Document wR0ym7eBG6q01872oJM71da3

toxicology lid apflilo pilvrmacolocy 9, 501-504 (1966) Chronic Oral Toxicity to Rats of a Vinyl Chloride-Vinyl Acetate Copolymer Henry F. Smytii, Jr., and Carrol S. Weil Chemical Hygiene Fellowship, Mellon Institute, Pittsburgh, Pennsylvania 15213 Received July 21, 1966 High molecular weight polymers are generally accepted as safe for food contact, although there is a dearth of published evidence. In particular, no reports of long time experimental feeding of polyvinyl resins, widely used in food packaging, appear in the literature. In order to nil this gap, a study completed in, 1947 is presented. METHODS ! Sample. The sample was then characterized as vinyl resip VYNU.1 It was a copolymer of 95rc vinyl chloride and 5^c vinyl acetate, with a molecular weight of 25,000 to 30,0C0 as determined by the Staudinger method, or 200.000 as measured by osmotic pressure. The resin was produced in the form of particles with a diameter of 0.1 it that tended to agglomerate loosely. Animal management and observation. Each of the parental generation group con sisted of 12-15 Wistar-strain albino rats of each sex, approximately 6 weeks of age at the first dose. They were housed 4-6, half of each sex, in wire-bottom cages. Ten to 12 offspring of each sex. consisting of the first filial generation, were fed the diets until the end of the study and, as no differences were found from the parental generation rats, both generations were considered together. For the first IS months the basic diet consisted of a mixture of 100 parts of ground whole wheat, 5 parts of dried whole milk, and 2 parts of iodized table salt. Wheat then became unavailable to the local miller, and during the last 6 months a commer cial ground laboratory chow: was utilized. The growth curves of the rats showed no appreciable upset from the shift in basic diets. One group received the basic diet, one had Ufc VYNU added, the third had 12^b VYNU added, with no attempt made to correct for high nonnutrient content. The respective intakes of VYXU averaged 0.61 and 5.75 g.'kg, day. The observations made during the feeding were (1) tone and behavior of animals. (2) average food consumption, (3) body weight, (4) occurrence of death and infec tion, (5) red, white, and differential white blood cell counts, and (6) occurrence of pregnancy, number of pups born, and survival and growth of the pups. At death or sacrifice gross pathology was recorded, and neoplasms were sought. Body length was measured, and livers and kidneys were weighed. Organ weights were calculated as a percentage of body weight. Adrenal, small intestine, kidney, liver, lung, pancreas, spleen, testis, and neoplasms \ 1 Manufactured by 3 company known at that lime as lTnion Carbide Plastics Division. * Purina Laboratory Chow Meal, Ralston I'uiina Company, St. Louis, Missouri. sot SPI -12832 CHRONIC TOXICITY OF A VINYL COPOLYMER 503 TABLE 3 Liver and Kidney Weight Ratio Data on Rats Receiving Resin "VYNU in the Diet for One and for Taa-o Years Period of feeding Dietary level <7o> . Organ weight as percentage of body weight* Liver Kidney 1 Year 12 13 0 4J08 0.4J 3J05 031 3.12 0JS 0.79 0.18 036 0.05 0.64 0.12 2 Years 12 13 0 306 031 305 035 334 0.43 039 0.17* 0.66 0 06 0.70 0.10 Mean i SD. * f < 0.03. .____ histologically normal, and at two years livers of rats in the same group were numeri cally but not significantly lighter. Similarly, a slight, but statistically significant, de crease in mean relative kidney weight was seen at two years, but not at one year, with all sections histologically normal. Neither was considered to-be a deleterious effect from the inclusion of YYXU in the diet. Table 4 summarizes the reproduction results and does not suggest any effect. TABLE- 4 Rei-roduciion- or Rats" Receiving Resin- VYN'U in' the Diet for Two Years Dietary level (%) 12 13 0 Females of parentaj generation Total Infertile 51 51 10 1 Females of Fj generation Total Infertile 61 40 61 Total per female Litters born1 Pups born ali\-e* 63 33 S3 4.0 8.4 S3 47.8 28.7 453 30.4 51.6 41.0 Alive at 36S days of age. * Mean SD. The tissues of the 3S rats sacrificed for examination after one or two years were histopathologicnlly normal. An infective or traumatic cause of death was clear for all rats dying, and none of their tissues showed any histopathology not directly related to this cause. Careful search of all rats dying or sacrificed revealed only 6 neoplasms, possibly because half of the rats did not survive the lung infection into the second year of feeding. At the 12`,b level of YYXU there were two neoplasms in the mesentery, at the 1.5c/o level one uterine neoplasm, and the controls had one in the mesentery and two in the lung. DISCUSSION' This study', completed 20 years ago, differs in many respects from the design one would expect in a current study of the safety of a food-packaging resin. In particular, it would be preferable to add to animal diets only that fraction of the resin which transfers to food packaged in a formulation. Furthermore, were reproduction considered of sufficient importance to be studied, a separate group of animals would be desirable, with opportunity for mating provided only at rstrus. *V *\ SPI -12834 504 HENRY r. SMYTH, JR., AND CARROL S. WEIL SUMMARY Starling in 1944, albino rati of both sexes caged together were maintained for two years upon diets containing 1.57 and of a vinyl chloride-vinyl acetate copolymer. No effect attributable to the resin was found. REFERENCE .Fisiiex, R. A. (1938). Statistical Methods for Research ll'oricrs, 7th ed. Oliver & Boyd, Edin burgh and London. SPI - 12835 68686 Chemical Abstracts Vol. 66, 1967 Pg 646 contained 20 mg./m.*-884 mg./m.* of fluororg. impurities, and after them only 3.6 mg./m.* St. Janderka 68686w Hygienic evaluation of new technological processes In chemical industries. V. S. Filatova. Gig. Tr. Prof. Zabol. 10(11), 3-7(19G0)(Russ). In a hygienic examn. of a new poly vinyl chloride) (PVC) plant the most frequently occurring concns. of vinyl chloride, the chief noxious factor, were 10-44 mg./m.* (30 mg./m.* is an permissible threshold limit), com pared with 100 mg./m.' in old plants. The conen. of PVC dust after introduction of fluidized-bed drying was smaller by a factor of 27 than in the old Stroganov system VIS-76 ovens. A favorable hygienic effect of continuous production was observed in a hexamcthylcnediisocyanate plant, csp. after mechanization of labor-consuming operations and installation of remote control. Most frequently occurring concns. of hexamcthylcnediisocyanate in the air were 0-0.1 mg./m.', compared with the highest permis sible concn. 0.05 mg./m.* Analogous conditions were found in the production of AG salt (one of the initial materials in the production of nylon 66), where the intermediate product, licxa- methylcncdiamine, is obtained by hydrogenation of adiponitrile under a pressure of 160-180 atm., where the concn. of hexamcthylcncdiaminc, adiponitrile, and NH in the air were in all cases below the permissible, limit. Also in the production of .MeOH from coke oven gas the concn. of CO in the vicinity of circular pumps operating at 300-20 atm. did not exceed the sanitary limit. In a plant producing Cl by the continuous method under vacuum and equipped with new hermetic elec trolyzers BGK-17, the generation of heat for 1 ton of the product was 2 times and liberation of Cl gas 3-40 times lower than in plants with old electrolyzers. No Cl was detected in most samples and the Hg level was within the standard. But some of the new chem. plants are not yet up to sanitary standards, e.g. the concn. of vinyl chloride in the polymerization area of a PVC latex plant exceeded by 100% the limit, 2.28 kg. of vinyl chloride was liberated by 1 reactor in 1 hr. in the air. Sanitary measures are proposed to improve the conditions. St. Janderka 68687x Occupational hygiene in the production of resins from furfural. G. N. Nazyrov and Kh. Ya. Vengerskaya (Inst. Sanit., Hygiene, and Occup. Diseases, Tashkent). Gig. Tr. Prof. Zabol. 10(11), 56-60(196G)(Russ). The concn. of furfural, MeiCO, and PliOH vapors in the air of the Fergan chemical plant engaged in the production of furfural resins was detd. In the furfural-MejCO monomer plant, the most frequent concn. of furfural vapors was within the 0.0008-0.003 mg./l. range, and that of MejCO 0.007-0.01 mg./l., while in the furfural- MeiCO-epoxy resin plant, the usual concn. of furfural vapors ranged from 0.0 to 0.004 mg./l., and that of MejCO 0.0-0.01 mg./l. In the furfural-MejCO-PhOH-HCHO resin shop, the most frequent concn. of furfural vapors averaged 0.0- 0.002 mg./l., while the concn. of MejCO and PhOH vapors were 0.0-0.006 and 0.0-0.002 mg./l., resp. To improve the existing conditions, it is recommended to improve the general and local ventilation systems, as well as to shift to more mechanized and automatic procedures. A. A. Horvath 68688y Prevention of air pollution with mercury inside industrial premises of synthetic fiber plants. M. N. Korshun. Gig. Tr. Prof. Zabol. 10(11), 18-22(1966)(Russ). Av. concns. of Hg fumes in the air of the chem. labs, of the synthetic fiber plant examd., in the mercerization and precuring areas at 27-9, was 400-500% that of the permissible limit. It decreased gradu ally in the conditioning and xanthation areas. Higher concns. of Hg fumes were found in places where alkali or alkali cellulose came in contact with the air. At the opening of precuring and conditioning tubes, in which alkali cellulose is held the longest, the concns. of Hg fumes was the highest, 0.17 and 0.20 mg./m.* Decreases of Hg fumes in the xanthation and subsequent stages may be due to treatment of alkali cellulose with CSj, binding Hg and pptg. its sulfide. Analysis of lab. samples of 100 ml. of NaOH and 60 g. of alkali cellulose, kept 48 hrs. in hermetically sealed glass flasks, revealed that NaOH-treated cellulose ac quires the ability to liberate Hg fumes; alkali cellulose liberates during prematuration most of the Hg; alkali cellulose treated with CSi did not liberate Hg fumes during an exposure of 48 hrs. But there is no method for the detn. of Hg in alkali cel lulose; the methods recommended by GOST did not give pos. results. Lab. analyses have revealed sorbed Hg on the walls of soda station, mercerization, and precuring area. Secondary Hg sources may be also wooden construction elements and furniture. Measures are proposed to improve the condition. St. Janderka 68689z Problems of Industrial hygiene in the production of ANP chemical flotation agents. S. Ya. Krivshin. Gig. Tr. Prof. Zabol. 10(11), 28-32(19f36)(Russ). Chem. flotation agents ANP-1 and ANP-2, used for the enrichment of iron, phosphorite, talc-magnesite, and other ores are hydrochloride salts of tetraand pentadecylamines and begin to decomp, at temps, above 100*. Despite their wide-spread use, there are no data on their toxic characteristics. They cause dystrophic lesions of liver and kidneys, affect the permeability of wall vessels, disturbances in central nervous system, and irritation of mucous membrane of the eyes and upper respiratory tract. The permissible limi recommended is 1 mg./m.' Starting raw materials in thei production arc high mol. paraffins, HNOi, and HC1. The plan atm. is polluted by MeOH, N oxides, 1ICI, amines, and the: salts. Pcntadccylaminc is liberated in all stages of productior esp. in the synthesis of the flotation reagent and its purificatioi the concn. of pcntadccylamine was 3-5 mg./m.* Escape of the- substances into the atm. was caused by corrosion of the seals t amines and their salts. App. and building constructions wc; polluted by amines and their salts at the rate of 0.01-1 .CX mg./cm.' In dermatological examn. of 120 workers cases < professional dermatitis, chiefly in app. operators and locksmith were observed. The amines and their salts had a pronounce sensitizing effect on the skin. Arterial hypotension (90-6 mm 65-60 mm.) was found in 68% of 25 persons examd.; 48' had increased permeability of vessel walls. Introduction of son sanitary measures (full mechanization of the process, sealing c the app., replacement of rubber seals by Teflon, shielding < samplers, use of "biol. gloves" or IEP-1 paste) helped to in prove the conditions. St. Janderka 68690t Experimental materials contributing to the establisl ment of hygienic standards for urea-formaldehyde resins. L. 1 Ducva. Gig. Tr. Prof. Zabol. 10(11), 39-43(19G6)(Russ The direct relation between the damaging and sensitizing effec of resins on the skin and their general resorptive action, dependir upon the amt. of free HCHO contained was established. T1 pollution of industrial plants with HCHO vapors, which produt harmful action on the organism of workers because of the allergic and irritative effects, may depend upon the amt. < residual monomer contained. For this reason, the max. redi of free HCHO in urea-HCHO resins is needed. J. Pich 6869 lu Hygienic evaluation of some petrochemical Industrie; E. A. Kapkaev, L. V. Trofimova, N. A. Enikeeva, and A. K Monkevich. Gig. Tr. Prof. Zabol. 10(11), 22-8(1966)(Russ. Gas impurities are the chief factor affecting working conditio in a petrochcm. plant; they may contain 4-8 ingredient! Toxic substances in plants examd. for the most part did nc exceed the sanitary limit, but considerable pollution of the atn was observed in some places (opening and repair of the app cleaning of inner surfaces, analyses of samples). In isoprene acetylene, BuOH plants, where the concn. of single toxic sut stances is not high, functional disturbances wert observed i workers owing to the combined effect of ingredients. Th highest concns. of toxic substances was in the pumping area! An important factor is corrosive substances which impair th hermcticity of the app. and scalings. Concrete, bricks, plaste walls, oil coatings, and other building materials in butadient isoprene, a-methylstyrcne, butadiene-methylstyrene, butadiene styrene, polybutadiene, and polyisoprenc rubber plants adsorbe many toxic substances. Benzene, isopropylbenzene, and o methylstyrene were desorbed from building materials after man hrs. The plant atm. may be intensively polluted also b by-products, which may be more toxic than the final product! Acrolein vapors were detected in a high-pressure polyethylen plant. Toxic substances, in amts, exceeding permissible limit; were found regularly on outside installations: hydrocarbons 10 520, ammonia 2-920, aldehydes 7-44, a-methylstyrene 2-56 and benzene 6-29 mg./m.' The air in some plants involved ii petrochem. synthesis was polluted to a height of 22 m. St. Janderka 68692v Work condition and health status of plant personne engaged in the production of epichlorohydrin. L. I. Pet'ko E. Sh. Gronsbcrg, L. N. Cherova, and V. I. Filina (Inst. Ind Hyg. Occupational Diseases, Gorki). Gig. Tr. Prof. Zabol 10(11), 52-4(1966)(Russ). Examn. of chem. plants producin; epichlorohydrin (I) showed higher than max. permissible concns of I, HC1, and glycerol dichlorohydrin in the atm. Clin examn. of 82 workers did not prove any specific pathol. changes Ivo Hynie 68693w Vision of workers engaged in the production o synthetic fatty acids and issues relative to setting hygienic standards for the alcohol content in the air. Yu. L. Egorov G. A. Petropavlovskaya, E. O. Saksonova, and V. N. Ermakova Gig. Tr. Prof. Zabol. 10(11), 33-8(1966)(Russ). Rabbits ex posed to the effect of sprayed decyl ale. in a concn. approachin; the max. permissible one (200 mg./m.') and at 0.058 mg./l demonstrated the presence of conjunctive keratites, a decreasec "b" wave on the electrorctinogram, and lengthened retino cortical time. Degenerative alterations of the nerve cells ir the brain, together with an intense proliferation of glia occurrec in the optic nerve. Considering the effect of decyl ale. on the vision organs it is proposed to lower the max. permissible concn. to 10 mg./m.* (0.01 mg./l.). J. Pich 68694x Assessment of lead exposure in po!y(vinyl chloride! manufacture and suggestions for control measures. V. Smolcic (Zavod zastitu zdrawlja, Split, Yugoslavia). Ark. Hig. Rada Toksikol. 17(3), 309-16(1966)(Croat). Pb concn. was studied in samples of air collected in 3 Yugoslav plants manufg. poly- (vinyl chloride). The air was pumped through filter papers SPI-12836 3u95l -30*59 TOXICOLOGY | Vol. 50 J 2t(| streptomycin nscorblnnto. dthyrirostroptoniyrln psnthotcnntc, paeo- myrln. florlmyctn and kanamycln are prr*< rtrd. Complex compounds erf dlhydroslrcptomycln wllh ascorbic, pnnthotcnlc or p-amlnnsalyclllc ^ eld arc less toxic than streptomycin sulfate or dlhydrostreptomycln. All above dlhydrostreptomycln derivatives may be used In cases with side effects of streptomycin sulfate. Pasomyctn is preferable since It combines 2 main antituberculous preparations (dlhydrostreptomycin and PAS). Florlniycln and kanamycln are more toxic than streptomycin sulfate or dlhydrostreptomycln and their derivatives. These antibiotics should be limited by patients with progressive processes and streptomycin resistance. Florlmyeln and kanamycln are ototoxic and should be used only In stationary conditions with constant examination of hearing.--Authors. t 30951. TAYLOR, T. G., K. M. L. MORRIS, and JEAN KIRKLEY. (Agr. Res. Counc. Poultry Res. Cent., Edinburgh, Scot., UK.) Effect of dietary excesses of vitamins A and D on some constituents or the Elo<a oT chicks: ~ORff J NlfTR 22(4): 713-721" 19687--Groups of chicks'were given diets containing 4 levels of vitamins A and D, 1, 10, 100 and 1000 times the basal level, In all 16 combinations, with the object of investigating a possible antagonism between the 2 vitamins. Only diets containing 1000 times the basal level (approx. 1700 times the dietary requirements) of 1 or both vitamins depressed growth and Induced changes In the blood. The packed cell volume was substantially reduced from 4 wk of age In the chicks given the highest level of vitamin A. This was probably due to an effect of the vitamin on the fragility of the red cells and thus on their life span. Chicks given the toxic level of vitamin D showed an Increase In plasma Ca and a decrease In plasma inorganic P. The highest level of vitamin A depressed plasma Ca without influencing plasma Inorganic P. Increasing amounts of vitamin A given in combination with the highest level of vitamin D caused a progressive Increase In the plasma inorganic P. The highest level of dietary vitamin A significantly Increased the activity In the plasma of 3 lysosomal enzymes: acid phosphatase, -glucuronidase and arylsulphatase. Excess vitamin D given in conjunction with the basal level of vitamin A significantly depressed the plasma acid phosphatase and the activity of this enzyme increased with increasing amounts of vitamin A. Excess vitamin D had no influence on the other hydrolases studied. A marked antagonism between the effects of excessive amounts of the 2 vitamins occurred only In respect of their actions on the plasma levels of Ca, inorganic P and acid phosphatase, all of which are involved In bone metabolism. --Authors. 30952. TUMARKIN, R. I. (N. F. Gamaleya Inst. Epidemiol. Micro biol., Acad. Med. Sci. USSR, Moscow, USSR.) K voprosu o mekhanizme toksicheskogo deistvlya antlblottkov tetratslklinovoi gruppy na pechen'. [Mechanism of the toxic etlect of the tetracycline group of antibiotics on the llver.|~ANTIBi<mia~13(7): 647-652. 1968. [fengl. sum.l --Chlortetracycline in high doses in rats Increased histidine deaminase and urokanlnase activity. Oxytetracycllne had a slight effect on histldlnedeamlnase activity and suppressed urokanlnase activity. Tetra cycline effect was similar to that of oxytetracycllne. Chlortetracycline has a higher toxicity.--Author. 30953. TYUL'MANKOV, V. N., and B. K. LUGOVSKII. Sosudistye oslozheneniya pri lechenlt pstkhicheski bol'nykh aminazlnom. [Vascular complications during aminazine [chlorbromazlne] treatment of mental patients.| jfc'H NEtJROPATOL PSlKJHLAt IM S S KORSAKOVA 68(1): 111-115. 1968. [Engl. sum.]--The main syndromes were cerebral hemorrhages and thrombotic vascular affections of vitally important organs. Aminazine probably increases coagulability. A thorough control (including laboratorial and tests) of old patients and patients with hypertensive disease must be made In the process of aminazine treatment.--From auth. sum. t 30954. WEISS. HARVEY J. (Mt. Sinai Hosp., New York, N. Y., USA.), LOUIS M. ALEDORT, and SHAUL KOCHWA. The effect of salicylates on the hemostatic properties of platelets in man. J CLIN INVEST 47(9): 2169-2)80. lUus'.' 1968.7-ingesttoh of T.5 g of aspirin, but not of sodium salicylate, produced a significant prolonga tion of the bleeding time in 6 normal male subjects when compared with the effects of a placebo. Similar differences in the effect of the 2 drugs on platelets was also observed. Aspirin ingestion resulted in impaired platelet aggregation by eonnectivc tissue and was associated with a decreased release of platelet ADP; sodium salicylate had no effect on these \alues. In vitro, Incubation of platelet-rich plasma with an optimum aspirin concentration of 0.045 mg/ml inhibited both the adhesion of platelets to connective tissue and the release of ADP as well as the 2ndary wave of platelet aggregation produced with ADP or epinephrine. Sodium salicylate had no effect on these reactions, which were also normal in patients with von Wlllebrand's disease. The Inhibitory effect produced by ingesting a single 1.8 g dose of splrin was detectable for 4-7 days at which time salicylate was no onger detectable In the blood, which suggested an irreversible effect on the platelet. Aspirin also inhibited the release of platelet ATP, txit had no effect on the platelet surface charge, available platelet ATP or ADP, or the destruction of ADP by plasma ADPase. These studies support the hypothesis that ingestion of asptrtn, In contrast to sodium salicylate, prolongs the bleeding time by Inhibiting the release of platelet ADP, perhaps reflecting the findings In other cell systems that aspirin alters membrane permeability.-*Authors. 30955. ANONYMOUS. The ktdnrv and oral calcium therapy^ ANNINTF.RN MFD 00(5)r`TMI-rO!5.' ' I!W.--Iti.miJ. Ca< <>j 1 valuable as an antacid, severe and possibly Irreversible injury to the kidney may occur from its prolonged use in conjunct ton with a high milk intake. Evidence of renal function disturbance may be shown by a rise In serum creatinine and renal N. During treatment with CaCOs a patient's serum Ca levrl should be watched for early signs of Ca nephropathy wtthtn the 1st 7 days of treatment. INDUSTRIAL TOXICOLOGY (See also "Pathology" under Respiratory System; "Environmental Health - 'Occupational Health,' and 'Radiation Health' " under Public Health) 30958. GANDEVTA, BRYAN. (Div. Thorac. Med., Univ. N. S. W.. Sydney, N. S. W., Aust.) Pulmonary function In asbestos worker**: A three-year follow-up etu^y. AMER REV llESP PIS 96(3): TOTTFT Ulus. I&S1?. [SpanTand Fr. sum.[--Ventilatory capacity and ventilatory response to a standard exercise test were measured in a series of 41 male workers In a factory making asbestos products, and was repeated about 3 1/3 yr Later. Twelve men left the industry during the lntermln. They had a significantly lower vital capacity after adjustment for age, and a significantly higher ventilatory requirement for exercise than those who remained in the Industry. This pattern of function?.! abnormality contrasts with that found in subjects admitting to persistent cough and sputum, in whom a significant reduction was demonstrated in age-adjusted forced expiratory volume at i sec. In a control series, observed and predicted changes in pulmonary function over the observation period showed reasonable agreement. The asbestos workers showed a greater decrease In forced expiratory volume at 1 sec. than predicted, and possibly greater changes in vital capacity and ventilatory require ment for exercise. The trend toward functional abnormality is con sistent with, although not indicative of, the development of asbestoals. Serial pulmonary function tests are likely to be more Informative than serial roentgenograms.--From auth. sum. 30957. HARRIS, D. KENWIN, and W. G. F. ADAMS. Acro-osteolyiii occurring in men engaged in the polymerization of vinyl chloride. BRIT MED j 5567. 712-Y14. Jllus. f^f.'-'Two'caTes of acroosteolyeis occurring In men engaged in the polymerization of vinyl chloride are described. The bones affected were the terminal phalanges of the fingers and the sacroiliac Joints, but In 1 case the patella and in the other the phalanges of the feet were involved. The condition was accompanied by Raynaud's phenomenon and skin lesions. This condition is probably a self-limiting disease.--Authors. 30958. SAMEDOV, I. G. O nespetsiflcheskikh proyavleniyakh aeistviya uglevodorodov v malykh kontsentratslyakh. [Nonspecific manifestations of low concentrations of hydrocarbons.] AZLKB MED Zri r. 56-61. lSsT! From: REF ZH OTD VYP FARMAKOL KHIMIOTER SREDSTVA TOKSIKOL, 1968, No. 4.54.915. (Translation) --Workers were tested at a petroleum-processing plant where the concentration of hydrocarbon vapors did not exceed the maximum allowable (0.07-0.48 mg/1. Rabbits and guinea pigs were treated under various static regimes with the vapors of gasoline B-70 at 0.95-1.1 ml/l, 4 hr/day, 6 Umcs/woek for 4 mo. The workers and the animals showed a rise In the concentration of blood acetylcholine and eplnephrine-Iikc substances. Animals treated constantly and evenly with increasing hydrocarbon concentrations showed these tendencies, but they were less marked. Cholinesterase activity in the workers did not differ from that of controls, but it was reduced in treated animals, especially when the treatment was with fluctuating concentrations of hydrocarbons. Pseudocholinesterase activity did not change In either persons or animals. Dally urinary excretion of 17-kctostcrolds by treated rabbits was of a phasic character: the elevated activity of the adrenocortical function was soon replaced by reduced activity. Only under the action of sharply fluctuating hydrocarbon concentrations was there a prolonged rise in 17-ketosteroid excretion. Maximum depression in the concentration of vitamins C and Bj in the blood, urine, and organs was noted m animals treated with steadily and evenly Increasing and also sharply fluctuating hydrocarbon concentrations. Changes in the electrolyte metabolism with low concentrations was Insignificant. The principal changes with low hydrocarbon concentrations were In the functional condition of the autonomic and endocrine systems (changes in the metabolism of mcdlatlng substances and vitamins and in adreno cortical function). These changes are probably nonspecific and of a compensatory-adaplatlonal nature. Over a certain period they may lead to persistent and even organic changes. 30959. SPAK, IVAR. (Dep. Surg., Lanslasarettet, Hassleholm, 9wed.) Finger injury caused by paint spray gur ACTA CHIR SPI -12837 Published Under the Auspices of The Boord cf Trustee* THE JOURNAL of the American Medical Association r A X\* K i.i L- j VOL 201, NO 8, AUGUST 21, 1967 Occupational Acroosteolysis Report of 31 Cases Hex II ll'i/son, MI), U'llliani E. McCormick, A/S, Caroll E. Tatum, MI), and John L. Creech, MD In 31 cases of acroosteolysis of the hands of workmen derma. Some have clubbing of the fingers. Only a few associated with vinyl chloride (CH^CHCI) polymerization of the cases have sought medical attention because processes, the osteolysis was specific to the distal pha of symptomatic complaints; the majority have been langes of hands and was frequently associated with Ray found through x-ray examinations of the hands. naud's symptoms. Affected personnel ranged in age from A summary of the physical findings of the ob 26 to 47. The disorder is believed to have resulted from served cases is shown in Table 1, and a detailed de a combination of physical insult, chemical insult, and scription of the two predominantly common symp personal idiosyncrasy. The specific causes are unknown. toms follows; The prevalence was found to be less than 3% among Raynaud's Phenomenon.--This symptom com employees performing similar work. No cases were found plex has occurred in varying degrees, with one or in workmen using or processing the polymer or manu both hands involved. Generally, its effect is observed facturing commercial resins. as marked discomfort on exposure to cold. None of the cases have exhibited vascular changes of the feet. uring mid-1961, several complaints came to our A unilateral sympathectomy performed on one of D attention of soreness and tenderness of the the most seriously affected cases relieved most of fingertips of workmen in a manufacturing plantthe symptoms on that side. The acroosteolysis was polymerizing vinyl chloride (CH..CHC1). Compre not altered by the sympathectomy. hensive examinations of these individuals revealed Roentgenological Changes.--The most unique nothing of significance except a "Raynaud-like phe characteristic of this syndrome is the unusual roent nomenon" of the hands, and in some cases, definite genological findings. These are described as acroos changes of the distal phalanges wove apparent on teolysis and are illustrated in Fig 1. It may be present roentgenograms of the hands. Since then we have in all of the fingers and readily observable, or only in observed additional cases of this unusual syndrome. one finger and barely discernible, as illustrated in It is the purpose of this manuscript to summarize Fig 2. X-ray films of the feet, as well as those of the our observations. long bones and of the skull have been made in some of these cases, with no osteolysis found other than Description of Syndrome in the distal phalanges of the hands. To date we have observed 31 cases of hand dis orders among .1.000 personnel involved in vinyl chloride manufacturing and polymerization. All have been men. between I he ages of 26 and -17. We have not observed any ethnic or racial tendency for tin: syndrome. The great majority have been char acterized by two common factors: symptoms likened to those ascribed to Raynaud's phenomenon and aeroosleolysis of the distal phalanges. A few have had no symptoms hut have the roentgenogrnphic evidence of aeroosleolysis. Several of the patients have external skin lesions on the dorsal surfaces of the hands and forearms, with a rope-like appear1 anee resembling changes somevimes seen in selero- l imn (In' Mi-du.i! Mu r.ii'ii. 11 1' t'.imdritTi (V. Akron, (lino. KopviiU toiitu r.is to ;>0U S Main St. Akvm, Oluo41!ll8 tl)r. Wil son). Acroosteolysis is a rare clinical entity, with only 72 cases of the familial type reported up to 1965. ac cording to Cheney in his excellent review.1 The diagnosis of acroosteolysis requires expert roent genological technique and knowledge. It has been our observations that early cases of acroosteolysis will be missed by the roentgenologist not familiar with this condition. All of the cases on which we are reporting have been confirmed by at least two ex perienced roentgenologists working independently. We established the following roentgenographic criteria for our diagnoses. These are the result of our having viewed several thousand x-ray films of the hand in our search for the cause of the syn drome. j. General: Rocntgenographicallv,acroosteolysis, as found in workers who are exposed to vinyl 577 SPI -12838 83 578 ACROOSTLOLYSIS-WILSON ET AL chloride and polyvinyl chloride manufacturing processes, is somewhat different from that found in familial osteoporosis with acroosteolysis and in fa milial osteosclerosis with acroosteolysis. In osteopo rosis with acroosteolysis then; may be compression fractures in the spine, and basilar impression of the skull, along with destruction of the midpha langes. None of these findings have been seen in these workers. The changes in the distal phalanges are similar in both conditions. Osteosclerosis acroosteolysis observed by Andren Table 1.--Summary of Symptoms and Findings Symptoms Acroosteolysis without Raynaud's symptoms, one hand Acroosteolysis without Raynaud's symptoms, both hands Acroosteolysis with Raynaud's symptoms, one hand Acroosteolysis with Raynaud's symptoms, both hands No. of Cases 4 5 5 17 Total 31 Clubbing of fingers Skin nodules 8 8 tit aP (University Hospital, Malmo, Sweden) in twins showed diffuse sclerosis, with cortical thick I ening of the shafts of the long bones and clubbing of the metaphyseal ends. The phalanges of the hands and metaearpals were foreshortened, and the distal phalanges showed acroosteolytic changes. The feet showed the same changes, except that the distal phalanges were not fragmented. There has been no evident destruction in the mid or proximal phalanges of the thumbs or fingers of these individuals and no evidence of a lytic, destruc tive lesion in the feet. We have not observed any loss of calcium salt in the bones of the wrist and remaining bones of the hand and phalanges in any of these individuals, ! and there has been no evident sclerosis of the wrist and hand bones. 2. Mild stage: The earliest change found in acroosteolysis in these workers has been a loss of the cortex of one or more of the tufts of the distal pha langes, with no destruction of the tuft or shaft of the distal phalanx. The next more advanced stage may be a small, half-moon cut in the cortex of the tuft of one or more 2. Mild stage of acroosteolysis with half-moon de fect of distal phalanx of mid finger. 1. Acroosteolysis with involvement of distal phalanges of all fingers. 81 SPI -12839 JAMA. Aug 21, 1967 Vol 201, No 8 ACROOSTEOLYSIS--WILSON ET AL 579 <lisl;il phalanges, or a so-called slice effect along one or more of I lie l uffs. Figure 2 illustrates the small, half-moon cut in the cortex of the distal phalanx of the mid-finger. 2. Advanced stage: A more severe lytic destruc tion may he a complete loss of the tuft and a por tion of the shaft, of one or more distal phalanges as illustrated in Fig 1 in which the tuft of the distal phalanx of the right thumb and the tuft of the distal phalanx of the left fifth finger are completely absent. Additionally, there may be in the same hand a portion of the distal rim of the tuft remaining, with loss of the proximal portion of the tuft and a portion of the shaft of the phalanx, which can also be identified in the remaining phalanges in Fig 1. This loss may he of a transverse nature through the shaft and the tuft, or of an oblique type loss of bone struct ure. 4. Healing stage: In this phase, there is often definite fragmentation of the remaining tuft and of the filled-in area where the previous destruction was noted through the shaft of the distal phalanx. This may go on to a complete bony union or remain as a fibrous union with fragmentation. In Fig 3 and 4, x-ray films of the same individual well demon strate this. This employee had almost complete reunion of the multiple fragments when first seen in November 1965 and again in November 1966 (Fig 3). In the latter, the completely healed shafts and tufts of the distal phalanges are indicated by no residual fragmentation with fibrous union. There is a definite shortening of the shaft and a widening of ! I jV r 3. Above, Acroosteolysis with marked fragmentation of distal phalanges in November 1965. Below, Same individu al in November 1966. "1 I I 1 L JAMA, Aug 21. 19G7 Vol 201, No 8 SPI -12840 i 85 t>80 ACROOSTEOLYSIS--WILSON ET AL the shaft: and tuft, both in the transverse and the anteroposterior diameter. This is most likely due to a combination of constant pressure, and by the nor mal tension of the soft tissues, particularly the ten dons to the distal phalanges. Occupational Aspects of Syndrome Based upon our observations of these 31 cases, it appears as if this syndrome may be of occupational origin and is somehow related to the process of vi nyl chloride polymerization. Its specific cause if not presently known. We are performing extensive re search in an effort to find the cause. Two other pa pers referring to the condition have appeared in the literature. The publication by Suciu et al' contains no specific information, and merely alludes to some hand problem. That of Cordier et al* presents case histories with symptoms similar to many of the cases wo describe. This syndrome differs from idiopathic and familial acroosteolysis in that only the hands are involved. Vinyl Chloride Polymerization Process Polyvinyl chloride is a widely used synthetic resin. It has been manufactured commercially for more than 30 years and is used in upholstery fabric, floor and wall tile, wire insulation, phonograph records, and many other commonly used commodities. For many of these uses, the resin (CH-CHClh is mixed with oilier materials to achieve the desired physical characteristics. The hand syndrome occurs apparent ly only in those people exposed to vinyl chloride or to other chemicals used in the manufacturing process of the resin itself or both. In addition to our exami Table 2.--Age Distribution of Cases Acroosteolysis Without Age Group Raynaud't Symptoms 2029 1 30-39 4 40-49 4 Acroosteolysis With Raynaud's Symptoms 4 12 6 nations of 3,000 personnel performing vinyl chloride manufacturing and polymerization, we have exam ined more than 1,000 individuals who handle the finished resin or xvho process it into plastic prodducts. No cases of acroosteolysis have been found in these 1,000 persons. Basically, the manufacture of polyvinyl chloride consists of polymerizing vinyl chloride. The reac tion is accomplished in closed containers (polymerizers) with suitable catalysts and emulsifiers. Copolymers, formed by combining vinyl chloride with other monomers, create variations of the homopolymer. These are commercially produced. Following polymerization, the resin is washed, dried, and sold as a finely divided white powder. The polymerization operations are carried out in closed processes and provide little opportunity for employee exposure. Following the completion of the polymerization reaction, periodic cleaning of the walls and agitator of the polymerizer is necessary. The frequency of this cleaning and its method varies with the type of material used in these vessels and with different manufacturers. The most common practice has been to accomplish the cleaning man ually by using hand scraping techniques, with work ers spending several hours each day on this job assignment. Personnel performing this job are com monly referred to as "polycleaners." 4. Left, Healed acroosteolysis with only minor roentgenographic changes. Right, Same individual one month after crushing injury to midfinger. if * I l __ K(> SPI -12841 JAMA. Aug 21, 1967 Vol 201. No 8