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Description of key information

Overall, although there are no guideline carcinogenicity studies on acetic acid, there is sufficient information from animal studies to conclude on the local and systemic carcinogenic potential of acetic acid.  Humans are exposed to acetic acid/acetate, throughout life, from many food sources and it is a key intermediate in critical biochemical processes of living organisms. Consequently it is unlikely that acetic acid will express systemic carcinogenic potential.
Additional investigative animal studies using acetic acid have confirmed that although it is an irritant at the site of first entry, at concentrations below the threshold for sustained local irritation and proliferative response, there is no evidence of any carcinogenic potential at the sites of first contact. Acetic acid is classified as corrosive.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Overall there is sufficient information to conclude on the local and systemic carcinogenic potential of acetic acid and to conclude that at concentrations below the threshold for dermal toxicity there is no local or systemic carcinogenic potential. Classification is not warranted.


Additional information

Acetic acid, as an active substance, has been considered under the fourth stage of the re-evaluation programme of the Plant Protection Product Directive 91/414/EEC (provisions of Regulation (EC) No 1112/2002) for use as a herbicide on e.g. pome and stonefruit, ornamental shrubs, paths. The decision has been made that it is included in Annex I of that Directive (Commission Directive 2008/127/EC of 18 December 2008 amending Council Directive 91/414/EEC to include several active substances) and therefore the use of acetic acid as a Plant Protection Product it is therefore regarded as registered under REACh (Article 15 of EC Reg 1907/2006). The toxicology endpoints addressed under Dir. 91/414/EECto conclude on toxicological hazard are directly comparable with those under REACh.

EFSA supported the recommendations by the rapporteur Member State and the result of the examination in accordance with the provisions of Article 24a of Regulation 2229/2004 stating that there are clear indications that it may be expected that this use of acetic acid does not result in any harmful effects on human health (EFSA, 2013).

The Draft Assessment Report (EU DAR, 2008) states that “Long-term toxicity/carcinogenicity studies in animals with oral exposure are not necessary, considering that humans are exposed to orally ingested acetic acid from various food sources and there is no evidence that such exposure is causally related to toxic effects and an increased cancer incidence. Therefore, no new animal toxicity studies conforming to long-term toxicity or carcinogenicity test guidelines are necessary for Annex I inclusion of acetic acid.”

Acetic acetic was more recently reviewed as a feed additive (EFSA, 2012). Acetic acid, calcium acetate and sodium diacetate are listed in the EU Register of Feed Additives as preservatives for use with feed for all animal species without restrictions. There is now an application for the re-authorisation of acetic acid and these salts as preservatives in feed and for a new use of acetic acid as preservative in water for drinking. They may be used alone or in combination with other organic acids typically in a concentration 200 to 2,500 mg acetate/kg complete feedingstuffs. Acetic acid and its salts are considered equivalent when compared on a molar basis. Based on the comparison between consumer and target animals exposure to acetic acid and the limited experimental data available for chickens and the dogs fed diets containing acetate, a maximum concentration of 2,500 mg acetic acid/kg complete feed (or 1000 mg/L water for drinking) is considered safe for poultry, pigs and pet animals. The tolerance of ruminants is considerably higher. No data is available for salmonids. Given the complete and rapid metabolism of acetate, the use of acetate in animal nutrition is not expected to contribute to human exposure. Acetic acid and its salts are bulk industrial chemicals and the hazards for those handling these substances are well known and documented. Acetates are normal components of the diet of humans and animals and are produced in molar quantities in the gastrointestinal tract. They are fully metabolised and so do not pose a risk to the environment. Acetic and its salts have the potential to act as preservatives in feedingstuffs and water for drinking (EFSA 2012).

EFSA also published aScientific Opinion on the substantiation of health claims related to acetic acid and maintenance of normal blood pressure (ID 1447) pursuant to Article 13(1) of Regulation (EC) No 1924/20061 (EFSA 2011) in which they concluded “In weighing the evidence, the Panel took into account that although one animal study showed an effect of acetic acid administration on systolic blood pressure, results from two human intervention studies are conflicting, and that a sustained effect of orally administered acetic acid on blood pressure is unlikely because of its rapid absorption and clearance from the circulation after consumption.”

In addition to consideration of the status under EC Dir. 91/414/EEC, it is also approved for use as a food additive by the Joint FAO/WHO Expert Committee on Food Additives (Rome, 11-18 October, 1966). In the USA acetic acid is affirmed as Generally Recognised as Safe (GRAS) by the US FDA (21CFR184.1005) and has also been exempted from the requirement of a tolerance under the US EPA Federal Food, Drug, and Cosmetic Act (FFDCA).

This current review of the repeat-dose toxicity of acetic acid has and similar overall conclusions have been reached. Below is the discussion of the weight of evidence that has been considered in this review.

Non-human information

A thorough review of the available data concluded that acetic acid has no significant genotoxic activity (CSR section 5.7).  No guideline, long-term carcinogenicity studies are available for acetic acid, however two investigative studies, one oral (Alexandrov et al., 1989), and one dermal (Slaga et al., 1975), each of 8 months duration, are available. 

In the first of these, a study designed to compare the influence of acetic acid on the carcinogenic effect of N-nitrososarcosin ethylester (NSEE) has been reported (Alexandrov et al., 1989).  One group of 20 rats received NSEE (dosed orally 5 times per week) and also received 0.5 mL of commercial vinegar (3% acetic acid in water) intraoesophageally by gavage 3 times per week for 6 months and then received the vinegar only for a further 2 months. Another group of 9 rats received vinegar only for 8 months and another group of 18 rats received NSEE only for 6 months. After 8 months animals were autopsied and the oesophagus and forestomach examined histopathologically.

As anticipated, rats treated with the carcinogen NSEE had high incidences of pre-neoplastic lesions and papillomas and carcinomas of the oesophagus and forestomach.  Acetic acid administration, alone, did not induce tumours, however hyperplasia of the oesophagus and forestomach were reported.  The relevance of the hyperplasia observed in this experimental model could not be determined due to the lack of appropriate controls and the unusual means of dosing. In combination, that is administration of vinegar in addition to treatment with NSEE, increased numbers of tumours of the oesophagus were reported.  This finding is again consistent with the hyperplastic response observed in the tissues following intraoesophageal gavage with acetic acid that would be likely to enhance the effects of the carcinogen, NSEE.  Other organs were not evaluated.

In the second study, topically applied acetic acid was used as a promoter for tumour development in mice that were initiated with beta-propiolactone or dimethylbenzyl[a]anthracene (Slaga et al., 1975).  The concentrated acid (glacial acetic acid) was applied dermally 1-3 times per week (at doses of 1-40 mg/animal) for 32 weeks. Control animals received acetic acid, dermally, once per week.  The incidence of papillomas and carcinomas was recorded and lesions were removed at random for histological verification.

A single dermal application of acetic acid at doses of up to 40 mg/animal, in mice initiated with beta-propiolactone or dimethylbenzyl[a]anthracene, did not induce excessive mortality. However, more than one weekly application of 10-40 mg acetic acid caused excessive mortality. 33% of mice died when 10 mg acetic acid/animal was applied dermally 3 times per week and approximately 50% of mice died when 20 mg was applied twice a week. No further details regarding these deaths are available.

Concentrations of glacial acetic acid above 2 mg/mouse, topically applied, induced skin irritation and associated hyperplasia. At 10 mg/mouse, the LOAEL for dermal effects, elevated DNA synthesis was sustained for a period 12-24 hours post-exposure, which is consistent with cell proliferation (EU DAR, 2008). In regard to the promoting activity of acetic acid, in the absence of significant local and systemic toxicity of acetic acid, only a weak promoting activity in mice, pretreated with dimethylbenzyl[a]anthracene or beta-propiolactone, was reported. However under the conditions of this 8-month study, concentrated acetic acid was concluded (EU DAR, 2008) to have no carcinogenic potential

The results of both these studies confirm that acetic acid is an irritant at the site of first entry. This is consistent with the physiochemical properties of an acid which is capable of producing aqueous solutions of very low pH (25% solution of acetic acid has pH less that 2) and the material is labelled under DSD and CLP as corrosive. However, at concentrations below the threshold for sustained local irritation and proliferative response, there is no evidence of any carcinogenic potential at the sites of first contact.

Human information

Although these animal studies consider carcinogenic events at sites where local toxicity was expressed, little information may be added regarding systemic carcinogenic potential.  Uptake (pulmonary, oral or dermal) of acetic acid is likely to be the rate-limiting process of its disposition in animals and humans, as high-turnover endogenous metabolic pathways such as the Citric Acid Cycle will efficiently remove excess acetate (~0.5 mg/kg bw acetate per minute) such that high systemic concentrations are unlikely (Smith et al., 2007). 

Considering that humans are exposed to acetic acid/acetate from food sources and that it is a key intermediate in critical biochemical processes of living organisms (intermediate in catabolism and in anabolic synthesis, e. g., in the formation of glycogen, fatty acid synthesis as well as cholesterol synthesis, in the acetylation of amines, in the conversion into alanine and subsequent incorporation into proteins of plasma, liver, kidney, gut mucosa, muscle, and brain) (Health Council of the Netherlands, 2004), it seems that systemic carcinogenic potential is rather unlikely. An epidemiological study comparing local food consumption patterns in Japan with geographical distributions of gastro-intestinal cancers, vinegar consumption was reported to be negatively associated with standardised mortality ratios for all cancers of the gastro-intestinal tract, including bile ducts and pancreas (Hara et al., 1985).


EFSA (2011)Scientific Opinion on the substantiation of health claims related to acetic acid and maintenance of normal blood pressure (ID 1447) pursuant to Article 13(1) of Regulation (EC) No 1924/2006; EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); EFSA Journal 2011;9(6):2199

EFSA (2012)Scientific Opinion on the safety and efficacy of acetic acid, sodium diacetate and calcium acetate as preservatives for feed for all animal species; EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP); EFSA Journal 2012;10(2):2571

EFSA (2013): Conclusion on the peer review of the pesticide risk assessment of the active substance acetic acid; EFSA Journal 2013;11(1):3060