tnduitrial Hygiene Symposium 0x1 a cancer control program for high boiling catalytically cracked oils is excellent example of teamwork and leadership in industrial hygiene MELLON INSTITUTE
bg Indudrial EVfldene FoundatoOn H. H. Schrenk,'Research Director
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primary efforts of thc industrial hygienist are directed toward the control of environmental factors to prevent adverse effects on the health and wrllbeing of the workers. However, before proper control measures can be instituted i t is necessary to recognize and evaluate the hazardous nature of the materials being handled. When advance knowledge of the hazardous nature of a substance or occupation is available, recognition, evaluation, and control are a matter of applying basically well-established procedures. Unfortunately, in the past, it has frequently required a dramatic episode resulting in death or serious injury to call our attention t o the hazardous nature of certain substances or occupations, and basic research and development of control procedures has followed. As the field of industrial hygiene has advanced, more and more effort has bcen directed toward the evaluation of potential hazards and the introduction of control measures before any adverse effects occur. A recent series of articles (1-4) dealing with a cancer control program for high boiling catalytically cracked oils is an excellent example of this objective. These articles are the result of a fundamental and comprehensive investigation which was instituted and is being conducted because of the potentially hazardous nature of the materials even though no evidence of adverse effects has been observed. Preliminary Tests. The first commercial fluid catalytic cracking unit was put into operation in 1942. In addition to such products as gasoline, kerosene, home heating oils, and Diesel oils, there is a residual material which contains high boiling polycydic aroniatic hydroc$rbons. This residual material is known as high boiling catalytically cracked oil, slurry oil, or clarified oil, after removal of the catalyst. Certain high boiling polycyclir aromatic hydrocarbons are known t o be carcinogenic; hence, it was suspected that this residuai material might constitute a potential cancer hazard and a comprehensive, systematic study was initiated by the Standard Oil Co. of New Jersey. Preliminary tests were made with a high boiling fraction of oil obtained from an experimental fluid-cracking operation using white albino mice, black mice, rabbits, rats, guinea pigs, and monkeys. The reHE
February 1952
sulta of these preliminary tests indicated
that the material tested had a carcinogenic potency comparable t o some of the most active coal tars described in the literature. White mice were selected as the most satisfactory experimental animal, as tumors were produced somewhat sooner than with black mice and much more rapidly than with monkeys. Benign tumors were produced more rapidly with rabbits, but cancers appeared far less readily. Tumors did not occur in the rats and guinea pigs. Subsequent large scale testing was carried out using 30 mice for each sample, and approximately 400 samples from refihery and laboratory operations have been tested. A graphical method of presenting the data shows at a glance the rate of appearance of papillomas and cancers, the final yield of both types of tumors, and the death of tumor- and nontumor-bearing animals. For convenience in comparing the potency of different samples, a simple numerical expression based on the relation of a cancer index to tumor index was also devised. Results are presented on five types of materials. Catalytically Cracked Oils. Tests were conducted on ten catalytically cracked oils. Five of these proved t o be highly carcinogenic, two moderately so, and three essentially negative. The next series of tests was conducted with various fractions of an active oil. The fractions that distilled below 700' F. did not produce tumors. The fractions that distilled between 700' and 800" F. produced some benign papillomas but no cancers. The distillate above 800' F. was the most carcinogenic portion. The fraction distilling between 950' and 965' F. was the most potent single fraction. The activity of the six fractions between 800' and 1010' F. indicated that probably more than one carcinogenic substance was present. The active fraction represented less than 3% of the total product. Tests were made on two feed stock samples t o answer the question as to whether the carcinogenic material existed prior t o fluid catalytic cracking or whether it was produced in the cracking process, The feed stocks were found to be only slightly active, producing benign tumors but no cancers. The strong carcinogenic activity therefore is not due to the feed stock but
results from the cracking process. Another series of t e s t s w a s conducted to obtain information on the chemical nature of the carcinogenic materials. Some of the active oil was adsorbed on a silica gel column and then eluted with heptane, cumene, and acetone. The heptane fraction which contained the nonaromatic constituents and represented 68y0 of the original sample was without carcinogenic activity. Both the cumene and acetone fractions which contained the aromatic derivatives showed greater carcinogenic activity than the original sample, thue showing that a concentration of the active substances had been obtained. Specially Treated or Blended Oils. Tests were conducted to explore the pousibility of removing the carcinogenic constituents from the high boiling catalytically cracked material. Other active adsorbents other than silica gel, mild hydrogenation, and treatment with sulfuric acid were tried. Further studies were not conducted as the results were not sufficiently encouraging. It was found that blending the carcinogenic fraction with an inactive oil effectively reduces the activity. Little change was noted in blends containing about 50y0 potent oil, but below this level, activity decreased and blends containing no more than about 10% potent oil had little, if any, activity. Waxes. Eight "slack" waxes obtained from pressing operations were tested. The slack waxes showed a low order of carcinogenic activity when compared t o the high boiling catalytically cracked material. The aromatic extract from these slack waxes showed increased activity. The results indicated that the carcinogenic activity of the slack waxes is due to the aromatic constituents of the oils from which the waxes are pressed and are not due to the paraffins. Petroleum Tars. Petroleum tars showed some carcinogenic activity which varied with the process from which it wa.s obtained. Fractionation of a steam-cracked tar showed increased activity for the higher (Continued on p a g e 108 A ) boiling
INDUSTRIAL AND ENGINEERING CHEMISTRY
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Industrial Hygiene fractions as was obtained with the catalytically cracked oils. American Shale Oil. The reported carcinogenic activity of oil obtained from Scottish shale raised the question of the possible activity of oils from American shale. A sample of total shale oil obtained from the U. S. Bureau of Mines was shown to have a low order of carcinogenic activity. The fraction that distilled below 550' F. was negative, but the fraction between 550" and 700" F. contained carcinogenic materials. The fraction that distilled above 700" F. was negative. Chemical Studies. It is obvious that the foregoing studies could not have been carried out without assistance from the chemist in preparing and characterizing the various fractions and materials. But another and more practical aspect of these studies is the correlation of certain laboratory tests with tumor potency. The use of the mouse tests requires too lengthy a time-period to be used for control purposes. Hence, a rapid laboratory assay which would permit predicting the carcinogenic activity with some accuracy would be a valuable tool for control purposes. Four methods that have been tried for correlating tumor potency with certain chemical and physical properties are described. A rather good correlation was obtained between tumor potency determined by mouse test and ultraviolet absorptFon spectra. Another test based on the selective extraction of polynuclear aromatic compounds by means of an aqueous caffein solution followed by spectrographic analysis of the extract also shows good promise. A third procedure is based on the Diels-Alder reactions of the oils with maleic anhydride and a fourth method employs a chromatographic separation and refractometric measurements. This work is continuing and further developments may be expected. Control Measures. Although theexperimental biologioal studies and the chemical and physical investigations to eliminate or diminish carcinogenic activity are continuing, 20 recommendations have already been put into effect in the seven refineries affiliated with the Standard Oil Co. of New Jersey which have fluid catalytic cracking units, The recommendations are:
ing skin abnormalities. Swarthy or dark skinned persons with good personal hygiene are preferable. 4. Employees who show warts or other skin lesions should be removed and assigned to employment where future exposure to the oil would not occur. o. Employees with skin lesions should be given prompt medical attention. 6. Protective clothing such as apron, gloves, boots, etc., should be worn when working with the oils to prevent skin contact. 7. Employees should be instructed not to touch the scrotum or face with oily hands because a high percentage of occupational cancers from other agents occur in these areaa. 8. Employees should be instructed to wash thoroughly with soap and water to remove any oil from the skin. Experiments with mice have shown that the number of tumors produced by active oil can be materially reduced by washing with soap and water shortly after application of the oil. 9. Employees should be instructed to take a shower bath if their work is such that there is a reasonable possibility that contact of the oil with the skin has occurred. 10. Employees should wear clean work clothing daily. 11. It is considered desirable to provide facilities for cleaning clothes contaminated with the oils so that the cleaning process can be carried out under proper supervision. 12. Refinery equipment should be arranged to reduce points of potential contact to a minimum. 13. Equipment containing these oils should be identified by color and appropriate signs indicating the hazards. 14. Employees whose work entails contact with the oils should be informed of the hazard and be instructed in proper precautionary measures. 15. Constant supervision of precautionary measures is essential to ensure the proper functioning of the control program. 16. Periodic visitseat approximately 6month intervals should be made to the plant by a representative of the medical department. 17. Precautionary measures should be taken to eliminate inhalation of oil vapor or mist. 18. Adequate personnel and equipment should be provided so that the program can be carried out satisfactorily. 19. The extent to which blends with inactive oil can be utilized as a control procedure should be investigated. 20. Complete reports covering the industrial hygiene and clinical phases of the program should be prepared semiannually.
LMerature cZted 1. Restrict number of employees exposed by assigning selected groups of workers to jobs involving contact with the oils. This procedure has particularly reduced the number of mechanical and maintenance personnel involved. 2. Make periodic medical examinations of exposed persons a.t 3- to 12-month intervals with particidar reference to the presence of warts, papillomas, tumors, cancers, dermatitis, or other skin abnormalities. 3. Employees should be selected by the medical department to avoid individuals who have an excessive number of pre-exist-
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(1) Blanding, F. H.. et aE.,Arch. I d . Hug. & Occupational Med., 4, 335 (1951). (2) Fischer, H. G . M., et al., Ibid., 4, 315 (1951). (3) Holt, J. P., et aE., Ibid., 4, 325 (1951). (4) Smith, W. E.,et al., Ibid., 4, 299 (1951). Correspondence concerning this column will he forwarded promptly if addressed to the author, c/o Editor, INDUSTRIAL AND ENQINEERINQ CHEMISTRY, 1155--16th St., N.W., Washington 6, D. C.
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