Pentasodium triphosphate

Endpoint summary

Description of key information

Sodium Tripolyphosphate (Curafos) was assessed in a series of oral repeated dose toxicity studies in rats and dogs. A publication summarizes the main findings from several unpublished company studies although limited details were reported on the test results (Hodge, 1964). However, the full laboratory reports of these tests were available and are considered a Key Study because of the complete information contained in them. A toxicologist expert assessment of these laboratory reports was obtained and used as the basis for this section.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

225 mg/kg bw/day

Additional information

STPP was administered for 1 month to groups of 5 male weanling (6-week old) rats at doses of 0.2, 2.0 and 10% in the diet (Hodge, 1964). One control group received the basal diet only, one additional control group received the basal diet supplemented with 10% Sodium chloride, and one control group received 5% orthophosphate. Growth reduction was observed at the high dose of 10%, and in the control group receiving basal diet with 10% sodium chloride. Enough calcium was added to the diet to ensure a "reasonably balanced" ratio of calcium to phosphorus (no further details). Growth was normal in rats receiving 2% sodium tripolyphosphate. No data were available on food consumption, clinical signs, or haematology. An increased relative kidney weight was observed at the highest dose of STPP and in the control group supplemented with NaCl. Histopathological examination showed tubular necrosis in the kidneys of rats treated at 10% sodium tripolyphosphate, and in the control group with 5% orthophosphate. Only inflammatory changes of the renal pelvis were observed at 2%, while normal kidneys were observed at 0.2%. Based on the renal effects, the NOEL was determined to be 0.2%.

Assuming a 0.4 kg rat eats about 18 g of food per day, the NOEL for the 1-month diet study is therefore estimated to be 90 mg/kg/day for STPP. Furthermore, in this study, other groups of rats received similar doses of other inorganic condensed phosphates (sodium hexametaphosphate, sodium trimetaphosphate and sodium tetrametaphosphate), which produced similar effects, especially at 10%.

Sodium tripolyposphate was further assessed in a 104-week oral repeated dose study in rats (Hodge, 1964). A preliminary assay was conducted with groups of 14 male rats, at doses of 0.2%, 2% and 10% STPP for 1 month. The effects described above for the previous study (growth retardation, increase in kidney weights, and tubular degeneration and necrosis of the kidneys) were again observed at the highest dose. In the main 2-year study, males and females rats (50 animals per dose group and per sex) received 0.05, 0.5 and 5.0% of STPP in the diet. Mortality, food consumption, body weights were monitored. At the end of the treatment period, organ weights, haematology, urine analysis, bone analysis and histopathology were evaluated. Growth retardation was observed in the high dose group in males (throughout the study period) and females (slight during the first year, then more obvious during the second year). High mortality was reported in males and females due to several epidemics during the study. The high dose group was more affected (up to 80% in females of the 5% dose during the second year of the study). Concerns about potential altered calcium to phosphorus balance were addressed by conducting bone analysis. Femur analysis of the high dose group (5%) showed a slight increase in water content and slight decrease in organic matter as compared to the control group. No anomalies were observed at the bone radiography. The ash contents and ratios calcium to phosphorus were normal in both sexes of the high dose group. The effects observed after repeated oral ingestion of high doses of STPP were anaemia observed after 1 year of treatment at 5% (decrease in red blood cells counts, haemoglobin values and haematocrits), and mainly renal effects. In the high dose group (5%), kidney weights were increased in males, and relative liver and kidney weights were found increased in females. Histopathological examination showed enlargement of the kidney associated with tissue changes such as dilated convoluted tubules, hyaline casts, interstitial fibrosis between the dilated tubules, fibrotic glomeruli and intertubular calcification also in the group receiving the 5 % dose.

Based on the renal effects (nephrocalcinosis), the NOEL was estimated to be 0.5% for the 2-year repeated dose study in rats. Assuming a 0.4 kg rat eats about 18 g of food per day, the NOEL is estimated to be 225 mg/kg/day

The most applicable NOEL is therefore 225 mg/kg/day as this is the highest NOEL bellow the lowest LOAEL