Document MoKrrXmnYzZzRxO9Jd4dMayvL

- Vi.-- ```is'* *J'V'C.-+X?:'>'<%"^- ' rAL HEALTH*';; Amer. In- ' I.: An Immunojup. Med. 1:319, .-, W. D., and ne Toxicity: 1. : and Tolerance istr. Health 14: nt of Tolerance Edema, Amer. J. E. J.; Wagner, danger, H. E.: Mice Following seated at 138th honical Society, ung einer VorKoncentrationen ms, Arch. Exp. ski, 0. J., and deity of Oi-HOi ss. J. 22:21, 1961. :r, W. D., and 'oxicity Studies: aimals Following 4 Arch. Industr. ion of the Acute es of Nitrogen, i :181, 1957. D. E., and Bed: Health Hazards Welding Shop, 58. /. 4, March, 1962 lAW ;;ts.C0DBGSU-1 335 Toxic and Health Effects of Plastics and Resins JOHN A. 2APP, JR. WILMINGTON, DEL / Twenty-five years ago a discussion of the toxic and health effects of plastics and resins would have been relatively easy on 2 counts. There were relatively few syn thetic plastics and resins in common use, and such uses as were common were relatively trivial in comparison with competitive ma terials. World War II gave great impetus to the use of synthetic plastics and resins. On the one hand they were able to replace natural materials, particularly metals and natural rubber, which were often in short supply. On the other hand synthetic materials, e.g., nylon,.turned out to be superior to available natural materials for certain uses. Following World War II, plastics in evitably assumed a greater role in peace time applications. Many of the plastics were not suited to these uses, and things made of plastic were often looked down upon as poor substitutes for the genuine article. This situation, however, soon worked itself out. For one thing, there were important de velopments in technology, and the synthetic plastics and resins actually became better Submitted for publication Nov. 10, 1961. Presented at 26th Annual Meeting of Industrial Hygiene Foundation, Pittsburgh, Oct 25-26, 1961. Haskell Laboratory for Toxicology and Indus trial Medicine, E. I. du Pont de Nemours & Com pany. materials. For another, their proper spheres of usefulness were better recognized, so that the right plastic was selected to fill a given need. It is difficult to define plastics and resins in a very meaningful way. Chemically, they are very large molecules, called polymers, formed by the linking up of small molecules, called monomers, into large cohesive chain like units. If only 1 monomer is involved in forming the polymer, it is called a homopolymer. If 2 different monomers are in volved, the polymer is called a copolymer; if 3, a terpolymer, etc. Polymers can be classified in several other ways. If the monomers simply link up into long chains by joining bonds, and nothing is eliminated in the process, the polymer is called an addition polymer. An example is shown in Figure 1. If the linking up of monomers is ac complished by the elimination of part of the monomeric molecules, the resulting polymer is called a condensation polymer. An example is shown in Figure 2. If the long-chain polymer molecules are not joined laterally to one another, the plastic or resin is usually flexible, because the molecular chains slide against each other when a deforming force is applied. This flexibility can be increased by mixing in G-3-G- H-* a [hO-R-COOhJ- H[ofl-COjn OB (n-l)H20 #thyln polythylj* hydroxy sold polyester Fig. 1.--Addition polymerization. Fig. 2.--Condensation polymerization. 125 ! ar i f. j I?,, i* i? ,!l; If 3: M r=t* I.--Thermoplastic Polymers Z/iRCHIVES 'OF ENVIRONMENTAL HEALTH 2.--Thermosetting Polymers Polyethylene Polystyrene PolyacryUtes PdynMthaerytetes Polyvinyl chloride Polyamide (nylon) TFE floorocwbon resins Saturated polyesters ("Dacron" Phenol formaldehyde resins Amine formaldehyde resins Epoxy resins Alkyd resins Unsatorsted polyester resins It has frequently been stated of the SSi plastics and resins that the molecules are with the polymer molecules an internal so big and so chemically inert that they are . lubricant, known as a plasticizer. also physiologically inert. If ingested, they :. It is characteristic of polymers that they are too big to be absorbed from the gastro soften when exposed to heat and when soft intestinal tract and hence pass through can be made to flow and assume desired unchanged. If placed in contact with the shapes. When cooled, they again become skin, they are too big to/penetrate or react y-' hard. Some polymers, if reheated, become with the skin. If inhaled as dust, they behave soft again; these are the thermoplastic as typically "inert" ^usts do in the lung. resins. Other polymers, when heated for These statements are in all probability true ; the first time, undergo further chemical for most of the molecules comprising the .reactions in which cross links develop be polymer. The exceptions relate in general tween polymer chains, holding them rigid to the oligomers, and in some cases even in the position assumed as a result of the to the monomers, which make up a small first heating. These are the thermosetting fraction of the total polymer molecules. resins, and they do not soften on reheating For example, polyethylene manufactured like the original polymer. Examples of by the high-pressure process came into use thermoplastic and thermosetting resins are as a container for foods about 1946. The shown in Tables 1 and 2. average molecular weight of the polymer When we say that polymers are chains usually ranged from 5,000 to about 40,000. of large molecular weight, no particular Its structure is essentially that of a longdegree of largeness is specified. If only a chain aliphatic hydrocarbon. It is insoluble few molecules are linked together, the re in almost all solvents at room temperature, sultant molecule is called an oligomer. So, although it swells in contact with hydro a polymer is larger than an oligomer in that carbon solvents like hexane or heptane, |. ''. if contains many rather than a few monomer benzene, lubricating oils, and the like. The units. It is also apparent that a polymer may be composed of polymer chains of varying length. When a monomer polymerizes, a chain builds up in length until something terminates the process. Termination may occur sooner in some chains than in others. If the process is random, the final polymer will be a statistical distribution of molecular chains of varying size, and the molecular swelling is due to the penetration of the polymer chains by the solvents. It is no wonder that the U.S. Food and Drug Administration in 1951 listed polyethylene as a suitable resin for use as a food packaging film1 on the basis of its structure and physical properties. By the summer of 1958, however, the Food and Drug Administration learned that commercial polyethylene contained a low weight of the resultant mixture can only be expressed in terms of average and stand ard deviation, of normality or skewness of distribution, etc. In general, the average molecular weight fraction that might become a component of a fatty food contacting the ^?0 polyethylene. When the Food Additives Amendment of 1958 became effective, the Qq molecular weight of the polymer will be of Food and Drug Administration confirmed the order of thousands or millions. the prior sanction status of polyethylene as 126 Vol. 4, March, 1962^ - \TOXIC Zapp BFG37051 ir d of the ecules are it they are sted, they he gastro3 through with the :e or react ley behave the lung, bility true rising the in general :ases even ip a small olecules. aufactured ie into use 1946. The e polymer *-* 40,000. longs insoluble mperature, ith hydror heptane, t like. The on of the It is no and Drug ethylene as packaging icture and vever, the anted that led a low flat become tacting the Additives ective, the confirmed i-thylene as March, 1962 " ga4 V a\ . -> h|?H (CH2)5 C0ja0H (n-l) H20 ' Fig 3.1--Type 6 nyl<4 >_ pallon-oprolotaa Type 6 Nylon : w' - polyepsiloncaprolactam. a food packaging resin only with respect deliberately supplied in an -incompletely ' to its use cm nonfatty foods. It permitted its polymerized state in order that the user ; continued use in contact with fatty foods might complete the process at the site of ^ only on an extension-of-time basis pending application. Examples of this would be the further study and evaluation of the data. acrylic denture materials and the poly- : The sequel to this is that all 13 producers of polyethylene in the United States assembled data on. the chemical identity of the low molecular weight fraction in their various polyethylenes and on the amount extractable by fatty foods. This information enabled the Food and Drug Administration to establish specifications for polyethylenes suitable for contact with fatty as well as nonfatty foods, and a regulation setting forth the specifications was issued in June, 1961.2 This example merely illustrates the fact that polymer molecules are not all of the same large size and that some are small enough to be diffusible from the plastic or resin. As with polyethylene, the low molecular weight fraction is not necessarily harmfut, but its safety must be evaluated. Some plastics and resins may actually contain unreacted monomer. Type 6 nylon, which is polyepsiloncaprolactam, is an example (Fig. 3). The epsilon caprolactam monomer is water soluble, diffusible, and a weak skin sensitizer. It can be removed from the polymer by washing with hot water. Phenol formaldehyde resins as well as other formaldehyde resins sometimes contain free formaldehyde in sufficient con centration to be detectable by odor. The free formaldehyde can be kept to safe limits, however, by adequate curing of the resin. It might be wdl to note at this point that exposure to monomers and low molecular weight polymers is much more apt to occur during the manufacture of these materials urethane insulating materials or lacquers. . '-i ' In the former application, molding powder composed of polymethyl methacrylate is mixed with liquid monomer, an activator, and color. The monomer acts both as a plasticizer for the polymer and as a bonding agent as it itself is polymerized. Since methyl methacrylate monomer is a skinsensitizer, a number of dentists and dental technicians have experienced dermatitis problems. The resulting polymerized denture material, however, has rarely caused any trouble for the patients. Polyurethane resins are likewise often supplied in "prepolymer" form for final polymerization at the site of application. A typical application is that of the polyurethane foamed insulation materials.4 Figure 4 shows how a typical polyurethane prepolymer (I) is formed by the reaction, in the absence of water, of a diisocyanate (usually toluene diisocyanate, or TDI) and a glycol. The glycol now terminates with isocyanate groups (-NCO) and has acquired urethane groups (-RNH COOR'-) in the process. The prepolymer contains a slight excess of TDI. If water and a catalyst are added to the prepolymer, a further reaction takes place as shown in Figure S. This reaction is exothermic. As polymerization takes place the CO2 evolved "foams" the mixture which grows more viscous and rigid under the combined influence of heat and increasing molecular weight and traps the CO2, thusgiving the final cured foam plastic. In th^ thatn during their subsequent use. Thus the manufacturer is more liable to toxicity and 2 0CH-R-NC0 + HO-R *-OH CO health problems from monomers than is the user of the finished plastic or resin. In some cases, however, the plastic or resin is 0CM-R-MHC0* 0 -R-0C0HHi--R-NCO (if!}) ------------------------- o Fig. 4.--Reaction of diisocyanate with polyol. Zapp 127 1 BFG37052 <**# __ rW^4.^5?4^^r-.". --1 33d -^i'0%i1RCHlVES OF ENVIRONMENTAL HEALTH i'^v -* ' -s ... '_ jafcfer* bow a m m MCO (I) + h2o -> afs&io&y---' /' " OCT - * MBCOHH = BCO (II) CO2f> .: VFigf. 5.--Polymerization of pdyisocyanate resin. H^'process, small amounts of TDI monomer g&z&mav be volatilized. . Toluene diisocyanate is not a highly toxic `-.^material, but it is extremely irritating to the `respiratory tract and may cause asthma-like TSf' attacks which begin several hours after [jL-yv exposure and clear up without after-effects ' yy in a few more hours. Repeated exposure to .TDI vapors may produce an allergic i sensitization of the respiratory tract in susceptible individuals. y - Since polyurethane resins are being formed in place on a rather large scale, rV- there has been an unusual amount of interest f* in the definition of the safe upper limit of .^concentration of the monomer in the air, . variously called the Threshold Limit Value, >. Hygienic Limit, or MAC. Largely based on work in Du Pont's Haskell Laboratory,4 the American Conference of Governmental Industrial Hygienists (ACGIH) in 1956 established a tentative Threshold Limit ~ Value of 0.1 ppm for toluene diisocyanate, TDI, and this has prevailed until this year when the ACGIH lowered the Threshold Limit Value to 0.02 ppm. It may be of .- current interest to comment briefly on the respective numbers and the reasons for the : change. Bearing in mind that TDI and other -y similar monomeric diisocyanates are more , < irritating than toxic and that they are capable of producing allergic sensitization, the safe . level in the atmosphere should be that which does not produce primary irritation or - induce sensitization of exposed workers. Our . estimate of such a level, based on animal exposures, was 0.1 ppm, and Ehrlicher in Germany * arrived independently at the same - value. Some cases of respiratory sensitization . have occurred, however, in some plants in which the TDI concentration was supposedly ; maintained at or below 0.1 ppm. It was ' assumed, therefore, that susceptible workers exposed to 0.1 ppm of TDI could become sensitized and the safe upper limit was, accordingly, revised downward to 0.02 ppm. Whether the assumption is valid and the revision justified, I do not know. So far as I have been able to learn, there is no proof that sensitized workers did not occasionally receive gross overexposures prior to be coming sensitized. Only time will tell whether 0.02 ppm will prove to be a more correct estimate of the safe level than 0.1 ppm. The important point, however, is that one should avoid, to the greatest extent possible, exposure to chemicals which are capable of causing allergic sensitization. It is a tricky business, for example, to find out just how much poison ivy you eta pull up with your bare hands before you become sensitized, and persons exposed to the monomeric diisocya nates should take all indicated precautions to keep their exposure at a minimum. The finished cured polyurethane resins are not sensitizers, because any exposed isocyanate groups would react with water vapor in the air and be destroyed. A second health and toxicity problem in connection with plastics and resins arises from the fact that the commercial materials are seldom just collections of big molecules. As was mentioned before, flexibility in plastics is a reflection of the ability of individual polymer chains to slide against each other in response to an applied force. The cohesive forces between polymer chains can be reduced by means of internal lubricants called plasticizers. Usually a good plasticizer can be characterized as a poor solvent for the polymer, which possesses low volatility and hence is not lost quickly from the plastic or resin. Sometimes plasticizers are supplemented by nonvolatile liquids which are not in themselves plasticizers but which can supplement the effect of pias- ticizers by acting as inert diluents. These ^ are called softeners. CO Plasticity can also be enhanced, however, CP in some polymers by copolymerization of the principal monomer with a small amount Q of a second monomer which, while a fixed yj 128 Vd. 4, March, 1962 TOXICH part of th plasticize! Unplas example, be used i water or { by the sebacate, becomes c such thin: and auton recall an lymer of t transparer suspender: which wa: tin maleat cizers* TT that nonp< can becom testifies to component excluded i come into with huma Plasticiz added to p properties, to stabilize tion by lig to retard o Dyes or pi color. Perl and resins to the Fea establishing ingredients polymeric substrates i foods. It plastics an< than just p sider mole evaluating relating to fair to stat problems wl the use of overwhelmii Zapp BFG37053 c ~2.. -* Lw, : 'A;, s NTAL HEALTH''-* pper limit was, 1' o 0.02 ppm. io ,alid and the know. So far as iere is no proof not occasionally s prior to be rime will tell e to be a more afe level than rver, is that one extent possible, are capable of . It is a tricky 4 out just how 1 up with your sensitized, and neric diisocyaed precautions inimum. rethane resins any exposed ct with water oyed. ty problem in ns arises materials !>ig molecules, flexibility in te ability of slide against ipplied force. >lymer chains of internal >ually a good d as a poor >ossesses low prickly from i plasticizers ttile liquids sticizers but xt of plasents. These d, however, :rization of rail amount tile a fixed March, 1962 TOXICITY OF PLASTICS AND RESINS ''J/t 339 part of the polymer chain, acts as an internal plasticizer. x '' ' ' ' ' `\ Unplasticized polyvinyl chloride, for example, is a rather rigid material and can be used for such applications as pipes for water or process chemicals. When plasticized by the addition of organic phthalate, sebacate, or phosphate esters, however, it becomes quite flexible and can be used for such things as raincoats, shower curtains, and automobile upholstery. Perhaps you will recall an early use of the plasticized copo lymer of vinyl chloride and vinyl acetate for transparent wrist watch bands, garters, and suspenders and will recall the dermatitis which was attributed to the use of dibutyl tin maleate and dibutyl sebacate as plasti cizers. The example both points up the fact that nonpolymeric components of a plastic can become health or toxicity problems and testifies to the skill with which such toxic components have since been carefully excluded from plastics which are likely to come into prolonged or repeated contact with human skin or with food products. Plasticizers are not the only materials added to plastics and resins to modify their properties. Chemicals are sometimes added to stabilize the polymer against decomposi tion by light or heat. Others may be added to retard oxidation by atmospheric oxygen. Dyes or pigments may be added to impart color. Perhaps this complexity of plastics and resins can be illustrated by reference to the Federal Register of Aug. 8, 1961, establishing a regulation on permissible ingredients for continuous resinous and polymeric coatings to be used on metal substrates (i.e., can liners) in contact with foods. It amply indicates the fact that plastics and resins may be more complex than just polymers and that we must con sider molecules other than polymers in evaluating health and toxicity problems relating to such plastics and resins. It is fair to state that such toxicity and health problems which have arisen in the past from the use of plastics and resins have been overwhelmingly due to the nonpolymeric components rather than to the basic polymers. There is another area, however, in which health problems have arisen in connection with plastics and resins, and this concerns not the plastics and resins as such but rather their decomposition products under the influence of heat. One of the earliest indications of hazard from this source came from the Cleveland Clinic disaster of 1929, in which stored nitrocellulose base x-ray film caught fire. Dense brown fumes spread through the hospital, and 125 persons were killed. Death appeared, in most cases, to have been caused by inhalation of carbon monoxide and nitrogen oxides,7 both of which were thermal decomposition products of nitro cellulose. Nitrocellulose is an outstandingly hazard ous material so far as combustion is con cerned, but it is characteristic of organic polymers that they will begin to decompose at some critical temperature and thereafter decompose at an increasing rate as the temperature is raised above the critical temperature. Some, like nitrocellulose, will bum freely if ignited; others, like Teflon TFE-fluorocarbon resin will not bum spon taneously but will nevertheless decompose if sufficient heat is applied externally. As plastics and resins find more extensive use as replacements for older materials, it is natural that there be increasing concern lest exposure to excessive heat or fire result in the production of unusually toxic atmos pheres. It will not be possible to cover the pyroly sis products of all plastics and resins in this discussion, but mention will be made of some general principles pertaining to the toxicity of the products arising from any conflagration. Specific mention will be made of polyethylene, of the synthetic textile material Orion acrylic fiber, of certain foamed plastics and natural rubber, and of the Teflon TFE fluorocarbon resins. Conflagrations can be divided broadly into 2 classes, those which are well venti lated, and those which are poorly ventilated. Zapp 129 .0 ill w.; Pcr,ri031 ir .XT' 340 Mmzm 'ENVIRONMENTAL 'health |Siv:;>A. well-ventilated conflagration is .one - in which there is free access of air to the fire, v-': In this event the gaseous products of combustion are dissipated rapidly by the sn^"strong thermal currents, and injury, if it ^^^risoccurs, is almost always due to thermal effects alone. / . =- A poorly ventilated conflagration is one ^S^in which the access of air is restricted. In this case, there are several consequences. ' First, combustioh does not go to completion. !.Sfe-V If the combustible material contains carbon, :^|.>'c'as it usually does, carbon monoxide will be T C,\ formed as well as carbon dioxide. Second, y . there will be a depletion of oxygen in the air in the vicinity of the fire. Third, there will be heat. And finally, there will be special pyrolysis products characteristic of the substances being burned. If injury occurs, it will be due to heat, oxygen lack, and carbon monoxide as well as to the special pyrolysis products. It is my belief, which is based on World War II research with flame throwers,8 that the 3 factors heat, oxygen lack, and carbon monoxide are usually of more overriding importance as toxic factors than the more esoteric special products of combustion. Of course, there may be situations, as in the Geveland Ginic disaster, where the products of a poorly ventilated combustion may be transported some distance by natural or forced ventilation, and in these cases, heat ceases to be a significant lethal factor. This does not invalidate the generalization that gaseous products of combustion are of little importance as lethal factors in a well- ventilated conflagration and that carbon monoxide, oxygen lack, and heat are apt to be the most important lethal factors in a poorly ventilated conflagration, regardless of what material is being burned. Polyethylene may be taken as a partic ularly simple example, in the chemical sense, of a plastic or resin; it is made up of chains of CH2 groups and is therefore a hydrocarbon. It resembles the paraffin waxes but is less of a heterogeneous mixture than the paraffin waxes. It bums slowly in an excess of air, producing CO2 and H20 as the end-products of combustion. If the burning were poorly ventilated, combustion would be incomplete, and CO would be produced as well as CO2. If polyethylene is heated in air to about 250 C it melts, sublimes, and to a degree decomposes with out burning. Animals,,exposed to air passed over the heated polyethylene show signs of respiratory distress and may die. The causative lethal ^gent or agents were not identified in experiments which we carried out some years ago, but it was noted that the air containing the decomposition products of polyethylene would decolorize a dilute solution of potassium permanganate if bubbled through it. This would suggest the presence of unsaturated compounds like aldehydes, which are also formed during the pyrolysis in air of natural hydrocarbons. In summary, polyethylene would present roughly the same health and toxicity prob lems on combustion or pyrolysis as one would expect from paraffin wax or similar natural hydrocarbons. Orion polyacrylonitrile may be looked upon as a polyethylene in which 1 of the 4 hydrogens is replaced by a nitrile group. (Fig. 6). The presence of the multiple cyanide groups on the polymer, as well as the considerable toxicity of the monomer, raised the question as to whether the com bustion of Orion might not result in the release of dangerous quantities of HCN or of acrylonitrile. The Underwriters' Labora tories undertook an investigation of this point* In one type of experiment Orion fabrics were subjected to direct flame in the presence of excess or deficient air. In Acrylonitrile CH Fig. 6.--Orion acrylonitrile. CO poly- 00 O Q:r> Vol. 4, March, 1962 TOA to tl comb woof Tabi F. Polyu Polya Polyu Noopt Babb Polyr Zcrpt BFG37055 rr 1^4c>-r v-Ti 'MENTAL'HEALTH y v -:::^v;A ^ er' -- it "is made up s is therefore a ..-. s the paraffin waxes neous mixture than imms slowly in an r CO2 and H2O as ombustion. If the itilated, combustion ind CO would be . If polyethylene is t 250 C it melts, ; decomposes withposed to air passed lene show signs of d may die. The agents were not which we carried it was noted that mposition products decolorize a dilute permanganate if would suggest the compounds like 0 formed during iral hydrocarbons, aie would present ir " 'oxicity prob1 iysis as one n wax or similar may be looked which 1 of the 4 a nitrile group, of the multiple ymer, as well as >f the monomer, vhether the comiot result in the ities of HCN or writers' Laboratigation of this qieriment Orion direct flame in deficient air. In 6.--Orion polyitrile. >1. 4, March, 1962 trTOXlCTTr OF PLASTICS AND RESINS 4'.; : - . - . * 57 'another type, the Orion fabrics were heated in ah atmosphere of nitrogen in an electric furnace which reached a peak temperature of 600 C. In both types, gaseous decomposition products were collected and analyzed. Similar tests were carried out with fabrics of cotton, silk, acetate and viscose rayon, and wool. . The conclusions of the Underwriters' Laboratories with respect to Orion acrylic fibers were as follows: When these acrylic fiber fabrics bum in an ex cess of air (oxygen excess), the chief constituents of the gaseous products of combustion and thermal decomposition include carbon dioxide, together with small amounts of oxides of nitrogen as re corded in Table V. Under conditions of oxygen deficiency, the combustion and decomposition prod ucts of the acrylic fiber fabrics include carbon dioxide; and small amounts of carbon monoxide, hydrocyanic add, ammonia, and oxides of nitrogen. When the acrylic fiber fabrics are subjected to thermal decomposition (pyrolysis) in atmospheres of nitrogen (air absent) the volatile products in dude relatively large amounts of hydrocyanic acid, ammonia, hydrogen and methane, together with smaller amounts of unsaturated hydrocarbons as shown in Table VI. Both silk and wool behaved similarly to the Orion fabrics in that relatively large amounts of HCN were evolved only when the pyrolysis was carried out in a nitrogen atmosphere. The final conclusions of the Underwriters' Laboratories were as follows: The fire hazards of textile fabrics made from these, acrylic fibers are in a dass with those pre sented by cotton, acetate rayon, and viscose rayon fabrics of similar weight and weave. The life hazards of the combustion and thermal decomposition products of these acrylic fiber fab rics under fire conditions are judged to be similar to those presented by the fumes evolved during combustion or thermal decomposition of silk or woolen fabrics. V j-'\ - - fi. . ' 4. * ,.'341, ; 'V ' , This illustrates several things. The syn-' thetic fiber material Orion polyacrylonitrile, like other plastics and resins, does decompose ' under the influence of heat; its decomposi-/ tion and combustion products are toxic.' But the same statements apply to the natural polymers silk and wool and cotton, and the over-all hazard from the combustion and decomposition of Orion is judged to be similar to that from silk or wool. The substitution, therefore, of a synthetic plastic or resin for a natural one does not neces sarily increase the hazard that already existed with respect to the natural materials. A similar question arose about the safety of various synthetic foam plastics as com pared with natural rubber. To answer this question we carried out experiments with foamed polyurethane, polyvinyl chloride, neoprene, and natural rubber.4 The results are shown in Tables 3, 4, and 5. It can be seen from Table 3 that polyvinyl chloride foam was the least thermostable, in that it experienced 43% weight loss and killed 2 of 4 rats at an exposure tempera ture of 200C. Foamed polyurethane, neoprene, and natural rubber all decomposed to a certain extent at 250 C, and all produced some deaths in exposed animals (Table 4). At 560 C decomposition was essentially complete within 10 minutes except for neoprene (Table 5). Since the samples were smaller in this case than in the exposures at 200 C and 250 C, no deaths occurred except for 1 animal exposed to polyvinyl chloride. In all cases death was due to pulmonary congestion and edema regardless of the foamed resin responsible. Again it can be seen that certain synthetic foamed plastics and resins are similar to a Table 3.--Pyrolysis of Elastomeric Foams at 200 C for 6 Hours Table 4.--Pyrolysis of Elastomeric Foams at 250 C for 6 Hours Foam Polyurethane A Polyurethane B Polyurethane C Neoprene Robber latex Polyvinyl chloride Sample Wt,, Qm. 5.07 6.03 5.07 5.53 5.03 4.70 % wt. Loss 5.3 4.6 3.6 8.1 3.6 43.3 Mortality 0/4 0/4 0/4 0/4 0/4 2/4 Foam Polyurethane A Polyuratbine B Polyurethane C Neoprene Robber latex Sample Wt., Om. 0.85 6.20 0.72 5.07 OjOT Loss 40.8 20.5 26.5 45.4 160 Mortality 1/4 1/4 0/4 1/4 4/4 Zapp 131 1 m Iff I, BFG37056 ir VjV' - Z. J=V?Vj 342 ---------------------------- .,,-...,. --** ARCHIVES 6f' ENVIRONMENTAL HEALTH Table 3.--Pyrolysis of Elastomeric Foams at 560 C for 10 Minutes ' Fom Polyuiethane A Polyurethane B Polyurethane C Neoprene Rubber latex Polyvinyl chloride 8ampie Wt., Qm. 2.00 2.00 2.00 2.00 2.00 2.00 %wt. Lax 100 07.3 100 75.4 93.6 S6.7 Mortality 0/2 0/2 0/2 0/2~ 0/2 1/2 s foamed natural product with respect to hazard from thermal decomposition prod ucts. A history of safe use of the natural product would imply that a similar history of safe use could be anticipated for the synthetic materials. One should not make the assumption that - all synthetic plastics and resins will be as safe as any natural material they might replace. But neither should one assume that the natural materials give harmless pyrolysis products because they have proved to be free , from a practical hazard in actual use. In ' judging the safety of a synthetic resin for > a proposed use. the hazard from combustion or thermal decomposition should be com pared under equivalent conditions with that of alternative materials which have, if possible, a history of similar use Finally, it may be of interest to discuss briefly the hazards of combustion or thermal decomposition of the Teflon TFE fluoro carbon resins, both because the volume of Our correspondence indicates a lively current interest in them and because of certain interesting features of the story. Table 6.--Acute Toxicity of Tetrafiuoroethylene Structure CFp=CF, Acute Inhalation Toxicity lor Rats LCn, ppm * 7. ' 40,000 * Data from studies at Haskell Laboratory; 4-boor exposure. The Teflon TFE fluorocarbon resins are analogs of polyethylene in which all of the hydrogens of polyethylene are replaced by fluorine atoms. The monomer, tetrafluoroethylene, while more toxic than ethylene, is still quite low in toxicity, the LCso being 40,000 ppm for 4-hour exposure of rats (Table 6). It polymerizes readily to poly mers of very large molecular weight, which are characterized by their extreme chemical inertness and thermostability. Male and female weanling rats in our laboratory fed diets containing 25% of finely ground Teflon TFE resins for 90 days showed no signs of toxic effects and no pathological changes detectable by gross or microscopic examination of the tissues. Teflon TFE resins are among the most thermostable of all the synthetic plastics and resins, being rated for continuous use at 260 C. At this temperature the weight loss is from 0.0001% to 0.0006% per hour (Table 7), depending on the type resin. Since the TFE resins soften at 327 C, the melting point of lead, they are not likely to be serviceable for continuous use at or above this temperature, but they can stand brief exposures for short periods of time to temperatures as high as 540 C. The TFE Table 7.--Weight Loss and Ventilation Recommendations for Teflon Fabricated Resins Above 450 F Temperature rC Initial Weight Loss, %/Hr - Teflon 1,5,7TFE Resin Teflon 6,3(h TFE Resin Teflon 100FEP Resin 450 230 0.00005 to 0.0001 to 0.0001 0.0002 500 200 0.0001 0.0000 550 290 0.0003 000 320 0.0005 0.0015 0.0046 650 340 e.oois 0.014 700 370 0.004 0.002 * 750 400 0.000 0.08 800 425 0.15 0.15 0.0004 0.001 0.01 0.08 0.08 0J Air Recommendations Cu. Ft/Min/Lb Resin Teflon 1, 5,7TFE Resin Teflon 0,30TFE Resin Teflon 100FEP Resin 0.12 0.50 0.86 0.21 0.66 1.2 4.2 9 18 325 1.3 3.5 10 33 73 180 325 2.1 21 42 180 650 Note: Air recommendations represent tbe volume ofair to reduce faaeoot products to levels found safe through long experience In processing Teflon resins. 132 Vol. 4, March, 1962 BFG37057 tr 'L HEALTH fiwyroethylene '/; . -or Rats a* -hoar exposure. resins are all of the tplaced by etrafluoroethylene, -Ceo being ; of rats to polybt, which chemical tale and tory fed ground wed no lological roscopic le most plastics y~ use i *s r hour resin. C, the rely to above brief ne to TFE 50 F ssin 100wiu ce In 962 ^pHt TOXICITY OF PLASTICS AND RESINS,., ":C . *'Tr-'.' ppjie^.'v."1?;K 343 resins do not' liquefy on exposure to heat '' occurrence has followed the smoking of but decompose by giving off gases and tobacco contaminated with dust or particles particulate matter commonly referred to. as . of Teflon. In the minority of cases it has sublimate. If thermal decomposition is followed close proximity to freshly sintered carried out in the absence of air, more than Teflon articles as they have been removed 95% of the decomposition products is the from the sintering oven. monomer, tetrafluoroethylene.10 If carried In the ordinary course of events one would out in the presence of air, the monomer study polymer fume fever in the laboratory is still the major decomposition product, but by producing it in experimental animals at temperatures from 200 C to 400 C small breathing air drawn over Teflon resins amounts of other fluorocarbon gases of 3 heated to various temperatures. One would to 5 C atoms, HF, and silicon tetrafluoride find the lowest temperature at which the have been detected. At about 400 C small syndrome occurred, and one would analyze amounts of a highly toxic C compound, the pyrolysis products at that temperature perfluoroisobutylene, begin to appear, but and would identify by the process of elimi this gas has not been detected below nation the causative agent. One could then 380 C.11-12 determine the threshold concentration of the Teflon TFE resins can be ignited by agent needed to produce the polymer fume flame, since the gaseous decomposition fever and could then estimate a Threshold products will bum at 690 C, but once the Limit Value or MAC for man. Unfortu flame source is removed, the Teflon itself nately, experimental animals do not get will not continue to support combustion. The polymer fume fever any more than they get ultimate combustion products are CO2, CF4, metal fume fever, so this avenue of approach and HF. No free fluorine gas has been was closed. detected among the pyrolysis or combustion On a priori grounds, one could assume products of Teflon, and its formation is not that the likelihood of getting polymer fume favored by thermodynamic considerations.12 fever would depend (1) cm the temperature All of the above would lead one to con of the Teflon resin, because this determines clude that heated Teflon TFE resins should the decomposition rate; (2) on the quantity not present an appreciable life hazard, and of Teflon being heated, because a large this has been borne out both by laboratory quantity of Teflon at a given temperature experiment and by a history of use covering might release as much of the causative more than a quarter of a century. To the agent as a smaller quantity of Teflon at a best of our knowledge, no one has ever higher temperature, and (3) on the time been killed by exposure to the thermal duration of exposure, since this would decomposition or combustion products of determine the amount of contaminated air the Teflon resins. taken into the lungs. However, the Teflon resins do present on Since industrial processors of Teflon exposure to heat a unique toxicity and resins may handle many pounds per day, health problem which became evident even it was felt that a conservative recommenda before the product became commercial. tion would be that one should provide Sufficiently hot Teflon gives off something ventilation if Teflon were heated above the which when inhaled produces in man a temperature at which pyrolysis is just condition like metal fume fever. It has detectable. This was estimated to be roughly been variously called polymer fume fever18 200 C or 400 F. At or below this tempera or "the shakes." Like metal fume fever, it ture the quantity of Teflon handled and the resembles influenza so far as symptoms are exposure time should be irrelevant, since concerned, and it passes off without treat the Teflon simply wouldn't be giving off ment or after-effects in a matter of hours pyrolysis products. This, then, was the basis or at most a day or two. In most cases its for Du Pont label warnings to provide .~ -.PnrVl . i: !> Zapp 133 ^^^Sf4v;?S^r%' ^v$s "op'enVJronM'^T^mealth :J*M;i^!^5.T*i Q L//u>4nf.'/.i 0^i#^A^-'--it^tMilfMA /vau- *Ijm. 5 Table 8.--Mortality Ratios- -Resulting from the Toxicity Tests on Various Polymer-Insulated f, ' Wires .:' V'l' f * ^ rv\ : H-'r; l' --* ,Wir* Insulation ` SfficoM rubber V Nytoo-polyvinyl chloride r*' Polyvinji chloride -.V " Kel-P Pyrolysis Temperature 200 C 280 0 300 C 0/2 0/2\ 2/2 0/3 0/3 0/2 0/2 0/2 0/2 0/2 0/2 2/2 -- 0/2 2/2 ;^SS4."-Cventilation or respiratory protection if the W > Teflon were heated above 200 C or 400 F. . It was directed to people handling large .'p^V'quantitie8 of Teflon in industry. For such purposes the recommendation is adequate ys^Ec but perhaps overconservative, because the 2 Vi ' conditions under which polymer fume fever -V is known to occur involve much higher ?' > temperatures, 370-430 C in the sintering V operations and perhaps up to 538 C in burning tobacco. On the other hand, the quantity of Teflon consumed in a burning V cigarette was bound to be small and yet V; was capable of evoking the syndrome. V? In the intervening years little more has V. been learned about polymer fume fever. ' v We now suspect that the causative agent :>V has a very brief life time and that a short -; - travel path from source to lung, ideally, as v in smoking, is an important factor. We have .. obliged a dog to "smoke" repeatedly through -- ___ ____ 1 _ _ '11__ __ _i__"_* - a face mask cigarettes containing up to 200 mg. of Teflon. It produced neither the polymer fume fever nor any other observable harmful effect. We conclude from this that there is a wide margin of safety between the quantity of Teflon producing the polymer fume fever in man and that which might cause more drastic or lethal effects. We are inclined to suspect the particulate matter evolved during the pyrolysis of Teflon more than the gases, simply because metal fume fever is caused by a particulate. It would' undoubtedly be much more satisfying if we could both identify the causative factor of the polymer fume fever and assign an MAC value to it. The American Conference of Governmental Industrial Hygienists has, in fact, made 2 attempts to supply at least a number. In 1960 they assigned a tentative threshold limit value of 0.005 ppm to Teflon pyrolysis products without specifying what products. In the 1961 list the tentative value is 0.05 mg. per cubic meter "as F." I know of no scientific basis, however, for either of these numbers. In a laboratory situation one can, of course, kill animals by exposing them to the pyrolysis products of Teflon resins. Table 8 compares the toxicity of the pyrolysis products of Teflon and other resins used as wire insulation materials. The toxicity of the Table 9.--Per Cent Mortality in Animals* Exposed to Pyrolysis Products from "Teflon" 6 TFE Resin Simple No. OF-* OFT EF1 EF-* EF-S SF-4 300 0 0 ot -- 380 25 79 100 0 8 0 Of Pyrolysis Temperature, C 375 o' Rite 9 Rats Mice Rabbits aaloes pigs -- 63 -- -- -- 400 -- -- ot 0 425 * Unless otherwise Indicated, mortality Bfure* lie for rats, t Exposure included 30 <?, 3 9 rats; 10 9 ala; 4 tf table* pigs; 1 <?, 1 9 rabbit. t On* of two (nine* pits died. OE indlata production prior to 1958; BF. current production. 134 Vol. 4, March, BFG37059 'NT rr  -'; :*' ^SzZ-V&S&Sk - -'V*^-* .... _ _ . MENTAL HEALTH: r2^!1 taining up to r. ed neither the my other observable Iude from this that of safety between m producing the aan and that which c or iethal effects, ect the particulate the pyrolysis of :es, simply because d by a particulate. be much more both identify the rfymer fume fever ralue to it. The yf Governmental . in fact, made 2 ist a number. In ive threshold limit Teflon pyrolysis g what products, ive value is 0.05 I know of no ir either of these ne can, of fc 0 them to the a resins. Table 8 : the pyrolysis :r resins used as ie toxicity of the cts from 4, March, 1962 'i-TOXlC/T m PLASTICS ANHRESINS,^m0r;^ 345' Teflon resins is not* outstanding. It' is interesting also that improvement in proc essing techniques over the past few years has made it possible to prepare tetrafluoroethylene monomer of higher purity than heretofore and has resulted in a significant increase in the temperature at which the polymer can kill laboratory animals. This is shown in Table 9.. There is one other item about the health and toxicity hazards of the Teflon resins which illustrates a human frailty rather than a property of the resin. Sometime in the middle 1950's there arose a rumor that a machinist had smoked a cigarette con taminated with a little Teflon and had subsequently died. In its most extreme form the rumor stated that the machinist took one puff and that his lungs filled up with fluid, and he died within 5 minutes. It is interesting that the vehicle by which this rumor spread was official safety bulletins issued by responsible industrial concerns and by mili tary installations. In no case did a bulletin state that the fatality had occurred in the company or installation issuing the bulletin. An aircraft plant on the West Coast, for example, attributed the incident to a certain eastern Air Force installation. Another Air Force installation attributed it to the aircraft plant on the West Coast. In no case were we able to pin down the alleged event to an actual occurrence. In 1958 the Inspector General, U.S. Air Force, issued the follow ing statement: "Although the rumor appeared in several local Air Force publications, a complete investigation by the Air Force Medical Service has proved it to be completely unsub stantiated. There is no known case of Teflon toxicity which has occurred in Air Force or Air Force-Contractor facilities."14 Within the past 12 months the same old rumor has enjoyed a remarkable resurrec tion. It appeared, for example, in at least 3 safety bulletins issued in the Pittsburgh area as well as in other sections of the country and again including some Air Force installa tions. The features were identical with the earlier cycle. The alleged death never occurred in the facility issuing the bulletin" whose authors copied the story from some one else's bulletin or based it on verbal information from someone who had seen or heard of such a bulletin. One company quite recently copied the story from a bulletin long since disavowed by its origi nators and sent 137 copies of its version to locations in the United States, Canada, and Mexico. And while this company states that each of these locations has since received a retraction, one can predict that the original will live longer than the retraction. On July 13, 1961, and again pa Oct. 20, 1961, the U.S. Air Force reiterated, in a message to all Air Force installations, the fact that the rumor had never been substantiated in spite of thorough investigation. But in spite of all this, the rumor marches on. The latest example, to my knowledge, appears in the Oct. 21, 1961, issue of the Canadian Medical Association Journal18 as a letter to the editor over the signature of an industrial physician from British Columbia. This letter contains verbatim chunks from a safety bulletin issued in New York in October, 1960, and rescinded in December, 1960. The author states that his information is derived from a publication of the British Columbia Fire Chiefs' Association, and he apparently was unaware of the ultimate source of his words. The Journal editorialized on the letter, comment ing, "When a hazard is reported... sufficient evidence must be given to allow the reader to judge, on the spot, whether the conclusion is justified. These criteria have been ful filled . . . in . . . [the] letter that appears elsewhere in this issue." The human frailty illustrated by this recital is, of course, our readiness to accept and repeat rumors without checking the facts, simply because the rumor sounds credible. It is not confined to matters of health and toxicity but is perhaps accentuated in that field, to which many popular fads ] and fancies bear witness. It has been ' encouraging, however, to find that many ^ industrial hygienists, toxicologists, and , physicians have been quick to question the I Zapp 135 Uggy BFG37060 i *ilf II If ;! ' !i ! V Ji. > KM Jr" i* h I ' ' 1! ' ; 5 i:- h < V- - .. fl;.. tJi u-Ml feps trlsj ! |:s | . i4 i- , . *1rr* 1t . U .H 346 :;s4 WM. s&* ^ARCHIVES OF ENVIRONMENTAL HEALTH accuracy of the rumor and have been" of ife great assistance in securing its retraction. It has not been possible in this discussion te to cover systematically the health and toxicity aspects of all of the synthetic plastics and resins, and I have sought instead to illustrate broad areas with a few specific examples. Additional information can be found in the review articles of Schwartz,1* Harris,17 and Wilson and McCormick18 as well as in the Plastics Safety Handbook11* issued by the Society of the Plastics Industry and the National Safety Council. As a class, the plastics and resins are not as exempt from health and toxicity problems as one might have supposed them to be on the grounds of their large molecular weight and chemical inertness. There are problems of monomers, of low molecular weight fractions, of adjuvants, and of thermal decomposition and combustion products, and we must be alert for them. The recognition of problems, however, is the first requisite for their solution, and the synthetic plastics and resins of today are much safer than their predecessors. - It is likely that plastics and resins will continue to find expanding uses in our technology. With sufficient effort it should be possible to make sure that they will be as safe as, or safer than, the older materials which they will be replacing. John A. Zapp, Jr., Haskell Laboratory for Toxicology & Industrial Medicine, E. I. du Pont de Nemours & Co., Wilmington, Del. REFERENCES 1. Lehman, A. J.: Chemicals in Foods: A Re port to the Association of Food and Drug Officials on Current Developments, Bull. Ass. Food Drug Off. 15:82, 1951. Z Larrick, G. P.: Food Additives, Fed. Reg: 26:5226 (Pt 121, June 10) 1961. 3. Moncrieff, R. W.: `Artificial Fibers, New York, John Wiley & Sons, Inc., 1954. 4. Zapp, J. A., Jr.: Hazards of Isocyanates in Polyurethane Foam Plastic Production, A.M.A. Arch. Industr. Health 15:324, 1957. 5. Ehrlicher, H.: Industriehygienische und arbeitsmedizinische Massnahmen bei der Verwendung von Isocyanaten (`Desmodur'), Arbeitsschutz 12: 276, 1956. 6. Zeisler, E. P.: Dermatitis from Elasti-Glass Garters and Wrist Watch Straps, JA.M.A. 114: 2540, 1940. 7. The Hazard of Toxic Gases from Combustion of Roentgen-Ray Films, Editorial, J.A.M.A. 92: 1764, 1929. 8. Zapp, J. A., Jr.: The Toxicology of Fire, Medical Division Special Report No. 4, U S. Army Chemical Corps, 1951. 9. Underwriters' Laboratories: Miscellaneous Hazard 5148, (Oct ,16) 1960. 10. Madorsky, S. L.: Thermal Degradation of Polymers, S.P.E.J. 17:665 (July) 1961. 11. Am. lnd. Hyg. Assoc., Hygienic Guide Series: `Teflon' TFE Fluorocarbon Resins and Their Decomposition Products, Industr. Hyg. J. 20:436, 1959. 12. Handling and Use of Teflon' Fluorocarbon Resins at High Temperatures, Polychemicals Department, Wilmington, Del., E. I. du Pont de Nemours & Co., 1961. 13. Harris, D. K.: Folymer-Fume Fever, Lancet 2:1008, 1951. 14. Inspector General, U.S. Air Force: Rumor of Death Caused by `Teflon', TIG Briefs 10: (6) March 17, 1958. 15. Mack, G. J.: Toxicity of Decomposition Products of Teflon,' Canad. Med. Ass. J. 85:955 (Oct 21) 1961. 16. Schwartz, L.: Dermatitis from Synthetic Resins, J. Invest Derm. 6:239, 1945. 17. Harris, D. K.: Some Hazards in the Manu facture and Use of Plastics, Brit J. Industr. Med. 16:221, 1959. 18. Wilson, R. H., and McCormick; W. E.: Plastics--The Toxicology of Synthetic Resins, Industr. Med. Surg. 24:491, 1955. 19. Plastics Safety Handbook, Society of the Plastics Industry and National Safety Council, New York, Soc. of Plastics Industry, 1959. w < 136 Vol. 4, March, 1962 tr