Document O3RMy4m58aEJEZoVnQj9JBn51

FILE NAME: BF Goodrich (BFG) DATE: 1948June DOC#: BFG027 DOCUMENT DESCRIPTION: Journal Article - Industrial Medicine INDUSTRIAL MEDICINE Volume 17 JUNE 1948 Number 6 Medical Problems Encountered in the Manufacture of American--Made Rubber REX H. W ILSO N , M.D., G LE N N V. H O U G H , M.D., and W ILLIAM E. M cCO RM ICK, Medical Division, The B. F. Goodrich Company, Akron, Ohio T HE manufacture of synthetic rubber, prefer ably called American-made rubber, on an ex tensive scale is a recently developed United States industrial enterprise brought about by' necessity during World War II. Since much of the early research and development prior to World War II was done in the Research Labora tories of The B. F. Goodrich Company, under the direction of Dr. Waldo Semon, the potential health hazards were brought to the attention of the Medical Division at an early date. Manufacture of American-made rubber pro gressed to the extent that during the recent war the vital rubber needs of our allies as well as our own were largely supplied by American-made rubber. . Since the war practically every product previously made with crude rubber can be, or is, made with American-made rubber from syn thetic plants scattered over the United States. In 1947, for example, half of this nation's record rubber consumption was American-made. In the production of American-made rubber, many chemical compounds are utilized. Some of these have been used in rubber manufacturing process es for a long period of time, and their chemical and toxicological properties are well known. Other compounds are new and very little has been written concerning them. Mallette2 in 1943 discussed industrial hygiene problems encountered in synthetic rubber manu facture, while a previous description of the health hazards encountered in the manufacture of synthetic rubber was made by Wilson1 in 1944. This paper deals with medical experiences en countered in the manufacture of the butadiene type American-made rubber. The ingredients known or suspected of causing health problems are discussed in some detail. The chemistry of certain compounds used as various catalysts and modifiers in the manufacturing processes is fa miliar, and since they are used either in small amounts or are not particularly toxic, they will not be discussed in this paper. Specific examples of these are: Dodecylmercaptan, rosin acid soap, hydrochloric acid, sodium sulfite, diisopropyl dixanthogen disulfide, soap, sulphuric acid, Glau bers salt, ferric sulfate, potassium persulfate, sodium chloride, phenyl beta naphthylamine. The principal basic chemicals used in the manufacture of butadiene type American-made rubber are: 1. Acrylonitrile with a chemical formula of CH2: CH CN. 2. Styrene with a chemical formula of C6H5 CH:CH2. 3. Butadiene with a chemical formula of CHo: CH CH:CH2. ` Acrylonitrile ("'HEMICAIi and Physical Properties:23 Acrylonitrile (vinyl cyanide), with a structural H formula of CH2=C-- C--N, is a colorless volatile liquid boiling at 77.3 C. It has an ethereal odor, and is partially soluble in water. It has a mole cular weight of 53.06 and specific gravity of 0.806 (20C). Mode of Action and Symptomatology: Exposure of various laboratory animals, in cluding monkeys, to acrylonitrile15 in amounts* varying from 90 to 635 p.p.m. (parts of vapor or gas per million parts of air) demonstrates that the symptomatology of all animals, except guinea pigs, is that of a typical nitrile exposure. These symptoms include initial respiratory stim ulation followed by rapid shallow breathing, slow gasping spasmodic abdominal type respira tions, generalized convulsions, coma and finally death. Biochemical studies16 in this same group of animals showed that sodium nitrite in doses of 50 m g/kg of body weight exhibited a protec tive and antidotal effect when administered be fore and immediately after the animal's expo sure. No signs of cumulative action were found in laboratory animals exposed to concentrations of 56 p.p.m. Our own observations, on workmen handling cleaning operations in polymerizers with expo sures varying from 16-100 p.p.m. for 20 to 45 minutes, show that the most frequent symptoms include dull headache, fullness in the chest, ir ritation of all mucous membranes including the eyes, nose and throat, a feeling of a p p r e h e n s io n and nervous irritability. Some workmen com plain of intolerable itching of the skin with no demonstrable dermatitis. When direct skin con Page 200 INDUSTRIAL MEDICINE June, 19-% tact occurs, it causes a direct irritation and ery 2. In cases where poisoning is induced by oral thema followed by bleb formation, desquamation ingestion, lavage stomach with a solution com and slow' healing-. Wilson1 reported several cases posed of 52 gm. of sodium thiosulphate dis of acrylonitrile poisoning that developed mild solved in a liter of water. jaundice and low grade anemia and leukocytosis. 3. Inject intravenously 10 cc. of 3% aqueous Given orally the minimal fatal dose in labora solution of sodium nitrite at rate of 2-5 cc. per tory rats is stated14 to be 150 mg/kilo body minute, then 50 cc. of 36% solution of sodium weight. Symptoms in these animals included res thiosulphate piratory changes, cyanosis, convulsions and 4. Give artificial respiration if necessar;. death. 5. Oxygen may be given by mask or nasal Pathology and Laboratory Findings: Pathological changes reported16 in laboratory animals include hemosiderosis, indicating blood destruction, which was found to be proportional to the amount of exposure, renal irritation with hyaline casts in the straight collecting tubules, subacute interstitial nephritis and occasionally a subacute bronchopneumonia. Medical observa tions in industries where acrylonitrile is used have noted some evidence of liver and kidney irritation in employees, which cleared up prompt ly on removal from exposure. The probable range of exposure in these cases varied between 15 to 100 p.p.m. Cephalin flocculation, blood choles terol, urinalysis, blood pressure, arid the blood non-protein-nitrogen content are valuable tests in - determination of liver and kidney damage associated with nitrile exposure. Four workmen exposed to acrylonitrile in cleaning operations of polymerizers in our plant were checked to determine blood thiocyanate levels in relation to nitrile exposure. The concentration of acryloni trile in these polymerizers ranged from 16 to 109 p.p.m. With exposure to concentrations of acrylonitrile up to 22 p.p.m. for 30 minutes, the blood thiocyanate level was normal when deter mined 2V2 hours after exposure. When the ex posure was 50 p.p.m. for 30 minutes, the blood thiocyanate level had not returned to normal after 12 hours removal from exposure. These findings suggest that the amount of nitrile ac cumulated in the body even in minimal exposures catheter. When signs of poisoning persist or reappear, the sodium nitrite and thiosulphate may te re peated, using half the quantity originally used In any case a second injection of the ant dotal solutions (using y2 the original quantities) may be given two hours later for prophylactic pur poses. Vitamins Bt and C have been benefic al m preventing weight loss to laboratory animals ex posed to acrylonitrile over long periods of time. Prophylaxis: Atmospheric concentrations should not ixceed 20 p p.m. This necessitates enclosure of pro cesses to the maximum degree possible ar d the effective use of mechanical exhaust venti ation Skin contact should be avoided, not only because of the compound's vesicant action, but aho be cause of possible toxic systemic effects, n the case of skin contact with the concentratec com pound, immediate washing with copious quan tities of soap and water is necessary. If spilled on the clothing, the clothes should be immediate ly removed and a shower taken by the indi :idual. The effect of chronic low-grade atmospheric or skin exposures on humans is still undetermined. It is, therefore, advisable that working person nel be given periodic physical examination;, with special emphasis on hematology and liver and kidney functions. The determination of the thio cyanate level in both blood and urine has been sugested as an index of overexposure. is not easily eliminated and the detoxification capacity of the body is easily exceeded. These Styrene (Monomeric) findings correlate with animal experimentation HEMICAL and Physical Properties: in which it was found that only one-third of ^ Styrene (phenyl ethylene, vinyl benzere) is a the lethal dose of acrylonitrile is destroyed in the colorless liquid with a boiling point of 144.T'C following 24-hour period after exposure. and a melting point of --31C. with a chrracter- Determinations in Small Amounts in A ir:1419 istic disagreeable odor. Its structural formula is This can be carried out by exercising the prin ciple that acrylonitrile under proper conditions can be converted to ammonia and acrylic acid. The reaction proceeds stoichiometrically so that one molecule of acrylonitrile yields one molecule of ammonia. Ammonia is determined either by titration19 or colorimetrically.14 Mode of Action and Symptomatology: In man, concentrations of 1,300 p.p.n . cause extreme eye and nose irritation. This symptom, complex in itself, affords a definite safegu ard against voluntary exposure to acutely hazardous Treatment: concentrations. Laboratory animals13 exposed Because of its mode of action, patients with for 12-hour periods to vapor concentra .ions of a c r y l o n i t r i l e p o is o n in g should receive immediate approximately 5,000 p.p.m. had symptoms of ly the following routine treatment for cyanide local irritation in the eyes, nose and mucou- poisoning: membranes, followed by primary effects on the 1. Break an amyl nitrate ampule in a hand central nervous system with incoorc.ination. kerchief and hold it directly under patient's nose tremors, loss of equilibrium and finally loss of for 20 seconds every three minutes. consciousness. No other significant changes ate BSP fvo l. r. ( noted : posurewith b . irrita i: could ! A stud in an ,. . mem hr flowed ` hours muscul, % ibrium . Sigi- m etallii fgk.long af ir recti y p: ~ Whei -directly ,,m atiti s ^that of fiand to 'Path ol< ^ The pared : |to styr gto be j ex |Vol verri' aoun^affecte-. ^deaths ystem doni a Sforkrr. of Change aits as total b Se no .hav, als j SPOSI: |In this Deter i SkMon errnii, vapors Sethy sty tra-\ photo r feat Bed .ic ?phs Che 5m itili idle per v.. Vol. 17. No. 6 INDUSTRIAL MEDICINE Page tOl noted in laboratory animals given repeated ex posures for periods varying up to six months with 650 p.p.m. In man, however, eye and nose irritation is marked at this concentration and could not be tolerated except for brief periods. A study of exposure of humans17 indicated that in an atmosphere of 800 p.p.m. eye and mucous membrane irritation resulted, immediately fol lowed by listlessness and sleepiness. After three hours exposure to this concentration, lack of muscular coordination and interference of equil ibrium, depression, and weakness resulted. A metallic taste continued in most of the subjects long after interruption of exposure. In experimental animals ingestion produces local irritation of the gastro-intestinal tract dir ectly proportional to the amount ingested. When styrene comes in contact with the skin directly, it produces an irritation and its der matitis-producing qualities are comparable to that of the other hydrocarbons, such as benzene and toluene. Pathological Changes and Laboratory Findings: The outstanding pathological lesions encoun tered in tissue examination of animals exposed to styrene in varying concentrations are found to be pulmonary congestion, hemorrhage, edema and exudation. The degree of pathological in volvement appears to vary directly with the amount of exposure. The kidneys and liver are affected as in any acute intoxication. Acute deaths in laboratory animals are central nervous system in origin. Delayed deaths are from pneu monia resulting because of initial lung irritation. Workmen exposed to 500 p.p.m. for varying per iods of time presented no significant pathological changes and had no variation from the normal limits in chest x-rays or in laboratory examin ations of urine and blood. A marked rise of total benzoic acid ranging from two to six times the normal (Quick method) has been reported18 to have appeared in the urine of laboratory ani mals proportionate to the amount of styrene exposure. No hematological changes were noted in this same series. Determination of Styrene '*>. A ir:22 Monomeric styrene can be quantitatively de termined in the atmosphere by absorbing the vapors in a solvent (such as carbon disulfide, methyl alcohol, or ethyl alcohol). The amount of styrene present can be determined by either ultra-violet spectrophotometry, infra-red spectro photometry, or nitration. Treatment of Exposure: Bed rest with general supportive and sympto matic treatment is indicated. A complete phy sical examination should be made with special emphasis on investigation of the respiratory sys tem. Prophylaxis: . The enclosure of all manufacturing processes, accompanied by necessary mechanical exhaust ventilation should be used wherever styrene is handled. Atmospheric concentrations should never exceed 400 p.p.m. and should be preferably maintained below 200 p.p.m. The former value has been tentatively established by the Ameri can Standards Association. However, there is good evidence to believe that concentrations at this level are too irritating to operating person nel for prolonged exposures. If skin contact oc curs, with the concentrated compound, immedi ate washing with copious quantities of soap and water is necessary. If spilled on the clothing, the clothes should be immediately removed and a shower taken. Individuals working with sty rene should be examined periodically. Hemato logical studies are of questionable value in low grade exposures. Butadiene (erythrene, divinyl) hemical and Physical Characteristics: Butadiene is a colorless gas with an aromatic odor. It has a molecular weight of 54.09 and a boiling point of -- 4.7C. The structural formu la is CH2=CH-- c h = c h 2. Mode of Action: The passage of butadiene into the blood in vivo following inhalation is a process of simple diffusion of the gas from the alveoli of the lungs. It is rapidly eliminated in exhaled air without causing any significant pathological changes in the body, outside of its narcotic effect at very high concentrations. Symptoms of Over Exposure: Butadiene is practically innocuous aside from its narcotizing and anethetizing effect at very high concentrations. Human subjects exposed to 8,000 p.p.m. complained of eye irritation, blur ring of vision, coughing, nasal congestion, and drowsiness.17 Subsequent repeated exposures gave no indication of cumulative action. A com plete examination of the chest including an x-ray, blood examination and urinalysis were not in formative. Subsequent follow-up examinations were also negative. In laboratory animals17 sub jected to high exposures, irritation of all of the mucous membranes and the respiratory tract occurs along with varying degrees of narcosis. Acute deaths are due to pulmonary edema. De layed deaths are due to chemical pneumonia fol lowing pulmonary irritation. Experimentation with butadiene in laboratory animals indicates that butadiene is not a safe general anesthetic because there is not complete muscular relax ation even in the fourth stage. Death ensues rapidly when the laboratory animal is kept in deep anesthesia for any length of time. Pathology and Laboratory Findings: No pathological changes or laboratory find ings in the exposures of humans. No progressive changes have been reported in laboratory ani mals exposed to butadiene in concentrations of 600 to 6,700 p.p.m. for a period of 7% hours per day, six days per week for eight months.17 At the higher levels o f e x p o s u re ( 6,700 p.p.m. or more) for the same period of time, some cloudy swelling was found in the livers of these animals. No significant changes in blood or urine Page 202 INDUSTRIAL MEDICINE June, 19U8 were found in any of the studies made on labor atory animals. Method of Detection in Atmosphere: Under proper conditions iodine pentoxide oxi dizes butadiene completely with the liberation of 2.2 molecules of iodine. The amount of lib erated iodine can be determined by titration with sodium thiosulfate. Treatment: Workmen anesthetized with or suffering from exposure to butadiene should recover completely, providing they are removed from exposure while respiration and heart action are still strong. Oxygen by inhalation should be administered un til the pulse and blood pressure remain normal and the color is good. Symptomatic treatment in indicated. Prophylaxis : Of the three basic materials used in the manu facture of butadiene type American-made rub ber, butadiene is the least toxic. Special precau tions need to be observed in handling the com pound from a fire and explosive standpoint. These include enclosure and mechanical exhaust ventilation and will in most cases automatically control the health hazard. There is no apparent systemic injury to humans in concentrations be low 5,000 p.p.m. Any complaints which include eye and respiratory irritation, headache and ver tigo might be considered as indicative of exces sive exposure. T n the processing of butadiene-type American1 made rubber into products, a number of chemicals are used. These include aromatic hy drocarbons, chlorinated hydrocarbons, petroleum distillates, ketones, acetates, alcohols and carbon disulfide. These compounds are all toxic in vary ing degrees and present certain medical problems in their handling. Specific methods for determin ing the atmospheric concentrations of these chemicals can be found in Jacob's20 text. Aromatic Hydrocarbons 'T'HE aromatic hydrocarbons are used exten sively in the processing of American-made rubber. Of these, benzene (benzol, C6H6) ; to luene (toluol, C6H5CH3) ; and xylene (xylol, CeH4(CH3) 2) are the principal ones. These com pounds are of value because of the fact that they are excellent solvents. Benzene ("HEMICAL and Physical Properties: Benzene is one of the most dangerous of the in dustrial solvents. It is a colorless coal tar distill ate with a rather pleasant characteristic odor. It boils at 80.2 C and has a specific gravity of 0.879. The commercial varieties usually used in industry may contain from 2 to 10% toluene, xylene, olefine, paraffin, and carbon disulfide. h"cC <3>h- The structural formula is HI H *C- H H Mode of Action and Symptomatology: As pointed out by Wilson3 benzol poisoning may result from absorption of benzene by either the respiratory tract, the alimentary tract, or probably the skin. Cases of poisoning in human beings have been found with exposures to at mospheric conditions as low as 25 p.p.m. Con centrations of 50 to 100 p.p.m. are considered to be safe for the average person. Individual sus ceptibility varies. Acute benzol poisoning is rare. The symptoms of an acute case are refer able to the central nervous system. There are muscular tremors, salivation, violent twitching, exhaustion, narcosis, paralysis, commlsions, and death from paralysis of the respiratory center. Patients exposed to concentrations of vapors between 50 and 500 p.p.m., with the average concentration being about 100 p.p.m. show symp toms of lassitude, malaise, nausea, vomiting, diz ziness, and headaches.3 Macular dermatitis may appear. As exposure continues symptoms become more severe. Hemorrhages under the skin and from the body cavities may occur. In one case ecchymosis and petechiae were the first symp toms noted. At the time of appearance the blood count was normal. In five days the white blood cell count was 500. Diplopia, especially for close distances, occurs in some cases. If the person is highly susceptible, or if the exposure has been great and prolonged, he may get physiologic or functional depression of the bone marrow.. This varies in degree from a slight hematopoietic sup pression to a total bone marrow aplasia. The symptoms of a total aplasia are usually those of benzol absorption followed by prostra tion. On the other hand, it is sometimes strange how well the patient may appear. Aside from fatigue there may be no other complaints. The best index of benzol absorption is the blood count. All components of the blood are affected, being lowered. Most important, the total leucocyte count falls. Special reference should be made to the differential count. The ratio of pplymorphonuclear cells to monocytes is changed. The number of monocytes increases and the polymorphonuclear cells decrease. The red blood cell count is lowered. The hemoglobin usually falls. It has been reported by some in vestigators that the leucocyte count may be ele vated at first. However, when this occurs it is quickly followed by a general lowering of the count. The platelet count is lowered, dropping to practically zero in severe cases. The reticulo cyte count is also lowered. The prothrombin time is normal. The resulting picture is one of aplas tic anemia. One patient exhibited a count of 125 white blood cells, 1,500,000 red blood cells, and 25% hemoglobin. This patient died with bron chopneumonia. The red blood cells exhibit anisocytosis, poikilocytosis, and polychromatophilia. In all patients showing a marked blood reduc tion, a bone marrow biopsy should be done. The degree of aplasia can be determined, and usually an accurate prognosis can be made. Patients with total aplasia usually die. Patients with Vol. 17, No. 6 INDUSTRIAL MEDICINE Page tOS partial aplasia have a prognosis dependent upon the amount of regeneration present. Urine ex aminations are usually negative. The blood pres sure may be lowered. Aplastic anemia is to be differentiated from agranulocytosis and acute leukemia. The sym- toms of all of these diseases are very similar. In agranulocytosis the red blood cell and platelet counts are usually essentially normal. In acute leukemia the white blood cell count may be nor mal, raised, or lowered with the differential count showing a marked increase in very young white blood cells. The liver and spleen are usual ly enlarged in acute leukemia and are normal in aplastic anemia and agranulocytosis. The lymph nodes are normal in aplastic anemia and agranu locytosis and are usually enlarged in leukemia. Sore throat is common in leukemia and especially so in agranulocytosis. It must be recognized that the differential diagnosis between these three diseases may be difficult. Bone marrow studies usually reveal the proper diagnosis. Treatment: In patients with mild benzene intoxication, with or without a change in the blood count, the treatment is permanent removal from exposure. These patients will return to normal in a few days with no medication. In patients, where absorption is sufficient to cause a marked change in the blood picture, more active treatment is necessary. These patients are placed at absolute bed rest. Multiple small whole blood transfusions (about 250 cc.) are given as often as once daily. One patient was given 50 transfusions, another 36. The patient may be alkalinized with sodium or potassium cit rate. When severe reactions occur, blood plasma may be used in place of whole blood. Direct bone marrow transfusions may be given as often as twice weekly. In this procedure 2 to 5 cc. of bone marrow are removed from the sternum of a compatible donor and introduced directly into the sternum of the patient. From the same donor 250 cc. of blood are drawn and transfused into the patient. This is followed by 1,000 cc. of normal saline solution. Ten milligrams of liver are given intramuscu larly daily. Large daily doses of liver, iron, cal cium, phosphorus, yellow bone marrow, and mul tiple vitamins are given by mouth. A total of ^^0 JtaJiJQiLmg. of . ascorbic acid are given daily :by mouth. Ar full diet is prescribed. The pa tient's general hygiene is improved as much as possible. Bleeding areas are stopped if at all possible. Pentnucleotide has been used and found to be effective in some cases. The poor resistance in these patients is due to the lowered leucocyte count. Secondary in fection, the most common of which is a Vincent's organism infection of the mouth, is one of the causes of death. For certain types of severe secondary infection sulfadiazine and antibiotics are indicated. The response to therapy is slow since a con siderable time is necessary for the bone marrow to regenerate. One patient was under treatment for twelve months, at which time he still had a low hemoglobin and red blood cell count. Splenec tomy may be considered in some refractory cases. Any treatment, at best, is not wholly satisfactory. Extreme caution must be observed in the hand ling of this compound. In too many patients the disease proves fatal. Prophylaxis: Prophylaxsis is discussed at the end of this section on aromatic hydrocarbons. Toluene * /'"'HEMICAL and Physical Properties: Toluene is a colorless,highly refractive inflam mable liquid obtained from tolu and other resins, and from coal tar. It boils at 110.4C. and has an odor somewhat similar to that of benzene. It is insoluble in water and is miscible with alcohol, ether, chloroform, carbon disulfide and petroleum benzine. Its specific gravity is about 0.865 at 25C. Its structural formula is / \ C H 3. Toluene constitutes two to 10% of commercial benzene. It is used extensively in the rubber, lacquer, and munition industries. Mode of Action and Symptomatology: As pointed out by Wilson4 the pathologic mani festations of exposure to toluene are a matter of controversy. The conclusions reached by var ious authors are in decided variance with one another. Toluene poisoning is probably caused by ab sorption through the respiratory system, the skin, and the alimentary tract. The absorbed va pors exert a progressive depressant action on the central nervous system and the bone marrow. Toluene is also a pronounced irritant to mucous membranes. A factor to be considered whenever it is employed is individual susceptibility. Ex posure to concentrations of toluene from -200 to 500 p.p.m. for six to eight hours will in most persons cause tiredness and lassitude. Concen trations over 500 p.p.m. for one to three hours are definitely dangerous and will cause symp toms attributable to depression of the central nervous system and the bone marrow. Treatment: Toluene may be assumed to be a dangerous chemical. Definite precautions should be taken whenever it is used. The treatment of toluene poisoning is the same as that of benzene poi soning. Prophylaxis : Prophylaxsis is discussed at the end of this section on aromatic hydrocarbons. Xylene f^HEMlCAL and Physical Properties: Xylene is a colorless liquid with a mildly irri ta tin g odor somewhat similar to that of gasoline. It is insoluble in water and miscible with most organic solvents. It boils in a range from 138C to 144C. Its specific gravity is approximately I :j'"J 1,1" 11 1 i . Page 20U INDUSTRIAL MEDICINE June, 19U8 : V ol. 0.870 at 20"C. The commercial grade of xylene Chlorinated Hydrocarbons expos i is a mixture of the ortho, meta, and para isomers and usually contains as an impurity small quan tities of benzene and toluene. The formula of 'T'he chlorinated hydrocarbons used in the man ufacture of American-made rubber are: 1. Carbon tetrachloride (tetrachlormethane) ; ually liver r. [sympt I f xylene is CeH4(CH3) 2. CC14. ilate ti Mode of Action and Symptomatology : 2. E t h y l e n e dichloride (dichlorethane) Treat Xylene is stated to possess more severe nar C2H4C12. - A c. cotic properties than benzene. Xylene poisoning 3. Tetraehlorethane (acetylene tetrachloride) imade is relatively uncommon because its volatility is C,H2C14. tion t lower than that of benzene or toluene. Chronic 4. Trichlorethylene ( e t h y l e n e trichloride) .chest. poisoning does occur. There is some evidence C2HC13. Un sal that xylene exerts an action on the blood form 5. Perchlorethylene (tetrachlorethylene) C2C14. .drate, ing organs similar to that of benzene. Cases Chemical and Physical Properties: (tent n of aplastic anemia have been attributed to xylene These compounds have varying uses. Some Lported vapors. There have been some cases reported in are. used.as solvents,.others are used in fire ex )ther } tGoepremniaanwliittehrantourreedoufctlieounkionpreendiacealnlsd. thrombocy tthiningnueisrhs,erisn,"tahirecfprryodculecatnioenrs;o"fdpehgroetoagserrasp,hliaccqfiulmer, ioablssoerbvt i Treatment: and as anthelmintics. Their many uses are tdainag The treatment of xylene poisoning is compar chiefly based upon their solvent properties and roph able to that of benzene poisoning. Prophylaxis of Aromatic Hydrocarbons: because some are non-inflammable. Mode of Action and Symptomatology: Wor Atmospheric concentrations should not exceed Most physicians are thoroughly familiar with the values shown in Table I. In order to ac the action of carbon tetrachloride on the human bbese itics, complish this,mechanical exhaust ventilation will, in most cases, be necessary. Skin contact should system and do not realize that the other members of the chlorinated hydrocarbon group are also ithol 5>r thy be avoided. Blood counts, including hemoglobin, extensively used in manufacturing processes. ispec red and white cell, and differential determina The most toxic of the group is tetrachloreth 1th ; tions should be made on all exposed personnel at least every three months. Sternal bone marrow ane, having, according to Matruchot,5 a com parative toxicity of 6.0. Carbon tetrachloride is joule |anic Ienxadmiviindautailosnswsithhoubldloobde doorneboonne sumsapricrioowusacbansoers. ltiisvteedtobxyicitthye osfam2.e6,aturtihcohrloarsethhaylveinneg oaf c1o.m0,pparear p n a malities should be considered for immediate and chlorethylene of 1.4, and ethylene dichloride of Snide Wpehrmeraenveenrtpotrssainbslefe, ranaawtateymfprtomshouthldesbee smolavdeenttso. H1.6e.altAh cSceorrvdiicneg,21tothDe amviasximaunmd tahlleowUa.blSe. coPnucbelnic role substitute less toxic solvents for the aromatic tration of carbon tetrachloride is 100 parts per IE hydrocarbons. million. According to Elkins7 this level is too < high and should be reduced to 50 parts per mil Yer. T able I. lion. li S uggested Maximum Allowable Concentrations The symptoms of over-exposure to the chlor aes (Parts per million parts of air) inated hydrocarbons usually start with a feeling ' S' Acetone ..................................................................... 600 of drowsiness which, if exposure continues, is air Acrylonitrile ............................................................. 20 accompanied by anorexia, nausea, vomiting, ab ice Amyl (iso) acetate ............................................. 200 dominal pain, diarrhea, headache, and dizziness. le Amyl alcohol .......................................................... 100 Benzene ..................................................................... 100 Jaundice may develop. Oliguria progressing into Bin r Butadiene ................................................................. 5000 Butyl acetate .......................................................... 200 anuria may also develop. In some cases bron i * Butyl alcohol .......................................................... 100 chitis or bronchial pneumonia occurs, especially rds Carbon tetrachloride ............................................. 100 if free Cl or HC1 tis present. Some cases present Carbon disulfide ..................................................... 20 E thyl acetate .......................................................... 400 Ethyl alcohol .......................................................... 1000 Ethylene dichloride ............................................... 100 hypertension. A constriction of the visual color fields has also been noted. Polyneuritis has been described. The mode of action is that of a nar Gasoline ..................................................................... 500 H eptane ..................................................................... 600 Hexane ..................................................................... 1000 Propyl (iso)acetate .............................................. 200 cotic with direct or indirect effects on the cen tral nervous system. The chlorinated hydrocar bons also act as hepato-toxics, probably causing Propyl (iso)alcohol ............................................... 400 Methyl alcohol ......................................................... 200 Methyl amylketone .............................................. 200 cirrhosis of the liver. This is especially noted when the diet has been deficient in calcium or Methyl ethylketone .............................................. 200 Methyl isobutyl ketone .......................................... 200 N aphtha (petroleum ) ......................................... 600 Perchlorethylene (tetrachlorethylene) .............. 200 Propyl acetate ......................................................... 200 there has been a depletion of body protein. The kidneys may be affected, the lesion being des cribed as destruction of the epithelium with the stroma left intact. Hypertension and azotemia Stoddard solvent ..................................................... 500 Styrene ..................... 200 Tetraehlorethane ..................................................... 10 may accompany the kidney involvement. Clinton states8 ``that the renal injury is usually the pre Tetrachlorethylene ................................................. 200 dominant result of exposure to carbon tetrachlo Toluene ..................................................................... 200 Trichlorethylene ..................................................... 200 Varsol ....................................................................... 600 ride. The lungs may be involved with either a bronchitis or bronchial pneumonia resulting, Xylene ....................................................................... 200 especially if free Cl or HC1 is present." Acute \'Oh 17, No. 6 INDUSTRIAL MEDICINE Page 05 exposure to the chlorinated hydrocarbons is usuallv manifested by narcotic intoxication, with ver and kidney damage in six to 24 hours. The symptoms of chronic poisoning usually simu late those of portal cirrhosis. f realm ent: A careful evaluation of the patient should be made including liver function tests, kidney func tion tests, electrocardiogram, and x-ray of the chest. Intravenous glucose should be given either in saline and distilled water. A high carbohy drate, high protein diet with a normal fat con tent is recommended. Methionine has been re ported to be of benefit by some investigators. Others state that it is of no value. Choline has also been used. The patient should be kept under observation until all signs of liver and kidney damage have disappeared. Prophylaxis of Chlorinated Hydrocarbons: Workers should be carefully selected. The obese and the under nourished individual, nephritics, diabetics, individuals with lung and liver pathology and those having an enlarged thymus or thyroid should be rejected. Frequent physical inspections of exposed individuals should be made with particular attention being paid to kidney and liver function. Atmospheric concentrations' should not exceed those listed in Table I. Me chanical exhaust ventilation is usually required to maintain these levels. Skin contact should be avoided. Petroleum Distillates hemical and Physical Properties: Gasoline (unleaded), hexane, heptane, Stoddard solvent, Varsol, and naphtha are mixtures of hy drocarbons, paraffins, olefins, cycloparaffins (naph thenes), aromatics, and other impurities includ ing sulphur. Cracked gasoline may also carry a fairly high percentage of benzol. These sub stances are frequently referred to by the general name of benzine. This is to be distinguished from benzene (benzol). They are colorless liquids with gasoline-like odors. They have varying boil ing points ranging from approximately 70C up wards. They are inflammable. The specific gra vity varies from approximately 0.65 to 0.78. The volatility of these distillates is a factor in deter mining their toxicity for industrial use. The chemical formula of hexane is CH3*(CH2)h'CHj. The formula of heptane is CHS(CH2) 3"CH3. The others are mixtures with no single formula. Mode of Action and Symptoms: These distillates are narcotics, and it is pos sible to produce complete anesthesia with heavy doses. However, their anesthetic properties are much less than those of the aromatic and chlor inated hydrocarbons. For this reason they may be more desirable for commercial use. Drinker and associates, in studying the effects of gasoline vapors,8 found that concentrations from 270 to 500 p.p.m. were tolerable. Neuro muscular symptoms began at about 900 p.p.m. Mild intoxication at 2,600 p.p.m. The susceptibility of humans varies greatly. Acute poisoning produces the symptoms of a nar cotic. There is fullness of the head, headache, blurred vision, dizziness, unsteady gate, and nausea. The patient becomes irritable. Burning of the eyes, dimness of vision are common com plaints. It is of interest to note that on exposure to air the symptoms become increased. Massive exposures may cause sudden collapse, coma, and death. In fatal cases there is usually some blood vessel damage with small hemorrhages into the organs. Bronchitis, lung edema, cellular damage of the kidneys, liver and the spleen have been described. The symptoms of chronic poisoning are usually central nervous system in origin. Epileptiform seizures, unconsciousness, tonic muscular spasms, lancinating pains in the limbs, coldness and numbness in the hands, loss of strength, loss of memory, drowsiness, dimness of vision, confusion and dullness of mentality, and tremors have all been described. Degeneration of the pyramidal tracts have been described by Dorner.10 The effect of chronic petroleum distillate poisoning on the blood is a matter of controversy. It is usually felt that the effect of gasoline fumes on the blood differs from that of benzene only in degree. It must also be mentioned that certain petroleum distill ates are suspected of containing carcinogenic substances. At the present time considerable re search is being performed along this line. Treatment: The treatment of acute petroleum distillate poisoning should be directed towards the preven tion of respiratory and circulatory collapse. Fol lowing intense exposures pulmonary edema us ually occurs. Oxygen therapy, preferably using a face mask and positive pressure, is indicated. Saturated clothing should be removed. Circula tory and respiratory stimulants may be neces sary. Bronchopneumonia may develop. The an tibiotics may then be necessary. Most of these patients are quite nervous and restless. Sedation may be indicated. Conjunctivitis may be treated by dropping 1:1,000 adrenalin solution into the eyes four times daily, followed by cold applica tions. Boric acid ophthalmic ointment may also be used. Iron medication should be given if an anemia develops. The maximum allowable concentrations of --gasoline have-been-stated to vary from 100 to tqoO o.D.m. The values for these materials are indicated in Table I. These solvents are not con sidered to be severely toxic and in most cases the values are based more on personal comfort than on toxic requirements. Skin contact should be avoided. Ketones T N the manufacture of American-made rubber, acetone (dimethyl ketone), methyl ethyl ke tone (butanone), methyl isobutyl ketone, and methyl amyl ketone are used. Chemical and Physical Properties: The ketones are colorless, volatile, inflammable Page 206 INDUSTRIAL MEDICINE June, 19US liquids with a fruity-like odor. Their chemical formulas are: Acetone-- CH3-CO'CH3; methyl ethyl ketone-- CHs'CO'CLH.;; methyl isobutyl ketone-- CH3-CO'C4H9; methyl amyl ketone-- CH3-CO-CsH n . Their boiling points range from 56C (acetone) to 152"C (methyl amyl ketone). Their specific gravities range from 0.79 to 0.82. They are useful because of their high volatility and solvent power. Mode of Action and Symptomatology: In our experience no cases of occupational dis ease have been attributed to the ketones. A nar cotic action has been attributed to acetone when given to animals. It is known that when indi viduals a r e exposed to moderate concentrations of acetone, it may be found in "the urine without clinical symptoms being noted. It is wise to sus pect that the ketones have a narcotic action and may cause a depression of the body temperature, respiration and heart rate. Exposure to exces sive atmospheric concentrations of most of the ketones results in severe optic and respiratory ir ritation. Treatment: Treatment is entirely symptomatic. Prophylaxis: Atmospheric concentrations should be main-' tained below the values given in Table I. Per sonal comfort is the determining factor as to the tolerable atmospheric concentration. Skin con tact should be avoided. Acetates 'T'he following acetates are used in the manu1 facture of American-made rubber: Methyl, ethyl, propyl, isopropyl, butyl, and isoamyl. Chemical and Physical Properties: The chemical formulas of the acetates are: Methyl-- CH3C 02CH3; ethyl-- CH3C02C2H5; propyl-- CH3C02CH2C2H5; isopropyl -- CH3C 02CH (CH3) 2; butyl -- CH3C02CH2CH2C, Hs ; and isoamyl-- CH3-CO, CH2CH2CH-(CH3) 2. They are colorless, volatile, inflammable liquids. Their specific gravities vary from 0.87 to 0.92. Their boiling points vary from 57C to 142C. They have a mildly pleasant odor. They are used as solvents. Mode of Action and Symptomatology: This group of substances has an irritating ac tion on the respiratory passages. They are also irritating to the eyes and may cause a slight narcosis. In general, the acetates are considered to be among the safest of the solvents. No cases have ever been reported of genuine acetate poisoning. Treatment: Treatment is entirely symptomatic. Prophylaxsis: The suggested maximum allowable concentra tions for these materials are shown in Table I (page 203). These solvents are not considered severely tox ic, and in most cases the values are based more on comfort than on toxic requirements. Frequently in rubber processing, the atmospheric concen trations can be adequately controlled by means of enclosure and natural ventilation. Skin con tact may result in dermatitis and should there fore be avoided. Alcohols A4"ethyl, ethyl, isopropyl, amyl, and butyl alco hol are all used in the manufacture of Amer ican-made rubber. Chemical and Physical Properties: Their chemical formulas are: Methvl-- CH3 OH, ethyl-- C.,HsOH; isopropyl-- (CH3)oCH OH; butyl-- C2H5CH2CH2OH; and amyl-- C5H n OH. They are colorless, inflammable, volatile liquids with characteristic odors. Their specific gravi ties vary from 0.79 to 0.81. Their boiling points vary from 65C to 138"C. They are used as sol vents. Mode of Action and Symptomatology: Methyl alcohol is a source of grave injury to many industrial workers. It has a specific action on the optic nerve, and with long enough ex posure, blindness may result. The action is that of inflammation of the optic nerve followed by atrophy. A considerable amount of methyl alco hol poisoning was noted during prohibition days when wood alcohol was used in large amounts with subsequent optic nerve degeneration and blindness. The other alcohols, because of their vola tility are not considered to be especially dan gerous. Cases of narcotic poisoning have been attributed to them but not proved. The higher alcohols, like butyl and amyl, have in addition an irritant action as well as some poisonous action on the protoplasm. Treatment: If methyl alcohol is taken internally, the use of an emetic is indicated. Four per cent sodium bicarbonate, as a gastric lavage, is excellent. When the toxic action results from absorption through the skin, a lavage is of no benefit Be cause an acidosis results, due to the formation in the system of formic acid from the methyl alcohol, sodium bicarbonate or sodium lactate in travenously is advisable. It can also be given by mouth. This treatment should be continued until the acidosis has been corrected. The patient should be kept warm and symptomatic treatment offered. With the exception of the eyes most ab normalities from chronic exposure clear up after removal of the exposure. The treatment of ex posure to the other alcohols is entirely symp tomatic. Prophylaxis: Atmospheric concentrations should be kept be low the values shown in Table I. As with all sol vents prolonged skin contact should be avoided. This is especially true of methyl alcohol, which can be absorbed/through the skin in sufficient quantities to be harmful. Periodic physical ex aminations of personnel exposed to methyl al cohol should be made at two to three month in- sVOL. 1 y Servais fexamii ;Carbor ARB for mhur i Scan-ir. facturluzed . me, i n y 'ku c S id th e ityl ala! >f Atom yl-- CB CH Offl 5h u o1 2 liquid] c gravi g pointl i as si ijiiry m c acti<| ugh es i is thifl 3wed bf iyl alcqjj on d an amounfi ion ana. :r !lj ill ve ueda ' Thl have in| s some th ai sodi uni '-celienti orption' ifit rmation^ methylj tate in" iven by Jd until patient; atment.11 '.ost a b -1 p after 4 of ex- ' symp- ept b e-! all solvoided.. which. c: hy, al-' ith in-^| VOL. 17, No. 6 INDUSTRIAL MEDICINE Page 207 tervals. This should include an ophthalmologic examination. Carbon Disulfide /"'arson disulfide has played an important part for many years in the rubber industry. Sul phur is incorporated into both crude and Amer ican-made rubber. It is also used in the manu facture of viscose rayon. It has long been recog nized as an industrial poison. Chemical and Physical Properties: The chemical formula is CS2- It is a colorless, highly inflammable liquid with a characteristic odor. The specific gravity is 1.26: The boiling point is 46C. It is used as a solvent. Mode of Action and Symptomatology: The Pennsylvania Department of Labor and Industry11 has done a complete series of clin ical, anatomical, and experimental studies on carbon disulfide. Poisoning was found to be pre sent even when exposure was not great. It was found that chronic carbon disulfide intoxication may involve all parts of the central and peripher al nervous systems beginning with psychic symp toms. Later peripheral neuropathy and damage to the cranial nerves, decrease of corneal and pupillary reflexes, as well as pyramidal and extra pyramidal signs occur. Varying degrees of Par kinsonism were also observed. The commonest form of carbon disulfide poisoning is neuritis which may affect any of the nerves but most commonly involves the nerves of the limbs and certain of the cranial nerves. Both the motor and sensory nerve fibers are affected causing abnormal sensations and loss of power. Pain is usually associated with these symptoms. The most striking and disastrous effects are upon the brain. The mental symptoms run the gamut from simple irritability and depression to manic depressive insanity. The most important point is the prevention of such poisoning. Treatment: There is no specific treatment for chronic car bon disulfide poisoning. A diet high in vitamin content with an adjunct of vitamin B complex may be of value. Liver extract may be given. For the acute case, five to 7% carbon dioxide in oxy gen inhalations should be used along with res piratory and circulatory stimulants. Prophylaxis: This is one of the most toxic of industrial sol vents. Atmospheric concentrations should not exceed 20 p.p.m. This necessitates the use of the compound in only those places where proper en closure and ventilation can be provided. Its high volatility further adds to the control demands. Skin contact must be avoided. Periodic phy sical examinations, which include a careful evalu ation of neurological symptoms should be made at monthly intervals on all exposed personnel. At the first intimation of any unusual symptoms indicative of carbon disulfide over-exposure, the employee should be removed from contact with the compound. The drinking of alcoholic bever ages by exposed personnel should be discouraged. Summary ' T h e principal ingredients of butadiene-type American-made rubber are enumerated and discussed. Toxicological properties, results of over-exposure, treatment of over-exposure and prophylaxis are described. An attempt has been made to review and coordinate the current litera ture with the author's personal experiences and observations. Bibliography 1. W ilson. R. H .: H ealth H azard s E n countered in th e M anu fa c tu re of S y n th etic R ubber. J .A .M .A .. 124: 701-793, {March 11) 1944. 2. Mallette, F . S ,: In d u s tria l H ygiene in S y n th e tic R ubber M an u fac tu re . I ndustrial Medicine. 12: 495, 1943. 3. W ilson, R. H .: Benzol P oisoning In In d u stry . J . Lab. & C lin. Med.. 27:12 1517-1521, (S ep te m b e r) 1942. 4. W ilson, R. H .: T oluene P oisoning. 123; 1106 1108. (Sec. 25) 1943. 6. H am ilton, Alice, and J ohn sto n e. R. T .: In d u s tria l Toxicology. P. 636, O xford U n iv ersity P ress, 1945. 6. Davis. P . A .: C arbon T e trac h lo rid e as an In d u s tria l H az a rd . J .A .M .A .. 123: 962. 1943. 7. ELKINS. H . B .: M axim um Allowable C o n cen tratio n s 1. C arbon T etrach lo rid e. J . Ind. H yg . & T o z.. 24: 233-235, 1942. 8. 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