,3, and 30 mg of 1,3-butadiene per m3 of air resulted in structural changes in hematopoetic organs (especially the spleen) and thinning of nuclear endothelium. Also noted was a decrease in the content of nucleic acid of splenic cells and disintegration of red blood cells in the pulp of the spleen (CA75: 107773e). A study of marrow smears from rats exposed to mixtures of a-methylstyrene and 1,3-butadiene by inhalation was made over a period of 10-120 days. Changes were observed in immature granulocytes and in slightly differentiated cells. SS and SH groups in erythrocytes decreased in the initial period, increased in the intermediate period, and decreased again later. Changes observed in nucleoproteins, anino acids, and functional proteins were a function of dosage (CA73:129116d). -7- ------- Chronic exposure of rabbits to a combination of toluene and 1,3-butadiene for a 2 month period of time caused an increase in the albumin/globulin ratio of the bone marrow with a decrease in total protein (Faustov and Lobeevay 1970) . / A statistically reliable reduction in hemoglobin con- centration in rabbits resulted from oral administration of 40 mg 1,,3-butadiene in vegetable oil/kg over a 7-month course (BA52:69712) Plasma An increased level of total SH groups in the blood was reported as a result of inhalation of 99.8 mg 1,3-butadiene and 5.2 mg a-methylstyrerie/m3 air in rats (CA78: 106680x). However, another study using oral administration to rabbits of 40 mg/kg 1,3-butadiene in vegetable oil over a 7-month course did not change. the number of free SH groups (BA52: 69712). An increase in cholesterol content in the blood of 84 rats, particularly cholesterol esters, was noted after 120 days of inhalation of 1,3-butadiene and/or a-methylstyrene. An increase from 29.3 to 64.9 mg% was observed (CA75: 96903u). Exposure to 1,3-butadiene and a-methylstyrene resulted in a decrease in total serum protein, but an increase in the a2- globulin fraction (CA75:107786m). Changes in the immunological state were observed after an 81-day course of inhalation of 1.0, 3.0, and 30 mg/m3 1,3-butadiene/m3 air (CA75:107777J) in experi- mental animals which can be related to changes in globulin/albumin levels. -8- ------- 2.2.1.4 Liver Decreased liver metabolism was noted with chronic exposure of rats to 1,3-butadiene and a-methylstyrene by inhala- tion. Decreased levels of ascorbic acid and thiamine in the liver were found (CA78: 106680x). Also indicated was disturbed metabolism of carbohydrates, fats, and proteins. In another study specific disturbance of lipid and carbohydrate metabolism was observed in rats, especially a decrease in glycogen and accumulation of lipids in hepatic areas after a 60-120 day course of inhalation of a mixture of 0.05 mg 1,3-butadiene and 0.005 mg a-methylstyrene/Jl. Chronic inhalation of a-methylstyrene and 1,3-butadiene affected lipid metabolism and increased the cholesterol contents of rat livers from 119 to 246.2 mg7» (CA75:107720k). Redistribution of total proteins and ribo- nucleoproteins in liver cells is noted with decreases in protein content in the cytoplasm of vacuolated cells (CA75: 107780e) of rats subjected to chronic exposure by inhalation of butadiene and a-methylstyrene. Hepatic ATP content increased as did the ratio of ATP to ADP with acute inhalation poisoning (Oura and Reiha, 1966). Chronic inhalation of a mixture of 1,3-butadiene (0.05 mg/H) and a-methylstyrene (0.005 mg /a) caused disturbances in the lipid and carbohydrate metabolism in rats, evidenced by a decrease in glycogen and an increase in lipids in hepatic cells (CA75:107779m). Chronic exposure of rabbits to 1,3-butadiene (100 mg/m3) produced granular dystrophy in the liver (Batkina, 1966). Specific histopathologic changes noted in the liver are similar to those previously described for the heart (BA53:5577). -9- ------- 2.2.1.5 Kidneys Chronic inhalation exposure of rats to mixtures of 1,3- butadiene and a-methylstyrene caused symptoms similar to protein dystrophy (CA75:107797r). During the course of the experiment renin granules disappeared from the epithelioid cells but later reappeared (CA75:107797r). Increased concentrations of urinary hippuric acid are noted in rats exposed to fumes of heated butadiene rubber containing butadiene and N-phenyl-B-naphthylamine (CA71: 41988n). Other researchers report changes in the urine composition of rats exposed to butadiene and a-methylstyrene by inhalation. Decreased thiamine levels and urinary excretion of riboflavin, coporphyrins, and ascorbic acid were reported (CA78: 106680x). Morphologic changes in the kidneys are similar to those described for liver and heart (BA53:5577). Small round cell infiltrations and congestion in the kidneys were reported in rabbits chronically exposed to 100 mg/m3 1,3-butadiene levels (Batkina, 1966). 2.2.1.6 Respiratory System Chronic exposure of rats to 100 mg/£ 1,3-butadiene and 5.27 mg/£ a-methylstyrene vapors initially altered bronchial epithelium, caused proliferation of beaker cells, and increased permeability of blood vessels. Later, this significant hyper- secretory state in the.connective tissue structures of the lungs resulted in reactive cell production. Toward the end of the experiment, sclerotic processes developed in the perivascular and peribronchial zones with a decrease in the permeability of blood vessels. Irritation of the respiratory tract was noted -10- ------- in mice exposed by inhalation to mixtures of butadiene and N-phenyl-3-naphthylamine. Morphologic changes noted with oral administration of 100 rag/kg 1,3-butadiene daily for 2.5 months included thickening of the interalveolar septa and minor lympho- histiocytic infiltration (BA53.:5577) . A study of chronic exposure of rats to .butadiene vapor concentrations of 3 mg/in3 for 81 days caused some changes in the epithelium of the mucous membranes of the lungs and nose (CA69:12741e) Chronic exposure of rabbits to 1,3-butadiene (100 mg/m3) resulted in pulmonary vessel congestion, pronounced emphysema, and inflammatory small-cell infiltration around the bronchi. (Batkina, 1966). 2.2.1.7 Skin Changes in epidermis, connective tissue,-hair, glands, and neuron fibers of rat skin caused by inhalation of butadiene and a-methylstyrene disappeared 30-60 days after discontinuation of treatment (CA81: 100372p). 2.2.1.8 Nervous System Histological changes occurred in rats given 100 mg/kg 1,3-butadiene for 2.5 months. The cytoplasm of the cells of the brain and sympathetic ganglia showed granular and hydropic dystrophy, cytolysis, neuronophagia, homogenatipn of the vascular walls and disturbances of their permeability (HEEP/72/03574). A study conducted by Shugaev published in 1969 related toxicity of various hydrocarbons, including butadiene, to brain concentrations in rats, mice, and cats. Acute atmospheric exposure at levels of 270 mg/fc for mice and 280 mg/£ for rats -11- ------- was the method of administration. In cats the butadiene was found to concentrate in the white nervous tissue. The author recommends that toxicity criteria be based on minimum lethal concentrations in the medulla oblongata. This recommendation is based on the fact that death during acute intoxication is a result of the hydrocarbon concentration in this organ inducing respiratory arrest (Shugaev, 1969). Another study reported by Shugaev (CA69: 50596u) reports higher concentrations of 1,3- butadiene in the medulla oblongata than in the cerebellum or cerebral cortex. Chronic inhalation by laboratory animals of 1,3, and 30 mg/m3 butadiene in air resulted in functional disturbances of the central nervous system (CA75: 107777J). Rabbits anesthetized repeatedly with 20 to 25% butadiene in air reportedly regained balance and muscular control in about 2 minutes. No tissue changes were noted (Anonymous, 1963). Chronic exposure by inhalation of 5 mg a-methylstyrene and 100 mg butadiene per m3 air caused a decrease in cholinesterase activity in experimental animals. Acetylcholinesterase activity in rabbits administered butadiene orally for 7 months at concen- trations of 0.4 mg, 4 mg, and 40 mg per kg in vegetable oil was not affected (BA52: 69712). Acute exposure of mice to 50,000; 100,000; and 200,000 mg 1,3-butadiene per m3 produced changes in the nervous system. Chronic exposure of rats and rabbits at concentration levels of 2200 mg/m3 and 100 mg/m3 also produced nervous system disorders (Batkina, 1966). 2.2.1.9 Gastrointestinal Tract No alteration of gastric functions was reported. One study (BA53:5577) reported lyniphohistiocytic infiltration of the gastrointestinal tract after a 2.5 month course of oral adminis- tration of 100 mg 1,3-butadiene/kg daily. -12- ------- 2.2.2 Various Metabolism Disturbances Disturbances in vitamin metabolism were noted in one study of rats subjected to butadiene (99.8 mg/m3) and a-methylstyrene (5.2 mg/m3). The ascorbic acid level in the blood, liver, and brain was low as was the thiamine level in the liver and urine. Urinary excretion of riboflavin and ascorbic acid were noted (CA78: 106680x). Rabbits given oral doses of 40 mg 1,3-butadiene per kg in vegetable oil showed an increase in fructose 1,6-diphosphate aldolase activities (BA52: 69712). -13- ------- 2.3 Observed Effects on Humans Industry workers are exposed to mixtures of butadiene, styrene, chloroprene, dimethyl dioxane, ct-methyl styrene, cata- lysts, hydrogen sulfide, carbon monoxide, aerylonitrile, acrolein, aromatic amines, ammonia and/or mixtures of saturated or unsat- urated hydrocarbons, through either direct contact or inhalation. Thus, observed effects cannot usually be attributed solely to butadiene. Observed effects on humans are described in terms of organs and organ systems in this section. 2.3.1 Circulatory System Workers exposed to butadiene, styrene, and ethylbenzene for eight years exhibited dyatrophic changes in the myocardium affecting contractile activity, symptoms of hypotension, and changes in capillary resistance (CA81:140347r). A hypotensive effect was also noted in workers exposed to a butadiene-styrene mixture under clinical and subclinical conditions (CA61:1169h). Persons working with styrene, ethylbenzene, and 1,3- butadiene showed symptons of an increase in capillary permeability and a high resistance to blood flow as compared to control sub- jects (CA70:80662a). A study of 60 persons employed in the syn- thetic' rubber industry showed that prolonged contact with styrene, butadiene, and ethylbenzene decreased capillary stability. Changes were noted in pictures obtained with a capillaroscope (CA81:67974m). Sixty butyl rubber workers in contact with buta- diene, styrene, and ethylbenzene were studied using electro- cardiograms and ballistocardiograms. The results were compared with those for a group of persons having no contact with the hydrocarbons. A deviation in the heart contraction function was noted in the rubber workers as compared to those in the -14- ------- the control group; however, the deviations did not exceed physiological norms. Changes were noted in the phase structure of the systole, but no changes were noted in contraction of the myocardium (CA81:67973k). Functional disorders of the cardiovascular system re- sulted from prolonged exposure to a-methylstyrene and butadiene in rubber production workers (CA81:140388e). Sixty petroleum industry employees having prolonged contact with styrene, buta- diene, and ethylbenzene were compared to a group having no hydro- carbon contact. Oscillograms were obtained and analyzed to determine hydrocarbon effect on vascular tonus. The tonus of the peripheral vascular system was lower in exposed persons than for the control group and was distinctly unsymmetrical in exposed persons (CA81:67971h). Batkina studied synthetic rubber workers in the buta- diene, separation and purification area who had been exposed to more than 100 mg/m3 of butadiene vapor for prolonged periods. Other unsaturated hydrocarbons were present in insignificant concentrations. One hundred workers were given periodic medical examinations over a 10-15 year period. A tendency toward hypo- tension was noted (Batkina, 1966). Three hundred sixty-five persons employed for three years in a chemical factory were exposed to the combined effects of benzene, cyclohexane, and butadiene. The toxicity of the chemicals was studied with attention to the age of the workers. They were described in three age groups: Group 1 was comprised of 67 subjects aged 18 to 21; group 2 had 122 members aged 22 to 25; and group 3 had 176 members aged 26 to 35. Toxic effects were ascribed to the presence of benzene because its MAC was exceeded most frequently. Butadiene concentration was con- siderably below its MAC. Low blood pressure and changes in -15- ------- vascular tone were noted with a larger percentage of cases being reported among group 1 workers than in other groups (Doskin, 1971). Angina was prevalent among workers in synthetic rubber production (CA80:63401d). 2.3.2 Hematopoietic Organs, Formed Elements, and Plasma Workers in a vulcanization plant were exposed to vapors containing 32 to 40 mg/tn3 of butadiene mixed with styrene, oil aerosol, formaldehyde, methanol, sulfur dioxide, acrolein, aromatic amines, ammonia, acrylic acid nitrile, and carbon monoxide. Vulcanization operators performed heavy'work under conditions of high air temperature, radiant heat, and noise. Investigation of these workers showed decreases in hemoglobin, red blood cell count, reticulocytes, and thrombocytes in peripheral blood. These changes were ascribed to the presence of styrene and "other components of the mixture" (Volkova and Bagdinov, 1969). Toxic effects on the blood of chemical plant workers in three age groups described in Section 2.3.1 were studied in detail. Again, the effects were ascribed to benzene rather than to butadiene or cyclohexane which were present in lower concen- trations . Blood counts and tests of the functional state of circulating leukocytes and medullary hematopoiesis were performed. Healthy new employees provided hematological- data for the control group. Noted hematological disturbances included thrombocytopenia, disturbed erythropoiesis, and nonnochromic anemia with a tendency toward hyperchromia after one year of employment. When benzene concentrations were reduced to the MAC, normal to high RBC levels occurred. -16- ------- White blood cell changes included leukocytosis followed by leukopenia, lymphocytocis, and disturbed phagocytic capacity of neutrophils (deterioration in functional capacity of granulo- cytes). Investigations of medullary hematopoiesis indicated an intensified proliferation of medullary elements (myelokaryo- cytes). The content of reticular cells and lymphocytes was high in the marrow tissue. Again, hematological alterations occurred most frequently among group 1 (younger) workers (Doskin, 1971, CA74:57085p). The butadiene production workers studied by Batkina who were exposed to butadiene concentrations greater than 100 mg/m3 with insignificant amounts of other hydrocarbons showed blood changes. Leukopenia, an increase in erythrocyte sedi- mentation rate, and decrease in hemoglobin were reported. De- creases in phagocytic activity of neutrophils were also noted (Batkina, 1966). The blood of rubber production workers exposed to styrene and butadiene concentrations exceeding the MAC was found to contain increased cholesterol and lecithin. The con- tent of B-proteins was increased while that of a-lipoproteins was decreased. The fraction of globulin was increased, while blood serum albumins were decreased (CA81:67970g, CA80:40675g). A drop in blood albumins and an increase in y- and 8-globulins were also noted in clinical studies with styrene-butadiene mixtures. Styrene-butadiene rubber workers showed changes in peripheral blood including leukopenia, lymphocytosis, throtnbo- cytopenia, and reticulocytosis (CA61:1169h). The toxic effects of 1,3-butadiene and ot-methylstyrene in peripheral blood of 1406 synthetic rubber production -17- ------- workers have been studied. Results were compared with a control group of 200 civil engineering employees having no chemical con- tact. Noted changes included increased hemoglobin and erythro- cytes, decreased color index, leukocytosis, eosinophilia, neutropenia, relative lymphocytesis, monocytosis, both increased and decreased thrombocytes, and a decrease in intracellular content of glycogen, lipids, and peroxidase in leukocytes (CA78:88310v). 2.3.3 Liver Clinical studies of the chronic effect of a mixture of butadiene and styrene on healthy workers indicated that 35 percent showed liver enlargement and a decrease in functional tests (CA61:1169h). Workers employed in synthetic rubber pro- duction showed positive reactions for antihepatic antibodies indicating pathological changes which can be used for diagnoses of early toxic liver disorders (CA80:633902). The relationship between the excretory function of the liver and the secretory function of the .stomach in workers ex- posed to butadiene and styrene in synthetic rubber production was investigated. While marked suppression of liver function was noted, there was no parallelism between liver test factors and stomach secretory function (CA80:148759b). Liver and bile duct diseases were observed among workers in synthetic rubber plants where styrene and butadiene concentrations were from 20 to 100 and 85 to 93 mg/m3, respectively, in 1960. Both concentrations were reduced to below 20 mg/m3 by 1970 (CA80:136939x). Volkova and Bagdinov reported that styrene and butadiene "have a selective effect" on diseases of the liver and bile duct. The incidence of such diseases was found to be -18- ------- 7.6 cases per 100 workers exposed to vulcanization gases con- taining butadiene, styrene, and many other impurities (Volkova and Bagdinov, 1969). 2.3.4 Kidneys Kidney malfunctions were reported to be prevalent in workers involved in monomer production and in isolation of synthetic rubber from reaction products. Catalysts were reported to produce such toxic effects (CA80:63401d). 2.3.5 Respiratory System Butadiene-styrene mixtures were reported to cause lariyngotrachyitis and sometimes bronchitis among healthy workers studied under clinical conditions (CA61:1169h). Acute catarrh of the upper respiratory tract occurred often among workers in a synthetic rubber plant with chronic exposure to butadiene and styrene (CA80:63401d). Chronic exposure produced increasing tendency toward pathological changes in the upper respiratory tract (CA80:136939x). An investigation of chemical hazards in the braided hose department of Gates Rubber Company was performed. The study included sampling and analysis of ambient air for 1,3- butadiene. Sampling was.conducted on two days, and the con- centration of butadiene was below the detection limit of the gas chromatographic method used. Other chemicals in use in- cluded styrene, isocyanates, resorcinol, vinyl pyridine, and formaldehyde. Approximately 2200 types of hose are produced in small lots in the work area and 540 chemicals are employed. A medical evaluation of employees included completion of a question- naire by seventeen persons. A significant number of respondents reported cough, runny nose and sore throat. It was concluded -19- ------- that there was sufficient evidence to indicate a hazard for upper respiratory tract irritation most likely associated with styrene, butadiene, vinyl pyridine, resorcinol or a combina- tion of these (Gunter.and Lucas, 1973). Medical examinations of vulcanization workers exposed to butadiene, styrene and numerous other contaminants were per- formed. Investigations indicated that 26.6 percent of diseases resulting in absenteeism involved influenza and catarrh of the upper respiratory tract and 10.9 percent involved tonsillitis. Thirty-three percent of the workers examined exhibited sub- atrophic mucosal changes in the nose, throat and larynx. The extent of such disorders was related to length of employment. Olfactory perception was altered and a high incidence of hyposmia (decreased sensitivity to odors) was noted (Volkova and Bagdinov, 1969). A statistical treatment of medical records of rubber plant workers indicated a marked rate of increase in respiratory diseases with years of service (CA82:47351y). 2.3.6 Skin The vulcanization workers described previously (Volkova and Bagdinov, 1969) had abnormally dry palms with superficial cracks. Pyoderma was noted in 15.2 percent of workers due partly to constant friction of skin against rubber articles. Three cases of urticaria were noted among the workers in the braided hose department of Gates Rubber Company. The incidence was thought to be abnormally high. The possibility that it resulted from chemical substances in the working environ- ment was acknowledged. Nearly half of the employees related problems of subsiding dermatitis (Gunter and Lucas, 1973). -20- ------- Medical records of 679 workers in a synthetic rubber plant were analyzed in two groups. One group contained workers in contact with styrene, butadiene, butane, butylene, benzene, H2SO.», and catalysts. The other group contained workers with no contact with chemicals. Group 1 had 21.7 percent skin dis- eases and tuberculosis, while the second group had only 3.3 percent (CA82:47350x). Workers in a synthetic rubber plant exposed to air containing a-methylstyrene, dodecylmercaptan, Neozone D, and butadiene in concentrations exceeding the MAC were affected with dermatosis (CA81:110878x). 2.3.7 Eyes Sensitivity of the human eye was investigated in studies to determine the upper limit for a single exposure to butadiene. Increased sensitivity was noted at concentrations of 4.0 mg/m3 but not at 3.6 mg/m3 (CA69:12741e). Workers in the braided hose department of Gates Rubber Company are routinely exposed to numerous chemicals, one of which is butadiene. Burning, itching, red eyes were job-related symptoms indicated in employee questionnaires. Viral or allergic conjunctivitis and corneal ulceration were observed, but it is not clear that these problems were caused by exposure to butadiene. Industrial hygienists concluded that a hazard responsible for eye irritation existed in the work area (Gunter and Lucas, 1973). Conjunctivitis was noted as an effect of exposure to butadiene and styrene mixtures in clinical tests on healthy workers in synthetic rubber production (CA61:1169h). -21- ------- 2.3.8 Nervous System In a study of vulcanization workers exposed to styrene, butadiene, oil fog ,• formaldehyde..,,; methano.lv -hydrogen sulfide, , - -. / " ' ' '' ' • acrolein, aromatic hydrocarbons, ammonia, aerylonitrile, and carbon monoxide, styrene vapor was found to be the product most frequently present in concentrations exceeding the MAC in breath- ing zones. The increase in time expenditure and the percentage of errors in the execution of tests attested to the effect of the "complex of unfavorable factors" on the state of the central nervous system (the attention function). The effect was more pronounced in the case of workers who had been employed for a longer time. Studies of workers exposed to complex mixtures con- taining 30-40 mg/m3 of butadiene and 10-20 mg/m3 of styrene and working under conditions of high temperature suggested strain on the thermoregulatory system and disturbances in the function of the olfactory analyser. Raised olfactory thresholds and a high incidence of hyposmia were reported. Diseases of the peripheral nervous system inlcuding radiculitis, neuralgia, and lumbago caused 17.6 percent of the cases of absenteeism among the vulcanization operators in 1966 (Volkova and Bagdinov, 1969). . Doskin studied chemical plant workers exposed to benzene levels exceeding the MAC and butadiene and cyclohexane at concentrations below the MAC. He reported that workers in the youngest of three age groups had most frequent complaints of neurological disorders such as asthenovegetative syndrome (Doskin, 1971). In tests to determine the upper limit for a single exposure of butadiene, the odor threshold value was found to be 4 mg/m3. Electroencephalograms showed an effect at concentra- tions of 3 mg/m3 (CA69:12741e). -22- ------- Clinical data on 679 synthetic rubber plant workers for a ten-year period were analyzed to determine disease rate. Diseases of the nervous system were found in 44.5 percent of workers exposed to butadiene, styrene, butane, butylene, benzene, H2SOi» and catalysts. Only 26.7 percent of plant workers having no contact with the compounds had nervous system diseases (CA82:47350x). Synthetic rubber production workers exposed to buta- diene and styrene, styrene alone, chloroprene, mixtures of saturated and unsaturated hydrocarbons, dimethyl dioxane, and ct-methylstyrene manifested symptoms of narcosis on a background of asthenic and neurasthenic reactions (CA61:1169h). Workers in shops producing latex and in shops recover- ing SKMS-30 rubber were exposed to 1,3-butadiene and a-methyl- styrene. An adverse effect on the nervous system was noted, but the type of effect was not described in the abstract. Workers reacted differently to the action of the gas and some showed asthenia. Changes were observed to be transient (CA78: 88318d). 2.3.9 Gastrointestinal Tract A significantly higher incidence of diseases of the digestive organs was reported in a study of synthetic rubber plant workers in Russia exposed to styrene, butadiene, butane, butylene, benzene, H2SOi», and various catalysts when compared to workers not having contact with those substances. The group studied included a total of 679 workers. Digestive system disease occurred in 66.6 percent of the exposed group as opposed to 33.3 percent in the group not exposed (CA82:47350x). -23- ------- An antacid condition which was resistant to histamine treatment was noted by Russian researchers in 68 of 130 subjects exposed to butadiene and styrene. Five of thirty control sub- jects exhibited antacid conditions which responded readily to histamine treatment. Significant stomach disorders are at- tributed to exposure to these hydrocarbon substances (CA74:138804z) Russian researchers unsuccessfully attempted to relate liver test factors to stomach secretory function in synthetic rubber workers exposed to butadiene and styrene. Hypoacidic, normacidic, and hype.racidic stomach conditions were mentioned with no indication of frequency of occurrence or cause of the conditions (CA80:148759b). Observations of healthy synthetic rubber plant workers under clinical and subclinical conditions revealed a hypotensive effect causing alterations in the gastrointestinal tract in- the form of hypacid and anacid gastritis (CA61:1169h). 2.3.10 Endocrine System Functional changes in the endocrine glands of 70 workers in the synthetic rubber industry have been attributed both to the prolonged effect of butadiene and styrene and to an upset in the nervous control of endosecretion. Functional changes occurred primarily in the adrenal, thyroid, and pancreas of workers with a history of upsets of the endocrine system (CA73:107692m, CA72:11080p). -24- ------- 3.0 Environmental Aspects This section summarizes information concerning re- ported environmental levels of 1,3-butadiene and the chemical behavior of the compound in air and water. 3.1 Occurrence Table 1 summarizes data on the occurrence and reported levels of butadiene in environmental samples. The abstracts of sources in Russian provided data on butadiene levels in work areas. These were often described in terms of the maximum allow- able concentration (MAC) which was 100 mg/m3 in 1966. However, a study published in that year indicated that 10 mg/m3 would be a more effective MAC (Batkina, 1966). From Table 1 it is appar- ent that the butadiene concentration in the air in work areas in Russian factories without emission controls exceeded 100 mg/m3. Butadiene levels in the air in the braided hose department of the Gates Rubber Company were reported in 1973 to be below 1000 ppm on two occasions on which sampling occurred (Gunter and Lucas, 1973). Data on levels of butadiene in point source emissions were not found. An abstract describing combustion gases from burning butadiene copolymers did not mention the presence of butadiene. Butadiene is present in cigarette smoke (Osborne, 1956) and gasoline vapors (Stephens and Burleson, 1967). Quan- titative data on butadiene concentration in automobile exhaust were not found; however, Altshuller described the rate of buta- diene disappearance in irradiated exhaust samples (Altshuller et al, 1962). Table 1 shows that butadiene levels in urban ambient air are well described in the literature. The concentration -25- ------- Table 1. REPORTED OCCURRENCE AND LEVELS OF 1,3-BUTADIENE IN THE ENVIRONMENT Sample Descriptions Cigarette Smoke Stack gases from laboratory combustion of copolymers containing butadiene Air in factory containing emissions from polymer-modified concrete (SKS-65GP latex) Air in shoe factories in areas where SKS-30 latex materials are worked Ambient air at sites located 2000 to 8000 meters from synthetic rubber plant Air in synthetic rubber rubber plants Air in dimethyl terephthalate manufacturing facility in winter Air in rooms with butadiene- styrene rubber floor covering Butadiene separation and puri- fication facility in synthetic rubber plant Ambient air in Santiago, Chile Early morning ambient air in Riverside, California Reported Butadiene Concentration -2 0.1-0.3x10 cc/puff Butadiene concentration exceeded maximum allowable concentration (MAC) by a factor of 5 to 10. 85-93 mg/m3 in 1960 5-20 mg/m3 in 1970 0.7 to 1.7 mg/m3 The butadiene concentration was found to be above the MAC >100 mg/m Remarks Butadiene was not mentioned in the abstract Butadiene was present Butadiene was observed The MAC was not given in the abstract Butadiene was not present Reference Osborne, 1956 CA60:69398 CA77-.029900 CA78:47439a 2-9 ppb CA80:40656b CA80:136939x CA81:175496r CA76:76122f Batkina, 1966 CA62:15336d Stephens and Burleson, 1967 ------- Table 1 (Continued). REPORTED OCCURRENCE AND LEVELS OF 1,3-BUTADIENE IN THE ENVIRONMENT Sample Descriptions Ambient air during air pollution episode in afternoon Ambient air in Los Angeles, California Air in workshops where polyester resins are used as binders in plastic production Air in vicinity of synthetic rubber plant to ^ ! Air in working premises of plants for production of butadiene- acrylonitrile rubber Air in working areas at a plant for manufacturing SKMS-30 rubber Air in working areas of butadiene- a-methylstyrene rubber plant Reported Butadiene Concentration up to 0.7 ppb 0.004 ppm 0.01 to 0.0009 mg/1 Butadiene concentration exceeded the MAC by a factor of 1.5 to 3.0 Remarks Butadiene concentra- tion was.measured but not reported in the abstract Butadiene was monitored. The concentration was not reported in the abstract Butadiene was measured. Specific results were not given in the abstract. The MAC was exceeded for some compounds in 40% of the samples Reference S tephens and Burleson, 1967 Glasson and Tuesday, 1970 CA81:175460z CA82:76697w CA55:23883a CA75:112601b CA76:37127s Ambient air in downtown Los Angeles and Azusa, California Gasoline vapor 1-2 ppb (avg) 0.001 ppm Altshuller, et al, 197 Stephens and Burleson 1967 ------- depends on the time of day and is generally below 10 ppb. Buta- diene levels in ambient air near a rubber manufacturing plant have been measured (CA80:40656b) but not reported in English. 3.2 Reactivity At ambient conditions butadiene is a colorless gas. It is easily liquefied and is stored under pressure or at temper- atures below 35°F. Butadiene is soluble in organic solvents. The solubility in water is 735g/106g water (McAuliffe, 1966). The compound is highly reactive, and both gas and liquid are highly flammable. Inhibitors must be added to the pure material to prevent polymerization and explosive peroxide formation. Flammable and explosive limits in air are described in the lit- erature (Osugi, et al, 1965; Hawley, 1971). Table 2 gives some physical properties. Table 2. PHYSICAL PROPERTIES OF 1,3-.BUTADIENE Boiling point -4.41°C Specific gravity of 0.6211 liquid at 20°C Vapor pressure at 0°C 17.65 psia The chemcial behavior of butadiene in the atmosphere is well described in the literature. However, very little data were found describing its presence and reactivity in aqueous waste streams. Recent studies on pollution control in the -28- ------- synthetic rubber industry contained no data on the concentra- tion of butadiene in aqueous waste streams (Sittig-, 1975). A high chemical oxygen demand (COD) level was noted for raw waste from the industry, while biochemical oxygen demand (BOD) was reported to be much lower. Organic constituents in the waste- waters were reported to be resistant to biological oxidation (Sittig, 1975). Wastewaters from the Hiils Chemical Works, at which a variety of chemicals were produced, were reported to contain butadiene and other organics (CA49:11216b). The aqueous wastes could not be treated biologically. Wastes containing butadiene were steam treated and filtered through flue ash in a test pro- gram. Color and odor were removed and the permanganate demand was reduced. It was reported that soot contained in the ash promoted butadiene polymerization. The polymerization rate was enhanced by the addition of lime. A butadiene removal method was devised consisting of steam treatment, mixing of the waste with another waste stream containing lime, and addition of soot sludge. Effluent from this treatment method contained no buta- diene. Table 3, which describes waste from a butadiene pro- duction plant, contains data on total organic carbon (TOC) and COD. Both of these parameters could be a measure of the level of butadiene in the wastewater. However, butadiene concentra- tions were not reported. -29- ------- Table 3. COMPOSITION OF WASTE FROM A BUTADIENE PLANT3 (Gloyna and Ford, 1970) pH 8-9 TOD 100 - 200 g/m3 filtered COD 200 - 375 g/m3 suspended solids 200 - 500 g/m3 total solidsb 3000 - 4000 g/m3 a Flow rate 0.417 m3/Mg (100 gal/ton of product) Mostly sulfates and chlorides Butadiene reactivity in the atmosphere has been studied because hydrocarbons are involved in the production of the strongly oxidizing compounds which are the constituents of photo- chemical smog. Hydrocarbons react with nitric oxide and oxygen species in photochemical reactions which produce peroxyacetyl nitrates, nitrogen dioxide, ozone, and oxidized forms of the hydrocarbons (EPA, 1975). Hydrocarbons vary in their degree of reactivity in atmospheric oxidation reactions, depending on their chemical structure. Olefins are the most reactive followed by aromatics, paraffins, and naphthenes (CA59:8038f). Olefins are so reactive that their residence time in the atmosphere is short (CA62:15336d; Stephens, 1966). Reaction occurs at the double , bond to form oxidation products such as aldehydes. Glasson and Tuesday measured the photooxidation rate of nitric oxide in the presence of various hydrocarbons using.long-path infrared spec- trophotometry. Mixtures of N2, 02, NO, N02 and butadiene were irradiated and the rate of N02 formation was monitored. The NO photooxidation rate at 79°F in the presence of butadiene was -30- ------- 4.3 ppb/tnin. Other olefins were more reactive than butadiene (Glasson and Tuesday, 1970b). In another study published in 1970, Glasson and Tuesday described the effects of NO and butadiene concentration on the rate of NO thermal oxidation at 29°C. The rate constant for NO thermal oxidation in the presence of butadiene was 0.44 x 10"3/ ppm min. Acrolein and formaldehyde were identified as NO- butadiene reaction products. The reaction of N02 and butadiene was also studied. The rate of decrease of N02 concentration in a butadiene-air mixture was measured. The rate constant for the N02-butadiene reaction was 0.4 x lO'Vppm min. Olefin photooxidation has been studied in laboratory experiments using irradiated automobile exhaust-air mixtures. The rate of decrease of olefin concentration was measured using a wet chemical analysis (Altshuller, 1962).. The rates and pos- sible mechanisms of reactions of olefins with oxygen atoms, ozone and nitric oxide have been described (Stephens, 1966a and 1966b). Stephens and Burleson collected air samples, subjected the samples to irradiation, and measured changes in hydrocarbon concentrations. Samples were acquired in early morning hours before natural photolysis occurred. Table 4 summarizes analyti- cal results for butadiene. The butadiene concentration de- creased to zero with UV irradiation of the sample but remained constant in the dark. Samples collected during afternoon pol- lution episodes contained butadiene concentrations less than 0.7 ppb (Stephens and Burleson, 1967). -31- ------- Table 4. RESULTS OF UV IRRADIATION OF AMBIENT AIR CONTAINING BUTADIENE Butadiene Concentration in ppb After 24 hr UV After 24 hr Original Irradiation Original in Dark Sample Description Ambient air, 3/10/66, 7:50- 8:00 PST, heavy haze, 55-608F Ambient air, 12/22/65, 7:40- 8:00 PST, light haze, 45-50°F Ambient air, 3/3/66, 8:05- 8:25 PST, moderate haze, 40-458F 2.6 9.0 2.4 0. 2.8 2.0 2.6 2.0 Altshuller, et al, described how olefins disappeared more rapidly in ambient air than other hydrocarbons due to their faster rate of photolysis. The butadiene concentration in ambient air was reported to decrease by a factor of three from morning to mid-afternoon (Altshuller, et al, 1971). -32- ------- 4.0 BIBLIOGRAPHY Abeles, F.B. and H.E. Gahagan III, "Abscission: The Role of Ethylene, Ethylene Analogs, Carbon Dioxide, and Oxygen", Plant. Physiol. £3 (8), 1255-58 (1968). Altshuller, Aubrey P., Lois J. Lage, and Stanley F. Sleva, "Determination of Olefins in Combustion Gases and in the Atmosphere", Am. Ind. Hyg. Assoc. J. 23, 289-95 (1962). Altshuller, Aubrey P., et al., "Hydrocarbon Composition of the Atmosphere of the Los Angeles Basin - 1967", Environ. Sci. Technol. 5_ (10), 1009-16 (1971). Anonymous, "1,3-Butadiene (Erythrene, Vinylethylene). Hydrogen Sulfide", Am. Ind. Hyg. Assn. J. 24, 91-94 (1963). Batkina, I.E., "Maximum Permissible Concentration of Divinyl Vapors in the Air of Work Areas", Gig. Sanit. _31 (12), 18-22 (1966). Doskin, V.A., "Significance of Age in the Reaction of the Organism to the Combined Effect of Hydrocarbons", Gig. Sanit. 3j5 (3), 47-51 (1971). -33- ------- Environmental Protection Agency, Office of Air Quality Planning and Standards, Control of Photochemical Oxidants. .Technical Basis and Implications of_ Recent Findings. EPA-450/2-75-005. Research Triangle Park, N.C., July 1975. Faustov, A.S. and N. Lobeeva, "Action of Some Chemical Substances on the Protein Content of Serum and Bone Marrow", Gig. Saint. _35_ (8) , 112-13 (1970) . Glasson, William A. and Charles S. Tuesday, "Atmospheric Thermal Oxidation of Nitric Oxide in the Presence of Dienes", Env. Sci. Techno1. £ (9), 752-57 (1970 a). , . Glasson, William A. and Charles S. Tuesday, "Hydrocarbon Reactivities in the Atmospheric Photooxidation of Nitric Oxide", Env. Sci. Technol. £ (11), 916-24 (1970b). Gloyna, E.F. and D.L. Ford, The Characteristics and Pollution '•\ Problems Associated with Petrochemical Wastes. FWPCA Contract No. 14-12-461. Ada, Oklahoma, Robert S. Kerr Water Research Center, February 1970. Gunter, Boddy J. and James B. Lucas, .Health Hazard Evaluation/ Toxicity Determination. Gates Rubber Company, Denver, Colorado. PB 229508. Cincinnati, Oh., NIOSH, 1973. -34- ------- Haagen-Smit, A.J., et al., "Investigation on Injury to Plants from Air Pollution in the Los Angeles Area", Plant Physiol. 27, 18-34 (1952). Hawley, Gessner G., Condensed Chemical Dictionary, 8th ed., N.Y., Van Nostrand Reinhold, 1971, pp. 133-34. Heck, Walter W. and Gerald Pires, Growth o£ Plants Fumigated with Saturated and Unsaturated Hydrocarbon Gases and their Derivatives Misc. Pub. MP-603. College Station, Tx., Texas Agricultural Experiment Station, Texas A & M, August 1962. McAuliffe, Clayton, "Solubility in Water of Paraffin, Cycloparaffin, Olefin, Acetylene, Cycloolefin, and Aromatic Hydrocarbons", J. Phys. Chem. 7£ (4), 1267-75 (1966). Osborne, J. Scott, Stephen Adamek, and Marcus E. Hobbs, "Some Components of Gas Phase of Cigaret Smoke", Anal. Chem. 28, 211-15 (1956). Osugi, Jiro, Horonobu Kubota, and Katsukuni Ueba, "Explosion Limits of Butadiene-Air Mixtures", Rev. Phys. Chem. 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(9), 326 (1969). -36- ------- BA 5_2_: 69712 Shvartsapel', F.S., "A Study of the Toxic Properties of 1, 3 - Butadiene in Chronic Experiments", Tr. Perm. Med. Inst. 8j2, 174-79 (1970). BA j>3_:5577 Donetskaya, E.I. and F.S. Shvartsapel1, "Morpho- logical Studies of the Organs of White Rats Under the Action of 1,3 - Butadines in Subacute Experiments. Tr. Perm. Med. Inst. 82, 223-25 . (1970). BA 60:69398 van Grimbergen, M., G. Reybrouck, and H. van de Voorde, "Air Pollution Due to the Burning of Thermoplastics", Zentralbl. Bakteriol. Parasitekd. Infektionskr. Hyg., Erste Abt., Prig. Reihe B., Hyg. Praev. Med. 16J) (2) , 139-47 (1975). CA _4_9:11216b Bordo, J.A. , "Treatment of Waste Waters from a Chemical Factory", Wasserwirtschaft 41, 239-46 (1951). CA 5j>:23883a Babanov, G.P., "Problems of Industrial Hygiene in the Production of Synthetic Butadiene - Acrylonitrile Rubbers", Gig. Tr. Prof. Zabol. £ (12), 7-12 (1960). -37- ------- CA 5_9:8038f Stephens, E.R. and W. E. Scott, "Relative Reactivity of Various Hydrocarbons in Polluted Atmospheres", Proc. Am. Petrol. Inst., Sect III 42, 665-70 (1962). CA j>lp:1169h Orlova, A.A. and E.A. Solov'eva, "Clinical Picture of Chronic Exposure to Various Chemicals Used in Synthetic Rubber", Tr. Voronezhsk. Med. Inst. £7, 86-87 (1962). CA 6J2:15336d Martinez, Jorge Foncillas, "Determination of Olefins in the Atmosphere of Santiago, Chile", Anales Fac. Quim. Farm., Univ. Chile 15, 198-203 (1963). CA 6£:118540s Ripp, G.Kh. and T.M. Lyutikova, "Effect of Divinyl and Cracking Gas on the Blood Pressure Under Experimental Conditions", Nauch. Tr. Omsk. Med. Inst. 1966 (69), 86-89. CA 66/. 118541t Ripp, G. Kh. and T.M. Lyutikova, "Some Hematological Indexes in Experimental Chronic Intoxication with Divinyl and Cracking Gas", Nauch. Tr. Omsk. Med. Inst. 1966 (69), 90-92. -38- ------- CA 6_9:12741e Ripp, G. Kh. , "Hygienic Basis for the Permissible Concentration of Butadiene in the Atmosphere", Biol. Deistvie Gig. Znachenie Atmos. Zagryaznenii 1967 (10), 33-54. CA_.69_:50596u Shugaev, B.B., "Distribution and Toxicity of Aliphatic Hydrocarbons in Body Tissues", Farmakol. Toksikol. 3jL (3) , 360-63 (1968) . CA 7_0:80662a Alekperov, 1.1., V.G. Knabengof, and M.I. Vinokurova, "Capillaroscopic Studies and Determination of the Stability of Capillaries in Persons Working with 1,3-Butadiene, Styrene, and Ethylbenzene", Azerb. Med. Zh. £5 (.10), 58-61 (1968). CA 7_l:41988n Stasenkova, K.P., "Experimental Materials for Evaluating the Toxicity of 1,3-Butadiene Rubber", Toksikol. Nov. Prom. Khim. Veshchestv. 1968 (10), 90-99. CA. 7_2:11080p Bashirov, A. A., "Functional Changes in Endocrine Glands Due to Butadiene and Styrene", Gig. Tr. Prof. Zabol. L3 (13), 40-41 (1969). CA 7_2:30037w Skuja, K., "Combined Effect of Butadiene and Toluene on Rat Estrous Cycle", Akush. Ginekol. (Moscow) 45 (9), 67-68 (1969). -39- ------- CA 7_3:107692m Bashirov, A.A., "Functional Changes in Endocrine Glands Due to Butadiene and Styrene", Gig. Tr. Prof. Zabol. 13 (7), 40-41 (1969). CA 7J3:129116d Molodyuk, A.V. , "Histochemistry of Marrow Cells Under Normal Conditions and After Inhalation of a - Methylstyrene and Bivinyl Vapors", Nauch. Tr., Omsk. Med. Inst. 1968 (86), 160-67. CA7^:57085p Zorina, L.A., E.V. Lyadova, and V.A. Doskiri, "Dynamics of Poisoning in Workers Exposed to a Combined x Effect of Benzene and Other Hydrocarbons (Cyclo- hexane, 1,3-Butadiene)", Gig. Tr. Prof. Zabol. 14 (8), 14-18 (1970). CA 7_4:97300m Pokrovskii, V.A. and R.I. Volchkova, "Effect of Some Organic Poisons on Blood Formation Processes", Tr. Voronezh. Cos. Med. Inst. 13_ (4), 61-64 (1968). CA 7J_:138804z Bashirov, A.A. , "Effect of Histamine on the Stomach in Antacid Gastritis in Subjects Occupationally Exposed to Aromatic Hydrocarbons", Ter. Arkh. ^2 (12), 41-44 (1970). -40- ------- CA 7_5: 96881k Bul'Bakov, K.S., "Pathomorphology of the Heart During the Chronic Action of a- Methylstyrene and 1,3- , Butadiene Mixtures on Animals", Nauch. Tr., Omsk. Med. Inst. 1969 (88), 269-73. CA 7_5:96900r Morozov, G.I., "Morphological Changes in White Rat Testicles During the Action of a- Methylstyrene and 1,3-Butadiene Vapors on the Animals", Nauch. Tr., Omsk. Med. Inst. 1969 (88), 249-53. CA 7_5:96902t Morozov, G.I., "Morphological Changes in the Internal Sex Organs of Female White Rats During the Action of Vapors of a - Methylstyrene Alone and Mixed with 1,3-Butadiene on the Animals", Nauch. Tr., Omsk. Med. Inst. 1969 (88), 254-60. CA 7_5:96903u Chukreev, E.F., "Effect of the Long-term Action of Small Concentrations of a - Methylstyrene Alone and in a Mixture with 1,3-Butadiene on the Cholesterol Level in the Serum of Animals", Nauch. Tr., Omsk. Med. Inst. 1969 (88), 261-64. -41- ------- CA 21:107720k Chukreev ,. E.F., "Effect of the Long-term Action of Small Concentrations of a - Methylstyrene Alone and Mixed with 1,3-Butadiene on the Cholesterol Level in the Liver of Animals", Nauch. Tr., Omsk. Med. Inst. 1969 (88), 265-68. CA 7_5:107749b Kuz'min, V.I.., "Pathomorphological Changes in the Lungs of White Rats Under the Action of 1,3-Butadiene and a- Methylstyrene Vapors", Nauch. Tr. , Omsk. Med. Inst. 1969 (88), 215-19. CA 7_5:107773e Molodyuk, A.V., V.V. Semchenko, and G.Kh. Ripp, "Micro- scopic Changes in the Spleen of Experimental Animals During the Inhalation of 1,3-Butadiene", Nauch. Tr., Omsk. Med. Inst. 1969 (88), 170-73. CA 7_5:107774f Nikiforova, A.A., G. Kh. Ripp, and I.I. Taskaev, "Action of 1,3 - Butadiene on the Structural Elements of Kidneys and Hearts", Nauch. Tr., Omsk. Med. Inst. 1969 (88), 166-69. CA 7_5_:107776.h Eikhler, Yu. N., "Experimental Evaluation of the Effectiveness of Curative-Preventive Ration During the Action of a- Methylstyrene and 1,3- Butadiene on Animals", Nauch. Tr., Omsk. Med. Inst. 1969 (88), 92-98. -42- ------- CA 75/107777J Ripp, G.Kh., "Toxicohygienic Characteristics of 1,3-Butadiene", Nauch. Tr. , Omsk. Med. Inst. 1969 (88), 10-18. CA 75:107779m Lambina, S.A., "Dynamics of the Level and Distribution of Glycogen and Lipids in the Liver of Rats Under the Effect of Chronic Inhalation Priming with a Mixture of 1,3-Butadiene and a- Methylsty- rene", Nauch. Tr., Omsk. Med. Inst. 1969 (88), 174-78. CA 75:107780e Lambina, S.A., "Changes in the Level of Ribonucleopro- teins and Total Protein in the Liver of Rats ':" Under the Effect of Chronic Inhalation Priming with a Mixture of 1,3-Butadiene and a - Methylstyrene", Nauch. Tr., Omsk. Med. Inst. 1969 (88), 179-84. CA 2JK 107786m Matusov, I.E., "Effect of 1,3-Butadiene and a - Methyl- styrene on Some Blood Indexes for an Experimental Animal", Nauch. Tr.. Omsk. Med. Inst. 1969 (88), 289-96. CA 75: 107797r Serebrennikov, O.A., "Renin Level in the Kidneys of Experimental Animals During Chronic Poisoning with Mixtures of a- Methylstyrene and 1,3 - . . Butadiene", Nauch. Tr., Omsk. Med. Inst. 1969 (88), 244-48. -43- ------- 1; •-4 CA 75:112601b Dvoryaninova, N.K. and V.V. Khorobrykh, "Working Conditions in a Shop for the Formation of SKMS- 30 Rubber at the Omsk Synthetic Rubber Plant", Nauch. Tr., Omsk. Med. Inst. 1969 (88), 62-67. CA 75:116947s Molodyuk, A.V., "Histological and Histochemical Changes in Tissue Components of Hematogenic Organs of Experimental . Animals During the Action of a - Methylstyrene and 1,3-Butadiene Vapors", Nauch. Tr., Omsk. Med. Inst. 1969 (88), 231-39. CA ^6_: 37127s Tsai, L.M., "Hygienic Characteristics of the Rubber Industry", Zdravokhr. Kaz. 30_ (2) , 57-58 (1971). CA 2JL:76122f Zolkin, G.A., "Hygienic Assessment of Zliriolit Synthetic Rubber Coating for Floors", Gig. Sanit. 3_7^ (1) , 25-29 (1972). CA 77:29900 Tarkhanova, S.I. and G.F. Slipchenko, "Hygienic Evaluation of Finishing Building Materials Based on SKS-65GP Latex", Sb. Tr., Vses. Nauch. - Issled. Inst. Nov. S. 29, 14-18 (1971). CA 78:47439a Volkov, Z.A., "Hygienic Problems in the Industrial Use of Chloroprene and Divinylstyrene Latexes", Probl. Sin. , Issled-.. Svoistv Pererab. Lateksov 1971, 23-25. -44- ------- CA 78:88310v Khusainova, F.A., "Peripheral Blood Indexes in Workers Employed in the Production of Butadiene a- Methylstyrene Rubber", Tr. Azerb. Nauch. - Issled. Inst. Gig. Tr. Prof. Zabol. 1971 (7), 172-75. GA 78:88318d Gus'kova, K.P., "Effect of Occupational Factors in the Production of Synthetic Rubber on the Nervous System of Workers in Some Shops", Nauch. Tr. Omsk. Med. Inst. 1971 (107), 88-94. CA 78:106680x Fadewa, Z.M. and Yu. N. Eikhler, "Experimental data on the Combined Action of 1,3-Butadiene and ot-Methylstyrene and Animals" ,' Nauch. Tr. . Omsk. Med. Inst. 1971 (107), 166-74. CA 80:40656b D'yachkov, V.I., et al., "Evaluation of Air Pollution Due to Emissions from a Synthetic Rubber Plant", Sb. Nauch. Tr.> Kuibyshev. Nauch. -Issled. Inst. Gig. 1972 (7), 94-96. CA 80:40675g Lukoshkina, L.P. and I.I. Alekperov, "State of Lipid-Protein Metabolism in Persons Working with 1,3-Butadiene and Styrene", Gig. Tr. Prof. Zabol, 1973 (8), 42-44. -45- ------- CA 80:63390z Balan, G.M. and L.N. Sergeta, "Immunological Reaction in Patients with Chronic a - Methylstyrene and Butadiene Intoxication", Zdravookhr. Kaz. 1973 (8), 42-43. CA 80:63401d Faustov, A.S., "Toxic Conditions in the, Production of Synthetic Rubbers", Tr. Voronezh. Med. Inst. 1972 (87), 10-16. CA 80;136939x CA 80:148759b Faustov, A.S., "Toxic Factors of Low Intensity During the Production of Synthetic Rubbers", Sb. Nauch. Tr. Kuibyshev. Nauch. - Issled. Inst, Gig. 1972 (7), 168-69. Bashirov, A.A., "Relation Between Excretory Function of the Liver and Secretory Function of the Stomach in People Working with Petroleum Hydrocarbons", Azerb. Med. Zh. 5jO (12) , 62-66 (1973). CA 81:34129m Zlobina, N.S. and L.A. Dueva, "Allergic Action of Polybutadiene Latex SKDP and its Volatile Products", Gi£ Tr. Prof. Zabol. 1974 (3), 52-54. -46- ------- CA 81:67970g Lukoshkina, L.P., "Effect of Petroleum Hydrocarbons on Some Aspects of the Lipid-Protein Metabolism of Workers in Butadiene-Styrene Rubber Production", Tr. Azerb. Nauch. - Issled'. Inst. Gig. Tr. Prof. Zabol. 1970 (5), 17-21. CA 81:67971h Alekperov, I.I., V.G. Knabengof, and M.I. Vinokurova, "Oscillographic Study of Vessel Tone and Hemodynamics of Persons Working with Petroleum Hydrocarbons", Tr. Azerb. Nauch. - Issled. Inst. Gig. Tr. Prof. Zabol.1970 (5), 22-30. CA 81:67973k CA 81:67974m Alekperov, I.I., M.I. Vinokurova, and V.G. Knabengof, "Combined effect of Styrene, Butadiene, and Ethyl- benzene on the Contractile Function of the Myocardium", Tr. Azerb. Nauch.-Issled..Inst. Gig. Tr. Prof. Zabol. 1970 (5), 46-55. Vinokurova, M.I., "Capillaries of Workers in a Synthetic Rubber Plant", Tr. Azerb. Nauch.- Issled. Inst. Gig. Tr. Prof. Zabol. 1970 (5), 56-64. -47- ------- CA 81:100372p Nikiforova, A.A., "Reversible Damage to the Skin of Experimental Animals Subjected to the Inhalation of Butadiene and ci - Methylstyrene", Mater. Nauch. Sess., Posvyashch. 50-Letuyu Obrazov. SSSR, Omsk. Cos. Med. Inst. 1972, 871-73. CA 81:110878x CA 81:140347r CA 81:140388e Mirzoyan, I.M. and L.M. Tsai, "Working Conditions and Hygienic Study of the Polymerization Works Of the Karaganda Synthetic Rubber Plant", Vop. Gig. Tr. Profzabol. Mater. Nauch. Konf. 1971, 250-52 (1972). Vinokurova, M.I., "Combined Effect of Styrene, Butadiene, and Ethylbenzene on the Functional Indexes of the Cardiovascular System", Tr. I Azerb. Nauch. - Issled. Inst. Gig. Tr. Prof. Zabol. 1969 (4), 21-26 (1970). Konstantinovskaya, A.S., "State of the Coronary Vessel System of Workers in Butadiene - Methylsty- rene Rubber Production", Vop. Gig. Tr. Profzabol, Mater. Nauch. Konf. 1971, 194-96 (1972). CA 8_l:175460z Kozik, I.V., "Hygienic Characteristics of New Polyester Resins", Gig. Tr. Prof. Zabol. 1974 (7) , 9-12. -48- ------- CA 81:175496r Lyashenko, K.S. and A.T. Sidenko, "Improvement of Working Conditions in the Manufacture of Dimethyl Terephthalate", Gig.Tr. Prof. Zabol. 1974 (9), 42-43. •CA 82:47350x Abdullaeva, R.G., "Disease Rate of Synthetic Rubber Plant Personnel (According to Clinical Data for 10 Years)", Tr. Azerb. Nauchno-Issled. Inst. Gig. Tr. Prof. Zabol. 1973 (8), 140-44. CA 8£:47351y Abdullaeva, R.G,. , "Differentiated Study of the Disease Rate of Workers at a Synthetic Rubber Plant (According to Clinical Data)", Tr. Azerb. Nauchno - Issled» Inst. Gig. Tr. Prof. Zabol. 1973 (8), 145-48. CA 82:76697w Aliverdieva, Sh. S. and K.I. Minchuk, "Atmospheric Air Pollution in the Industrial Area of a Synthetic Rubber Plant", Tr. Azerb. Nauchno - Is^sled. Inst. Gig. Tr. Prof. Zabol. 1973 (8), 59-61, -49- ------- 5.0 ADDITIONAL REFERENCES Chaeganov, A.I. and O.B. Porembski'i, "Early Complications of Sclerosing Therapy of Varicose Veins", Vestn. Khir. 113 (11), 121-25 (1974). TOXBIB 75:68504. Elliot, Robert W. and Harry Watts, "Diffusion of Some Hydrocarbons in Air. Regularity in the Diffusion Coefficients of a Homologous Series", Can. J. Chem. 5£ (1), 31-34 (1972). CA 76:103889v. Faustov, A.S., I.B. Batkina, and N.V. Lobleva, "Toxic-hygienic Evaluation of the Production of Polybutadiene Synthetic Rubber", TJC. , Voronezh. Cos. Med. Inst. 7_3 (4), 53-60 (1968). CA ;M:74476j. Faustov, A.S. and N.V. Lobeeva, "Action of Some Chemical Compounds on the Protein Composition of Blood and Bone Marrow Puncture Sera", Gig. Saint. 25_ (8), 112-13 (1970). TOXBIB 71:130752. Filov, V.A., "Thermodynamic Activity of Some Industrial Poisons— \ Evaluation of the Activity in the Toxicology of Volatile Organic Compounds", Tr. Nauchn. Sessii Leningr. Nauchn.- Issled. Inst. Gig. Tr. Prof. 1958, 223-31. CA 5_6:13199b. Hanst, Phillip L., et al., "Atmospheric 03 - Olefin Reactions", ACS, Div. Petrol. Chem., Prepr. £ (4), A7-A16 (1959). CA 55:27006d. -50- ------- Leighton, Phillip A. and William A. Perkins, "Photochemical Secondary Reactions in Urban Air", Air Pollution Foundation (Los Angeles) Kept. £4, 212 pp. (1958). CA 5_3:3559b. Matinian, G.V., "The Method of Poisoning of Experimental Animals by Inhalation", Zh. Eksp. Klin Med. 9 (4), 24-27 (1969). TOXBIB 701:229 957. Menyailo, A.T. and M.V. Pospelov, "Reaction of Ozone with Olefins", Usp. Khim. 36_ (4), 662-85 (1967). CA 6J7:R99534v. Mitin, lu. V., "Changes in the Upper Respiratory Tract in Isoprene Rubber Production Workers", Zh. Ushn. Nos. Gorl. Bolezn. 2_9 (6), 79-83 (1969). TOXBIB 70;227168. Pitts, J.N., Jr., W.A. Rummer, and R.P. Steer, "Chemiluminescent Reactions of Ozone with Olefins and Sulfides", Env. Sci. Techno1, 5 (10), 1045-47 (1971). CA 75_: 132678k. Pokrovskii, V.A., "Professional Hazards in the Production of Synthetic Rubber. I", Gig. Sanit. 1953 (9), 17-23. CA 4_8:7329c. Saltzman, Bernard E., "Kinetic Studies of Formation of Atmospheric Oxidants", Ind. Eng. Chem. 50_, 677-82 (1958). CA 52^: 122853c. -51- ------- Sautin, A.I., N.I. Kaznina, and L.B. Es'kova-Soskovets, "Sanitary Hygienic Evaluation of Shoes Made of Synthetic Polymers", Gig. Sanit. 37 (11), 60-63 (1972). KEEP 73;10416. Schilling, R.S.F., "Developments in Occupational Health During the Last Thirty Years", J. Roy. Soc. Arts. Ill (5088), 933-84 (1963). CA 6£:6120f. Sharnberger, R.J., "Inhibitory Effect of Vitamin A on Carcinogenesis", J. Natl. Cancer Inst. 47_ (3), 667-73 (1971). TOXBIB 72-.105710. Vol'fson, N.I., "Precancerous Changes in the Epithelium of the Uterine Cervix and Vagina Following the Intravaginal Insertion of a Plastic Sponge", Biull. Eksp. Biol. Med. 6_7_ (4), 91-95 (1969). TOXBIB 69-.206933. Volkova, Z.A., et al., "Work Conditions and the State of Health of Workers Engaged in Hot Vulcanization of Footwear Rubber", Gig. Tr. Prof. Zabol. 1£ (1), 31-34 (1970). CA 7_3:28560p. Zorina, L.A., E.V. Diadova, and V.A. Doskin, "Dynamics of Poisoning in Workers Subjected to the Combined Effect of Benzene and Other Hydrocarbons (Cyclohexane and Divinyl)", Gig. Tr. Prof. Zabol. 14 (8), 14-18 (1970). TOXBIB 71;152118. -52- ------- |