3-(1-(4-amino-3-methyl-5-sulphonatophenyl)-1-(4-amino-3-sulphonatophenyl)methylene)cyclohexa-1,4-dienesulphonic acid

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from authoritative databases

Data source

Reference

Reference 1

Reference Type:

other: Authoritative database

Title:

Hazardous Substances Data Bank (HSDB) for Methanesulfonic acid

Author:

U.S National Library of Medicine

Year:

2010

Bibliographic source:

Hazardous Substances Data Bank (HSDB) for Methanesulfonic acid, U.S National Library of Medicine, 2010

Reference 2

Reference Type:

secondary source

Title:

High Production Volume Information System (HPVIS) for Methanesulfonic acid (75-75-2)

Author:

USEPA

Year:

2009

Bibliographic source:

High Production Volume Information System (HPVIS) for Methanesulfonic acid (75-75-2); Available from November 20, 2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Buehler test

Principles of method if other than guideline:

To assess the skin sensitization potential of Methanesulfonic acid on guinea pig skin according to Buehler method

GLP compliance:

no

Type of study:

Buehler test

Justification for non-LLNA method:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Methanesulphonic acid

EC Number:

200-898-6

EC Name:

Methanesulphonic acid

Cas Number:

75-75-2

Molecular formula:

CH4O3S

IUPAC Name:

methanesulfonic acid

Test material form:

liquid

Details on test material:

Name of the test chemical: Methanesulfonic acid
Molecular Formula:CH4O3S
Molecular Weight: 96.1056 g/mol
InChI: 1S/CH4O3S/c1-5(2,3)4/h1H3,(H,2,3,4)
Substance Type: Organic
Physical State:Liquid

Specific details on test material used for the study:

Name of the test chemical: Methanesulfonic acid
Molecular Formula:CH4O3S
Molecular Weight: 96.1056 g/mol
InChI: 1S/CH4O3S/c1-5(2,3)4/h1H3,(H,2,3,4)
Substance Type: Organic
Physical State:Liquid

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Spragu e Dawley , Indiana
- Age at study initiation: No Data available
- Weight at study initiation:
males: 429.6 ± 18.8g
females: 400.5 ± 27.6g

Study design: in vivo (non-LLNA)

Induction

Route:

epicutaneous, open

Vehicle:

water

Concentration / amount:

Concentration :50%
Amount : 0.3 ml

Day(s)/duration:

6 hours

Adequacy of induction:

not specified

Challenge

No.:

#1

Route:

epicutaneous, open

Vehicle:

water

Concentration / amount:

25%

Day(s)/duration:

24 hours

Adequacy of challenge:

not specified

No. of animals per dose:

20

Details on study design:

RANGE FINDING TESTS: Yes
A preliminary study was conducted in order to determine the concentrations to be tested in the main study. The irritation potential of methane sulfonic acid 70% at levels of
undiluted, 50%, 25%, 10%, 5%, 2.5%, 1% and 0.5% was evaluated in two groups of four animals each. Four levels of test material were evaluated per animals. Dilutions were obtained with distilled water (w/v). 0.3 ml of different solutions was applied into a 25 mm Hill Top Chamber, which were placed on animals clipped back for 6 hours. The day after, animals were depilat ed and two hours later, examined for irritation, according the following scale. Another score was performed 40h after exposure.

Grading scheme for Pilot Study
-Grading system:
0: no reaction
±: slight, patch y erythema
1: slight but confluent or m oderate
patchy erythema
2: moderate erythema
3: severe erythema wi th or without oedema

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours
- Test groups: 5 males + 5 females
- Control group: 5 males + 5 females
- Site: left shoulder
- Frequency of applications: Thrice in 14 days
- Duration: 14 days
- Concentrations: 50%-0.3ml

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 1 (on day 28)
- Exposure period: 24 hrs
- Test groups: 5 males + 5 females
- Control group: 5 males + 5 females
- Site: right flank
- Concentrations: 25%-0.3ml
- Evaluation (hr after challenge):24hrs

Challenge controls:

vehicle control used

Positive control substance(s):

not specified

Results and discussion

Positive control results:

no data available

In vivo (non-LLNA)

Results

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

25%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no data available

Remarks on result:

no indication of skin sensitisation

Any other information on results incl. tables

RESULTS OF PILOT STUDY:

Undiluted methane sulfonic acid 7 0% produced grades of 2, 1 and ±, with oedema, blanching and scabbing on two sites. 50%, 25%, 10%, 5%, 2.5% and 1% produced grades of ±, while 0.5% produced grades of ± and 0. Consequently, the 50% concentration was chosen for use at induction for the test group, since it caused no greater than mild to moderate primary irritation. Moreover, the 25% concentration was selected for challenge, because it caus ed no more than slight irritation.

RESULTS OF TEST

-Sensitization reaction: None of the test animals responded with a skin grade that would have been suggestive of sensitization

Applicant's summary and conclusion

Interpretation of results:

other: Not sensitizing

Conclusions:

20 guinea-pigs were induced by 50% of methane sulfonic acid 70% solution (i.e. 35% of methane sulfonic acid) and challenged by 25% of methane sulfonic acid 70% solution (i.e. 17.5% of methane sulfonic acid). None of the test animals responded with a skin grade that would have been suggestive of sensitization.
Hence, methane sulphonic acid can be considered to be not sensitizing to the skin of Hartley guinea pigs.

Executive summary:

The dermal sensitization potential of Methanesulfonic acid was assessed in guinea pigs according to Buehler method.

The irritation potential of methane sulphonic acid 70% at levels of undiluted, 50%, 25%, 10%, 5%, 2.5%, 1% and 0.5% was evaluated in two groups of four animals each prior to the sensitization study.The 50% concentration from the preliminary study was chosen for use at induction for the test group, since it caused no greater than mild to moderate primary irritation. Moreover, the 25% concentration was selected for challenge, because it caused no more than slight irritation.

20 Hartley guinea pigs (10/sex) were induced by 50% of methane sulphonic acid. On day 1, dermal application of 0.3 ml of test substance (treated group) or with the vehicle (control group) was performed on the left shoulder. On day 7, the same region received another topical application. On day 14, this same site was treated by a last topical application. All these applications lasted approximately 6 hours. On day 28, all the animals were challenged with 0.3 ml of the test substance at the concentration of 25% in their right flank. The challenge exposure lasted for 24 hours. Water served as vehicle control and 5guinea pigs/sex were used in the control group. The dermal reactions were observed and scored 24 hours after the challenge exposure.

20 guinea-pigs were induced by 50% of methane sulphonic acid 70% solution/ (i.e. 35% of methane sulphonic acid) and challenged by 25% of methane sulphonic acid 70% solution (i.e. 17.5% of methane sulphonic acid). None of the test animals responded with a skin grade that would have been suggestive of sensitization.

Hence, methane sulphonic acid can be considered to be not sensitizing to the skin of Hartley guinea pigs.