Dangerous and cancer-causing properties of products and chemicals in the oil refining and petrochemical industries. Part XXX: Causal relationship between chronic myelogenous leukemia and benzene-containing solvents.

Benzene and benzene-containing products and solvents have long been associated with bone marrow toxicity. Both animal studies and human epidemiological studies have shown statistically significant increases of leukemia and other lymphohematopoietic cancers in workers exposed to benzene. The most common leukemia that has been associated with benzene exposure, also called benzene poisoning, is acute myelocytic leukemia (AML). A review of the epidemiological literature on workers exposed to benzene or benzene-containing solvents and products shows, without question, that this exposure is significantly related to other types of leukemia and lymphoma. In this article, we review the literature on the relationship between benzene exposure and chronic myelogenous leukemia (CML) and find that benzene and benzene-containing products are significantly related to morbidity and mortality from CML.

Causal relationship between non-Hodgkin's lymphoma and exposure to benzene and benzene-containing solvents.

Non-Hodgkin's lymphoma (NHL) is a malignant neoplasm of the lymphatic system made up of mainly B cell lymphocytes. A large number of studies have shown significant associations between NHL and benzene or benzene-containing solvents and products. This article summarizes studies detailing these associations and indicates those that are significant. Based on an analysis of the literature and the weight of evidence from numerous studies, it is reasonable to conclude that exposure to benzene or to solvents or products containing benzene is causally related to NHL.

Causal relationship from exposure to chemicals in oil refining and chemical industries and malignant melanoma.

Malignant melanoma has been thought to be related mainly to exposure to the sun or radiation. A review of the scientific literature reveals many significant correlations between benzene and benzene-containing solvents in the workplace and the occurrence of malignant melanoma, particularly in sites that have never been exposed to sunlight. A comparison of positive correlations between such exposure and malignant melanoma by independent investigators and negative findings by investigators with industry affiliations reveals that this difference, at least in part, may account for the discrepant findings. Based on independent studies, it is reasonable to conclude that malignant melanoma is causally related to employment-related chemical exposures in the petroleum refining industry.

Remembering Professor Cesare Maltoni.

Professor Cesare Maltoni, a renowned leader in the research of the hazards of carcinogens in the workplace, died on January 22, 2001 at the age of 70. Born in Faenza (Ravenna), Italy on November 17, 1930, he received his M.D. degree from the University of Bologna in 1954-1955. He was Director of the Institute of Oncology of Bologna (1964 to 1997), Director of the Bologna Centre for the Prevention and Detection of Tumours and Oncological Research (1966 to 1989), and Scientific Director, European Foundation of Oncology and Environmental Sciences "B. Ramazzini" from 1993 until he died. Maltoni conducted long-term carcinogenic studies on some 200 agents. He was the first to demonstrate that vinyl chloride is a carcinogen that produces, among other tumors, angiosarcoma of the liver. He was the first to show that benzene is a powerful multipotential carcinogen. Maltoni authored more than 700 original scientific publications, books, and proceedings. He was editor and coeditor of many journals. Among his many awards were the Stokinger Award, American Conference of Governmental Industrial Hygienists (ACGIH), Kansas City, 1995; International Award "B. Ramazzini" of the Collegium Ramazzini, Washington, 1995; International I.J. Selikoff Memorial Award, Washington, 1995; and the Sigillum Magnum of the University of Bologna, 1997. Many fellow Ramazzinians and his coworkers wish to be considered part of the group of, as he once wrote, his "always family friends" and to remember happy moments when we were together. A man of great stature and many contributions, Cesare Maltoni will never be forgotten.

Carcinogenic effects of benzene: Cesare Maltoni's contributions.

Cesare Maltoni's contributions to understanding, identifying, and characterizing widely used commercial chemicals in experimental animals are among the most important methods developed in the history of toxicology and serve to protect working men and women, the general population, and our environment from hazardous substances. Maltoni developed experimental methods that have reached the "platinum standard" for protection of public health. Benzene was among the 400 or more chemicals that Maltoni and his associates tested for carcinogenicity. In 1976, Maltoni reported that benzene is a potent experimental carcinogen. Maltoni's experiments clearly demonstrated that benzene is carcinogenic in Sprague-Dawley rats, Wistar rats, Swiss mice, and RF/J mice when administered by inhalation or ingestion. Benzene caused carcinomas of the Zymbal gland, oral cavity, nasal cavities; cancers of the skin, forestomach, mammary glands, and lungs; angiosarcomas and hepatomas of the liver; and hemolymphoreticular cancers. Thus, benzene was shown to be a multipotential carcinogen that produced cancers in several species of animals by various routes of administration. On November 2, 1977, Chemical Week reported that Maltoni provided a "bombshell" when he demonstrated the "first direct link" between benzene and cancer. In this paper, I shall summarize early experiments and human studies and reports; Maltoni's experimental contribution to understanding the carcinogenicity of benzene in humans and animals; earlier knowledge concerning benzene toxicity; and benzene standards and permissible exposure levels.

Carcinogenicity of methyl-tertiary butyl ether in gasoline.

Methyl tertiary butyl ether (MTBE) was added to gasoline on a nationwide scale in 1992 without prior testing of adverse, toxic, or carcinogenic effects. Since that time, numerous reports have appeared describing adverse health effects of individuals exposed to MTBE, both from inhalation of fumes in the workplace and while pumping gasoline. Leakage of MTBE, a highly water-soluble compound, from underground storage tanks has led to contamination of the water supply in many areas of the United States. Legislation has been passed by many states to prohibit the addition of MTBE to gasoline. The addition of MTBE to gasoline has not accomplished its stated goal of decreasing air pollution, and it has posed serious health risks to a large portion of the population, particularly the elderly and those with respiratory problems, asthma, and skin sensitivity. Reports of animal studies of carcinogenicity of MTBE began to appear in the 1990s, prior to the widespread introduction of MTBE into gasoline. These reports were largely ignored. In ensuing years, further studies have shown that MTBE causes various types of malignant tumors in mice and rats. The National Toxicology Program (NTP) Board of Scientific Counselors' Report on Carcinogens Subcommittee met in December 1998 to consider listing MTBE as "reasonably anticipated to be a human carcinogen." In spite of recommendations from Dr. Bailer, the primary reviewer, and other scientists on the committee, the motion to list MTBE in the report was defeated by a six to five vote, with one abstention. On the basis of animal studies, it is widely accepted that if a chemical is carcinogenic in appropriate laboratory animal test systems, it must be treated as though it were carcinogenic in humans. In the face of compelling evidence, NTP Committee members who voted not to list MTBE as "reasonably anticipated to be a human carcinogen" did a disservice to the general public; this action may cause needless exposure of many to health risks and possibly cancers.