Sodium 3-[[(dimethylamino)thioxomethyl]thio]propanesulphonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-01-25 - 2016-02-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well-documented OECD 423 GLP guideline study without deviations on the registered substance itself.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

Adopted: 17th December 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Slovak National Accreditation Service

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Sodium 3-[[(dimethylamino)thioxomethyl]thio]propanesulphonate

EC Number:

242-644-7

EC Name:

Sodium 3-[[(dimethylamino)thioxomethyl]thio]propanesulphonate

Cas Number:

18880-36-9

Molecular formula:

C6H13NO3S3.Na

IUPAC Name:

sodium 3-[(dimethylcarbamothioyl)sulfanyl]propane-1-sulfonate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Sodium 3-[[(dimethylamino)thioxomethyl]thio]propanesulphonate, DPS
- Substance type: pure substance
- Storage condition of test material: Room Temperature: (20 ± 5°C)
- Other: Homogeneity: homogeneous

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Velaz Prague, Czech Republic
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 180 - 200 g
- Fasting period before study: yes, overnight
- Housing: The animals were housed in plastic cages suspended on stainless steel racks, up to 3 animals per cage in a room equipped with central air-conditioning. Bedding was Lignocel S3/4, Lufa - ITL GmbH, Germany
- Diet (e.g. ad libitum): A laboratory food Altromin (Altromin Spezialfutter GmbH, Germany) was offered in recommended doses each day approximately at the same time.
- Water (e.g. ad libitum): The animals received tap water for human consumption. Supply of drinking was unlimited. The quality of drinking water is periodical analysed (including microbiological control) and recorded.
- Acclimation period: The animals were acclimated under the conditions identical to the conditions during the experiment 5 days prior to the start of treatment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2° C
- Humidity (%): 55 ± 10 %
- Photoperiod (hrs dark / hrs light): 12-hour light /12-hour dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

Aqua pro Injectione

Details on oral exposure:

DOSAGE PREPARATION (if unusual):
The required amount of the test item (according body weight) was mixed with vehicle (Aqua pro Injectione) shortly before administration.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The starting dose could be selected from the fixed dose levels of 5, 50, 300, and 2000 mg/kg. Available information indicated test item is likely to be nontoxic considering to acute toxicity. A limit dose of 2000 mg/kg was used as a starting dose. One group of 3 females was dosed. Test itemrelated mortality was not observed during 24 hours and therefore in a second step another 3 females were treated at the same dose.

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 + 3

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed individually immediately after the administration of the test item and then 0.5, 1, 2, and 4 hours later. Then each animal was inspected daily for the next 14 days. Individual weights of animals were determined shortly before the test item was administered and weekly thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathological changes

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: All 6/6 females survived the limit dose of 2000 mg/kg.

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg of OECD Guideline 423 it can be concluded that the test item is classified in Category 5/Unclassified with a LD50 cut off value equal to or greater than 5000 mg/kg.

Mortality:

All 6/6 females survived the limit dose of 2000 mg/kg.

Clinical signs:

No mortality was observed during the study. Animals lived through observation period without important visible signs of intoxication. Neither change of health nor negative reactions were registered.

Body weight:

The body weights of all animals were increasing during the study. No body weight losses were observed between first and second week after administration. In 2 animals (No 3 and No 4), stagnation of body weight was observed.

Gross pathology:

All animals were necropsied. During necropsy, no macroscopically changes were noticed.

Any other information on results incl. tables

RESULTS

Administration Results

All 6/6 females survived the limit dose of 2000 mg/kg.

 

Table Administration Results

Sex	Dose	ID	Result	Sex	Dose	ID	Result
♀	2000 mg/kg	1	alive	♀	2000  mg/kg	4	alive
		2	alive			5	alive
		3	alive			6	alive

 

Clinical Observations

No mortality was observed during the study. Animals lived through observation period without important visible signs of intoxication. Neither change of health nor negative reactions were registered.

 

Table Clinical Observation

Observation	Time After Administration
	Hour					Day
	Immediately	0.5	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
Skin and Hair	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Eyes	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Mucosa	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Respiratory System	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Circulatory System	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
CNS	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Somatomotoric Activity	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Tremor	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Spasms	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Salivation	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Diarrhoea	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Lethargy	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Sleep	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Coma	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Death	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-

-No observed signs

 

Body Weight

The body weights of all animals were increasing during the study. No body weight losses were

observed between first and second week after administration. In 2 animals (No 3 and No 4),

stagnation of body weight was observed. Summary results of body weight development are

presented below.

 

Table Body Weight

Sex	Dose	ID	Body Weight (g)			Body Weight Difference (g)
			Initial	Week 1	Week 2	Week 1 - Initial	Week 2 - Initial	Week 2 - Week 1
♀	2000 mg/kg	1	200	205	210	5	10	5
		2	190	200	205	10	15	5
		3	195	200	200	5	5	0
		4	180	195	195	15	15	0
		5	185	205	220	20	35	15
		6	180	200	215	20	35	15

 

Necropsy

All animals were necropsied. During necropsy, no macroscopically changes were noticed.

 

Table Necropsy Results

Sex	Dose	ID	Result	Sex	Dose	ID	Result
♀	2000 mg/kg	1	no change	♀	2000 mg/kg	4	no change
		2	no change			5	no change
		3	no change			6	no change

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The study was conducted under GLP according to OECD guideline 423 on the registered substance itself. The method is to be considered scientifically reasonable with no deficiencies in documentation or any deviations. Hence, the results can be considered as reliable to assess the acute toxicity of Sodium 3-[[(dimethylamino)thioxomethyl]thio]propanesulphonate, DPS in rats. The test item administered to 6 females in limit dose of 2000 mg/kg did not cause death or any other signs of toxicity. Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg of OECD Guideline 423 it can be concluded that the test item Sodium 3-[[(dimethylamino)thioxomethyl]thio]propanesulphonate, DPS is classified in Category 5/Unclassified with a LD50 cut off value equal to or greater than 5000 mg/kg, after single oral administration to Wistar rats.

Executive summary:

The purpose of the present GLP study was to evaluate the potential toxic effect of the test item Sodium 3-[[(dimethylamino)thioxomethyl]thio]propanesulphonate, DPS when administered as a single oral dose to Wistar rats.

The procedure according to OECD Guideline 423 Acute Toxic Class (ATC) method was used. Available information indicated that the test item is likely to be non-toxic; therefore, a limit dose of 2000 mg/kg was used as a starting dose. Two groups of 3 females were dosed. All 6 females survived the limit dose. The limit dose of 2000 mg/kg did not cause death, evident signs of toxicity or body weight loss during the 14 day long observation period.

Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg of OECD Guideline 423 it can be concluded that the test item Sodium 3-[[(dimethylamino)thioxomethyl]thio]propanesulphonate, DPS is classified in Category 5/Unclassified with a LD50 cut off value equal to or greater than 5000 mg/kg, after single oral administration to Wistar rats.