Registration Dossier
Registration Dossier
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EC number: 201-069-1 | CAS number: 77-92-9
Carcinogenicity
Administrative data
Description of key information
Key value for chemical safety assessment
Justification for classification or non-classification
Based on the available supporting data, the long history of safe use in food and cosmetics, and the central role played by citric acid in metabolism, no classification is required according Regulation (EC) No 1272/2008.
Additional information
In a rat feeding study, animals dosed with 5% citric acid in the diet did not show an excess of tumours in comparison with control animals when tested over a period of 2 years (Horn et al., 1957). However, there was limited evidence that high doses of citrate salts increased the incidence of tumours produced by co-administration of known bladder carcinogens (Inouea et al., 1988; Ono et al., 1992; de Camargo et al. 1991; Fukushima et al.1986; Behnke et al., 1964). Where citric acid or citrate salts were administered alone during these studies, no dose-related tumours were noted.
No reliable carcinogenicity studies are available, however, further testing is not considered necessary because:
• The substance is not classified for mutagenicity; and
• There is no evidence from long term human exposure to citric acid that it is a carcinogen.
References:
Behnke, U, Ketz, H A, Taeufel, K, Hoffmann, F, (1964). Effect of Perorally Administered Citric Acid on Butter Yellow Carcinogenesis in Rats. Ernährungsforschung. Berichte und Mitteilungen, 9, 129-137.
de Camargo, J L, Shirai, T, Kato, T, Asamoto, M, Fukushima, S (1991). Summation effects of uracil and other promoters on epithelial lesion development in the F344 rat urinary bladder initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine. Jpn J Cancer Res. 82, 1220-1225.
Horn, J. Holland, E.G. Hazleton L.W. (1957) Food Additives, Safety of Adipic Acid as Compared with Citric and Tartaric Acid J. Agric. Food Chem. 5, 759–762.
Fukushima, S, Thamavit, W, Kurata, Y, Ito, N. (1986). Sodium citrate: a promoter of bladder carcinogenesis. Jpn J Cancer Res. 77, 1-4.
Inouea, T. Imaidaa, K. Suzukib, E. Okadab M. and Fukushima, S. (1988). Combined effects of l-ascorbic acid, citric acid or their sodium salts on tumour induction by N-butyl-N-(4-hydroxybutyl)nitrosamine or N-ethyl-N-(4-hydroxybutyl)nitrosamine in the rat urinary bladder Cancer Letters 40, 265-273.
Ono S, Kurata Y, Shichino Y, Sano M, Fukushima S. (1992). Synergism of environmental carcinogens and promoters on bladder cancer development initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine in F344 rats. Jpn J Cancer Res. 83, 955-963.
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