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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:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
LLNA method had not yet been adopted when this study was performed.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: granular
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 6X07A106
- Expiration date of the lot/batch: May 16, 1997

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: ambient temperature

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Test substance was dispersed in cold water, then heated to 80 degrees C for 10 minutes.
- Final dilution of a dissolved solid, stock liquid or gel: 10% and 30% dilution in water

FORM AS APPLIED IN THE TEST (if different from that of starting material): solution

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Germany
- Age at study initiation: 2-3 weeks
- Weight at study initiation: 175-400 g

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Day(s)/duration:
one week
Adequacy of induction:
other: Concentration in dermal application was highest tolerable irritating concentration with pretreatment with sodium lauryl sulfate.
Route:
intradermal
Vehicle:
other: FCA and vehicle 1:1
Day(s)/duration:
1 Day
Adequacy of induction:
other: selected test concentration
Route:
intradermal
Vehicle:
other: FCA and isotonic saline 1:1
Concentration / amount:
0%
Day(s)/duration:
1 Day
Challenge
No.:
#1
Route:
other: epicutaneous
Vehicle:
water
Concentration / amount:
10% and 30%
Day(s)/duration:
14 days after last induction
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
5 males and 5 females in the test group.
3 males and 3 females in the control group.
Details on study design:
RANGE FINDING TESTS:
A preliminary study was performed to determine the highest tolerated concentration. Three animals were injected intradermally with 1%, 3%, 10%, and 30% test substance in water. 30% was the highest concentration that could be injected. All animals showed necrosis at the 3%, 10%, and 30% injection sites at the 24 hr observation. At the 1% injection sites, all animals were given a dermal irritation score of 2, and abscesses were noted at 24 hrs after injection. Another three animals were tested by topical application at 10% and 30% test substance. No animals showed any irritation at either the 24 or 48 hr readings.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: 2 exposures 1 week apart
- Test groups: Test animals were injected with a solution of 1:1 FCA/isotonic saline, 0.3% test substance in water, and 0.3% test substance in FCA/water 1:1. One week later they were pretreated with SLS and given topical applicaiton of 30% test substance.
- Control group: Control animals were injected with a solution of 1:1 FCA/isotonic saline, water, and FCA/water 1:1. One week later they were pretreated with SLS and given topical applicaiton of water or empty patches.
- Concentrations: 10% and 30%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 14 days after last induction exposure
- Test groups: Topical application of 10% and 30% test substance.
- Control group: Topical application of 10% and 30% test substance.
- Concentrations: 10% and 30%
- Evaluation (hr after challenge): 24 and 48 hrs after removal of the patches.
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
30%
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
30%
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10% and 30%
No. with + reactions:
0
Total no. in group:
6
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10% and 30%
No. with + reactions:
0
Total no. in group:
6
Group:
positive control
Remarks on result:
not measured/tested

Any other information on results incl. tables

Dermal Reaction Scores In Challenge Test

Animal

24 hrs

48 hrs

Control Group

0

0

76

0

0

78

0

0

80

0

0

75

0

0

77

0

0

79

0

0

10% Test Substance

0

0

66

0

0

68

0

0

70

0

0

72

0

0

74

0

0

65

0

0

67

0

0

69

0

0

71

0

0

73

0

0

30% Test Substance

0

0

66

0

0

68

0

0

70

0

0

72

0

0

74

0

0

65

0

0

67

0

0

69

0

0

71

0

0

73

0

0

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
LMD is not sensitizing to skin.
Executive summary:

The skin sensitization potential of LMD was tested in an OECD Guideline 406 study. 5 male and 5 female guinea pigs were exposed to the test substance intradermally, and topically in exposures one week apart. A control group was exposed to vehicles only. 2 weeks later, both groups were exposed to the 10% and 30% of the test substance topically. No reactions were seen in any animals during the challenge exposure. The test substance is therefore not sensitizing to skin.