NEW NONFLAMMABL FORMULATIONS FOR
STERILIZING
SENSITIVE MATERIALS EDWARD 0. HAENN1,l WILBUR A. AFFENS,2 HARRY G. LENTOI3 ALFRED H. YEOMANS, and R. A. FULTON Entomology Research Division, Agricultural Research Service, U. S. Department of Agriculture, Beltsville, Md.
Great interest has been generated in the ethylene oxide method of sterilizing since the experimental work, detailed in this article, was done. Sterilization of articles, which up until now was considered impractical or impossible, is now possible. Skating rink operators are interested in sterilizing rental shoe skates; swimming pool operators are interested in sterilizing rental bathing suits; the list gets longer each day, as new areas of application open up.
S~IX~CE
ethylene oxide was discovered as an effective insecticide (4,5, 7) it has been so used extensively. For several years, the U. S. Army Chemical Corps Research and Development Command has investigated it for use as a sterilizing agent (77). T h e commercial preparation containing lOy0ethylene oxide and Present address, Food and Drug Administration, U. S. Department of Health, Education and Welfare, Washington 25, D. C . Present address, Naval Research Laboratory, U. s. Department of Defense, Washington 25, D. C . a Present address, Eastern Utilization Research and Development Division, Agricultural Research Service, U. S. Department of Agriculture, Philadelphia, Pa.
90% carbon dioxide commonly used as a fumigant must be packed in heavy compressed gas cylinders. The mixture is not homogeneous and is not well adapted for small-scale use. Therefore, these laboratories undertook to develop formulations of ethylene oxide for packaging in the small inexpensive low or medium pressure dispensers approved by the Interstate Commerce Commission and also in larger dispensers for decontaminating spaces up to several thousand cubic feet. The dispensed vapors alone or in any mixture with air must not propagate flame. The first formulation prepared contained 19% by weight of ethylene oxide in dichlorodifluoromethane, a composition based on data supplied by the Chemical Corps. This solution, however, dispensed vapor which was flammable in a narrow range of proportions mixed with air. Accordingly, additional flammability data were obtained in these laboratories. Early in this work the Jefferson Chemical Co., Austin, Tex., reported to the Chemical Corps its observation of flame propagation in a narrow range of air-ethylene oxide-dichlorodifluoromethane mixtures representing a proportion of only 18y0ethylene oxide (by weight) to 8270 dichlorodifluoromethane. For this work it was necessary to modify the conventional combustion-tube apparatus ( 6 ) . Compositions of ethylene oxide and dichlorodifluoromethane containing 1670 by weight or less of the oxide would not propagate flame upward in the 2-inch diameter tube when their vapors were mixed in any proportion with air. Limits so determined are usually valid for muchlarger spaces (6). However, because of certain anomalies between these limits
and those for the ethylene oxide-carbon dioxide-air system (9, 70) and because the Chemical Corps was studying the increased effectiveness of ethylene oxide sterilization at elevated temperatures in large-scale tests, additional flammabilitylimit ratios in the critical concentration range were determined at higher temperatures in a large combustion chamber so that wall effects would be nearly eliminated and test conditions would simulate fumigation conditions. These data showed that ethylene oxide content of formulations must be reduced to 12% or less.
Experimental Materials. Chemical Corps ethylene oxide (specification-minimum 99%) was used in this work. Lots containing polymer were redistilled before use. The chlorofluorohydrocarbons were refrigerant grade. Formulations were prepared in clean dry steel cylindersbreathing oxygen Type A-4, 104 cubic inches in capacity. Apparatus and Procedure. COMBUSTION TUBE. The tube, constructed according to Burden and Burgoye ( 3 ) , was modified to facilitate mixing of the gases (page 686). The inner surfaces of the stoppers were covered with a thin film of silicone grease. The ignition spark (about 8 inch, brass electrodes) was produced by a 1000-volt-ampere induction coil with a 60-cycle, 110-volt p i mary coil which generated 25,000 volts in the secondary. A pump with a stainless steel body and a Hycar flexible liner was incorporated in the vacuum system to mix the gases by circulation. The system was evacuated, gases were introduced in the desired proportions as determined by their partial pressures, VOL. 51, NO. 5
M A Y 1959
685
and dry air was admitted from storage over Drierite to atmospheric pressure. The gases were circulated through the pump- and tube-system for 5 minutes. The disconnected tube assembly was supported vertically near the hood, and the tube was lowered to producea '/*-inch space between its upper end and stopper. The ignition spark was induced, several times if necessary, and the movement of any flame was observed. The mixture was recorded as flammable only if the flame progressed to the top of the tube (6). Attempts to keep the top of the tube closed while igniting the mixture and maintaining an aperture at the bottom
RUBBER PIECE SPRING LOADE
GLASS TUBE 2" I.D 4' LON
'' D. BRASS 16 THDS./INCH
3/8
resulted in such an outpouring of the heavy gas burning around the outside of the aperture that this conventional procedure was abandoned. In a preliminary experiment with air and dichlorodifluoromethane in the system, part of the circulating gas stream was continuously bypassed through a thermal-conductivity instrument adapted here for determining dichlorodifluoromethane (7). The gas stream became constant in composition in 3 minutes and the dichlorodifluoromethane concentration checked very closely the quantity added as determined by partial pressure. For preparing mixtures in the ethylene oxide-dichlorodifluoromethane trichloromonofluoromethane-air system, the chlorofluorohydrocarbon gases were premixed in equal proportions by weight in a large cylinder before they were added to the combustion tube. I n this system 2.5% of the added trichloromonofluoromethane at the critical limit was absorbed in the circulation assembly. As such absorption constituted a small factor for safety in determining the limit, it was ignored. After each test the combustion tube, the stoppers, and the inlet tubes were 1%ashed with detergent solution, thoroughly rinsed with water, and dried in a jet of air. This procedure was necessary because acidic thermal-decomposition products of the dichlorodifluoromethane catalyzed the polymerization of ethylene oxide gas, producing a transparent film of liquid polymer on the walls of the container. LARGE COMBUSTIOS CHAMBER.The combustion chamber was a steel fumigation chamber having a cylindrical body with one end slightly concave. The other end was closed by a flanged plane steel cover. The cylindrical portion was 4 feet long and 2 feet in diameter. The concave end was 4 inches deep at the center. The capacity was 13.1 cubic feet. A series of five ports down one side was used in this or-
-
Table I.
der for manometer connection, exhaust pump connection, insulated electrode inlet, metal dial thermometer inlet, and input valve connection. A fourbladed fan, 10 inches in diameter, was mounted on a shaft passing through ballbearings in a short length of '/n-inch pipe tapped into the middle of the wall at about a 90" angle relative to the series of ports. The end of the shaft was fitted through a pipe end cap and sealed with an annular gasket of closed cell neoprene sponge. The shaft seal was not perfect under vacuum. Accordingly, when the chamber was to be evacuated, the pulley and pipe end cap were removed from the fan shaft and a capped pipe long enough to accommodate the protruding shaft was screwed onto the pipe bearing. The chamber was grounded, and a brass electrode tapped into it served as a grounding terminal for the spark gap and the heaters. Two strip heaters were bolted vertically to the outside of the chamber near the bottom; one, located between the series of ports and the fan, had a rating of 500 watts and the other, opposite the first, had a rating of 300 watts. The temperature control was an external wall contact-type thermostat. The spark gap ( 9 ' 6 4 inch) was maintained between pointed '/*-inch brass rods which were so mounted in the center of the chamber bottom that the gap was 1 foot from the nearest wall. Two pumps were used. A diaphragm pump of high capacity was effective to a pressure of about 5 inches of mercury, which was attained in about 10 minutes with both pumps operating; the highvacuum pump completed evacuation to about 3,'8 inch of mercury in about 30 minutes. The cover was sealed to the chamber by a gasket of closed-cell neoprene sponge '/2 inch thick and S/S inch wide, which was cemented to the flange at the top of chamber. This gasket material %'as the only one that did not leak without the cover bolted down when the chamber was either under vacuum
Flammability Limits in the Large Chamber a t Elevated Temperatures Are Higher
Mixtures of ethylene oxide and dichlorodifluoromethane. Barometric pressures 29.67-30.00 inches 1'01. % of
IGNITION POINTS RUBBER
PIECE
FOR T U B E
REMOVABLE SLOTTED PIE STEEL I" X 4" X 1/8 '' STEEL PIECE 31/2"X 3 1/2" X 3/32' WITH HOLE 23/e I' D
The spring-mounted combustion tube can b e easily disassembled for cleaning
686
Mixture in Air. Calcd. from Mole Ratio Weight Partial inputb CCLF2/C&O pressure" 1.91 28.9 29.4 2.07 26.8 2.24 31.0 31.3 32.5 32.3 2.44 32.9 32.8 13.0 87.0 33.0 2.55 12.5 87.5 33.0 2.67 30.1 29.9 12.0 88.0 30.8 31.6 31.8 32.1 32.3 35.3 35.1 Probable relative error +O.S%. a Probable relative error * l % . flame instead o l spark.
INDUSTRIAL A N D ENGINEERING CHEMISTRY
Composition of Mixture, % Wt.'Wt, C2H4O CC12F2 16.0 84.0 15.0 85.0 14.0 86.0
... ...
...
... ...
...
*
FlammaTemp., bility Test F. 112 92 122 110 108 f" 104 124 130 142 120 144 121 141 by match Ignition
++ + ++
NONFLAMMABLE FORMULATIONS or filled with circulating gas mixture at atmospheric pressure. An inner cover of '/'4-inch polymethacrylate plastic contained the gas mixture and permitted observation during the ignition tests. This cover was inset so that its top plane was ' / l e inch below the edge of the chamber. A hole 10 inches square in the plastic cover was sealed with saran film to provide instant pressure relief \\hen ignition occurred. At four equally spaced locations the edge of the plastic cover was squared off to produce apertures up to '1s inch wide, Lchich helped to maintain atmospheric pressure during the ignition tests. The same induction coil described above was used. An inclined mirror mounted several feet above the chamber permitted observation of the ignition test from a shelter about 10 feet distant. The sides of the chamber were insulated with 2-inchthick batts of rock wool supported and sealed with adhesive tape. The rock-wool blanket was fitted with a protective cover of polyethylene film. A large square of insulating material on top of the steel cover was secured with a film cover. When the temperature was high enough, the chamber was evacuated to a pressure of about inch of mercury, the heaters were turned off and air was admitted to a pressure of 5 or 6 inches of mercury. After the pressure and temperature became constant, they were recorded and the liquid formulation in a weighed cylinder was admitted through the bottom inlet valve until the pressure change was slightly less than the desired partial pressure. When the pressure had stabilized, more liquid was added in small increments until the desired pressure change was attained as closely as practicable. After the pressure and temperature were stabilized, they were again recorded, together with the weight of
formulation. Air was then admitted to within about 1 inch of atmospheric pressure. The cap was removed from the fan-shaft bearing, and the pipe cap with seal was slipped over the shaft and screwed tightly to the bearing. The pulley was fastened to the fan shaft and, after the small amount of air necessary to equalize the pressure with the atmosphere was admitted, the motor drive was started. Stirring for 5 minutes was proved adequate analytically in preliminary tests. After 5 minutes at about 1150 r.p.m. the fan was stopped, the temperature was noted, and the steel cover was removed from the chamber. Within 1 minute of the cessation of stirring the spark was induced several times and then continuously for a few seconds, if necessary. The mixture was considered capable of propagating flame if any flame progressed to the top of the chamber as observed in the mirror and by destruction of the saran film. After each test the fan was operated to exhaust the gases. The entire assembly was then washed with water containing a detergent, rinsed, and dried before re-using. Although in a few runs the components were added individually in the gas phase, considerable difficulty in attaining desired ratios was experienced, particularly because of the temperature changes. As it was not advisable for the heaters to be on during the runs, temperature control was not as close as desirable. The aim was to obtain sufficient data at not less than 130' F. to assure that the ratio of chlorofluorohydrocarbon to ethylene oxide was high enough to prevent propagation of a flame in the gaseous mixture or in any air mixture.
flammability-limit curve for the ethylene oxide - dichlorodifluoromethane air system (Figure 1) indicates that forinulations with a mole ratio of dichlorodifluoromethane to ethylene oxide exceeding 1.89 would not produce with air any mixtures capable of propagating a flame. This ratio is calculated for a formulation containing 167, ethylene oxide by weight and 84% dichlorodifluoromethane. Figure 2 sholvs the flammability limits for the system including air, ethylene oxide, and a mixture of equal weights of dichlorodifluoromethane and trichloromonofluoromethane. The mole ratio of chlorofluorohydrocarbon to ethylene oxide required to prevent flame propagation in any mixture with air exceeds 2.10. The formulation corresponding to this ratio contains 14y0 ethj lene oxide. Large Combustion Chamber Apparatus Data for the ethylene oxidedichlorodifluoromethane-air system obtained in the large apparatus (Table I) show a flammability limit corresponding to a much lower proportion of ethylene oxide than that found with the combustion-tube apparatus. The flammability limit for this system corresponds to a formulation containing 12.570 eth>lene oxide by weight and having a mole ratio of dichlorodifluoromethane to ethylene oxide of 2.55. No flame propagation was indicated with the formulation containing 12% ethylene oxide with a corresponding mole ratio of 2.67 The data for the system with chlorofluorohydrocarbon mixtures (Table 11) show a flammability limit ratio about the same as that for the other system, and in this case corresponding to a much lower proportion of ethylene oxide than that found with the combustion-tube apparatus. However, because of the higher molecular weight of trichloro-
-
Results Combustion-Tube Apparatus.
The
0
O'
0.;
OI4
,
I
06
Ok
VOLUME
Figure 1. In a narrow range of concentrations the flammability limit extends t o a ratio of 1.89
IrJ
1'2
14
16
le
2b
22
RATIO ( C C I ~ F ~ + C C 1 3 F ) / C , ~ O
Figure 2. In a very narrow range of concentrations the flammability limit extends t o a ratio of 2.1 0 VOL. 51, NO. 5
M A Y 1959
687
Table II. Flammability Limits in the Large Chamber Are Nearly the Same for Mixed Chlorofluorohydrocarbons and for Dichlorodifluoromethanein These Systems Mixture of ethylene oxide and dichlorodifluoromethane plus trichloromonofluoromethone ( 1 Barometric pressure 29.57-29.92 inches
ComDosition of Mixture, % W./W. CClzF,
~~l~ ti^ (CClpFz
CzHaO
+ CClzF
12.0
88.0
2.51
11.0
89.0
2.77
+
CClaF)/ C&O
Probable relative error &l%. cover film failure.
CT,
of
Calcd. from Partial Weight pressurea input6 30.4 30.7 31.0 29.0 30.4
...
31.4
Probable relative error *0.5%.
Discussion A marked increase was noted in the flammability limit determined in a large chamber over that in smaller conventional apparatus. Stewart and Starkman (72) described similar results in the study of flammability limits of mixtures of aircraft fuels, oxygen, and inert gases. These data emphasize the caution needed in evaluating flammability limits determined in apparatus too small to reflect practical conditions of use. The flammability limits a t elevated temperatures are related to conditions that might be encountered in fumigating operations during the summer months in many areas. Moreover, fumigation at elevated temperature may be desirable to reduce the time necessary for complete sterilization or to effect sterilization at a lower concentration of ethylene oxide (77). The fact that the two chlorofluorohydrocarbon formulations recommended contain only 12% and 11% ethylene oxide by weight compared with 10% in the commercial carbon dioxide formulation suggests little advantage for the former except that the low pressures ( 3 to 5 atm.) of the homogeneous chlorofluorohydrocarbon formulations permit packaging them in inexpensive containers. I n fact, the much higher cost of the chlorofluorohydrocarbons might be expected to more than offset the slightly higher weight percentages of ethylene oxide in their formulations. However, if a chamber is completely evacuated before adding the sterilizing gas, the concentration of ethylene oxide attained at 1-atm. pressure with the chlorofluorohydrocarbon formulations (27% ethylene oxide in the gas phase) is almost three times that attained with the carbon dioxide formulation (loyoethylene oxide in the gas phase) and sterilization can be achieved in slightly more than one third of the time. I n the usual circumstances the
by wt.).
Mixture‘in Air,
30.3 30.5 30.9 28.8 30.0 30.4 31.3
monofluoromethane, the corresponding nonflammable formulation contains only 11% ethylene oxide.
688
Vol.
f1
Temp., O
F.
144 132 155 148 161 132 141
Flammability Test -c
++ -
Slight loss of gas in
sterilization space is not hermetically sealed and the loss of gas by displacement is a direct function of total gas volume added to the space. For each volume of ethylene oxide the carbon dioxide formulation adds 10 volumes of total gas as compared with less than 4 volumes from the new formulation. These deductions were confirmed in a comparative field test of the 1270 ethylene oxide-88% dichlorodifluoromethane formulation and the 1070 ethylene oxide-9OY0 carbon dioxide formulation at relatively low concentrations (2). The almost identical densities of ethylene oxide and carbon dioxide minimize the tendency for separating the gases, while the fact that dichlorodifluoromethane is about 23/4 times as dense as ethylene oxide, might be a serious disadvantage. However, a number of tests in spaces up to 2000 cubic feet revealed that the ratio of dichlorodifluoromethane to ethylene oxide did not drop below the ratio in the formulation, but tended to increase somewhat. Special care must be exercised in such tests to provide efficient circulation of the gases and to avoid direct impingement of the discharging formulation on nearby surfaces resulting in excessive condensation of ethylene oxide. I t must be emphasized that the ethylene oxide-dichlorodifluoromethane - trichloromonofluoromethane formulations have not yet been studied in similar large-space fumigations. Flammable ethylene oxide-chlorofluorohydrocarbon mixtures are noted to develop a considerable volume of irritating halogen acids in burning as do other flammable products containing fluorohydrocarbons. Ethylene oxide gas was capable of propagating flame in concentrations ranging from 3.6% by volume in air to 10070 ethylene oxide. These limits are identical with those of Burden and Burgoyne ( 3 ) for a closed tube. Hess and Tilton ( 8 )reported flammability of 100% ethylene oxide in a closed bomb. Coward and Jones (6) rejected these limits de-
INDUSTRIAL AND ENGINEERING CHEMISTRY
termined in sealed vessels and accepted the upper flammability limit as 80%. This work supports the 100% limit, for pure ethylene oxide gas can propagate a flame in a tube of acceptable dimensions even when the tube is open to maintain atmospheric pressure. Conel us ions
These formulations of ethylene oxide are not capable of propagating a flame in the vapor state either pure or mixed with any proportion of air at temperatures up to 130’F.: 1. Solutions of ethylene oxide in dichlorodifluoromethane that contain 1270 or less by weight of the oxide. 2. Solutions of ethylene oxide in a mixture of equal parts by weight of dichlorodifluoromethane and trichloromonofluoromethane that contain 11% or less by weight of the oxide. These formulations contain in the vapor state up to 2.7 times as great a concentration by volume of ethylene oxide as does the present commercial formulation of ethylene oxide with carbon dioxide. Accordingly the ethylene oxidechlorofluorohydrocarbon formulations are much more efficient sterilizing agents than the latter. Flammability limits of ethylene oxide gas mixed with chlorofluorohydrocarbon gases and air determined in a conventional combustion tube may not represent the limits in larger spaces. The upper flammability limit of ethylene oxide is 100%. Acknowledgment
George F. Mangan, Jr., rendered valuable assistance at the start of this work. David Henley and Daniel A. Mauser, Jr., assisted in many of the tests. literature Cited (1) Affens, W. A., Haenni, E. O., Fulton, R. A., Anal. Chem., to be published. ( 2 ) Affens, W. A., Haenni, E. O., Fulton, R. A., to be published. (3) Burden, F. A,, Burgoyne, J. H., Proc. Roy. Soc. (London) 199, 328-51 (1949). (4) Cotton, R. T., Roark, R. C., IND. ENG.CHEM.2 0 , 805 (1928). ( 5 ) Cotton, R. T., Young, H. D., Proc. Entomol. SOC.Wash. 31, 97-102 (1929). (6) Coward, H. F., Jones, G. W., U. S . Bur. Mines, Bull. 503, 155 pp., 1952. (7) Curme, G. O., Jr., Johnston, F., “Glycols,” p. 108, Reinhold, New York, 1952. (8) Hess, L. G., Tilton, V. V., IND.ENG. CHEM.42, 1251-8 (1950). (9) Jones, G. W., Kennedy, R. E., Zbid., 2 2 , 146-7 (1930). (10) Jones, R. M., Zbid., 33, 394-6 (1933). (11) Phillips, C. R., Kaye, S., Am. J . Hyg. 50, 270-305 (1949). (12) Stewart, P. B., Starkman, E. S., Chem. Eng. Progr. 53, 415-455 (1957).
RECEIVED for review July 21, 1958 ACCEPTED January 14, 1959 Work supported under contract from U. S.
Army Chemical Corps, Fort Detrick, Frederick, Md.
