Document DR5be4RGV9o1EVjnQ4q7kG44

0**ftf*r Things for B* 11*.*r Livmnq , . . through Chemistry FREON-5 PROPELLENTS TOXICITY OF PROPELLENTS By-. Fred T. Reed "Freon" Products Laboratory E. I. du Pont de Nemours & Company REPRINTED BY PERMISSION FROM THE OCTOBER 1960 ISSUE OF AMERICAN PERFUMER *0 00 Q uj Tst animals bing exposed to propoilent gas. The propellent h lead through a flow meter into a mixing chamber. Here, 20% by volume is mixed with a measured amount of air, and the whole run through a test chamber with the animals. Toxicity of Propellents I)I the mem property requirements which -in aerosol propellent must meet, certainly low toxicityheads the list. Vapor pressure, boilinj point, solvent power and flammability are critically important prop erties, but even if these properties were ideal, a propellent material would be completely unaccepta ble if it did not have a low order of toxicity. In the discussion which follows only those propellents are considered which meet this rather broad requirement of low-order toxicity. The primary concern in considering toxicity of aero sol propellents is inhalation. In addition, certain other areas are of interest, such as ingestion toxicity, skin sensitization and toxicity of decomposition prod ucts. In the last case, this usually is important only as thermal decomposition, as would occur when an aerosol product is sprayed into an open Hame. When chemical decomposition of the propellent occurs in the container, the product is normally unacceptable for its intended application and thus would not be marketed. Of the various types of toxicity men tioned. only inhalation toxicity has been extensiveU studied tor the manv compounds which ire used as By Fred T. Reed E. !. du Per; de Neo-cms i propellents. The most detailed information available covers the tluorinated hydrocarbon propellents ( Ref. 1 ). The Underwriters' Laboratories have investigated several of the tluorinated hydrocarbons. Their find ings are reported as jroup classifications. Tables II and III jive these jreup classifications tor all the common propellent.', uni some or die les.-. common 'propellents, fable !! s -mended r i retotvnee table to ji\e some idea >i da- ".'ne\ h ivini'oiiul' which EID11832 would fall into the very low (more toxic) Underwrit ers Laboratories classifications. Common materials with which the reader would normally be familiar were selected and, as is obvious, these materials list ed in Table It would be completely unacceptable as propellents. In the case of methyl chloride, CH:1C1. special handling conditions would be necessary be cause of its toxicitv if it were used as a propellent. The definition of the Underwriters Laboratories classes are 'risen in Table I. It is well to remind the reader at this point that this classification is based on inhalation toxicity onlv. Further details on this classification can be found in Ref. 1 and the refer ences contained therein. Where no information is available a blank space is indicated. Probably the most interesting point to note in Ta ble III is the fact that Propellents 12, 114, 114a, 152 and C31S are grouped in the highest classifica tion and indeed are less toxic than carbon dioxide. The latter normally constitutes a substantial percent age of the gases in the lungs which makes it quite apparent that those materials classified in Group 6 would be completely free of any inhalation hazards in their normal use as propellents. It is also worth noting that most of the compounds listed in Table III fall in a classification as high as carbon dioxide. Those few which fall below carbon dioxide, such as methylene chloride, still present no hazard in the quantities which are normally used in an aerosol product and in the manner in which the consumer uses the product. It would be advisable at this point to remind'the reader that none of these compounds will support life. Thus, should any situation occur where the oxy gen content of the atmosphere reaches such a low level as to fail to support life, then any of these compounds, if it is the only other gas present, be comes a serious hazard. This is a somewhat cumber some wav of saying that any of these propellents will cause suffocation if insufficient air is present. This becomes a problem onlv to the manufacturers of pro pellents and loaders of aerosol products. One might visualize the situation where a workman is asked to clean a tank which previously contained one of these propellent materials or possibly a solution of mate rials. including one of these propellents. The tank will certainly be filled with the vapors of the pro pellent and it is very likelv that essentially no air will be in the tank. Unless the tank is '-veil ventilated or the worker is wearing an air mask (not a gas mask '. he will surely suffocate. In addition to the Underwriters' Laboratories clas sifications a very useful tool in determining the in halation toxicity of the vapors of a liquid is to refer to the "Maximum Allowable Concentration'' ( M.A.C.) published in various references on safety. An ex cellent source of listings of M.A.C. values are those given by the American Conference of Governmental Industrial Hvgienists. These values are expressed as parts per million by volume of gas in air. It should further be explained that M.A.C. values are those levels of v apors which are harmless to humans under conditions or continued dailv exposure year in and year out. rims, they would be levels at which work ers eouid la' exposed to these gases throughout their working life time without injury. M.A.C. values are listed in Tables 11 and 111 for those compounds where the values have been published and a reasonable degree of accuracy indicated. Values listed in paren theses are extrapolated values. In the cases where this occurs in Table 111 the values are undoubtedly correct. The reader will note that none of the M.A.C. values listed exceed Lbl/O ppm except carbon dioxide. It has been the practice in reporting M.A.C. values that no compound be listed with a value exceeding 1,000- Carbon dioxide is a special case since it is a component of exhaled breath. As might be expected, some discrepancies occur between the Underwriters' Laboratories classifications and the M.A.C. values. From a practical standpoint this is of no importance to the marketing of aerosol products. It is quite un likely that anyone would consider using a propellent whose M.A.C. value is less than 100. Such a pro pellent would certainly place it in an Underwriters' Laboratories class of four or less. In addition to inhalation toxicity, ingestion toxicitv is becoming of greater interest to the aerosol field. Food products are already being marketed and many new ones contemplated. Included in Table III is a tabulation of approval by the Food and Drug Admin istration for the compounds listed. As yet, none of the halogenated compounds have been approved. The hydrocarbons, propane and butane, and the com pressed gas propellents, carbon dioxide, nitrous ox ide, nitrogen and air have all been approved. While the latter two compounds have not been specifically mentioned in any FDA listing, the writer assumes that there would be no question of their use since these gases normally occur in all food products. To the writer's knowledge, the only halogenated compound for which FDA approval is being sought is "Freon-Col 3". The Du Pont Company has sub mitted data to the Food and Drug Administration covering ingestion toxicitv studies with this compound and approv al is expected by mid-1960. The most difficult problem to overcome in obtain ing acceptance of the commonlv used propellent ma terials. namely the fluorinated hydrocarbons, is the generation of fluoride ion through hydrolysis on long term storage of aerosol food products with these pro pellents. While no acceptable tolerance level for fluo ride ion has been stated by the Food and Drug Ad ministration. it is almost certain that the generation of more than one or two ppm of fluoride ion per year would be unacceptable. This is an extremely difficult requirement to meet and it is very unlikely that any of the fluorinated hydrocarbons now being used by the aerosol industry could meet this require ment. even though some of them, such as Propellent 114, exhibit very low hydrolysis rates even in the presence of the acidic medium found in some food products. Little data are available on skin sensitization of the commonly used propellent materials. However, the writer is aware of no cases of skin sensitization caused by propellents despite the tremendous ex posure through the use of aerosol personal products. An obvious reason mr this lack of data is the in ability to conduct 'iic:-. tests because these materials are so volatile. Rabbit- '..- vsts be the Du pint (Tim- EID11833 pany , Bt-t. la ) have shown that the Propellents 12, It anil 114 cause no reaction. These tests were con ducted using a solution of the propellent in mineral oil at atmospheric pressure. Because of the low solu bility of the propellents at atmospheric pressure, the concentration of propellent in the test solution was necessarily low. Nonetheless, this would represent realistic conditions. All or the liquefied propellents are potential re frigerant, and as t.Oe render is aware, some of them are wide!;.' used as commercial refrigerants. This fact raises an important precaution which should be con sidered in handling and marketing aerosol products. If a workman or the consumer is sprayed by gross quantities of liquid propellent, freezing of the skin is a definite possibility. This is more often a problem with the workman than with the consumer since the consumer has considerable control of the aerosol as it is applied. Should he tend to spray an excessive quantity of the aerosol on his skin, he would be given adequate warning by the immediate chilling affect. It would certainly be wise, however, for the marketer of personal products to include on the label a warning against excessive spraying, with particular emphasis on spraying in the eyes. A final problem concerned with the toxicity of aerosol propellents is that arising from the decompo sition of the halogenated propellents in an open flame or on exposure to very hot surfaces. Considerable information on this problem can be obtained in Ref. 1. The main products of thermal decomposition from the halogenated propellents are. halogen acids, car bon dioxide and traces of phosgene. Phosgene is quickly hydrolyzed to carbon dioxide and hydrochlo ric acid. The literature indicates that the toxicity of phosgene and the halogen acids are essentially equiv alent. Phosgene, probably because it was used as a war gas. has often been stated as the real danger of decomposing halogenated propellents. This is not true. The halogen acids are equally as dangerous and are present in considerably greater quantities. Fortunately, thermal decomposition is not a serious problem. The halogen acids are so irritating that, even at concentrations below any seriously toxic level, a person normally cannot remain in such an atmos phere. For example, should a housewife spray an aerosol insecticide directly into an open gas flame in her kitchen for a sufficient period of time to gen erate quantities of decomposition products, she would be driven from the room immediately by the irritating effects of the halogen acids. If the reader is interested in exploring this problem in greater de tail. he is referred to Ref. 1 and the references con tained therein. In summary, it appears that the commonly used propellent materials present no hazard from inhalation. As a rough guide, those compounds falling in LTnder-. writers' Laboratories classification of 5 and 6 or having M.A.C. values above 500 appear to be perfectly safe to use. Borderline conditions probably occur at Underwriters' Laboratories class -4 and M.A.C. values of 100-500. Any materials rated below these values would wiidouhtediv be unacceptable. For aerosol products which art' to be untested, it would appear that the formulator is limited to the compressed gas es indicated in Table III. The remaining two general areas of toxicity, skin sensitization and thermal de composition products, do not appear to be serious problems. Underwriters' Laboratories Classification 1 2 3 4 4-5 5a 5b 6 Table I Definition 0.5 to i vol. % serious injury in 5 minutes 0.5 to 1 vol. % serious injury in 30 minutes 2 to 2.5 vol. % serious injury in 1 hour 2 to 2.5 vol. % serious injury in 2 hours Less toxic than 4 and more toxic than 5 Much less toxic than 4 bur more toxic than 6 Data indicate classing as 5a or 6 20 vol. Vo no injury in 2 hours Compound SO a nh3 ecu CH3CI Table li Underwriters' laboratories Classification 1 2 3 4 Maximum Allowable Concentration 10 ppm 100 25 100 Table 111 Propellent Underwriters' Laboratories Classification n, cci-f 12, CCI2Fj 21, CHCUF 22, CHCIF2 30, CH2CI2 113, ccif3cc:-f 114. CCIF2CC!F; 114a, CCUFCFj 142b. CH ,CCiFi 152a, CH:CHF2 160, CH]CH2CI 1140. CHh=CHC 5a 6 5 5a 4-5 4-5 6 6 5a 6 4-5 (6) Maximum Allowable Concentration 1,000 ppm 1,000 1,000 1,000 500 (1,000) 1,000 (1,0001 1,000 500 Food and Drug Administration Approval No No No No No No No No No No No No C318, CFjCFiCFjCF:! co3 N;0 n2 Air Propane n-Butane i-8utane 6 5a 6 5 5b 5b 5b (1,000) 5,0C0 (1,000) 0,000) (U0OO) No Yes 'Yes) (Yes) Yes Yes Yes Yes References 1. Fluorinated hydrocarbons: 'Freon" Technical Bulletin $-16, E. I. du Pont de Nemours & Co., Inc., Wilmington, Delaware. la. "Aerosol News", Vol. 1, No. 2, p. 6, 1956, E. I. du Pont de Nemours & Co., Inc., Wilmington, Delaware. 2. Chlorinated hydrocarbons: Aerosol Age, p. 49, February, 1960. 3. Hydrocarbons: Goodhue and Franz, Proceedings, CSMAJ, p. 27, May, 1957. 4. "Freon-C318" Propellent: Blodgett and Webster, Aerosol Age, June, 1959. 5. Nitrous Oxide-, ibid 6. Carbon Dioxide: Haase, Aerosol Age, p. 24, July, 1959 7. \Aethvlene -niortde: Seed. Aerosol Age. o. 27 June, 1956: <eub- ier, Aerosol Age. o. 49, ^eoruarv, I960. 3. Vinyl cblonae: <euDler. Aerosol Age, o. 49. Feoruarv, i960. EID11834