Pentasodium triphosphate

Carcinogenicity

Description of key information

Although STPP is subject to widespread dispersive use, it is not classified as a mutagen or genotoxin.   The basic structure has no structural alerts for carcinogenicity or genotoxicity.  Inorganic phosphate is a naturally-occurring nutrient essential for mammalian survival.

Justification for classification or non-classification

Taken together, all three chronic toxicity/carcinogenicity studies indicate a common toxicity profile for all three salts: (1) no treatment-related increase in tumour incidence at the highest dose or any dose tested; (2) no increased mortality due to treatment; (3) some growth retardation at the highest dose tested, occasionally at the mid-dose level; (4) only minor effects on some red cell haematological parameters and organ weights and (5) target organ generally identified as the kidney, though effects were not observed with STMP.

Due to the common structural features as inorganic phosphate salts of sodium ion, the evaluation for the same endpoints on all three salts and the same or similar findings in all three studies on chronic toxicity/carcinogenicity, it is concluded that STPP is not expected to be carcinogenic in rats and that the current study on STPP(Hodge 1959, 1964) and the studies on STHP and STMP provide adequate data to support this conclusion. 

Additional information

The major effect of feeding high doses of STPP for two years is toxicity to the kidneys and reduced red blood cell counts and haemoglobin concentration in the blood. The Hodge study (1959, 1964) was conducted prior to the institution of good laboratory practice guidelines and to the currenct OECD Guideline 453. Therefore, the study has deficiencies when examined according to today’s standards. The study is considered a Klimisch Code 2, reliable with restrictions. The conclusions regarding the hazard identification of STPP are supported by data on sodium hexametaphosphate (SHMP) and sodium trimetaphosphate (STMP), both of which are structurally similar to STPP. All three inorganic phosphate salts exhibited a lack of carcinogenicity when tested in two year chronic toxicity/carcinogenicity studies.

In theManual for Investigation of HPV Chemicals, Chapter 3: Data Evaluation (2005), Section 3.1.6 Weight-of-the-Evidence Analysis, requires the use of a weight-of-the-evidence analysis during the assessment of data quality and adequacy.  The guidance permits the pooling of several studies, one or more of which may be inadequate, to satisfy a specific SIDS element. In the current case, available data exist on two other sodium inorganic phosphate salts which are similar in structure to STPP. In a chronic toxicity/carcinogenicity study on sodium hexametaphosphate (SHMP), no treatment-related increase in tumour incidence was observed at any dose in rats administered the salt at doses of 0.05, 0.5 and 5.0% in the diet for 24 months (IUCLID Robust Study Summary included as supplemental information). Similarly, in a chronic toxicity/carcinogenicity study on sodium trimetaphosphate (STMP), no treatment-related increase in tumour incidence was observed at any dose in rats administered the salt at doses of 0.1, 1.0 and 10.0% in the diet for 24 months (IUCLID Robust Study Summary included as supplemental information). For both compounds the studies were conducted prior to good laboratory practice guidelines and OECD Guideline 453; thus, these studies have similar deficiencies to the study on STPP.