Methanesulphonic acid

Endpoint summary

Description of key information

Methanesulphonic acid (MSA) is corrosive to the skin (pH value <2), public available information states LD50 oral between 300 and 2000 mg/kg bw and LD 50 dermal between 200 and 2000 mg/kg bw. 

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:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with GLP.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Qualifier:

according to guideline

Guideline:

other: EPA 40 CFR Part 792

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Inc., Portage, Michigan
- Weight at study initiation: 205.3 g mean (males), 204.7 g mean (females)
- Diet (e.g. ad libitum): PMI certified Rodent Chow #5002
- Water (e.g. ad libitum): tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 38-61
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 0.38, 0.75, 1.13 ml/kg bw

MAXIMUM DOSE VOLUME APPLIED: 1.13 ml/kg bw

Doses:

500, 1000, 1500 mg/kg body weight

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: observations: no data; weighing: every 7 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, mortality, necropsy

Statistics:

The LD50 was determined separately for both sexes using the method of Litchfield and Wilcoxon.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 157.5 mg/kg bw

95% CL:

748 - 1 791.1

Remarks on result:

other: 70 % methane sulfonic acid

Sex:

male

Dose descriptor:

LD50

Effect level:

860.1 mg/kg bw

95% CL:

540.1 - 1 369.7

Remarks on result:

other: 70 % methane sulfonic acid

Sex:

female

Dose descriptor:

LD50

Effect level:

2 407.6 mg/kg bw

95% CL:

944.2 - 6 139.2

Remarks on result:

other: 70 % methane sulfonic acid

Mortality:

Males: 1/5, 3/5, and 4/5 deaths at 500, 1000, and 1500 mg/kg bw, respectively.
Females: 1/5, 0/5, and 3/5 deaths at 500, 1000, and 1500 mg/kg bw, respectively.

Clinical signs:

other: The most notable clinical abnormalities observed during the study included salivation, breathing abnormalities, wobbly gait, decreased activity, decreased defecation, rough haircoat, urine/fecal stain and dark material around the facial area.

Gross pathology:

The most notable gross internal findings were observed in the animals that died and included abnormal content and reddened/thickened mucosa and discolouration in the digestive tract, dark red foci on the liver and blackish-purple spleens. No significant gross findings were observed at necropsy on day 14.

Other findings:

- Potential target organs: Digestive tract

Table: Mortalities during 14 days of observation period

Dose group (mg/kg bw)	No. of animals	Study day														Mortality
		0	1	2	3	4	5	6	7	8	9	10	11	12	13-14
500	5 M	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1/5
1000	5 M	3	0	0	0	0	0	0	0	0	0	0	0	0	0	3/5
1500	5 M	1	1	1	1	0	0	0	0	0	0	0	0	0	0	4/5
500	5 F	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1/5
1000	5 F	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0/5
1500	5 F	1	1	1	0	0	0	0	0	0	0	0	0	0	0	3/5

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 157.5 mg/kg bw

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to OECD guideline with GLP, acceptable with restrictions.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

Limit dose: 1000 mg/kg

Qualifier:

according to guideline

Guideline:

other: 49 CFR 173.132

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Millbrook Breeding Labs, MA
- Weight at study initiation: males 2.5-3.1 Kg, females 2.8-3.0 Kg
- Housing: 1 per cage
- Diet (e.g. ad libitum): Fresh PMI rabbit chow
- Water (e.g. ad libitum): drinking water
- Acclimation period: 1 week


ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- % coverage: 10
- Type of wrap if used: no data

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, distilled water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5 ml/kg bw
- Concentration (if solution): 200 mg/ml
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

1000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observations 1 and 2 hours postdose and once daily thereafter; dermal responses 24 hours postdose and on days 7 and 14; weighing pretest and at termination
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 1 000 mg/kg bw

Mortality:

No mortality occured, all animals survived the application of 1000 mg/kg bw Methane Sulfonic Acid.

Clinical signs:

other: Instances of few faces were the only abnormal physical signs noted during the observation period. Dermal responses were slight to well defined on day 1, absent to severe on day 7 and absent to slight on day 14.

Gross pathology:

Necropsy results were normal.

No necrosis reported under the study conditions chosen.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Additional information

The substance is classified as corrosive to the skin. Therefore, in accordance with the REACH information requirements (column 2 of the REACH Annexes VII and VII) testing for acute toxicity does not need to be conducted.

 

Nevertheless, some reliable and relevant information on the acute toxicity is publically available (ElfAtochem1997/Elfatochem1998) stating LD50 values (oral-gavage) between 300 and 2000 mg/kg (even if corrected to active ingredient) bw in male and female rats applicating 70% MSA or anhydrous MSA. These acute oral effects were not observed when MSA was neutralised with NaOH (see 7.8.1, Chevron 2005).

Additionally information from a acute dermal toxicity study with rabbits according to OECD 402 shows no deaths up to and including 1000 mg/kg bw (MBRL 2002) but in a less reliable supporting dermal toxicity studies 2/3 animals where found death 24h after dermal application of 2000 mg/kg bw (Pennwalt 1978). Therefore a acute dermal toxicity category 4 ghs, eu is assumed.

Further Saturation concentration (1.88mg/m3) of MSA does not lead to acute toxic (systemic) effects in mice (Pennwalt 1976).

All these effects may also be attributed to the corrosive nature of the test substance therefore no further testing is suggested.

Justification for classification or non-classification

Acute effects are due to the corrosive properties of MSA. These effects observed lead to some deaths in higher dosegroups. Thereforee MSA has to be labeled as follows:

EU classification according to Annex I of Directive 67/548/EEC: Xn; R21/22 Harmful in contact with skin and if swallowed.

GHS classification (GHS UN rev.3, 2009): CAT 4 (oral), H302: Harmful if swallowed and CAT 4 (dermal), H312: Harmful in contact with skin..

Furthermore due to the corrosive character which causes the toxic effect an irritation of respiratory system can not be excluded when inhaled. Therefore MSA is further classified as STOT SE 3, H335: May cause respiratory irritation.