Registration Dossier

Toxicological information

Direct observations: clinical cases, poisoning incidents and other

Currently viewing:

Administrative data

direct observations: clinical cases, poisoning incidents and other
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
between August 2006 and May 2008
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference Type:
Change in renal function after sodium phosphate preparation for screening colonoscopy
Seol DC, Hong SN, Kim JH, Sung IK, Park HS, Lee Jh and Shim CS
Bibliographic source:
World Journal of Gastroenterology (2010) April 28; 16(16): 2010-2016

Materials and methods

Study type:
study with volunteers
Endpoint addressed:
other: STOT: renal toxicity
Test guideline
no guideline followed
Principles of method if other than guideline:
The authors performed a retrospective study on the results from patients who received health check-up services as part of an employer-provided wellness program performed between August 2006 and May 2008 and who were followed up for 12-24 mo. Prior to screening colonoscopy, 224 patients underwent bowel cleansing with oral sodium phosphat (NaP group) and 113 patients with polyethylene glycol (PEG group). The control group comprised 672 age-matched patients. We compared the changes in the creatinine levels and the glomerular filtration rates (GFRs) from baseline to 12-24 mo between the NaP, PEG, and control groups using two-way repeated measured analysis of variance. In addition, multivariate linear regression analysis was performed to assess the risk factors for a decreased GFR.
GLP compliance:

Test material

Constituent 1
Reference substance name:
monobasic sodium phosphate monohydrate and dibasic sodium phosphate heptahydrate in aqueous solution
monobasic sodium phosphate monohydrate and dibasic sodium phosphate heptahydrate in aqueous solution
Details on test material:
- Name of test material (as cited in study report): oral sodium phosphate (NaP). Research in to the identity of oral sodium phosphate used by healthcare professionals for this purpose has revealed that the test substance consists of monobasic sodium phosphate and dibasic sodium phosphate heptahydrate in aqueous solution.


Type of population:
See table 1 below.
Ethical approval:
not applicable
Route of exposure:
Reason of exposure:
Exposure assessment:
not specified
Details on exposure:
An oral NaP solution (Fleet®; Unimed Pharm. Inc., Seoul, Korea) or PEG (Colyte 4L®; Taejun Pharm. Co. Ltd., Seoul, Korea) was used for bowel preparation. Two doses of oral NaP solution (45 mL) were given at least 10-12 h apart. Each dose was taken with at least 250 mL of liquid, followed by an additional fluid intake of at least 1 L. The second dose was taken in the same manner and at least 3 h before the procedure. The dosing of PEG was as follows: No solid food was consumed for at least 2 h prior to ingestion of the solution.
PEG (240 mL every 10 min) was consumed until the rectal output was clear or 4 L had been consumed. The colonoscopy was performed 4-6 h after bowel cleansing.
Age, race, gender, and clinical data sufficient to calculate an abbreviated Modification of Diet in Renal
Disease Study Group (MDRD) glomerular filtration rate (GFR) were collected. The creatinine level on the day of the health check-up was recorded as the patient’s baseline renal function. The creatinine concentration at the follow-up health check-up 12-24 mo later was recorded. The GFR was calculated using the abbreviated MDRD formula: GFR (mL/min per 1.73 m2) = 186 × (serum creatinine) - 1.154 × (age) - 0.203 × 0.742 (if female). Serum creatinine and GFR at the initial health checkup were considered the baseline levels and at the followup health check-up at 12-24 mo were considered the follow-up level. In the current study, we excluded subjects with a baseline creatinine level > 1.5 mg/dL or chronic renal disease.

Results and discussion

Clinical signs:
There was no significant difference between the baseline and follow-up levels of mean creatinine levels and the calculated MDRD GFR between groups. The baseline creatinine level for the NaP group ranged from 0.5-1.5 mg/dL (mean, 1.12 ± 0.15 mg/dL), with a calculated MDRD GFR ranging from 35 to 143 mL/min per 1.73 m2 (mean, 69.03 ± 7.74 mL/min per 1.73 m2). Serum creatinine at 12-24 mo follow-up ranged from 0.4-3.0 mg/dL (mean, 1.01 ± 0.15 mg/dL), and GFR was 22-175 mL/min per 1.73 m2 (mean, 66.46 ± 7.78 mL/min per 1.73 m2). There was no significant difference in the changes in serum creatinine between the NaP and PEG group (P = 0.980) or the NaP and control group (P = 0.173). No significant difference was not found in the changes in GFR between the NaP and PEG group (P = 0.764) or the NaP and control group (P = 0.143). In addition, although creatinine level and GFR deterioration occurred at the 12-24 mo interval, there was no significant difference in the changes in creatinine levels and GFRs between the NaP, PEG, and control groups (P = 0.992 and P = 0.233, respectively).

Any other information on results incl. tables

Statistical analysis:

No significant risk factor for the changes in serum creatinine was found. The NaP bowel preparation also was not associated with the creatinine change (P= 0.366). On the other hand, results of multivariate linear regression analysis indicated that the GFR change was only associated with the baseline GFR (P< 0.001). Based on the multiple linear regression model, when all other variables remained constant, the change in GFR decreased by 0.14 units for every 1-unit increase in GFR at baseline. The NaP bowel preparation was not associated with the GFR change (P= 0.269). However, the model was used to select the significant variables for the change in the GFR rather than predicting the change in the GFR level since theR2value was low.



Differences in predisposition to NaP-related kidney injury may result from allelic variations in sodium phosphate transporters or factors influencing their expression and cellula trafficking.

With respect to exposure misclassification, our patients lacked data on nephrotoxic medications, including renin angiotensin system inhibitors, diuretics, non-steroidal antiinflammatories, and radio-contrast material. There was unavoidable selection bias involving patients who received PEG because of our purgative selection. Thus, the presumably high-risk population was a lower proportion of the NaP group compared with the PEG group.

Applicant's summary and conclusion

In conclusion, the changes in renal function in patients who used NaP was similar to healthy controls or PEG treated patients. Further studies are warranted to validate and generalise the findings. Nonetheless, careful attention must be taken with patient selection, especially in patients with impaired renal function, and appropriate dosing of oral NaP (45 mL dose taken twice daily, 6-12 h apart) to prevent renal toxicity. Adequate hydration (at least 2-3 L of clear fluid throughout the cleansing period) is important during colon cleansing with oral NaP.