Methanesulphonic acid

Endpoint summary

Description of key information

Based on the pH value (< 2), the Methanesulphonic acid (MSA) is classified as corrosive to the skin, this is unterlined by in vitro (Corrositex) and in vivo test (mouse tail contact) indicating a corrosive potential GHS Cat 1B. Further an OECD 405 similar eye irriation test with rabbits shows servere irritating / corrosive effects.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation / corrosion

Remarks:

in vitro

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 435 (In Vitro Membrane Barrier Test Method for Skin Corrosion)

Principles of method if other than guideline:

Corrositex continuous time monitor assay was used to detect the corrosive potential of the test substance. This assay is used as a standardized and quantitative in-vitro corrosivity test. The test is based on the time that is required for the test sample to pass through a biobarrier membrane and produce a change in the Chemical Detection System. Both anhydrous methane sulfonic acid (MSA) and 70 % MSA were tested.

GLP compliance:

no

Species:

other: in vitro Corrositex Assay

Type of coverage:

other: not applicable

Vehicle:

other: unchanged (no vehicle) for anhydrous MSA and water for 70% MSA

Amount / concentration applied:

TEST MATERIAL
- Concentration (if solution): anhydrous and 70 % MSA

Duration of treatment / exposure:

4 hours, single exposure

Observation period:

4 hours

Number of animals:

not applicable

Details on study design:

Corrositex Assay:
- The Corrositex Biobarrier Membranes consist of a reconstituted collagen matrix was placed onto the CDS solution contained in test vials. The biobarrier membrane batch was qualified by testing the positive control (NaOH), a blank vial serves as negative control. Prior to testing a qualification screen and a categorization screen are performed to validate if the assay is appropriate for testing of the substance and to categorize the test substance as weak or strong acid/base, respectively.
- For testing, 500 µl of the test substance are placed on the membrane, 4 replicates are prepared and tested at the same time.
- Once the test substance is placed on the membrane disc, the vials are continuously observed for the first 10 minutes and then at approximately 5-minute intervals for up to 4 hours. The elapsed time from test substance application until CDS colour change is recorded.


SCORING SYSTEM:
Time required for CDS (chemical detection system) colour change (minutes):
0 to 3 min: corrosive (Packing Group I, GHS Cat 1A)
> 3 to 60 min: corrosive (Packing Group II, GHS Cat 1B)
> 60 to 240 min: corrosive (Packing Group III, GHS Cat 1C)
> 240 min: non-corrosive

Irritant / corrosive response data:

Average break-through time (mean of 4 determinations): 7 min 02 s (70 % methane sulfonic acid) and 3 min 43 s (anhydrous).

Results corrosivity test:

Test Article		Break Through Time (min:sec)
Sponsor's designation	MA Number	Vial 1	Vial 2	Vial 3	Vial 4	Mean	Packing group	pH*
70 % Methane Sulfonic Acid	95BW22	7:20	7:00	6:50	6:57	7:02	II	0
Methane Sulfonic Acid	95BW23	3:50	3:38	3:50	3:35	3:43	II	0
NaOH	-	12:23	NA	NA	NA	12:23	NA	NA

*100 µl/ml solution in deionized water NA - Not Applicable

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions (lack of detailed documentation)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

lack of detailed documentation

Principles of method if other than guideline:

Single administration of 0.1 ml of the test substance was placed in the conjuctival sac of one eye of each of two rabbits. The treated eye of one of the two animals was rinsed with flowing water (initiated 20 to 30 seconds after instillation and continued for one minute). The treated eye of the other animal was kept unwashed. The reaction was then scored periodically for 7 days.

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eyes served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): undiluted (anhydrous solution)

Duration of treatment / exposure:

eye of one rabbit was washed out after 20 seconds and eye of another rabbit was not washed out

Observation period (in vivo):

7 days (the reaction was abserved at 10 min, 1h, 2h, 3h, 4h, 24h, 48h, 72h, 4 days, 5 days, 6 days and 7 days)

Number of animals or in vitro replicates:

2

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: with flowing water for 1 minute (only one animal)
- Time after start of exposure: 20 seconds

SCORING SYSTEM: irritation responses were scored (no data on scoring system)

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

unwashed eye

Time point:

other: 24-48-72 h

Score:

4

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

unwashed eye

Time point:

other: 24-48-72 h

Score:

0

Reversibility:

other: no effects

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

washed eye

Time point:

other: 24-48-72 h

Score:

4

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

washed eye

Time point:

other: unwashed eye

Score:

0

Reversibility:

other: no effects

Irritant / corrosive response data:

Unwashed eye:
The reaction involved all ocular tissues and occured immediately. The conjunctivae became completely necrotic (white) without evident swelling. The iris was dilated with ragged edges and failed to react to light. The cornea opacified completely within 24 hours.

Washed eye:
The reaction did not differ significantly from that of the unwashed eye.

Other effects:

Each instillation caused excruciating pain.

Irritation scores:

Time	Unwashed eye				Washed eye
	Cornea	Iris	Redness	Chemosis	Cornea	Iris	Redness	Chemosis
10 min	2	2	N	0	2	2	N	0
1 h	2	2	N	0	2	2	N	0
2 h	2	2	N	0	4	?	N	0
3 h	2	2	N	0	4	?	N	0
4 h	2	2	N	0	4	?	N	0
24 h	4	?	N	0	4	?	N	0
48 h	4	?	N	0	4	?	N	0^D
72 h	4	?	N	0	4	?	N	0^D
4 days	4	?	N	0	4	?	N	0^D
5 days	4	?	N	0	4	?	N	0^D
6 days	4	?	N	0	4	?	N	0^D
7 days	4	?	N	0	4	?	N	0^D

N: total necrosis

D: discharge

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

The available information from acute dermal toxicity testing and on the pH value (<2) meet already the criteria for classification of MSA as corrosive to the skin, therefore no further animal test is suggested.

 

Nevertheless, the further available information shows that MSA is corrosive to biomembranes based on the results of Corrositex continuous time monitor assay (ElfAtochem 1995). This assay is used as a standardized and quantitative in-vitro corrosivity test. The test is based on the time that is required for the test sample to pass through a biobarrier membrane and produce a change in the Chemical Detection System. Both anhydrous MSA and 70 % MSA were tested. The average break-through time (mean of 4 determinations) were found to be 7 min 02 s (70 % methane sulfonic acid) and 3 min 43 s (anhydrous) indicating corrosive potential (GHS Cat 1B; EU R34). This result is furthermore underlined by a less reliable 1h mouse tail contact study showing corrosive results (Pennwalt 1976).

The eye irritation potential was investigated in an old and lower reliable OECD 405 similar study with rabbits (Pennwalt 1978). As servere cornea effects were observed (grading 4) and the effects were not reversible within 7 days the substance was to be servere irritating / corrosive to eye.

Summarising MSA is corrosive to skin GHS, CAT 1B.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

There is sufficient information available which warrant classification of methanesulfonic acid as corrosive to the skin. According to Annex VI to the CLP regulation (EC) 1272/2008 the substance meet criteria for C, R34 and Category 1B according to GHS criteria. Classification as corrosive implies also serious eye damage.

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.