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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
Study period:
1996-04-25 to 1996-05-28
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

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:
The GPMT is an accepted method for hazard identification of skin sensitising substances as recommended in "ECHA guidance R.7a: Endpoint specific guidance".

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Luperox 223-M-75 (Di-(2-ethylhexyl)-peroxydicarbonate)
- Substance type: organic peroxide
- Physical state: colourless liquid
- Analytical purity: 75.8% in isodecan
- Lot/batch No.: 802-9409-01
- Storage condition of test material: at -20°C and protected from light

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: Centre d´Elevage Lebeau, 78950 Gambais, France
- Age at study initiation: approx. 3 month
- Weight at study initiation: 327 +/-18 g (males), 347 +/- 16 g (females)
- Housing: individually
- Diet (e.g. ad libitum): free access
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 12
- 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:
Induction: intradermal injection of 2.5 % (w/w) Luperox 223-M-75 in a mixture paraffin oil/Isododecan
topical application of Luperox 223-M-75 undiluted
Challenge: topical application of 50% (w/w) Luperox 223-M-75 in Isododecan
topical application of Luperox 223-M-75 undiluted
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
Induction: intradermal injection of 2.5 % (w/w) Luperox 223-M-75 in a mixture paraffin oil/Isododecan
topical application of Luperox 223-M-75 undiluted
Challenge: topical application of 50% (w/w) Luperox 223-M-75 in Isododecan
topical application of Luperox 223-M-75 undiluted
No. of animals per dose:
20 (10 males and 10 females)
Details on study design:
RANGE FINDING TESTS: preliminary test to determine the concentrations to be tested in the main study

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: intradermal and topical application -> 2
- Exposure period: 48 h exposure of topical application
- Test groups: application of the 0.5 ml test substance: intradermal 2.5% (w/w) in a mixture paraffin oil/isododecan; topical application: undiluted
- Control group: group 1: intradermal and topical application of the vehicle; group 2: intradermal application 50% (w/w) isododecane in paraffin oil and topical application of the solvent Isododecan undiluted
- Site: dorsal region between the shoulders
- Frequency of applications: 1
- Duration: 10 days
- Concentrations: 2.5% (w/w) in a mixture paraffin oil/isododecan; undiluted;

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 1 (24 h)
- Exposure period: 24 h
- Test groups: 1 test group
- Control group: 2 control groups
- Site: right and left flank
- Concentrations:
Control group 1: test substance and isododecan in original form
Control group 2: isododecan 50% (w/w) in paraffin oil and in its original form
Treated group 3: test substance concentration 50% (w/w) in paraffin oil and in its original form
- Evaluation (hr after challenge): scoring after 24 h, 48 h, and after 72 h
Challenge controls:
Isododecan at 50% (w/w) in paraffin oil and undiluted
Positive control substance(s):
yes
Remarks:
recent study with positive sensitizer: 2,4-dinitro chlorobenzene

Results and discussion

Positive control results:
2,4- dinitro chlorobenzene in a concentration of 1% (w/w) induced positive skin sensitization reactions in 75 % of the guinea-pig

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50%
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 20.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
75.8 % in Isododecan
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 75.8 % in Isododecan. No with. + reactions: 20.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50%
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 20.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
75.8 % in Isododecan
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 75.8 % in Isododecan. No with. + reactions: 20.0. Total no. in groups: 20.0.

Any other information on results incl. tables

Table 1: Control group 1 skin reactions

Sex

Animal number

24 h Erythema

24 h Oedema

48 h Erythema

48 h Oedema

72 h Erythema

72 h Oedema

LF

RF

LF

RF

LF

RF

LF

RF

LF

RF

LF

RF

Male

61

0

0

0

0

0

0

0

0

0/S

0/S

0

0

 

62

0/S

0

0

0

0/S

0

0

0

0/S

0/S

0

0

 

63

0

0

0

0

0

0

0

0

0/S

0/S

0

0

 

64

0

0

0

0

0

0

0

0

0/S

0/S

0

0

 

65

0

0

0

0

0

0

0

0

0/S

0/S

0

0

Female

81

0

0

0

0

0

0

0

0

0/S

0/S

0

0

 

82

0

0

0

0

0

0

0

0

0/S

0/S

0

0

 

83

0

0

0

0

0

0

0

0

0/S

0/S

0

0

 

84

0

0

0

0

0

0

0

0

0/S

0/S

0

0

 

85

0

0

0

0

0

0

0

0

LS

0

0

0

 

Table 2: Control group 2 skin reactions

Sex

Animal number

24 h Erythema

24 h Oedema

48 h Erythema

48 h Oedema

72 h Erythema

72 h Oedema

LF

RF

LF

RF

LF

RF

LF

RF

LF

RF

LF

RF

Male

66

0

0

0

0

0

0

0

0

0/S

0/S

0

0

 

67

0

0

0

0

0

0

0

0

0/S

0/S

0

0

 

68

0

0

0

0

0

0

0

0

0/S

0/S

0

0

 

69

0

0

0

0

0

0

0

0

0/S

0/S

0

0

 

70

0

0

0

0

0

0

0

0

0/S

0

0

0

Female

86

0

0

0

0

0

0

0

0

0/S

0/S

0

0

 

87

0

0

0

0

0

0

0

0

0

0/S

0

0

 

88

0

0

0

0

0

0

0

0

0

0/S

0

0

 

89

0

0

0

0

0

0

0

0

0/S

0/S

0

0

 

90

0

0

0

0

0

0

0

0

0/S

0/S

0

0

 

Table 3: Treated group skin reactions

Sex

Animal number

24 h Erythema

24 h Oedema

48 h Erythema

48 h Oedema

72 h Erythema

72 h Oedema

LF

RF

LF

RF

LF

RF

LF

RF

LF

RF

LF

RF

Male

71

2/S/A

2/S/A

0

0

LS

LS

2

2

0/S

0/S

0

2

 

72

2/S/A

2/S/A

0

0

LS

LS

2

2

0/S

0/S

2

2

 

73

2

2

2

2

2

2

2

2

LS/A

0/S

2

2

 

74

2

2

0

0

2/S

2/S

0

0

0/S

0/S/A

0

0

 

75

1

1

0

0

2/S

1/S

0

0

LS/A

LS

0

0

 

76

2

2

0

0

1/S

2/S

0

0

LS/A

0/S

0

0

 

77

3/S/A

3/S/A

2

2

4/S

4/S

2

2

LS/A

2/S

2

2

 

78

1

2

0

2

2/S

3/S

2

2

LS/A

LS/A

2

2

 

79

2

2

0

0

3/S

3/S

2

2

0/S

0/S

0

0

 

80

1

2

0

0

LS

2/S

2

2

0/S

0/S/A

0

0

Female

91

2/S

2/S

2

2

LS

LS

2

2

LS

LS

0

0

 

92

2/S

2/S

2

2

3/S

4/S

2

2

LS/A

LS/A

0

0

 

93

1

2

2

2

2/S

2/S

2

2

LS/A

LS

0

0

 

94

2

2

2

2

3/S

3/S

2

2

LS/A

LS/A

0

0

 

95

2

2

2

2

LS

LS

2

2

LS

LS

2

2

 

96

3/S

3/S

2

2

3/S

LS

2

2

LS/A

LS

0

0

 

97

2

2

2

2

LS

LS

2

2

0/S

LS

0

0

 

98

2

2

2

2

LS

LS

2

2

LS

LS

0

0

 

99

3

3

0

0

2/S

2/S

0

0

LS/A

0/S

0

0

 

100

2/S

3

2

2

LS

LS

2

2

LS

LS

2

2

LF: left flank

RF: right flank

S: dryness of the skin

A: crusts

LS: scoring masked by a severe dryness of the skin

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Cutaneous reactions attributable to the sensitization potential of the test item were observed in 100% of the test animals. The reactions are not attributable to the solvent Isodecan
Executive summary:

In a dermal sensitization study with Di-(2-Ethylhexyl)-Peroxydicarbonate (2.5%) in isododecan,40 Dunkin-Hartley Guinea Pigs (10/sex) were tested using the method of Magnusson and Klingman (GPMT). Positive control was 2,4-dinitro chlorobenzene; Isododecan was tested as solvent control.
In the treated group, marked cutaneous reactions, similar on both flanks, were observed. Slight to severe erythema (grade 1 to 4) were noted in all animals at the 24 h and the 48 h readings. These reactions were attributed to a sensitizing effect in 100% treated animals. No clinical signs and no mortality were observed. The body weight gain was normal.

 In this study, Chemical Di-(2-Ethylhexyl)-Peroxydicarbonate is a dermal sensitizer.