Trisodium orthophosphate

Carcinogenicity

Description of key information

A number of recent publications have hypothesised a link between very high or very low dietary phosphate levels and tumourigeneisis (typically using potassium or sodium orthophosphates as the test substance). The most recent publications have been included as a representation of the typical investigations performed in this area. These data are not sufficient to fulfil the guideline requirement for carcinogenicity and are not considered to be adequate or reliable for use in risk assessment and/or classification and labelling. As such these studies are provided for completeness of the data set only.

Justification for classification or non-classification

The data provided are not suitable for use in classification and labelling, in accordance with Regulation 1272/2008. Inorganic phosphates are not considered to be carcinogens.

Additional information

A number of recent publications have focussed on the hypothesis that dietary phosphate (usually as potassium or sodium orthophosphate) levels may be linked to cancer growth rates.

The studies included in this endpoint are the most relevant and recent of these. The studies themselves are not considered to fulfil the requirements for the assessment of the carcinogenic potential of inorganic phosphates and are therefore only included for completeness and as a representation of the on-going research in to inorganic phosphates.

The following studies have been included:

- Jin et al, 2009, High Dietary Inorganic Phosphate Increases Lung Tumorigenesis and Alters Akt Signaling. American Journal of Respiratory and Critical Care Medicine. 179: 59-68

- Xu et al, 2010, Low Dietary Inorganic Phosphate Stimulates Lung Tumorigenesis Through Altering Protein Translation and Cell Cycle in K-rasLA1 Mice. Nutrition and Cancer, 62(4), 525–532

-Camalier et al, 2010, Elevated Phosphate Activates N-ras and Promotes Cell Transformation and Skin Tumorigenesis. Cancer Prevention Reseach. 3(3): 359-370

These studies are not considered to be appropriate for use in a regulatory context as a number of deficiencies in the methodology exists (please see individual endpoint records for a description of the deficiencies).

Whilst the studies are not sufficient for the consideration of carcinogenicity under REACH or CLP, the studies do provide an interesting insight into the ubiquitous nature of phosphate in cellular processes such as signalling and gene transcription in mice.

The studies do not, however, provide evidence of a causal relationship between tumourigenesis and dietary inorganic phosphate and in many cases the conclusions drawn are based on in vitro methods that do not consider the body’s metabolic and homeostatic mechanisms.

In addition, the studies focus on specific biological processes and signals but do not take into account the multi-factorial nature of most cancers, nor any inter-species differences making the results difficult to interpret. The interpretation of the results is further complicated by the amount of phosphate used in the feed for the mice tested. In particular mice eat a greater amount of food everyday based on their body weight than humans do. Thus, feeding the same percentage of body weight of phosphates to a mouse would result in a much greater total amount consumed relative to its body weight than it would in a human. 

It is not considered relevant to further investigate the carcinogenicity of sodium and potassium orthophosphates in the literature or via in vivo testing.