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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
publication
Title:
Dietary saccharin kinetics
Author:
Wayne A Colburn PhD, Ihor Bekersky PhD and H Peter Blumenthal MD Nutley, N.J
Year:
1981
Bibliographic source:
Clinical Pharmacology and Therapeutics (1981) 30, 558–563; doi:10.1038/clpt.1981.203

Materials and methods

Objective of study:
absorption
distribution
excretion
metabolism
Test guideline
Qualifier:
according to guideline
Guideline:
other:
Principles of method if other than guideline:
Data is from Clinical Pharmacology and Therapeutics journal
GLP compliance:
not specified

Test material

Constituent 1
Reference substance name:
Saccharin
IUPAC Name:
Saccharin
Constituent 2
Chemical structure
Reference substance name:
1,2-benzisothiazol-3(2H)-one 1,1-dioxide
EC Number:
201-321-0
EC Name:
1,2-benzisothiazol-3(2H)-one 1,1-dioxide
Cas Number:
81-07-2
Molecular formula:
C7H5NO3S
IUPAC Name:
1,2-benzisothiazol-3(2H)-one 1,1-dioxide
Details on test material:
- Name of test material (as cited in study report): 1,2-benzisothiazol-3(2H)-one 1,1-dioxide
- Substance type: Organic
- Physical state: solid
Radiolabelling:
no

Test animals

Species:
human
Strain:
not specified
Sex:
female

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
not specified
Details on exposure:
Six adult female subjects who use saccharin-containing products in their diet were asked to take divided equal doses of saccharin every 6 hr to maintain their average daily intake for 3 days.

At the end of this period, each subject took a single dose that was equal to one divided dose.
Saccharin concentrations in plasma and urine samples were used to assess the kinetic profile.
Duration and frequency of treatment / exposure:
Average daily intake ranged from 100 to 300 mg/
day. Daily dose was divided by four to establish the 6-hr dose size
Doses / concentrations
Remarks:
Doses / Concentrations:
100 to 300 mg/ day (average)
No. of animals per sex per dose / concentration:
Six women
Control animals:
not specified

Results and discussion

Main ADME resultsopen allclose all
Type:
absorption
Results:
Saccharin is absorbed rapidly and completely by the subjects who take it daily with maximum concentrations in plasma in 0.5 to 1.0 hr. Maximum plasma concentrations and areas under the plasma concentration-time curves were proportional to the dose.
Type:
distribution
Results:
Saccharin is distributed into tissues as a function of lean rather than total body mass. The volume of distribution (Vβ) is large, indicating extensive distribution of saccharin outside of the vascular space though it shows little , no affinity for fat.
Type:
metabolism
Results:
No details on metabolism provided but there are reports that suggest no metabiolites of saccarin as being detected in humans as well as animals administered saccharin
Type:
excretion
Results:
Subjects who take saccharin daily eliminate it with mean half life of elimination of 7.5 hr (range 5.5 to 9.0 hr). Renal clearance (clearance via urine) exceeded glomerular (clearance via faeces) filtration rate in all cases

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Saccharin is absorbed rapidly and completely by the subjects who take it daily with maximum concentrations in plasma in 0.5 to 1.0 hr.

Maximum plasma concentrations and areas under the plasma concentration-time curves were proportional to the dose
Details on distribution in tissues:
Saccharin is distributed into tissues as a function of lean rather than total body mass. The volume of distribution (Vβ) is large, indicating extensive distribution of saccharin outside
of the vascular space even though it shows little or no affinity for fat.

These observations are
consistent with the presence of one or more high-retention compartments within the body
(which has been reported in studies in animals)
Details on excretion:
Subjects who take saccharin daily eliminate it with mean half life of elimination of 7.5 hr (range 5.5 to 9.0 hr).

Renal clearance (clearance via urine) exceeded glomerular (clearance via faeces) filtration rate in all cases

Metabolite characterisation studies

Metabolites identified:
no
Details on metabolites:
No metabolites detected

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results
From the above information on absorption, distribution, metabolism and excretion of saccharin; the bio-accumulation potential appears to be low.
Executive summary:

Six adult female subjects who use saccharin-containing products in their diet were asked to take divided equal doses of saccharin every 6 hr to maintain their average daily intake for 3 days.Saccharin concentrations in plasma and urine samples were used to assess the kinetic profile.

 Saccharin absorption was rapid with maximum concentrations in plasma in 0.5 to 1.0 hr.

Maximum plasma concentrations and areas under the plasma concentration-time curves were proportional to dose. Renal clearance exceeded glomerular filtration rate in all cases.