Sodium ethanolate

Carcinogenicity

Justification for classification or non-classification

In regard of the caustic properties of sodium ethanolate, secondary exposure to ethanol is considered to be low and no cancerogenicity from ethanol is expected. No classification for cancer is proposed

Additional information

No data/information is available for sodium ethanolate. But several animal and human studies are available for reaction product ethanol.

Animal data:

NTP (2004) reported a combined chronic toxicity / carcinogenicity study with ethanol (CAS: 64-17-5). This study was designed and conducted to determine the long-term toxicity and carcinogenicity of urethane in ethanol. Here, groups of mice were exposed to ethanol at concentrations of 2.5 and 5% in drinking water for a period of 2 years, with control groups consuming drinking water alone. The only significant cancer finding was a dose related increase in the rate of hepatocellular adenomas for male mice in comparison with the concurrent controls. The species of mouse used in this study is known to have a high spontaneous incidence of these tumors. In comparison to historic controls, the incidence rate in the ethanol dosed animals was not high and the controls were significantly lower (although it should be noted that no historic control information was available for animals on the study diet used.) Analysis of the data using the Benchmark dose approach showed a BMDL10 of 1400 mg/kg for liver adenomas in males. There was no significant increase in tumor rates (including mammary tumors) in females. Synopsis: Females: NOAEL>4400 mg/kg (cancer), Males: NOAEL>4250 mg/kg (based on historic control data), Males BMDL10=1400 mg/kg (based on concurrent control data)

In a study published by Holmberg et al. (1994) the carcinogenic potential of ethanol was assessed. Here, groups of rats were exposed to ethanol at concentrations of 1 % and 3 % in a liquid semi-synthetic diet for a period of 2 years, approximately equivalent to 1 and 3 g/kg respectively. Each dose group used a control matched for caloric content using glucose. From the data it was possible to conclude that ethanol did not cause any treatment related increase in tumors and the no effect level was identified as > 3 g/kg.

The only significant findings in animals are of low concern for the following reasons:

- tumor type is known to have a high background incidence in the species coupled with significantly low incidence in concurrent control compared to historic control.

- lack of progression to malignancy at 'lower' exposure levels (bearing in mind context of very high doses anyway, well above normal limit dose values).

- single sex response.

- single species response.

The International Life Sciences Institute published an extensive review of the health issues relating to alcohol consumption (“Health issues relating to alcohol consumption”, ILSI, 1999) and concluded that ethanol is not a carcinogen by standard laboratory tests using animals.

Human data:

Several human data are available and have been evaluated by the IARC. The IARC concluded that there is some evidence that consumption of alcoholic beverages is causally related to cancer in the oral cavity, pharynx (excluding nasopharynx), larynx, oesophagus and liver (IARC monographs on the evaluation of carcinogenic risks to humans. Alcohol Drinking”, volume 44, 1988). More recently, breast cancer and colorectal cancer was added to this list (IARC monographs on the evaluation of carcinogenic risks to humans. Consumption of Alcoholic beverages and ethyl carbamate (urethane)”, volume 96, 2007). But they also reported no conclusive evidence of a link with cancer in any other organ. In addition, the UK Committee on the Carcinogenicity of Chemicals in Food, Consumer Products and the Environment reviewed the 1988 IARC monograph with the objective of estimating the relative risks of developing the cancers identified as causally associated with alcohol drinking (Sensible Drinking”, Report by the UK department of Health, 1995). The committee estimated the level of alcohol drinking which produced convincing evidence of an increase in the relative risk of cancer at susceptible sites. They concluded that there is no convincing evidence that the carcinogenic effects of alcoholic beverages in humans occurs as a result of the mutagenic effect. For the oral cavity, pharynx, larynx and oesophagus, alcohol consumption in excess of 30-40g per day is necessary before there is a convincing increase in the relative risk of cancer. The overall conclusion of this review was that consumption of between 3-4 units of alcohol per day (21-28g ethanol) does not accrue significant health risks. The German MAK commission have also reviewed the data on ethanol and agreed that carcinogenisis of the mouth, throat, larynx and gullet are as a result of local irritancy effects. They also concluded that there is no convincing evidence that ethanol can produce hepatocellular tumors alone and that cirrhosis as a pre-cancerous lesion probably plays a casual role. The most sensitive cancer end point was breast cancer. For this reason, available epidemiology data that has looked at the link between drinking and breast cancer has been summarised here.

Several human data are available. It should be noted that all epidemiology data are generated to assess the hazard from the consumption of alcoholic beverages. In this assessment, the results are extrapolated as far as possible to assess the conceivable hazards that could result from other forms of exposure to ethanol. A case-control study was conducted among 437 newly-diagnosed breast cancer cases and 922 residence and age-matched controls to examine the association between drinking patterns of alcoholic beverages (particularly wine) and breast cancer (Bessaoud and Daures, 2008). Women who reported an average consumption of less than 1.5 drinks per day (equivalent to 10 - 15 g ethanol/day) had a lowered risk of breast cancer when compared to non-drinkers. A retrospective case-control study, involving 989 women with breast cancer and 1350 (non-cancer) hospital controls, reported an increased breast cancer risk for women consuming at least 13.8 g ethanol/day (Deandrea et al., 2008). A cohort study among 70,033 women, 2829 of whom developed breast cancer, found no significant increase in breast cancer risk for those consuming <1 drink/day versus lifelong alcohol abstainers (Li et al., 2009). An increasing risk was found for those consuming 1-2 drinks/day or >=3 drinks/day possibly connected a hormone-related mechanism. In a study with 153,582 participants (58,515 cases and 95,067 without the disease) published by Beral in 2002, no statistically significant increased risk of breast cancer with a median daily intake of alcohol below approximately 8 g could be found. High consumption of 15-24g/day only became associated with increased risk. A study with more than 40,000 cases estimated that an average of one drink per day (about 12 g alcohol/day) is associated with a 10% increase in breast cancer risk, compared to non-drinkers (Ellison et al., 2001). Feigelson et al. (2003) reported a study with 66,561 women where the multivariate relative risks (RR) and 95% confidence intervals (CI) for categories of daily alcohol intake and risk of incident breast cancer were not statistically significantly increased in postmenopausal women consuming less than 15 g alcohol per day, compared to non-drinkers. Only in the highest category of alcohol consumption (at least 15 g/day), the risk of incident breast cancer was statistically significantly increased. In a study, involving more than 100,000 women and published by Garland et al. (1999), the RR and 95% CI for categories of daily alcohol intake and risk of invasive breast cancer were not statistically significantly increased at any intake level up to and including the highest consumption group (> 20 g/day). Only women who reported consuming either 5-6 drinks/week or more than 6 drinks/week between the ages of 23-30 showed a marginally statistically significantly increased risk of invasive breast cancer. Horn-Ross et al. (2004) reported a study in 103,460 teachers. The RR and 95% CI for categories of total daily alcohol intake through drinking alcoholic beverages and risk of invasive breast cancer were not statistically significantly increased in those women consuming less than 20 g/alcohol day. A marginally statistically significant increase in breast cancer risk was observed in those who reported consuming > 20 g alcohol/day in the past year. A publication by Smith-Warner et al. (1998) reported no statistically significant increase in breast cancer risk where the women were consuming on average less than 30 g alcohol/day (studies included 322,647 women). Only in those who consumed between 30 to 60 g alcohol/day compared to the non-drinkers was a significant association found. For alcohol intakes less than 60 g/day, breast cancer risk increased linearly with increasing alcohol intake but this relationship only reached statistical significance at above about 15 g alcohol/day. Tjonneland et al. (2003) described a cohort study in 23,778 women which showed that the RR and the 95% CI for breast cancer were not statistically significantly increased in women who self-reported consuming less than 24 g alcohol/day, compared to the "reference group" (who reported ingesting up to 6 g alcohol/day). However, in those consuming between 24 and 60 g alcohol/day showed a statistically significant increased risk of breast cancer. Although the trend between total alcohol intake and breast cancer showed a statistically significant increase in risk per 10 g/day increment in alcohol consumption, this does not appear to apply at low levels of consumption. Zhang et al. (1999) reported a study where a total of 5048 women were selected (with a total of 287 incident breast cancer cases). The RR and the 95% CI for average daily alcohol intake and risk of incident breast cancer were not statistically significantly increased (<5 g/day, 5 to <15 g/day and≥15 g/day) indicating no association with increased breast cancer risk. A population-based case control epidemiology study published by Beasley et al, (2010) examined 1000 breast cancer cases with controls. The authors reported that the study provided evidence that any alcohol intake increases risk of breast cancer. However, the data presented does not appear to provide evidence for this. With full correction for confounding factors, an adjusted OR=1.25, 95% CI=0.99–1.58 was obtained for 'any lifetime use' of alcohol versus total abstention. The only parameter that showed a statistically significant correlation was of questionable biological likelihood ('one drink per month for more than one year'). For that reason, the study did not provide evidence for any likely hazard relating to the use of ethanol. Suzuki et al. (2010) reported a prospective cohort study based on the Japanese population. Here, no significant link was found between moderate alcohol consumption (<150 g/week) and drinking 3/4 times per week and breast cancer. The data does conclusively indicate that exposure to small amounts of ethanol does not cause a significant increase in breast cancer. Cumulative exposure to ethanol from inhalation or dermal exposure could not reach the higher exposure levels where there is some evidence for increase effects in humans. This is without even considering the evidence suggesting that breast cancer may be hormone mediated and therefore likely to involve a threshold mechanism, in which case blood ethanol concentrations are likely to be more important rather than cumulative exposure. The available data support the hypothesis that ethanol is extremely unlikely to pose any breast cancer risk at the levels of exposure encountered through industrial or other consumer use.

In regard of the caustic properties of sodium ethanolate, secondary exposure to ethanol is considered to be low and systemic toxicity from ethanol to be absent.