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I I I I I I I I I AFIATOXINS constituents of waste. Additionally, EPA's Carcinogen Assessment Group considers aflatoxins m be potential[ycarcinogenic. FDA, under the Federal Food, Drug and Cosmetic Act (FD&CA) and the Public Service Act, regulates any materials or ingredients rhar could be contaminated with aRacoxins. QSF{A regulates aRatoxins under rhe Hazard Communication Standard and as a chemical hazard in laboratories. Regulations are summarized in Volume 11, Table A-I. Alcoholic Beverage Consumption; First listed in the Ninth Report on Carcinogens Carcinogenicity Consumption of alcoholic beverages is known to be a human rarcinogtm based on su$icienc evidence of carc'tnogeniciry from human studies that indicate a causal relationship between consumption of alcoholic beverages and cancer in humans (reviewed in IARC V.44, 1988; Longnedacr and Enger, 1996). Studies indicate rhat the risk of canccr 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 ca.se 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, pharynz, larynx, and esophagus is influenced by other factors, especially smoking. However, smoking does not explain the observed increased risk of cancars associated with increased alcoholic beverage consumpdon No adequate experimental animal carcinogeniciry studies of alcoholic beverages have been reported in the literature. Studies sped6cally examining the carcinogenicity of ethanol in animals have not yielded results that would suggest that dte ethanol component of akoholie beverages is solely responaible for the increases in cancer observed in people consuming alcoholic beverages. Additional Information Relevant to Carcinogenesis or Possible NTecitanisms of Carcinogenesis Increased frequencies of chromosomal aberrations, sister chromatid exchanges, and aneuploidies have been found in the peripheral lymphocytes of alcoho6es Erhanol-free estracrs of some alcoholic beverages induced sister chromatid ezchangtxio human cdlt in vimr and mutations in baaeru (]ARC V.44, 1988).' The mechanims by-whicb mnntmpdott of alcoholic beverages can cause cancers in htunapAit}3qt established.. Proper6es. .nO ~l~k s ~a71e~ sw= .. Ethanoi and wqrq atn constituents of most alcoholic beverages. I1te amwrtF,c7dfaool consumed in a standard measure of most drinks is simitaqtf,prrbea„wine, and spirits (10-14 g). The ethanol in theae bevesages comesfrom the fermentation of carbohydrates by yeast. Althougb: ethanatcan be chemically synthesized from ethylene, alcohol synthesis for usa in beverages is rtot. employed by the aboholic beverage indusrry because of the pre.amsoe of impuritiesfrom tbesynthetic process (IARC.V.44s 1988), Bea, wine, and spirits also contain volatile and nonvolatile Savoe compounds that originate fmm raw materiaLr, fermentation, wooden esln used for maturation, and synthetic substances added to specially flavored beverages. The exatt composition of many beverages is confidential business information, though much published data KNOWN TO BE n HVMAN CAHONOG£N defines the organic compounds usually present at low levels. Several of the components and contaminants identified in beer, ~cine, and spirits are known or suspected human carcinogens. induding acetaldehyde, nitrosamines, aFlatoxins, ethyl carbamare lurethanL asbestos, and arsenic compounds (IAftC V.44, 1988; NTP, 1998). Use The IARC monograph described in detail the use of alcoholic beverages. Consumprion trends, including overall level of alcohol consumption, beverage choice, age and sex differences, and temporal variations, differ among and within societies. Parrerns of alcohol consumption have been observed to vary on a global scale, largely independent of regional differences or economic and social changes (fARC V.44, 1988). A downward trend in alcohol consumption was observed in the United Srates and many European countries from the turn of the twentieth century until the period between the world wars. Alcohol consumption then increased, approaching the peak levels of the nineteenth century, until the 1970s and 1980s, when consumption rates slowed, leveled off, or, for the United States, decreased (NIAAA, 1997). Alcohol consumption in the United States increased from the 1940s until the early 1980s, then began to decrease steadily; by 1993, consumption had declined to the lowest level since 1964. Per capita consumption figures were derived by estimating total alcohol use, based on sales and shipment data, of the U.S. population aged 14- years or older. Apparent per capita consumption expressed in gallons of pure alcohol was 1.6 in 1940, -2.2 in 1964 and 1993, and -2.8 ca. 1980 (NIAAA, 1997). A 1990 National Alcohol Survey gathered data regarding the demographic distribution of drinking patterns in the United Statez (Midanik and Clark, 1994). Respondents were dassifred as current drinkers (any use of alcohol beverages in the preceding year), weekly drinkers (any alcoholic beverage use at least weekly during the preceding year), and drinkers of five or more drinks (drinking five or more drinks on one occasion weekly or more often during the preceding year). Of the men surveyed, 71.2% were current drinkers, 40.0% were weekly drinkers, and 6.5% were in the five drinks group. In the group reporting the highest alcohol consumption, men aged 18-29, 76.5% were current drirrkerr,. 44.4% were weekly drinkcrs, and 11.0% were in the five drinks group. The same age group reported the highest consumption among women: 69.7% were current drinkers, 19.7% were weekly drinkecs, and 3.0% were in the five drinks group. Whett dam from all age groups of women were combined, 59.4%were current drinkars.18.8%were weeklydrinlmrs, and 1.4% were in the five drinks gmtip.. These figures alf n:presenr deaeases in alcohol consumption as measured by a similar survey conducted in 19" Respondente were grouped by ethnicity and religious afftliation. The survey found no statistically signifinnt differeaces in alcoho4 use among ethnie groups, but conservative Protestaan reported signifstnntly lovre alcohol consumption in all three categories (bfidaniE and CJadq 1994)~ ., Per capita conatmption of wine and beer in the United Stares was relatively stable over the period, begnning irr the nrly 1980s and continuing into thr1990rvvhes owa(i alcohol consumption wu falling (William: ee aL. 1995t ared by NIAAA.,1997). Most of the deceax in U. S. alcohol coosurnpeioa tan be attributed to decreased consumption of spiritsa.ThoegJtwiocbarmade much leas of a contri4ustioa ro. the total vohttrse oEU.Sk aleohad consumption than beer or spiritr, per cspita mnsumpeion of wine was the same in 1993 as it was in 1977, wwhile consumptim,oispitio fell by a6nost 35% over the same paiod. Per sapita cottaumptioo-of beer decreased from 1991 to 1985 Strcnnoed dtereaftefs and ia,1993 wu 1% betowe 1977 consumption kvelt (NIMA, 1997). 2073777283

I nholic ,fcF I n, I Icu ol largely ng-er,e States u u w y ng e five or n e rin s, group. ~ n aged m s, gwec n the fle , -esent urvey v~d Fi t -tvative ll a I ue s .Os and on as ':o e cr d ss of a 'n n 3 st d from W 17 ' EY KNOWN To SEA HUMAN CANClNOGEN Production A11 alcoholic beverages are produced by the Fermentation of fruit or orher vegetable matter. Most commercial and home production involves (ermenred beverages that are classified, based cn raw materials and production methods used, as beer, wine, or spirits, although smaller quantities of other kinds of fermented beverages (cider, rice wine, palm wine, etc.) are also produced. Beer is produced by fermentation of malted barley or other cereals with the addition of Itops. Wine'ss made from fermentation of grape juice or crushed grapes; forrified wines include additional distilled spirits. Distilled sprnrs, so named because of liquid distillation after sugar Fermentation to increase the akohol content, originate from sources of starch or sugar, including cereals, molasses from sugar beeu, grapes, potatoes. cherries, plums, and other fruits (IARC V,44, 1988). [n 1990, American wine production was 4,520 thousand Mg, beer production was 374,529 thousand hecrolirers, and spirit production was 18,454 chousand hecmlirers (ARF, i994). World total production of dte same beverages was 29,010 thousand Mg, 1,088,742 thousand heaolirers, and 57,756 thousand hecrolirers, respectively. Regulations A March 1999 search of the most recent editions of the Code of Federal Regulations found no regulations requiring warnings on alcoholic beverage labels of an increased risk of cancer due to alcoholic beverage consumpeion. (Labels on saccharin-containing wines, distilled spirits, and malc beverages, however, must warn of amcrr risk from saccharin consumption [27 CFR 4.32, 5.32, and 7.22, respecuvely, enforced by the BATF (Bureau of Alcohol, Tobacco and Firearms), Department of the Treasury)). FDA regulates health claims information on food labels. Thus, labels on low fat foods may make the health claim that diets low in fat "may" or "might" reduce the risk of some cancers with several provisions (21 CFR 100.73 Health dairns dietary lipids and cancer). Optional information allowed includes identification of risk factors for development of cancer. Alcohol consumption is one of the risk factors that FDA lists. The same opt'sossal infotmation may be added to labels stating there is a reduced risk of cancer for diets high in fiber- conraining grain products, fruits, and vegetables (21 CFR 101.76, 21 CFR 101.78), KChere is no separate CAS Registry Number assigned to alcoholic beverage consumption. 4-Aminobiphenyl (4-Aminodiphenyi) CAS No. 92-67-1 First Listed in the Firrr.4mnrre! Xqnrt oa Carrinogenr l:BrCSrlogenlGltY 4-Aminobiphenyl is known to be a hr<man rarcinogen based on suf5dent evidence of cardnogenieity in bumans (IARC V.1, 1972; G1RC 5.1, 1979; IARC S.4, 1982; IARC S.7, 1987), The ertear of urinary bladder cancer risk associated with exposure to 4- aminobiphenyl was 6rar documented by a descriptive study in which 19 of 171 men exposed to the compound developed urinary bladder tnmors. Sn another survey of cancer mortality among workers ar a chemiral plant pcoducitg a variety of chemialt; a renfold invcase in mortality from urinary bladder cancer was reported. REFpN70N CdHerNOGENs, N/NIN EWiWN 4-AMINOBIPNENYL (4-AMINOD/PHENYL) An iARC Working Group reported rhat there is sut7icient evidence of carcinogenicity of 4-aminobiphenvl in experimental animals (iARC V.1, 1972; IARC 5.1, 19'9~ f.jRC S.S, 1982; L-\RC 5.7, i987). When adminisrered by gavage, 4-ammobiphenyl induced carcinoma of the urinary bladder in mice and r.rhbits. \l'h<n administered in the dier, $-aminobiphenvl induced neoplasnss at various sirss. including dose-related increases in rhe incidence oF angiosarcomas, in mice. When administered in the diet, ihe compound induced carcinoma of the urinary bladder in dogs. EY'hen administeced by subcutaneous injection, 4-aminobiphenyl induced mammary gland and intestinal rumors in rats and hepamntas in newborn m ice o F barh sexes. Properties 4-Aminobiphenyl occurs as colorless crystals which rurn purple upon oxidation. it has a floral odor. It is slighdy soluble in cold water and soluble in hoc water, non-polar solvents, and lipids. ',Vhen heated to decomposition, it emits toxic fumes of nitrogen oxides Itip,l. Use 4-Aminobiphenyl presendy has no commercial use in the United States, although it was formerly used as a rubber antioxidant and a dye intermediate (HSDB, 1997). The compound has also been used as a research chernical and as a reagenc for detecting sulfates (Merck, 1983; Sittig, 1985). Production 4-.Aminobiphenyl is no longer produced cornmercially in the United States, as is the case in most countries of the world, because of its carcinogenic effects (HSDB, 1997)- Current 1998 editions of Chemcyclopedia and the Chemical Buyers Directory identified no domestic suppliers of the chemical (Rodnan, 1997; Tilton, 1997). The 1979 TSCA Inventory identifred one producer of 4- aminobiphenyl in 1977, but no volume was reported. From 1975 rhrough 1977, EPA reported only one producer of 4-aminobiphenyi (TSCA,1979}- FJ(posure The primary routes of potential human exposure to 4-aminobiphenyl are dermal contact, ingestion, and inhalation. Consumers could possibly be exposed by ingesting foods with food additives containing trace amounts of 4-aminobiphenyl as a eontaminant. The chemical has also been found in tobacco smoke (H56B, 1997). Mainstream cigarette smoke is reported m contain 4.6 nglcigarerre of 4- ami»obiphenyl, whfle sidesrream smoke contains 140 nglcigarette of the chemieal (Patrianakos and Hoffmann, 1979). Current studies have focused on the relationship between exposure to environmental robacco smoke and levels of hemoglobin (Hb) adduces of 4- aminobiphenyl in pregnant women- Nonsmokers in one study were found to have 14% as much 4-aminobiphenyl-Hb addua as smokers (Hammond a al-, 1993). The mean kvel among fifteen pregnant smokers was 194 pg/g, while that for forty pregnant nonsmokers was 22 pg/g. A d'uea relationship was observed bctween environmental tobacco smoke exposure and both the median and mean 4- aminobiphenyl-Hb adduct levels in nonsmokers In addition, the results showed a sntistically significant relationship between the week4y avrnge exposute to environmental robacro smoke during the third trimester of pregnancy and the levels of 4-arttinobiphenyl-Hb adduces found at the time of delivery. Through chromatographic « chniques, significantly elevated levels of 4-aminobiphenyl-Hb adducts have been detected in marernal smokers and the cortesponding feral blood samples compared to nonsmokers, with a strong correlation between maternal and fecai exposures to 4- arninobiphenyl {pinorini-Godly and Myers, 1996}. The study thus 2073777284

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