Results of Long‐Term Experimental Studies on the Carcinogenicity of Methyl Alcohol and Ethyl Alcohol in Rats

Soffritti, Morando; Belpoggi, Fiorella; Cevolani, Daniela; Guarino, Marina; Padovani, Michela; Maltoni, Cesare

doi:10.1111/j.1749-6632.2002.tb04924.x

Cited by 80 publications

(78 citation statements)

References 21 publications

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“…Since then, two adequately designed long-term animal studies have clearly demonstrated that ethanol causes a dose-related increase in cancer in mice and rats at sites similar to those observed in humans (liver and oral cavity). 4,5 As a result of this new evidence, the 2007 IARC evaluation concluded that there is sufficient evidence in experimental animals for the carcinogenicity of ethanol. 2 Furthermore, substantial mechanistic evidence has become available in humans who are deficient in aldehyde dehydrogenase that acetaldehyde, which is the first metabolite of ethanol, may accumulate and contribute to the causation of malignant esophageal tumors.…”

mentioning

confidence: 99%

Comparative risk assessment of carcinogens in alcoholic beverages using the margin of exposure approach

Lachenmeier

Przybylski

Rehm

2012

Intl Journal of Cancer

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Alcoholic beverages have been classified as carcinogenic to humans. As alcoholic beverages are multicomponent mixtures containing several carcinogenic compounds, a quantitative approach is necessary to compare the risks. Fifteen known and suspected human carcinogens (acetaldehyde, acrylamide, aflatoxins, arsenic, benzene, cadmium, ethanol, ethyl carbamate, formaldehyde, furan, lead, 4‐methylimidazole, N‐nitrosodimethylamine, ochratoxin A and safrole) occurring in alcoholic beverages were identified based on monograph reviews by the International Agency for Research on Cancer. The margin of exposure (MOE) approach was used for comparative risk assessment. MOE compares a toxicological threshold with the exposure. MOEs above 10,000 are judged as low priority for risk management action. MOEs were calculated for different drinking scenarios (low risk and heavy drinking) and different levels of contamination for four beverage groups (beer, wine, spirits and unrecorded alcohol). The lowest MOEs were found for ethanol (3.1 for low risk and 0.8 for heavy drinking). Inorganic lead and arsenic have average MOEs between 10 and 300, followed by acetaldehyde, cadmium and ethyl carbamate between 1,000 and 10,000. All other compounds had average MOEs above 10,000 independent of beverage type. Ethanol was identified as the most important carcinogen in alcoholic beverages, with clear dose response. Some other compounds (lead, arsenic, ethyl carbamate, acetaldehyde) may pose risks below thresholds normally tolerated for food contaminants, but from a cost‐effectiveness point of view, the focus should be on reducing alcohol consumption in general rather than on mitigative measures for some contaminants that contribute only to a limited extent (if at all) to the total health risk.

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mentioning

confidence: 99%

Comparative risk assessment of carcinogens in alcoholic beverages using the margin of exposure approach

Lachenmeier

Przybylski

Rehm

2012

Intl Journal of Cancer

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“…Methanol administered in drinking water induced a statistically significant increase in the incidence of lymphomas/leukaemias in female rats in a study carried out by the ERF (Soffritti et al, 2002a). However, with the exception of the ERF drinking water study no other studies have been reported in the peer-reviewed literature on the potential carcinogenicity of methanol in laboratory animals (IPCS, 1997).…”

Section: Discussionmentioning

confidence: 94%

“…Soffritti et al suggested however that the increase in lymphomas/leukaemias in aspartametreated female rats could be related to the metabolite methanol, which is in turn metabolised to formaldehyde in both humans and rats (Soffritti et al, 2002a). Methanol administered in drinking water induced a statistically significant increase in the incidence of lymphomas/leukaemias in female rats in a study carried out by the ERF (Soffritti et al, 2002a).…”

Section: Discussionmentioning

confidence: 99%

Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) related to a new long‐term carcinogenicity study on aspartame

2006

EFS2

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Aspartame has undergone extensive testing in animals and studies in humans, including four animal carcinogenicity studies conducted during the 1970s and early 1980s. These studies, together with studies on genotoxicity, were evaluated by regulatory bodies worldwide and it was concluded that they did not show evidence of genotoxic or carcinogenic potential for aspartame. Since its approval, however, the safety of aspartame has been repeatedly questioned, with discussions focusing not only on the safety of aspartame itself, but also on the safety of its breakdown products, aspartic acid, phenylalanine and methanol. All these substances occur naturally in the body. In response to such questions, the SCF undertook a further review of all the data on aspartame in 2002 and concluded that there was no need to revise the outcome of their earlier risk assessment or the previously established Acceptable Daily Intake (ADI) for aspartame, of 40 mg/kg body weight (bw).The AFC Panel has assessed the new carcinogenicity study, using not only the ERF publications but also a more extensive report provided to EFSA by the ERF at the end of 2005 and further data from the same study provided by ERF in April 2006. The Panel noted that this lifetime study, using more dose groups and more animals per group than conventional carcinogenicity studies, represented a substantial effort and had the potential to be more sensitive to low incidence effects. After its evaluation the Panel considers that the study has flaws which bring into question the validity of the findings, as interpreted by the ERF. In particular, the high background incidence of chronic inflammatory changes in the lungs and other vital organs and tissues and the uncertainty about the correctness of the diagnoses of some tumour types were major confounding factors in the interpretation of the findings of the study.The Panel's conclusions on the findings of the ERF study include the following:• The increased incidence of lymphomas/leukaemias reported in treated rats was unrelated to aspartame, given the high background incidence of chronic inflammatory changes in the lungs and the lack of a positive dose-response relationship. It is wellknown that such tumours can arise as a result of abundant lymphoid hyperplasia in the lungs of rats suffering from chronic respiratory disease. The most plausible explanation of the findings in this study with respect to lymphomas/leukaemias is that they have developed in a colony suffering from chronic respiratory disease. The slight increase in incidence of these tumours in rats fed aspartame is considered to be an incidental finding of the ERF study and can therefore be dismissed.• The preneoplastic and neoplastic lesions of the renal pelvis, ureter and bladder occurring primarily in female rats along with renal calcification were most probably treatment-related, at least at the higher doses. It is widely accepted that the effect is a high dose effect of irritant chemicals or chemicals producing renal pelvic calcification as a result of im...

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“…' Soffritti et al [2007] addressed the issues of how they characterized and aggregated lymphomas/leukemias in their aspartame study. There are not only other cites besides the lung reported for lymphoma occurrence in the ERF aspartame studies but also the frequent occurrence of lymphoma in other cites was reported for methanol and MTBE as well [Belpoggi et al, 1998;Soffritti et al, 2002]. Shoeb et al state that the Pratt et al [2006] review asserts that ''nearly all of the rats had bronchopneumonia.''…”

Section: Replymentioning

confidence: 99%

Response to letters to the editor: Caldwell et al. [2008]

Caldwell

Jinot

DeVoney

et al. 2008

Environ and Mol Mutagen

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Results of Long‐Term Experimental Studies on the Carcinogenicity of Methyl Alcohol and Ethyl Alcohol in Rats

Cited by 80 publications

References 21 publications

Comparative risk assessment of carcinogens in alcoholic beverages using the margin of exposure approach

Comparative risk assessment of carcinogens in alcoholic beverages using the margin of exposure approach

Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) related to a new long‐term carcinogenicity study on aspartame

Response to letters to the editor: Caldwell et al. [2008]

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