Disodium 3,3'-dithiobis[propanesulphonate]

Endpoint summary

Description of key information

Acute Toxicity Oral: Acute study oral (gavage), rat (Sprague-Dawley) m/f (OECD guideline 401, GLP): LD50(oral) > 2000 mg/kg / LD0(oral) ≥ 2000 mg/kg
Acute Toxicity Oral: Acute study oral (gavage), rat (Wistar) m/f (OECD guideline 401, GLP), read-across from 1-Propanesulfonic acid, 3-mercapto-, monosodium salt: LD50(oral) = 3720 mg/kg / LD0(oral) ≥ 2500 mg/kg
Acute Toxicity Dermal: Acute study dermal (occlusive), rat (Wistar) m/f (OECD guideline 402, GLP): LD50(dermal) > 2000 mg/kg / LD0(dermal) ≥ 2000 mg/kg
Acute Toxicity Dermal: Acute study dermal (occlusive), rat (Wistar) m/f (OECD guideline 402, GLP), read-across from 1-Propanesulfonic acid, 3-mercapto-, monosodium salt: LD50(dermal) > 7500 mg/kg / LD0(dermal) ≥ 7500 mg/kg

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

9 June - 2 July 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

(The Department of Health of the Government of the United Kingdom)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd. , Margate , Kent , UK
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 212-229g (males) and 201-232g (females)
- Fasting period before study: overnight , until 3-4 hours after dosing
- Housing: animals were housed in groups of up to five by sex in solid-florr polypropylene cages furnished with woodflakes
- Diet : Rat and Mouse Expanded Diet No.1 (Special Diets Services Limited , Witham , Essex , UK) , ad libitum
- Water : mains drinking water , ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22
- Humidity (%): 48-55
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: distilled water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 1/2 , 1 , 2 and 4 hours after dosing and subsequently once daily for fourteen days . Individual bodyweights were recorded prior to dosing on Day 0 and on Day 7 and 14 .
- Necropsy of survivors performed: yes , the animals were sublected to gross pathological examination
- Other examinations performed: behavioural and clinical observations , gross lesions , bodyweight changes , mortality , other toxicological effects

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured during the study period

Clinical signs:

other: No signs of systemic toxicity were noted during the study

Gross pathology:

No abnormalities were noted at necropsy

Interpretation of results:

other: EU GHS criteria not met

Conclusions:

The study was performed according to the OECD TG401 without deviations and therefore considered to be of the highest quality (reliability Klimisch 1). The validity criteria of the test system are fulfilled. The test material did not induce mortality or treatment-related clinical signs. The test material was considered to be non-toxic under the conditions of the test.

Executive summary:

A study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley CD strain rat. The method followed that in the OECD Guidelines for Testing of Chemicals No. 401 "Acute Oral Toxicity" (adopted 24 February 1987) and Method B1 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). Following a range-finding study, a group of ten fasted animals (five males and five females) was given a single oral dose of test material as a solution in distilled water at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of dosing and were then killed and subjected to gross pathological examination. There were no deaths. No signs of systemic toxicity were noted during the study. All animals showed an expected gain in bodyweight during the study. No abnormalities were noted at necropsy. The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. No symbol and risk phrase are required according to EU labelling regulations.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

There are two studies to cover that endpoint available: One assessed with Klimisch 1 on SPS itself, and one assessed with Klimisch 2 on the read-across substance MPS. They both gave consistent results, i.e. the LD50(oral) is > 2000 mg/kg, the LD0(oral) ≥ 2000 mg/kg. Hence, the tonnage-driven data requirements under REACH are fully met and the database is of high quality.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Waiver provides scientific explanation, taking into account reliable information on SPS derived from i.a. a Klimisch 1 studies, why the study does not need to be conducted. So the overall data quality justifying data waiving is high.

Acute toxicity: via dermal route

Link to relevant study records

Reference

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

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.

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.

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

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

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

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.

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.

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

There are two studies to cover that endpoint available: One assessed with Klimisch 1 on SPS itself, and one assessed with Klimisch 2 on the read-across substance MPS. They both gave consistent results, i.e. the LD50(dermal) is > 2000 mg/kg, the LD0(dermal) ≥ 2000 mg/kg. Hence, the tonnage-driven data requirements under REACH are fully met and the database is of high quality.

Additional information

In all available studies consistently no indication is given that the substance would need to be classified as acute toxic or poses any relevant risk for humans, as the animal model is considered sufficient to assess the inherent hazard of the substance via the oral or dermal route. Testing for toxicity via inhalation was considered not necessary as it would reveal no additional information and is also scientifically not relevant due to the intrinsic properties of SPS, e.g. low vapour pressure. The tonnage-driven data requirements are hence fully met, no data gaps were identified, and SPS does not need to be classified as acute toxic.

Justification for selection of acute toxicity – oral endpoint
Most reliable study (Klimisch 1) via oral route on the registered substance itself. Selection would not have any influence on the fact that the substance does not require classification as both available studies indicate that no animal dies at the limit dose of 2000 mg/kg.

Justification for selection of acute toxicity – inhalation endpoint
Provides explanation why study does not need to be conducted.

Justification for selection of acute toxicity – dermal endpoint
Most reliable study (Klimisch 1) via dermal route on the registered substance itself. Selection would not have any influence on the fact that the substance does not require classification as both available studies showed that no animal died at the limit dose of 2000 mg/kg.

Justification for classification or non-classification

All available studies via the dermal or oral route revealed consistently LD50 and even LD0 (≥) values above 2000 mg/kg, which is the limit value for classification. Also, the given physico-chemical and toxicological data give no indication that testing for acute inhalation toxicity would result in LC50 values below 5 mg/L. Hence, classification criteria are not met and SPS does not need to be classified as acute toxic according to Regulation 1272/2008.