Sodium methanesulphonate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 July 2016 to 02 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 402 (Acute Dermal Toxicity)

Version / remarks:

OECD Guidelines for Testing of Chemicals No. 402. Acute Oral Toxicity – Acute Toxic Class Method. Adopted: 24 February 1987

Deviations:

yes

Remarks:

See "Any other information" for details

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

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:

male/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: 5 animals/sex
Sex: Male and female, female rats were nulliparous and non-pregnant
Age of animals at dosing: Young healthy adult rats
Body weight at treatment: Between 217 g and 250 g
Acclimatization period: 5 days
HusbandryAnimal health: Only healthy animals were used for the test. The health status was certified by the staff Veterinarian.Number of animal room: 245/9
Housing: Individual caging
Cage type: Type II. polypropylene/polycarbonate
Bedding: “Lignocel 3/4-S Hygienic Animal Bedding” and “Arbocel crinklets natural” nest building material 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: 20.8 – 24.8 °C
Relative humidity: 35 – 80%
Ventilation: 15-20 air exchanges/hour
Enrichment: Rodents were housed 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 No.: 278 5652, expiry date: 30 November 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

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The back of each animal was shaved (approximately 10% area of the total body surface) approximately 24 hours prior to treatment. The test item was applied as a single dose to the shaved skin and remained in contact with the skin for the 24-hour exposure period. Sterile gauze pads were placed on the skin of rats to cover the test item. These gauze pads were kept in contact with the skin using a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi occlusive plastic wrap for 24 hours.At the end of the exposure period, the area of skin treated with the test item was washed with water of body temperature.

Duration of exposure:

24 hours

Doses:

Doses
Justification of the doses:The test item was not expected to be lethal at 2000 mg/kg body weight (bw). A limit test was therefore performed at 2000 mg Sodium methanesulfonate /kg bw (equivalent to 4.23 mL/kg bw of SPS10LS, based on the analytics performed on 27 May 2016).A single dermal application was made and was followed by a 14-day observation period.

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not required

Details on study design:

OBSERVATIONS
Clinical Observations
Clinical observations were performed on the day of treatment at 1 and 5 hours after application of the test item and once each day for 14 days thereafter.Observations included the skin and fur, eyes and mucous membranes, the 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.
Skin Irritation:Adverse skin reactions at the site of application were recorded daily following the removal of the dressing.
Body Weight Measurement: The body weights were recorded on Day 0 (before test item administration) and on Days 7 and 14 just before necropsy.
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:

male/female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

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

Clinical signs:

There were no systemic clinical signs noted in any animal throughout 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

SEX: Male

Cage No.

Animal No.

Observations

Observation days

Frequency

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1h

5h

1

1777

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

2

1778

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

3

1779

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

4

1780

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

5

1781

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

DOSE LEVEL: 2000 mg/kg bw

SEX: Female

Cage No.

Animal No.

Observations

Observations days

Frequency

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1h

5h

6

1782

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

7

1783

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

8

1784

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

9

1785

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

10

1786

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

Remarks:

+ = present

h = hour (s)

Treatment day = Day 0

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

 

 

BODY WEIGHT DATA

DOSE LEVEL: 2000 mg/kg bw						SEX: Male
Cage No.	Animal No.	Body weight (g) Days			Body Weight Gain (g)
		0	7	14	0-7	7-14	0-14
1	1777	235	299	363	64	64	128
2	1778	217	277	324	60	47	107
3	1779	244	304	364	60	60	120
4	1780	245	306	358	61	52	113
5	1781	250	318	377	68	59	127
Mean:		238.2	300.8	357.2	62.6	56.4	119.0
Standard deviation:		13.0	15.0	19.8	3.4	6.8	9.0
DOSE LEVEL: 2000 mg/kg bw						SEX: Female
Cage No.	Animal No.	Body weight (g) Days			Body Weight Gain (g)
		0	7	14	0-7	7-14	0-14
6	1782	224	227	242	3	15	18
7	1783	218	256	275	38	19	57
8	1784	226	241	258	15	17	32
9	1785	220	245	266	25	21	46
10	1786	231	259	271	28	12	40
Mean:		223.8	245.6	262.4	21.8	16.8	38.6
Standard deviation:		5.1	12.8	13.0	13.3	3.5	14.7

 

NECROPSY FINDINGS

DOSE LEVEL: 2000 mg/kg bw					SEX: Male
Cage No.	Animal No.	Necropsy Date/ Necropsy Day	External Observations	Internal Observations	Organ/Tissue
1	1777	02 August 2016 Day 14	No external observations	No internal observations	Not applicable
2	1778	02 August 2016 Day 14	No external observations	No internal observations	Not applicable
3	1779	02 August 2016 Day 14	No external observations	No internal observations	Not applicable
4	1780	02 August 2016 Day 14	No external observations	No internal observations	Not applicable
5	1781	02 August 2016 Day 14	No external observations	No internal observations	Not applicable
DOSE LEVEL: 2000 mg/kg bw					SEX: Female
Cage No.	Animal No.	Necropsy Date/ Necropsy Day	External Observations	Internal Observations	Organ/Tissue
6	1782	02 August 2016 Day 14	No external observations	No external observations	Not applicable
7	1783	02 August 2016 Day 14	No external observations	No external observations	Not applicable
8	1784	02 August 2016 Day 14	No external observations	No external observations	Not applicable
9	1785	02 August 2016 Day 14	No external observations	No external observations	Not applicable
10	1786	02 August 2016 Day 14	No external observations	No external observations	Not applicable

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal lethal dose (LD0 value) of the test item Sodium methanesulfonate was found to be equal to or above 2000 mg/kg bw in male and female Crl:WI rats

Executive summary:

An acute dermal toxicity study was performed with test item Sodium methanesulfonate in Crl:WI rats, in compliance with OECD Guideline No.: 402. A limit test was carried out at 2000 mg Sodium methanesulfonate/kg body weight (equivalent to 4.23 mL/kg bw of SPS10LS) in both sexes (5 rats/sex). The test item was applied as a single dermal 24-hour exposure followed by a 14-day observation period. Clinical observations were performed on all animals at 1 and 5 hours after dosing and daily for 14 days thereafter. Body weight was measured prior to dosing on Day 0 and on Days 7 and 14. Gross macroscopic examination was performed on all animals at the end of the 2-week observation period (Day 14).

Sodium methanesulfonate did not cause mortality at the dose level of 2000 mg/kg bw. There were no systemic clinical signs noted in any animal throughout the study. No local dermal signs were observed after treatment with the test item during the 14 days observation period. 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 dermal lethal dose (LD0 value) of the test item Sodium methanesulfonate was found to be equal to or above 2000 mg/kg bw in male and female Crl:WI rats.