1,2-benzisothiazol-3(2H)-one 1,1-dioxide, sodium salt

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1972

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Scientific publication, no GLP.

Objective of study:

metabolism

Principles of method if other than guideline:

Saccharin labelled with t4C in the carbonyl group was administered orally to albino rats and the amounts excreted and retained in the body were determined by radioassay A method was developed for the separation and quantitative determination of saccharin and its hydrolytic products, o-sulphamoylbenzoic acid and ammonium o-carboxybenzenesulphonate.

GLP compliance:

no

Specific details on test material used for the study:

Saccharin sodium salt, saccharin labelled with 1+C in the carbonyl group and having a specific activity of 1.15 mc/g, o-sulphamoylbenzoic acid (CompoundI) and ammonium o-carboxybenzenesulphonate (Compound II) were obtained from Monsanto Co., St. Louis. Mo.

Radiolabelling:

yes

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

Two male and two female young adult Charles River albino rats, obtained from the Charles River Breeding Laboratories, North Wilmington, Mass. and weighing about 200 g.

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Duration and frequency of treatment / exposure:

On the morning of the first test day, after a 16-hr fast (water permitted), each rat was intubated with a solution of labelled saccharin in 1 70 aqueous methylcellulose. One male and one female each received 1-0 ml, containing 10 t~c of 14C activity, and one male and one female received 2-0 ml each (20 tzc). Similar doses of non-radioactive material have been well tolerated by animals. The solutions were administered using a hypodermic syringe
equipped with a ball-pointed intubation needle. The exact amount received by each animal was determined by weighing the syringe and needle before and after dosing.

Dose / conc.:

8.21 other: microC/rat

Dose / conc.:

17.54 other: microC/rat

Dose / conc.:

8.12 other: microC/rat

Dose / conc.:

18.27 other: microC/rat

No. of animals per sex per dose / concentration:

Two male and two female

Metabolites identified:

yes

Table 1.Recovery of 14 C activity from TLC plates following chromatography of whole urine samples from rats given an oral dose of[14C]saccharin

		Radioactivity
Animal no	Sample time interval (h)	Total urine (counts/min)	Saccharin (counts /min)	Saccharin (% of total)
1	12	5839	5149	99.7
	24	5717	5676	99.3
2	12	7314	7276	99.5
	24	5311	5280	99.4
	48	5335	5288	99.1
	72	2181	2178	99.9
3	12	5192	5171	99.6
	24	2673	2671	99.9
4	12	6032	6024	99.8
	24	3116	3098	994

 

The rats used in the radiotracer study showed no signs of toxicity during the study. Food and water consumption and excretory patterns were normal and there were no significant changes in body weight during the test period.

Conclusions:

The rats used in the radiotracer study showed no signs of toxicity during the study. Food and water consumption and excretory patterns were normal and there were no significant
changes in body weight during the test period.

Executive summary:

The study of metabolic fate of sodium sacchrin in rats was performed. Radiolabelled sodium saccharin was administrated orally to rats (2 male and 2 female).

It was found that almost all the saccharin was eliminated unchanged within 48 h, only traces of the other two compounds being found. The study conclusion is sodium saccharin, when administered orally to the albino rat, is neither stored nor metabolized.

Description of key information

Weight of evidence:

The study of metabolic fate of sodium sacchrin in rats was performed. Radiolabelled sodium saccharin was administrated orally to rats (2 male and 2 female).

It was found that almost all the saccharin was eliminated unchanged within 48 h, only traces of the other two compounds being found. The study conclusion is sodium saccharin, when administered orally to the albino rat, is neither stored nor metabolized.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential