Document jy43bpX1Ywq3MKjgxYwbnmw2Z

Toxicology of CO /oi / hd-Sra Plastics and Rubber --PLASTOMERS AND MONOMERS REX H. WILSON, M.D., F.A.C.P., and WILLIAM E. McCORMICK, M.S. The B. F. Goodrich Company, Ahron, Ohio he popular demand for all types of articles Tmade from plastics has been so tremendous that literally there has been created an en tirely new industry in the past several years. Many plants, large and small, are devoting their entire manufacturing facilities to "plastic" items. The demand for the compounds going into the composition of the plastic materials is so great that supplies of certain of them are short. Because the industry is new and because of the ingenuity of modern research, the compounds making up the plastics are ever changing. Also, as demands for different types of articles made from plastics are increasing, this creates a de mand for different types or kinds of plastics (Table I). Naturally, the kind of material needed for a plastic automobile body is different from the material needed for an elastic garden hose or a pair of stockings. I know of no other industry which better represents the creative genius of man than the so-called plastic industry. The cre ation at less cost of better things for better liv ing is the aim of the modern business man. To achieve this, there have been brought into exist ence the wonderful modern-day research labora tories. It is important to know the chemical properties of a compound and its toxicity. It is also impor tant to know how to work with it safely. Equally important is to know the treatment for overex posure to the toxic chemical to prevent perma nent damage or death. It would be impossible to name, let alone dis cuss, the toxicological properties of all of the chemical compounds being used in the plastic in dustry. It is worth-while to discuss the properties of some of the more common resins, plasticizers, stabilizers and solvents being used. Unfortunately, the toxicological properties of all of these are not too well defined. It is to the credit of people work ing in industrial medicine and hygiene that in- Presented at the Eleventh International Congress on Indus trial Medicine. Naples, Italy, September 13*19, 1954. dustry is becoming aware of the necessity for knowing the toxicity of its materials and is tak ing steps to insure that its employees are not exposed to materials that would harm them. Resins j^ehman1 in July, 1951, presented a list of resins both suitable and unsuitable for use as food packaging ingredients. He stated "that as a gen eral rule resins are so insoluble as a class that the chances of contamination by the solvent action of foods are rather slight." The types of resins he considered suitable for food use are: Polyvinyl chloride. Polyvinyl acetate. Polyvinyl chloride-acetate. Polyvinylidene chloride. Polystyrene. Polyethylene. Cellulose acetate. Regenerated cellulose. Terephthalic acid-ethylene glycol copolymer. Butadiene-acrylonitrile (Perbunan or Hycar synthetic rubber). Lehman classified as being unsuitable for use in food packages because of the lack of adequate data concerning their toxicity: Polyvinyl formal. Polyvinyl acetal. Polyvinyl butyral. Polymeric furfuryl alcohol. Coumarone-indene. Urea formaldehyde. Phenol formaldehyde. Aniline formaldehyde. A. Vinyl Type A^inyl chloride, vinylidene chloride, and vinyl v acetate readily polymerize. By proper com binations of one or more of these monomers, many polymer variations can be produced. These polymers, after properly mixing with plasticizers and stabilizers, are then used in hundreds of dif- Reprinted from Industrial Medicine and Surgery, 23:11, 479-48G, November, 1954 (Copyright, 1954, Industrial Medicine Publishing Company) BFG03691 0507001 ferent items. The tnree polymers, either indi vidually or associated with each other, are rela tively non-toxic.1 Seeler and associates studied the chronic tox icity of a copolymer of vinyl and vinylidene chlo ride.2 This work was done because the copolymer was being considered for use as a constituent of a plastic film for wrapping food products. They reported that rats fed a diet containing 5% vinyl and vinylidene chloride copolymer for two years showed no toxic effects. Two dogs were fed a diet containing 5% vinyl and vinylidene chloride copolymer without evidence of toxic effects. Some toxicological information also exists on the three monomers--vinyl chloride, vinylidene chloride, and vinyl acetate. Patty, Yant, and Waite3 investigated the acute effects of vinyl chloride on experimental animals and found this to be essentially narcosis. Carpenter and asso ciates,4 in range finding studies, observed that a vapor concentration of 32,000 ppm of vinylidene chloride resulted in a portion of deaths of the six rats exposed for four hours. The vapor toxicity is reported to be of the same order as ethylene dichloride.6 Carpenter and associates4 also re ported a level of 4,000 ppm of vinyl acetate pro duced some deaths under the same conditions. B. Acrylonitrile--Butadiene Type VARIOUS types of American made rubbers have v been studied physiologically. Among those found to be acceptable for food use are Perbunan and Hycar (polymers of acrylonitrile and buta diene). However, the manufacture of these items does present some health problems. Wilson and associates6 reported on the toxicity of acrylonitrile in 1948. They stated that, in their observations, workmen handling cleaning opera tions in polymerizers with exposures varying from 16-100 ppm for 20 to 45 minutes frequently show symptoms of dull headache, fullness in the chest, irritation of all mucous membranes includ ing the eyes, nose and throat, and a feeling of ap prehension and nervous irritability. Some work men complained of intolerable itching of the skin with no demonstrable dermatitis. Direct skin contact with acrylonitrile causes irritation and erythema followed by bleb formation, desquama tion and slow' healing. Wilson7 reported several cases of acrylonitrile poisoning in which there developed mild jaundice, low grade anemia and leucocytosis. Given orally the minimal fatal dose of acrylonitrile in laboratory rats is stated8 to be 150 mg/kilo body weight. Symptoms in these animals included respiratory changes, cyanosis, convulsions and death. Because the mode of action of acrylonitrile in the human system appears to be similar to that of cyanide, the treatment of overexposure to acrylonitrile was outlined by Wilson and asso ciates'1 to be the same as that for overexposure to cyanide. This treatment was proved to be life saving in several instances. Vitamins B, and C have been found to be bene ficial in preventing weight loss in laboratory ani mals exposed to acrylonitrile over long periods. Wilson and associates6 also suggested as a prophylaxis against overexposure to acrylonitrile that atmospheric concentrations should not ex ceed 20 ppm. This necessitates enclosure of pro cesses to the maximum degree possible, and the effective use of mechanical exhaust ventilation. Skin contact should be avoided, not only be cause of the compound's vesicant action, but also because of possible toxic systemic effects. In the case of skin contact with the concentrated compound, immediate washing with copious quan tities of soap and water is necessary. If spilled on clothing, the clothes should be immediately re moved and a shower taken by the individual. The effect of chronic low-grade atmospheric or skin exposures on humans is still undetermined. It is, therefore, advisable that working personnel be given periodic physical examinations, with special emphasis on hematology and liver and kidney functions. The determination of the thiocyanate level in both blood and urine has been suggested as an index of overexposure. Wilson and associates6 also reported on the toxicology of butadiene. They stated that buta diene is practically innocuous, aside from its nar cotizing and anesthetizing effect at very high concentrations. Human subjects who were ex posed to 8,000 ppm of butadiene complained of eye irritation, blurring of vision, coughing, nasal congestion, and drowsiness. Subsequent repeated exposures gave no indication of cumulative ac tion. A complete examination of the chest includ ing an x-ray, blood examination and urinalysis were not informative. Subsequent follow-up exam inations were also negative. In laboratory ani mals subjected to high exposures of butadiene, irritation of all of the mucous membranes and re spiratory tract occurs along with varying degrees of narcosis. Acute deaths are due to pulmonary edema. Delayed deaths are due to chemical pneu monia following pulmonary irritation. Experi mentation with butadiene in laboratory animals indicates that butadiene is not a safe general anesthetic because there is not complete muscu lar i-elaxation even in the fourth stage. Death ensues rapidly when the laboi'atorv animal is kept in deep anesthesia for any length of time. Wilson and associates0 stated that workmen anesthetized with or suffering from exposure to butadiene should recover completely, pi-oviding they are removed from exposure while respira tion and heart action are still strong. Oxygen by inhalation should be administered until the pulse and blood pressure remain noi'mal and the color is good. Symptomatic treatment is indicated. Special precautions need to be observed in handling the compound from a fire and explosive standpoint. These include enclosure and mechani cal exhaust ventilation and will in most cases automatically control the health hazard. There is no apparent systemic injury to humans in con centrations below 5,000 ppm. Any complaints which include eye and l-espiratory irritation, headache and vertigo might be considered as in dicative of excessive exposure. BFG03692 / 20507002 Common Plastics Acrylics Alkyds and Rosin Modifications Aminos (Urea and Melamine) Cellulose Plastic Materials Coumarone-Indene and Petroleum Resins Epoxies 'Fluorocarbons Nylon Phenolic and other Tar Acid Resins Polyethylene Polyester Resins Silicones Styrene Resins Vinyl Resins Table I. Uses Aircraft turrets, auto tail lights, brush backs, signs (Dynel, Acrilan, Orion textiles). Linoleum surfacings, paints for refrigerators and autos, ignition parts, magneto rotors. Buttons, dishes, laminated table tops, housings for kitchen appli ances. Display packaging, irrigation pipe, frames for eye-glasses (rayon and acetate textiles). Asphalt floor tiles, aluminum paints, waterproof coatings, print ing inks. Printed circuit backing, adhesives, surface coatings, transformer and motor laminates. Pump diaphragms, chemical tub ing, high temperature insulation. Gears, slide fasteners, combs, tumblers, tennis racket strings (nylon textile). Telephone handset, radio-TV cab inets, shell molding, dials, grind ing wheels, plywood. Squeezable bottles, semi-rigid kitch enware, packaging, coaxial cables. Reinforced plasties for auto bodies, boats, translucent panels (Dacron textiles). Insulation for generator coils, auto polishes, waterproof coatings, circuit breakers. Kitchen housewares, refrigerator parts, toys and novelties, wall tiles, lighting fixtures. Floor tile, packaging film, rain wear, toys, upholstery material, pipe and pipe fittings, valves, elec trical insulation, sponge, machine and structural parts, metal and fabric coatings. Properties Optical clarity, good weather re sistance, wide color range, shatter resistance, machinability. Fast curing, good dimensional sta bility, good electrical insulation, good heat resistance. Unlimited color range, good elec trical insulation, resistance to or ganic solvents. Toughness, high impact strength, ease of fabrication, lustrous finish, good electrical insulation. Resistance to water and caustic cleansers, compatibility with com pounding ingredients, glass. Excellent adhesion, resistance to chemicals and heat, can be cured at room temperatures. Extreme resistance to corrosive agents and solvents, wide tempera ture range, high impact strength. Good strength and toughness over wide temperature range, wear re sistance, self-lubricating. Hard and rigid, good temperature range, strong, good electrical in sulation, low water absorption. Inert to solvents, flexible and tough over wide temperature range, non toxic, odorless, tasteless. Weather resistance, can be formed with low pressure, strong, color ful, compatible with many fillers. Extreme heat resistance, low water absorption, good dielectric proper ties over wide frequency range. Lightest of commercial plastics, ex cellent moldability, unlimited color range, tasteless, odorless. Tough and strong, unlimited color range, excellent electrical insula tion, resistance to chemicals, oil and weathering. C. Miscellaneous Types COME of the newer synthetic resins which have been physiologically studied are the silicones, the polyethylene gylcols (carbowax compounds), and teflon (polytetrafluoroethylene). Rowe et alin found upon feeding guinea pigs for 50 days in amounts up to 3% of the daily diet no indication of toxicity with DC resins 993 and 2102. They also found that DC Pan Glaze possessed a very- low order of oral toxicity when fed to the rat. Shaffer and Critchfield11 concluded from their study of carbowax compounds 1,000, 1,540, 4,000 and 6,000 that no significant gastrointestinal ab sorption occurred when fed to rats. They also ad ministered intravenously compounds 1,000 and 6,000 to humans and found they were readily ex creted to a high degree. Polytetrafluoroethylene (Teflon) is a synthetic resin with exceptional resistance to both heat and chemicals. It is being used for electrical in sulation, for special types of tubing, for coating molds and bread pans, and for gasket materials in jet engines. Stokinger1- has described the ill effects which may result when Teflon is heated to about 360 F as well as from exposure to the finely divided polymer itself. These effects resem ble, in the case of the polymer, those of metal fume fever; in the case of the sublimate (result ing from heating the polymer) those of hydrogen fluoride poisoning. In using Teflon, adequate ven- 20507003 BFG03693 tilation is necessary to avoid ill effects. Lehman1 reports that baking tests have shown no signi ficant increase of the fluoride level of bread bak ing pans which have been coated with Teflon. Plasticizers T ehman in July, 1951,1 stated that plasticizers presented more serious toxicological problems than the resins because there is always the possi bility that these materials may be leached out by food substances. The plasticizers which have had adequate pharmacological study demonstrating their harmlessness in the amounts now used in finished commercial films are: Ethyl Phthalyl ethyl glycollate. p-tertiary Butyl phenyl salicylate. 3-(2-Xenoxyl)-1,2-epoxypropane. 2-Ethylhexyl diphenyl phosphate. Butyl phthalyl butyl glycollate. Glycerol monooieate. Acetyl tributyl citrate. Di-iso-butyl adipate. Lehman classified as unsuitable for food use the following: Dicyclohexyl phthalate. Dibutyl phthalate. Methyl phthalyl ethyl glycollate. Di-iso-octyl phthalate. Dioctyl adipate. Dibutyl sebacate. Dioctyl sebacate. Dicapryl sebacate. Seifter in 194313 made acute toxicity, chronic toxicity and skin irritation studies on dibutyl phthalate. His summary and conclusions were: 1. Dibutyl phthalate is a mild primary skin ir ritant for animals and humans. 2. Dibutyl phthalate taken by mouth is acutely toxic. 3. Dibutyl phthalate ingested daily over long periods of time in amounts up to 2.5 gm. per kilo gram of diet, does not produce chronic poisoning. Smith14 studied dibutyl phthalate and found the acute lethal oral dose to be about 8 gm. petkilogram. When administered chronically in the diet the maximum concentration which did not significantly reduce normal growth was 0.25%. The feeding of dibutyl phthalate even in the highest dietary concentrations did not provoke specific gross or microscopic pathologic changes. His findings also suggested that dibutyl phthalate was metabolized in the body in much the same way as the fat normally ingested in the diet. He did not feel that it was safe to incorporate dibutvl phthalate in films for wrapping foods even if the calculated safety factor was in excess of 1400. Seifter'3 in studying dicapryl phthalate made the following summary and conclusions: 1. Dicapryl phthalate is not a primary skin ir ritant for animals or humans. 2. When taken by mouth dicapryl phthalate has a low acute toxicity. 3. Ingested daily over long periods of time, in amounts up to 2.5 gm. per kilogram of diet, dicapryl phthalate does not produce chronic poi soning. Seifter in 194313 came to the following conclu sions concerning triethylene didecoate: 1. It is not a primary skin irritant for animals or humans. 2. When taken by mouth, it has a low acute toxicity. 3. Ingested daily over long periods of time in amounts up to 2.5 gm. per kilogram of diet, it does not produce chronic poisoning. Smith14 found that the acute lethal oral dose of butyl stearate was greater than 32 gm. per kilogram. When butyl stearate was administered chronically in the diet, the maximum concentra tion which did not significantly reduce normal growth was more than 6.25%. Butyl stearate in the highest dietary concentration did not provoke specific gross or microscopic pathologic change and in dietary concentrations of 6.25% had no adverse effect on fertility or the number of viable young in the litter. There was in this concentra tion slight retarded growth of the young. He felt that, based on the above data, butyl stearate when incorporated in films for wrapping foocf appeared to possess little, if any, potential haz ard for humans, the calculated safety factor be ing in excess of 1,400. Smith14 came to the conclusion that the acute lethal oral dose of methoxyethyl oleate was ap proximately 16 gm. per kilogram and when ad ministered chronically in the diet of rats, the maximum concentration, which did not signifi cantly reduce normal growth, was 0.01% to 0.05%. He found renal calculi in three of seven rats fed 1.25% methoxyethyl oleate for more than six months. He felt that methoxyethyl oleate was hydrolized by pancreatic lipases as rapidly as triolein. He did not feel that methoxyethyl oleate should be incorporated in films for wrapping food. Smith14 concluded that the acute lethal oral dose of dibutyl sebacate was between 16 and 32 gm. per kilogram and that when administered chronically in the diet of rats, the maximum con centration which did not significantly reduce nor mal growth was 6.25%, and that when fed in the highest dietary concentration, there were no spe cific gross or microscopic pathologic changes. Dibutyl sebacate in dietary concentrations of 6.25% had no adverse effect on fertility or the number of viable young in the litter. It did cause a slight retarded growth of the young. Smith felt that this plasticizer was metabolized in the body in much the same way as fat normally ingested in the diet, and that when it was incorporated in films for wrapping food appeared to possess little, if any, potential hazard for humans, the calcu lated safety factor being in excess of 1400. Mallette and Von Haam'3 state that dibutyl sebacate is a non-toxic plasticizer, with no irritating or sensitizing effect on the skin, and that dibutoxvethvl phthalate is a non-toxic plasticizer with no irritating or sensitizing effect on the skin. Mallette and Von Haam1'1 listed the following as non-toxic plasticizers: Di-2-ethylhexyl adipate. Dibutvl cellosolve azelate. 20507004 BFG03694 Cyclohexyl azelate. 2-ethylhexyl azelate. Methyl isobutyl carbinol azelate. Pentasol azelate. Diethylene glycol dicaprate. Dibutoxyethyl diglycol carbonate. Octadecene nitrile. Dibutoxyethyl phthalate. Dicapryl phthalate. Methylacetyl ricinoleate. Dioctyl sebacate. Dibutyl sebacate. "Plasticizer 50 B" (Barrett). "Plasticizer Ellicott H." "Plasticizer SC" (Drew). "Paraplex G-25" (Rohm & Haas). "Paraplex G-40" (Rohm & Haas). "Plastolein X-55" (Emery). They stated that five of the plasticizers ex amined showed a moderately toxic effect in lab oratory animals. They were dioctyl phthalate, butylbenzyl phthalate, "santicizer 140," "santicizer 141," and "flexol 8N8." Di(2-ethyl hexyl) phthalate (commercially re ferred to as dioctyl phthalate, DOP, and 2-ethyl hexyl phthalate) was studied by Hodge16 with respect to acute oral and intraperitoneal toxicity in rats and mice. He concluded that it had a very low order of toxicity. Shaffer, Carpenter and Smyth studied it in 1945.17 Their conclusions were that it is a chemical of low toxicity and that the health hazards involved in its use as a plasticizer are slight. Such injurious action as it does exert within the body appears to be due to the alkyl part of the molecule rather than to the phthalate portion. Mallette and Von Haam15 found that dioctyl phthalate had a moderately toxic effect in labora tory animals and that the intraperitoneal injec tion of dioctyl phthalate proved fatal in doses higher than 2 gm. per kilogram of body weight. Lower doses produced weight loss, leucocytosis, severe anemia and hematuria from which the an imals recovered after a month or two. No delayed effect or permanent injury was noted in the sur viving animals. They also showed that dioctyl phthalate had a moderate skin irritating effect. Carpenter, Weil and Smyth18 reported the re sults of feeding Di (2-ethyl hexyl) phthalate for two years to rats and for one year to both dogs and guinea pigs. They obtained relatively uni form responses from all three species, with the two-year "no effect" level for rats falling between .06 and .20 gm. kilogram per day, and the oneyear "no effect" level for both dogs and guinea pigs approximating .06 gm. per kilogram per day. Lehman1 reports that food packaging films con taining this compound as a plasticizer are satis factory for wrapping foods with a high water content, but are unsatisfactory for use with foods having a high fat content, because of the ready solubility of the plasticizer in fats and oils. Halpern and Weiss19 found no irritation or induced sensitivity when 200 humans were patch tested with vinyl film containing dioctvl phthalate as the plasticizer. In 1952 Mallette and Von Haam15 reported on other plasticizers, several of which they found to be moderately toxic to rats in acute exposures. These were: 1. Butylbenzyl phthalate was fatal in rats after intraperitoneal administration of doses higher than 1.8 gm. per kilogram of body weight. Oral administration of more than 4 gm. per kilogram of body weight proved equally fatal. The animals died after four to eight days, showing weight loss, apathy and leucocytosis. The histological exami nation of the organs revealed toxic splenitis and degenerative lesions of the central nervous sys tem with congestive encephalopathy, myelin de generation and glial proliferation. 2. "Santicizer 140" (monotolydiphenyl phos phate) proved fatal in intraperitoneal doses of higher than 1 gm. per kilogram of body weight. Oral doses up to 4 gm. were supported. Toxic ani mals became lethargic on the second or third day and a profuse diarrhea developed. They died with symptoms of paralysis. Autopsy showed a gen eralized capillary paralysis with severe edema and numerous hemorrhages in the brain. 3. "Santicizer 141" (2-ethyl hexyl diphenyl phosphate or mono octyl diphenyl phosphate) killed animals after intraperitoneal administra tion of doses higher than 2.4 gm., but oral ad ministration of 4 gm. per kilogram of body weight was tolerated. With the intraperitoneal administration the animals became paralyzed and lethargic. Recovery from non-fatal lesions was delayed. The histopathological examination dem onstrated a severe acute hemorrhagic encephalo pathy with cerebral edema, ganglion cell degen eration and small hemorrhages. As delayed ef fects, focal gliosis and persistent foci of myelin degeneration could be observed. Large fatal doses also proved a powerful hemolytic agent with marked vascular hemolysis, hemoglobinuria, and hemosiderosis of the spleen. 4. "Flexol 8N8" (N,N-di-beta-(2-ethyl hexyl) ethyl 2-ethyl hexvlamide) proved fatal in doses higher than 4 gm. per kilogram of body weight. The animals developed convulsions followed by paralysis. The histological examination of the brain gave the picture of toxic hemorrhagic en cephalopathy with, edema, swelling of ganglion cells and small hemorrhages. Their conclusions were that these four plasti cizers proved moderately toxic in doses from 0.6 to 2.4 gm. per kilogram of body weight. The toxic reaction was displayed by the erythrocytes, the blood capillaries and the central nervous system. They also found in their studies 17 plasticizers to be slight or moderate skin irritants. Three-- "Flexol 8N8," "Paraplex G-25," and "Paraplex G-40"--proved to be severe skin irritants. A moderate sensitizing effect on the skin was found by Mallette and Von Haam'5 to exist with diethylene glycol dicaprate, methylacetyl ricino leate, "Paraplex G-25," "Paraplex G-40," and "Santicizer 140." Seeler et al,-n in their studies on the chronic toxicity of acetyl tributyl citrate came to the fol lowing conclusions: 20507005 BFG03695 1. Rats showed no toxic effect after eating diets these compounds, however, possess a relatively containing 200 ppm, 2,000 ppm, and 20,000 ppm high degree of toxicity and they are objection of acetyl tributyl citrate for two years. able for use in items involving contact with hu 2. Dogs were given a daily oral dose of 140 mg. man food.1 There are, however, many plastic of acetyl tributyl citrate for two years without formulas for uses in products where toxicity is evidence of toxic effect. not of particular significance and consequently, Seeler et al,21 on making chronic toxicity one or more of these stabilizers can be safely studies of butyl phthalyl butyl glycollate came to used. Obviously, when these heavy metals are the following conclusions: used, adequate, safe handling procedures must 1. Rats fed diets containing 200 ppm, 2,000 be utilized in the manufacturing plant. These ppm, and 20,000 ppm of butyl phthalyl butyl involve the practice of good industrial medical glycollate for two years showed no toxic effect. and hygiene procedures. 2. Dogs were given a daily oral dose of 140 Lehman1 has also stated that zinc oxide, zinc mg. of butyl phthalyl butyl glycollate for two stearate and salts of manganese and copper are years without evidence of toxic effect. not objectionable as stabilizers in food wrapping The results of both acute and chronic oral feed material if not more than 50 ppm of the metal ing, as well as skin absorption and irritation with leaches out into the food. 2-ethylhexyl diphenyl phosphate (Santieizer 141) Some of the newer stabilizers for vinyl resins are given by Treon et al.22 These investigators are the organic tin compounds. Elemental tin has found the compound to be innocuous when ad been used for many years as a lining for food ministered orally to rabbits and rats in a single containers and is relatively harmless. The organ large dose. No effects, either irritative or system ic tin salts, however, while not known to be harm ic, were found as the result of keeping it in con ful have not thus far been shown to be sufficient tact with the abraded skin of rabbits for seven ly safe for use in food container applications. to 24 hours. Rats fed for two years on a diet con The plant manufacturing operations involving taining 1%, 0.125%, and 0.0625% by weight of the use of the organic tin stabilizers may present the compound showed no pathology, but did show some industrial health problems but again the a retarded growth rate at the 1% level. Dogs fed degree or extent of these is not known at the the compound at dietary levels of 2.5% for two present time. years showed retarded growth, but those fed a 1.5% level grew normally. V Solvents Treon, Cappel, and Sigmon have found23 that TN THE processing of plastics into products, a a high percentage of Santieizer 141 is excreted 1 number of chemicals are used. These include in the feces of both rabbits and humans un aromatic hydrocarbons, chlorinated hydrocar changed. Halpern and Weiss10 have shown that bons, petroleum distillates, ketones, acetates and films plasticized with Santieizer 141 are not ir alcohols. These compounds are all toxic in vary ritating and do not induce sensitivity in humans. ing degrees and present certain medical problems in their handling. Specific methods for determin Stabilizers ing the atmospheric concentrations of these A/Tany different materials are being used as chemicals can be found in Jacob's24 text. stabilizers for plastics. The specific type of The American Conference of Governmental Hy plastic with particular reference to its use, gov gienists25 suggested the maximum allowable con erns to a large degree the stabilizer to be selected. centrations of many of the more common solvents Obviously, uses such as that of food packaging in Table II. where there might be leaching of the stabilizer The aromatic hydrocarbons are used extensive into the food require materials that are not harm ly in the processing of plastics. Of these, benzene ful if ingested. Lehman1 states that the follow (benzol C6Hc); toluene (toluol, CcHr,CH3); and ing are not objectionable for food packaging: xylene (xylol, C0H4(CH3)2) are the principal Aluminum monostearate. ones. These compounds are of value because of Calcium acetate. the fact that they are excellent solvents. Calcium ethyl acetoacetate acetate. As pointed out by Wilson25 benzol poisoning Calcium carbonate. may result from absorption of benzene by either Calcium stearate. the respiratory tract, the alimentary tract, or Calcium glycerophosphate. probably the skin. Cases of poisoning in human Mono- di- and tricalcium phosphate. beings have been found with exposures to atmos Calcium oleate. pheric conditions as low as 25 ppm. Concentra Calcium ricinoleate. tions of 50 to 100 ppm are considered to be safe Magnesium stearate. for the average person. Individual susceptibility Magnesium glycerophosphate. varies; Acute benzol poisoning is rare. Mon-, di-, and trimagnesium phosphate. As pointed out by Wilson-7 the pathologic Disodium hydrogen phosphate. manifestations of exposure to toluene are a mat Ammonium potassium phosphate. ter of controversy. The conclusions reached by Some of the most efficient stabilizers from the various authors are in decided variance with one standpoint of performance, particularly for the another. Toluene poisoning is probably caused vinyl resins, are the heavy metal salts of barium, by absorption through the respiratory system, strontium, lithium, cadmium, and lead. All of the skin, and the alimentary tract. The absorbed BFG03696 f 20507006 Table II. Suggested Maximum Allowable Concentrations (Parts per million parts of air) Acetone ............................................................ 1000 Acrylonitr.ile .................................................... 20 Amyl acetate ................................................... 200 Amyl (iso) alcohol .......................................... 100 Benzene (benzol) ............................................. 35 Butadiene 1,3 ....................................................1000 Butyl acetate ................................................... 200 of 1.4, and ethylene dichloride of 1.6. According to Davis29 and the U.S. Public Health Service,30 the maximum allowable concentration of carbon tetrachloride is 100 parts per million. According to Elkins31 this level is too high and should be reduced to 50 parts per million. Many of the petroleum distillates are used. Gasoline (unleaded), hexane, heptane, Stoddard solvent, varsol, and naphtha are mixtures of hydrocarbons, paraffins, olefins, cycloparaffins Butyl alcohol ................................................... 100 (naphthenes), aromatics, and other impurities Carbon tetrachloride ........................................ 25 Ethyl acetate ................................................... 400 Ethyl alcohol ....................................................1000 Ethylene dichloride ........................................ 100 Gasoline ........................................................... 500 Heptane ........................................................... 500 Hexane ................... '........................................ 500 Propyl (iso) alcohol ........................................ 400 Methyl alcohol ................................................. 200 Methyl ethyl ketone ........................................ 100 Naphtha (petroleum) .................................... 500 including sulphur. Cracked gasoline may also carry a fairly high percentage of benzol. These substances are frequently referred to by the general name of benzine. This is to be distin guished from benzene (benzol). These distillates are narcotics, and it is possible to produce com plete anesthesia with heavy doses. However, their anesthetic properties are much less than those of the aromatic and chlorinated hydrocarbons. For this reason they may be more desirable for com Perchlorethylene (tetrachlorethylene) ...............200 mercial use. Drinker and associates, in studying Propyl acetate ................................................. 200 the effects of gasoline vapors32 found that con Stoddard solvent ............................................. 500 Tetrachlorethane ............................................. 5 Tetrachlorethylene ............................................ 200 Toluene ........................................................... 200 Trichlorethylene................................................. 200 Xylene ................. 200 centrations from 270 to 500 ppm were tolerable. Neuromuscular symptoms began at about 900 ppm; mild intoxication at 2,000 ppm. Acetone, methyl ethyl ketone, methyl isobutyl ketone, and methyl amyl ketone are also used. In our experience no cases of occupational disease vapors exert a progressive depressant action on have been attributed to the ketones. the central nervous system and the bone marrow. Methyl, ethyl, propyl, isopropyl, butyl and iso Toluene is also a pronounced irritant to mucous amyl acetate may be used. These solvents are not membranes. A factor to be considered whenever considered severely toxic and in most cases the it is employed is individual susceptibility. Ex allowable concentrations are based more on com posure to concentrations of toluene from 200 to fort than on toxic requirements. 500 ppm for six to eight hours will in most per Methyl, ethyl, isopropyl, amyl and butyl alco sons cause tiredness and lassitude. Concentra hol are all used at times in plastics manufacture. tions over 500 ppm for one to three hours are Methyl alcohol is a source of grave injury to definitely dangerous and will cause symptoms at many industrial workers. It has a specific action tributable to depression of the central nervous on the optic nerve, and with long enough expo system and the bone marrow. sure, blindness may result. The action is that of Xylene0 is stated to possess more severe nar inflammation of the optic nerve followed by cotic properties than benzene. Xylene poisoning atrophy. A considerable amount of methyl alco is relatively uncommon because its volatility is hol poisoning was noted during prohibition days lower than that of benzene or toluene. Chronic when wood alcohol was used in large amounts poisoning does occur. There is some evidence that with subsequent optic nerve degeneration and xylene exerts an action on the blood forming blindness. The other alcohols, because of their organs similar to that of benzene. Cases of volatility are not considered to be especially aplastic anemia have been attributed to xylene dangerous. Cases of narcotic poisoning have vapors. There have been some cases reported in been attributed to them but not proved. The German literature of leukopenia and thrombocy higher alcohols, like butyl and amyl, have in topenia with no reduction in red cells. addition an irritant action as well as some poi The commonly used chlorinated hydrocarbons sonous action on the protoplasm. in the plastic industry are: Carbon tetrachloride (tetrachlormethane) Summary CC14. 'J'HE advent of a great industry for the manu- Ethylene dichloride (dichlorethane) C2H4C12. A facture of articles of all kinds made from Tetrachlorethane (acetylene tetrachloride) various chemical compounds has created many C.H2C14. new problems for the industrial physician and Trichlorethylene (ethylene trichloride) CjHCl.-,. the industrial hygienist. Many of the compounds Perchlorethylene (tetrachlorethylene) C2Cl4. used are new.and very little, if anything, is The most toxic of the group is tetrachlorethane, known about their toxicity. Also, since there are having, according to Matruchot,28 a comparative no set formulas or recipes, each plastic article toxicity of 6.0. Carbon tetrachloride is listed by may have a different composition. the same author as having a comparative toxicity This paper attempts to discuss the toxicity of of 2.6, trichlorethylene of 1.0, perchlorethylene the more common compounds now being used in 20507007 BFG03697 plasties manufacture. Resins, plasticizers, stabil izers and solvents are discussed in some detail in regard to their toxic properties. The scarcity of knowledge of the properties of many of the chemicals is sufficient reason for further study. It is not enough for industry to make better things cheaper; it must also make them safely. Resume ^rticles made of a variety of chemical combina tions commonly called plastics have found in creasing favor with the consuming public. Many useful products can be made stronger, better looking, longer wearing and at lower costs em ploying these versatile new materials. The imagi native creativeness of the human mind is evident in our new world of plastics. To create these man made marvels, the research chemists and develop ment engineers have not only used known chem icals but also have created new ones. Unfortunately, many of the chemicals current ly used are known to be highly toxic. Even worse, the toxicity of many of the newer chemicals is not even known. Thus, industrial medicine and hygiene face serious problems both from known and potential toxic hazards. Considerable infor mation has been published concerning some of the chemicals now being used in plastic manu facture, and at the present time many chemicals are undergoing toxicological investigation. The authors of this paper have accumulated information on many of the resins, plasticizers, stabilizers and solvents being used in the manu facture of numerous plastic articles. It will be noted that the information is meager in some instances while in others it is quite complete, but, to our knowledge, this comprehensive summary on the toxicology of plastics has not heretofore been attempted. Among the authors' conclusions is that indus try must maintain strong Departments of Indus trial Medicine and Hygiene to control toxicolo gical hazards. Many industries are diversifying manufacturing activities and entering fields of endeavor for which previous experiences may not have prepared them. Highly toxic chemicals can not be successfully handled in a haphazard man ner and it is essential to invest money for toxi cological investigation, because to be without such programs is foolhardy and more expensive in the long run. No industry can afford to endanger the health of its people by knowingly exposing them to toxic materials. It is not enough for research chemists to dis cover a chemical combination, which will create a new sales masterpiece. The industrial hygien ist must also determine the toxicity of the chem icals involved and designate ways and means of handling them safely. If the sales potential of a new plastic does not warrant toxicological study, then the product should not be produced. Another conclusion of the authors is that much additional toxicological study is necessary on plastics, and it is hoped that the toxicology of plastics can be added to and made more complete, year after year. References 1. Lehman:, Arnold J.: Chemicals in Foods: A Report to the Association of Food and Drug Officials on Current Develop ments. Association of Food < Drug Officials of the United States, Vol. XV, No. 3, July, 1951. 2. Seeler, Albert O.: Clinton. Marshall, Boggs, Joseph, Drinker, Philip: Experiments on the Chronic Toxicity of a Copolymer of Vinyl and Vinylidene Chloride. Unpublished. 3. Patty, F, A., Yant,, W. P., and Waite. C. P.: Acute Response of Guinea Pigs to Vapors of New Commercial Organic Compounds. U.S. Public Health Reports, 45:1963 (1930). 4. Carpenter. C. P., Smith. H. F., and Pozzani, U. C.: The Assay of Acute Vapor Toxicity and the Grading and Interpreta tion of Results on 96 Chemical Compounds: J. Induct. Hyg. & Tox., 31:343. 1949. 5. Reinhardt, R. C.: Handling Vinylidene Chloride: Chem- teal dt Engineering News, 25:2136 (July 28) 1947. 6. Wilson. R. H.. Hough, Glenn V.. and McCormick. Wx. E. : Medical Problems Encountered in the Manufacture of American-Made Rubber. Indust, Med., 17:6 (June) 1948. 7. Wilson. R. H.: Health Hazards in the Manufacture of Synthetic Rubber. 124:701 (March 11) 1944. 8. Dudley. H. C., Neal, P. A.: Toxicology of Acrylonitrile: J. Idust. Hyg. & Tox., 24:27 (February) 1942. 9. Carpenter. C. P.. Shapper, C. B., Weil. C. F., Smyth. H. F.: Studies on Inhalation of Butadiene with a Comparison of its Narcotic Effect. J. Indust. Hyg. < Tox., 26:69, 1944. 10. Rowe, V. K., Spencer, H. C., and Bass, S. L.: Certain Commercial Silicones and Hydrolyzable Silicone Intermediates: J. Indust. Hyg. & Tox., 30:332 (November) 1948. 11. Shapper, C. B., Critchfield, F. H., and Carpenter, C. P.: The Absorption and Excretion of the Solid Polyethylene Glycols. J. Am, Pharm. Assoc., 36:152 (May) 1947. 12. Stokingsr, H. E.: Teflon--A Plastic with an Inhalation Hazard. Occupational Health, 13:86 (June) 1953. 13. Seipter. Joseph: Toxicity of Plasticizers.Unpublished. 1943. 14. Smith, Carl C.: Toxicity of Butyl Stearate, Dibutyl Sebacate, Dibutyl Phthalate, and Methoxyethyl Oleate: A.M.A. Arch. Induct. Hyg. & Occup. Med., 7:4, 310 (April) 1953. 15. Mallettb. F. S.. and Von Haam, E.: Studies on the Toxicity and Skin Effects of Compounds Used in the Rubber and Plastics Industries: A.M.A. Arch. Induct. Hyg. & Occup. Med.. 6:9. 231 (September) 1952. 16. Hodge, Harold C.: Acute Toxicity for Rats and Mice of 2-Ethyl Hexanol and 2-Ethyl Hexyl Phthalate. Proc. Soc. Exp. Biol & Med.. 53:20. 1943. 17. Shaffer, C. B., Carpenter, C. P., and Smyth. Jr., H. F. : Acute and Subacute Toxicity of Di(2-Ethy) Hexyl) Phthalate, J. Induct. Hyg. & Tox., 27:5 (May) 1945. 18. Carpenter. C. P.. Weil, C. S-, and Smyth, H. F.: Chron ic Oral Toxicity of Di(2-Ethy) Hexyl) Phthalate for Rata, Guinea Pigs and Dogs. A.M.A. Arch. Indust. Hyg. & Occup. Med., 8:219 (September) 1953. 19. Halpern, L. K., and Weiss. R. $.: Toxicity of 2-Ethyl Hexyl Diphenyl Phosphate. IV. Skin Sensitization Studies of Santicizer 141. A.M.A. Arch. Induct. Hyg. < Occup. Med., 8:284 (September) 1953. 20. Seeler, Albert O., Clinton. Marshall. Bogcs, Joseph. Drinker. Philip: Experiments on the Chronic Toxicity of Acetyl Tributyl Citrate. Unpublished. 21. Seeler, Albert O., Clinton. Marshall, Boggs, Joseph, Drinker. Philip: Experiments on the Chronic Toxicity of Butyl Phthalyi Butyl Glycollate. Unpublished. 22. Trbon, J. F., Deutra, F. R., and Cleveland, F. P.: Tox icity of 2-Ethyl Hexyl Diphenyl Phosphate: 1. Immediate Toxicity and Effects of Long Term-Feeding Experiments: A.M.A. Arch. Indust. Hyg. A Occup. Med., 8:170 (August) 1953. 23. Treon, J. F-, Cappel. B. S.. and Sigmon. H.: Toxicity of 2-Ethyl Hexyl Diphenyl Phosphate: II. Metabolie Fate in Man and Animals: A.M.A. Arch. Induct. Hyg. & Occup. Med., 8:266. 24. Jacobs. Morris B.: The Analytical Chemistry of Indus trial Poisons. Hazards and Solvents: Chemical Analysis, Vol. 1. 2nd Revised Edition. Interscience Publishers. Inc., New York. 1949. 25. American Conference of Governmental Industrial Hy gienists: Threshold Limit Values for 1954. A.M.A. Arch. Induct. Hyg. & Occup. Med., 9:530 (June) 1954. 2G. Wilson. R. H.: Benzol Poisoning in Industry. J. Lab. & Cln. M<<1. 27:12. 1517 (September) 1942. 27. Wilson, R. H.: Toluene Poisoning. J.A.M.A., 123:1106 (Sec. 25) 1943. 2S. Hamilton. Alice, and Johnstone, R. T.: Industrial Tox icology. n. 63C. Oxford University Press. 1945. 29. Davis, P. A.: Carbon Tetrachloride as an Industrial Haz ard. .1.A.M.A., 123:962. 1943. 30. (Jakakkk, Wm. (Editor) : Manunl of Industrial Hygiene, p. 264. W. B. Saunders Company. 1943, HI. Ki.kjns. H. R.: Maximum Allowable Concentrations: I. Carbon Tetrachloride. ./. Induct. Ilyy. it* Tox., 24:233. 1942. 32. Diunkk.k, P., Yac.lou. C. P.,*nnd Wakren. M. F. : The Threshold Toxicity of Gasoline. ./. fnduxt. Hyp. Tox., 25:225. 20507008 BFG03698