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Basic toxicokinetics

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basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
4 (not assignable)

Data source

Reference Type:
The pharmncokinetics of saccharin in man
Sweatman, T. W.. Renwick. A. G. & Burgess. C. D.
Bibliographic source:
Xemlhiotico 11, 531.

Materials and methods

Objective of study:
Test guideline
according to
Principles of method if other than guideline:
Three adult males were given IO mg sodium saccharin dihydrate/kg body weight intravenously and, 3 wk later. the same dose during a course of probenecid taken in doses I2 and 2 hr before and 2 hr after the intravenous dose. Blood and urine samples were collected at intervals t”or up to 4Shr lollowing the saccharin doses. The same subjects were also given an oral dose (Ig) or saccharin. both after an overnight last and, 2 wk later. following a standardized
brcaklast. Blood and urine samples were taken at intervals [or up to 96 hr and faeces were collected [or 96 hr lollowing the saccharin doses.
GLP compliance:
not specified

Test material

Details on test material:
- Name of test material (as cited in study report): 1,2-benzisothiazol-3(2H)-one 1,1-dioxide, sodium salt
- Substance type: organic
- Physical state: solid
not specified

Test animals

not specified

Administration / exposure

Route of administration:
other: Oral and intravenous
other: Probenecid
Duration and frequency of treatment / exposure:
Duration - 2 weeks
No. of animals per sex per dose:
3 Adult Males

Results and discussion

Preliminary studies:
The plasma-saccharin levels decreased rapidly after intravenous dosina. with a half-life of about 70 min. and recovery of the dose in the urine was complete within 48 hr.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Studies on the fate in humans of orally administered saccharin have shown almost complete absorption followed by the rapid excretion or the unchanged compound in the urine . The authors interpreted the curve following oral administration as an increase to peak determined by absorption from the stomach and upper intestine, an initially rapid decline in plasma levels resulting from either declining absorption rates or from elimination and a variable late. slow decline determined by absorption from the lower gut. The authors compare the results of this study with those of the previous investigation in rats and concluded that the absorption of orally administered saccharin in similar in both the species and the sweetner is rapidly eliminated from the blood larger by kindeys via renal tubular secretion.
Details on excretion:
Sodium Saccharin sweetener is rapidly eliminated by the blood largely by the kidneys via renal tubular secretion.
Approximately 90% of the oral dose was recovered in the urine and up to 8%, was present in lhe faeces within 96hr irrespective of whether or not breakfast had been taken belore dosing and it was calculated that about 85% of the dose was absorbed.

Applicant's summary and conclusion

Interpretation of results (migrated information): no bioaccumulation potential based on study results
Executive summary:

It is concluded therefore that there is little possibility of saturation of the renal clearance route of excretion at ‘normal’ esposure levels since the doses given in the present study were at least 20 times those estimated as the average daily intake.