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Plastics notice this material mat at PROTECTED BY COPYRIGHT IAV* mTLE 17 U.S. CODE) GC-IM , The Toxicology of Synthetic Resins REX H. WILSON, M.D., and WILLIAM E. McCORMICK, M.S., Akron, Ohio This presentation is the third revision of a. paper originally written 1 in 1954. It represents a compilation of the literature concerning the toxicological properties of synthetic resins. While not all-inclusive, the bibliography can be used as a reference for the investigator of the toxicology of plastics. The second revision2 was presented in November, 1955. Plastics is a familiar word to everyone. Who among us does not possess or use some thing made from a plastic ? The manufacture of plastic articles and materials is both big and little industry. A small shop with few employees can make profitably a plastic water pistol. A large company makes nylon stock ings or plastic garden hose. Automobile bodies and telephones are molded from plastics. These plastic articles are important to our social progress, and the jobs resulting from their manufacture are important to our national economy. Plastic compounds are ever changing. The public demand for articles made from plastics is so great that the growth possibili ties are seemingly endless. Vast sums of money are spent each year on plastic re search, resulting in new materials. The industrial physician and hygienist must know the toxic properties of these items. The working environment is only as safe as the industrial hygienist makes it. Any material can be handled safely if one knows what it is and then handles it properly. Overex posure to a toxic material represents care lessness or ignorance. Received for publication Xov. 18, 1959. The B. F. Goodrich Co. Presented at the Industrial Health Conference, Chicago, April 30, 1959. 56/536 Numerous papers have been written by authors from many different parts of the world concerning the general hazards of the plastic industry.3'8 Obviously, occupational hazards may exist in the production and processing of some plastic material.9 Toxic hazards can arise from the use of plastics which contain toxic substances, particularly in food-packaging applications where extrac tion into the food may occur. Polymerized synthetic resins, which form the base for many plastics, in themselves are usually not a hazard because of their insolubility and unreactivity. The risk arises from plas ticizers, lubricants, stabilizers, colors, and fillers used with them to form the finished plastic.10 There may also be significant hazards existing in the use or manufacture of the monomers of these resins, prior to polymerization. In this discussion we have separated the resins into general classifications. In so doing we appreciate that there is considerable overlapping in many instances. I. Acrylic Resins The acrylic resins are used in many differ ent ways including the making of aircraft turrets, automobile tail lights, brushbacks, signs, and various types of textiles. Non irritating contact lenses for the eye can be made from methyl methacrylate.11 These resins are extensively used in maxillofacial surgery. Prosthetic appliances for various parts of the human body_can be fashioned from acrylic plastic material. An acrylic plastic material is used as a replacement for blood vessels and heart valves because it|& does not promote the clotting of blood. CO Aubrey,13 Endler,14 Scholler,15 and otherCO medical reporters16 have stated that the41* PLASTICS acrylic resins of the synthe surgery and p tions. They f< than any othe: compatibility1 cosmetic surge tion. Human Intraocular aci a substitute for and one-half y eye operations evidence of e tion.18 The use of z for the femoral percentage of f ever, the septi< irritation by th duction of mali implanting of ; been reported,15 cases of malig human beings Laskin 21 ret which subcutan film in mice re: fibrosarcomas, tween 257 and Because of th further use of poses of femor theses, and jaw MacKay 21 re methacrylate in cranial defects, no significant re. when it was plat considered the i inert and innocu Morgenstem ; case of sensitizai its polymerizatic their use in dent; Patty23 statec methacrylate is ii antioxidants ha effects, particula: Wilson--McCormic een written by it parts of the hazards of the y, occupational >roduction and aterial.9 Toxic Jse of plastics :s, particularly where extracPolymerized the base for re usually not solubility and ; from plas, colors, and 1 the finished e significant nufacture , prior to eparated the ons. In so considerable nany differof aircraft brushbacks, tiles. Non eye can be e.n These axillofacial or various fashioned Vn acrylic acement12 because it >lood. and other that the PLASTICS acrylic resins have the best properties of all its inert properties, it was chosen to make an of the synthetic resins for use in facial artificial kidney. surgery and produce minimum tissue reac Karpov24-29 reported on the effects of tions. They feel that the acrylics are better monomeric methyl methacrylate vapors. than any other previous material for tissue Symptoms of irritability, tiredness, somno compatibility 17 and that they can be used in lence, headache, loss of appetite, and a drop cosmetic surgery without causing skin irrita in blood pressure--attributed to a disturb tion. Human implants have been made.18 ance of the dynamic equilibrum in the cortex Intraocular acrylic lenses have been used as of the brain caused by inhalation of these ] a substitute for the lenses of the eye for three vapors--were observed. In human beings it and one-half years and over 150 successful lowers the blood pressure. j eye operations have been reported without Deichman 21 and Spealman 28 have studied j evidence of excessive foreign-body reac- the effects of monomeric methyl methacry I tion.18 late vapors on laboratory animals. Deichman The use of an acrylic plastic replacement found that a concentration of 19 mg. per j for the femoral bone head has shown a high liter of air killed all exposed animals in 2.5 j percentage of failure due to sepsis.18 How- to 5 hours. Gross pathological changes were ! ever, the septic process is not from direct confined to the respiratory system. Spealman j irritation by the acrylic material. The pro observed that the vapors were more acutely duction of malignant tumors in rats by the toxic than acetone for mice and less than implanting of plastics of various types has those of ethyl acetate. An LGjo for mice for i been reported,19,20 but there are no reported three hours' exposure was found to be 55 mg. per liter. j cases of malignant growths developing in Karpov25 gave a suggested tolerance for human beings from their use. monomeric methyl methacrylate vapors in ' Laskin21 referred to an experiment in industrial establishments of 0.05 mg. per which subcutaneous implantation of acrylic liter. He also observed that the respiratory , film in mice results in a 25% incidence of mucosa may be irritated when vapor con fibrosarcomas. These tumors developed be centration reaches 0.25 mg. per liter. tween 257 and 469 days after implantation, Raines'20 called attention to the high j Because of these findings he cautioned toxicity of methyl methacrylate, widely used I further use of acrylic in humans for pur as a monomer in the polymerization of poses of femoral heads, intraocular pros- plastics and dentures. Upper limits of its theses, and jaw reconstruction. vapor concentration in air which are per MacKay 21 referred to the use of methyl missible are stated as 0.05 mg. per liter. methacrylate implants for the repair of Summary.--Methyl methacrylate vapors cranial defects. In over 100 cases he cited no significant reaction to the substance even when it was placed in infected wounds. He considered the plastic "biologically entirely inert and innocuous." have some systemic effects on the brain cortex and on the blood pressure, resulting in lowering. The acrylic resins themselves appear to be substances which can be used successfully as bone replacements, artificial eyes, and other prosthetic appliances. When Morgenstern and associate22 described a placed in certain regions of the human body, case of sensitization to methacrylic acid and however, they should be kept under observa its polymerization products resulting from tion because tumor formation, tissue reac their use in dental prosthesis. tion, and sepsis have been reported. Patty23 stated that polymerized methyl methacrylate is inert; only its stabilizers and II. Alkyd Resins \ antioxidants have adverse physiological The alkyd resins are being used in the effects, particularly dermatitis. Because of manufacture of linoleum surfacings, paints Wilson--McCormick 57/537 A. M. A. ARCHIVES OF INDUSTRIAL HEALTH for refrigerators and autos, ignition parts, magnetorotors, and food wrappings. Morris,30 on reviewing the reactions in volved in the production of aminoplasts, phenoplasts, and alkyd resins, stated that the finished products are dermatologically inert. Schwartz, Tulipan, and Birmingham31 found that the alkyd resins may produce dermatitis. Schwartz 32 reported that alkyd resins when used as finishes for textiles have caused some cases of dermatitis. Summary.--The alkyd resins are capable of causing occasional mild cases of dematitis. III. Amino (Urea and Melamine) Resins This group of plastics is used for many articles including buttons, dishes, laminated table tops, and housings for kitchen appli ances. They are used as soap fillers and finishes for textiles. They can be used to treat paper for food-wrapping purposes. Elkins 33 stated, "nitrogen bearing plastics, such as melamine, have been said to give off hydrogen cyanide when heated, but the quantities are apparently not sufficient to produce real danger." _ Hodgins 34 stated that heat-converted films of urea-formaldehyde-ethylene glycol resins used as food-wrapping material showed no toxic effect when fed to guinea pigs in single doses of 100 mg. Repeat doses to rats of 10 mg. per day for 30 days produced mild effects on the liver, kidney, and gastroin testinal tract. Moss,35 in studying the pyro lysis of melamine formaldehyde compounds, found that mixtures of 200 ppm carbon monoxide and 10 ppm hydrogen cyanide were produced which killed rats within 30 minutes. He noted that hydrogen cyanide increases the rate of respiration and, hence, intake of carbon monoxide. Schneider3* studied the effects on human skin of soaps containing urea-formaldehyde resin filler. No significant difference was observed be tween soaps filled with urea-formaldehyde and other soaps. Cases of dermatitis were found due to the fatty acids used. Segal37,38 found little indication of toxici ty in rats fed Amberlite resin, a polyamine formaldehyde resin, when diets containing 0.5% to 2% of the crude resin were used. There was no histological evidence of dam age resulting from ingestion of the resins noted. He stated that the over-all toxicity of Amberlite, even at 20%, is negligible. Markuson39 reported on the prevention and control of dermatitis due to formalde hyde resins. Vil'kovich 40 noted that the introduction of powdered aminoplastic resin, used in kitch enware, into the regular diet of,white mice led to 70% to 80% fatalities. He also found both hot and cold aqueous extracts, obtained by placing water into aminoplastic dishes, led to considerable intoxication. Schwartz31'32 felt that urea-formaldehyde resins, when used as finishes for textiles, caused occasional cases of dermatitis. Lehman 41 stated that a polymer of ureaformaldehyde is acceptable as a treatment of paper for food-wrapping purposes. He also stated that melamine formaldehyde polymer is satisfactory for the same purpose. Lieber,5 in discussing industrial derma titis, stated that the amino resins can affect many people who have hereditary hypersen sitivities. Summary.--The amino resins (urea and melamine) can in certain combinations, particularly melamine formaldehyde com pounds, pyrolyze into hydrogen cyanide and carbon monoxide. Urea-formaldehyde-ethyl ene glycol resins can safely be used as food wrapping material. The aminoplasts may be very toxic. Dermatitis has resulted in work ers handling these resins. IV. Cellulose Plastic Materials Cellulose plastic materials are used ex tensively in display packaging, irrigation pipe, frames for eyeglasses, cigarette filters, tire cord, and in rayon acetate textiles. Some of the cellulose plastics are suitable for io*^ packaging.42 Maramorosch43 stated that sheets of ciO lulose acetate were found to be toxic CD plants and fish. This toxicity is due Ur diethyl phthalate. q PLASTICS Oppenheimer tumors includin in groups of ra ously imbedding that additives, j do not account malignant tumoi Schwartz, Ti found only rare cellulose resins. Parmeggiani r the occupational production and i materials, stated cellulose acetate the air caused rr of the skin, and Summary.--C safely externally dermatitis. Inte There is some manufacture of V. Coum Coumarone-in manufacture of paints, waterpn and chewing gu Geiger44 stai resins present li from the point nessed by their ing gum. The n the use of the individuals exhi Cases of derr dling coumaront reported. Summary.-- of resins. The acquire a derm materials. During the i been marked ad technology of t) these resins art are available un< Wilson--McCormi %\> iM fc r JSTRIAL HEALTH .ets containing !e resin were used. 1 evidence of dam;tion of the resins over-all toxicity of is negligible, on the prevention due to tormalde- the introduction of >in, used in kitchliet of white mice as. He also found extracts, obtained >plastic dishes, led i. rea- formaldehyde ;hes for textiles, dermatitis, oolymer of ureaas a treatment of trposes. He also Idehyde polymer : purpose, idustrial derma- s can affect luary hypersen- ;sins (urea and combinations, laldehyde com mon cyanide and taldehyde-ethyle used as foodloplasts may be suited in work- Materials are used exng, irrigation garette filters, textiles. Some table for food sheets of celbe toxic to y is due to >1. June, 1960 PLASTICS Oppenheimer10'20 noted that malignant tumors including sarcomas were produced in groups of rats and mice by subcutane They are used in corrosion-resistant sur face coatings, molding compounds, castings, laminating or reinforcing plastics, encap ously imbedding cellophane dims. He stated that additives, plasticizers, etc., apparently do not account for the production of these sulating electronic circuits, printed circuit backing, and adhesives. Metal-to-metal bonding can be accomplished with an epoxy malignant tumors. adhesive. Schwartz, Tulipan, and Birmingham31 found only rare cases of dermatitis due to cellulose resins. Lea and associates 45 have attempted to assess in a general manner the irritating and sensitizing capacity of the component ma Parmeggiani and associates,9 in discussing terials in the epoxy resin formulations. The the occupational risks and pathology in the production and manipulation of some plastic materials, stated that in the manufacture of cellulose acetate, the acetic acid content in the air caused mucosal irritation, blackening of the skin, and erosion of the teeth. Summary.--Cellulose plastics can be used safely externally. They only rarely produce dermatitis. Internal use may be hazardous. There is some occupational risks in the manufacture of cellulose acetate. resins were found to be irritating to the skin by means of human patch-testing. Hine and associates48 discussed the tox icity of six epoxy resins. Morris47 stated that exposure to epoxy resins in industry has resulted in dermato ses. He said that the epoxies, the curing agents, and some of the additives are severe skin irritants. Bourne 48 stated that contact with triethylenetetramine used as a polymerizing agent V. Coumarone-Indene Resins will give rise to an erythema of the face Coumarone-indene resins are used in the manufacture of asphalt floor tiles, aluminum paints, waterproof coatings, printing inks, and arms. Dorman49 stated that uncured liquid epoxy resins and amine type curing agents and chewing gum. are capable of causing allergic epidermal Geiger44 stated that coumarone-indene eczema. He outlined preventive measures resins present little if any industrial hazard that can be undertaken. from the point of view of toxicity, as wit Grandjean50 stated that dermatoses oc nessed by their. long-continued use in chew curred in half the workers using an epoxy ing gum. The main hazards are involved in resin in 11 factories making electrical the use of the monomers, to which some , equipment. individuals exhibit allergic tendencies. Pitt and Paul 51 stated that a series of Cases of dermatitis among workers han ;V-hydroxy alkyl-polyamines were evaluated dling coumarone-indene resins 31 have been as cross linking agents for polyepoxy resins. reported. The availability of these cross Unking Summary.--A relatively nontoxic variety of resins. The hypersensitive person can acquire a dermatitis from handling these materials. agents with lower toxicity offers a means of overcoming one of the major deterrents in the widespread utilization of epoxy resins. Summary.--The epoxy resins are rela VI. Epoxies tively inert chemically and are resistant to During the past few years there have been marked advances made in the chemical technology of the epoxy resins. Currently these resins are widely manufactured and are available under a variety of trade names. heat. Severe skin irritation can occur in their manufacture and use. They must be handled with care. The curing agents used with these resins appear to be the primary cause of the skin irritant effects. Wilson--McCormick 59/539 u L S* A. M. A. ARCHIVES OF INDUSTRIAL HEALTH VII. Fluorocarbons The fluorocarbons are used in the manu facture of such articles as pump diaphragms, chemical tubing, high temperature insula tion, coating of molds and bread pans, and gasket material in jet engines. Teflon is being used extensively in surgery for su tures and tubing. Recent work by Zapp and associates52 indicates various fluorine compounds to be present in the decomposition products, the specific ones, as well as the amounts of each, depending on the temperature of de composition. In the range of 300 to 360 C. hexafluorethane was observed; above 380 C, an extremely toxic compound, octafluoroisobutylene, was detected; from 500 to 550 C, the chief pyrolysis products were tetrafluoroethylene, hexafluoropropylene, octafluorocyclobutane, octafluoroisobutylene, a C5 olefin, and a complex mixture of perfluoroolefins. Fairhall53 stated that polytetrafluoroethylene (Teflon) is physiologically inert and has been rated as nontoxic. However, when heated above 400 C, unidentified volatile gases are evolved which may be toxic. In halation of Teflon dust appears to produce a condition resembling metal-fume fever. Pulmonary edema may result. Stokinger 54 stated that industrial hazards from Teflon are due to exposure to its dust and to its decomposition products derived from heating. In the first instance, a con dition resembling metal-fume fever, "the shakes," is observed. The effect usually dis appears within 24 hours with no after-effect. There is pain and aching in muscles and joints, accompanied by chills and profuse perspiration alternating with fever. When heated above 360 F, the Teflon sublimate is believed to contain absorbed hydrogen fluoride. This can produce irritation of nasal membranes and may ultimately result in pulmonary edema. Wilson and McCormick1 stressed the need for adequate ventilation when using Teflon to avoid ill effects. 60/540 LaVeen,55 in reporting on the tissue re action to plastics used in surgery, made special reference to Teflon. He felt that it could be safely used. However, Oppenheimer 19 noted that malignant tumors have been induced by Teflon when it was im bedded in rodents. Treon and associates 114 reported animal fatalities resulting from exposure to the decomposition products of Teflon and Kel-F when heated to 752 F. Lehman42 found that polytefrafluoroethylene, when used as a coating for bread pans, created no significant increase in the fluoride level of the bread. Sendroy,58 in studying the effects of pyrolyzed products of PTFE (a fluorocarbon polymer) when used on electric motor wind ings, under conditions simulating those on submarine operations, concluded that no carbon monoxide hazard would exist with operating conditions in exces.>of 250 C but that excessive concentrations of fluorine compounds might arise. Summary.--The fluorocarbons are ex tremely resistant to corrosive agents and solvents. The end-products are inert and nontoxic, but toxic decomposition products may be produced. Inhalation of Teflon dust may cause an effect resembling "metal-fume fever." Irritation of the mucous membraties and pulmonary edema can occur from inhal ing the decomposition products. VIII. Nylon Nylon is used extensively in the manu facture of gears, slide fasteners, combs, tumblers, tire cord, tennis racket strings, and textiles. It is used as surgical suture material, catheters, and toothbrush bristles. Experiments57 have proved that the type of nylon polymer used in yams is not toxic and does not cause any skin reaction. Nylon has met the rigid suture requirements of the medical profession. Gipstein 58 reported that a papulovesiculav' dermatitis was observed on a 20-year-otjrf woman and found that patch tests revealeaK. that the nylon fabric, dyed or undyed, v.'^} the agent. ._ Q Vot. 21, lune, PLASTICS Inderfurth 59 finished nylon property and cr use as suture m ties confirms tb Last8 noted from nylon cath stated that nylc applicable for b< Nylon button used for opening of the heart. Ah made of nylon a safely. Blunt17 noted for tissue inertnt to six months, : silk or cotton. T protein reaction ? months. Oppenheimer 1 nant tumors hav. bedding nylon in Summary.--Ny material. The fs world have prove hose. In spite of occasional cases c titis have been rej planted in the hun tissue reaction. IX. Pt The phenolic res facture of telephoi sulation, radio-TV molding, dials, gr surgical braces, an prosthetic devices. Demole62 studie formaldehyde resir action on gastric ac short duration, anc on the proteolytic e Elkins 63 reporte hyde varnishes ha\ producers of derm; Vedorov 84 made sensitization and de Wilson--McCormick IAL HEALTH issue reurgery, made Ie felt that it ;ver, Oppen- tuniors have 1 it was int oned animal jsure to the hi and Kel-F lytetrafluoroig for bread :rease in the sets of pyrofluorocarbon motor windig those on ed that no exist with f 250 C but of fluorine is are ex?~=nts and irt and in products Teflon dust metal-fume membranes from inhal- the manus, combs, ;t strings, cal suture h bristles. t the type not toxic on. Nylon ments ot jvesicular )-year-okl revealed 'yed, was 'une, 1^60 PLASTICS \ Inderfurth 39 stated that undyed and un finished nylon possessed no toxicological property and caused no skin reaction. Its use as suture material and toothbrush bris tles confirms this report. ! Last60 noted no intra-arterial toxicity from nylon catheters, and Schweisheimer*l . stated that nylon was well tolerated and applicable for bone sutures, j Nylon button type closures 12 are safely . used for openings between the two auricles I of the heart. Also surgical tubing has been J made of nylon and has been used perfectly . safely. Blunt1T noted that nylon, when studied for tissue inertness in dogs for periods up , to six months, showed less reaction than ` silk or cotton. There was a small foreignprotein reaction about the implant after six months. Oppenheimer19 noted that some malig nant tumors have been induced from im* bedding nylon in rodents. Summary.--Nylon is a perfectly safe material. The fashionable women "of the world have proved this by wearing nylon hose. In spite of its widespread use, only occasional cases of proved contact derma titis have been reported. Nylon can be im planted in the human body with little or no i tissue reaction. IX. Phenolic Resins The phenolic resins are used in the manu facture of telephone handsets, electrical in sulation, radio-TV cabinets, varnish, shell molding, dials, grinding wheels, plywood, surgical braces, and other external surgical prosthetic devices. Demole82 studied the effect of phenolformaldehyde resins on gastric juice. The action on gastric acidity was variable and of short duration, and there was no influence on the proteolytic enzymes. Elkins*3 reported that phenol-formalde hyde varnishes have been particularly bad producers of dermatitis. Vedorov1 made a clinical study of the sensitization and development of allergy in Wilson--McCormick chemical workers exposed to various sub stances including phenol-aldehyde resins. Luvoni63 reported that several foundry workers handling phenolic-cresolic resins developed an eczematous dermatitis. Re moval of the affected persons from exposure resulted in the disappearance of the skin affections. He felt that a form of allergy was responsible. a Sendroy36 stated that electric motors in sulated with CNSV, a phenolic resin, when operated continuously for 96 hours under conditions simulating submarine operation, gave off carbon monoxide in concentrations up to 1,620 ppm. Phenolic laminates12 have been safely used for braces and other external prosthetic devices. Fairhall 68 stated that dermatitis may re sult from repeated or prolonged contact with low concentrations of phenol in any form. It causes about 20% of the derma titis cases of the phenol-formaldehyde in dustry. Lieber 3 believed that phenolic resins may affect many people who have hereditary hypersensitivity. Summary--The phenolics as finished lam inates are inert and nontoxic. They can be used safely as external prosthetic appliances. Many workers exposed to these resins dur ing manufacturing processes have developed severe dermatoses. X. Polyethylene Polyethylene plastic is used in the manu facture of squeezable bottles, semirigid kitchenware, packaging materials, coaxial cables, surgical tubing, cartilage and bone substitutes, and surgical repair materials. Polyethylene12 is used safely in surgical repair, suture tubing, skull covering, plastic lung prosthesis, arterial reinforcement, and hernial repair. Polyethylene has been used extensively as surgical repair materials, both in and out of the body, with no apparent adverse effects. Occasional skin reactions have been reported. In general, it appears to be a perfectly safe, nontoxic, inert mate- *0 CQ CO sN) Q 3 61/54-1 A. M. A. ARCHIVES OF INDUSTRIAL HEALTH rial. It does not change composition when it is autoclaved. Patty7 stated that polyethylene is inert and that only its antioxidants and stabilizers have adverse effects. Lehman 42 found polyethylene to be satis factory as a food-packaging material. Bing68 stated that physical rather than chemical characteristics influence the body reaction to polyethylene. Implantation of irregular pieces causes more reaction. Poly ethylene mesh and nylon suture materials produce similar reactions. Macrophages are found to absorb a plastic sponge of formal ized polyvinyl alcohol formerly thought use ful as a permanent prosthesis. Tusing69 found no skin reactions and no evidence of systemic toxicity in rabbits after prolonged dermal contact with polyglycols. Because it has no adverse effect on body tissue 70 and is not affected by normal tem perature ranges, polyethylene is a satisfac tory substitute for human cartilage and bone. Tuell 71 stated that prolonged intravenous use of polyethylene tubing sometimes causes thrombophlebitis in the vein containing the tube. Tissue reactions are stated to arise from dicetyl phosphate in the mix or from the breakdown products of polyethylene which have been extruded at 250 C. Oppenheimer 19-9 found that malignant tumors including sarcomas were produced in groups of rats and mice by subcutaneous imbedding of polyethylene. Summary.--Polyethylene is a perfectly safe, nontoxic, inert material. It can be used as a surgical repair material both in and out of the body. Occasional tissue re action can occur, probably only in the sensitive person. XI. Polyester Resins The polyester resins are used in the man ufacture of reinforced plastics for automo bile bodies, boats, and translucent panels, and in Dacron textiles. They are excellent for the formation of artificial limbs. They are weather-resistant, can be formed with low pressure, are strong and colorful, and are compatible with many fillers. Very little has been reported concerning their relative toxicity. The end-products contain ing polyester resins are considered to be inert and nontoxic. Some of the organic peroxides used in their manufacture pre sent safety and dermatology problems. Polyester resins and glass cloth are used to form artificial limbs of light weight and great strength. Virtually no one seems to be allerg ic to this material.72 Lieber5 said polyester resins may have a dermatitis effect in people who have hered itary hypersensitivity. 9 Summary.--The polyester resins are rela tively inert, nontoxic materials. Virtuallv no one appears to be allergic to them. XII. Silicones The silicones are used for insulation for generator coils, auto polices, waterproof coatings, silicone rubber, and circuit break ers. They are used in the medical field r:i in needles, syringes, tubing, and in ointment bases. It is reported that silicones 74 in protective creams, suntan lotions, and other pharma ceutical preparations are nonsensitizing and nonirritating. Schoog75 found no evidence of silicone causing skin irritation and felt that it was safe to use it as an ointment base. Lesser7S stated that silicone fluids are practically inert physiologically and appear to be nontoxic. They have little or no effect when administered up to 2% of body weight. Certain silicone fluids cause a transitory conjunctival irritation in the eye but no corneal damage. Silicone-containing foods fed to rats showed a low order of toxicity. In skin tests silicone showed no irritation. Silicones used in the medical field in needles, syringes, taping, etc., are chemically inert and have no effect on blood samples taken for hematologic, bacteriologic, or biochemi cal study. Taylor78 reviewed the properties and their effects of the silicates and silicones. 62/542 Vol. 21, June, 1960 TRIAL HEALTH ;p- fillers. Very rning their roducts containmsidered to be of the organic anufacture pre problems. ; cloth are used ght weight and > one seems to sins may have dio have hered- resins are relaials. Virtually to them. insulation for s> waterproof circuit breaktedica! field 73 td in ointment protective f pharmamsitizing and e of silicone t that it was >ase. te fluids are ' and appear t or no effect body weight. a transitory eye but no lining foods of toxicity. 10 irritiition. d in needles, tically inert mples taken r biochemi- 'erties and d silicones. . June. 1960 PLASTICS Walker17 studied the toxicity of silicone insulation in submarines. Cutting78 noted that DC 200 silicone pro duced renal tubular damage when fed as 1% of the diet of rabbit; for three to four | months. DC Anti foam A caused widespread J cellular infiltration in the kidneys and the liver when fed as 0.25to lc/c of the diet * for the same period. ! MacDougall 79 reported that silicone rubI bers appeared to be nontoxic when used JI in tissue culture techniques. This was in contrast to results with vulcanized rubber. 1 Poleman 80 noted no acute or chronic toxic ' effects of methyl polysiloxane, anti foam sili| cone emulsion, and the resin used for coat- j ing capsules. i Rowe 81,82 studied methyl silicones, methyl * phenylsilicones, and methyl polysiloxane i and found them to be relatively nontoxic. He reported that DC .Anti foam A is very 1 low in chronic oral toxicity but did cause j transitory conjunctival irritation but no corj neal damage. * Lehman41,42 found methyl polysiloxane satisfactory for treating paper for food- , packaging applications, Lehman 42 approved of the use of poly styrene as a food-packaging material. Patty 85 stated that polystyrene is inert; however, the antioxidants and stabilizers may cause dermatitis. Struthers 88 reported that polystyrene may be used in contact with the skin and food without danger. Polystyrene, free from low molecular weight polymer or addition agents, presents no health hazard from oral inges tion. Oppenheimer19 reported that malignant tumors have resulted from imbedding poly styrene in rats. Lieber3 stated that polystyrene resins may have a dermatitis effect in many people who have hereditary hypersensitivity. Parmeggiani and associates9 stated that nervous excitation, leukopenia, and occa sional dermatitis followed exposure to ethyl benzene among polystyrene workers. Summary.--Polystyrene presents no health hazard from oral ingestion or skin contact, being inert and nontoxic. In its manufacture some hazards are encountered, especially from ethylbenzene. Dermatitis can occur. i Coppack83 reviewed the toxicological i problems of silicones and plastics associated j with organic chemicals in food processing. Oppenheimer19 noted malignant tumors were induced from imbedding silastic (sili cone) in rodents. Summary.--The silicones are practically physiologically inert and nontoxic. They j may cause a transitory conjunctival irrita tion when introduced into the eye but no corneal damage. Silicones are nonsensitiz ing and nonirritating. XIII. Polystyrene Polystyrene resins are used in the manu facture of kitchen housewares, refrigerator parts, food packaging, toys and novelties, wall tiles, and light fixtures, j Goggin 84 stated that polystyrene is non1 toxic and in molded form has no taste or odor. XIV. Vinyl Resins The vinyl resins are used in the manufac ture of floor tiling, packaging film, rainwear, toys, upholstery material, pipe and pipe fit ting, valves, electrical insulation, sponge, machine and structural parts, and metal and fabric coatings. They are used for plastic blood-transfusion equipment and an atomical repair film. Plastic blood-transfusion equipment87 made of vinyl with nylon and phenolic molded parts has no toxic properties. According to Lehman,4? several of the vinyl resins have been found to be satisfac tory for food-packaging materials. Morris 88 studied the dermatological and chemical aspects of 'the vinyl plastics. Patty89 stated that vinyl chloride and vinyl acetate plastics have proved to be inert; only their antioxidants and stabilizers have ad verse physiological effects. Wilson--McCormick 63/543 A. M. A. ARCHIVES OF INDUSTRIAL HEALTH PLASTICS Pulaski 90 noted no signs of toxicity when large amounts, even up to 20 liters, of poly vinyl pyrrolidone had been given to human subjects. There is some storage of polyvinyl pyrrolidone in the tissues. He also stated that a decision as to the presence of chronic toxicity has not been determined as yet. Armstrong91 , .stated that dextran and polyvinyl pyrrolidone are much superior to saline in the maintenance of blood volume after venisection. Systemic allergic reac tions occurred in some subjects who re ceived dextran but in none who received polyvinyl pyrrolidone. Bernhard92 stated that polyvinyl pyrroli done is not toxic, antigenic, pyrogenic, or infectious. Lesser 93 stated that polyvinyl pyrrolidone is nontoxic by oral administration, skin ab sorption, inhalation, or injection. Studies made on its storage in the body do not show any toxic effects. However, Hueper94 has reported poly vinyl pyrrolidone to be carcinogenic to rats, and Lusky and Nelson 95 produced fibrosar coma in rats with multiple subcutaneous injections. Wilson and McCormick1 reported no signs of toxicity in a chronic study of a vinyl-vinylidene chloride copolymer with which rats were fed for two years and dogs for one year at a dietary level. Geon polyvinyl chloride96 was found least toxic in a series of experiments on resins for use in the chest cavity. Vinyl copolymers and polyvinyl alcohols are reported under study for anatomical repair purposes. Oppenheimer 19,20 did note that some ma lignant tumors resulted from imbedding polyvinyl chloride film in rodents. Hedri and associates97 stated that poly vinyl chloride V-10 is considered unsuitable for use in surgery due to toxic effects in the liver, kidney, and spleen of dogs and mice. These effects appear to be related to high monomer content and lead contamina tion of the V-10. Roubal and Pokorny98 stated that acne on the face and forearms of workers han 64/544 dling polyvinyl chloride sheets or products is caused by chlorinated naphthalene. Addition of paraffin to prevent adhesion facili tates the rise of this chemical to the surface and should be avoided. Tuell71 stated that polyvinyl chloride decs not change chemical composition upon auto claving. Parmeggiani 9 stated that in the manufac ture of polyvinyl chloride only slight signs of irritation existed. Summary.--The vinyl resing'are used for a variety of purposes. Polyvinyl pvrrolidone (PVP) is nontoxic and can be used in the human body. Polyvinyl chloride (PVC) has been stored with little reaction in the chest cavity. Some slight skin irritntions have been observed in workers manu facturing PVC. j : ; XV. Polyurethanes This class of polymers ds relatively ik-w. having been commercialized in the United States primarily during the past decade. They are high molecular weight polymers and may be used in the manufacture of ad hesives, plastics, rigid or elastic foams, or synthetic rubber. Finished polymers are rather inert chemi cally and no more hazardous than more common plastics or rubbers. The polymers are manufactured from a class of materials called diisocyanat-.s. These materials present serious inhalation hazards. Common raw materials are toluene diisocyanate (TDI), methylene bis (4-phenyl isocyanate) (MDI), and para phenylcuc diisocyanate (PPDI). , : ' In general, all the diisocyanates so far investigated show similar toxicological prop erties. Animal experimentation and limited human experience indicate that this type of chemical is extremely hazardous via inhala tion. In acute inhalation studies on TDI, Zapp99 found that 600 ppm for six hoursyJ was lethal to rats, while 60 ppm was not^Sk Animals which died showed acute puImo-CO nary congestion and edema. Six exposuresCD averaging 9 ppm, killed three of six rats.^J Vol. 21, June, o Thirty six-ho caused micros chitis. Zapp c powerful irri respiratory tr to 2 ppm of experimental hazard of bn Zapp 109 sta nate polymers monomers ma eyes, and resj actions. Polyt virtually no si Pyrolysis proc are not more 1 elastomers test Industrial u cases of asthm serious. The high ini the fact that TDI is 0.1 pp It is intere threshold of T means that od< of hazardous i Summary.-- tively new clas polymers are no toxic hazar During mai health hazards isocyanates. T1 and in small at mucous membr type of effect, in their use. C workmen is de The B. F. Goc I 1. Wilson, R. Toxicology of F and Monomers, Ii 2. Wilson, R. Plastics--The Tt Indust. Med. 24:4 3. Danishevskii, Industrial Toxicc Wilson--McCorm. IfBYHT riiafiaadag RIAL HEALTH '.' r products u cne. Additdhesion facili- to the surface .1 chloride does ion upon auto- i the manu fat ly slight signs >s are used for winyl pyrrolid can be used vinyl chloride little reaction ;ht skin irrita/orkers manu- es datively new, n the United past decade, ght polymers :a<-ture of ad- foams, or inert chemis than more ured from a iiisocyanates. js inhalation Is are toluene >is (4-phenyl a phenylene lates so far logical prop- and limited this type of > via- inhalnes on TDI, r six hours m was not. :ute pulmo: exposures, of six rats. ?, June, I960 PLASTICS Thirty six-hour exposures of 1 to 2 ppm caused microscopic evidence of tracheobron chitis. Zapp concluded that TDI is a rather powerful irritant to the eyes, skin, and respiratory tract. Chronic exposures to 1 to 2 ppm of TDI resulted in bronchitis in experimental animals with the attendant hazard of bronchial pneumonia. Zapp 100 stated that, although polyisocya nate polymers are physiologically inert, the monomers may cause irritation to the skin, eyes, and respiratory tract and allergic re actions. Polyurethane foam plastics caused virtually no skin irritation or sensitization. Pyrolysis products show some toxicity but are not more hazardous than those of other elastomers tested. Industrial use of TDI has caused many cases of asthmatic type reactions, some very serious. The high inhalation toxicity is reflected in the fact that the threshold limit value for * TDI is 0.1 ppm.101 It is interesting to note that the odor threshold of TDI is about 0.4 ppm, and this means that odor cannot serve as a*warning of hazardous concentrations. Summary.--The polyurethanes are a rela tively new class of polymers. The finished f polymers are inert chemically and present no toxic hazards. During manufacture severe industrial health hazards occur because of the use of isocyanates. 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Inderfurth, K. H.: Toxicological Propertiestv (of Nylon), Nylon Technology, McGraw-Hill^' 60. Last, J. F Catheters in Phy 112:719, 1950. 61. Schweishei Rayon and Silk 1948. 62. Demote, 1 Resins on Acidit Helvet. med. act 63. Elkins." 64. Vedorov, I Reactivity of th> Biol. (U.S.S.R.) 65. Luvoni, R Cresolic Resins, 1 66. Fairhall, L. 2, Baltimore, Th< pp. 316-317. 67. Patty 68. Bing, J.: T1 Plastics, Acta patl 105:16, 1955; CA 69. Tusing, T. Toxicity of a Se Am. Pharm. A. S 70. Plastic Bone 71:33, 1949. 71. Tuell, S. W. of Plastic Intraver western University 72. New Limbs 32:116, 1954. 73. Lesser, M. Pharmacy, Drug 1953. 74. Next to the 75. Schoog, M.: for Dermatology, , 76. Taylor, H.: Hazards: Some of dustry, Brit M. Bi 77. Walker, H. cone Insulation in Engia 67:1142, 19 78. Cutting, W. < ford M. Bull. 10:2 79. MacDougall, Silicone Rubber a 172:124, 1953. 80. Poleman, G., Tests Concerning t Arzneimittel-Forsch 81. Rowe, V. K, on Certain Commer Silane Intermediate 30:332, 1948. 82. 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F., et al.: The Toxicity of the Products Formed by the Thermal Decomposition of Certain Organic Substances, Am. Indust. Hyg. A. Quart. 16:187, 1955. A Study /. The HERBERT H. CORI The effect o enzyme system several instanc from this latx single exposur 1,500 ppm of results in mi glutamic-oxalac and in serum esterase values posures. In vie felt that a more of carbon tetr: systems might relationship bet' response and th The present effect of single various concenti ride vapor on se male and femal carbon tetrachlo animals' food on serum enzyn gated. In addit'n carbon tetrachlor been studied in nature of the ch; suiting from exp ride vapor. Experim Male and female strain, 150-200 gm. Received for pub! From the Institute Department of Dem gan Medical School. This work was si Grant RG5727(R1), U.S. Public Health :