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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report date:
2003

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
Cited as Directive 96/54/EC, B.6
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Chemical structure
Reference substance name:
Methanesulphonyl chloride
EC Number:
204-706-1
EC Name:
Methanesulphonyl chloride
Cas Number:
124-63-0
Molecular formula:
CH3ClO2S
IUPAC Name:
methanesulfonyl chloride
Details on test material:
Origin: Atofina, Riverview plant
Batch: 1491F10CD1
Dry extract: 99.9 %

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories France, L’Arbresle, France.
- Age at study initiation: 1-2 months old
- Weight at study initiation: 458 ± 19 g for the males and 383 ± 16 g for the females
- Housing: individually in polycarbonate cages with stainless steel lid
- Diet (e.g. ad libitum): 1096 pelleted diet (SAFE, Villemoisson, Epinay-sur-Orge, France)
- Water (e.g. ad libitum): drinking water filtered by a FG Millipore membrane (0.22 micron)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 30 to 70
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air.
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
paraffin oil
Concentration / amount:
Intradermal: 2 mg/l
Epicutaneous: 200 mg/ml
Challenge: 200, 50 or 20 mg/ml
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
Intradermal: 2 mg/l
Epicutaneous: 200 mg/ml
Challenge: 200, 50 or 20 mg/ml
No. of animals per dose:
20, test group, 10 control group
Details on study design:
Methanesulfonyl chloride was provided as a 200.25 mg/mL solution in paraffin oil for ease of manipulation.
Thirty guinea pigs were allocated to two groups: a control group of five males and five females and a treated group of ten males and ten females.
On day 1, three pairs of intradermal injections were performed in the interscapular region of all animals:
* Freund's complete adjuvant (FCA) diluted to 50% with 0.9% NaCl (both groups),
* test item at the concentration of 2 mg/mL (i.e. solution at 1%) in paraffin oil (treated group) or vehicle alone (control group),
* test item at the concentration of 2 mg/mL (i.e. solution at 1%) in a mixture FCA/0.9% NaCl (50/50) (treated group) or vehicle at the concentration of 50% in a mixture FCA/0.9% NaCl (50/50) (control group).
On day 8, the animals of the treated group received a topical application of the test item at the concentration of 200 mg/mL in paraffin oil (i.e. undiluted solution) to the same test site, which was then covered by an occlusive dressing for 48 hours. The animals of the control group
received an application of vehicle under the same experimental conditions.
On day 22, all animals of both groups were challenged by a cutaneous application of the test item at the concentration of 200 mg/mL in paraffin oil (i.e. undiluted solution) to the right flank. The test item was maintained under an occlusive dressing for 24 hours. The vehicle was applied to the left flank under the same experimental conditions.
Skin reactions were evaluated approximately 24 and 48 hours after removal of the dressing.
As equivocal cutaneous reactions were noted after the first challenge, a second challenge application was performed on day 40. For this second challenge application, a control group of ten naive animals (five males and five females) was included in the study. The test item in paraffin oil was applied at the concentration of 50 mg/mL (i.e. solution at 25% (w/w)) to the left flank and at the concentration of 20 mg/mL (i.e. solution at 10% (w/w)) to the right flank of
animals of all groups, under the same experimental conditions as for the first challenge application.
At the end of the study, animals were killed without examination of internal organs.
No skin samples were taken from the challenge application sites.
Positive control substance(s):
yes
Remarks:
Mercaptobenzothiazole

Results and discussion

Positive control results:
Mercaptobenzothiazole at the concentration of 20% (w/w) induced positive skin sensitization reactions in 80% (8/10) guinea pigs.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
200 mg/ml
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
discrete or patchy erythema (grade 1)
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 200 mg/ml. No with. + reactions: 8.0. Total no. in groups: 10.0. Clinical observations: discrete or patchy erythema (grade 1).
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
200 mg/ml
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
moderate or intense erythema (grade 2 or 3)
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 200 mg/ml. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: moderate or intense erythema (grade 2 or 3).
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
200 mg/ml
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
discrete or moderate erythema (grade 1 or 2)
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 200 mg/ml. No with. + reactions: 9.0. Total no. in groups: 10.0. Clinical observations: discrete or moderate erythema (grade 1 or 2).
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
200 mg/ml
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
moderate or intense erythema (grade 2 or 3)
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 200 mg/ml. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: moderate or intense erythema (grade 2 or 3).
Reading:
rechallenge
Hours after challenge:
24
Group:
other: naive control group
Dose level:
50 mg/ml
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: other: naive control group. Dose level: 50 mg/ml. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
50 mg/ml
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
discrete erythema (grade 1)
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 50 mg/ml. No with. + reactions: 2.0. Total no. in groups: 10.0. Clinical observations: discrete erythema (grade 1).
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
50 mg/ml
No. with + reactions:
13
Total no. in group:
18
Clinical observations:
discrete or moderate erythema (grade 1 or 2)
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 50 mg/ml. No with. + reactions: 13.0. Total no. in groups: 18.0. Clinical observations: discrete or moderate erythema (grade 1 or 2).
Reading:
rechallenge
Hours after challenge:
48
Group:
other: naive control group
Dose level:
50 mg/ml
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: other: naive control group. Dose level: 50 mg/ml. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
50 mg/ml
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
discrete erythema (grade 1)
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 50 mg/ml. No with. + reactions: 2.0. Total no. in groups: 10.0. Clinical observations: discrete erythema (grade 1).
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
50 mg/ml
No. with + reactions:
11
Total no. in group:
18
Clinical observations:
discrete or moderate erythema (grade 1 or 2)
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 50 mg/ml. No with. + reactions: 11.0. Total no. in groups: 18.0. Clinical observations: discrete or moderate erythema (grade 1 or 2).
Reading:
rechallenge
Hours after challenge:
24
Group:
other: naive control group
Dose level:
20 mg/ml
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: other: naive control group. Dose level: 20 mg/ml. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
20 mg/ml
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
discrete or moderate erythema (grade 1 or 2)
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 20 mg/ml. No with. + reactions: 9.0. Total no. in groups: 10.0. Clinical observations: discrete or moderate erythema (grade 1 or 2).
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
20 mg/ml
No. with + reactions:
18
Total no. in group:
18
Clinical observations:
discrete to intense erythema (grades 1 to 3)
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 20 mg/ml. No with. + reactions: 18.0. Total no. in groups: 18.0. Clinical observations: discrete to intense erythema (grades 1 to 3).
Reading:
rechallenge
Hours after challenge:
48
Group:
other: naive control group
Dose level:
20 mg/ml
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: other: naive control group. Dose level: 20 mg/ml. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
20 mg/ml
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
discrete or moderate erythema (grade 1 or 2)
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 20 mg/ml. No with. + reactions: 9.0. Total no. in groups: 10.0. Clinical observations: discrete or moderate erythema (grade 1 or 2).
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
20 mg/ml
No. with + reactions:
18
Total no. in group:
18
Clinical observations:
discrete to intense erythema (grades 1 to 3) with crust
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 20 mg/ml. No with. + reactions: 18.0. Total no. in groups: 18.0. Clinical observations: discrete to intense erythema (grades 1 to 3) with crust.

Any other information on results incl. tables

No systemic clinical signs and no deaths related to treatment were noted during the study.
After the first challenge application, a discrete or moderate erythema was observed in 9/10 animals of the control group.
In the treated group, a moderate or intense erythema was noted in all animals. Dryness of the skin, crusts (which have sometimes masked the evaluation of erythema) and oedema were also recorded.
After the second challenge application, no cutaneous reactions were observed in the animals of the control group 3.
In the control group 1, a discrete erythema was observed on the left flank of 2/10 animals and a discrete or moderate erythema was noted on the right flank of 9/10 animals at the 24 and 48-hour readings.
In the treated group, a discrete or moderate erythema was recorded on the 

left flank of 13/18 animals at the 24-hour reading and 11/18 animals at the 48-hour reading. On the right flank, a discrete to intense erythema was observed in all animals at the 24-hour reading; it was masked by crusts in most of them at the 48-hour reading. Oedema and dryness of the skin were noted in almost all animals.
These results confirmed those of the first challenge application. The cutaneous reactions observed in all the animals of the treated group after the first challenge application, which were of higher severity than those recorded in the animals of the control group, were therefore attributed to delayed contact hypersensitivity.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
According to the maximization method of Magnusson and Kligman, Methanesulfonyl chloride induces delayed contact hypersensitivity in 20/20 (100%) guinea pigs.

Classification: sensitizing
Executive summary:

In a test performed according to the maximization method of Magnusson and Kligman, the OECD guideline #406 and the GLP, methanesulfonyl chloride (purity 99.9%) was administered to guinea pigs at the concentrations of 2 mg/ml intracutaneously and 200 mg/ml in paraffin oil under an occlusive patch.

The challenge concentration of 200 mg/ml under an occlusive patch induced delayed contact hypersensitivity in 20/20 (100%) guinea-pigs.Methanesulfonyl chloride was considered as a strong skin sensitizer.