Dipotassium methanedisulphonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 September 2017 - 24 October 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dipotassium methanedisulphonate

EC Number:

228-543-0

EC Name:

Dipotassium methanedisulphonate

Cas Number:

6291-65-2

Molecular formula:

CH4O6S2.2K

IUPAC Name:

dipotassium methanedisulphonate

Test material form:

solid

Test animals

Species:

rat

Strain:

Wistar

Remarks:

RccHan: WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animal Breeding Facility, Jai Research Foundation
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 9 to 10 weeks
- Weight at study initiation: 182 to 206.9 g
- Fasting period before study: overnight prior to dosing until three hours post-dosing
- Housing: 3 females in polypropylene rat cages covered with stainless steel grid top. Autoclaved clean rice husk was used as the bedding material. Wooden blocks were provided as enrichment material.
- Diet (e.g. ad libitum): Ad libitum. Teklad Certified Global High Fiber Rat/Mice Feed manufactured by Envigo, USA. The quality of feed is regularly monitored at Jai Research Foundation.
- Water (e.g. ad libitum): Ad libitum. UV sterilized water filtered through Reverse Osmosis water filtration system. The quality of water is regularly monitored at Jai Research Foundation.
- Acclimation period: 6 to 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 23°C
- Humidity (%): 49 to 67%
- Air changes (per hr): At least 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours contimuous light (06.00 to 18.00 h) and 12 hours darkness.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 mg/mL and 200 mg/mL
- Amount of vehicle (if gavage): 10 mL
- Justification for choice of vehicle: recommended by OECD 423 guideline

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: without preliminary information, the selected starting dose is 300 mg/kg body weight.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: toxicity and mortality at 30 min, 1h, 2 h, 3h, 4h, 6 h after adminitration. Morbidity and mortality twice a day and clinical sings daily during 14 days. Weighing= D0 (prior to dosing) then on D7, and D14.
- Necropsy of survivors performed: yes. At termination, macroscopic observation was observed.
- Other examinations performed:
Clinical observations: evaluation of skin and fur, eyes and mucous membranes, respiratory and circulatory effects, autonomic effects and central nervous system effects, behavioural pattern, somatomotor activity and observation of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

ca. 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study.

Clinical signs:

other: No clinical sign was observed in rats treated with 300 and 2000 mg/kg body weight.

Gross pathology:

External and visceral examination of terminally sacrificed rats did not reveal any abnormality.

Any other information on results incl. tables

Table 1: Mortality

Dose (mg/kg body weight)	Set N°	Number of Rats Used	Mortality after Dosing
			At Hour		On Day
			0.5 - 4	6	1	2	3	4 - 7	8 - 14
300	I	3	0	0	0	0	0	0	0
	II	3	0	0	0	0	0	0	0
2000	III	3	0	0	0	0	0	0	0
	IV	3	0	0	0	0	0	0	0

Table 2: Individual and Mean Body Weight (g) and Body WeightChange (%)

Dose (mg/kg body weight)	Date and Time of Dosing (am)	Rat N°	Volume of Dose Administered (mL)	Body Weight (g) on Day			Percent Body Weight Change on Day
				0	7	14	7	14
300	September 26, 2017 and 10:10 am	1	1.94	194.3	218.4	246.0	12.4	26.6
		2	1.88	187.8	207.2	230.8	10.3	22.9
		3	1.99	198.8	223.1	238.6	12.2	20.0
	Mean			193.6	216.2	238.5	11.6	23.2
	Standard Deviation (±)			5.5	8.2	7.6	1.2	3.3
	September 28, 2017 and 9:45 am	4	1.98	198.3	215.8	236.2	8.8	19.1
		5	1.99	199.3	216.9	236.5	8.8	18.7
		6	1.92	192.1	215.6	238.6	12.2	24.2
	Mean			196.6	216.1	237.1	9.9	20.7
	Standard Deviation (±)			3.9	0.7	1.3	2.0	3.1
2000	October 02, 2017 and 10:00 am	7	2.06	206.3	220.8	246.1	7.0	19.3
		8	2.07	206.9	223.5	236.3	8.0	14.2
		9	2.03	203.2	220.4	237.8	8.5	17.0
	Mean			205.5	221.6	240.1	7.8	16.8
	Standard Deviation (±)			2.0	1.7	5.3	0.8	2.6
	October 10, 2017 and 10:10 am	10	1.82	182.0	194.1	208.1	6.6	14.3
		11	1.85	185.4	211.5	224.1	14.1	20.9
		12	1.91	191.2	205.9	221.7	7.7	16.0
	Mean			186.2	203.8	218.0	9.5	17.1
	Standard Deviation (±)			4.7	8.9	8.6	4.1	3.4

Key: Day 0 = Before dosing

Applicant's summary and conclusion

Interpretation of results:

other: Not classified (CLP Regulation EC no. 1272/2008)

Conclusions:

The LD50 of the test item is higher than 2000 mg/kg body weight by oral route in the rat. The LD50 cut-off may be considered to be 5000 mg/kg body weight by oral route in the rat.

Executive summary:

The acute oral toxicity of the test item has been tested in accordance with OECD Test Guideline 423, following GLP. 12 female Wistar rats divided in 4 groups were administered sequentially with test item by oral gavage. The first set of 3 female rats was given a single dose of 300 mg/kg body weight. No mortality was observed at this dose level, so the second set of 3 female rats was treated at the same dose level. No mortality was observed at this dose level, so the third set of 3 female rats was treated at the higher dose level of 2000 mg/kg bw. As no mortality was observed at this dose level, the fourth set of 3 female rats was treated at the same dose level of 2000 mg/kg bw. The body weight evolution of the animals remained normal during the study. No clinical signs were observed. The macroscopic examination of the animals at the end of the study did not reveal treatment related effects. The LD50 of the test item is higher than 2000 mg/kg body weight by oral route in the rat. The LD50 cut-off of the test item may be considered to be 5000 mg/kg body weight by oral route in the rat.