Registration Dossier

Administrative data

Description of key information

The potential of the substance to induce delayed contact hypersensitivity was investigated using the Maximization method of Magnusson and Kligman (OECD 406, GLP). The result of the Guinea Pig Maximisation Test indicates that the substance was a skin sensitizer.

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
Reliability:
1 (reliable without restriction)
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Justification for non-LLNA method:
Study predates LLNA REACH requirements
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Route:
intradermal and epicutaneous
Route:
epicutaneous, occlusive
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
20 %
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
Slight erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 20 %. No with. + reactions: 4.0. Total no. in groups: 10.0. Clinical observations: Slight erythema.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10 %
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
Slight erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10 %. No with. + reactions: 4.0. Total no. in groups: 10.0. Clinical observations: Slight erythema.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
20 %
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
Slight to well-defined erythema with or without slight oedema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 20 %. No with. + reactions: 6.0. Total no. in groups: 10.0. Clinical observations: Slight to well-defined erythema with or without slight oedema.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10 %
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
Slight to well-defined erythema with or without slight oedema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10 %. No with. + reactions: 6.0. Total no. in groups: 10.0. Clinical observations: Slight to well-defined erythema with or without slight oedema.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
20 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 20 %. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 10 %. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
20 %
No. with + reactions:
1
Total no. in group:
5
Clinical observations:
Dryness and sloughing of the epidermis
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 20 %. No with. + reactions: 1.0. Total no. in groups: 5.0. Clinical observations: Dryness and sloughing of the epidermis .
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 10 %. No with. + reactions: 0.0. Total no. in groups: 5.0.
Parameter:
SI
Remarks on result:
other: Not applicable
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: Not applicable

7.4.1.2: Dermal reactions observed after the challenge application:

Group

Animal number

E=Erythema

O =Oedema

Skin reaction (hour after removal of dressing)

Results

Positive (+)

Negative (-)

Inconclusive (±)

24 hours

48 hours

A

P

A

P

Control group

1990

E

0

0

1*

0

 

O

0

0

0

0

1991

E

0

0

0

0

O

0

0

0

0

1992

E

0

0

0

0

O

0

0

0

0

1993

E

0

0

0

0

O

0

0

0

0

1994

E

0

0

0

0

O

0

0

0

0

Treated group

1995

E

1

1

1

1

+

O

0

0

1

1

1996

E

0

0

0

0

-

O

0

0

0

0

1997

E

1

1

2

2

+

O

0

0

1

1

1998

E

0

0

0

0

-

O

0

0

0

0

1999

E

0

0

0

1

-

O

0

0

0

0

2000

E

0

0

2Td

2*

+

O

0

0

1

1

2001

E

1

1

2

2

+

O

0

0

1

1

2002

E

0

0

0

0

-

O

0

0

0

0

2003

E

0

0

1

0

-

O

0

0

0

0

2004

E

1

1

1

2

+

O

0

0

0

1

* Dryness and sloughing of the epidermis

Td Thickening, dryness and sloughing of the epidermis

A Anterior site, exposed to the test item, 20% w/v in vehicle

P Posterior site, exposed to the test item, 10% w/v in vehicle

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

The potential of the test substance to induce delayed contact hypersensitivity was assessed in guinea pigs according to OECD guideline 406 and in compliance with Good Laboratory Practice.

The induction phase was realized both by the intradermal route on day 1 (Test material 2.5% in Alembicol D (coconut oil)) and by the cutaneous route on day 8 (Test material 60% in Alembicol D) in 2 groups of guinea pigs: 5 in the control group and 10 in the treated group. The challenge phase was realized on day 22 by cutaneous application of the test material at 20% and 10% in Alembicol D. The cutaneous reactions were scored 24 and 48 hours after the challenge phase.

Hexyl cinnamic aldehyde was used as a positive control and induced positive sensitization responses for nine of the ten test animals and therefore confirmed the sensitivity and reliability of the study.

In the control group, at the 24 and 48-hour readings, no cutaneous reactions were observed except in 1 animal at the 48 -hour reading that showed dryness and sloughing of the epidermis after challenge with the concentration of 20% .In the treated group, a slight erythema (grade1) was noted in 4 of the 10 animals at the 24 hour reading for both concentrations.

At the 48 hour reading, a slight or well-defined erythema (grade 1 or 2) together with a slight oedema (grade 1) was observed in 5 of the 10 animals. In addition, thickening, dryness and sloughing of the skin was noted in 1 animal.

The persistent cutaneous reactions observed in 5 of the 10 animals of the test item-treated group were attributed to delayed contact hypersensitivity.

It was therefore concluded that the test substance was a skin sensitizer.



Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The test substance induced delayed contact hypersensitivity in 5 out of 10 (50%) guinea pigs with an intradermal induction dose of 2.5% .

Since more than 30% of the animals responded to an intradermal induction dose of more than 1%, the substance is considered as a moderate sensitizer and is therefore classified as a Skin Sensitizer category 1 and sub- category 1B according to Regulation (EC) No. 1272/2008 and its subsequent amendments on classification, labeling and packaging (CLP) of substances and mixtures.