Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From 1993-10-07 to 1993-11-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test article name : Sodium methylmercaptide
CAS RN: 5188-07-8
Origin: Elf Aquitaine, Lacq
Batch: 93-7074

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Centre d'élevage Lebeau, 78950 Gambais, France
- Age at study initiation: no data
- Weight at study initiation: 404 +/- 26 g for males and 410 +/- 20 g for females
- Housing: individually in polycarbonate cages
- Diet (ad libitum): Guinea-pigs sustenance reference 106 diet, UAR, France
- Water (e.g. ad libitum): filtered tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 50 +/- 20
- Air changes: non-recycled and filtered
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
physiological saline
Concentration / amount:
1st application: Induction 1 % active substance intracutaneous
2nd application: Induction 1 % active substance occlusive epicutaneous
3rd application: Challenge 10 % active substance occlusive epicutaneous
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
1st application: Induction 1 % active substance intracutaneous
2nd application: Induction 1 % active substance occlusive epicutaneous
3rd application: Challenge 10 % active substance occlusive epicutaneous
No. of animals per dose:
10 for control, 20 for the test substance
Details on study design:
Thirty guinea-pigs (15 males and 15 females) were allocated to 2 groups: a control group 1 (5 males and 5 females) and a treated group 2 (10 males and 10 females). The sensitization potential of the test substance was evaluated after a 10-day induction period during which time the animals were treated with the vehicle (control group) or the test substance (treated group). 
On day 1, in presence of Freund's complete adjuvant, 0.1 ml of the test substance at a concentration of 1 % in the vehicle was administered by intradermal route. 
On day 8, 0.5 ml of the test substance at a concentration of 1 % in the vehicle was applied by cutaneous route during 48 hours by means of an occlusive dressing. 
After a period of 12 days without treatment, a challenge cutaneous application of 0.5 ml of the vehicle (left flank) and 0.5 ml of the test substance at a concentration of 10% in the vehicle (right flank) were administered to all animals. The test substance and the vehicle were prepared on a dry compress then applied to the skin and held in place for 24 hours by means of an occlusive dressing. Cutaneous reactions on the challenge application sites were then evaluated 24 and 48 hours after removal of the dressing. After the final scoring period, the animals were sacrificed.  No skin samples were taken from the challenge application sites from all the animals.
Challenge controls:
0.5 ml of the vehicle (left flank)
Positive control substance(s):
yes
Remarks:
The sensitivity of the guinea-pigs in C.I.T. experimental conditions were checked in a concurrent study with a positive sensitizer: Dinitro 2.4 Chlorobenzene (DNCB).

Study design: in vivo (LLNA)

Positive control substance(s):
other: DCNB

Results and discussion

Positive control results:
The guinea pig showed a satisfactory sensitization response in 100 % using the positive sensitizer (DCNB).

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.5 ml of a 10% solution
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.5 ml of a 10% solution. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.5 ml of a 10% solution
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5 ml of a 10% solution. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
1st reading
Group:
positive control
Dose level:
0.5 ml of a 0.5% solution
No. with + reactions:
5
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. Group: positive control. Dose level: 0.5 ml of a 0.5% solution. No with. + reactions: 5.0. Total no. in groups: 5.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.5 ml of a 0.5% solution
No. with + reactions:
5
Total no. in group:
5
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.5 ml of a 0.5% solution. No with. + reactions: 5.0. Total no. in groups: 5.0.

Any other information on results incl. tables

No clinical signs and no deaths were noted. After 24 and 48
hours following removal of the dressing of the cutaneous
challenge (test substance), no cutaneous reactions were   
recorded. 

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
According to the maximization method established by Magnusson and Kligman, no cutaneous reactions attributable to the sensitization potential of the test substance, SODIUM METHYLMERCAPTIDE, at the maximum non-irritant concentration of 10% were observed in guinea-pigs.

Classification: not sensitizing
Executive summary:

Sodium methanethiolate was tested in an OECD Test Guideline 406 skin sensitization study (maximization test) with guinea pigs. Induction was accomplished by an intradermal injection of a 1% solution of sodium methanethiolate in Freund’s adjuvant on day 1 followed by a topical application of a 1% solution of sodium methanethiolate on day 8 (covered for 48 hours) to 10 animals/sex in the treated group and 5 animals/sex in the control. On day 22, a challenge dose of a 10% solution of sodium methanethiolate was applied topically (covered for 24 hours). Skin reactions were evaluated 24 and 48 hours following the removal of the dressing after the challenge dose. No clinical signs or deaths were observed. At 24 and 48 hours following the removal of the dressing after the challenge dose, no cutaneous reactions were recorded. It was concluded that sodium methanethiolate is not a skin sensitizer. Satisfactory sensitization response was observed using the positive control, dinitrochlorobenzene.