Sodium methanesulphonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 July 2016 to 12 August 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

OECD Guidelines for Testing of Chemicals No. 423. Acute Oral Toxicity – Acute Toxic Class Method. Adopted: 17 December 2001

Deviations:

yes

Remarks:

see "Any other information" for details

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Sodium methanesulphonate

EC Number:

219-203-2

EC Name:

Sodium methanesulphonate

Cas Number:

2386-57-4

Molecular formula:

CH4O3S.Na

IUPAC Name:

sodium methanesulfonate

Test material form:

liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Species and strain: Crl:WI Wistar rats
Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld
Hygienic level at arrival: SPF
Hygienic level during the study: Standard housing conditions
Number of animals: 6 animals, 3 animals/group
Sex: Female, nulliparous and non-pregnant
Age of animals at dosing: Young healthy adult rats, 8 weeks old
Body weight at treatment: 186 – 190 g
Acclimatization period: 7-8 days
HusbandryAnimal health: Only healthy animals were used for the test. The health status was certified by the staff Veterinarian.Number of animal room: 245/4
Housing: 3 animals / cage
Cage type: Type II. polypropylene/polycarbonate
Bedding: Lignocel 3/4-S Hygienic Animal Bedding” produced by J. Rettenmaier & Söhne GmbH +Co.KG (D-73494 Rosenberg, Germany) was available to animals during the study.
Nesting: Arbocel crinklets natural produced by J. Rettenmaier & Söhne GmbH + Co.KG (D-73494 Rosenberg, Germany) was available to animals during the study.
Lighting period: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 19.7 – 24.7 °C
Relative humidity: 31 - 77%
Ventilation: 15-20 air exchanges/hour
Enrichment: Animals were housed by group to allow social interaction and with deep wood sawdust bedding to allow digging and other normal rodent activities.The temperature and relative humidity were recorded twice daily during the acclimatisation period and throughout the study.
Food and Water Supply: Animals received ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany (batch number: 278 5652, expiry date: 31 October 2016), ad libitum, and tap water from the municipal supply, as for human consumption from a 500 ml bottle, ad libitum.
Animal Identification: Animals were individually identified using numbers written on the tail with an indelible marker pen. The numbers were given on the basis of CiToxLAB Hungary Ltd.' S Master File, for each animal allocated to the treatment groups. The cages were identified by cards, with information about study code, sex, dose group, cage number and individual animal numbers.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test item was administered as a single dose without using any vehicle.Justification of the dose:The initial dose level was selected by the Study Director to be that which is most likely to produce mortality in some of the dosed animals. In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose (equivalent to 4.23 mL/kg bw of SPS10LS, based on the analytics performed on 27 May 2016).Initially, three female animals were treated with 2000 mg/kg bw of the test item. No mortality was observed, therefore further 3 animals were treated at the dose level of 2000 mg/kg bw. As no mortality was observed in this second dose group, further testing was not required according to the test guidelines (OECD 423, Commission Regulation (EC) NO 440/2008 of 30 May 2008, B.1.Tris).

Doses:

A single oral treatment was carried out by gavage for each animal. The test item was administered at the dose level of 2000 mg/kg body weight (equivalent to 4.23 mL/kg bw of SPS10LS).

No. of animals per sex per dose:

Initially, three females (Group 1) were treated at a dose level of 2000 mg/kg bw. A confirmatory group of three females (Group 2) was treated at the same dose level.

Control animals:

no

Details on study design:

Procedure
A single oral gavage administration was followed by a 14-day observation period. On the night before treatment, the animals were fasted. The food but not water was withheld during an overnight period. Animals were weighed just before treatment. The test item was administered by oral gavage in the morning. The food was returned 3 hours after the treatment.

OBSERVATIONS
Clinical Observations
Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Individual observations were performed on the skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Body Weight Measurement
The body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly Thereafter.

NECROPSY
Macroscopic examination was performed on all animals. The animals were sacrificed by exsanguination under pentobarbital anaesthesia (Euthanimal 40%; Lot No.: 1409236-06, Expiry Date: September 2017, Produced by: AlfasanNederland BV, Woerden, Netherlands). After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded.

Statistics:

Not specified

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Sodium methanesulfonate did not cause mortality at a dose level of 2000 mg/kg bw.

Clinical signs:

All animals were symptom free during the study.

Body weight:

Body weight gains of Sodium methanesulfonate treated animals during the study showed no indication of a test item-related effect.

Gross pathology:

There was no evidence of the macroscopic observations at a dose level of 2000 mg/kg bw.

Other findings:

No further findings specified in the study report.

Any other information on results incl. tables

CLINICAL OBSERVATIONS

DOSE LEVEL: 2000 mg/kg bw, Treatment on Day 0                                                                                         SEX: Female

Cage No.

Animal Number

Observations

Observation days

Frequency

0

1

2

3

4

5

6

7-14

30’

1h

2h

3h

4h

6h

1

1945

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

1946

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

1947

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

2

1948

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

1949

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

1950

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

Remarks:

+ = present

h = hour  ‘ = minute

Frequency of observation = number of occurrence of observation/ total number of observations

 

BODY WEIGHT DATA

DOSE LEVEL: 2000 mg/kg bw, Treatment on Day 0                      SEX: Female

Cage No.	Animal Number	Body Weight (g) Days				Body Weight Gain (g)
		-1	0	7	14	-1 – 0	0 – 7	7 – 14	-1 – 14
1	1945	200	186	228	248	-14	42	20	48
	1946	204	190	228	253	-14	38	25	49
	1947	203	189	225	251	-14	36	26	48
2	1948	197	187	222	242	-10	25	20	45
	1949	203	188	240	255	-15	52	15	52
	1950	205	190	235	239	-15	45	4	34
Mean:		202.0	188.3	229.7	248.0	-13.7	41.3	18.3	46.0
Standard deviation:		3.0	1.6	6.7	6.3	1.9	6.4	8.1	6.3

 

NECROPSY FINDINGS

DOSE LEVEL: 2000 mg/kg bw, Treatment on Day 0                                                                                      SEX: Female

Cage No.	Animal Number	Necropsy Date/ Necropsy Day	External Observations	Internal Observations	Organ/Tissue
1	1945	11 August 2016 Day 14	No external observations recorded	No internal observations recorded	Not applicable
	1946	11 August 2016 Day 14	No external observations recorded	No internal observations recorded	Not applicable
	1947	11 August 2016 Day 14	No external observations recorded	No internal observations recorded	Not applicable
2	1948	12 August 2016 Day 14	No external observations recorded	No internal observations recorded	Not applicable
	1949	12 August 2016 Day 14	No external observations recorded	No internal observations recorded	Not applicable
	1950	12 August 2016 Day 14	No external observations recorded	No internal observations recorded	Not applicable

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD0 value of the test item Sodium methanesulfonate was found to be equal to or above 2000 mg/kg bw in female Crl:WI rats.

Executive summary:

The single-dose oral toxicity study with Sodium methanesulfonate was performed according to the acute toxic class method (OECD 423 and Commission Regulation (EC) No 440/2008 of 30 May 2008, B.1.Tris) in Crl:WI rats.

Two groups of three female Crl:WI rats were treated with the test item at a dose level of 2000 mg/kg bw (Group 1 and Group 2). A single oral treatment was carried out by gavage for each animal after an overnight food withdrawal. Food was made available again 3 hours after the treatment. The test item was administered at the dose level of 2000 mg/kg body weight (equivalent to 4.23 mL/kg bw of SPS10LS). Initially, three females (Group 1) were treated at a dose level of 2000 mg/kg bw. As no mortality was observed, a confirmatory group (Group 2) was treated at the same dose level. No mortality was observed in the confirmatory group; therefore no further testing was required according to OECD 423 and Commission Regulation (EC) NO 440/2008 of 30 May 2008, B.1.Tris. Clinical observations were performed at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weight was measured on Days -1, 0, 7 and before necropsy (Day 14). All animals were subjected to a necropsy and a macroscopic examination.

Sodium methanesulfonate did not cause mortality at a dose level of 2000 mg/kg bw. All animals were symptom free during the study. Body weight gains of Sodium methanesulfonate treated animals during the study showed no indication of a test item-related effect. There was no evidence of the macroscopic observations at a dose level of 2000 mg/kg bw.

Under the conditions of this study, the acute oral LD0 value of the test item Sodium methanesulfonate was found to be equal to or above 2000 mg/kg bw in female Crl:WI rats.