Sodium dihydrogenorthophosphate

Endpoint summary

Additional information

A number of investigations have been carried out into the effects of sodium phosphate (administered as the preparation oral sodium phosphate - OSP) on renal function when administered in large doses to cleanse the bowels (bowel purge) of patients prior to colonoscopy exist. OSP preparations are generally consists of monobasic sodium phosphate monohydrate and dibasic sodium phosphate heptahydrate in a stable, aqueous solution.

 

As this application of sodium phosphates is outside the scope of REACH, for completeness, the following data have been included in the form of study summaries:

 

- Brunelli SM, 2009, Association Between Oral Sodium Phosphate Bowel Preparations and Kidney Injury: A Systematic Review and Meta-analysis.

- Seol DC et al, 2010, Change in renal function after sodium phosphate preparation for screening colonoscopy.

 

The systematic review and meta-analysis written by Brunnelli SM (2009) has been included as it discusses all the literature published and makes an assessment on the reliability of the data collected and the conclusions drawn in the published literature. It also provides a conclusion of the safety of sodium phosphate preparations for this use. The paper written by Seol DC et al, is included as it was published after the 2009 meta-analysis and review of the literature.

 

Phosphate-induced injury has been observed at high does in rats and a number of case studies have suggested a potential association between the use of high doses of oral sodium phosphates (in medical applications) and kidney injury. It was therefore the aim of the aforementioned authors to investigate this potential link.

 

The systematic review of the literature (Brunelli SM,2009) identified a number of problems with the case studies performed and reported; these included:

 

- Inconsistent reporting of results

- Study heterogeneity – studies were not performed in the same way, differences in populations, disease state, controls and timings of observations.

- Reporting of results – there was no standard for defining kidney damage.

 

Therefore despite the fact that Brunelli found 93 studies of potential interest, only 6 met the criteria for inclusion in the analysis (criteria required that each study be a primary data report, include a control group and have examined the association between OSP (and control) use and kidney functional outcomes).

 

The subsequent analysis of this data concluded that an association between OSP administration and kidney injury could not be discerned.

 

The study by Seol et al, investigated the changes in renal function at 12-24 months following the use of OSP prior to colonoscopy. In this study Seol concluded that the changes in renal function in patients who used OSP were similar to that of healthy controls or patients treated with an alternative bowel purge (polyethylel glycol (PEG)).

 

Therefore, both papers were in agreement that no definite link could be confirmed. Both studies did however suggest that patients who already have impaired kidney function may be more at risk from potential phosphate-induced kidney injury than the general population. On the other hand OSP is indicated to be more tolerable than alternative purges, so its use may result in increased willingness of patients to undergo colonoscopy. In addition, it was also noted that inadequate hydration prior to dosing with OSP may contribute to a potential effect.

 

 

It is therefore concluded that whilst the work on the use of oral sodium phosphate and the potential effects on renal function is not complete or adequate to arrive at clear conclusions for this specific medical application, an effect on the kidneys would not be seen at the normal levels of intake for inorganic phosphates (the maximum tolerable daily intake is 70 mg/kg bw of P/day) nor at a level likely to occur during occupation exposure and it is therefore not considered appropriate to investigate this further for the purpose of REACH registration.