Document 3eDzJ9XmnpRvxojGRXd4Q8yra

JOURNAL OF Pharmaceutical November 1964- volume 53, number 11 Sciences Review Article. Toxicity, Untoward Reactions, and Related Considerations in the Medical Use of Plastics By JOHN AUTIAN CONTENTS year. The spectrum of uses today defies any PAGE ordinary listing, and it now appears possible that I. Introduction........................................ 1289 with the correct choice of plastic any desired # II. Toxicity and Untoward Reactions.. 1290 property can be achieved. For the most part A. General........................................ 1290 the medical and other ancillary professions have B. Direct Effect on Tissue accepted these plastic items with a great deal of (Acute).................................... 1290 confidence--a confidence which perhaps is not 1. Pure Plastic....................... 1290 entirely justified. Part of this acceptance of 2. Compounded Plastics........ 1291 plastics for any and all uses stems from a lack of C. Direct Effect on Tissue knowledge on the subject of plastics by clini (Chronic)--Cancer................ 1291 cians, nurses, pharmacists, and hospital adminis D. Indirect Effect on Tissue.......... 1293 trators. Other segments of the population are 1. Leaching of a Constituent also .finding that certain polymeric materials and into Solution........................ 1293 their additives might cause harmful effects to 2. Leaching of a Constituent the purchaser, as may be witnessed by recent and Other Consequences findings in the United States that a plastic mold to Blood............................... 1294 ing toy has caused over 1000 skin irritations.1 III. Complications Arising from Plastic It seems logical then that as more information is Prostheses accumulated by medical and allied professions on A. General........................................ 1295 plastics, a greater safety feature will be forth B. Vascular Prostheses................... 1295 coming, not only to patients but also to the gen C. Subcutaneous Prostheses........ 1297 eral public. This review attempts to cover some D. Synthetic Adhesives................. 1298 of the problems encountered in the use of plastics IV. Plastics and Drug Activity............... 1298 in medicine and is intended to alert those in V. Drug-Plastic Considerations............. 1299 terested in them that consequences--from very VI. Need for Standards............................. 1299 minor to extremely Serious--may fall upon the VII. References............................................ 1300 user or patient if proper safeguards are not taken. rI 'he fifties ushered into the medical and related professions a host of devices or items of one type or another composed in part or whole of a plastic material. Nearly a geometric increase in the use of these plastic items has occurred each Knowledge of this type can help all segments of the public health professions and their suppliers to produce and use only those items which insure absolute safety for intended use. In this review the author has attempted to Received from the Drug-Plastic Research Laboratory, University of Texas, Austin. 1 Prom U. S. Department of Health. Education nod Wel fare. Pood and Drug Administration, Newt Release, May 17. 1003. 1289 \ SPI -12805 1290 Journal of Pharmaceutical Sciencet cover the general field (without claiming a com plete coverage) of toxicity and untoward reac tions which have or may have a direct or indirect effect u]k>ii the welfare of the patient. TOXICITY AND UNTOWARD REACTIONS General Toxicity or tissue sensitivity reactions in animals can take place by two distinct routes: (a) by direct contact of the plastic material or product with tissue and (6) by indirect contact with tissue, such as injection or application of a solution (drug product, nutritional product, blood, etc.) which has had previous contact with a'plastic. A number of reports have appeared /in the past discussing the toxicity of various poly ! mers and the other ingredients which are utilized to prepare a plastic product (1-8). For the most part these reports have dealt with industrial health problems in relation to the manufacturing of a plastic material. As is well known, many of the chemicals used in the synthesis of a polymer arc highly toxic if proper care is not tnken to safeguard the health of the worker. However, the discussion presented in this section will deal with the finished plastic material. Texts by Rolf (9) and Wesolowski (10) should be referred to for more detailed and specific information on the use of plastics in medicine and surgery. Direct Effect on Tissue (Acute) Pure Plastic (No Additives).--It is a natural biological consequence that any material intro duced into tissue will show some degree of re activity, even if this cannot be truly detected with present means of analysis. Results and conclusions must be viewed as relative and in comparison to a standard state. This "standard state," of course, poses a problem since dif ferent investigators may use different standards -for comparison, -Many nf ItiA rApm-tc, or at least differing opinions, dealing with plastics should be examined in the light of what has been said. One other additional factor is relevant, however, in regard to plastics, especially when the same gencrically named plastic has been used by more than one group with varying results. Since there are no standards for plastics to be used in medical practice, it is very probable that the "same" plastic might not actually be the same, even though the difference may not be apparent by visual observation. A great body of evidence is readily obtainable to support the claim that a pure plastic material is inert when in contact with normal, healthy, unbroken, or untraumatized tissue such as the skin or mucous membrane (11-13). The use of synthetic yarns in various clothing apparel for a number of years by millions of persons with little incidence to tissue reactivity attests to this state ment. Unfortunately, less information is avail able as to the effect of a pure plastic introduced into tissue of ill or diseased patients. Early reports of tissue sensitivity, dermatoses, or other untoward reactions ascribed to a pure polymer may be--in the light of present knowl edge--traced to the presence of monomers or other low molecular weight polymers rather than to the polymer itself. A good example of this may be seen by referring to the literature in both the dental and ophthalmic professions where acrylic resins were used (and, of course, are used) as prosthetic devices. For one reason or another in these early uses of the acrylic resins, the monomer was not completely polym erized and this caused the tissue response. Contact lenses have caused some difficulty to a small number of patients out of the nearly 5 million wearers. Recently, however, a report pointed out that 14 proved cases of blindness or ncar-blindncss were attributed to contact lenses (14). One suspected cause of blindness is the possibility of a chemical impurity in the plastic migrating onto the surface of the eye. Patty (15), LaVeen and Barberio (16), and Scales (17) have emphasized the importance of the removal of the monomers before actual medical use. There have been instances of tissue response to other polymeric materials, but most of these can also be traced to factors other than the polymeric material. Harris (12) states that the final polymerized chemical (plastic) is inert to tissue and cites the studies by Schwartz (18), Morris (11), Hine el al. (19), Zapp (20), and Calnan et al, (21), to support his contention. The reader should note, however, that these reports were based upon experiments on the skin. Introduction of a pprp plastic into the tissue (subcutaneous, intramuscular, intraperitoneal, etc.) has been found in numerous instances to be well tolerated by the host tissue (at least for short periods), but it would be incorrect to assume that tissue sensitivity will not appear. There is difficulty in assessing the results from this type of investigation since the reaction or lack of reaction will depend upon such factors as its particular site of implant, the size of implant, the degree of blood supply, the possible trauma effect of implantation, and the time of tissue contact. It is also possible that even here a reaction might have been caused by a contamina tion of one form or another rather than by the pure plastic. Some authors have assumed that tissue re SPI -12806 Vol. 53, No. 11, November 1964 1291 activity was due to the pure polymer after short contact with tissue. For example, Harrison et al. (22) indicated that Dacron, Ivalon, nylon, Orion, and Teflon did produce some tissue sensitivity when subcutaneously implanted in dogs. In their study nylon was found to be the least acceptable, while Teflon was the most tolerated plastic in the series. Usher and Wal lace (23) found that nylon, Orion, Dacron, and Teflon were less tolerated in dogs (up to 1 week) than Marlex. Longer periods of contact with tissue (perhaps up to a year) might produce further tissue reactions, depending upon the particular plastic. Little and Parkhouse (24) investigated a num ber of plastic materials as to their potential tissue reactivity in guinea pigs and noted that a correlation could be established between crystal lite size in the plastic or the size of an added filler to the plastic and the incidence to fibroblast reactions. They employed X-ray diffraction methods to approximate the size of the crystal lites or fillers. Results of their study demon strated that the silicones and low-density and medium-density polyethylene produced little incidence to reactions whereas other types of plastics could elicit responses. Compounded Plastics (Polymer plus Addi tives).--The propensity of toxic responses in animals and humans would seem to increase for those plastic materials which require the presence of other ingredients to impart a specific desired property. The evidence to support this previous statement is more difficult to find in the literature since little practical use is made of compounded plastics by surgeons as possible prosthetic devices. In recent years, however, more use is being made of compounded plastics such as polyvinyl chloride for tubings and protective coverings. For example, in-dwelling catheters and other types of catheters which arc introduced into a natural body orifice or inserted through a surgical procedure will have contact with tissue which might be susceptible to a leached constituent from the plastic material. Actual clinical reports of this occurrence have been rare in the past, but results from several animal studies do indicate that toxicity of leached constituents is a real possibility. The work of Brewer and Bryant (25) may lx: cited as an example to demonstrate that even certain commercially available plastic devices used in medical practice can cause tissue sensitivity when implanted in various animal tissues for short periods of time. Lawrence el al. (26) conducted a toxicity study on a number of commercially available plastic administration devices arid found that out of 48 samples tested by intramuscular implantation in animals, 25 were found to cause a reaction after 1 week of contact. Most of these devices were tubings of the vinyl type and were packaged in scaled cartons ready for use. This particular investigation indicated that one or more in gredients in the tubings were being released to the tissue. Even though the actual offending agent was not ascertained, it was demonstrated that the plasticizers were not the causative agents in producing tissue reactions. Gas chromatographic techniques suggested that the offending agent was one of the additives in corporated in the plastic in minute quantities. Alcoholic extraction of the "toxic" tubings re moved the offending agent from the tubing. The above authors make a very poignant conclusion in their paper. They state the following: The question of course may now be raised that the tubings which are reported in this paper were never intended to be implanted either in animals or humans; consequently, for their intended use, they may be quite safe. Ques tions of this sort can best be answered by stating that good public health practice would seem to dictate that no plastic item should contain an ingredient which has a potential harmful in gredient that might leach into a solution to be administered to a patient. Autian et al. (27) noted that one type of vinyl urinary bag caused tissue reaction in animals, while a similar type of bag from another manu facturer showed no ill effects. On a number of occasions in-dwelling catheters have caused problems in patients. Bansmer el al. (28) documented a number of complications when catheters were placed into the inferior vena cava. Some of the complications were local thrombosis, thrombosis with embolism, sup purative thrombophlebitis with septicemia, and chemical necrosis. Derrick, in animal experi ments, .concluded that intra-aortic catheters cannot be left for a prolonged period of time with out precipitating thrombosis and embolism to vital areas (20). Several reports have also appeared indicating that in-dwelling catheters have been severed and lost in the arm of patients (30) . The break in the catheter may have been due to a bending action on the catheter with movements of the arm. Urinary catheters have increased the incidence to bactcriuria in patients . (31) . The exact reason or reasons for these catheters causing the infection is still unclear. Direct Effect on Tissue (Chronic)--Cancer Since no evidence has appeared in humans that a certain plastic material is the causative agent SPI -12807 1292 Journal of Pharmaceutical Sciences in the production of tumors, there might lie a natural tendency to discount these "inert" materials (plastics) as ])ossible carcinogens. At the moment we must lie content to view certain animal cx|icrimentations which have demonstrated that long implantations of plastic materials cause responses which would rightly Ik considered as carcinogenic. Turner (.'12) apjKars to have been one of the first to delect the carcinogenic activity of plastics, In 1!)41 he reported his findings which showed that implanted Makefile disks in rats guve rise to sarcomas at the site of implants. In the latter part of the forties, Oppcubeimer el al. (33) observed that cellophane wrapped around rat kidneys for a ]Kriod of 24 mouths gave rise to , tumors. This was a chance discovery since these investigators were actually experimenting on hypertension. Further work hy the Oppenlieimcr group reported in 1952 (34) that various types of plastic films caused-treertam percentage* of sarcomas in rodents tested. Druckrey and Sehntahl (35) were able to produce sarcomas in rats at the site of implantation with regenerated cellulose film. These authors noted that the tumors were produced in a strain of rats which had shown no spontaneous disposition to sar comas during a prior 12-ycar period. In 1953, Oppenhcimer el al. (30) reported the testing of a number of films by implantation in mice and rats. They found the production of malignant tumors when films of regenerated cellulose, pure and impure polyethylene, poly vinyl chloride, Silastic, Teflon, Dacron, poly styrene, and nylon were used. Druckrey and Schmahl (37), in a continuation of their earlier studies, reported that they had produced tumors in rats with a number of polymers, while the team of Laskin et al. (38) observed a 25% oc currence of fibrosarcomas in mice after im plantation of methyl methacrylate film. Further work by the Oppenhcimer group (3942), reports by Bering el al. (43), Nothdurft (44), I-fueper (45-47), Russell el al. (48), and Bing (49) clearly show the incidence of sarcomas when various types of plastics are implanted in animals. An analysis of the previous workers' data and conclusions offers two schools of thought con cerning the causative mechanism of polymer cancer. A minority group, particularly Ilueper (47) and Druckrey and Schmahl (35, 37), have advanced the hypothesis that a chemical or a physicochemical interaction between the polymer and the tissue is the chief causative factor in the production of tumors, while a much larger group of investigators, i.e., Oppenhcimer et al. (.`111), Nothdurft (44), and Russell el al. (48) support the physical or nonsjiecific theory of polymer carcinogenesis. The chemical theory viewers postulate that such factors as end groups, free radicals, complex formation iKtwccn the polymer and protein, degradation products of the polymer, and/or the presence of impurities in the plastic might initiate cancer production. On the other hand, those of the physical theory approach point out that many chemically unrelated substances cause cancer, but a specific substance in a number of physical forms, i.e., film, perforated film, powder, size of implants, smoothness of im plant, etc., may or may not cause cancer. The physical theory school would seem to believe that induction of tumors by plastics is indirect and may Ik due, in a large part, to a general interference with normal cell growth at the interface between the plastic and the tissue. Tlweiitical-factor,-either stated or implied by this group, is the total uninterrupted surface contact. For example, films which have in duced tumors will show less tendency to do so when they are perforated, and powders of the polymer show little or no tendency to cause tumors. Horning and Alexander (50) have observed a correlation between the size of the surface area of the implant and tumor production, while a recent report by Oppenhcimer et al. (51) confirms that powdered plastic materials when implanted do not seem to act as carcinogenic agents.2 However, Hueper (47) disagrees with the physical theory group and reinterprets the results of other workers, as well as the results of his own study, to support the chemical or physicochemical thesis as the causative factor in polymer cancer. Therefore, it must be ob vious that much more experimental work must be done to define clearly the causative factor which is responsible for the production of tumors when various types of plastics are implanted in animals. In general, there appears to be a minimum induction period, depending upon the animal, before a tumor will develop from an implanted plastic. Oppenheimer et al. (41) noted that if implants are removed from their sheath (pocket or capsule which will form around an implant) within a 0-montli period, no tumors will develop in rats. If the implants arc kept in place for a longer period than 6 months and then removed, tumors will develop. However, tumor response, 9 It should be noted that for the same unit weight of plas tic, a powder will have more surface area than a film, but the |K>wder will not have an uninterrupted contact with the tissue. SPI -12808 Vol. 51, No. II, November 1964 1293 mav Ik eliminated after the O-month period, if both the implant and the sheath around the implant are removed. This would indicate that once the cells have readied a certain point of alteration, the reaction cannot be reversed even when the causative agent (plastic) is removed. Nothdurft (44) also paid attention to the sheath surrounding the implant as a factor to be considered in tumor production. What has been noted in animals has, up to the present time, not been seen in man. In fact, Harris (52) points out that from his knowledge of S000 eases of breast plasty in humans, not one case of cancer was noted due to the plastic im plant. Several reports (53, 54) have indicated, however, that tuinorlikc manifestations in several humans could be traced to the use of aerosol hair products which contained polymeric material, but the evidence cannot be considered conclusive. The experiments performed in an imals ranged for a period of several years which in man might mean an equivalent of 15 to 30 years. Since implanted prosthetic devices are of comparatively recent vintage, no sure pre diction of either noncarcinogenic or carcinogenic activity can be postulated at this time. The surgeon must weigh the merits of implantation in saving or prolonging life with regard for the possible risk involved. Indirect Effect on Tissue Leaching of a Constituent into Solutions.-- Another problem is the possibility of one or more ingredients from a plastic device leaching into blood, parenteral products, and other solu tions during storage, collection, and administra tion. These will be referred to as "indirect effect on tissue" since the plastic itself will not have actual contact with tissue. Two questions might be raised here: (a) is an ingredient or ingredients being leached into a solution which will then be injected into animals or humans and (b) is that ingredient or ingredients toxic to the host? If the answer to the first question is a definite "No," then there may be little need to seek an answer to the second. At first glance, the pre vious statement would seem reasonable, but a deeper penetration into the plastic problem will reveal a number of factors which will influence the migration rate of a constituent from the plastic into the solution. Of course, it is as sumed here that the plastic is a compounded plastic or has been treated with one or more agents to improve the quality of the device. A plastic device in contact with saline solution may reveal no leaching, but in another solvent system or at another pi I there may Ik significant quantities of the leached constituent in the solution. The problem Ijccomcs even more complicated when one considers the variety of parenteral products which could come in con tact with a plastic device. Several years ago, Autian and Brewer re ported in a study on a disposable hypodermic needle having a plastic hub that a constituent was being released by certain needles from the plastic hub to a saline solution which on intra venous injection caused the death of mice (55). Further work by Brewer and Bryant (25) op various disposable devices demonstrated that compounded plastic materials may or may not cause a toxic effect when first exposed to several parenteral solvent systems and then injected by different routes into animals. It is pertinent at this point of the review to mention that very little appears to be known concerning the toxicity of a number of agents which can be formulated into certain types of plastics. Certain countries, for example, the United States, have very stringent regulations on food packaging materials. Physical and bio logical testing must be performed on these packaging materials before they can be employed as food containers. The biological tests invari ably involve long oral feeding tests in groups of animals to ascertain the safety of the substance. Unfortunately, this same information often appears to be used to indicate that the additives approved for food packages will also be safe when they are parts of plastic devices to be used in medicine. Of course, this assumption may be true, but on the other hand strict obedience to this doctrine could present possible harm. Documentation of this statement is not easy in regard to humans, but preliminary animal experiments by Meyers et al. (56) on a group of citric acid esters used as plasticizers revealed how false oral testing programs can be when they arc extrapolated to parenteral administra tion. The aforementioned workers studied the behavior response to parenteral administration of these esters in rats, mice, frogs, and rabbits. They noted that all of the esters exhibited a marked effect on the central nervous system. A single dose (depending on the particular ester) killed these animals in a period of several hours. Death was not due to citrate intoxication as may have been anticipated, but due to another mechanism not yet elucidated. The question arises regarding what actions other ingredients used in plastic formulations may have on animals and upon sick persons by routes other than oral if they leach out into a solution. SPI -12809 Vnl. S3, No. 11, November 1964 1295 plastic tul>c into blood can occur. In their evaluated biologically to prevent any unneces study they noted that when they changed from sary hazard to the patient. Reuse of certain glass tubing to a particular polyvinyl chloride components by S|iecific washing, rinsing, and tubing, premature cardiac arrest and ventricular sterilization should require further evaluation fibrillation occurred on the isolated perfused of the comiioncnt since these treatments may rat's heart. The important point to be made here affect the plastic material sufficiently which in is that these authors indicated that some brands turn may produce an untoward effect in the pa of polyvinyl chloride did show this adverse tient. Clearly, more research is needed in this reaction. area for better patient protection. Keith el al. (70) reported that one batch of plastic tubing enhanced the hemolytic effect on perfused blood. This observation suggested to Hirose and associates (71) that the significant COMPLICATIONS ARISING FROM PLASTIC PROSTHESES General increase in the incidence of renal complications The use of synthetic materials as a prosthesis during extracorporeal circulatory bypass in dates back to the year 1890 when Fraenkel patients in their hospital might be due to the repaired a bony defect in the skull by the use particular plastic and the ethylene oxide method of celluloid (74). Since that time and especially used for sterilization. These investigators noted within the last 15 years, an array of uses has that ethylene oxide sterilization increased the been found for plastic materials within the body tendency to hemolysis in blood samples stored for both physiological and cosmetic needs (10). in plastics but that the particular plastic would Many of these surgical procedures with sub also influence the rate of hemolysis.* sequent implantations of the plastic prosthesis There is, therefore, the very serious conse have permitted extension of human life or have quence in extracorporeal circulation in humans given certain forms of comfort to the patient. that the wrong brand of tubing might release Many problems still need to be studied in detail a constituent into the blood and thereby produce before an ideal synthetic device becomes pos * one or more untoward reactions. sible. The following section attempts to bring Another problem has arisen in the use of plastic some of these problems into focus with past tubing in heart lung machines. Usually the experiences by various investigators. tubing or tubings are coated with silicone, and if the silicone actually has not been baked on Vascular Prostheses the plastic, which in many cases might be the The general success of surgical procedures in case, there is the possibility of the blood washing the replacement of segments of diseased or failing particles of the silicone from the plastic into the aortas and peripheral arteries with homografts circulating blood. A report of this occurring soon made it evident that the supply of these in humans has been given by Lindberg el al. homografts or even heterografts would not ful (72). In their study 10 patients had died after fill the anticipated needs. Thus, it was quite open heart surgery. On necropsy, clear, re natural for the surgeon to turn to the various tractile emboli were found in the capillaries of polymeric materials as synthetic vascular re the kidney, brain, and heart. The emboli were placements. investigated and found identical to the silicone One need not go too far back into the literature used in the coating of the tubings. Further work to note that most animal and clinical experiences on animals substantiated the human results with synthetic prostheses have occurred within that silicone coatings can cause embolization the last 7 or 8 years, even though Deterling (75) and death. Similar results were noted by Helms- refers to Vinylon-N yarn being used as a vessel worth el al. (73), who found silicone emboli in substitute in dogs in 1951. Since 1957, the two the glomeruli of the kidney of patients and most used plastic materials for synthetic grafts animals. The silicone was traced to the oxy have been Dacron and Teflon; but Ivalon, genator pump which had been silicone treated for nylon, Vinylon-N, Orion, Fortisan, polyethylene, debubbling. and polypropylene have had some initial success. Here it is important to remember that as new Much experience has now been accumulated materials are introduced into one or more of the on Ivalon. It might be of interest to review components in various types of extracorporeal this material as a synthetic substitute for vessels 0 apparatus, it is imperative that the material be from its original success to its final demise. A number of excellent properties such as * It was found that if the ethylene oxide sterilited plastic was kept for 7 days prior to its contact with blood, the ns had no effect oo the blood. porosity, compressibility, ease in handling, and ease in molding made this material attractive SPI -12811 1296 Journal of Pluirmaceulical Sciences as a vessel substitute. Early rc)>orts by Slmtn- Some controversy exists as to the actual way el al. (7(i), Ellis and Kirklin (77), Hobcl al. causative factor or factors inducing thrombi (78), and Eilcli and Denman (7!)) were ex formation in synthetic vessels. Change in tremely encouraging in regard to Ivalon as a flow rate of blood and turbulence of flow due to vessel replacement; however, Dcterling (75), the synthetic graft has been believed to be a as early as 1950, had some reservations in the factor in thrombi formation (90). Szilagyi use of Ivalon, for he noted that the material (91) has viewed thrombi formation in synthetic could not withstand the pressure in the thoracic grafts as possibly due to the nonrcactivity aorta unless highly compressed. Creech et al. of a particular plastic material. The implication (80) , in a report to the Society for Vascular here is that arteriogenesis will be delayed and Surgery in 105(1, reported some unfavorable that the intima will not adhere firmly to the results with Ivalon in clinical practice. Rob synthetic vessel. A recent study of Phillips (81) reversed his earlier impression of the value of et al. (92) disputes both the turbulent flow and the Ivalon; in fact, he no longer advocates its use, nonrcactivity theories as causative agents; as an arterial replacement. This reversal of in turn, it postulates that thrombosis formation opinion also has been enunciated by Fitch el al. is a direct consequence of a foreign body-- (82) . They now state the following: "The use especially if that body is relatively nonporous. of Ivalon grafts as arterial conduits in the human They found in their study on Teflon that woven patient is unjustified due to the hazards of Teflon caused a greater degree of thrombi thrombosis, aneurysmal formation, rupture, and formation than the knitted material. The anastomotic disruption.'' A recent report by knitted Teflon, more porous than the woven Payne and Kirklin (88) on a number of patients form, permitted fibrous tissue to invade the having had reconstruction surgery performed on interstices of the fiber, resulting in greater the right ventricular outflow tract with several adherence of the fibrin lining in the vessel. plastic materials noted that Ivalon was an un Other investigators also have pointed out the satisfactory material. Further support of the importance of porosity in regard to synthetic inadequacies of Ivalon is given by Adler and materials used as vascular substitutes (90, 93- Darby (84), who noted marked changes in 95). physical properties of Ivalon after tissue contact. Biogenic conditions will alter physical prop In the light of present knowledge, it would appear erties of synthetic materials, even though much that Ivalon no longer merits a position as a still needs to be done to elucidate the actual worthy substitute for vessel replacement either mechanism underlying such physical changes. in man or other animals. It is fairly well established now that polar As early as 195C an attempt was made to polymeric compounds such as nylon, Orion, assess actual clinical experiences in the use of etc., will show greater changes of properties synthetic materials as vessel substitutes in than the very nonpolar compounds, exemplified humans. This assessment became a preliminary by Teflon after long contact with tissue. Tensile report which has been mentioned previously (80). strength measurements (for elastic properties) The report relates the success of aortic replace have been conducted for a number of synthetic ments with one or more of the synthetic materials polymers before and after implantation in tissues. (*'.., Ivalon, nylon, Fortisan, Orion, Dacron, For example, it has been reported that nylon Vinyl-N, and Teflon). Less success was found will lose from 20 to 25% of its original tensile for synthetic materials when these were used strength after 7 to 18 months of tissue contact as replacements for peripheral arteries. Critical (80). Other materials also will change sig factors causing the failures of the peripheral nificantly, but to varying degrees. This has vessels were the relatively small diameters of prompted some to believe that elastic properties these vessels, the great length, and the crossing might be a critical factor to consider when a of flexion areas. decision is made to use a sjiecific synthetic There appears to be general agreement today material as a vessel substitute. Present evi that vessels less than 5 mm. in diameter will fail. dence, however, gives little emphasis to tensile Most likely these failures will be due to the strength as a factor in success or failure of grafts propensity of thrombi formation. Harrison (80). A revealing study by Newton et al. (90) (S5, 80) found this to be the case with nylon. apparently confirms this fact. In their studies Dacron, Orion, Ivalon, and Teflon in his studies. (in vivo) they noted that various arterial substi Further confirmation of this fact is given by tutes showed differing elastic properties within a Dale and his group (87, 88), as well as by Cate 6-month period; but after this time period, (89). they all tended to stiffen and reach a constant SPI -12812 J, ,Ynl. 5 No. 11 November l 964 1297 clastic value. They concluded that the constant (108)--have observed this serious problem. value was due to the formation of sear tissue Gott el al. (104) have noted the importance of within the implanted arterial substitute. electrical charge on the plastic (positive charge As has been mentioned for synthetic materials, in comparison to the negative charge on the blood a degree of success has been made for grafting of particles) and found that this charge could be vessels having larger diameters than 5 min., reduced or eliminated by coating the valve with while, conversely, little success with vessels colloidal graphite. The coating resulted in smaller than 5 mm. A number of investigators producing an extremely smooth surface which recently have observed that homografts have apparently dissipated or reduced the positive proven more successful postoperatively over charge, thereby decreasing the incidence to synthetic materials when surgical grafts were thrombosis. To date these authors have been ]>erformed on smaller vessels falling below able to coat polycarbonate, polyvinyl, and the inquinal ligament. Irvine et al. (97) noted methyl methacrylate; their results appear this to be the case in a study of 95 patients who encouraging. However, final success or failure underwent a total of 100 femoropoplitcal by must wait for long-term studies in both animals pass treatments. Cockett and Maurice (98) and humans. in a 9-ycar observation of direct arterial surgery for claudication and ischaemia of legs, concluded Subcutaneous Prostheses that the synthetic materials were not functioning Reconstructive surgery on or near the surface up to the level of homografts or other surgical of deformatives, either natural or induced by techniques not involving synthetic materials. disease, accident, etc., has restored many It should be obvious that for vessels large or patients to a normal manner of life. The small other factors must enter the picture which synthetic materials have been used for this type can give rise to success or failure of synthetic of surgery for approximately 15 years with grafts. In this respect it is interesting to various degrees of success. As with other note the suggestion of Wesolowski and associates plastic implants, real problems have been en (99) , who have contributed a great deal to surgery countered which have led to replacement of the in techniques and knowledge in regard to vessel original implant or to complete failure after vary and tissue substitutions. These investigators ing periods of time. have concluded that the ideal synthetic vascular Breast plasty has gained some popularity in graft material should meet the following stand the past to relieve psychic disturbance caused by ards: (n) no toxicity or no allergenic potential, actual or imagined hypoplastic breasts. Even (ib) no deterioration of the synthetic filler upon though cosmetic acceptance can be achieved biological implantation for prolonged periods of by the use of plastic implants behind the breast, time, (c) desirable mechanical handling properties the material gradually becomes firm and loses of being easily scrunched, crimped, and twisted, its initial resiliency (105, 10G). The implant (d) very low implantation porosity, and (e) may also shrink in size or "fall" from its original very high healing porosity or fibroblasting position, thus creating further psychic disturb jicrmeabilitv. To achieve the last two require ance. Hamit (10G) lists a numlier of complica ments (d and e), Wesolowski el al. (99) fashioned tions which might result from breast plasty, compounded prosthetic vascular grafts (a core such as infection, drainage, increasing firmness of resorbable material which has been wrapped of the plastic material, disruption of breast with multifilament polymer). These com function or appearance, development of draining pounded materials were found to be superior sinuses, and possible carcinogenic activities of (in animals) to the conventional monoplastic the plastic material. Polyvinyl sponge has shown material. Similar results with a gelatin-im the greatest number of failures up to the present, pregnated Dacron prosthesis by Jordan et al. and it is hoped that newer materials such as (100) also have been reported. silicone rubbers and polyurethanes might prove Surgical skill has made it possible to replace more satisfactory. Harris (52) appears to be faulty or defective cardiac valves in humans. quite satisfied with a special type of poly Unfortunately, studies in canines and humans urethane for breast plasty. have revealed survival rates not as encouraging Various other reconstructive procedures on the as had initially been anticipated. The most face and other surface portions of the body have serious drawback to the synthetic valves has been performed with, in some instances, amazing been the severity of thrombosis formed on the success. Favorable initial results, however, valve. A number of investigators--Frater and must be weighed against long-term usage and Ellis (101), KolfT et al. (102), and Muller et al. the possible complications which will be ever SPI -12813 im Journal a/ Pharmaceutical Sciences present willi u foreign body. It will l>c in cavity. Biological mechanism for death still teresting to see liow plasties such us the dimethyl has not been elucidated by these workers, and silicones and the various halogenalcd carbons the possibility of carcinogenic activity is still to will perform over long usage. Encouraging be decided. The above workers in their con reports on these materials for subcutaneous cluding remarks refer to a 1948 paper (118) in prosthescis have lieen given by Brown el al. which the following sentence was quoted: (U)7). ``Clinical use of cellophane, polythene, or any Synthetic Adhesives other plastic carries with it the urgent require ment of knowledge of both the chemical and One can see great advantages for adhesive physical characteristics of the product being materials which can replace the usual nail, used," Lewers el al. (117) maintain this state clamp, cast, and other means of closing or holding ment to be true with the synthetic adhesives. segments of tissue or' bone together. Fruitful progress has been made in this direction in the PLASTICS AND DRUG ACTIVITY past 4 fyears in surgery with the advent of In recent years pharmaceutical scientists have polymeric materials which, when actuated in recognized the potential of polymeric materials /some fashion, can become a tenacious adhesive as vehicles for prolonging the action of medicinal ' for tissue. agents. Some success has been achieved in In 11)58, Mandcrino and Salvatore (108) compounding the drug with an insoluble poly were able to restore broken bones by the use of meric material which can then be taken by oral polyurethane material which acted as a very ingestion, the drug 1wing released over a pro powerful adhesive agent, fixing the break in a longed time period as the tablet or pellet travels very short period of time. Since then con along the alimentary tract. Similar dosage siderable use has l>ecn made of this material for forms also have been suggested for long-term the same purpose (109-111). To some it is implantation of certain hormones. Advantages considered as a form of "bone glue," but others to both the patient and clinician of the above are not quite so convinced of this fact (112). dosage forms are clear (one-time administration Up to the present no definite tissue reactions instead of multiple-drug administration) if have been reported (which could be attributed to certain unknown complications do not appear. the polymer), but sufficient time must elapse Two hazards, even though they many appear before a complete evaluation can be made. only as remote possibilities, should be con A great number of synthetic adhesive materials sidered. The first of these is the release of a have been produced in the last decade, but for greater quantity of the drug than planned due to the most part these had little place in medical uncertain biological manifestations on the dosage practice, since for one or more reasons they form. The second is the possible irritating were quite noxious to tissue. Then in 1959, or sensitizing effect the particular plastic might Coover and co-workers (113) demonstrated the have on the tissue when implantation therapy is unusual adhesive properties of alkyl 2-cyano employed. It remains to be seen whether acrylates, the chief one being that the monomer these hazards will materialize in the future when (as a liquid) polymerizes when spread between more prolonged or sustained dosage forms are two surfaces and pressed. The change from a used. liquid state to a solid (as the adhesive) takes Several investigators, in particular Garb (119), place with little or no change in volume, en Scholtz (120), Sulzberger and Witten (121), and hancing the adhesive quality. Experimental Hall-Smith (122), have noted that plastic films surgical applications, in particular for blood will aid the percutaneous absorption of a number vessel repairs, have been performed by a number of topical drugs. Such reports have stimulated of workers using the above-mentioned monomer other clinicians to consider the use of plastic (114-116). In general, few tissue responses have films to decrease the usual concentration of the ` been''noted' By mbsT"wSrlcefs, "but a* word of 'drug when applied" topically! Lack'of knowl caution should be noted for these adhesive agents edge of the influence of these polymeric materials since there appear to be some differences in the on the physical and chemical properties of drugs compound when purchased from different sources. regarding their rate of penetration and diffusion Lewers el al. (117) have noted that certain of into the skin may lead to unexpected toxic or the synthetic adhesives have a distinct toxic untoward reactions. Vickers and Fritsch (123) effect. For example, in animals they found have documented this fact with several cases * that both the monomer and the polymer caused where naphazoline was the test drug and Saran death when injected into the liver and peritoneal the plastic film. These aforementioned authors SPI - 12814 1>,Vol. No. 11, November 1964 1299 give the following warning: "The knowledge of the vast increase in percutaneous absorption due to Sarau occlusion might tempt clinicians plastic device will Ire safe for intended use. Standards must be created for "medical use" plastics as well as standards for the final plastic to try to increase the effectiveness of other topical preparations with possible serious or even disastrous consequences." device. These standards obviously must in clude biological, physical, and chemical methods of testing. Finally, these standards must be DRUG-PLASTIC CONSIDERATIONS come part of the official compendia to insure legal status. Less recognized as a problem, probably due to the paucity of reports published, is the con sequences which might result when a drug or drug product is kept in contact with a plastic material used as a container or administrative device (121-131). These problems may be collectively grouped into five general categories: (n) Permeation--Oxygen or other gases per meating the plastic material and causing an incompatibility or, conversely, a volatile con stituent in the drug product passing out of the container or device. (b) Leaching--One or more ingredients mi grating from the plastic into the drug solution. (c) Sorption (including adsorption and ab sorption)--One or more constituents being removed from the drug solution into the plastic by a sorption process. (d) Chemical Reactivity--One or more ingredi ents reacting by covalent bonding with the polymer or one of the additives in the plastic. (e) Alteration in the Physical Properties of Plastics--Depending to an extent on one or more of the above or due to environmental effects, the container or device may undergo sufficient changes to no longer function as originally intended. The above five considerations have been reviewed in some detail in previously published papers (132, 133) and thus will not be discussed any further in this review, except to emphasize that both the manufacturer and the user must share in the responsibility of safeguarding the health of the patient when plastic devices are to function as containers or devices for storing or administering drug products. Autian (58) has published a guide to hospitals in the selection of plastic devices, while The University of Texas Medical Center has under taken the task of developing its own standards for plastics [see report by Autian and Nieolaides (134)]. Brewer and Bryant were the first in this country to publish biological methods of testing of plastics to be used in medical practice (25). Workers in other countries recognizing the plastics problems have recommended also that stricter controls be maintained on plastics and have suggested a number of testing pro cedures (135-137). Guess and Autian (138) have presented a tentative protocol for the bio logical testing of plastic materials. In this country the Pharmaceutical Manufacturers' Association with support from the Society of Plastics Industry has developed a group of biological and physical chemical tests for plastics to be used with drug products. Much work still remains to be done now and in the future before adequate standards are developed. Certainly, greater emphasis should be given to basic studies on plastics as they are related to medicine. In the past such support from industrial groups interested in plastics has been minimal, but it is hoped that a reversal of this trend will soon be forthcoming. There is also a need for better communication among groups working to manufacture and distribute plastic items to the medical profession. Often one group is not aware of what the other group has done to a plastic item. This point is clearly brought into focus by Bender (139), a consulting engineer, in his excellent article dealing with the trend toward plastics in surgery and medicine. The plastics problem is such a vital health NEED FOR STANDARDS issue that it no longer can be kept as an "inci dental" hazard with the ever-increasing use of An analysis of what has been reviewed in this plastics in all phases of medical practice. Good paper should note that plastics are not so safe public health practice requires as much emphasis as originally thought. In no manner docs this on measures to prevent a potential danger from suggest that plastics should be banned or elim becoming a serious reality as to combat the inated from medical practice. Such an expres danger once it has occurred. Perhaps the best sion would be ridiculous and certainly is not example of this in the past years is the pesticide tenable to the many outstanding advantages to issue brought into shocking public attention by be gained by the use of the synthetic polymeric materials. Rather, a method should be sought which would insure that a particular plastic or Rachel Carson's "Silent Spring." Even though adverse criticism was given to the author for having overplayed the problem based upon SPI -12815 1300 tl Journal of Pharmaceutical Science, meager scientific evidence, it was interesting to note that the President's Science Advisory Com mittee has made a number of recommendations to prevent some of the possible consequences il luminated in the book "Silent Spring" (140). In much the same way, though on a much smaller scale, plastics for medical practice deserve equal attention. REFERENCES (1) Harrii, D. K., Bril. J. 1mi. Utd . 10. 2.V,(19Vi). (2) Wilson, R- H., nod McCormick. W. E.. Ind. hied. Surg., 23, 479(1054). (3) Ibtd., 24, 491(19.55). (4) Ucbcr, E. E . Brit. Plastics. 28, 428<l9.Vi). (5) Rogers. J. C.. A M.A. Arch. Ind. Health. 12, 470 (1955). (6) Fn'rhall, L. T.. ''Industrial Toxicology," 2od cd., The Williams & Wilkins Co., Baltimore. Md., 1H7, pp. 291-. (7) Harris. D. K . Brit. J. Ind. Ifed.. 18. 221(1939). (8) Wilson. R. H.. and McCormick. W. .. A.M.A. Arch. Ind. Health. 21, 536(1960). (9) Rolf. H., "Kuoststoffe in der Mcdizio." Johann Ambrosius Barth. Lripsifc, Germany. lD.Vi. (10) Wesofowski. S. A.. ''Evaluation of Tissue and Proa- thetic Vascular Grafts," Charles C Thomas, Springfield, 111., 1962. (11) Morris, G. E., Arch. ind. B*g. Occupational Med., 5, 37(1952). (12) Harris. D. K.. Brit. J. Dermoid.. 72, 1QV1960). (13) Cranch. A. G.. Ind. Utd.. IS, I6 IV46 (14) "Eye on Contact Lenses." Xrwsxeek. 83, 70^ March 30, 1964). (15) Patty. F. A., ed.. ''Industrial Hygiene and Toxi cology," Vol. II, Industrial Publishers. luc.. New York. N'. Y., 1949, p. 1105. (161 La Veen, H. H., and Barbcrio. J. R..Ann. Surg., 129, jsiivsv;. ,(17) Scales, J. T., proc. Roy. Soc. Med.. 48.847(1953). (18) Schwarts, L..J. Invest. Dermaul.. 6 23V1945). (19) Hine. C. H.. et al.A.MA. Arch. Ind. Beahk, 17,129 (1958). (20) Zapp, J. A.. <bid.. 25, 324'ffcf7>. (21) Calnan, C. D., Marten. R. H.. and Wilson. H. T. H., first. Med. J., 2, 544(1958). (22) Harrison, J. H., Swanson. D. S-. az>d Lincoln. A_ F., AM.A. Arch. Surg.. 74, 139<1957r (23) Usher. F. C.. and Wallace. S. A.. ibtd .76,967(1958). (24) Little, K., and Parkbouse. J,, Lancet. 1982, W7. (25) Brewer, J. H., and Bryant. H_ EL. Tns Jocvkal, 49, 652(1960). (26) Lawrence. W. H.. et al.. ibtd. 52, 958'19G3j. (27) Autian. J.. et al.. "An Evaluation of Two Urinary Bags as to Their Biological Activity re Amman/ presented at the A.A.A.S. Cleveland. Ohio ptreer. lAereabo 1983. (28) Bansmer. G.. Keith. D.. and Te^acL H.. J. Am. hied. Assoc.. 167, 1605(1058). (29) Derrick. J. R.. Surgery. 54. 34.5 lk3 (30) Taylor, F. W.. and Rutberfjrd. C. E . Arch. Surg.. 86, 177(1963). (31) Cox, C. E.. and Hinmaa. F.. J; . J. 4a. Med Assoc., 178, 919(1961). (32) Turner. F- C.. J. Xail. Cane* /**-' . 2. hi J5*41 . (33) Oppenheimer, B. ft.. Op;*S5saer E T-. and Stout, A. F., Proc. Soc. FLxftl. Bid. Me 67. ZZ IS 4S . (34) Ibid.. 79, 366(1952). (35) Druckrey, H., and Sckaukl D., Z- Xttmr'cwsck.. 75, 353(1952). (36) Oppenheimer, B. S-. eS al. Scorn te. 118, 30* I9A3 . (37) Druckrey. H.. and Sdumkl, D,, A a* L'm: Intern. Contra Cancrum, 10, 119(1951). (38) Laskio, D. M.. Robinaon. L B^ and U'cnamo. J. P.. Proc. Soc. Exptl. Bid. Afed- 7. 3S> !X34 (39) Oppenheimo-. B. S..ef I--Caa^er Jeer . 15,33! 1913.. (40) Oppenheimer, B. S.f at ml- Ac* f'tw inter*. Contra Centrum, 15, 659(1959). .(41) Oppenheimer. B. S.. et al-. Conner, 11. 204 '19561. (42) Danishefsky. 1.. at al.. Center In. 19 1234 1959;. (43) Bering. E. A., rs ai.. ibid- 15. IW . (44) Xothdurft, H.. Sainrwiixw\ci-i42, 75T955'>. (45) Hueper. W- C.. A.MA. A-cn. 7,5*I959i. (46) Hueper. W. C.. Am. J. Cut Pash-*. 54. S2S I960;. (47) Hueper. W. C.. Path. Mscr:H:L 24- 77 1961). (48) Russell, F. E.. at al.. J. Xcl- Ccn-xe Inti.. 25, 305 (1959). (49) Bing, J., Acta Paikai. J/ir ri:i. Sccn.i.. 105, 16 (1955). (50) Horning, E. S.. and Alexander P. *vv Cancer Campaign. 35th Annual Report Part ST 44-A>. J9l>7. (51) Oppenheimer. E. T.. c . Ctxur Res . 21, 132 (1961). (52) Harris. H. I.. J. Intern. CS*rg- n.t 35.8V) 19811. (53) Bcrinaon. M.. Fiance. 1. J sad Bin bm-w H T.. New Engl. J. Med., 258, 471(1956 . f.M> Edrhton. B. C.. Lanul. 27. 112<m). (55) Autian, J., and Brewer, J. H., Am. J. Boat Si IS, 313(1958). (56) Meyers, D. &.. Autian, }., and Guess w 'Toiicity of a Series of Citric Acid Esters Used' > p,*- tieixers." presented to the A.Pm.A., Miami Beach ___ !?' May 1963. . (57) Autian, J., Am. J, Hoap. Phorm., If, 329(19fttt (58) Autian, J., Bull. Parenteral Drug Assoc ti* /' (190622)).. " ,0> ** (59) Knudston. K. F., Am, J. Clin. Pathol., 21, 813rio*i (60) Bordet, J..and Geogou. O.. Ann. Inst. Ipastcm, */ 822(1903). *V, (61) Jaqucs, L. B., al al.. Can. lied. Assoc. J m (1946). -.*- (62) Walter, C.W., `'SurgicalForum: Clinic*! Cn^__ _ * 1950." Vol. I. W. B. Saunders, Co., Philadelphia Pa to*?1' p. 483. * (63) Strumta, M. M., Colwell, L. S., and Ducan A i 3 Ijsb\.. Clin. Med., 53, 106(1959). * ' U, (64) Ballinger, W. F., and Cohn, H. B., Surgery it? ju (1961). 4,fl1 (65) Wiener. A. S-. J. Am. Mtd. Assoc., 175, 644(ltMtf (66) Gardner, P. H.. Howell, D., and Hirsch. R n Lai. Clin. Med.. 43, 196(1954). * /- (67) Klein. E., et al.. Bibliotheca Boematd., 7, 382(195A\ (68) Stewart. J. W.. and Sturridge. M. F., Lancet, 19& (69) Meyler, F. L.. WiUebrands, A. F., and Durrer n Circulation kes., 8, 44(1960). (70) Keith. H. B., et al., J. Thoracic CardioaascuLm '<* Surg., 4i, 404(1961). *** (71) Hiroae, T., Goldstein, R., and Bailey, C. P <u 45,245(1963). '* ^ (72) Lindberg. D. A. B., et al.. Am. J. Pathol., 50. tw ' (1961). (73) The Bulletin, Dow Corning Center for Aid to Medical Research. S, 7(1963): (74) Fraenkel. A., WV*. Klin. Woehschr., 3, 4?3(18&0> through Stinson. X. E.. Nature, 18S, 678(1960). *- (75) Detrrling. R. A., Jr.. Transplant. Bull., 3,125(1956) (76) Shuraway, K. E.. Gliedman, M. L., and Lewis F I * Surg. Gynecol. Obstel.. 100, 703(1955). ` (77) Ellis. F. H.. Jr., and Kirklin, J. W., Postgrad. Mad 20, 494(1956). (78) Rob. C. G . Eastcott, H. H. G.. and Owen, r firt/. J. Surg., 43, 449(1956). (79) Fitch. E. A., and Denman, F. T., A.MA * --A Surg., 75, 1027(1957). (80) Creech. O.. Jr., at al.. Surgery, 41, 62(195? (81) Rob. D., Transplant. Bull., 4, 51(1957). (82) Fitch. E. A.. Denman, F. R., and Waldron. G. W A.IS.A. Arch. Surg.. 81, 824(1960). (83) Payne, W. S., and Kirklin, J. W.. Ann. Surg., 154,53 0961). (84) Adler. R. H.. and Darby, C.. I*. 5. Armed Forces Med J.. 11, 1349(1960). (85) Harrison. J. H.. Am. J. Surg.. 95, 3(1958). (86) Hamson, J. H., Surg. Cysrrol. Obstel.. 108, 433 (1959). (87) Dale. W. A., and Kigutdula. F. N., AM.A Arch. Surg.. 78,246(1959). (88) Dale. V. A-. and Mavor. G- E., Bril, J. Surg., 46, 305(1959) (89) Cate. W. R.. Jr.. Am. Surgeon. 25, 523(1959). (90) Edwards. W. S . and Tapp. J. S-. Surgery, 38, 61 (1955). (91) Seilagyi. D. E.. Sarg. Clin. North Am.. 39, 1523 (1959). <92> Phillips. C E., Jr . DeWecae. J. A., and Campcti, F. L . A M.A. Arch- Surg.. 82,38(1961). <93' Edwards. W. S . Sarg. Forum. 8, 446(1957). i94 Knna. G . and Begg. C. F.. Sargcry. 42,622(1957). it*.5* Wesolowski. S. A., et al.. ibid., 50,61(1961). >9C Newton W. T.. Stokes, J. M . and Butcher. H. R., Jr ibid . 46, 579-1959 . t97) Irvine, W. T.. Kenyon, J. R., and Stiles, F. J., BHl Med. J . 1963,360. k ;PS> Coekett. F. B-. and Maurice. B. A., ibid.. 1963,353. (99) Wesolowski. S. A., et al.. Surgery, 53, 45(1963). <100* Jordan, G L, Jr., et al.. ibid.. S3, 19(1963). (1011 Frater. R. W. M., and Ellis. F- H.. Jr.. "Prnatbetk 5'alves for Cardiac Surgery." Charles C Thomas. Publisher. Springfield. IU.. 1961. p 244. 102 < Kotff. U\ J., at al., ibid., p. 199. vl03i Muller. W. H . Jr.. Littlefieid. J. B., and Damaann, J. R.. Jr., ibid., p. 493. (104) Gott. V. L., at al.. 5rgrry, 50, 382(1961). (105) Kisksddes. Vi. S.. Plastic Rrcoustruc. Sort., 15, 79 U (106) Hamit. H. F.. A M.A. Ards. Surg., 75, 224(1957). (107l Brown. J. B.. Obwilm. D. A., and Fryer, XL P.. Asa. Surg.. 152,534(1960). (106) Maaderino. M. P.. and Salratore. J., Med. Sd., 4* 215(1956'. ,1091 Salvatore. J. E.. and Manderino. M. P-. Ann. Sarg.. 149. 107<1958. (110) Manderino. M. P.. sod Sal-siort. J. E., Am. J. Surg.. 97, 442 1959'. till) Redler. I.. Brown. G. G., Jr., sod Trekefl, W. V., Southern Med. J.. 53,392(1960). (112) Macoomb. R. K.. Hollenbcrg. C.. and Zingg, W., Sarg. Fenm. II, 454.1960). SPI -12816 Vol- S3, No. 11, November 1964 (113) Coover, H. W., Jr., el al.. Soc. Plostus Eng. J., 15* 413(1959). (114) Nathan. J. S.. et al.. Ann. Surg.. 152, 648(11*50). (115) Carton. C. A., et al., J. Senrasurg., 18, 188(1901). (116) Bloomfield, S.. Barnert. A. H.. and kanter. P.. Am. r Ophthal.. 55. 742(1963). (117) Lewers, D. T., Just-Viera. J. O., and Yeager, G. H., Maryland State Med. J., 12, 141(1963). (118) Yeager, G. H., and Cowley, K. A.. Ann. Surg.. 128, 509(1948). (119) Garb. J.. AM.A. Arch. Dermatol.. 81.606(1960). (120) ScfaolU. J. R.. ibid., 84. 1029(1961). (121) Sulxberger, M. B.. and Witten. V. H.. ibid.. 84. 1027 (1961). (122) Hall-Smith, S. P., Bril. Med. J.. 2. 1233(1962). (123) Vickers, C. F. H.. and Fritsch. W. D.. A.hfJi. Arch. Dermatol., 87. 139(1963). (124) Autian, J., and Dborda, C. N., A m. J. Hasp. Pharm., 16, 176(1959). (125) Marcus, E., Kim, H. K., aod Autian. J.. This Iouknal. 48, 457(1959). (126) Kim. H. K., and Autian. J.. ibid.. 49, 227(1960). (127) Autian, J., and Shaikh. Z. 1., Dauc Stakdaids, 28, 103(1960). 1301 (128) Guess, W. L.. Worrell, L. F., and Autian, J.. Am. J. Hosp. Pkorm.. 19, 370(1962). (129) Richards. J. M . aod Whittet, T. D.. Ckrmtit Druggist, 169, 16(1958). (130) Denoel. A., and Fagard, J., J. Pharm. Belg.. 14, (11/12), 384(1960). (131) Fagard. J., ibid., 15, (3/4), 126(1961). (132) Autian. J.. This Jouknal. 52, 1(1963). (133) Ibid., 105(1963). (134) Nicolaides, M. J., and Autian, J., Hospitals, 55, 63 (1961). (135) Thomas, J. J., and Lagrange, G., J. Pharm. Belg., 16, (3/4), 59(1962). (136) Braun, B., and Kummell, H. J., Dent. ApolhekerZtg., 105, 467(1963). (137) Braun, J., J.Mondial Pharm., 1963, (No. 3), 151. (138) Guess, W. L., and Autian, J., "Biological Testing of Plastics to Be Used in Medical Practice," presented at the 6th Pan American Congress of Pharmacy and Biochemistry, Mexico City, December 1963. (139) Bender, R. J., Plastics Design Process., 3. 14(1963). (140) Anon., Science, 140, 878(1963). * J SPI -12817 Vol. C.2, 1905 14321 23--Sewage and Wastes 14322 contain 17 g. NnOH/1., 10 g. NajS/1., and 110 g. NajCOi/1.; tanning of grccn-saltcd steer hide were carried out on a lab they were treated by pptn. of the sulfide S (by adding 50 g. of scale, and the individual wastes from various operations of thi polyaerylamidc/m.* water, followed by the addn. of 7.3 kg. of processes were collected and analyzed. The individual waste FcSO/kg. NajS and filtration of the ppt.) or by evapn. to a seemed to be classified into two groups, although they varie< NaOJI content of 25% (the NajS and NajCOa pptd. and were widely in characteristics and vol. The continuously discharge! removed by filtration) and utilization of the resulting soln. in the a wastes, such as the wash waters from mech. operations and wash purification of the pyrolysis gas. A. Aladjem ing operations were, in general, the weaker waste, although the; Effect of iron and thiocyanates on the purification of waste were large in vol. The wastes, such as those from soaking, lim from gold extracting plants by the ion-exchange method. I. D. ing, and tanning operations were the stronger wastes, and all c Fridman, L. N. Kuznetsova, and B. L. Scrcbryanyi. Zh. them were discharged intermittently. The wastes from pr< Prikl. Khim. 38(3), 482-7(1905)(Russ). The effect of complex_tanning operations were, in general, alk., and were rich in di; ions of Fe such as Fc(CN)4_ add of NCS- on the sorptive capac- solved and suspended org. solids. Their ratio of B.O.D. t ity, a, of anion-exchange resins for CN- was studied with resin chcm. O demand (C.O.D.) was much larger than those of th AB-17 contg. (a) 6% and (ft) 16% divinylbenzene. The irrever- wastes from tanning operations. The wastes from chrome tann siblc sorption of Fe(CN V- lowered a. The effect increased with ing processes were low in pH and contained a large amt. of dir the concn. of Fe(CNV- and was higher with (a) than with (ft). solved inorg. matter and a considerable amt. of toxic Cr salts Dil. acids did not regenerate CN- from the complex anion of Fe. The vegetable tanning wastes constituted the worst fraction Desorption of Fe with 0.5N HC1 was greater than with 0.2N of tannery wastes, although they were small in vol. Th HtSO, and a of AB-17 in the SO< form was 1.5-2 times lower vegetable tanning waste accounted for only 8% of the tota than in the Cl "form. The results were ascribed to the formation vol., but carried about 47% of the total C.O.D. II. Chang of Fe4Fe[Fe(CN)] and Fe[Fe(CN)i]i. The effect of SCN" of the composition of the wastes by mixing and storage ions was similar to that, of the Fe anion. In the presence of Ibid. 267-75. A part of the composite wastes was stored for SCN-, a of (a) decreased from 6.8 to 1.6% and that of (ft) from -- few days and redn. of the pollutional strength of the wastes wa 4.9 to 0.37%. The extn. of cyanide in the process of desorption examd. Furthermore, a survey of the compn. of wastes dis in every cycle was 80%. GBJR . charged from a vegetable tannery was carried out. It was foum Monitoring Kraft Mill combustion processes by gas chroma- that the pollutional strength of the composite wastes from prt tography. F. N. Rhoad (Union Bag-Camp Paper Corp., Savan- tanning operations increased with the amt. of mixed limin, nah, Ga.). Southern Pulp Paper Mfr. 28(3), 60, 62 , 64(1965) wastes, but more redn. of pollutional strength during storage wa (Eng). CO, Oi, N, CH,, CO, and Hi in lime kiln flue gases are 6 attained by increasing the ratio of liming wastes. As regard detd. by the use of a modified gas chromatograph. The carrier both the composite wastes from chrome tanning, dyeing, am gas is He for all components except Hi, and Hi is detd. by using fat-liquoring operations, and the composite wastes from vegetabh Ni as carrier on a duplicate sample. The path of the sample is tanning and bleaching processes, their pollutional strength wa; through an 8-in. silica gel column, one side of the thermal cond. greatly reduced by mixing with the combined wastes from pre detector, a 24-ft. C-22 acid-washed firebrick column, a 6-ft.__tanning operations. The survey of vegetable tannery waste: mol. sieve column, and the other side of the detector. The col- revealed that the compn. of the wastes varies widely from time tc umn temp, was 40, and carrier gas flow rate was about 100 ml./ time, and the suspended matter is usually very difficult to settle, min. This arrangement has the carrier gas passing one side of ' but when pH of the wastes was raised above 11, owing to the the detector while one component passes the other side. Polar- large amt. of alk. wastes discharged from pretannery, the sus- ity is switched after the COj peak is recorded. The sample is pended matter and some of the dissolved matter coagulated and dried by passage over CaSO< prior to entry into the sample loop, d formed large rapidly-settleable floes. V. Effect of the treatment The detection ranges, in % by vol., are: COi 0.1-20, Oi 0.1-22, with lime. Ibid.(7), 317-28. A study was made of the purifica- Nj 0.1-80, CH4 0.1-10, CO 0.1-10, H,0.1-10. Several hrs. are tion of tannery wastes by flocculent sedimentation by using Ca- required to purge the system of He after changing to the Nj (OH)) as a coagulant. The efficiency of the treatment with lime carrier. F. B. O'Neal varied with the properties of tannery wastes. Usually the C.O.- Use of the reaction with diazotized sulfanilic acid to determine__D. and the suspended matter content of tannery wastes, varying phenols in waste waters from rosin-turpentine oil production. 1300-4500 and 1360-2500 ppm., were reduced by about 50-87 and K. K. Lebedev. Sb. Tr., Tsentr. Nauchn.-Issled. i Procktn. 60-90%, resp., by increasing the pH value of the wastes to 11.5- Inst. Lesokhim. Prom. No. 15, 119-22(1963)(Russ). This re- 12.0 by the addn. of lime and settling for 30 rain.-2 hrs. When action cannot be used owing to interferences from terpenes. FcCU was used in conjunction with lime, further purification was Olaf Thomsen secured. For the neutralization of the supernatant liquor of Purification of sulfite pulping waste by adsorption. D. e lime treated wastes, bubbling of CO> into the liquor was very Ruzickova and V. Sccova. Sb. Vyskum. Prac Odboru Celulozy effective, although further purification of the liquor could not be Papiera 9, 73-116(1964XCzech). Pulp mill waste contg. 200- expected by this neutralization. Tannin and Cr salts in the 5000 mg./l. org. matter, obtained from Ca(HSOj)2, NaHSO wastes were completely removed by coagulating with lime, but scmichcm., and NajSOjsemichem. pulps, were purified by adsorp- the partial hydrolyzates of protein were difficult to remove by tion on slag, washed coke (I), waste lignite, and coke fly ash (II). this treatment. VI. Effect of anaerobic digestion. Harukazu Their adsorption isotherms disclosed max. capacities for II and -- Toyoda and Akira Futami. Ibid. 329-37. When an artificial possibly I. The optimum grain size was 1-2 mm. and the flow waste contg. tannin was digested in the anaerobic condition, rate 0.1-0.2 m.Vm.yhr. Expressed as O consumed by the some C.O.D. components of the waste were gradually accumu- waste, II adsorbed 20.9 g. O/kg. when a filter tube was used and iated in digesters, and the treatment of the waste became gradu- 31.16 g. when a continuous filter was used. With intermittent ally difficult. Treatability of vegetable tannery wastes by the flow, the adsorbent could be partly regenerated because of , anaerobic digestion process was dependent upon the character oxidn. The effluent approached pH 7 after treatment, hence the ' of the wastes, and in general the composite vegetable tannery pH of the original waste was irrelevant. The sulfite pulp wastes were able to be treated by the anaerobic digestion proc- effluents were freed from up to 70-95% oxidables and dry matter ess, provided an acclimatized sludge was used and loadings of was reduced ~50%. Advantages of the adsorption method in- wastes were suitably adjusted. For instance, when the wastes elude low space requirements and cheap refuse low-cost raw ma- ranging from 880 to 2500 ppm. of B.O.D. were employed, and terials. Biochem. methods require large nrcas. R. Ripa __their loadings were adjusted to 0.2 to 1.0 g. B.O.D./l./day, it Water economics and possibility of agricultural utilization of was possible to treat the wastes continuously, and a B.O.D. sewage from sugar factory at Baworow. l'iotr Frochal. Gaz, redn. of about 78-00% and a C.O.D. redn. of 60-77% were ob- Woda Tech. Sanit. 38(8), 271-6(1904)(Pol). It is proposed to tained. VII. Effect of step-wise treatments by anaerobic di- usc the sewage from a sugar factory contg. an av. of N 62.3, gestion, activated sludge, and chemical precipitation. Ibid. P)Os 9.2, KiO 73.8, and CaO 215.0 mg./l. as a fertilizer. This 338-46. Effluents from anaerobic digestion of vegetable tan- application would lower the surrounding water contamination, g nery wastes were further treated by chcm. pptn. adsorption, Irena Kloczko and(or) activated sludge processes, and their effectiveness was Rate constants in the reaction of biochemical oxygen demand compared. Some of the components of the wastes removed by of spent sulfite liquor wastes. Czeslaw Leszczynski, Zofia each process differed mutually, and by treating the effluents from Skwara, and Jerzy Zielinski (Inst. Cclulozowo-Papierniczy, Lodz, anaerobic digesters successively by these processes addnl. B.O.D. Poland). Gaz, Woda Tech. Sanit. 38(10), 335-7(1964XPol). and C.O.D. removals were obtained, and a higher degree of puri- Overall waste from a paper mill and those from a pulp mill were-fication was attained. For instance, when a vegetable tannery dild. 1:25, 1:100, or 1:250, and B.O.D. was detd. by diln. and waste having 3784 ppm. of C.O.D. was used as a sample, about manomctric methods. The B.O.D. of the overall waste varied 70% of the C.O.D. was removed by the anaerobic digestion proc- from 57 to 762 mg. O/l., and in wastes from the pulp mill it ranged ess, and when the effluent from the anaerobic digesters was fur- 74-716 mg. O/l. The rate const, of biochem. oxicln. was in the ther treated by the activated sludge process about 90% of C.O.D. 2 cases 0.19 and 0.20, resp. Irena Kloczko i was removed, and the effluent from the aerators could be further The treatment of tannery wastes. I. Properties of the n treated with FeCli or lime, or with activated C with the results of wastes from various parts of the tanning process. Harukazu about 94 to 98% and 99 to 99.6% removals of C.O.D., resp. Toyoda, Tetsuo Yarisawa, Akira Futami, and Masayoshi RCTT Kikkawa. Tokyo Kogyo Shikensho Hokoku 59(6), 246-56(1964) "7 Characteristics and treatment of waste waters from production (Japan); cf. CA 62, 6262ft. Chrome tanning and vegetable of vinyl resins. Boleslaw Kotulslri (Zaklady Chem., Oswiedm, SPI -12818 14323 Chemical Abstracts 14324 Vol. 62, 190.' Poland). Gaz, Woda Tech. Sanit. 38(10), 300-0(1004)(Pol). Waste waters from the production of CIIjCHCI and from its polymerization by both emulsion and suspension methods arc considered. Sewage from CHiCHCl production contained C,H, <2.5, HC1 15-80, aldehydes <1, and CHjCHCl 100-400 mg./I. Sewage from emulsion and suspension polymerization plants had, resp.: pH 6--7 and 8; dry residue 1.0-10.0 and 8.8, CHjCHCl 0.5-9.0 and 1.3, and surface-active agents 0.02-0.2 and 6.0 g./l.; oxidizability 0.1-0.6 and 2.0, chdm. O demand Natl. I.ab., Oak Ridge, Tenn.). Chem. Eng. Progr., Symp. Ser 60(63), 32-40(1964 )(ICng); cf. Duckham, et at., following abstr The feeds investigated were TBP-26 solvent extn. waste. Dare wnstc, and conventional Purex formaldehyde-treated wasti The waste was coticd. by evapn. and by steam-stripping of th HNOi- The coned, soln. was then introduced into the heate calcincr pot where it was denitrated, brought to a solid cake, an calcined. The process is workable and safe. Albert E. Nugent, Jr. 0.2-2.0 and 8.8, and B.O.D. B.l-0.6 and 2.0 g. O/l. It was Development of fluidized bed waste _calcination process found that polymerized CHjCHCl is most efficiently removed by__J. A. Buckham, L. T. Lakey, and J. A. McBride (Phillips Petro coagulation and sedimentation. Optimum dose of coagulant Co., Idaho Falls, Idaho). Chem. Eng. Progr., Symp. Se A1j(S04)j.18Hj0 for sewage from suspension polymerization is 60(53), 20-31( 1964)(Eng); cf. Tomlinson, CA 60, 3866c. All 0.1-1.0 g./l. For sewage from emulsion polymerization thermal mann, et at., CA 60, 15584<f, Whatley, et at., preceding abst coagulation is advisable. Irena Kloczko A plant-scale, fluidized bed calcination process was construct! ^ Characteristics and purification of waste waters from produc to utilize a totally continuous process for the conversion of aq. tion of vinyl resins. Boleslaw Kotulski (Zaklady Chem., high-level radioactive wastes into compact granular solids, Oswiecim, Poland). Gaz, Woda Tech. Sanit. 39(2), 46-9(1965) feed soln. of Al(NOj)j waste was injected into a heated bed < (Pol). The phys.-chem. characteristics and toxicity for living granular solids, such as sand seed particles. The bed was mail organisms (Daphnia magna) were studied for waste waters from tained at 300-600, and the thermal decompn. of the feed soh the production of monomers and polymers of CHjCHOAc (I) and caused its solid reaction products to build up in layers on the be CHiCCli. Sewage from the synthesis of I had pH ~4, O con- particles. The introduction of fluidizing gases, such as air, ca sumption ~500, chem. O demand ~19,000, and B.O.D. ~2000 -- ried the gaseous products from the bed to scrubbers. Amorphoi mg. O/l., and a Zn content ~80 g./l. The sewage killed living and a-AljOi were the chief solid reaction products. The redn. i organisms even when dild. 1:10000. The degree of pollution of waste vol. was 17-fold for 80% a-AIjOi of bulk d. 1.6 g./cc. an other sewage studied was much greater. In coagulation with 10-fold for amorphous AljOj of bulk d. 0.95 g./cc. CaO and NaCl, the former was more efficient. The sewage from Albert E. Nugent, Jr. polymerization and copolymerization of CHjCClj contained many Purification of radioactive waste solutions with inorganic ns morg. salts and had relatively low toxicity. Irena Kloczko tural ion exchangers. I. The use of silicate clay as ion exchai Role of hydroxides and carbonates in the flocculation and sedi ger. G. Sachse and E. Leibnitz (Zentralinst. Kernphys. mentation during the clarification of sewage from viscose produc Dresden, Ger.). Kcrnenergie 4(8), 633-6(1961)(Ger); cf. C. tion. O. P. Sinev. Dokl. XV-oi [Pyatnadtsatoi] nauchn. Konf. 62, 24426. Clay from the Radgendorf region was analyzed am Novocherk. Politekhn. Inst. Stroit. Sekts., Novocherkassk 1964, characterized by electron microscopy, differential thermal analy 75-6(Russ). Fe(OH),, Zn(OH),, Mg(OH),, and CaCO, im sis, and x-ray analysis for the purpose of using it for the concn. o proved flocculation and sedimentation of hydrated cellulose, the liquid radioactive waste. The stabilization ;sf the clay fo which in turn accelerated the hydrolysis of metal salts, coagula use in the column operation was also examd. by mixing poly tion of hydroxides, and crystn. of CaCOi. The optimum pH for acrylate with the clay. IV. Leaching resistance of radioactive the flocculation and sedimentation of suspended solids was 10.5- annealing products of clay from the Radgendorf region. Ibid 11.5. From Ref. Zh,, Khim. 1964, Abstr. No. 231326. 5(3), 187-90(1962). The clay samples which adsorbed ,I7C: MVRK "Sr, and u,Ce were heated at 120-900 and the leaching of th Pilot plant denitration of Purex waste with sugar. E. A. activity with HjO was examd. at room temp, and 80. Whe Coppinger (Gen. Elec. Co., Richland, Wash.). AEC Accession heat-treated at 700, 0.02% of mCs, 0.4% of "Sr, and 0.3% c No. 35243, Rept. No. HW-77080. Avail. OTS, 16 pp.(1963) 1MCe were leached, but with the clay treated at 900, <0.05% c (Eng). A plant flowsheet was developed and successfully demon- "Sr and 1MCe were leached; thus leaching of the activity df strated in pilot plant equipment.. A l AM sugar soln. was added__creased with the heat-treating temp. N. Oi to 25 1. waste for 12 hr. at 100, and the mixt. was digested for 18 hr. The initial HNO concn. was 6.14Af. The residual was 0.94 and 0.90Af after 12 and 18 hr. of digestion, resp. A residual C content equivalent to 1.9 and 0.4% of the total C fed as sugar was present after 12 and 18 hr. of digestion, resp. About 19 moles HNOt were destroyed per "mole of sugar fed. Foaming was produced during batch denitration with sugar by adding 0.4 g. dibutylphosphate/1. of synthetic waste. The addn. of 0.2 g. Dow-Coming Antifoam B/l. of waste reduced foam levels by about a factor of 2. An induction period of ~6-9 min. was observed before the reliction started. The length of the indue- Removal of cobalt and chromium by precipitation and ion ex change on 60il, lignite, and dinoptilolite from citrate-containin radioactive liquid waste. D. B. Hawkins. AEC Accession Nc 35235, Rept. No. IDO-12036. Avail. OTS, 24 pp.(1964XEng) "Co and "Cr can be removed from sep. waste streams contg ammonium citrate and alk. permanganate by a combined proc ess of pptn. and ion exchange. The general procedure used wa to neutralize the alk. permanganate with HjSOi and to combin' this soln. with the ammonium citrate soln. causing the oxidn. o the citrate. The Co and Cr originally present as complex anion "TM^tek tocationic fmmTy tm^roce^ and^venge, tion penriod increased as initial sugar addn. rates were reduced. Gentle air sparging reduced the induction period by about a factor of 2. The use NaNOj as a means of decreasing the induction period was not successful. Sugar soln. was added to cold waste, and the mixt. was heated to det. the pot pressures and tower --f.ro--m soln. by the MnOi--ppft. formed by redn. of the permanganate The Co and Cr remaining in soln. were then removed by ion ex change on lignite, soil, and dinoptilolite. Distribution cocffs for Co and Cr were 56 and 1.2, 800 and 36, and 24 anc^O.l for soil, lignite, and dinoptilolite, resp. Lignite used in combination pressure drops that could be developed under abnormal condi- . wkh the oxidn._pptn. step resuited in the removal of >99.7% o! tions A decrease in pot vacuum of 30 m.HjOand a tower pres- > a Co and 96 ot ^ ,,Cr from ^ waste stjreams. Fr0It oraPr0f 8 ,n` ?' were ?bs.e7ed hen 20 1. Of waste and Nud ^ Abs(f $19) 4713(1964). 2.71.2.5-Af sugar soln. were mixed together and rapidly heated to _ ' .. t\ 100. From Nucl. Set. Abstr. 17(20), 4704(1963). TCNG .N- TCNG _ AL "eri Report of invention-solvent extraction process for recovery of (USSR) 18(3), 268-70(1965XRuss). A review is given of the re strontium, cerium, rare earths, and cesium from radioactive Ports n : title subject that were presented at the Third In waste solutions. Lane A. Bray (Gen. Elec. Co., Richland, ternational Conference on the peaceful uses of Atomic Energy Wash.). AEC Accession No. 5988, Rept. No. HW-75537. Avail. OTS, 14 pp.(1962)(Eng). A solvent extn. process is de scribed which removes Sr, Ce, Cs, and rare earths from acid solns. (pH 3-5) in 1 operation. The process is based on the use Geneva 1964. A. Aladjem Biochemical research methods of the phenomenon and of the efficiency of the purification of waste by activated sludge. Lydia Vaicum. Hidroteh. Gospodarirea Apelor Meteorol. (Bucharest) of a solvent composed of 4-rec-butyl-2-(a-methyibenzyl)phenol 0 9(10), 646-9(1964)(Rom). A review is given of the mechanism.1 and bis(2-ethylhexyl)phosphoric add in a diluent, such as involved in the purification of waste by activated sludge and o: Soltrol 170. Data are presented on the extn. of Sr, -Ce, and Cs the methods used to control them. Edgar Perry under varying conditions. From Nucl. Set. Abstr. 19(4), 681- Biological purification of pulp-manufacturing effluents. M. A (1965). TCNG Evilevich. Tr. Vses. Nauchn.-Issled. Inst. Tsellyulozn.-Bu Equipment for a counterflow sorption using natural sorbent mazhn. Prom. No. 49, lll-31(1964XRuss). Biol, purificatior suspensions. V"Vesely, I. Napravnik, S. Gaderka, M. Paar, of effluents of the Svetogorsk pulp and paper mill was studiec and L. Maze! AEC Accession No. 6879, Rept. No. UJV- in pilot plant equipment with a capacity of 120 cu.m./day 1108/64. Avail. AEC, 14 pp.(1964XEng). A method for Fundamental prindples of the process used and ealens. of the countercurrent sorption of radionuclides from aq. waste by using process variables are discussed. To carry out the process, th< bentonite and tuff was developed on a lab. scale. The tuff effluents must be subjected to the following preliminary treat- showed relatively high extn. coefis. esp. for Cs. Values for Sr ^ ment: removal of coarse fibers; redn. of the concn. of fines tc were lower and depended on Ca ion concn. An industrial jiroc- 76 mg./l.; deodorization through removal of HjS, SOj, and tner- ess carried out in conical-bottomed mixers is outlined. From captans; neutralization; and enrichment with nutrient element: Nud. Set. Abstr. 19(4), 792(1966). TCNG (N and P). Measures must be taken to control foaming, to keep Engineering development of nuclear waste pot calcination. the compn. of the effluents const., and to introduce automation M. E. Whatley, C. W. Handler, and J. C. Suddath (Oak Ridge and remote control. The oxidn. capadty of aeration tanks SPI -12819 Vol. G1J, 1905 4877 71--Plant-Growth Regulators 4878 Tin- effects of soaking seeds ill various concns. of gibberellic acid size but prolonged the keeping qualities of uncut flowers by de on germination was liotd. for different plants. Increased total laying first-petal necrosis and 50% petal necrosis by as much as seed germination was obtained in the case of Hyoscyamus mulicas, 35%. I-awrciicc P. Miller Lcpidium sativum, Nepeta cataria, and Lilhospermum officinale. Effects of A'-dimethylaminosuccinamic acid (B-Nine) on However, no effect was observed in Peganum harmala, and an ad vegetative and fruit characteristics of apples, pears, and sweet verse effect was obtained in seeds of Digitalis purpurea. < cherries. L. P. Batjcr, Max W. Williams, and George C. R. L. DeVauIt Martin (U.S. Dept, of Agr:, Wenatchee, Wash.). Proc. Am. Role of gibberellic acid in the growth response of yeast cells to Soc. Hart. Sci. 85, 11-16(1964)(Eng). Sprays (for the most part auxin. Naohiko Yanagishima (Univ. of Osaka, Japan). Phy 500 to 2000 ppm. applied 3 times at 10-day intervals beginning 15 siol. Plantarum 18(2), 300-12( 19G5)(Eng); cf. 04 60, 4477/. to 17 days after full bloom) markedly reduced shoot growth and In respiration-sufficient diploid strains of Saccharomyces ellip- _ increased the amt. of bloom the following spring. Reduced soides, cells were elongated by auxin when gibberellic acid (GA)" growth was accompanied by shorter iuternudesaml 80-100% more was given, together with auxin. When preculturcd in the pres leaves per linear unit. Other effects were a redn. in fruit size, ence of GA, cells were elongated by a-naphthaleneacetic acid larger leaves, delay in blossoming, shorter fruit stems (Golden (XAA) or by indoleacetic acid (IAA); but when precultured Delicious), and advanced maturity of sweet cherries. with NAA or IAA, cells were not elongated by GA. In a respira Lawrence P. Miller tion-deficient mutant, whose cell elongation was stimulated by | Effects of A'-dimethylaminosuccinamic acid (B-Nine) on apple auxin without the aid of GA under special cultural conditions, quality. Max W. Williams, L. P. Batjcr, and George C. Martin the response of cells to auxin was not affected by GA under (U.S. Dept, of Agr., Wenatchee, Wash.). Proc. Am. Soc. Hort. ordinary cultural conditions. J J Willaman Sci. 85, 17-19(1964)(Eng). Sprays at 1000 to 2000 ppm. ap Effect of merapid on growth of plants. Stefan Peterfi and plied 3 times shortly after full bloom largely prevented the de Edith Brugovitzky (Babes-Bolyai Univ., Cluj, Romania). velopment of scald on Red Delicious apples in storage and sig Physiol. Plantarum 18(2), 359-67( 1985)(Ger). Several cyto-" nificantly extended the shelf life after removal from storage. static effects of merapid (I) (polymethylene glycol) were demon There were no significant differences in sol. solids, pH, and total strated on radish, mustard, lupine, broadbean, beet, corn, wheat, titratable acidity. There was less water-sol. pectin and slightly and 2 algae, Coccomyxa dispar and Stigeoclonium variabile. A more total pectin in the fruit from treated trees after storage. given concn. of 1 inhibited germination of mustard and radish, but greatly' stimulated germination of sugar beet. When in Lawrence P. Miller Ethylene action and the ripening of fruits. Stanley P. Burg hibition occurred, amylase and catalase activities were reduced; and Ellen A. Burg (Univ. of Miami, School of Med., Miami, when stimulation occurred, these enzymes were increased. I Fla.). Science 148(3674), 1190-6(1965)(Eng). Mostly a re at 0.01-1.0% prevented division and growth of the algae cells. view of reported evidence that C,H. is a fruit-ripening hormone. J. J. Willaman Kinetic studies of the author are discussed which indicate that Effect of gibberellic acid on elongation and geotropically in COj competitively inhibits the tissue swelling effect of CjHi on duced curvature of Avena coleoptiles. W. E. Norris, Jr., and _ .etiolated pea stem tissue, and that the effect of Oj can be ex Beatrice Brotzman (S. W. Texas State Coll., San Marcos). Physiol. Plantarum 18(2), 403-9(1965)(Eng). Gibberellic acid (I) at 0.1 ppm. stimulated section elongation. Mixts. of I and indoleacetic acid showed no synergistic action on elongation. I plained by postulating that it must be present at the receptor site for the CiH. Their studies on the CjH-like activity of various compds. indicate CjHi binds at a metallic receptor site in tissues. John M. Lawrence at 1.0 ppm. increased the amt. of geotropically induced curva Certain physiologic actions of kinetin in small concentrations. ture resulting after stimulation for 90 min., but did not cause a i Kunihiko Shono and Toshio Yamaki (Univ. Tokyo). Sci. detectable effect on elongation of the intact coleoptile tip. Papers Coll. Gen. Educ., Univ. Tokyo 13, 203-11(1963)(Eng). J. J. Willaman In the presence of 1 mg. of indoleacetic acid (I)/I., 0.1 mg. of Effects of substituted phenols on bud formation and growth kinetin (II; 6-furfurylaminopurine)/]. promotes wt. increase of of tobacco tissue cultures. T. T. Lee and F. Skoog (Univ. of the callus and that of the original tissue of hypocotyl quantities Wisconsin, Madison). Physiol. Plantarum 18(2), 386--402. .of Helianthus annuus; however, growth is hindered by 0.01 mg. (1965)(Eng). The tissues were grown on nutrient medium of H/I. In the presence of 0. 01-10 mg. 1/1.0.1 and 1 mg. II/l. in supplemented with 4.6 uM kinetin and 1.1-2.8 uM indoleacetic crease the wt. of carrot root crowns; 0.01 rag. II/l. inhibits acid. Compds. tested were fronr-cinnamic acid, phenylpyruvic the growth. II concns. of >0.1 mg./l. increase the wt. and the acid, L-phenylalanine, 4-hydroxyphenylpyruvic add, b-tyrosine, growth of the cotyledon crowns of H. annuus; the growth is in 2-, 3- and 4-monohydroxycinnamic acids, caffeic acid, l-3,4- hibited by about 10 mg. of H/I. The expansion of hypocotyl dihydroxyphenylalanine, ferulic and benzoic acids, 2-, 3-, and 4- cross sections is inhibited by 1 and 10 mg. U/l. (in the presence of hydroxybenzoic acids, 4-hydroxybenzaldehyde, 4-methoxy- and of 1 mg. 1/1.); however, it is promoted by 0.01 and 0.001 mg. of 4-hydroxybenzoic, 2,4-, 2,5- and 3,4-dihydroxybenzoic, phenyl- II/l. From CZ 1964(48), Abstr. No. 1215. MNCR acetic, 2-hydroxyphenylacetic and 3,4-dihydroxyacetic acids, The persistence of two novel methoxyurea preparations in the phenol, catechol, and hydroquinone. In stimulating bud soil. K. Homburg and F. Mariouw Smit (Farbwerke Hoechst formation, the monohydroxy compds. were more active than the A.-G,, Amsterdam). Z. Pfiantenkrankh. Pflanzenschutz, unsubstituted ones, and OH substitution at the 4- or 2-position' "Sonderh. 2, 145-50(1964). Linuron (Afalon) and monolinttron was more effective than at the 3-position. In the benzoic acid (Aresin) were applied to a moor soil that contained 40% huraos derivs., the presence of both OH and a carbonyl was beneficial, and to an impoverished sand, at 1, 2, 4, and 8 kg./ha., to a but neither group was essential. 3,4-Dihydroxy derivs. and clay sand contg. 20% humus, at 1.5 kg./ha., and to a day-sand ferulic and sinapic acids inhibited bud formation. The 2,4- soil contg. 15% humus, at 3 kg./ha. Soil samples were tested and 2,5-dihydroxybenzoic acids were weakly active, and the for phytotoxicity to oats, by comparison of the wts. of seedlings 2,3,4- and 3,4,6-trihydroxybenzoic acids were inactive. The with those grown in treatments with known amts, of the herbi evidence with phenylacetic acid derivs. was that their action on cides applied directly to test pots. One month after the applica bud formation was limited to cultures with the higher kinetin tions, 40% linuron and 60% monolinuron remained and no evi levels. Dihydroxyphenols enhanced callus growth, whereas the dence of residues of up to 2 kg. applications could be found after monohydroxy phenols and related compds. which induced bud 3 months. Linuron was inactivated more rapidly than mono- formation tended to inhibit growth. In order of decreasing, - linuron. With the same rainfall, the disappearance was more auxin effectiveness were 2-methoxyphenylacetic, phenylacetic, rapid the higher the humus content. Residues of the excessive 2- and 4-hydroxyphenylacetic and 4-hydroxyphenylacetic acids. dosages of 4 and 8 kg./ha. were found after 6 months. No resi J. J. Willaman dues were found in the saady soils in the 15-20-cm. depth, Inhibition of the germination of mustard seeds by saturated E. L. Green fatty acids. N. Le Poidevin (Roy. Vet. Coll., London). Phyto Gas-liquid chromatograph; of organic herbicides. Jun chemistry 4(3), 625-6(1965)(Eng). Germination of Sinapts alba Kanazawa. Bunseki Kagaku 14(5), 481-3( 1965XJapan). A seeds was inhibited by a scries of satd. fatty acids when applied at concns. of 0.01-0.1%. The greatest inhibition was with nonanoic add. J. B. Harborne State of investigations into (2-chloroethyl)trimethylammonium chloride (CCC) and related compounds with special considera thermal cond. detector and 1 m. X 4 mm. stainless steel col umns packed with 4 stationary phase liquids (5%) on 48-60- mesh Cclite 545, operated at 190 with a 75 ml./min. He-flow rate were used for analysis of 11 herbicides (2,0-dichlorobenzonitrile. Me 2-inethyI-4-chIorophenoxyacctatc, Me 2,4-dichloro- tion of their effect and possible application in agriculture. Mar "phenoxyacetate, DNOC, l'CP, 3,4-dicliloropropionanilide, 2,4- ian Michniewicz. Postepy Nauk Rolniczych 11(6), 25-38(1904) (Pol). A thorough review of recent world literature with a bibliography of 58 titles. Anna H. Kofflcr dichlorophenyl-4-nitrophenyl ether, 2-mcthyl-4-chlorophenox;- aceto-o-chloroanilide, propazine, siinazine, and prometryn). Fire to 10 pi. sample soln. (10% in IICOMe or MeiCO) was in Keeping quality, flower size, and flowering response of three jected into a vaporizer at --240. Of the stationary phase varieties of Easter lilies to gibberellic acid. James D. Kelley k liquids used (high-vacuum silicone grease, FS-12C5, Sli-30, and and Allen L. Schlamp (Univ. of Kentucky, Lexington). Proc. poly(ethylene adipate) (i'EGAE)), l'EGAE showed compara Am. Sac. Hort. Sci. 85, 631--4(1964)(Eng). Gibberellic acid, tively high resolution. Y. fto 6-1500 or 0-2000 ppm., was applied to buds of the varieties. The use of chemical agents for the control of couch grata. Croft, Ace, and Nellie White, when from 1-6.5 in. long. The II. Ansorge (lust. Suatgut- Ackerbau. llallc, Ger.). Deut. treatments had no significant effect on time of Dowering or flower Larulwirtsch. 15, 128-31X 1904)(Ger). Tests were run on the SPI -12820