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

Endpoint summary

Description of key information

The substance 1,2-benzisothiazol-3(2H)-one 1,1-dioxide sodium salt was found to be not irritating in skin and eye category.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The data from read across chemical 1,2-benzisothiazol-3(2H)-one 1,1-dioxide sodium salt is considered to be just the salt coumpound of the target chemical and which have more than 87.8 % structural similarity. Thus it is expected to have the similar toxicological impact.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

-Sex: Female

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes

Duration of treatment / exposure:

14 days

Observation period:

The site of application was observed for skin reaction if any. The intact skin site of application of each animal was observed for signs of erythema and oedema and the responses were scored following Draize’s method at 60 min., 24, 48 and 72 hours after application.

Number of animals:

3

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 72 hours

Score:

0

Max. score:

4

Reversibility:

no data

Remarks on result:

other: Not irritating

Other effects:

Skin reaction
The test compound Sodium saccharin applied at the dose level of 0.5 gm on shaven back skin of rabbit did not produced any irritation to skin during period of observation.

Clinical Signs
The test compound Sodium saccharin applied on the shaven back skin of rabbit did not produce any clinical signs of toxicity throughout the examination period of 14 days.

INDIVIDUAL ANIMAL DERMAL IRRITATION SCORES

 

Rabbit No.	Sex	INTACT SKIN
		3 Min.		4 Hours		24 Hours		48 Hours		72 Hours		14 days
		Erythema	Oedema	Erythema	Oedema	Erythema	Oedema	Erythema	Oedema	Erythema	Oedema	Erythema	Oedema
01	F	0	0	0	0	0	0	0	0	0	0	0	0
02	F	-	-	0	0	0	0	0	0	0	0	0	0
03	F	-	-	0	0	0	0	0	0	0	0	0	0
Total		0	0	0	0	0	0	0	0	0	0	0	0
Mean		0	0	0	0	0	0	0	0	0	0	0	0
Grand Total		0.00

 

Dermal Irritation Index: 0.0/4 = 0.0

CLINICAL SIGNS

 

SEX	ANIMAL NO.	Time (Min.)	Time (Hours)					Time (Day)
		3	1	4	24	48	72	14
FEMALE	01	N	N	N	N	N	N	N
	02	N	N	N	N	N	N	N
	03	N	N	N	N	N	N	N

 

N: No Clinical Signs

C: Clinical Signs Observed

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The result obtained from present experimentation reveals that the test compound 1,2-benzisothiazol-3(2H)-one 1,1-dioxide, sodium salt (Sodium saccharin) in the dermal irritation study is non irritant to the skin of New Zealand white rabbits when applied to the shaven back intact skin.

Finally, it is concluded from the dermal irritation study 1,2-benzisothiazol-3(2H)-one 1,1-dioxide, sodium salt (Sodium saccharin) can be classified under non irritant tested at dose level of 0.5 gm in New Zealand white rabbits.

Executive summary:

The result obtained from present experimentation reveals that the test compound 1,2-benzisothiazol-3(2H)-one 1,1-dioxide, sodium salt (Sodium saccharin) in the dermal irritation study is non irritant to the skin of New Zealand white rabbits when applied to the shaven back intact skin.

Finally, it is concluded from the dermal irritation study 1,2-benzisothiazol-3(2H)-one 1,1-dioxide, sodium salt (Sodium saccharin) can be classified under non irritant tested at dose level of 0.5 gm in New Zealand white rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The data from read across chemical 1,2-benzisothiazol-3(2H)-one 1,1-dioxide sodium salt is considered to be just the salt coumpound of the target chemical and which have more than 87.8 % structural similarity. Thus it is expected to have the similar toxicological impact.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Test System
1.     Test Species                           : New Zealand white rabbit
2.     Age                                           : 10 to 12 weeks
3.     Sex                                           : Female
4.     Body weight range                : 1.60kg ±200g
5.     No. of animals                        : Three
6.     Acclimatization                       : The rabbit was acclimatized to standard laboratory condition for 24 hours in experimental room before study.

Vehicle:

unchanged (no vehicle)

Controls:

yes

Duration of treatment / exposure:

Irrigation:
The eyes of the test animal did not washed for at least 24 hours following instillation of the test compound. At 24 hours a washout may be used if considered appropriate.
Dose level:
A dose of 0.1gm of test substance was applied into the one eye of the rabbits. The other eye, which remains untreated, serves as a control.

Observation period (in vivo):

The eyes were examined at 1, 24, 48 and 72 hours after test substance application. The grades of ocular reaction (conjunctiva, cornea and iris) were recorded at each observation. To determine the reversibility of the effect the animal was observed normally for 21 days. Any other lesions in the eye viz pannus, staining were observed and scored accordingly. Examination of reactions was facilitated by use of biomicroscope and hand slit lamp. After recording the observations at 24 hours, the eyes were further examined with the aid of fluorescein. Individual animal weight before and during the study was also observed

Number of animals or in vitro replicates:

3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 72 hours

Score:

1

Max. score:

3

Reversibility:

fully reversible

Other effects:

Irritation Scoring
The test compound Sodium saccharin when applied to the eye of New Zealand white rabbit at the dose level of 0.1 gm did not produced any lesions such as pannus, staining throughout the observation period of 72 hours. However some blood vessels of conjunctiva were observed hyperemic at 1 to 24th hour after the application of test substance.
Clinical Signs
The test compound Sodium saccharin applied in conjunctival sac of rabbits did not show any observable clinical signs throughout the observation period of 21 days.

GRADING OF OCULAR LESIONS

 

S.NO	SEX	OBSERVATION	Score				Total score
1	F		1 hour	24hours	48 hours	72 hours
		Cornea	0	0	0	0	0
		Iris	0	0	0	0	0
		Conjunctivae	1	0	0	0	1
		Chemosis	0	0	0	0	0
2	F	Cornea	0	0	0	0	0
		Iris	0	0	0	0	0
		Conjunctivae	1	0	0	0	1
		Chemosis	0	0	0	0	0
3.	F	Cornea	0	0	0	0	0
		Iris	0	0	0	0	0
		Conjunctivae	1	0	0	0	1
		Chemosis	0	0	0	0	0
Grand total							3
Total mean							1

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The result obtained from current Acute Eye Irritation study concludes that the test compound 1,2-benzisothiazol-3(2H)-one 1,1-dioxide, sodium salt (Sodium saccharin) in the amount of 0.1gm is practically non irritant to the eyes of New Zealand white rabbit when applied at the dose level of 0.1 gm.

Executive summary:

The result obtained from current Acute Eye Irritation study concludes that the test compound 1,2-benzisothiazol-3(2H)-one 1,1-dioxide, sodium salt (Sodium saccharin) in the amount of 0.1gm is practically non irritant to the eyes of New Zealand white rabbit when applied at the dose level of 0.1 gm.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation :-

The result obtained from present experimentation reveals that the test compound 1,2-benzisothiazol-3(2H)-one 1,1-dioxide, sodium salt (Sodium saccharin) in the dermal irritation study is non irritant to the skin of New Zealand white rabbits when applied to the shaven back intact skin.

Finally, it is concluded from the dermal irritation study 1,2-benzisothiazol-3(2H)-one 1,1-dioxide, sodium salt (Sodium saccharin) can be classified under non irritant tested at dose level of 0.5 gm in New Zealand white rabbits.

The inference is drawn based on the read across chemical 1,2-benzisothiazol-3(2H)-one 1,1-dioxide sodium salt which have more than 87.8 % structural similarity.

 

Eye irritation

The result obtained from current Acute Eye Irritation study accoording to OECD 405 guideline concludes that the test compound 1,2-benzisothiazol-3(2H)-one 1,1-dioxide, sodium salt (Sodium saccharin) in the amount of 0.1gm is practically non irritant to the eyes of New Zealand white rabbit when applied at the dose level of 0.1 gm. Thus based on this result it can be concluded that the test substance is not classified as eye irritant as per the criteria of CLP regulation.

The inference is drawn based on the read across chemical 1,2-benzisothiazol-3(2H)-one 1,1-dioxide which have more than 87.8 % structural similarity. Also this is the sodium salt of the target substance.

Justification for selection of skin irritation / corrosion endpoint:
The result obtained from present experimentation reveals that the test compound 1,2-benzisothiazol-3(2H)-one 1,1-dioxide, sodium salt (Sodium saccharin) in the dermal irritation study is non irritant to the skin of New Zealand white rabbits when applied to the shaven back intact skin.

Finally, it is concluded from the dermal irritation study 1,2-benzisothiazol-3(2H)-one 1,1-dioxide, sodium salt (Sodium saccharin) can be classified under non irritant tested at dose level of 0.5 gm in New Zealand white rabbits.

Justification for selection of eye irritation endpoint:
The result obtained from current Acute Eye Irritation study concludes that the test compound 1,2-benzisothiazol-3(2H)-one 1,1-dioxide, sodium salt (Sodium saccharin) in the amount of 0.1gm is practically non irritant to the eyes of New Zealand white rabbit when applied at the dose level of 0.1 gm.

Justification for classification or non-classification

The available studies indicate that substance 1,2-benzisothiazol-3(2H)-one 1,1-dioxide is not classified as a skin and eye irritant according to CLP regulation.