Re: Institute for Environmental Health Sciences

Consumption of alcoholic beverages is known to be a human carcinogen based on sufficient evidence of carcinogenicity from human studies that indicate a causal relationship between consumption of alcoholic beverages and cancer in humans (reviewed in IARC V. 44, 1988; Longnecker and Enger, 1996). Studies indicate that the risk of cancer is most pronounced among smokers and at the highest levels of consumption. Consumption of alcoholic beverages is causally related to cancers of the mouth, pharynx, larynx, and esophagus. Cohort and case control studies in a variety of human populations are notable for their consistency in reporting the presence of moderate to strong associations with dose-response relationships for these four sites. Evidence also supports a weaker but possibly causal relation between alcoholic beverage consumption and increased risk of cancers of the liver and breast (Longnecker, 1994). The effect of a given level of alcoholic beverage intake on absolute risks of cancer of the mouth, pharynx, larynx, and esophagus is influenced by other factors, especially smoking. However, smoking does not explain the observed increased risk of cancers associated with increased alcoholic beverage consumption. No adequate experimental animal carcinogenicity studies of alcoholic beverages have been reported in the literature. Studies specifically examining the carcinogenicity of ethanol in animals have not yielded results that would suggest that the ethanol component of alcoholic beverages is solely responsible for the increases in cancer observed in people consuming alcoholic beverages.

MECHANISMS OF CARCINOGENESIS
Increased frequencies of chromosomal aberrations, sister chromatid exchanges, and aneuploidies have been found in the peripheral lymphocytes of alcoholics. Ethanol-free extracts of some alcoholic beverages induced sister chromatid exchanges in human cells in vitro and mutations in bacteria (IARC V. 44, 1988). The mechanism by which consumption of alcoholic beverages can cause cancers in humans is not established.

KNOWN TO BE A HUMAN CARCINOGEN NINTH REPORT ON CARCINOGENS

STRONG INORGANIC ACID MISTS CONTAINING SULFURIC ACID
CAS No. 7664-93-9 (Sulfuric Acid)
First listed in the Ninth Report on Carcinogens
CARCINOGENICITY

Occupational exposure to strong inorganic acid mists containing sulfuric acid is known to be a human carcinogen, based on sufficient evidence of carcinogenicity from studies in humans that indicate a causal relationship between exposure to strong inorganic acid mists containing sulfuric acid and human cancer (reviewed in IARC V. 54, 1992). Occupational exposures to strong inorganic acid mists containing sulfuric acid are specifically associated with laryngeal and lung cancer in humans. Steenland et al. (1988) reported on studies of one U. S. cohort of male workers in pickling operations in the steel industry, which showed excesses of laryngeal cancer after adjusting for smoking and other potential confounding variables [standardized incidence rate ratio (SIR)for laryngeal cancer was 2. 30 (95%confidence interval [CI ], 1. 05-4. 36)]. In a ten-year follow-up, Steenland (1997) reported a laryngeal cancer rate ratio of 2. 2 (95%CI, 1. 2-3. 7), consistent with previous findings from this cohort. In a nested case-control study of workers in a U. S. petrochemical plant, Soskolne et al. (1984)found a dose-response for laryngeal cancer risk among workers exposed to moderate (odds ratio [OR ] of 4. 6;;95%CI, 0. 83-25. 35)or high levels (OR of 13. 4;95%CI, 2. 08- 85. 99)of sulfuric acid. In a Canadian population based case-control study, after controlling for tobacco and alcohol use and including only the most specific exposure scale, Soskolne et al. (1992)also observed a dose-response for laryngeal cancer risk in workers exposed to sulfuric acid mist, with ORs of 2. 52 (95%CI, 0. 80-7. 91)at the lowest level of exposure and 6. 87 (95% CI, 1. 00-47. 06)at the highest. A report of a similar population based case-control study in Canada by Siemiatycki (1991)suggested an increase in risk for oat-cell carcinoma of the lung (rate ratio [RR ]of 2. 0;90%CI, 1. 3-2. 9). Steenland and Beaumont (1989), reporting on the same U. S. cohort of male workers in pickling operations described by Steenland et al. (1988), found an excess of lung cancer in these workers after adjusting for smoking and other potential confounding variables [standardized mortality ratio (SMR)for lung cancer was 1. 36 (95%CI, 0. 97-1. 84)]. No adequate experimental animal carcinogenicity studies of sulfuric acid or strong inorganic acid mists containing sulfuric acid have been reported in the literature. ADDITIONAL INFORMATION RELEVANT TO CARCINOGENESIS OR POSSIBLE MECHANISMS OF CARCINOGENESIS The manufacture of isopropyl alcohol by the strong acid process, which uses sulfuric acid, has been identified by IARC as known to cause an increased incidence of cancer of the paranasal sinuses in workers (reviewed in IARC V. 15, 1977). O S O OH HO