Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
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
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".
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
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
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
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
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.

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

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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Sensitisation potential of the test item was observed in 100 % of test animals in a GMPT (OECD guideline 406). The reactions are not attributable to the solvent isododecane, which failed to induce any sensitising cutaneous reaction. According to the ECHA guidance on information requirements R.8, Appendix 10, the test item is considered a moderate sensitizer (100 % positive reaction after induction with 2.5 % test item).


Migrated from Short description of key information:
GLP guideline study according to OECD 406

Justification for selection of skin sensitisation endpoint:
(key study) GLP guideline study

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Sensitisation potential of the test item was observed in 100 % of test animals in a GMPT (OECD guideline 406). The reactions are not attributable to the solvent isododecane, which failed to induce any sensitising cutaneous reaction.