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Diss Factsheets

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: scientifically acceptable and sufficient documented

Data source

Reference
Reference Type:
publication
Title:
A new protocol and criteria for quantitative determination of sensitization potencies of chemicals by guinea pig maximization test
Author:
Nakamura A, Momma J, Sekiguchi H, Noda T, Yamano T, Kaniwa MA, Kojima S, Tsuda M, Kurokawa Y
Year:
1994
Bibliographic source:
Contact deramitis 31, 72-85 (1994)

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
The sensitization test was performed almost in accordance with the original procedure of Magnusson and Kligman with some modifications. Female albino guinea pigs of the Hartley strain were used as experimental animals. Five animals were used in each experimental group. Each group of animals was sensitized by injection of given concentration of the chemical. 21 days after the initial intradermal injection, 0.1 ml aliquots of various concentrations of test chemical in the vehicle were applied to the shaved area of the flank of each animal for challenge. All concentrations adopted are lower than the irritant concentrations. The challenge was done by the open patch test method. The chemical was left in place for 24 hours.
Dermal response of each challenge site was evaluated 48 h after the challenge application. Evaluation of skin reactions was done by scoring erythema and edema formation of each challenge concentration.
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was published 1994. At this time an OECD guideline for a LLNA was not available.

Test material

Constituent 1
Chemical structure
Reference substance name:
Phenyl isocyanate
EC Number:
203-137-6
EC Name:
Phenyl isocyanate
Cas Number:
103-71-9
Molecular formula:
C7H5NO
IUPAC Name:
isocyanatobenzene
Details on test material:
PIC (phenyl isocyanate) was purchased from Tokyo Kasei Kogyo Co. Ltd.

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
female

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: induction: intradermal injection/topical = ethanol/propylene glycol; Challenge: topical = acetone
Concentration / amount:
Induction -intradermal injection. 0, 200, 2000 ppm
Induction - topical: 0, 2000 ppm
Challenge - topical: 0, 2, 20, 200, 2000 ppm
Challengeopen allclose all
Route:
epicutaneous, open
Vehicle:
other: induction: intradermal injection/topical = ethanol/propylene glycol; Challenge: topical = acetone
Concentration / amount:
Induction -intradermal injection. 0, 200, 2000 ppm
Induction - topical: 0, 2000 ppm
Challenge - topical: 0, 2, 20, 200, 2000 ppm
No. of animals per dose:
Five animals per dose were used in each experimental group

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
other: induction intradermal: 0 ppm, induction topical: 0 ppm, challenge 0 ppm
Dose level:
0 ppm (challenge)
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: other: induction intradermal: 0 ppm, induction topical: 0 ppm, challenge 0 ppm. Dose level: 0 ppm (challenge). No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
48
Group:
other: induction intradermal: 0 ppm, induction topical: 0 ppm, challenge 2 ppm
Dose level:
2 ppm (challenge)
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: other: induction intradermal: 0 ppm, induction topical: 0 ppm, challenge 2 ppm. Dose level: 2 ppm (challenge). No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
48
Group:
other: induction intradermal: 0 ppm, induction topical: 0 ppm, challenge 20 ppm
Dose level:
20 ppm (challenge)
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: other: induction intradermal: 0 ppm, induction topical: 0 ppm, challenge 20 ppm. Dose level: 20 ppm (challenge). No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
48
Group:
other: induction intradermal: 0 ppm, induction topical: 0 ppm, challenge 200 ppm
Dose level:
200 ppm (challenge)
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: other: induction intradermal: 0 ppm, induction topical: 0 ppm, challenge 200 ppm. Dose level: 200 ppm (challenge). No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
48
Group:
other: induction intradermal: 0 ppm, induction topical: 0 ppm, challenge 2000 ppm
Dose level:
2000 ppm (challenge)
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: other: induction intradermal: 0 ppm, induction topical: 0 ppm, challenge 2000 ppm. Dose level: 2000 ppm (challenge). No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
48
Group:
other: induction intradermal: 200 ppm, induction topical: 20000 ppm, challenge 0 ppm
Dose level:
0 ppm (challenge)
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: other: induction intradermal: 200 ppm, induction topical: 20000 ppm, challenge 0 ppm. Dose level: 0 ppm (challenge). No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
48
Group:
other: induction intradermal: 200 ppm, induction topical: 20000 ppm, challenge 2 ppm
Dose level:
2 ppm (challenge)
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: other: induction intradermal: 200 ppm, induction topical: 20000 ppm, challenge 2 ppm. Dose level: 2 ppm (challenge). No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
48
Group:
other: induction intradermal: 200 ppm, induction topical: 20000 ppm, challenge 20 ppm
Dose level:
20 ppm (challenge)
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: other: induction intradermal: 200 ppm, induction topical: 20000 ppm, challenge 20 ppm. Dose level: 20 ppm (challenge). No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
48
Group:
other: induction intradermal: 200 ppm, induction topical: 20000 ppm, challenge 200 ppm
Dose level:
200 ppm (challenge)
No. with + reactions:
3
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: other: induction intradermal: 200 ppm, induction topical: 20000 ppm, challenge 200 ppm. Dose level: 200 ppm (challenge). No with. + reactions: 3.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
48
Group:
other: induction intradermal: 200 ppm, induction topical: 20000 ppm, challenge 2000 ppm
Dose level:
2000 ppm (challenge)
No. with + reactions:
5
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: other: induction intradermal: 200 ppm, induction topical: 20000 ppm, challenge 2000 ppm. Dose level: 2000 ppm (challenge). No with. + reactions: 5.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
48
Group:
other: induction intradermal: 2000 ppm, induction topical: 20000 ppm, challenge 0 ppm
Dose level:
0 ppm (challenge)
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: other: induction intradermal: 2000 ppm, induction topical: 20000 ppm, challenge 0 ppm. Dose level: 0 ppm (challenge). No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
48
Group:
other: induction intradermal: 2000 ppm, induction topical: 20000 ppm, challenge 2 ppm
Dose level:
2 ppm (challenge)
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: other: induction intradermal: 2000 ppm, induction topical: 20000 ppm, challenge 2 ppm. Dose level: 2 ppm (challenge). No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
48
Group:
other: induction intradermal: 2000 ppm, induction topical: 20000 ppm, challenge 20 ppm
Dose level:
20 ppm (challenge)
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: other: induction intradermal: 2000 ppm, induction topical: 20000 ppm, challenge 20 ppm. Dose level: 20 ppm (challenge). No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
48
Group:
other: induction intradermal: 2000 ppm, induction topical: 20000 ppm, challenge 200 ppm
Dose level:
200 ppm (challenge)
No. with + reactions:
3
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: other: induction intradermal: 2000 ppm, induction topical: 20000 ppm, challenge 200 ppm. Dose level: 200 ppm (challenge). No with. + reactions: 3.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
48
Group:
other: induction intradermal: 2000 ppm, induction topical: 20000 ppm, challenge 2000 ppm
Dose level:
2000 ppm (challenge)
No. with + reactions:
4
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: other: induction intradermal: 2000 ppm, induction topical: 20000 ppm, challenge 2000 ppm. Dose level: 2000 ppm (challenge). No with. + reactions: 4.0. Total no. in groups: 5.0.

Any other information on results incl. tables

With an induction of 2 or 20 ppm no skin sensitization (0/5) were found, but an induction of 200 ppm (3/5) or 2000 ppm (4/5 and 5/5) animals revealed clear signs of skin sensitization. A maximal reaction was found with an intradermal induction with 200 ppm and a topical induction with 2000 ppm followed by a challenge with 2000 ppm. As a result phenyl isocyanate was positive under the conditions of this assay.

Applicant's summary and conclusion

Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification as Skin Sens. 1A is justified.
Executive summary:

The sensitization test was performed almost in accordance with the original procedure of Magnusson and Kligman with some modifications. Female albino guinea pigs of the Hartley strain were used as experimental animals. Five animals were used in each experimental group. Each group of animals were sensitized by injection of given concentration of the chemical. 21 days after the initial intradermal injection, 0.1 ml aliquots of various concentrations of test chemical in the vehicle were applied to the shaved area of the flank of each animal for challenge. All concentrations adopted are lower than the irritant concentrations. the challenge was done by the open patch test method. the chemical was left in place for 24 hours.

Dermal response of each challenge site was evaluated 48 h after the challenge application. Evaluation of skin reactions was done by scoring erythema and edema formation of each challenge concentration.

With an induction of 2 or 20 ppm no skin sensitization (0/5) were found, but an induction of 200 ppm (3/5) or 2000 ppm (4/5 and 5/5) animals revealed clear signs of skin sensitization. A maximal reaction was found with an intradermal induction with 200 ppm and a topical induction with 2000 ppm followed by a challenge with 2000 ppm. As a result phenyl isocyanate was positive under the conditions of this assay.