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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: study is comparable to the Buehler test described in OECD Guideline 406 with acceptable restrictions (low number of animals, no negative control, low concentration of the test substance at challenge)

Data source

Reference
Reference Type:
other: microfiche
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Principles of method if other than guideline:
equivalent to OECD 406 (skin sensitation)
GLP compliance:
yes
Type of study:
Buehler test

Test material

Constituent 1
Chemical structure
Reference substance name:
Octadecyl isocyanate
EC Number:
204-019-7
EC Name:
Octadecyl isocyanate
Cas Number:
112-96-9
Molecular formula:
C19H37NO
IUPAC Name:
1-isocyanatooctadecane

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals
- Pretest body weight range: 276 - 362 g
- Housing: single
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least one week

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
inductions 1 to 9: 0.1 % (0.5 ml)
challenges 1 and 2: 0.1 % (0.5 ml)
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
inductions 1 to 9: 0.1 % (0.5 ml)
challenges 1 and 2: 0.1 % (0.5 ml)
No. of animals per dose:
10
Details on study design:
PRELIMINARY SCREEN:
Prior to the initiation of the study, a preliminary screen was conducted topically using six healthy male Hartley Albino guinea pigs to determine the highest non-irritating concentration of the test article. Based on the irritation scores at 6 and 24 hours, the preliminary screen indicated that the highest non-irritating concentration of the test article was 0.1 %.

SENSITIZATION STUDY:
- Site preparation: Forty-eight hours prior to the first dose, the dorsal area of each animal was clipped free of hair with an Oster Model 2 Clipper. The area was approximately 5 x 10 cm, i.e., 10% of the body surface. Forty-eight hours prior to the 3rd and 6th doses, the area was clipped, if necessary. Forty-eight hours prior to the first challenge, the area was clipped.
- Experimental design:
lnduction: Based on the results of the preliminary screen, 0.5 ml of the test article or DNCB concentration was applied beneath a Hill Top chamber on one site posterior to the left shoulder. The chamber was covered with plastic 2 mils thick and secured with adhesive tape. The animals were placed in a restrainer. The patch was allowed to remain in place for six hours after which the plastic and patch were removed. The induction dose was administered every Wednesday, Friday and Monday for three consecutive weeks, a total of nine 6-hour insults.
Challenge: Fourteen days after the last induction. the animals were challenged in the same manner at both the site of induction and at a new site posterior to the right shoulder. Forty-eight hours after the first challenge, a second challenge was performed on the same sites as the first challenge.
- Type and frequency of observations: The treated sites of each animal were examined at 6, 24 and 48 hours after each induction and challenge. Redness was scored using the numerical Draize scoring code. Additional signs were described. The animals were observed once daily for mortality and toxicity. Body weights were recorded pretest and at termination.
- Analysis of data: A score of 2 or more at challenge in 20% or more of the animals is indicative of a sensitizing response.
Positive control substance(s):
yes
Remarks:
DNCB (dinitrochlorobenzene)

Study design: in vivo (LLNA)

Statistics:
no data

Results and discussion

Positive control results:
All animals exhibited positive responses following both 6 hour challenge exposures to a non-irritating 0.1 % concentration of DNCB.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
other: challenge I
Hours after challenge:
6
Group:
test chemical
Dose level:
0.1 %
No. with + reactions:
7
Total no. in group:
10
Clinical observations:
at least well defined erythema (Draize code 2)
Remarks on result:
other: Reading: other: challenge I. . Hours after challenge: 6.0. Group: test group. Dose level: 0.1 % . No with. + reactions: 7.0. Total no. in groups: 10.0. Clinical observations: at least well defined erythema (Draize code 2).
Reading:
other: challenge II
Hours after challenge:
6
Group:
test chemical
Dose level:
0.1 %
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
at least well defined erythema (Draize code 2)
Remarks on result:
other: Reading: other: challenge II. . Hours after challenge: 6.0. Group: test group. Dose level: 0.1 % . No with. + reactions: 8.0. Total no. in groups: 10.0. Clinical observations: at least well defined erythema (Draize code 2).

Any other information on results incl. tables

OCTADECYL ISOCYANATE:

- Induction: Erythema was generally absent to well defined during the induction phase. One animal exhibited moderate to severe erythema during the first induction.

- Challenge: Due to the moderate to severe response of one animal during the first induction, interpretation of the challenge reactions were based on the individual induction responses. Seven of ten animals exhibited positive responses to the first 6 hour challenge exposure to a 0.1% concentration of the test article. Eight of ten animals exhibited positive responses following the second challenge.

- Systemics: All animals survived in generally good health. Instances of emaciation and soiling of the anogenital area were noted during the study.

- Conclusion: Octadecyl isocyanate is a sensitizer.

DNCB:

- Induction: Erythema was absent to slight during the first two inductions, and absent to well defined during inductions 3 and 4.Thereafter, erythema was generally mild to severe.

- Challenge: All animals exhibited positive responses following both 6 hour challenge exposures to a non-irritating 0.1% concentration of DNCB.

- Systemics: All animals survived in generally good health with one animal exhibiting instances of emaciation and soiling of the anogenital area.

- Conclusion: DNCB (dinitrochlorobenzene) is a sensitizer.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Executive summary:

A Buehler test in guinea pigs revealed a skin sensitising potential of octadecyl isocyanate (0.1% induction and challenge conc., >= 70 % incidence of sensitisation) according to a method similar to OECD Guideline 406.

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