- Email: [email protected]
Are orthotolidine and dianisidine health hazards to laboratory workers?
Clin. Biochem. 7, 3-4 (1974) GUEST EDITORIAL
ARE ORTHOTOLIDINE AND DIANISIDINE HEALTH HAZARDS TO LABORATORY W O R K E R S ?
The aromatic amines benzidine, o-tolidine (3,3'dimethylbenzidine; n o t toluidine), and dianisidine (3,3'-dimethoxybenzidine) have been commonly employed in clinical laboratories: mainly for the detection of traces of blood, but also in the quantitation of chlorine in w a t e r and of glucose by the glucose oxidase method. These compounds appear in solutions, tablets, and various dipsticks for laboratory use. Paul Brodeur has recently w r i t t e n a series of articles in the N e w Y o r k e r on chemical hazards to health of factory workers in the U.S.A. He dealt mainly with the hazards of asbestos ; but in the final article 1 he commented on the handling of benzidine and other known c/Lrcinogens. The U.S. Dep a r t m e n t of Labor is apparently engaged in setting standards for exposure of factory workers. But w h a t about the exposure of laboratory personnel to known or suspected carcinogens? Exposure to benzidine is now generally recognized as a cause of bladder cancer. According to Rye, et al'-' its m a n u f a c t u r e by the Upjohn. Company in the U.S.A. was discontinued in 1965. The authors claim that no known cases of human cancer from exposure to o-tolidine or dianisidine have been reported. But they conclude that these compounds should be considere:l as toxic materials whose h u m a n carcinogenicity has not been established. Searle :~ reported t h a t U.K. Government regulations set up in 19674 prohibited the use and m a n u f a c t u r e of substances believed to be carcinogenic; this included benzidine and its salts. The regulations also control the m a n u f a c t u r e and uses of o-tolidine and dianisidine and their salts. Pliss and Zabezhinsky n in the Soviet Union found t h a t o-tolidine was carcinogenic in rats and recommended that care be exercised in its use, in both industry and the laboratory. According to Lipkin 6 the m a n u f a c t u r e of o-tolidine was discontinued in the Soviet Union in 1971 because of its carcinogenicity. P e r h a p s the best s u m m a r y of the carcinogenic hazards of the aromatic amines is the review by George T in a series of papers on laboratory safety. He points out t h a t U.K. regulations do not apply to clinical laboratories, because they are not factories under the Act; but it was recommended that the use of liquid reagents t h a t include any of these amines is no longer justified. George refers to the Chester Beatty Research Institute's "Precautions for laboratory workers who handle carcinogenic amines "s , issued in 1966. George raises the question of the legal position of a Head of a
4
EDITORIAL
Department, if a worker should develop cancer of the urinary tract and if a potential carcinogen had not been eliminated from the laboratory for clinical reasons. Several recent textbooks of clinical chemistry have been examined. Varley 9 warns of hazards of all three amines and refers to the Chester Beatty pamphlet on precautions. Kachmar in Tietz's text lo also warns that there is no advantage in replacing benzidine with o-tolidine because all the diaminodiphenyl derivatives are weakly carcinogenic. White, Erickson, and Stevens 11 give no warnings whatever• I have also looked at several commercial chemical catalogs. Those from the Aldrich Chemical Co. and from Koch-Light list benziding as a carcinogen, but the entries for otolidine and dianisidine have no warning. The Fisher catalog states that benzidine and o-tolidine are "non-mailable." The J. T. Baker, British Drug Houses, and Matheson, Coleman & Bell lists have no warnings for any of these compounds. Laboratory scientists in North America have been rather casual about the possible hazards of the aromatic amines. Surely, products containing them should be labeled with a w a r n i n g as to possible health hazards. Furthermore, directors of clinical laboratories should establish adequate procedures for their handling and, where possible, eliminate or minimize their use.
H. BRUCE COLLIER Professor Emeritus of Pathology University of Alberta Edmonton T6G 2G3 Alberta
REFERI~N.CES I. 2. 3. 4.
Brodeur, P. (26 Nov 1973). The New Yorker, 126-179. Rye, W. A., Woolrich, P. F., Zanes, R. P. {1970). J. Occup. Med. 12, 211-215. Searle, C. E. (1970). Chem. in Britain, 6, 5-10. The Carcinogenic Substances Regulations. 1967. SI No. 879. London H.M. Stationery Office. 5. Pliss, G. B. and Zabezhinsky, M. A. (1970). U.S. Nat. Cancer Inst. J. 45, 283-295. 6..Lipkin, I. L. (1972). Gig Sanit, 37, 101; (1972) Chem. Abstr. 77, 92433j. 7. George W.H.S. (1971). Ann. Clin. Biochem. (London), 8, 130-132. 8. Royal Cancer Hospital, London, Chester Beatty Research Institute. Precautions for Iaborato~T workers who handle carcinogenic aromatic amines. 7 pp (1966); reprinted with additional notes (1971). 9. Varley, H. (1969). Practical Clinical Biochemistry, 4th ed. William Heinemann, London; Interscience Books New York. 10. Kachmar, J. F. in Tietz, N.W. (ed). (1970). Fundamentals of Clinical Chemistry, W. B. Saunders Co, Philadelphia, London and Toronto, p 281. 11. White, W. L., Eriekson, M. M. and Stevens, S. C. (1970). Chemistry for Medical Technologists, 3rd ed C. V. Mosby Co, St. Louis, Mo.
ARE ORTHOTOLIDINE AND DIANISIDINE HEALTH HAZARDS TO LABORATORY W O R K E R S ?
The aromatic amines benzidine, o-tolidine (3,3'dimethylbenzidine; n o t toluidine), and dianisidine (3,3'-dimethoxybenzidine) have been commonly employed in clinical laboratories: mainly for the detection of traces of blood, but also in the quantitation of chlorine in w a t e r and of glucose by the glucose oxidase method. These compounds appear in solutions, tablets, and various dipsticks for laboratory use. Paul Brodeur has recently w r i t t e n a series of articles in the N e w Y o r k e r on chemical hazards to health of factory workers in the U.S.A. He dealt mainly with the hazards of asbestos ; but in the final article 1 he commented on the handling of benzidine and other known c/Lrcinogens. The U.S. Dep a r t m e n t of Labor is apparently engaged in setting standards for exposure of factory workers. But w h a t about the exposure of laboratory personnel to known or suspected carcinogens? Exposure to benzidine is now generally recognized as a cause of bladder cancer. According to Rye, et al'-' its m a n u f a c t u r e by the Upjohn. Company in the U.S.A. was discontinued in 1965. The authors claim that no known cases of human cancer from exposure to o-tolidine or dianisidine have been reported. But they conclude that these compounds should be considere:l as toxic materials whose h u m a n carcinogenicity has not been established. Searle :~ reported t h a t U.K. Government regulations set up in 19674 prohibited the use and m a n u f a c t u r e of substances believed to be carcinogenic; this included benzidine and its salts. The regulations also control the m a n u f a c t u r e and uses of o-tolidine and dianisidine and their salts. Pliss and Zabezhinsky n in the Soviet Union found t h a t o-tolidine was carcinogenic in rats and recommended that care be exercised in its use, in both industry and the laboratory. According to Lipkin 6 the m a n u f a c t u r e of o-tolidine was discontinued in the Soviet Union in 1971 because of its carcinogenicity. P e r h a p s the best s u m m a r y of the carcinogenic hazards of the aromatic amines is the review by George T in a series of papers on laboratory safety. He points out t h a t U.K. regulations do not apply to clinical laboratories, because they are not factories under the Act; but it was recommended that the use of liquid reagents t h a t include any of these amines is no longer justified. George refers to the Chester Beatty Research Institute's "Precautions for laboratory workers who handle carcinogenic amines "s , issued in 1966. George raises the question of the legal position of a Head of a
4
EDITORIAL
Department, if a worker should develop cancer of the urinary tract and if a potential carcinogen had not been eliminated from the laboratory for clinical reasons. Several recent textbooks of clinical chemistry have been examined. Varley 9 warns of hazards of all three amines and refers to the Chester Beatty pamphlet on precautions. Kachmar in Tietz's text lo also warns that there is no advantage in replacing benzidine with o-tolidine because all the diaminodiphenyl derivatives are weakly carcinogenic. White, Erickson, and Stevens 11 give no warnings whatever• I have also looked at several commercial chemical catalogs. Those from the Aldrich Chemical Co. and from Koch-Light list benziding as a carcinogen, but the entries for otolidine and dianisidine have no warning. The Fisher catalog states that benzidine and o-tolidine are "non-mailable." The J. T. Baker, British Drug Houses, and Matheson, Coleman & Bell lists have no warnings for any of these compounds. Laboratory scientists in North America have been rather casual about the possible hazards of the aromatic amines. Surely, products containing them should be labeled with a w a r n i n g as to possible health hazards. Furthermore, directors of clinical laboratories should establish adequate procedures for their handling and, where possible, eliminate or minimize their use.
H. BRUCE COLLIER Professor Emeritus of Pathology University of Alberta Edmonton T6G 2G3 Alberta
REFERI~N.CES I. 2. 3. 4.
Brodeur, P. (26 Nov 1973). The New Yorker, 126-179. Rye, W. A., Woolrich, P. F., Zanes, R. P. {1970). J. Occup. Med. 12, 211-215. Searle, C. E. (1970). Chem. in Britain, 6, 5-10. The Carcinogenic Substances Regulations. 1967. SI No. 879. London H.M. Stationery Office. 5. Pliss, G. B. and Zabezhinsky, M. A. (1970). U.S. Nat. Cancer Inst. J. 45, 283-295. 6..Lipkin, I. L. (1972). Gig Sanit, 37, 101; (1972) Chem. Abstr. 77, 92433j. 7. George W.H.S. (1971). Ann. Clin. Biochem. (London), 8, 130-132. 8. Royal Cancer Hospital, London, Chester Beatty Research Institute. Precautions for Iaborato~T workers who handle carcinogenic aromatic amines. 7 pp (1966); reprinted with additional notes (1971). 9. Varley, H. (1969). Practical Clinical Biochemistry, 4th ed. William Heinemann, London; Interscience Books New York. 10. Kachmar, J. F. in Tietz, N.W. (ed). (1970). Fundamentals of Clinical Chemistry, W. B. Saunders Co, Philadelphia, London and Toronto, p 281. 11. White, W. L., Eriekson, M. M. and Stevens, S. C. (1970). Chemistry for Medical Technologists, 3rd ed C. V. Mosby Co, St. Louis, Mo.