Disodium 3,3'-dithiobis[propanesulphonate]

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2015-05-26 - 2015-08-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well-documented GLP OECD guideline study without relevant deviations on the registered substance itself

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

The relative air humidity exceeded 70% a few times. These changes were temporary and did not influence the study course and results.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

yes

Remarks:

The relative air humidity exceeded 70% a few times. These changes were temporary and did not influence the study course and results.

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: Standard Operating Procedure SOP/T/21: „Acute dermal toxicity study”

Deviations:

yes

Remarks:

The relative air humidity exceeded 70% a few times. These changes were temporary and did not influence the study course and results.

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Disodium 3,3'-dithiobis[propanesulphonate]

EC Number:

248-324-3

EC Name:

Disodium 3,3'-dithiobis[propanesulphonate]

Cas Number:

27206-35-5

Molecular formula:

C6H14O6S4.2Na

IUPAC Name:

disodium 3,3'-disulfanediyldipropane-1-sulfonate

Constituent 2

Reference substance name:

1- Propanesulfonic acid, 3,3'-dithiobis-, disodium salt

IUPAC Name:

1- Propanesulfonic acid, 3,3'-dithiobis-, disodium salt

Constituent 3

Reference substance name:

disodium 3,3'- dithiobis[propanesulphonate]

IUPAC Name:

disodium 3,3'- dithiobis[propanesulphonate]

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report): SPS
- Substance type: pure substance
- Storage condition of test material: room temperature (20 ± 5°C)

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Wistar male and female rats (Cmdb: WI; outbred) coming from the husbandry of laboratory animals of the Experimental Medicine Centre at the Medical University in Białystok
- Age at study initiation: 8 weeks (males), 11 weeks (females)
- Weight at study initiation: average 267.8g (males) resp. 217.6g (females)
- Fasting period before study: no
- Housing: After the application of the test item, each animal was housed individually. After the removal of the test item from the animals’ skin, there were five rats in one cage. Each sex was kept separately.
- Diet (e.g. ad libitum): “Murigran” standard granulated fodder (batch number: 3/15, 4/15, 5/15) produced by Wytwórnia Koncentratów i Mieszanek Paszowych AGROPOL, Motycz, ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 – 24 °C
- Humidity (%): 35 – 75%
- Air changes (per hr): about 16 times/hour
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: 10% of the body surface area
- Type of wrap if used: gauze patch, PCV foil, elastic bandage and a sticking plaster

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with water
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg b.w.
- Concentration (if solution): substance was moistened with a few drops of wwater
- For solids, paste formed: yes

Duration of exposure:

24h

Doses:

2000 mg/kg b.w.

No. of animals per sex per dose:

5/sex/dose

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: general conditions twice a day or once a day (on days off), clinical observations once a day, body weight on day 0, 7, 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, other: clinical observations, detailed gross examination which comprised the observation of the external body surface, all natural apertures, and the cranial, thoracic, and abdominal cavities with thei r contents

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: All animals survived the 14 day observation period.

Effect levels 2

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: All animals survived the 14 day observation period.

Mortality:

All animals survived the experiment.

Clinical signs:

other: Following single application of the test item, the animals did not exhibit any general clinical signs. No pathological changes on the treated skin were noticed.

Gross pathology:

The gross examination did not reveal any pathological changes in the examined animals.

Any other information on results incl. tables

Table 1 -Clinical signs-overall list

Dose (mg/kgb.w.)	Sex	Day after application	Number of living animals	Rat number
				1	2	3	4	5
		0	5	NC	NC	NC	NC	NC
		1	5	NC	NC	NC	NC	NC
		2	5	NC	NC	NC	NC	NC
		3	5	NC	NC	NC	NC	NC
		4	5	NC	NC	NC	NC	NC
		5	5	NC	NC	NC	NC	NC
		6	5	NC	NC	NC	NC	NC
	males	7	5	NC	NC	NC	NC	NC
		8	5	NC	NC	NC	NC	NC
		9	5	NC	NC	NC	NC	NC
		10	5	NC	NC	NC	NC	NC
		11	5	NC	NC	NC	NC	NC
		12	5	NC	NC	NC	NC	NC
		13	5	NC	NC	NC	NC	NC
2000		14	5	NC	NC	NC	NC	NC
		0	5	NC	NC	NC	NC	NC
		1	5	NC	NC	NC	NC	NC
		2	5	NC	NC	NC	NC	NC
		3	5	NC	NC	NC	NC	NC
		4	5	NC	NC	NC	NC	NC
		5	5	NC	NC	NC	NC	NC
		6	5	NC	NC	NC	NC	NC
	females	7	5	NC	NC	NC	NC	NC
		8	5	NC	NC	NC	NC	NC
		9	5	NC	NC	NC	NC	NC
		10	5	NC	NC	NC	NC	NC
		11	5	NC	NC	NC	NC	NC
		12	5	NC	NC	NC	NC	NC
		13	5	NC	NC	NC	NC	NC
		14	5	NC	NC	NC	NC	NC

NC =no changes

 

Table 2 - Body weights of the animals (g) - overall list.

Dose (mg/kgb.w.)	Sex	Rat number	Day of experiment / Body weight(g)			Body weight gain(g) (0-14)
			0	7	14
		1	284	293	330	46
		2	247	269	282	35
	males	3	254	267	284	30
		4	270	271	292	22
2000		5	284	310	339	55
		1	216	225	243	27
		2	208	220	230	22
	females	3	211	221	232	21
		4	225	226	242	17
		5	228	227	233	5

Applicant's summary and conclusion

Interpretation of results:

other: EU GHS criteria not met

Conclusions:

The study was conducted under GLP according to OECD guideline 402 on the registered substance itself. The method is to be considered scientifically reasonable with no deficiencies in documentation. Hence, the results can be considered as reliable to assess the acute oral toxicity in rats.
Following single application of SPS at a dose of 2000 mg/kg bw, the animals did not show any general clinical signs. No pathological changes on the treated skin of males and females were found. All animals survived the experiment. During the 14-day experiment, body weight gain was found in all animals. Gross examination did not reveal any pathological changes in the examined animals. So it may be stated that the median lethal dose (LD50) of SPS is greater than 2000 mg/kg b.w. Since no animal showed at no observation time any pathological changes on the treated skin or other signs of irritation, it may be concluded that, under the conditions of this test, SPS does not need to be considered as irritating to rat skin.
According to the Regulation (EC) No. 1272/2008, it may be concluded that SPS is beyond categorization.

Executive summary:

In an acute dermal toxicity study (OECD 402), groups of 8-11 weeks old Wistar (Crl: WI(Han); outbred) rats (5/sex) were dermally exposed to moistened disodium 3,3'-dithiobis[propanesulphonate])(SPS) for 24 hours on 10% of body surface area at a dose of 2000 mg/kg bw under occlusive coverage. Animals then were observed for 14 days.

 

Following single application of the test item, the animals did not show any general clinical signs. No pathological changes on the treated skin of males and females were found. All animals survived the experiment. During the 14-day experiment, body weight gain was found in all animals. Gross examination did not reveal any pathological changes in the examined animals. Hence, the following results could be gained:

 

LD0(dermal) ≥ 2000 mg/kg bw

LD50(dermal) > 2000 mg/kg bw

 

SPS is of low Toxicity based on the LD50 determined. Since no animal showed at no observation time any pathological changes on the treated skin or other signs of irritation, it may be concluded that, under the conditions of this test, SPS does not need to be considered as irritating to rat skin.

According to Regulation (EC) No. 1272/2008, it may be concluded that SPS is beyond categorization.